Nonmelanoma Skin Cancer

Military dermatologists are charged with caring for a diverse population of active-duty members, civilian dependents, and military retirees. Although certain risk factors for cutaneous malignancies are common in all of these groups, the active-duty population experiences unique exposures to be considered when determining their risk for skin cancer. One subset that may be at a higher risk is military pilots who fly at high altitudes on irregular schedules in austere environments. Through the unparalleled comradeship inherent in many military units, pilots “hear” from their fellow pilots that they are at increased risk for skin cancer. Do their occupational exposures translate into increased risk for cutaneous malignancy? This article will survey the literature pertaining to pilots and skin cancer so that all dermatologists may better care for this unique population.

Epidemiology

Anecdotally, we have observed basal cell carcinoma in pilots in their 20s and early 30s, earlier than would be expected in an otherwise healthy prescreened military population.¹ Woolley and Hughes² published a case report of skin cancer in a young military aviator. The patient was a 32-year-old male helicopter pilot with Fitzpatrick skin type II and no personal or family history of skin cancer who was diagnosed with a periocular nodular basal cell carcinoma. He deployed to locations with high UV radiation (UVR) indices, and his vacation time also was spent in such areas.² UV radiation exposure and Fitzpatrick skin type are known risk factors across occupations, but are there special exposures that come with military aviation service?

To better understand the risk for malignancy in this special population, the US Air Force examined the rates of all cancer types among a cohort of flying versus nonflying officers.³ Aviation personnel showed increased incidence of testicular, bladder, and all-site cancers combined. Noticeably absent was a statistically significant increased risk for malignant melanoma (MM) and nonmelanoma skin cancer (NMSC). Other epidemiological studies examined the incidence rates of MM in the US Armed Forces compared with age- and race-matched civilian populations and showed mixed results: 2 studies showed increased risk,^4,5 while a third showed decreased risk.⁶ Despite finding opposite results of MM rates in military members versus the civilian population, 2 of these studies showed US Air Force members to have higher rates of MM than those in the US Army or Navy.^4,6 Interestingly, the air force has the highest number of pilots among all the services, with 4000 more pilots than the army and navy.⁷ Further studies are needed to determine if the higher air force MM rates occur in pilots.

Although there are mixed and limited data pertaining to military flight crews, there is more robust literature concerning civilian flight personnel. One meta-analysis pooled studies related to cancer risk in cabin crews and civil and military pilots.⁸ In military pilots, they found a standardized incidence ratio (SIR) of 1.43 (95% confidence interval [CI], 1.09-1.87) for MM and 1.80 (95% CI, 1.25-2.80) for NMSC. The SIRs were higher for male cabin attendants (3.42 and 7.46, respectively) and civil pilots (2.18 and 1.88, respectively). They also found the most common cause of mortality in civilian cabin crews was AIDS, possibly explaining the higher SIRs for all types of malignancy in that population.⁸ In the United States, many civilian pilots previously were military pilots⁹ who likely served in the military for at least 10 years.¹⁰ A 2015 meta-analysis of 19 studies of more than 266,000 civil pilots and aircrew members found an SIR for MM of 2.22 (95% CI, 1.67-2.93) for civil pilots and 2.09 (95% CI, 1.67-2.62) for aircrews, stating the risk for MM is at least twice that of the general population.¹¹

Risk Factors

UV Radiation
These studies suggest flight duties increase the risk for cutaneous malignancy. UV radiation is a known risk factor for skin cancer.¹² The main body of the aircraft may protect the cabin’s crew and passengers from UVR, but pilots are exposed to more UVR, especially in aircraft with larger windshields. A government study in 2007 examined the transmittance of UVR through windscreens of 8 aircraft: 3 commercial jets, 2 commercial propeller planes, 1 private jet, and 2 small propeller planes.¹³ UVB was attenuated by all the windscreens (<1% transmittance), but 43% to 54% of UVA was transmitted, with plastic windshields attenuating more than glass. Sanlorenzo et al¹⁴ measured UVA irradiance at the pilot’s seat of a turboprop aircraft at 30,000-ft altitude. They compared this exposure to a UVA tanning bed and estimated that 57 minutes of flight at 30,000-ft altitude was equivalent to 20 minutes inside a UVA tanning booth, a startling finding.¹⁴

Cosmic Radiation
Cosmic radiation consists of neutrons and gamma rays that originate outside Earth’s atmosphere. Pilots are exposed to higher doses of cosmic radiation than nonpilots, but the health effects are difficult to study. Boice et al¹⁵ described how factors such as altitude, latitude, and flight time determine pilots’ cumulative exposure. With longer flight times at higher altitudes, a pilot’s exposure to cosmic radiation is increasing over the years.¹⁵ A 2012 review found that aircrews have low-level cosmic radiation exposure. Despite increases in MM and NMSC in pilots and increased rates of breast cancer in female aircrew, overall cancer-related mortality was lower in flying versus nonflying controls.¹⁶ Thus, cosmic radiation may not be as onerous of an occupational hazard for pilots as has been postulated.

Altered Circadian Rhythms
Aviation duties, especially in the military, require irregular work schedules that repeatedly interfere with normal sleep-wake cycles, disrupt circadian rhythms, and lead to reduced melatonin levels.⁸ Evidence suggests that low levels of melatonin could increase the risk for breast and prostate cancer—both cancers that occur more frequently in female aircrew and male pilots, respectively—by reducing melatonin’s natural protective role in such malignancies.^17,18 A World Health Organization working group categorized shift work as “probably carcinogenic” and cited alterations of melatonin levels, changes in other circadian rhythm–related gene pathways, and relative immunosuppression as likely causative factors.¹⁹ In a 2011 study, exposing mice to UVR during times when nucleotide excision repair mechanisms were at their lowest activity caused an increased rate of skin cancers.²⁰ A 2014 review discussed how epidemiological studies of shift workers such as nurses, firefighters, pilots, and flight crews found contradictory data, but molecular studies show that circadian rhythm–linked repair and tumorigenesis mechanisms are altered by aberrations in the normal sleep-wake cycle.²¹

Cockpit Instrumentation
Electromagnetic energy from the flight instruments in the cockpit also could influence malignancy risk. Nicholas et al²² found magnetic field measurements within the cockpit to be 2 to 10 times that experienced within the home or office. However, no studies examining the health effects of cockpit flight instruments and magnetic fields were found.

Final Thoughts

It is important to counsel pilots on the generally recognized, nonaviation-specific risk factors of family history, skin type, and UVR exposure in the development of skin cancer. Additionally, it is important to explain the possible role of exposure to UVR at higher altitudes, cosmic radiation, and electromagnetic energy from cockpit instruments, as well as altered sleep-wake cycles. A pilot’s risk for MM may be twice that of matched controls, and the risk for NMSC could be higher.^8,11 Although the literature lacks specific recommendations for pilots, it is reasonable to screen pilots once per year to better assess their individual risk and encourage diligent use of sunscreen and sun-protective measures when flying. It also may be important to advocate for the development of engineering controls that decrease UVR transmittance through windscreens, particularly for aircraft flying at higher altitudes for longer flights. More research is needed to determine if changes in circadian rhythm and decreases in melatonin increase skin cancer risk, which could impact how pilots’ schedules are managed. Together, we can ensure adequate surveillance, diagnosis, and treatment in this at-risk population.

Military dermatologists are charged with caring for a diverse population of active-duty members, civilian dependents, and military retirees. Although certain risk factors for cutaneous malignancies are common in all of these groups, the active-duty population experiences unique exposures to be considered when determining their risk for skin cancer. One subset that may be at a higher risk is military pilots who fly at high altitudes on irregular schedules in austere environments. Through the unparalleled comradeship inherent in many military units, pilots “hear” from their fellow pilots that they are at increased risk for skin cancer. Do their occupational exposures translate into increased risk for cutaneous malignancy? This article will survey the literature pertaining to pilots and skin cancer so that all dermatologists may better care for this unique population.

Epidemiology

Anecdotally, we have observed basal cell carcinoma in pilots in their 20s and early 30s, earlier than would be expected in an otherwise healthy prescreened military population.¹ Woolley and Hughes² published a case report of skin cancer in a young military aviator. The patient was a 32-year-old male helicopter pilot with Fitzpatrick skin type II and no personal or family history of skin cancer who was diagnosed with a periocular nodular basal cell carcinoma. He deployed to locations with high UV radiation (UVR) indices, and his vacation time also was spent in such areas.² UV radiation exposure and Fitzpatrick skin type are known risk factors across occupations, but are there special exposures that come with military aviation service?

To better understand the risk for malignancy in this special population, the US Air Force examined the rates of all cancer types among a cohort of flying versus nonflying officers.³ Aviation personnel showed increased incidence of testicular, bladder, and all-site cancers combined. Noticeably absent was a statistically significant increased risk for malignant melanoma (MM) and nonmelanoma skin cancer (NMSC). Other epidemiological studies examined the incidence rates of MM in the US Armed Forces compared with age- and race-matched civilian populations and showed mixed results: 2 studies showed increased risk,^4,5 while a third showed decreased risk.⁶ Despite finding opposite results of MM rates in military members versus the civilian population, 2 of these studies showed US Air Force members to have higher rates of MM than those in the US Army or Navy.^4,6 Interestingly, the air force has the highest number of pilots among all the services, with 4000 more pilots than the army and navy.⁷ Further studies are needed to determine if the higher air force MM rates occur in pilots.

Although there are mixed and limited data pertaining to military flight crews, there is more robust literature concerning civilian flight personnel. One meta-analysis pooled studies related to cancer risk in cabin crews and civil and military pilots.⁸ In military pilots, they found a standardized incidence ratio (SIR) of 1.43 (95% confidence interval [CI], 1.09-1.87) for MM and 1.80 (95% CI, 1.25-2.80) for NMSC. The SIRs were higher for male cabin attendants (3.42 and 7.46, respectively) and civil pilots (2.18 and 1.88, respectively). They also found the most common cause of mortality in civilian cabin crews was AIDS, possibly explaining the higher SIRs for all types of malignancy in that population.⁸ In the United States, many civilian pilots previously were military pilots⁹ who likely served in the military for at least 10 years.¹⁰ A 2015 meta-analysis of 19 studies of more than 266,000 civil pilots and aircrew members found an SIR for MM of 2.22 (95% CI, 1.67-2.93) for civil pilots and 2.09 (95% CI, 1.67-2.62) for aircrews, stating the risk for MM is at least twice that of the general population.¹¹

Risk Factors

UV Radiation
These studies suggest flight duties increase the risk for cutaneous malignancy. UV radiation is a known risk factor for skin cancer.¹² The main body of the aircraft may protect the cabin’s crew and passengers from UVR, but pilots are exposed to more UVR, especially in aircraft with larger windshields. A government study in 2007 examined the transmittance of UVR through windscreens of 8 aircraft: 3 commercial jets, 2 commercial propeller planes, 1 private jet, and 2 small propeller planes.¹³ UVB was attenuated by all the windscreens (<1% transmittance), but 43% to 54% of UVA was transmitted, with plastic windshields attenuating more than glass. Sanlorenzo et al¹⁴ measured UVA irradiance at the pilot’s seat of a turboprop aircraft at 30,000-ft altitude. They compared this exposure to a UVA tanning bed and estimated that 57 minutes of flight at 30,000-ft altitude was equivalent to 20 minutes inside a UVA tanning booth, a startling finding.¹⁴

Cosmic Radiation
Cosmic radiation consists of neutrons and gamma rays that originate outside Earth’s atmosphere. Pilots are exposed to higher doses of cosmic radiation than nonpilots, but the health effects are difficult to study. Boice et al¹⁵ described how factors such as altitude, latitude, and flight time determine pilots’ cumulative exposure. With longer flight times at higher altitudes, a pilot’s exposure to cosmic radiation is increasing over the years.¹⁵ A 2012 review found that aircrews have low-level cosmic radiation exposure. Despite increases in MM and NMSC in pilots and increased rates of breast cancer in female aircrew, overall cancer-related mortality was lower in flying versus nonflying controls.¹⁶ Thus, cosmic radiation may not be as onerous of an occupational hazard for pilots as has been postulated.

Altered Circadian Rhythms
Aviation duties, especially in the military, require irregular work schedules that repeatedly interfere with normal sleep-wake cycles, disrupt circadian rhythms, and lead to reduced melatonin levels.⁸ Evidence suggests that low levels of melatonin could increase the risk for breast and prostate cancer—both cancers that occur more frequently in female aircrew and male pilots, respectively—by reducing melatonin’s natural protective role in such malignancies.^17,18 A World Health Organization working group categorized shift work as “probably carcinogenic” and cited alterations of melatonin levels, changes in other circadian rhythm–related gene pathways, and relative immunosuppression as likely causative factors.¹⁹ In a 2011 study, exposing mice to UVR during times when nucleotide excision repair mechanisms were at their lowest activity caused an increased rate of skin cancers.²⁰ A 2014 review discussed how epidemiological studies of shift workers such as nurses, firefighters, pilots, and flight crews found contradictory data, but molecular studies show that circadian rhythm–linked repair and tumorigenesis mechanisms are altered by aberrations in the normal sleep-wake cycle.²¹

Cockpit Instrumentation
Electromagnetic energy from the flight instruments in the cockpit also could influence malignancy risk. Nicholas et al²² found magnetic field measurements within the cockpit to be 2 to 10 times that experienced within the home or office. However, no studies examining the health effects of cockpit flight instruments and magnetic fields were found.

Final Thoughts

It is important to counsel pilots on the generally recognized, nonaviation-specific risk factors of family history, skin type, and UVR exposure in the development of skin cancer. Additionally, it is important to explain the possible role of exposure to UVR at higher altitudes, cosmic radiation, and electromagnetic energy from cockpit instruments, as well as altered sleep-wake cycles. A pilot’s risk for MM may be twice that of matched controls, and the risk for NMSC could be higher.^8,11 Although the literature lacks specific recommendations for pilots, it is reasonable to screen pilots once per year to better assess their individual risk and encourage diligent use of sunscreen and sun-protective measures when flying. It also may be important to advocate for the development of engineering controls that decrease UVR transmittance through windscreens, particularly for aircraft flying at higher altitudes for longer flights. More research is needed to determine if changes in circadian rhythm and decreases in melatonin increase skin cancer risk, which could impact how pilots’ schedules are managed. Together, we can ensure adequate surveillance, diagnosis, and treatment in this at-risk population.

Military dermatologists are charged with caring for a diverse population of active-duty members, civilian dependents, and military retirees. Although certain risk factors for cutaneous malignancies are common in all of these groups, the active-duty population experiences unique exposures to be considered when determining their risk for skin cancer. One subset that may be at a higher risk is military pilots who fly at high altitudes on irregular schedules in austere environments. Through the unparalleled comradeship inherent in many military units, pilots “hear” from their fellow pilots that they are at increased risk for skin cancer. Do their occupational exposures translate into increased risk for cutaneous malignancy? This article will survey the literature pertaining to pilots and skin cancer so that all dermatologists may better care for this unique population.

Epidemiology

Anecdotally, we have observed basal cell carcinoma in pilots in their 20s and early 30s, earlier than would be expected in an otherwise healthy prescreened military population.¹ Woolley and Hughes² published a case report of skin cancer in a young military aviator. The patient was a 32-year-old male helicopter pilot with Fitzpatrick skin type II and no personal or family history of skin cancer who was diagnosed with a periocular nodular basal cell carcinoma. He deployed to locations with high UV radiation (UVR) indices, and his vacation time also was spent in such areas.² UV radiation exposure and Fitzpatrick skin type are known risk factors across occupations, but are there special exposures that come with military aviation service?

To better understand the risk for malignancy in this special population, the US Air Force examined the rates of all cancer types among a cohort of flying versus nonflying officers.³ Aviation personnel showed increased incidence of testicular, bladder, and all-site cancers combined. Noticeably absent was a statistically significant increased risk for malignant melanoma (MM) and nonmelanoma skin cancer (NMSC). Other epidemiological studies examined the incidence rates of MM in the US Armed Forces compared with age- and race-matched civilian populations and showed mixed results: 2 studies showed increased risk,^4,5 while a third showed decreased risk.⁶ Despite finding opposite results of MM rates in military members versus the civilian population, 2 of these studies showed US Air Force members to have higher rates of MM than those in the US Army or Navy.^4,6 Interestingly, the air force has the highest number of pilots among all the services, with 4000 more pilots than the army and navy.⁷ Further studies are needed to determine if the higher air force MM rates occur in pilots.

Although there are mixed and limited data pertaining to military flight crews, there is more robust literature concerning civilian flight personnel. One meta-analysis pooled studies related to cancer risk in cabin crews and civil and military pilots.⁸ In military pilots, they found a standardized incidence ratio (SIR) of 1.43 (95% confidence interval [CI], 1.09-1.87) for MM and 1.80 (95% CI, 1.25-2.80) for NMSC. The SIRs were higher for male cabin attendants (3.42 and 7.46, respectively) and civil pilots (2.18 and 1.88, respectively). They also found the most common cause of mortality in civilian cabin crews was AIDS, possibly explaining the higher SIRs for all types of malignancy in that population.⁸ In the United States, many civilian pilots previously were military pilots⁹ who likely served in the military for at least 10 years.¹⁰ A 2015 meta-analysis of 19 studies of more than 266,000 civil pilots and aircrew members found an SIR for MM of 2.22 (95% CI, 1.67-2.93) for civil pilots and 2.09 (95% CI, 1.67-2.62) for aircrews, stating the risk for MM is at least twice that of the general population.¹¹

Risk Factors

UV Radiation
These studies suggest flight duties increase the risk for cutaneous malignancy. UV radiation is a known risk factor for skin cancer.¹² The main body of the aircraft may protect the cabin’s crew and passengers from UVR, but pilots are exposed to more UVR, especially in aircraft with larger windshields. A government study in 2007 examined the transmittance of UVR through windscreens of 8 aircraft: 3 commercial jets, 2 commercial propeller planes, 1 private jet, and 2 small propeller planes.¹³ UVB was attenuated by all the windscreens (<1% transmittance), but 43% to 54% of UVA was transmitted, with plastic windshields attenuating more than glass. Sanlorenzo et al¹⁴ measured UVA irradiance at the pilot’s seat of a turboprop aircraft at 30,000-ft altitude. They compared this exposure to a UVA tanning bed and estimated that 57 minutes of flight at 30,000-ft altitude was equivalent to 20 minutes inside a UVA tanning booth, a startling finding.¹⁴

Cosmic Radiation
Cosmic radiation consists of neutrons and gamma rays that originate outside Earth’s atmosphere. Pilots are exposed to higher doses of cosmic radiation than nonpilots, but the health effects are difficult to study. Boice et al¹⁵ described how factors such as altitude, latitude, and flight time determine pilots’ cumulative exposure. With longer flight times at higher altitudes, a pilot’s exposure to cosmic radiation is increasing over the years.¹⁵ A 2012 review found that aircrews have low-level cosmic radiation exposure. Despite increases in MM and NMSC in pilots and increased rates of breast cancer in female aircrew, overall cancer-related mortality was lower in flying versus nonflying controls.¹⁶ Thus, cosmic radiation may not be as onerous of an occupational hazard for pilots as has been postulated.

Altered Circadian Rhythms
Aviation duties, especially in the military, require irregular work schedules that repeatedly interfere with normal sleep-wake cycles, disrupt circadian rhythms, and lead to reduced melatonin levels.⁸ Evidence suggests that low levels of melatonin could increase the risk for breast and prostate cancer—both cancers that occur more frequently in female aircrew and male pilots, respectively—by reducing melatonin’s natural protective role in such malignancies.^17,18 A World Health Organization working group categorized shift work as “probably carcinogenic” and cited alterations of melatonin levels, changes in other circadian rhythm–related gene pathways, and relative immunosuppression as likely causative factors.¹⁹ In a 2011 study, exposing mice to UVR during times when nucleotide excision repair mechanisms were at their lowest activity caused an increased rate of skin cancers.²⁰ A 2014 review discussed how epidemiological studies of shift workers such as nurses, firefighters, pilots, and flight crews found contradictory data, but molecular studies show that circadian rhythm–linked repair and tumorigenesis mechanisms are altered by aberrations in the normal sleep-wake cycle.²¹

Cockpit Instrumentation
Electromagnetic energy from the flight instruments in the cockpit also could influence malignancy risk. Nicholas et al²² found magnetic field measurements within the cockpit to be 2 to 10 times that experienced within the home or office. However, no studies examining the health effects of cockpit flight instruments and magnetic fields were found.

Final Thoughts

It is important to counsel pilots on the generally recognized, nonaviation-specific risk factors of family history, skin type, and UVR exposure in the development of skin cancer. Additionally, it is important to explain the possible role of exposure to UVR at higher altitudes, cosmic radiation, and electromagnetic energy from cockpit instruments, as well as altered sleep-wake cycles. A pilot’s risk for MM may be twice that of matched controls, and the risk for NMSC could be higher.^8,11 Although the literature lacks specific recommendations for pilots, it is reasonable to screen pilots once per year to better assess their individual risk and encourage diligent use of sunscreen and sun-protective measures when flying. It also may be important to advocate for the development of engineering controls that decrease UVR transmittance through windscreens, particularly for aircraft flying at higher altitudes for longer flights. More research is needed to determine if changes in circadian rhythm and decreases in melatonin increase skin cancer risk, which could impact how pilots’ schedules are managed. Together, we can ensure adequate surveillance, diagnosis, and treatment in this at-risk population.

Atypical fibroxanthoma (AFX) is a low-grade dermal malignancy comprised of atypical spindle cells.¹ Classified as a superficial fibrohistiocytic tumor with intermediate malignant potential, AFX has an incidence of approximately 0.24% worldwide.² The tumor appears mainly on the head and neck in sun-exposed areas but can occur less frequently on the trunk and limbs in non–sun-exposed areas. There is a 70% to 80% predominance in men aged 69 to 77 years, with lesions primarily occurring in sun-exposed areas of the head and neck.³ A median period of 4 months between time of onset and time of diagnosis has been previously established.⁴

When AFX does occur in non–sun-exposed areas, it tends to be in a younger patient population. Clinically, it presents as a rather nondescript, firm, erythematous papule or nodule less than 2 cm in diameter. Atypical fibroxanthoma most often presents asymptomatically, but the tumor may ulcerate and bleed, though pain and pruritus are uncommon.5 Findings are nonspecific, and the diagnosis must be confirmed with biopsy, as it can resemble other common dermatological lesions. The pathogenesis of AFX has been controversial. Two different studies looked at AFX using electron microscopy and concluded that the tumor most closely resembled a myofibroblast,^6,7 which is consistent with current thinking today.

Atypical fibroxanthoma is believed to be associated with p53 mutation and is closely linked with exposure to UV radiation due to its predominance in sun-exposed areas. Other predisposing factors may include prior exposure to UV radiation, history of organ transplantation, immunosuppression, advanced age in men, and xeroderma pigmentosum. The differential diagnosis for AFX encompasses basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, adnexal tumor, and pyogenic granuloma.

Case Report

A 93-year-old man was referred to our clinic for treatment of erosive pustular dermatosis of the scalp with photodynamic therapy (PDT). He had a more than 20-year history of multiple skin lesions including basal cell carcinoma, squamous cell carcinoma, and actinic keratoses (AKs). For one year prior to the current presentation the patient had concerns of pustules, scaling, itching, and scabbing on the scalp. The patient admitted that the pruritus caused him to pick at the scabs on the scalp. He had previously been treated with lactic acid 12% neutralized with ammonium hydroxide, tacrolimus, and halobetasol, all to no avail.

On physical examination, the lesions appeared erosive with crusting and granulation tissue (Figure 1A). The presentation was consistent with erosive pustular dermatosis of the scalp. Biopsy revealed granulation tissue. The patient underwent PDT and prednisone treatment with improvement. Additional biopsies revealed AKs. His condition improved with 2 PDT sessions but never fully cleared. During the PDT sessions, the patient reported intense unilateral headaches without visual changes. The headaches were intermittent and not apparently related to the treatments. He was referred for a temporal artery biopsy and rebiopsy of the remaining lesion on the scalp. The temporal artery biopsy was negative. The lesion that remained was a large nodule on the vertex scalp, and biopsy revealed AFX.

Immunohistochemical marker studies for S-100 and cytokeratin were negative. Invasion into subcutaneous fat was encountered (Figure 2A). Highly atypical spindle cells and mitoses were present (Figure 2B). Neoplastic cells were noted adjacent to nerve (Figure 2C). Excision of the lesion was curative, and his symptoms of pain and erosive pustular dermatosis resolved weeks thereafter (Figure 1B). The area of erosive pustular dermatosis was not excised, but symptoms resolved weeks following excision of the AFX.

Comment

Our case of AFX is unique due to the patient’s atypical presentation of severe pain. Because AFX usually presents asymptomatically, pain is an uncommon symptom. Based on the histologic findings in our case, we suspected that neural involvement of the tumor most likely explained the intense pain that our patient experienced.

The presence of erosive pustular dermatosis of the scalp also is interesting in our case. This elderly man had an extensive history of actinic damage and had reported pustules, scaling, itching, and scabbing of the scalp. It is possible that erosive pustular dermatosis was superimposed over the tumor and could have been the reason that multiple biopsies were needed to eventually arrive at a diagnosis. The coexistence of the 2 entities suggests that the chronic actinic damage played a role in the etiology of both.

Classification
There is a question regarding nomenclature when discussing AFX. Atypical fibroxanthoma has been referred to as a variant of undifferentiated pleomorphic sarcoma, which is a type of soft tissue sarcoma. Atypical fibroxanthoma can be referred to as undifferentiated pleomorphic sarcoma if it is more than 2 cm in diameter, if it involves the fascia or subcutaneous tissue, or if there is evidence of necrosis.³ Atypical fibroxanthoma generally is confined to the head and neck region and usually is less than 2 cm in diameter. In this patient, the presentation was consistent with AFX, as there was evidence of necrosis and invasion into the subcutaneous fat. The fact that the lesion also appeared on the scalp further supported the diagnosis of AFX.

Pathology
Biopsy of AFX typically reveals a spindle cell proliferation that usually arises in the setting of profound actinic damage. The epidermis may or may not be ulcerated, and in most cases, it is seen in close proximity to the overlying epidermis but not arising from it.8 Classic AFX is composed of highly atypical histiocytelike (epithelioid) cells admixed with pleomorphic spindle cells and giant cells, all showing frequent mitoses including atypical ones.9 Several histologic subtypes of AFX have been described, including clear cell, granular cell, pigmented cell, chondroid, osteoid, osteoclastic, and the most common spindle cell subtype.9 Features that indicate potential aggressive behavior include infiltration into the subcutaneous tissue, vascular invasion, and presence of necrosis. A diagnosis of AFX is made by exclusion of other malignant neoplasms with similar morphology, namely spindle cell squamous cell carcinoma, spindle cell melanoma, and leiomyoscarcoma.9 As such, immunohistochemistry plays a critical role in distinguishing these lesions, as they arise as part of the differential diagnosis. A panel of immunohistochemical stains is helpful for diagnosis and commonly includes but is not limited to S-100, Melan-A, smooth muscle actin, desmin, and cytokeratin.

Sampling error is an inherent flaw in any biopsy specimen. The eventual diagnosis of AFX in our case supports the argument for multiple biopsies of an unknown lesion, seeing as the affected area was interpreted as both granulation tissue and AK prior to the eventual diagnosis. Repeat biopsies, especially if a lesion is nonhealing, often can help clinicians arrive at a definitive diagnosis.

Treatment
Different treatment options have been used to manage AFX. Mohs micrographic surgery is most often used because of its tissue-sparing potential, often giving the most cosmetically appealing result. Wide local excision is another surgical technique utilized, generally with fixed margins of at least 1 cm.¹⁰ Radiation at the tumor site is used as a treatment method but most often during cases of reoccurrence. Cryotherapy as well as electrodesiccation and curettage are possible treatment options but are not the standard of care.

Atypical fibroxanthoma (AFX) is a low-grade dermal malignancy comprised of atypical spindle cells.¹ Classified as a superficial fibrohistiocytic tumor with intermediate malignant potential, AFX has an incidence of approximately 0.24% worldwide.² The tumor appears mainly on the head and neck in sun-exposed areas but can occur less frequently on the trunk and limbs in non–sun-exposed areas. There is a 70% to 80% predominance in men aged 69 to 77 years, with lesions primarily occurring in sun-exposed areas of the head and neck.³ A median period of 4 months between time of onset and time of diagnosis has been previously established.⁴

When AFX does occur in non–sun-exposed areas, it tends to be in a younger patient population. Clinically, it presents as a rather nondescript, firm, erythematous papule or nodule less than 2 cm in diameter. Atypical fibroxanthoma most often presents asymptomatically, but the tumor may ulcerate and bleed, though pain and pruritus are uncommon.5 Findings are nonspecific, and the diagnosis must be confirmed with biopsy, as it can resemble other common dermatological lesions. The pathogenesis of AFX has been controversial. Two different studies looked at AFX using electron microscopy and concluded that the tumor most closely resembled a myofibroblast,^6,7 which is consistent with current thinking today.

Atypical fibroxanthoma is believed to be associated with p53 mutation and is closely linked with exposure to UV radiation due to its predominance in sun-exposed areas. Other predisposing factors may include prior exposure to UV radiation, history of organ transplantation, immunosuppression, advanced age in men, and xeroderma pigmentosum. The differential diagnosis for AFX encompasses basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, adnexal tumor, and pyogenic granuloma.

Case Report

A 93-year-old man was referred to our clinic for treatment of erosive pustular dermatosis of the scalp with photodynamic therapy (PDT). He had a more than 20-year history of multiple skin lesions including basal cell carcinoma, squamous cell carcinoma, and actinic keratoses (AKs). For one year prior to the current presentation the patient had concerns of pustules, scaling, itching, and scabbing on the scalp. The patient admitted that the pruritus caused him to pick at the scabs on the scalp. He had previously been treated with lactic acid 12% neutralized with ammonium hydroxide, tacrolimus, and halobetasol, all to no avail.

On physical examination, the lesions appeared erosive with crusting and granulation tissue (Figure 1A). The presentation was consistent with erosive pustular dermatosis of the scalp. Biopsy revealed granulation tissue. The patient underwent PDT and prednisone treatment with improvement. Additional biopsies revealed AKs. His condition improved with 2 PDT sessions but never fully cleared. During the PDT sessions, the patient reported intense unilateral headaches without visual changes. The headaches were intermittent and not apparently related to the treatments. He was referred for a temporal artery biopsy and rebiopsy of the remaining lesion on the scalp. The temporal artery biopsy was negative. The lesion that remained was a large nodule on the vertex scalp, and biopsy revealed AFX.

Immunohistochemical marker studies for S-100 and cytokeratin were negative. Invasion into subcutaneous fat was encountered (Figure 2A). Highly atypical spindle cells and mitoses were present (Figure 2B). Neoplastic cells were noted adjacent to nerve (Figure 2C). Excision of the lesion was curative, and his symptoms of pain and erosive pustular dermatosis resolved weeks thereafter (Figure 1B). The area of erosive pustular dermatosis was not excised, but symptoms resolved weeks following excision of the AFX.

Comment

Our case of AFX is unique due to the patient’s atypical presentation of severe pain. Because AFX usually presents asymptomatically, pain is an uncommon symptom. Based on the histologic findings in our case, we suspected that neural involvement of the tumor most likely explained the intense pain that our patient experienced.

The presence of erosive pustular dermatosis of the scalp also is interesting in our case. This elderly man had an extensive history of actinic damage and had reported pustules, scaling, itching, and scabbing of the scalp. It is possible that erosive pustular dermatosis was superimposed over the tumor and could have been the reason that multiple biopsies were needed to eventually arrive at a diagnosis. The coexistence of the 2 entities suggests that the chronic actinic damage played a role in the etiology of both.

Classification
There is a question regarding nomenclature when discussing AFX. Atypical fibroxanthoma has been referred to as a variant of undifferentiated pleomorphic sarcoma, which is a type of soft tissue sarcoma. Atypical fibroxanthoma can be referred to as undifferentiated pleomorphic sarcoma if it is more than 2 cm in diameter, if it involves the fascia or subcutaneous tissue, or if there is evidence of necrosis.³ Atypical fibroxanthoma generally is confined to the head and neck region and usually is less than 2 cm in diameter. In this patient, the presentation was consistent with AFX, as there was evidence of necrosis and invasion into the subcutaneous fat. The fact that the lesion also appeared on the scalp further supported the diagnosis of AFX.

Pathology
Biopsy of AFX typically reveals a spindle cell proliferation that usually arises in the setting of profound actinic damage. The epidermis may or may not be ulcerated, and in most cases, it is seen in close proximity to the overlying epidermis but not arising from it.8 Classic AFX is composed of highly atypical histiocytelike (epithelioid) cells admixed with pleomorphic spindle cells and giant cells, all showing frequent mitoses including atypical ones.9 Several histologic subtypes of AFX have been described, including clear cell, granular cell, pigmented cell, chondroid, osteoid, osteoclastic, and the most common spindle cell subtype.9 Features that indicate potential aggressive behavior include infiltration into the subcutaneous tissue, vascular invasion, and presence of necrosis. A diagnosis of AFX is made by exclusion of other malignant neoplasms with similar morphology, namely spindle cell squamous cell carcinoma, spindle cell melanoma, and leiomyoscarcoma.9 As such, immunohistochemistry plays a critical role in distinguishing these lesions, as they arise as part of the differential diagnosis. A panel of immunohistochemical stains is helpful for diagnosis and commonly includes but is not limited to S-100, Melan-A, smooth muscle actin, desmin, and cytokeratin.

Sampling error is an inherent flaw in any biopsy specimen. The eventual diagnosis of AFX in our case supports the argument for multiple biopsies of an unknown lesion, seeing as the affected area was interpreted as both granulation tissue and AK prior to the eventual diagnosis. Repeat biopsies, especially if a lesion is nonhealing, often can help clinicians arrive at a definitive diagnosis.

Treatment
Different treatment options have been used to manage AFX. Mohs micrographic surgery is most often used because of its tissue-sparing potential, often giving the most cosmetically appealing result. Wide local excision is another surgical technique utilized, generally with fixed margins of at least 1 cm.¹⁰ Radiation at the tumor site is used as a treatment method but most often during cases of reoccurrence. Cryotherapy as well as electrodesiccation and curettage are possible treatment options but are not the standard of care.

Atypical fibroxanthoma (AFX) is a low-grade dermal malignancy comprised of atypical spindle cells.¹ Classified as a superficial fibrohistiocytic tumor with intermediate malignant potential, AFX has an incidence of approximately 0.24% worldwide.² The tumor appears mainly on the head and neck in sun-exposed areas but can occur less frequently on the trunk and limbs in non–sun-exposed areas. There is a 70% to 80% predominance in men aged 69 to 77 years, with lesions primarily occurring in sun-exposed areas of the head and neck.³ A median period of 4 months between time of onset and time of diagnosis has been previously established.⁴

When AFX does occur in non–sun-exposed areas, it tends to be in a younger patient population. Clinically, it presents as a rather nondescript, firm, erythematous papule or nodule less than 2 cm in diameter. Atypical fibroxanthoma most often presents asymptomatically, but the tumor may ulcerate and bleed, though pain and pruritus are uncommon.5 Findings are nonspecific, and the diagnosis must be confirmed with biopsy, as it can resemble other common dermatological lesions. The pathogenesis of AFX has been controversial. Two different studies looked at AFX using electron microscopy and concluded that the tumor most closely resembled a myofibroblast,^6,7 which is consistent with current thinking today.

Atypical fibroxanthoma is believed to be associated with p53 mutation and is closely linked with exposure to UV radiation due to its predominance in sun-exposed areas. Other predisposing factors may include prior exposure to UV radiation, history of organ transplantation, immunosuppression, advanced age in men, and xeroderma pigmentosum. The differential diagnosis for AFX encompasses basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, adnexal tumor, and pyogenic granuloma.

Case Report

A 93-year-old man was referred to our clinic for treatment of erosive pustular dermatosis of the scalp with photodynamic therapy (PDT). He had a more than 20-year history of multiple skin lesions including basal cell carcinoma, squamous cell carcinoma, and actinic keratoses (AKs). For one year prior to the current presentation the patient had concerns of pustules, scaling, itching, and scabbing on the scalp. The patient admitted that the pruritus caused him to pick at the scabs on the scalp. He had previously been treated with lactic acid 12% neutralized with ammonium hydroxide, tacrolimus, and halobetasol, all to no avail.

On physical examination, the lesions appeared erosive with crusting and granulation tissue (Figure 1A). The presentation was consistent with erosive pustular dermatosis of the scalp. Biopsy revealed granulation tissue. The patient underwent PDT and prednisone treatment with improvement. Additional biopsies revealed AKs. His condition improved with 2 PDT sessions but never fully cleared. During the PDT sessions, the patient reported intense unilateral headaches without visual changes. The headaches were intermittent and not apparently related to the treatments. He was referred for a temporal artery biopsy and rebiopsy of the remaining lesion on the scalp. The temporal artery biopsy was negative. The lesion that remained was a large nodule on the vertex scalp, and biopsy revealed AFX.

Immunohistochemical marker studies for S-100 and cytokeratin were negative. Invasion into subcutaneous fat was encountered (Figure 2A). Highly atypical spindle cells and mitoses were present (Figure 2B). Neoplastic cells were noted adjacent to nerve (Figure 2C). Excision of the lesion was curative, and his symptoms of pain and erosive pustular dermatosis resolved weeks thereafter (Figure 1B). The area of erosive pustular dermatosis was not excised, but symptoms resolved weeks following excision of the AFX.

Comment

Our case of AFX is unique due to the patient’s atypical presentation of severe pain. Because AFX usually presents asymptomatically, pain is an uncommon symptom. Based on the histologic findings in our case, we suspected that neural involvement of the tumor most likely explained the intense pain that our patient experienced.

The presence of erosive pustular dermatosis of the scalp also is interesting in our case. This elderly man had an extensive history of actinic damage and had reported pustules, scaling, itching, and scabbing of the scalp. It is possible that erosive pustular dermatosis was superimposed over the tumor and could have been the reason that multiple biopsies were needed to eventually arrive at a diagnosis. The coexistence of the 2 entities suggests that the chronic actinic damage played a role in the etiology of both.

Classification
There is a question regarding nomenclature when discussing AFX. Atypical fibroxanthoma has been referred to as a variant of undifferentiated pleomorphic sarcoma, which is a type of soft tissue sarcoma. Atypical fibroxanthoma can be referred to as undifferentiated pleomorphic sarcoma if it is more than 2 cm in diameter, if it involves the fascia or subcutaneous tissue, or if there is evidence of necrosis.³ Atypical fibroxanthoma generally is confined to the head and neck region and usually is less than 2 cm in diameter. In this patient, the presentation was consistent with AFX, as there was evidence of necrosis and invasion into the subcutaneous fat. The fact that the lesion also appeared on the scalp further supported the diagnosis of AFX.

Pathology
Biopsy of AFX typically reveals a spindle cell proliferation that usually arises in the setting of profound actinic damage. The epidermis may or may not be ulcerated, and in most cases, it is seen in close proximity to the overlying epidermis but not arising from it.8 Classic AFX is composed of highly atypical histiocytelike (epithelioid) cells admixed with pleomorphic spindle cells and giant cells, all showing frequent mitoses including atypical ones.9 Several histologic subtypes of AFX have been described, including clear cell, granular cell, pigmented cell, chondroid, osteoid, osteoclastic, and the most common spindle cell subtype.9 Features that indicate potential aggressive behavior include infiltration into the subcutaneous tissue, vascular invasion, and presence of necrosis. A diagnosis of AFX is made by exclusion of other malignant neoplasms with similar morphology, namely spindle cell squamous cell carcinoma, spindle cell melanoma, and leiomyoscarcoma.9 As such, immunohistochemistry plays a critical role in distinguishing these lesions, as they arise as part of the differential diagnosis. A panel of immunohistochemical stains is helpful for diagnosis and commonly includes but is not limited to S-100, Melan-A, smooth muscle actin, desmin, and cytokeratin.

Sampling error is an inherent flaw in any biopsy specimen. The eventual diagnosis of AFX in our case supports the argument for multiple biopsies of an unknown lesion, seeing as the affected area was interpreted as both granulation tissue and AK prior to the eventual diagnosis. Repeat biopsies, especially if a lesion is nonhealing, often can help clinicians arrive at a definitive diagnosis.

Treatment
Different treatment options have been used to manage AFX. Mohs micrographic surgery is most often used because of its tissue-sparing potential, often giving the most cosmetically appealing result. Wide local excision is another surgical technique utilized, generally with fixed margins of at least 1 cm.¹⁰ Radiation at the tumor site is used as a treatment method but most often during cases of reoccurrence. Cryotherapy as well as electrodesiccation and curettage are possible treatment options but are not the standard of care.

SAN FRANCISCO – Patients with high-risk keratinocyte carcinomas sometimes present with neurologic symptoms mimicking Bell’s palsy or trigeminal neuralgia, making the diagnosis of these perineural tumors challenging, Siegrid Yu, MD, said at the annual meeting of the Pacific Dermatologic Association.

Eventually, skin manifestations can land them in a dermatologist’s office. “There is a high incidence of delayed diagnosis and misdiagnosis, which affects the outcome of these patients,” said Dr. Yu of the department of dermatology, University of California, San Francisco.

She presented several cases illustrating the central role that dermatologists can play in the diagnosis and management of high-risk keratinocyte carcinomas. “All of these patients were seen by various doctors, sometimes multiple times, without a diagnosis,” she said.

Perineural invasion occurs in 2.6%-6% of squamous cell carcinoma (SCC) cases and 2% of basal cell carcinoma (BCC) cases. “Perineural invasion presenting with neurologic symptoms is not that common, which is part of why I think it’s easy to misdiagnose these patients,” said Dr. Yu, director of the Mohs Micrographic Surgery and Cutaneous Oncology Fellowship at the UCSF Dermatologic Surgery and Laser Center. In many cases, patients were diagnosed as having Bell’s palsy or trigeminal neuralgia for years before being diagnosed with skin cancer.

SAN FRANCISCO – Patients with high-risk keratinocyte carcinomas sometimes present with neurologic symptoms mimicking Bell’s palsy or trigeminal neuralgia, making the diagnosis of these perineural tumors challenging, Siegrid Yu, MD, said at the annual meeting of the Pacific Dermatologic Association.

Eventually, skin manifestations can land them in a dermatologist’s office. “There is a high incidence of delayed diagnosis and misdiagnosis, which affects the outcome of these patients,” said Dr. Yu of the department of dermatology, University of California, San Francisco.

She presented several cases illustrating the central role that dermatologists can play in the diagnosis and management of high-risk keratinocyte carcinomas. “All of these patients were seen by various doctors, sometimes multiple times, without a diagnosis,” she said.

Perineural invasion occurs in 2.6%-6% of squamous cell carcinoma (SCC) cases and 2% of basal cell carcinoma (BCC) cases. “Perineural invasion presenting with neurologic symptoms is not that common, which is part of why I think it’s easy to misdiagnose these patients,” said Dr. Yu, director of the Mohs Micrographic Surgery and Cutaneous Oncology Fellowship at the UCSF Dermatologic Surgery and Laser Center. In many cases, patients were diagnosed as having Bell’s palsy or trigeminal neuralgia for years before being diagnosed with skin cancer.

SAN FRANCISCO – Patients with high-risk keratinocyte carcinomas sometimes present with neurologic symptoms mimicking Bell’s palsy or trigeminal neuralgia, making the diagnosis of these perineural tumors challenging, Siegrid Yu, MD, said at the annual meeting of the Pacific Dermatologic Association.

Eventually, skin manifestations can land them in a dermatologist’s office. “There is a high incidence of delayed diagnosis and misdiagnosis, which affects the outcome of these patients,” said Dr. Yu of the department of dermatology, University of California, San Francisco.

She presented several cases illustrating the central role that dermatologists can play in the diagnosis and management of high-risk keratinocyte carcinomas. “All of these patients were seen by various doctors, sometimes multiple times, without a diagnosis,” she said.

Perineural invasion occurs in 2.6%-6% of squamous cell carcinoma (SCC) cases and 2% of basal cell carcinoma (BCC) cases. “Perineural invasion presenting with neurologic symptoms is not that common, which is part of why I think it’s easy to misdiagnose these patients,” said Dr. Yu, director of the Mohs Micrographic Surgery and Cutaneous Oncology Fellowship at the UCSF Dermatologic Surgery and Laser Center. In many cases, patients were diagnosed as having Bell’s palsy or trigeminal neuralgia for years before being diagnosed with skin cancer.

Optical coherence tomography (OCT) is a noninvasive imaging technique that is cleared by the US Food and Drug Administration as a 510(k) class II regulatory device to visualize biological tissues in vivo and in real time^.1-3 In July 2017, OCT received 2 category III Current Procedural Terminology (CPT) codes from the American Medical Association—0470T and 0471T—enabling physicians to report and track the usage of this emerging imaging method.⁴ Category III CPT codes remain investigational and therefore are not easily reimbursed by insurance.⁵ The goal of OCT manufacturers and providers within the next 5 years is to upgrade to category I coding before the present codes are archived. Although documented advantages of OCT include its unique ability to effectively differentiate and monitor skin lesions throughout nonsurgical treatment as well as to efficiently delineate presurgical margins, additional research reporting its efficacy may facilitate the coding conversion and encourage greater usage of OCT technology. We present a brief review of OCT imaging in dermatology, including its indications and limitations.

RELATED VIDEO: Imaging Overview: Report From the Mount Sinai Fall Symposium

Types of OCT

Optical coherence tomography, based on the principle of low-coherence interferometry, uses infrared light to extract fine details from within highly scattering turbid media to visualize the subsurface of the skin.² Since its introduction for use in dermatology, OCT has been used to study skin in both the research and clinical settings.^2,3 Current OCT devices on the market are mobile and easy to use in a busy dermatology practice. The Table reviews the most commonly used noninvasive imaging tools for the skin, depicting the inverse relationship between penetration depth and cellular resolution as well as field of view discrepancies.^2,6-8 Optical coherence tomography technology collects cross-sectional (vertical) images similar to histology and en face (horizontal) images similar to reflective confocal microscopy (RCM) of skin areas with adequate cellular resolution and without compromising penetration depth as well as a field of view comparable to the probe aperture contacting the skin.

RELATED VIDEO: Noninvasive Imaging: Report From the Mount Sinai Fall Symposium

Conventional OCT
Due to multiple simultaneous beams, conventional frequency-domain OCT (FD-OCT) provides enhanced lateral resolution of 7.5 to 15 µm and axial resolution of 5 to 10 µm with a field of view of 6.0×6.0 mm² and depth of 1.5 to 2.0 mm.^2,6,8 Conventional FD-OCT detects architectural details within tissue with better cellular clarity than high-frequency ultrasound and better depth than RCM, yet FD-OCT is not sufficient to distinguish individual cells.

Dynamic OCT
The recent development of dynamic OCT (D-OCT) software based on speckle-variance has the added ability to visualize the skin microvasculature and therefore detect blood vessels and their distribution within specific lesions. This angiographic variant of FD-OCT detects motion corresponding to blood flow in the images and may enhance diagnostic accuracy, particularly in the differentiation of nevi and malignant melanomas.^8-11

High-Definition OCT
High-definition OCT (HD-OCT), a hybrid of RCM and FD-OCT, provides improved optical resolution of 3 μm for both lateral and axial imaging approaching a resolution similar to RCM making it possible to visualize individual cells, though at the expense of lower penetration depth of 0.5 to 1.0 mm and reduced field of view of 1.8×1.5 mm² to FD-OCT. High-definition OCT combines 2 different views to produce a 3-dimensional image for additional data interpretation (Table).^7,8,12

Current CPT Guidelines

Two category III CPT codes—0470T and 0471T—allow the medical community to collect and track the usage of the emerging OCT technology. Code 0470T is used for microstructural and morphological skin imaging, specifically acquisition, interpretation, and reading of the images. Code 0471T is used for each additional skin lesion imaged.⁴

Current Procedural Terminology category III codes remain investigational in contrast to the permanent category I codes. Reimbursement for CPT III codes is difficult because it is not generally an accepted service covered by insurance.⁵ The goal within the next 5 years is to convert to category I CPT codes, meanwhile the CPT III codes should encourage increased utilization of OCT technology.

Indications for OCT

Depiction of Healthy Versus Diseased Skin
Optical coherence tomography is a valuable tool in visualizing normal skin morphology including principal skin layers, namely the dermis, epidermis, and dermoepidermal junction, as well as structures such as hair follicles, blood vessels, and glands.^2,13 The OCT images show architectural changes of the skin layers and can be used to differentiate abnormal from normal tissue in vivo.²

Diagnosis and Treatment Monitoring of Skin Cancers
Optical coherence tomography is well established for use in the diagnosis and management of nonmelanoma skin cancers and to determine clinical end points of nonsurgical treatment without the need for skin biopsy. Promising diagnostic criteria have been developed for nonmelanoma skin cancers including basal cell carcinoma (BCC) and squamous cell carcinoma, as well as premalignant actinic keratoses using FD-OCT and the newer D-OCT and HD-OCT devices.^9-17 For example, FD-OCT offers improved diagnosis of lesions suspicious for BCC, the most common type of skin cancer, showing improved sensitivity (79%–96%) and specificity (75%–96%) when compared with clinical assessment and dermoscopy alone.^12,14 Typical OCT features differentiating BCC from other lesions include hyporeflective ovoid nests with a dark rim and an alteration of the dermoepidermal junction. In addition to providing a good diagnostic overview of skin, OCT devices show promise in monitoring the effects of treatment on primary and recurrent lesions.^14-16

In Vivo Excision Planning
Additionally, OCT is a helpful tool in delineating tumor margins prior to surgical resection to achieve optimal cosmesis. By detecting subclinical tumor extension, this preoperative technique has been shown to reduce the number of surgical stages. Pomerantz et al¹⁷ showed that mapping BCC tumor margins with OCT prior to Mohs micrographic surgery closely approximated the final surgical defects. Alawi et al¹⁸ showed that the OCT-defined lateral margins correctly indicated complete removal of tumors. These studies illustrate the ability of OCT to minimize the amount of skin excised without compromising the integrity of tumor-free borders. The use of ex vivo OCT to detect residual tumors is not recommended based on current studies.^6,17,18

Diagnosis and Treatment Monitoring of Other Diseases
Further applications of OCT include diagnosis of noncancerous lesions such as nail conditions, scleroderma, psoriatic arthritis, blistering diseases, and vascular lesions, as well as assessment of skin moisture and hydration, burn depth, wound healing, skin atrophy, and UV damage.² For example, Aldahan et al¹⁹ demonstrated the utility of D-OCT to identify structural and vascular features specific to nail psoriasis useful in the diagnosis and treatment monitoring of the condition.

Limitations of OCT

Resolution
Frequency-domain OCT enables the detection of architectural details within tissue, but its image resolution is not sufficient to distinguish individual cells, therefore restricting its use in evaluating pigmented benign and malignant lesions such as dysplastic nevi and melanomas. Higher-resolution RCM is superior for imaging these lesions, as its device can better evaluate microscopic structures. With the advent of D-OCT and HD-OCT, research is being conducted to assess their use in differentiating pigmented lesions.^8,20 Schuh et a^l9 and Gambichler et al²⁰ reported preliminary results indicating the utility of D-OCT and HD-OCT to differentiate dysplastic nevi from melanomas and melanoma in situ, respectively.

Depth Measurement
Another limitation is associated with measuring lesion depth for advanced tumors. Although the typical imaging depth of OCT is significantly deeper than most other noninvasive imaging modalities used on skin, imaging deep tumor margins and invasion is restricted.

Image Interpretation
Diagnostic imaging requires image interpretation leading to potential interobserver and intraobserver variation. Experienced observers in OCT more accurately differentiated normal from lesional skin compared to novices, which suggests that training could improve agreement.^21,22

Reimbursement and Device Cost
Other practical limitations to widespread OCT utilization at this time include its initial laser device cost and lack of reimbursement. As such, large academic and research centers remain the primary sites to utilize these devices.

Future Directions

Optical coherence tomography complements other established noninvasive imaging tools allowing for real-time visualization of the skin without interfering with the tissue and offering images with a good balance of depth, resolution, and field of view. Although a single histology cut has superior cellular resolution to any imaging modality, OCT provides additional information that is not provided by a physical biopsy, given the multiple vertical sections of data. Optical coherence tomography is a useful diagnostic technique enabling patients to avoid unnecessary biopsies while increasing early lesion diagnosis. Furthermore, OCT helps to decrease repetitive biopsies throughout nonsurgical treatments. With the availability of newer technology such as D-OCT and HD-OCT, OCT will play an increasing role in patient management. Clinicians and researchers should work to convert from category III to category I CPT codes and obtain reimbursement for imaging, with the ultimate goal of increasing its use in clinical practice and improving patient care.

Optical coherence tomography (OCT) is a noninvasive imaging technique that is cleared by the US Food and Drug Administration as a 510(k) class II regulatory device to visualize biological tissues in vivo and in real time^.1-3 In July 2017, OCT received 2 category III Current Procedural Terminology (CPT) codes from the American Medical Association—0470T and 0471T—enabling physicians to report and track the usage of this emerging imaging method.⁴ Category III CPT codes remain investigational and therefore are not easily reimbursed by insurance.⁵ The goal of OCT manufacturers and providers within the next 5 years is to upgrade to category I coding before the present codes are archived. Although documented advantages of OCT include its unique ability to effectively differentiate and monitor skin lesions throughout nonsurgical treatment as well as to efficiently delineate presurgical margins, additional research reporting its efficacy may facilitate the coding conversion and encourage greater usage of OCT technology. We present a brief review of OCT imaging in dermatology, including its indications and limitations.

RELATED VIDEO: Imaging Overview: Report From the Mount Sinai Fall Symposium

Types of OCT

Optical coherence tomography, based on the principle of low-coherence interferometry, uses infrared light to extract fine details from within highly scattering turbid media to visualize the subsurface of the skin.² Since its introduction for use in dermatology, OCT has been used to study skin in both the research and clinical settings.^2,3 Current OCT devices on the market are mobile and easy to use in a busy dermatology practice. The Table reviews the most commonly used noninvasive imaging tools for the skin, depicting the inverse relationship between penetration depth and cellular resolution as well as field of view discrepancies.^2,6-8 Optical coherence tomography technology collects cross-sectional (vertical) images similar to histology and en face (horizontal) images similar to reflective confocal microscopy (RCM) of skin areas with adequate cellular resolution and without compromising penetration depth as well as a field of view comparable to the probe aperture contacting the skin.

RELATED VIDEO: Noninvasive Imaging: Report From the Mount Sinai Fall Symposium

Conventional OCT
Due to multiple simultaneous beams, conventional frequency-domain OCT (FD-OCT) provides enhanced lateral resolution of 7.5 to 15 µm and axial resolution of 5 to 10 µm with a field of view of 6.0×6.0 mm² and depth of 1.5 to 2.0 mm.^2,6,8 Conventional FD-OCT detects architectural details within tissue with better cellular clarity than high-frequency ultrasound and better depth than RCM, yet FD-OCT is not sufficient to distinguish individual cells.

Dynamic OCT
The recent development of dynamic OCT (D-OCT) software based on speckle-variance has the added ability to visualize the skin microvasculature and therefore detect blood vessels and their distribution within specific lesions. This angiographic variant of FD-OCT detects motion corresponding to blood flow in the images and may enhance diagnostic accuracy, particularly in the differentiation of nevi and malignant melanomas.^8-11

High-Definition OCT
High-definition OCT (HD-OCT), a hybrid of RCM and FD-OCT, provides improved optical resolution of 3 μm for both lateral and axial imaging approaching a resolution similar to RCM making it possible to visualize individual cells, though at the expense of lower penetration depth of 0.5 to 1.0 mm and reduced field of view of 1.8×1.5 mm² to FD-OCT. High-definition OCT combines 2 different views to produce a 3-dimensional image for additional data interpretation (Table).^7,8,12

Current CPT Guidelines

Two category III CPT codes—0470T and 0471T—allow the medical community to collect and track the usage of the emerging OCT technology. Code 0470T is used for microstructural and morphological skin imaging, specifically acquisition, interpretation, and reading of the images. Code 0471T is used for each additional skin lesion imaged.⁴

Current Procedural Terminology category III codes remain investigational in contrast to the permanent category I codes. Reimbursement for CPT III codes is difficult because it is not generally an accepted service covered by insurance.⁵ The goal within the next 5 years is to convert to category I CPT codes, meanwhile the CPT III codes should encourage increased utilization of OCT technology.

Indications for OCT

Depiction of Healthy Versus Diseased Skin
Optical coherence tomography is a valuable tool in visualizing normal skin morphology including principal skin layers, namely the dermis, epidermis, and dermoepidermal junction, as well as structures such as hair follicles, blood vessels, and glands.^2,13 The OCT images show architectural changes of the skin layers and can be used to differentiate abnormal from normal tissue in vivo.²

Diagnosis and Treatment Monitoring of Skin Cancers
Optical coherence tomography is well established for use in the diagnosis and management of nonmelanoma skin cancers and to determine clinical end points of nonsurgical treatment without the need for skin biopsy. Promising diagnostic criteria have been developed for nonmelanoma skin cancers including basal cell carcinoma (BCC) and squamous cell carcinoma, as well as premalignant actinic keratoses using FD-OCT and the newer D-OCT and HD-OCT devices.^9-17 For example, FD-OCT offers improved diagnosis of lesions suspicious for BCC, the most common type of skin cancer, showing improved sensitivity (79%–96%) and specificity (75%–96%) when compared with clinical assessment and dermoscopy alone.^12,14 Typical OCT features differentiating BCC from other lesions include hyporeflective ovoid nests with a dark rim and an alteration of the dermoepidermal junction. In addition to providing a good diagnostic overview of skin, OCT devices show promise in monitoring the effects of treatment on primary and recurrent lesions.^14-16

In Vivo Excision Planning
Additionally, OCT is a helpful tool in delineating tumor margins prior to surgical resection to achieve optimal cosmesis. By detecting subclinical tumor extension, this preoperative technique has been shown to reduce the number of surgical stages. Pomerantz et al¹⁷ showed that mapping BCC tumor margins with OCT prior to Mohs micrographic surgery closely approximated the final surgical defects. Alawi et al¹⁸ showed that the OCT-defined lateral margins correctly indicated complete removal of tumors. These studies illustrate the ability of OCT to minimize the amount of skin excised without compromising the integrity of tumor-free borders. The use of ex vivo OCT to detect residual tumors is not recommended based on current studies.^6,17,18

Diagnosis and Treatment Monitoring of Other Diseases
Further applications of OCT include diagnosis of noncancerous lesions such as nail conditions, scleroderma, psoriatic arthritis, blistering diseases, and vascular lesions, as well as assessment of skin moisture and hydration, burn depth, wound healing, skin atrophy, and UV damage.² For example, Aldahan et al¹⁹ demonstrated the utility of D-OCT to identify structural and vascular features specific to nail psoriasis useful in the diagnosis and treatment monitoring of the condition.

Limitations of OCT

Resolution
Frequency-domain OCT enables the detection of architectural details within tissue, but its image resolution is not sufficient to distinguish individual cells, therefore restricting its use in evaluating pigmented benign and malignant lesions such as dysplastic nevi and melanomas. Higher-resolution RCM is superior for imaging these lesions, as its device can better evaluate microscopic structures. With the advent of D-OCT and HD-OCT, research is being conducted to assess their use in differentiating pigmented lesions.^8,20 Schuh et a^l9 and Gambichler et al²⁰ reported preliminary results indicating the utility of D-OCT and HD-OCT to differentiate dysplastic nevi from melanomas and melanoma in situ, respectively.

Depth Measurement
Another limitation is associated with measuring lesion depth for advanced tumors. Although the typical imaging depth of OCT is significantly deeper than most other noninvasive imaging modalities used on skin, imaging deep tumor margins and invasion is restricted.

Image Interpretation
Diagnostic imaging requires image interpretation leading to potential interobserver and intraobserver variation. Experienced observers in OCT more accurately differentiated normal from lesional skin compared to novices, which suggests that training could improve agreement.^21,22

Reimbursement and Device Cost
Other practical limitations to widespread OCT utilization at this time include its initial laser device cost and lack of reimbursement. As such, large academic and research centers remain the primary sites to utilize these devices.

Future Directions

Optical coherence tomography complements other established noninvasive imaging tools allowing for real-time visualization of the skin without interfering with the tissue and offering images with a good balance of depth, resolution, and field of view. Although a single histology cut has superior cellular resolution to any imaging modality, OCT provides additional information that is not provided by a physical biopsy, given the multiple vertical sections of data. Optical coherence tomography is a useful diagnostic technique enabling patients to avoid unnecessary biopsies while increasing early lesion diagnosis. Furthermore, OCT helps to decrease repetitive biopsies throughout nonsurgical treatments. With the availability of newer technology such as D-OCT and HD-OCT, OCT will play an increasing role in patient management. Clinicians and researchers should work to convert from category III to category I CPT codes and obtain reimbursement for imaging, with the ultimate goal of increasing its use in clinical practice and improving patient care.

Optical coherence tomography (OCT) is a noninvasive imaging technique that is cleared by the US Food and Drug Administration as a 510(k) class II regulatory device to visualize biological tissues in vivo and in real time^.1-3 In July 2017, OCT received 2 category III Current Procedural Terminology (CPT) codes from the American Medical Association—0470T and 0471T—enabling physicians to report and track the usage of this emerging imaging method.⁴ Category III CPT codes remain investigational and therefore are not easily reimbursed by insurance.⁵ The goal of OCT manufacturers and providers within the next 5 years is to upgrade to category I coding before the present codes are archived. Although documented advantages of OCT include its unique ability to effectively differentiate and monitor skin lesions throughout nonsurgical treatment as well as to efficiently delineate presurgical margins, additional research reporting its efficacy may facilitate the coding conversion and encourage greater usage of OCT technology. We present a brief review of OCT imaging in dermatology, including its indications and limitations.

RELATED VIDEO: Imaging Overview: Report From the Mount Sinai Fall Symposium

Types of OCT

Optical coherence tomography, based on the principle of low-coherence interferometry, uses infrared light to extract fine details from within highly scattering turbid media to visualize the subsurface of the skin.² Since its introduction for use in dermatology, OCT has been used to study skin in both the research and clinical settings.^2,3 Current OCT devices on the market are mobile and easy to use in a busy dermatology practice. The Table reviews the most commonly used noninvasive imaging tools for the skin, depicting the inverse relationship between penetration depth and cellular resolution as well as field of view discrepancies.^2,6-8 Optical coherence tomography technology collects cross-sectional (vertical) images similar to histology and en face (horizontal) images similar to reflective confocal microscopy (RCM) of skin areas with adequate cellular resolution and without compromising penetration depth as well as a field of view comparable to the probe aperture contacting the skin.

RELATED VIDEO: Noninvasive Imaging: Report From the Mount Sinai Fall Symposium

Conventional OCT
Due to multiple simultaneous beams, conventional frequency-domain OCT (FD-OCT) provides enhanced lateral resolution of 7.5 to 15 µm and axial resolution of 5 to 10 µm with a field of view of 6.0×6.0 mm² and depth of 1.5 to 2.0 mm.^2,6,8 Conventional FD-OCT detects architectural details within tissue with better cellular clarity than high-frequency ultrasound and better depth than RCM, yet FD-OCT is not sufficient to distinguish individual cells.

Dynamic OCT
The recent development of dynamic OCT (D-OCT) software based on speckle-variance has the added ability to visualize the skin microvasculature and therefore detect blood vessels and their distribution within specific lesions. This angiographic variant of FD-OCT detects motion corresponding to blood flow in the images and may enhance diagnostic accuracy, particularly in the differentiation of nevi and malignant melanomas.^8-11

High-Definition OCT
High-definition OCT (HD-OCT), a hybrid of RCM and FD-OCT, provides improved optical resolution of 3 μm for both lateral and axial imaging approaching a resolution similar to RCM making it possible to visualize individual cells, though at the expense of lower penetration depth of 0.5 to 1.0 mm and reduced field of view of 1.8×1.5 mm² to FD-OCT. High-definition OCT combines 2 different views to produce a 3-dimensional image for additional data interpretation (Table).^7,8,12

Current CPT Guidelines

Two category III CPT codes—0470T and 0471T—allow the medical community to collect and track the usage of the emerging OCT technology. Code 0470T is used for microstructural and morphological skin imaging, specifically acquisition, interpretation, and reading of the images. Code 0471T is used for each additional skin lesion imaged.⁴

Current Procedural Terminology category III codes remain investigational in contrast to the permanent category I codes. Reimbursement for CPT III codes is difficult because it is not generally an accepted service covered by insurance.⁵ The goal within the next 5 years is to convert to category I CPT codes, meanwhile the CPT III codes should encourage increased utilization of OCT technology.

Indications for OCT

Depiction of Healthy Versus Diseased Skin
Optical coherence tomography is a valuable tool in visualizing normal skin morphology including principal skin layers, namely the dermis, epidermis, and dermoepidermal junction, as well as structures such as hair follicles, blood vessels, and glands.^2,13 The OCT images show architectural changes of the skin layers and can be used to differentiate abnormal from normal tissue in vivo.²

Diagnosis and Treatment Monitoring of Skin Cancers
Optical coherence tomography is well established for use in the diagnosis and management of nonmelanoma skin cancers and to determine clinical end points of nonsurgical treatment without the need for skin biopsy. Promising diagnostic criteria have been developed for nonmelanoma skin cancers including basal cell carcinoma (BCC) and squamous cell carcinoma, as well as premalignant actinic keratoses using FD-OCT and the newer D-OCT and HD-OCT devices.^9-17 For example, FD-OCT offers improved diagnosis of lesions suspicious for BCC, the most common type of skin cancer, showing improved sensitivity (79%–96%) and specificity (75%–96%) when compared with clinical assessment and dermoscopy alone.^12,14 Typical OCT features differentiating BCC from other lesions include hyporeflective ovoid nests with a dark rim and an alteration of the dermoepidermal junction. In addition to providing a good diagnostic overview of skin, OCT devices show promise in monitoring the effects of treatment on primary and recurrent lesions.^14-16

In Vivo Excision Planning
Additionally, OCT is a helpful tool in delineating tumor margins prior to surgical resection to achieve optimal cosmesis. By detecting subclinical tumor extension, this preoperative technique has been shown to reduce the number of surgical stages. Pomerantz et al¹⁷ showed that mapping BCC tumor margins with OCT prior to Mohs micrographic surgery closely approximated the final surgical defects. Alawi et al¹⁸ showed that the OCT-defined lateral margins correctly indicated complete removal of tumors. These studies illustrate the ability of OCT to minimize the amount of skin excised without compromising the integrity of tumor-free borders. The use of ex vivo OCT to detect residual tumors is not recommended based on current studies.^6,17,18

Diagnosis and Treatment Monitoring of Other Diseases
Further applications of OCT include diagnosis of noncancerous lesions such as nail conditions, scleroderma, psoriatic arthritis, blistering diseases, and vascular lesions, as well as assessment of skin moisture and hydration, burn depth, wound healing, skin atrophy, and UV damage.² For example, Aldahan et al¹⁹ demonstrated the utility of D-OCT to identify structural and vascular features specific to nail psoriasis useful in the diagnosis and treatment monitoring of the condition.

Limitations of OCT

Resolution
Frequency-domain OCT enables the detection of architectural details within tissue, but its image resolution is not sufficient to distinguish individual cells, therefore restricting its use in evaluating pigmented benign and malignant lesions such as dysplastic nevi and melanomas. Higher-resolution RCM is superior for imaging these lesions, as its device can better evaluate microscopic structures. With the advent of D-OCT and HD-OCT, research is being conducted to assess their use in differentiating pigmented lesions.^8,20 Schuh et a^l9 and Gambichler et al²⁰ reported preliminary results indicating the utility of D-OCT and HD-OCT to differentiate dysplastic nevi from melanomas and melanoma in situ, respectively.

Depth Measurement
Another limitation is associated with measuring lesion depth for advanced tumors. Although the typical imaging depth of OCT is significantly deeper than most other noninvasive imaging modalities used on skin, imaging deep tumor margins and invasion is restricted.

Image Interpretation
Diagnostic imaging requires image interpretation leading to potential interobserver and intraobserver variation. Experienced observers in OCT more accurately differentiated normal from lesional skin compared to novices, which suggests that training could improve agreement.^21,22

Reimbursement and Device Cost
Other practical limitations to widespread OCT utilization at this time include its initial laser device cost and lack of reimbursement. As such, large academic and research centers remain the primary sites to utilize these devices.

Future Directions

Optical coherence tomography complements other established noninvasive imaging tools allowing for real-time visualization of the skin without interfering with the tissue and offering images with a good balance of depth, resolution, and field of view. Although a single histology cut has superior cellular resolution to any imaging modality, OCT provides additional information that is not provided by a physical biopsy, given the multiple vertical sections of data. Optical coherence tomography is a useful diagnostic technique enabling patients to avoid unnecessary biopsies while increasing early lesion diagnosis. Furthermore, OCT helps to decrease repetitive biopsies throughout nonsurgical treatments. With the availability of newer technology such as D-OCT and HD-OCT, OCT will play an increasing role in patient management. Clinicians and researchers should work to convert from category III to category I CPT codes and obtain reimbursement for imaging, with the ultimate goal of increasing its use in clinical practice and improving patient care.

Dermoscopy, or the noninvasive in vivo examination of the epidermis and superficial dermis using magnification, facilitates the diagnosis of pigmented and nonpigmented skin lesions.¹ Despite the benefit of dermoscopy in making early and accurate diagnoses of potentially life-limiting skin cancers, only 48% of dermatologists in the United States use dermoscopy in their practices.² The most commonly cited reason for not using dermoscopy is lack of training.

Although the use of dermoscopy is associated with younger age and more recent graduation from residency compared to nonusers, dermatology resident physicians continue to receive limited training in dermoscopy.² In a survey of 139 dermatology chief residents, 48% were not satisfied with the dermoscopy training that they had received during residency. Residents who received bedside instruction in dermoscopy reported greater satisfaction with their dermoscopy training compared to those who did not receive bedside instruction.³ This article provides a brief comparison of standard dermoscopy versus videodermoscopy for the instruction of trainees on common dermatologic diagnoses.

Bedside Dermoscopy

Standard optical dermatoscopes used for patient care and educational purposes typically incorporate 10-fold magnification and permit examination by a single viewer through a lens. With standard dermatoscopes, bedside dermoscopy instruction consists of the independent sequential viewing of skin lesions by instructors and trainees. Trainees must independently search for dermoscopic features noted by the instructor, which may be difficult for novice users. Simultaneous viewing of lesions would allow instructors to clearly indicate in real time pertinent dermoscopic features to their trainees.

Videodermatoscopes facilitate the simultaneous examination of cutaneous lesions by projecting the dermoscopic image onto a digital screen. Furthermore, these devices can incorporate magnifications of up to 200-fold or greater. In recent years, research pertaining to videodermoscopy has focused on the high magnification capabilities of these devices, specifically dermoscopic features that are visualized at magnifications greater than 10-fold, including the light brown nests of basal cell carcinomas that are seen at 50- to 70-fold magnification, twisted red capillary loops seen in active scalp psoriasis at 50-fold magnification, and longitudinal white indentations seen on nail plates affected by onychomycosis at 20-fold magnification.^4-6 The potential value of videodermoscopy in medical education lies not only in the high magnification potential, which may make subtle dermoscopic findings more apparent to novice dermoscopists, but also in the ability to facilitate simultaneous dermoscopic examinations by instructors and trainees.

Educational Applications for Videodermoscopy

To illustrate the educational potential of videodermoscopy, images taken with a standard dermatoscope at 10-fold magnification are presented with videodermoscopic images taken at magnifications ranging from 60- to 185-fold (Figures 1–3). These examples demonstrate the potential for videodermoscopy to facilitate the visualization of subtle dermoscopic features by novice dermoscopists, relating to both the enhanced magnification potential and the potential for simultaneous rather than sequential examination.

Final Thoughts

High-magnification videodermoscopy may be a useful tool to further dermoscopic education. Videodermatoscopes vary in functionality and cost but are available at price points comparable to those of standard optical dermatoscopes. Owners of standard dermatoscopes can approximate some of the benefits of a digital videodermatoscope by using the standard dermatoscope in conjunction with a camera, including those integrated into mobile phones and tablets. By attaching the standard dermatoscope to a camera with a digital display, the digital zoom of the camera can be used to magnify the standard dermoscopic image, enhancing the ability of novice dermoscopists to visualize subtle findings. By presenting this magnified image on a digital display, dermoscopy instructors and trainees would be able to simultaneously view dermoscopic images of lesions, sometimes with magnifications comparable to videodermatoscopes.

In the setting of a dermatology residency program, videodermoscopy can be incorporated into bedside teaching with experienced dermoscopists and for the live presentation of dermoscopic features at departmental grand rounds. By facilitating the simultaneous, high-magnification and live viewing of skin lesions by dermoscopy instructors and trainees, digital videodermoscopy has the potential to address an area of weakness in dermatologic training.

Dermoscopy, or the noninvasive in vivo examination of the epidermis and superficial dermis using magnification, facilitates the diagnosis of pigmented and nonpigmented skin lesions.¹ Despite the benefit of dermoscopy in making early and accurate diagnoses of potentially life-limiting skin cancers, only 48% of dermatologists in the United States use dermoscopy in their practices.² The most commonly cited reason for not using dermoscopy is lack of training.

Although the use of dermoscopy is associated with younger age and more recent graduation from residency compared to nonusers, dermatology resident physicians continue to receive limited training in dermoscopy.² In a survey of 139 dermatology chief residents, 48% were not satisfied with the dermoscopy training that they had received during residency. Residents who received bedside instruction in dermoscopy reported greater satisfaction with their dermoscopy training compared to those who did not receive bedside instruction.³ This article provides a brief comparison of standard dermoscopy versus videodermoscopy for the instruction of trainees on common dermatologic diagnoses.

Bedside Dermoscopy

Standard optical dermatoscopes used for patient care and educational purposes typically incorporate 10-fold magnification and permit examination by a single viewer through a lens. With standard dermatoscopes, bedside dermoscopy instruction consists of the independent sequential viewing of skin lesions by instructors and trainees. Trainees must independently search for dermoscopic features noted by the instructor, which may be difficult for novice users. Simultaneous viewing of lesions would allow instructors to clearly indicate in real time pertinent dermoscopic features to their trainees.

Videodermatoscopes facilitate the simultaneous examination of cutaneous lesions by projecting the dermoscopic image onto a digital screen. Furthermore, these devices can incorporate magnifications of up to 200-fold or greater. In recent years, research pertaining to videodermoscopy has focused on the high magnification capabilities of these devices, specifically dermoscopic features that are visualized at magnifications greater than 10-fold, including the light brown nests of basal cell carcinomas that are seen at 50- to 70-fold magnification, twisted red capillary loops seen in active scalp psoriasis at 50-fold magnification, and longitudinal white indentations seen on nail plates affected by onychomycosis at 20-fold magnification.^4-6 The potential value of videodermoscopy in medical education lies not only in the high magnification potential, which may make subtle dermoscopic findings more apparent to novice dermoscopists, but also in the ability to facilitate simultaneous dermoscopic examinations by instructors and trainees.

Educational Applications for Videodermoscopy

To illustrate the educational potential of videodermoscopy, images taken with a standard dermatoscope at 10-fold magnification are presented with videodermoscopic images taken at magnifications ranging from 60- to 185-fold (Figures 1–3). These examples demonstrate the potential for videodermoscopy to facilitate the visualization of subtle dermoscopic features by novice dermoscopists, relating to both the enhanced magnification potential and the potential for simultaneous rather than sequential examination.

Final Thoughts

High-magnification videodermoscopy may be a useful tool to further dermoscopic education. Videodermatoscopes vary in functionality and cost but are available at price points comparable to those of standard optical dermatoscopes. Owners of standard dermatoscopes can approximate some of the benefits of a digital videodermatoscope by using the standard dermatoscope in conjunction with a camera, including those integrated into mobile phones and tablets. By attaching the standard dermatoscope to a camera with a digital display, the digital zoom of the camera can be used to magnify the standard dermoscopic image, enhancing the ability of novice dermoscopists to visualize subtle findings. By presenting this magnified image on a digital display, dermoscopy instructors and trainees would be able to simultaneously view dermoscopic images of lesions, sometimes with magnifications comparable to videodermatoscopes.

In the setting of a dermatology residency program, videodermoscopy can be incorporated into bedside teaching with experienced dermoscopists and for the live presentation of dermoscopic features at departmental grand rounds. By facilitating the simultaneous, high-magnification and live viewing of skin lesions by dermoscopy instructors and trainees, digital videodermoscopy has the potential to address an area of weakness in dermatologic training.

Dermoscopy, or the noninvasive in vivo examination of the epidermis and superficial dermis using magnification, facilitates the diagnosis of pigmented and nonpigmented skin lesions.¹ Despite the benefit of dermoscopy in making early and accurate diagnoses of potentially life-limiting skin cancers, only 48% of dermatologists in the United States use dermoscopy in their practices.² The most commonly cited reason for not using dermoscopy is lack of training.

Although the use of dermoscopy is associated with younger age and more recent graduation from residency compared to nonusers, dermatology resident physicians continue to receive limited training in dermoscopy.² In a survey of 139 dermatology chief residents, 48% were not satisfied with the dermoscopy training that they had received during residency. Residents who received bedside instruction in dermoscopy reported greater satisfaction with their dermoscopy training compared to those who did not receive bedside instruction.³ This article provides a brief comparison of standard dermoscopy versus videodermoscopy for the instruction of trainees on common dermatologic diagnoses.

Bedside Dermoscopy

Standard optical dermatoscopes used for patient care and educational purposes typically incorporate 10-fold magnification and permit examination by a single viewer through a lens. With standard dermatoscopes, bedside dermoscopy instruction consists of the independent sequential viewing of skin lesions by instructors and trainees. Trainees must independently search for dermoscopic features noted by the instructor, which may be difficult for novice users. Simultaneous viewing of lesions would allow instructors to clearly indicate in real time pertinent dermoscopic features to their trainees.

Videodermatoscopes facilitate the simultaneous examination of cutaneous lesions by projecting the dermoscopic image onto a digital screen. Furthermore, these devices can incorporate magnifications of up to 200-fold or greater. In recent years, research pertaining to videodermoscopy has focused on the high magnification capabilities of these devices, specifically dermoscopic features that are visualized at magnifications greater than 10-fold, including the light brown nests of basal cell carcinomas that are seen at 50- to 70-fold magnification, twisted red capillary loops seen in active scalp psoriasis at 50-fold magnification, and longitudinal white indentations seen on nail plates affected by onychomycosis at 20-fold magnification.^4-6 The potential value of videodermoscopy in medical education lies not only in the high magnification potential, which may make subtle dermoscopic findings more apparent to novice dermoscopists, but also in the ability to facilitate simultaneous dermoscopic examinations by instructors and trainees.

Educational Applications for Videodermoscopy

To illustrate the educational potential of videodermoscopy, images taken with a standard dermatoscope at 10-fold magnification are presented with videodermoscopic images taken at magnifications ranging from 60- to 185-fold (Figures 1–3). These examples demonstrate the potential for videodermoscopy to facilitate the visualization of subtle dermoscopic features by novice dermoscopists, relating to both the enhanced magnification potential and the potential for simultaneous rather than sequential examination.

Final Thoughts

High-magnification videodermoscopy may be a useful tool to further dermoscopic education. Videodermatoscopes vary in functionality and cost but are available at price points comparable to those of standard optical dermatoscopes. Owners of standard dermatoscopes can approximate some of the benefits of a digital videodermatoscope by using the standard dermatoscope in conjunction with a camera, including those integrated into mobile phones and tablets. By attaching the standard dermatoscope to a camera with a digital display, the digital zoom of the camera can be used to magnify the standard dermoscopic image, enhancing the ability of novice dermoscopists to visualize subtle findings. By presenting this magnified image on a digital display, dermoscopy instructors and trainees would be able to simultaneously view dermoscopic images of lesions, sometimes with magnifications comparable to videodermatoscopes.

In the setting of a dermatology residency program, videodermoscopy can be incorporated into bedside teaching with experienced dermoscopists and for the live presentation of dermoscopic features at departmental grand rounds. By facilitating the simultaneous, high-magnification and live viewing of skin lesions by dermoscopy instructors and trainees, digital videodermoscopy has the potential to address an area of weakness in dermatologic training.

Atypical vascular lesions (AVLs) of the breast are rare cutaneous vascular proliferations that present as erythematous, violaceous, or flesh-colored papules, patches, or plaques in women who have undergone radiation treatment for breast carcinoma.^1,2 These lesions most commonly develop in the irradiated area within 3 to 6 years following radiation treatment.³

Various terms have been used to describe AVLs in the literature, including atypical hemangiomas, benign lymphangiomatous papules, benign lymphangioendotheliomas, lymphangioma circumscriptum, and acquired progressive lymphangiomas, suggesting benign behavior.^4-10 However, their identity as benign lesions has been a source of controversy, with some investigators proposing that AVLs may be a precursor lesion to postirradiation angiosarcoma.² Research has addressed if there are markers that can predict AVL types that are more likely to develop into angiosarcomas.¹ Although most clinicians treat AVLs with complete excision, there currently are no specific guidelines to direct this practice.

We report the case of a patient with a history of 1 AVL that was excised who developed 3 additional AVLs in the same breast over the course of 15 months.

Case Report

A 55-year-old woman with a history of obesity, hypertension, and infiltrating ductal carcinoma in situ of the right breast (grade 2, estrogen receptor and progesterone receptor positive) underwent a right breast lumpectomy and sentinel lymph node dissection. Three months later, she underwent re-excision for positive margins and started adjuvant hormonal therapy with tamoxifen. One month later, she began external beam radiation therapy and received a total dose of 6040 cGy over the course of 9 weeks (34 total treatments).

The patient presented to an outside dermatology clinic 2 years after completing external beam radiation therapy for evaluation of a new pink nodule on the right mid breast. The nodule was biopsied and discovered to be an AVL. Pathology showed an anastomosing proliferation of thin-walled vascular channels mainly located in the superficial dermis with notable endothelial nuclear atypia and hyperchromasia. There were several tiny foci with the beginnings of multilayering with prominent endothelial atypia (Figure 1). She underwent complete excision for this AVL with negative margins.

Six months after the initial AVL diagnosis, she presented to our dermatology clinic with another asymptomatic red bump on the right breast. On physical examination, a 4-mm firm, erythematous, well-circumscribed papule was noted on the medial aspect of the right breast along with a similar-appearing 4-mm papule on the right lateral aspect of the right breast (Figure 2). The patient was unsure of the duration of the second lesion but felt that it had been present at least as long as the other lesion. Both lesions clinically resembled typical capillary hemangiomas. A 6-mm punch biopsy of the right medial breast was performed and revealed enlarged vessels and capillaries in the upper dermis lined by endothelial cells with focal prominent nuclei without necrosis, overt atypia, mitosis, or tufting (Figure 3). Immunostaining was positive for CD34, factor VIII antigen, podoplanin (D2-40), and CD31, and negative for cytokeratin 7 and pankeratin. This staining was compatible with a lymphatic-type AVL.¹ A diagnosis of AVL was made and complete excision with clear margins was performed. At the time of this excision, a biopsy of the right lateral breast was performed revealing thin-walled, dilated vascular channels in the superficial dermis with architecturally atypical angulated outlines, mild endothelial nuclear atypia, and hyperchromasia without endothelial multilayering. Clear margins were noted on the biopsy, but the patient subsequently declined re-excision of this third AVL.

During a subsequent follow-up visit 9 months later, the patient was noted to have a 2-mm red, vascular-appearing papule on the right upper medial breast (Figure 2). A 6-mm biopsy was performed and revealed thin-walled vascular channels in the superficial dermis with endothelial nuclear atypia consistent with an AVL.

Comment

Fineberg and Rosen⁸ were the first to describe AVLs in their 1994 study of 4 women with cutaneous vascular proliferations that developed after radiation and chemotherapy for breast cancer. They concluded that these AVLs were benign lesions distinct from angiosarcomas.⁸ However, further research has challenged the benign nature of AVLs. In 2005, Brenn and Fletcher² studied 42 women diagnosed with either angiosarcoma or atypical radiation-associated cutaneous vascular lesions. They suggested that AVLs resided on the same spectrum as angiosarcomas and that AVLs may be precursor lesions to angiosarcomas.² Furthermore, Hildebrandt et al¹¹ in 2001 and Di Tommaso and Fabbri¹² in 2003 published case reports of individual patients who developed an angiosarcoma from a preexisting AVL.

The controversy continued when Patton et al¹ published a study in 2008 in which 32 cases of AVLs were reviewed. In this study, 2 histologic types of AVLs were described: vascular type and lymphatic type. Vascular-type AVLs are characterized by irregularly dispersed, pericyte-invested, capillary-sized vessels within the papillary or reticular dermis that often are associated with extravasated erythrocytes or hemosiderin. On the other hand, lymphatic-type AVLs display thin-walled, variably anastomosing, lymphatic vessels lined by attenuated or slightly protuberant endothelial cells. These subtypes have been suggested based on the antigens known to be present in certain tissues, specifically vascular and lymphatic tissue. Despite these seemingly distinct histologies, 6 lesions classified as vascular type displayed some histologic overlap with the lymphatic-type AVLs. The authors concluded that the vascular type showed greater potential to develop into an angiosarcoma based on the degree of endothelial atypia.¹

In 2011, Santi et al¹³ found that both AVLs and angiosarcomas share inactivation mutations in the tumor suppressor gene TP53, providing further evidence to suggest that AVLs may be precursors to angiosarcomas.

Although the malignant potential of AVLs remains questionable, research has shown that they do have a propensity to recur.³ In 2007, Gengler et al³ determined that 20% of patients with AVLs experienced recurrence after a biopsy or excision with varying margins; however, the group stated that these new vascular lesions might not be recurrences but rather entirely new lesions in the same irradiated field (field-effect phenomenon). Several other studies demonstrated that more than 30% of patients with 1 AVL developed more lesions within the same irradiated area.^3,14-16 Despite the high rate of recurrence documented in the literature, only 5 of more than 100 diagnosed AVLs have progressed to angiosarcoma.^1,3

Many differences can be noted when comparing the histology of AVLs versus angiosarcomas, though some are subtle (Table). Angiosarcomas display poorly circumscribed vascular infiltration into the subcutaneous tissue, multilayering of endothelial cells, prominent nucleoli, hemorrhage, mitoses, and notable aytpia. Atypical vascular lesions lack these features and tend to be wedge shaped and display chronic inflammation.^8,15,17-19 Atypical vascular lesions show superficial localized growth without destruction of adjacent adnexa, display dilated vascular spaces, and exhibit large endothelial cells.^{5,6,8,14,15,19,20} However, there is overlap between AVLs and angiosarcomas that can make diagnosis difficult.^{2,14,16,17,19} Areas within or just outside of an angiosarcoma, especially in well-differentiated angiosarcomas, can appear histologically identical to AVLs, and multiple biopsies may be required for diagnosis.^17,19,21

Conclusion

More research is needed in the arenas of classification, diagnosis, treatment, and follow-up recommendations for AVLs. In particular, more specific histologic markers may be needed to identify those AVLs that may progress to angiosarcomas. Although most AVLs are treated with excision, a consensus needs to be reached on adequate surgical margins. Lastly, due to the tendency of AVLs to recur coupled with their unknown malignant potential, recommendations are needed for consistent follow-up examinations.

Atypical vascular lesions (AVLs) of the breast are rare cutaneous vascular proliferations that present as erythematous, violaceous, or flesh-colored papules, patches, or plaques in women who have undergone radiation treatment for breast carcinoma.^1,2 These lesions most commonly develop in the irradiated area within 3 to 6 years following radiation treatment.³

Various terms have been used to describe AVLs in the literature, including atypical hemangiomas, benign lymphangiomatous papules, benign lymphangioendotheliomas, lymphangioma circumscriptum, and acquired progressive lymphangiomas, suggesting benign behavior.^4-10 However, their identity as benign lesions has been a source of controversy, with some investigators proposing that AVLs may be a precursor lesion to postirradiation angiosarcoma.² Research has addressed if there are markers that can predict AVL types that are more likely to develop into angiosarcomas.¹ Although most clinicians treat AVLs with complete excision, there currently are no specific guidelines to direct this practice.

We report the case of a patient with a history of 1 AVL that was excised who developed 3 additional AVLs in the same breast over the course of 15 months.

Case Report

A 55-year-old woman with a history of obesity, hypertension, and infiltrating ductal carcinoma in situ of the right breast (grade 2, estrogen receptor and progesterone receptor positive) underwent a right breast lumpectomy and sentinel lymph node dissection. Three months later, she underwent re-excision for positive margins and started adjuvant hormonal therapy with tamoxifen. One month later, she began external beam radiation therapy and received a total dose of 6040 cGy over the course of 9 weeks (34 total treatments).

The patient presented to an outside dermatology clinic 2 years after completing external beam radiation therapy for evaluation of a new pink nodule on the right mid breast. The nodule was biopsied and discovered to be an AVL. Pathology showed an anastomosing proliferation of thin-walled vascular channels mainly located in the superficial dermis with notable endothelial nuclear atypia and hyperchromasia. There were several tiny foci with the beginnings of multilayering with prominent endothelial atypia (Figure 1). She underwent complete excision for this AVL with negative margins.

Six months after the initial AVL diagnosis, she presented to our dermatology clinic with another asymptomatic red bump on the right breast. On physical examination, a 4-mm firm, erythematous, well-circumscribed papule was noted on the medial aspect of the right breast along with a similar-appearing 4-mm papule on the right lateral aspect of the right breast (Figure 2). The patient was unsure of the duration of the second lesion but felt that it had been present at least as long as the other lesion. Both lesions clinically resembled typical capillary hemangiomas. A 6-mm punch biopsy of the right medial breast was performed and revealed enlarged vessels and capillaries in the upper dermis lined by endothelial cells with focal prominent nuclei without necrosis, overt atypia, mitosis, or tufting (Figure 3). Immunostaining was positive for CD34, factor VIII antigen, podoplanin (D2-40), and CD31, and negative for cytokeratin 7 and pankeratin. This staining was compatible with a lymphatic-type AVL.¹ A diagnosis of AVL was made and complete excision with clear margins was performed. At the time of this excision, a biopsy of the right lateral breast was performed revealing thin-walled, dilated vascular channels in the superficial dermis with architecturally atypical angulated outlines, mild endothelial nuclear atypia, and hyperchromasia without endothelial multilayering. Clear margins were noted on the biopsy, but the patient subsequently declined re-excision of this third AVL.

During a subsequent follow-up visit 9 months later, the patient was noted to have a 2-mm red, vascular-appearing papule on the right upper medial breast (Figure 2). A 6-mm biopsy was performed and revealed thin-walled vascular channels in the superficial dermis with endothelial nuclear atypia consistent with an AVL.

Comment

Fineberg and Rosen⁸ were the first to describe AVLs in their 1994 study of 4 women with cutaneous vascular proliferations that developed after radiation and chemotherapy for breast cancer. They concluded that these AVLs were benign lesions distinct from angiosarcomas.⁸ However, further research has challenged the benign nature of AVLs. In 2005, Brenn and Fletcher² studied 42 women diagnosed with either angiosarcoma or atypical radiation-associated cutaneous vascular lesions. They suggested that AVLs resided on the same spectrum as angiosarcomas and that AVLs may be precursor lesions to angiosarcomas.² Furthermore, Hildebrandt et al¹¹ in 2001 and Di Tommaso and Fabbri¹² in 2003 published case reports of individual patients who developed an angiosarcoma from a preexisting AVL.

The controversy continued when Patton et al¹ published a study in 2008 in which 32 cases of AVLs were reviewed. In this study, 2 histologic types of AVLs were described: vascular type and lymphatic type. Vascular-type AVLs are characterized by irregularly dispersed, pericyte-invested, capillary-sized vessels within the papillary or reticular dermis that often are associated with extravasated erythrocytes or hemosiderin. On the other hand, lymphatic-type AVLs display thin-walled, variably anastomosing, lymphatic vessels lined by attenuated or slightly protuberant endothelial cells. These subtypes have been suggested based on the antigens known to be present in certain tissues, specifically vascular and lymphatic tissue. Despite these seemingly distinct histologies, 6 lesions classified as vascular type displayed some histologic overlap with the lymphatic-type AVLs. The authors concluded that the vascular type showed greater potential to develop into an angiosarcoma based on the degree of endothelial atypia.¹

In 2011, Santi et al¹³ found that both AVLs and angiosarcomas share inactivation mutations in the tumor suppressor gene TP53, providing further evidence to suggest that AVLs may be precursors to angiosarcomas.

Although the malignant potential of AVLs remains questionable, research has shown that they do have a propensity to recur.³ In 2007, Gengler et al³ determined that 20% of patients with AVLs experienced recurrence after a biopsy or excision with varying margins; however, the group stated that these new vascular lesions might not be recurrences but rather entirely new lesions in the same irradiated field (field-effect phenomenon). Several other studies demonstrated that more than 30% of patients with 1 AVL developed more lesions within the same irradiated area.^3,14-16 Despite the high rate of recurrence documented in the literature, only 5 of more than 100 diagnosed AVLs have progressed to angiosarcoma.^1,3

Many differences can be noted when comparing the histology of AVLs versus angiosarcomas, though some are subtle (Table). Angiosarcomas display poorly circumscribed vascular infiltration into the subcutaneous tissue, multilayering of endothelial cells, prominent nucleoli, hemorrhage, mitoses, and notable aytpia. Atypical vascular lesions lack these features and tend to be wedge shaped and display chronic inflammation.^8,15,17-19 Atypical vascular lesions show superficial localized growth without destruction of adjacent adnexa, display dilated vascular spaces, and exhibit large endothelial cells.^{5,6,8,14,15,19,20} However, there is overlap between AVLs and angiosarcomas that can make diagnosis difficult.^{2,14,16,17,19} Areas within or just outside of an angiosarcoma, especially in well-differentiated angiosarcomas, can appear histologically identical to AVLs, and multiple biopsies may be required for diagnosis.^17,19,21

Conclusion

More research is needed in the arenas of classification, diagnosis, treatment, and follow-up recommendations for AVLs. In particular, more specific histologic markers may be needed to identify those AVLs that may progress to angiosarcomas. Although most AVLs are treated with excision, a consensus needs to be reached on adequate surgical margins. Lastly, due to the tendency of AVLs to recur coupled with their unknown malignant potential, recommendations are needed for consistent follow-up examinations.

Atypical vascular lesions (AVLs) of the breast are rare cutaneous vascular proliferations that present as erythematous, violaceous, or flesh-colored papules, patches, or plaques in women who have undergone radiation treatment for breast carcinoma.^1,2 These lesions most commonly develop in the irradiated area within 3 to 6 years following radiation treatment.³

Various terms have been used to describe AVLs in the literature, including atypical hemangiomas, benign lymphangiomatous papules, benign lymphangioendotheliomas, lymphangioma circumscriptum, and acquired progressive lymphangiomas, suggesting benign behavior.^4-10 However, their identity as benign lesions has been a source of controversy, with some investigators proposing that AVLs may be a precursor lesion to postirradiation angiosarcoma.² Research has addressed if there are markers that can predict AVL types that are more likely to develop into angiosarcomas.¹ Although most clinicians treat AVLs with complete excision, there currently are no specific guidelines to direct this practice.

We report the case of a patient with a history of 1 AVL that was excised who developed 3 additional AVLs in the same breast over the course of 15 months.

Case Report

A 55-year-old woman with a history of obesity, hypertension, and infiltrating ductal carcinoma in situ of the right breast (grade 2, estrogen receptor and progesterone receptor positive) underwent a right breast lumpectomy and sentinel lymph node dissection. Three months later, she underwent re-excision for positive margins and started adjuvant hormonal therapy with tamoxifen. One month later, she began external beam radiation therapy and received a total dose of 6040 cGy over the course of 9 weeks (34 total treatments).

The patient presented to an outside dermatology clinic 2 years after completing external beam radiation therapy for evaluation of a new pink nodule on the right mid breast. The nodule was biopsied and discovered to be an AVL. Pathology showed an anastomosing proliferation of thin-walled vascular channels mainly located in the superficial dermis with notable endothelial nuclear atypia and hyperchromasia. There were several tiny foci with the beginnings of multilayering with prominent endothelial atypia (Figure 1). She underwent complete excision for this AVL with negative margins.

Six months after the initial AVL diagnosis, she presented to our dermatology clinic with another asymptomatic red bump on the right breast. On physical examination, a 4-mm firm, erythematous, well-circumscribed papule was noted on the medial aspect of the right breast along with a similar-appearing 4-mm papule on the right lateral aspect of the right breast (Figure 2). The patient was unsure of the duration of the second lesion but felt that it had been present at least as long as the other lesion. Both lesions clinically resembled typical capillary hemangiomas. A 6-mm punch biopsy of the right medial breast was performed and revealed enlarged vessels and capillaries in the upper dermis lined by endothelial cells with focal prominent nuclei without necrosis, overt atypia, mitosis, or tufting (Figure 3). Immunostaining was positive for CD34, factor VIII antigen, podoplanin (D2-40), and CD31, and negative for cytokeratin 7 and pankeratin. This staining was compatible with a lymphatic-type AVL.¹ A diagnosis of AVL was made and complete excision with clear margins was performed. At the time of this excision, a biopsy of the right lateral breast was performed revealing thin-walled, dilated vascular channels in the superficial dermis with architecturally atypical angulated outlines, mild endothelial nuclear atypia, and hyperchromasia without endothelial multilayering. Clear margins were noted on the biopsy, but the patient subsequently declined re-excision of this third AVL.

During a subsequent follow-up visit 9 months later, the patient was noted to have a 2-mm red, vascular-appearing papule on the right upper medial breast (Figure 2). A 6-mm biopsy was performed and revealed thin-walled vascular channels in the superficial dermis with endothelial nuclear atypia consistent with an AVL.

Comment

Fineberg and Rosen⁸ were the first to describe AVLs in their 1994 study of 4 women with cutaneous vascular proliferations that developed after radiation and chemotherapy for breast cancer. They concluded that these AVLs were benign lesions distinct from angiosarcomas.⁸ However, further research has challenged the benign nature of AVLs. In 2005, Brenn and Fletcher² studied 42 women diagnosed with either angiosarcoma or atypical radiation-associated cutaneous vascular lesions. They suggested that AVLs resided on the same spectrum as angiosarcomas and that AVLs may be precursor lesions to angiosarcomas.² Furthermore, Hildebrandt et al¹¹ in 2001 and Di Tommaso and Fabbri¹² in 2003 published case reports of individual patients who developed an angiosarcoma from a preexisting AVL.

The controversy continued when Patton et al¹ published a study in 2008 in which 32 cases of AVLs were reviewed. In this study, 2 histologic types of AVLs were described: vascular type and lymphatic type. Vascular-type AVLs are characterized by irregularly dispersed, pericyte-invested, capillary-sized vessels within the papillary or reticular dermis that often are associated with extravasated erythrocytes or hemosiderin. On the other hand, lymphatic-type AVLs display thin-walled, variably anastomosing, lymphatic vessels lined by attenuated or slightly protuberant endothelial cells. These subtypes have been suggested based on the antigens known to be present in certain tissues, specifically vascular and lymphatic tissue. Despite these seemingly distinct histologies, 6 lesions classified as vascular type displayed some histologic overlap with the lymphatic-type AVLs. The authors concluded that the vascular type showed greater potential to develop into an angiosarcoma based on the degree of endothelial atypia.¹

In 2011, Santi et al¹³ found that both AVLs and angiosarcomas share inactivation mutations in the tumor suppressor gene TP53, providing further evidence to suggest that AVLs may be precursors to angiosarcomas.

Although the malignant potential of AVLs remains questionable, research has shown that they do have a propensity to recur.³ In 2007, Gengler et al³ determined that 20% of patients with AVLs experienced recurrence after a biopsy or excision with varying margins; however, the group stated that these new vascular lesions might not be recurrences but rather entirely new lesions in the same irradiated field (field-effect phenomenon). Several other studies demonstrated that more than 30% of patients with 1 AVL developed more lesions within the same irradiated area.^3,14-16 Despite the high rate of recurrence documented in the literature, only 5 of more than 100 diagnosed AVLs have progressed to angiosarcoma.^1,3

Many differences can be noted when comparing the histology of AVLs versus angiosarcomas, though some are subtle (Table). Angiosarcomas display poorly circumscribed vascular infiltration into the subcutaneous tissue, multilayering of endothelial cells, prominent nucleoli, hemorrhage, mitoses, and notable aytpia. Atypical vascular lesions lack these features and tend to be wedge shaped and display chronic inflammation.^8,15,17-19 Atypical vascular lesions show superficial localized growth without destruction of adjacent adnexa, display dilated vascular spaces, and exhibit large endothelial cells.^{5,6,8,14,15,19,20} However, there is overlap between AVLs and angiosarcomas that can make diagnosis difficult.^{2,14,16,17,19} Areas within or just outside of an angiosarcoma, especially in well-differentiated angiosarcomas, can appear histologically identical to AVLs, and multiple biopsies may be required for diagnosis.^17,19,21

Conclusion

More research is needed in the arenas of classification, diagnosis, treatment, and follow-up recommendations for AVLs. In particular, more specific histologic markers may be needed to identify those AVLs that may progress to angiosarcomas. Although most AVLs are treated with excision, a consensus needs to be reached on adequate surgical margins. Lastly, due to the tendency of AVLs to recur coupled with their unknown malignant potential, recommendations are needed for consistent follow-up examinations.

To the Editor:

Paraneoplastic acrokeratosis (PA), also known as Bazex syndrome, is a rare paraneoplastic dermatosis first described in 1965 by Bazex et al.¹ This entity is clinically characterized by dusky erythematous to violaceous keratoderma of the acral sites and commonly affects men older than 40 years. In most reported cases, there has been an underlying primary malignant neoplasm of the upper aerodigestive tract²; however, some other associated malignancies also have been reported. Skin changes tend to occur before the diagnosis of the associated tumor in 67% of cases. The cutaneous lesions usually resolve after successful treatment of the tumor and relapse in case of recurrence of the malignancy.³

A 53-year-old woman who was a smoker with no relevant medical background was referred to the dermatology department with an itching psoriasiform dermatitis on the palms and soles of 2 months' duration. There were no signs of systemic disease. Physical examination revealed well-demarcated, dusky red, thick, scaly plaques on the soles with sparing of the insteps (Figure, A). Scattered symmetric hyperkeratotic plaques were present on the palms (Figure, B). We also detected onychodystrophy on the hands. Other dermatologic findings were normal. Histologic examination of a biopsy specimen of the left sole showed hyperkeratosis, focal parakeratosis, acanthosis, hypergranulosis, and a predominantly perivascular dermal lymphocytic infiltrate.

With the diagnostic suspicion of PA, blood tests, chest radiograph, and colonoscopy were performed without revealing abnormalities. Positron emission tomography and computed tomography also was performed, showing cervical, mesenteric, retroperitoneal, and inguinal adenopathies. Histologic examination of both inguinal adenectomy and cervical lymph node biopsy revealed Bcl-2-positive in situ follicular lymphoma (ISFL). Examination of an iliac crest marrow aspirate showed minimal involvement of lymphoma (10%). Follow-up imaging performed 4 months after diagnosis showed no changes. The patient was diagnosed with a low-grade chronic lymphoproliferative disorder with histologic findings consistent with ISFL presenting with small disperse adenopathies and minimal bone marrow involvement. The hematology department opted for a wait-and-see approach with 6-month follow-up imaging.

The skin lesions were first treated with salicylic acid cream 10%, psoralen plus UVA therapy, and methotrexate 20 mg weekly for 2 months without remission. Replacing the other therapies, we initiated acitretin 25 mg daily, achieving sustained remission after 6 months of treatment, and then continued with a scaled dose reduction. The patient remained lesion free 1 year after starting the treatment, with a daily dose of 10 mg of acitretin.

Paraneoplastic acrokeratosis has been traditionally described as a paraneoplastic entity mainly associated with primary squamous cell carcinoma (SCC) of the upper aerodigestive tract or a metastatic SCC of the cervical lymph nodes with an unknown origin.^4,5 However, uncommon associations such as adenocarcinoma of the prostate, lung, esophagus, stomach, and colon; transitional cell carcinoma of the bladder; small cell carcinoma of the lung; cutaneous SCC; breast cancer; metastatic thymic carcinoma; metastatic neuroendocrine tumor; bronchial carcinoid tumor; SCC of the vulvar region; simultaneous multiple genitourinary tumors; and liposarcoma also have been described.⁶ Regarding the association with lymphoma, PA has been reported with peripheral T-cell lymphoma⁷ and Hodgkin disease⁸; however, ISFL underlying PA is rare.

Follicular lymphoma is the second most common non-Hodgkin lymphoma in Western countries and comprises approximately 20% of all lymphomas.⁹ It is slightly more prevalent in females, and the majority of patients present with advanced-stage disease. Generally considered to be an incurable disease, a watchful-waiting approach of conservative management has been advocated in most cases, deferring treatment until symptoms appear.⁹

Histology of PA is nonspecific, as in our case. However, it facilitates a differential diagnosis of major dermatoses including psoriasis vulgaris, pityriasis rubra pilaris, and lupus erythematosus.

Paraneoplastic palmoplantar keratoderma also is characteristic of Howel-Evans syndrome, which is a rare inherited condition associated with esophageal cancer. In contrast to our case, palmoplantar keratoderma in these patients usually begins around 10 years of age, is caused by a mutation in the RHBDF2 gene, and is inherited in an autosomal pattern.¹⁰

The diagnosis in our case was supported by a typical clinical picture, nonspecific histology, and the concurrent finding of the underlying lymphoma. Treatment of PA must focus on the removal of the underlying malignancy, which implies the remission of the cutaneous lesions. Taking into account that a recurrence of the primary tumor leads to a relapse of skin manifestations while distant metastases do not cause a reappearance of PA, it could be suggested that pathogenetically relevant factors are produced by the primary tumor and by lymph node metastases but not by metastases elsewhere.

In this case, due to the wait-and-see approach, a specific treatment for the skin lesions was established. Although management of the skin itself generally is ineffective, there are isolated reports of response after corticosteroids, antibiotics, antimycotics, keratolytic measures, or psoralen plus UVA therapy.⁶ Wishart¹¹ used etretinate to achieve an improvement of PA. We also achieved good response with acitretin. Retinoids are known to have antineoplastic activity, which may have been helpful in both the patient we presented and the one reported by Wishart.¹¹ In summary, we propose adding ISFL to the expanding list of malignant neoplasms associated with PA, noting the response of skin lesions after acitretin.

To the Editor:

Paraneoplastic acrokeratosis (PA), also known as Bazex syndrome, is a rare paraneoplastic dermatosis first described in 1965 by Bazex et al.¹ This entity is clinically characterized by dusky erythematous to violaceous keratoderma of the acral sites and commonly affects men older than 40 years. In most reported cases, there has been an underlying primary malignant neoplasm of the upper aerodigestive tract²; however, some other associated malignancies also have been reported. Skin changes tend to occur before the diagnosis of the associated tumor in 67% of cases. The cutaneous lesions usually resolve after successful treatment of the tumor and relapse in case of recurrence of the malignancy.³

A 53-year-old woman who was a smoker with no relevant medical background was referred to the dermatology department with an itching psoriasiform dermatitis on the palms and soles of 2 months' duration. There were no signs of systemic disease. Physical examination revealed well-demarcated, dusky red, thick, scaly plaques on the soles with sparing of the insteps (Figure, A). Scattered symmetric hyperkeratotic plaques were present on the palms (Figure, B). We also detected onychodystrophy on the hands. Other dermatologic findings were normal. Histologic examination of a biopsy specimen of the left sole showed hyperkeratosis, focal parakeratosis, acanthosis, hypergranulosis, and a predominantly perivascular dermal lymphocytic infiltrate.

With the diagnostic suspicion of PA, blood tests, chest radiograph, and colonoscopy were performed without revealing abnormalities. Positron emission tomography and computed tomography also was performed, showing cervical, mesenteric, retroperitoneal, and inguinal adenopathies. Histologic examination of both inguinal adenectomy and cervical lymph node biopsy revealed Bcl-2-positive in situ follicular lymphoma (ISFL). Examination of an iliac crest marrow aspirate showed minimal involvement of lymphoma (10%). Follow-up imaging performed 4 months after diagnosis showed no changes. The patient was diagnosed with a low-grade chronic lymphoproliferative disorder with histologic findings consistent with ISFL presenting with small disperse adenopathies and minimal bone marrow involvement. The hematology department opted for a wait-and-see approach with 6-month follow-up imaging.

The skin lesions were first treated with salicylic acid cream 10%, psoralen plus UVA therapy, and methotrexate 20 mg weekly for 2 months without remission. Replacing the other therapies, we initiated acitretin 25 mg daily, achieving sustained remission after 6 months of treatment, and then continued with a scaled dose reduction. The patient remained lesion free 1 year after starting the treatment, with a daily dose of 10 mg of acitretin.

Paraneoplastic acrokeratosis has been traditionally described as a paraneoplastic entity mainly associated with primary squamous cell carcinoma (SCC) of the upper aerodigestive tract or a metastatic SCC of the cervical lymph nodes with an unknown origin.^4,5 However, uncommon associations such as adenocarcinoma of the prostate, lung, esophagus, stomach, and colon; transitional cell carcinoma of the bladder; small cell carcinoma of the lung; cutaneous SCC; breast cancer; metastatic thymic carcinoma; metastatic neuroendocrine tumor; bronchial carcinoid tumor; SCC of the vulvar region; simultaneous multiple genitourinary tumors; and liposarcoma also have been described.⁶ Regarding the association with lymphoma, PA has been reported with peripheral T-cell lymphoma⁷ and Hodgkin disease⁸; however, ISFL underlying PA is rare.

Follicular lymphoma is the second most common non-Hodgkin lymphoma in Western countries and comprises approximately 20% of all lymphomas.⁹ It is slightly more prevalent in females, and the majority of patients present with advanced-stage disease. Generally considered to be an incurable disease, a watchful-waiting approach of conservative management has been advocated in most cases, deferring treatment until symptoms appear.⁹

Histology of PA is nonspecific, as in our case. However, it facilitates a differential diagnosis of major dermatoses including psoriasis vulgaris, pityriasis rubra pilaris, and lupus erythematosus.

Paraneoplastic palmoplantar keratoderma also is characteristic of Howel-Evans syndrome, which is a rare inherited condition associated with esophageal cancer. In contrast to our case, palmoplantar keratoderma in these patients usually begins around 10 years of age, is caused by a mutation in the RHBDF2 gene, and is inherited in an autosomal pattern.¹⁰

The diagnosis in our case was supported by a typical clinical picture, nonspecific histology, and the concurrent finding of the underlying lymphoma. Treatment of PA must focus on the removal of the underlying malignancy, which implies the remission of the cutaneous lesions. Taking into account that a recurrence of the primary tumor leads to a relapse of skin manifestations while distant metastases do not cause a reappearance of PA, it could be suggested that pathogenetically relevant factors are produced by the primary tumor and by lymph node metastases but not by metastases elsewhere.

In this case, due to the wait-and-see approach, a specific treatment for the skin lesions was established. Although management of the skin itself generally is ineffective, there are isolated reports of response after corticosteroids, antibiotics, antimycotics, keratolytic measures, or psoralen plus UVA therapy.⁶ Wishart¹¹ used etretinate to achieve an improvement of PA. We also achieved good response with acitretin. Retinoids are known to have antineoplastic activity, which may have been helpful in both the patient we presented and the one reported by Wishart.¹¹ In summary, we propose adding ISFL to the expanding list of malignant neoplasms associated with PA, noting the response of skin lesions after acitretin.

To the Editor:

Paraneoplastic acrokeratosis (PA), also known as Bazex syndrome, is a rare paraneoplastic dermatosis first described in 1965 by Bazex et al.¹ This entity is clinically characterized by dusky erythematous to violaceous keratoderma of the acral sites and commonly affects men older than 40 years. In most reported cases, there has been an underlying primary malignant neoplasm of the upper aerodigestive tract²; however, some other associated malignancies also have been reported. Skin changes tend to occur before the diagnosis of the associated tumor in 67% of cases. The cutaneous lesions usually resolve after successful treatment of the tumor and relapse in case of recurrence of the malignancy.³

A 53-year-old woman who was a smoker with no relevant medical background was referred to the dermatology department with an itching psoriasiform dermatitis on the palms and soles of 2 months' duration. There were no signs of systemic disease. Physical examination revealed well-demarcated, dusky red, thick, scaly plaques on the soles with sparing of the insteps (Figure, A). Scattered symmetric hyperkeratotic plaques were present on the palms (Figure, B). We also detected onychodystrophy on the hands. Other dermatologic findings were normal. Histologic examination of a biopsy specimen of the left sole showed hyperkeratosis, focal parakeratosis, acanthosis, hypergranulosis, and a predominantly perivascular dermal lymphocytic infiltrate.

With the diagnostic suspicion of PA, blood tests, chest radiograph, and colonoscopy were performed without revealing abnormalities. Positron emission tomography and computed tomography also was performed, showing cervical, mesenteric, retroperitoneal, and inguinal adenopathies. Histologic examination of both inguinal adenectomy and cervical lymph node biopsy revealed Bcl-2-positive in situ follicular lymphoma (ISFL). Examination of an iliac crest marrow aspirate showed minimal involvement of lymphoma (10%). Follow-up imaging performed 4 months after diagnosis showed no changes. The patient was diagnosed with a low-grade chronic lymphoproliferative disorder with histologic findings consistent with ISFL presenting with small disperse adenopathies and minimal bone marrow involvement. The hematology department opted for a wait-and-see approach with 6-month follow-up imaging.

The skin lesions were first treated with salicylic acid cream 10%, psoralen plus UVA therapy, and methotrexate 20 mg weekly for 2 months without remission. Replacing the other therapies, we initiated acitretin 25 mg daily, achieving sustained remission after 6 months of treatment, and then continued with a scaled dose reduction. The patient remained lesion free 1 year after starting the treatment, with a daily dose of 10 mg of acitretin.

Paraneoplastic acrokeratosis has been traditionally described as a paraneoplastic entity mainly associated with primary squamous cell carcinoma (SCC) of the upper aerodigestive tract or a metastatic SCC of the cervical lymph nodes with an unknown origin.^4,5 However, uncommon associations such as adenocarcinoma of the prostate, lung, esophagus, stomach, and colon; transitional cell carcinoma of the bladder; small cell carcinoma of the lung; cutaneous SCC; breast cancer; metastatic thymic carcinoma; metastatic neuroendocrine tumor; bronchial carcinoid tumor; SCC of the vulvar region; simultaneous multiple genitourinary tumors; and liposarcoma also have been described.⁶ Regarding the association with lymphoma, PA has been reported with peripheral T-cell lymphoma⁷ and Hodgkin disease⁸; however, ISFL underlying PA is rare.

Follicular lymphoma is the second most common non-Hodgkin lymphoma in Western countries and comprises approximately 20% of all lymphomas.⁹ It is slightly more prevalent in females, and the majority of patients present with advanced-stage disease. Generally considered to be an incurable disease, a watchful-waiting approach of conservative management has been advocated in most cases, deferring treatment until symptoms appear.⁹

Histology of PA is nonspecific, as in our case. However, it facilitates a differential diagnosis of major dermatoses including psoriasis vulgaris, pityriasis rubra pilaris, and lupus erythematosus.

Paraneoplastic palmoplantar keratoderma also is characteristic of Howel-Evans syndrome, which is a rare inherited condition associated with esophageal cancer. In contrast to our case, palmoplantar keratoderma in these patients usually begins around 10 years of age, is caused by a mutation in the RHBDF2 gene, and is inherited in an autosomal pattern.¹⁰

The diagnosis in our case was supported by a typical clinical picture, nonspecific histology, and the concurrent finding of the underlying lymphoma. Treatment of PA must focus on the removal of the underlying malignancy, which implies the remission of the cutaneous lesions. Taking into account that a recurrence of the primary tumor leads to a relapse of skin manifestations while distant metastases do not cause a reappearance of PA, it could be suggested that pathogenetically relevant factors are produced by the primary tumor and by lymph node metastases but not by metastases elsewhere.

In this case, due to the wait-and-see approach, a specific treatment for the skin lesions was established. Although management of the skin itself generally is ineffective, there are isolated reports of response after corticosteroids, antibiotics, antimycotics, keratolytic measures, or psoralen plus UVA therapy.⁶ Wishart¹¹ used etretinate to achieve an improvement of PA. We also achieved good response with acitretin. Retinoids are known to have antineoplastic activity, which may have been helpful in both the patient we presented and the one reported by Wishart.¹¹ In summary, we propose adding ISFL to the expanding list of malignant neoplasms associated with PA, noting the response of skin lesions after acitretin.