Melanoma

Gerami et al (Clin Cancer Res. 2015;21:175-183) discussed the development and use of a genetic signature to predict the likelihood of metastasis from cutaneous melanoma. A genetic signature comprised of 28 prognostic genetic targets and 3 control genes was developed from the expression data available and reverse transcriptase–polymerase chain reaction analysis of more than 260 primary cutaneous melanoma cases was performed. Genetic expression data from public databases were used to identify genes that were similarly upregulated or downregulated in metastatic disease. The analysis of cutaneous melanoma and uveal melanoma tumors led to the selection of 54 gene targets that had different expression profiles for primary tumors compared with metastatic tumors. Of the 54 targets of interest, 20 were selected for further reverse transcriptase–polymerase chain reaction analysis based on genetic loci. Additionally, analysis of metastatic and nonmetastatic primary cutaneous melanoma tumors using a profile assay for uveal melanoma led to the selection of 5 additional gene targets. The sample set of cases included 107 stage I and stage II primary melanomas. Twenty cases had metastatic disease and 5 cases had regional recurrence.

Prediction of metastatic risk for this test was classified either as class 1 (low risk) or class 2 (high risk). In the development cohort, 43 of 107 cases were predicted to be class 2. All cases with documented metastatic progression were called class 2 (100% sensitivity), whereas 64 of 82 nonmetastatic cases were called class 1 (78% specificity; accuracy determined by the area under the receiver operating characteristic curve, 0.93). Kaplan-Meier survival analysis revealed that disease-free survival for the predicted classes was significantly different (P<.0001). Also, the median time to metastasis for class 2 cases was 2.5 years, whereas the median time for class 1 cases was not reached. Five-year disease-free survival was 100% for class 1 cases compared with 38% for class 2 cases.

What’s the issue?

Stage I cutaneous melanoma tumors have a 5-year overall survival rate of 91% to 97%. Although the majority of clinical stage I patients will be disease free at 5 years, some stage I patients will develop advanced disease. Furthermore, prognosis for clinical stage II and stage III cases by the TNM staging system is highly variable, as evidenced by a 5-year survival rate of 53% to 82% for stage II patients and a 5-year survival rate of 22% to 68% for stage III patients. However, up to 20% of stage I and stage II patients will die from the disease within 4 years of the initial diagnosis. This statistic can be difficult for patients, as it can be unclear which stage I and stage II patients are more at risk.

This test had a limited number of samples that were used to create this predictive tool. Would patients with stage I and stage II disease deemed to be high risk by this test benefit from adjuvant therapy and/or enhanced imaging protocols to allow for early detection of metastasis? Will you be recommending this test to your melanoma patients?

We want to know your views! Tell us what you think.

Gerami et al (Clin Cancer Res. 2015;21:175-183) discussed the development and use of a genetic signature to predict the likelihood of metastasis from cutaneous melanoma. A genetic signature comprised of 28 prognostic genetic targets and 3 control genes was developed from the expression data available and reverse transcriptase–polymerase chain reaction analysis of more than 260 primary cutaneous melanoma cases was performed. Genetic expression data from public databases were used to identify genes that were similarly upregulated or downregulated in metastatic disease. The analysis of cutaneous melanoma and uveal melanoma tumors led to the selection of 54 gene targets that had different expression profiles for primary tumors compared with metastatic tumors. Of the 54 targets of interest, 20 were selected for further reverse transcriptase–polymerase chain reaction analysis based on genetic loci. Additionally, analysis of metastatic and nonmetastatic primary cutaneous melanoma tumors using a profile assay for uveal melanoma led to the selection of 5 additional gene targets. The sample set of cases included 107 stage I and stage II primary melanomas. Twenty cases had metastatic disease and 5 cases had regional recurrence.

Prediction of metastatic risk for this test was classified either as class 1 (low risk) or class 2 (high risk). In the development cohort, 43 of 107 cases were predicted to be class 2. All cases with documented metastatic progression were called class 2 (100% sensitivity), whereas 64 of 82 nonmetastatic cases were called class 1 (78% specificity; accuracy determined by the area under the receiver operating characteristic curve, 0.93). Kaplan-Meier survival analysis revealed that disease-free survival for the predicted classes was significantly different (P<.0001). Also, the median time to metastasis for class 2 cases was 2.5 years, whereas the median time for class 1 cases was not reached. Five-year disease-free survival was 100% for class 1 cases compared with 38% for class 2 cases.

What’s the issue?

Stage I cutaneous melanoma tumors have a 5-year overall survival rate of 91% to 97%. Although the majority of clinical stage I patients will be disease free at 5 years, some stage I patients will develop advanced disease. Furthermore, prognosis for clinical stage II and stage III cases by the TNM staging system is highly variable, as evidenced by a 5-year survival rate of 53% to 82% for stage II patients and a 5-year survival rate of 22% to 68% for stage III patients. However, up to 20% of stage I and stage II patients will die from the disease within 4 years of the initial diagnosis. This statistic can be difficult for patients, as it can be unclear which stage I and stage II patients are more at risk.

This test had a limited number of samples that were used to create this predictive tool. Would patients with stage I and stage II disease deemed to be high risk by this test benefit from adjuvant therapy and/or enhanced imaging protocols to allow for early detection of metastasis? Will you be recommending this test to your melanoma patients?

We want to know your views! Tell us what you think.

Gerami et al (Clin Cancer Res. 2015;21:175-183) discussed the development and use of a genetic signature to predict the likelihood of metastasis from cutaneous melanoma. A genetic signature comprised of 28 prognostic genetic targets and 3 control genes was developed from the expression data available and reverse transcriptase–polymerase chain reaction analysis of more than 260 primary cutaneous melanoma cases was performed. Genetic expression data from public databases were used to identify genes that were similarly upregulated or downregulated in metastatic disease. The analysis of cutaneous melanoma and uveal melanoma tumors led to the selection of 54 gene targets that had different expression profiles for primary tumors compared with metastatic tumors. Of the 54 targets of interest, 20 were selected for further reverse transcriptase–polymerase chain reaction analysis based on genetic loci. Additionally, analysis of metastatic and nonmetastatic primary cutaneous melanoma tumors using a profile assay for uveal melanoma led to the selection of 5 additional gene targets. The sample set of cases included 107 stage I and stage II primary melanomas. Twenty cases had metastatic disease and 5 cases had regional recurrence.

Prediction of metastatic risk for this test was classified either as class 1 (low risk) or class 2 (high risk). In the development cohort, 43 of 107 cases were predicted to be class 2. All cases with documented metastatic progression were called class 2 (100% sensitivity), whereas 64 of 82 nonmetastatic cases were called class 1 (78% specificity; accuracy determined by the area under the receiver operating characteristic curve, 0.93). Kaplan-Meier survival analysis revealed that disease-free survival for the predicted classes was significantly different (P<.0001). Also, the median time to metastasis for class 2 cases was 2.5 years, whereas the median time for class 1 cases was not reached. Five-year disease-free survival was 100% for class 1 cases compared with 38% for class 2 cases.

What’s the issue?

Stage I cutaneous melanoma tumors have a 5-year overall survival rate of 91% to 97%. Although the majority of clinical stage I patients will be disease free at 5 years, some stage I patients will develop advanced disease. Furthermore, prognosis for clinical stage II and stage III cases by the TNM staging system is highly variable, as evidenced by a 5-year survival rate of 53% to 82% for stage II patients and a 5-year survival rate of 22% to 68% for stage III patients. However, up to 20% of stage I and stage II patients will die from the disease within 4 years of the initial diagnosis. This statistic can be difficult for patients, as it can be unclear which stage I and stage II patients are more at risk.

This test had a limited number of samples that were used to create this predictive tool. Would patients with stage I and stage II disease deemed to be high risk by this test benefit from adjuvant therapy and/or enhanced imaging protocols to allow for early detection of metastasis? Will you be recommending this test to your melanoma patients?

We want to know your views! Tell us what you think.

SAN FRANCISCO – Gay and bisexual men are about six times more likely to use tanning beds than straight men, and have about twice the risk of skin cancer, according to a review of California Health Interview Surveys and the 2013 National Health Interview Survey, which captured results for almost 200,000 adult men and women.

Overall, 5-11% of gay and bisexual men reported using tanning beds, versus about 1-3% of straight men. The lifetime history of skin cancer was about 4.3-6.6% among sexual minority men, but about 2.7-3.3% among straight men. The differences were statistically significant.

The study doesn’t prove cause and effect, but it does define a previously unrecognized group at higher risk for skin cancer, and a potential reason for it. Investigator Dr. Sarah Arron, associate professor of dermatology at the University of California, San Francisco, explained what the findings mean for practicing dermatologists in an interview at the annual meeting of the American Academy of Dermatology.

Meanwhile, the study found that gay and bisexual women were less likely than straight women to report using tanning beds, and less likely to report non-melanoma skin cancer.

[email protected]

SAN FRANCISCO – Gay and bisexual men are about six times more likely to use tanning beds than straight men, and have about twice the risk of skin cancer, according to a review of California Health Interview Surveys and the 2013 National Health Interview Survey, which captured results for almost 200,000 adult men and women.

Overall, 5-11% of gay and bisexual men reported using tanning beds, versus about 1-3% of straight men. The lifetime history of skin cancer was about 4.3-6.6% among sexual minority men, but about 2.7-3.3% among straight men. The differences were statistically significant.

The study doesn’t prove cause and effect, but it does define a previously unrecognized group at higher risk for skin cancer, and a potential reason for it. Investigator Dr. Sarah Arron, associate professor of dermatology at the University of California, San Francisco, explained what the findings mean for practicing dermatologists in an interview at the annual meeting of the American Academy of Dermatology.

Meanwhile, the study found that gay and bisexual women were less likely than straight women to report using tanning beds, and less likely to report non-melanoma skin cancer.

[email protected]

SAN FRANCISCO – Gay and bisexual men are about six times more likely to use tanning beds than straight men, and have about twice the risk of skin cancer, according to a review of California Health Interview Surveys and the 2013 National Health Interview Survey, which captured results for almost 200,000 adult men and women.

Overall, 5-11% of gay and bisexual men reported using tanning beds, versus about 1-3% of straight men. The lifetime history of skin cancer was about 4.3-6.6% among sexual minority men, but about 2.7-3.3% among straight men. The differences were statistically significant.

The study doesn’t prove cause and effect, but it does define a previously unrecognized group at higher risk for skin cancer, and a potential reason for it. Investigator Dr. Sarah Arron, associate professor of dermatology at the University of California, San Francisco, explained what the findings mean for practicing dermatologists in an interview at the annual meeting of the American Academy of Dermatology.

Meanwhile, the study found that gay and bisexual women were less likely than straight women to report using tanning beds, and less likely to report non-melanoma skin cancer.

[email protected]

SAN FRANCISCO – Older white men are most at risk to die from skin cancer after organ transplants, especially if they’ve had a heart or lung transplant, according to a review of more than a half million U.S. organ transplants from 1987-2013.

It’s long been known that skin cancer is far more likely after solid organ transplants, but it hasn’t been clear until now who’s most likely to die from the disease.

Overall, there were 985 skin cancer deaths following transplant, or 32 deaths per 100,000 patient-years. For white men over 50 years old with thoracic transplants, however, there were 183 deaths per 100,000 patient-years. In contrast, the age-adjusted death rate from malignant melanoma in the general population is 2.7 per 100,000 patient-years.

Investigator Dr. Sarah Arron, associate professor of dermatology at the University of California, San Francisco, explained what to do about the findings in an interview at the annual meeting of the American Academy of Dermatology.

[email protected]

SAN FRANCISCO – Older white men are most at risk to die from skin cancer after organ transplants, especially if they’ve had a heart or lung transplant, according to a review of more than a half million U.S. organ transplants from 1987-2013.

It’s long been known that skin cancer is far more likely after solid organ transplants, but it hasn’t been clear until now who’s most likely to die from the disease.

Overall, there were 985 skin cancer deaths following transplant, or 32 deaths per 100,000 patient-years. For white men over 50 years old with thoracic transplants, however, there were 183 deaths per 100,000 patient-years. In contrast, the age-adjusted death rate from malignant melanoma in the general population is 2.7 per 100,000 patient-years.

Investigator Dr. Sarah Arron, associate professor of dermatology at the University of California, San Francisco, explained what to do about the findings in an interview at the annual meeting of the American Academy of Dermatology.

[email protected]

SAN FRANCISCO – Older white men are most at risk to die from skin cancer after organ transplants, especially if they’ve had a heart or lung transplant, according to a review of more than a half million U.S. organ transplants from 1987-2013.

It’s long been known that skin cancer is far more likely after solid organ transplants, but it hasn’t been clear until now who’s most likely to die from the disease.

Overall, there were 985 skin cancer deaths following transplant, or 32 deaths per 100,000 patient-years. For white men over 50 years old with thoracic transplants, however, there were 183 deaths per 100,000 patient-years. In contrast, the age-adjusted death rate from malignant melanoma in the general population is 2.7 per 100,000 patient-years.

Investigator Dr. Sarah Arron, associate professor of dermatology at the University of California, San Francisco, explained what to do about the findings in an interview at the annual meeting of the American Academy of Dermatology.

[email protected]

KAUAI, HAWAII – If you’re thinking of offering dermoscopy to your patients, which are the best machines for your practice? Are there advantages to having one machine or several? And will you need to do certain kinds of biopsies instead of others?

Dr. David L. Swanson of the Mayo Clinic in Scottsdale, Ariz., was this year’s featured dermoscopy expert at the annual Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation. He shared his top tips for helping physicians maximize the latest in this technology for the benefit of your patients.

Skin Disease Education Foundation and this news organization are owned by the same parent company.

[email protected]

On Twitter @whitneymcknight

KAUAI, HAWAII – If you’re thinking of offering dermoscopy to your patients, which are the best machines for your practice? Are there advantages to having one machine or several? And will you need to do certain kinds of biopsies instead of others?

Dr. David L. Swanson of the Mayo Clinic in Scottsdale, Ariz., was this year’s featured dermoscopy expert at the annual Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation. He shared his top tips for helping physicians maximize the latest in this technology for the benefit of your patients.

Skin Disease Education Foundation and this news organization are owned by the same parent company.

[email protected]

On Twitter @whitneymcknight

KAUAI, HAWAII – If you’re thinking of offering dermoscopy to your patients, which are the best machines for your practice? Are there advantages to having one machine or several? And will you need to do certain kinds of biopsies instead of others?

Dr. David L. Swanson of the Mayo Clinic in Scottsdale, Ariz., was this year’s featured dermoscopy expert at the annual Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation. He shared his top tips for helping physicians maximize the latest in this technology for the benefit of your patients.

Skin Disease Education Foundation and this news organization are owned by the same parent company.

[email protected]

On Twitter @whitneymcknight

The Diagnosis: Spindle Cell Malignant Melanoma With Perineural Invasion

The incidence of melanoma has steadily increased in the United States since the 1930s when the incidence was reported at 1.0 per 100,000.¹ In 1973 melanoma incidence was 6.8 per 100,000, and by 2007 the rate increased to 20.1 per 100,000.² The American Cancer Society projects 73,870 new cases of melanoma in 2015, with melanoma as the fifth most common cancer in males and the seventh most common in females.³ Melanoma-related deaths are projected to be 9940. The lifetime probability of developing melanoma is 1 in 34 for males and 1 in 53 for females. Twice as many males are estimated to have melanoma-related deaths compared to females. The 5-year relative survival rate is 93% for white individuals and 75% for black individuals.³

Spindle cell melanoma is a rare variant of melanoma that was originally described by Conley et al⁴ in 1971. The lesion represents 2% to 4% of all melanomas and presents in older patients on sun-exposed skin as a pink or variably pigmented nodule measuring an average of 2 cm.⁵ Males are affected more than females, and prominent neural invasion is present in 30% to 100% of cases.^6-10 Neural invasion can result in nerve palsies and/or dysesthesia. Because half of these lesions are amelanotic, they are often clinically misdiagnosed prior to biopsy.¹¹

Histopathologically, these lesions can be quite challenging. Spindle cell melanoma histologically is an intradermal lesion composed of spindle cells distributed in bundles, fascicles, or nests, or singly between collagen fibers of the dermis. Other spindle tumors such as spindle cell squamous cell carcinoma, atypical fibroxanthoma, dermatofibrosarcoma protuberans, angiosarcoma, and leiomyosarcoma have a similar presentation with hematoxylin and eosin stain. The diagnostic process for spindle cell tumors is greatly aided by immunohistologic analysis. Spindle cell melanoma usually shows immunoreactivity with S-100. Human melanoma black 45, CD57, and neuron-specific enolase usually do not stain, and CD68 has been demonstrated in a minority of cases.

The initial biopsy specimen in our case displayed a dense dermal atypical spindle cell proliferation with hematoxylin and eosin stain. The differential diagnosis of the proliferation included desmoplastic melanoma, spindle cell squamous cell carcinoma, leiomyosarcoma, angiosarcoma, and atypical fibroxanthoma. Immunostains were used to further study the lesional biopsy. Cytokeratin 34bE12, CK5/6, cerium ammonium molybdate 5.2, CK7, epithelial membrane antigen, CK18, high-molecular-weight cytokeratin, S-100, Melan-A, human melanoma black 45, smooth muscle actin, desmin, CD68, CD34, CD10, and p63 were studied. The atypical dermal spindle cells were positive for S-100. S-100 and Melan-A highlighted an increased number of single melanocytes at the dermoepidermal junction. Other markers were negative.

A 1.0-cm wide excision to fascia was performed. Routine hematoxylin and eosin stain showed atypical dermal spindle cells with perineural invasion (Figure 1). The malignant spindle cells were S-100 positive (Figure 2). The spindle cells were negative for high-molecular-weight cytokeratin, CK5/6, p63, Melan-A, A103, microphthalmia, and tyrosinase. These findings confirm melanoma of the spindle cell type.

Figure 1. A routine hematoxylin and eosin section showed an atypical dermal spindle cell infiltrate (A)(original magnification ×40). Higher magnification showed a malignant dermal spindle cell infiltrate with increased mitoses (B)(original magnification ×100), atypical mitoses (C)(original magnification ×100), and spindle cells with perineural invasion (D)(original magnification ×100). Figure 2. Spindle cell infiltrate with S-100 positivity (original magnification ×100).

The lesion was a Clark level V melanoma with a Breslow thickness of at least 12 mm. Perineural invasion was noted and the mitotic index was 7 cells/mm2. Vascular and lymphatic invasion was negative and ulceration was present. Tumor-infiltrating lymphocytes were brisk, resulting in a pathologic staging of pT4NXMX.

On initial histologic study with hematoxylin and eosin stain, spindle cell melanoma lesions tend to be generally quite thick. Manganoni et al¹² reported in their series a Breslow thickness ranging from 2.1 to 12 mm with a mean of 5.8 mm.

Treatment in our case involved a second wide incision to fascia with an additional 2-cm margin. The role of sentinel lymph node biopsy (SLNB) remains undefined. Patients with spindle cell melanoma have a lower frequency of positive sentinel lymph nodes than nondesmoplastic melanomas.¹³ As such, the need to perform SLNB has not been determined.^13-15 Our patient had a history of breast cancer. The lesion appeared on the left side of the back and she pre-viously had a complete axillary lymphadenectomy on the left axillae. She declined SLNB. A systematic workup by the oncology service was negative. Continued follow-up has revealed no recurrent disease and recent workup was negative for metastatic disease.

Many studies report the increased incidence of local recurrence after excision for spindle cell melanoma as compared to non–spindle cell melanoma,^16-18 which is likely related to perineural invasion as in our patient.

Spindle cell melanoma is a rare tumor that is often amelanotic and difficult to diagnose clinically. Routine hematoxylin and eosin staining shows a dermal spindle cell tumor. Immunohistochemical study is of great aid in defining the tumor. The clinician and pathologist must work together to correctly diagnose and treat this lesion.

The Diagnosis: Spindle Cell Malignant Melanoma With Perineural Invasion

The incidence of melanoma has steadily increased in the United States since the 1930s when the incidence was reported at 1.0 per 100,000.¹ In 1973 melanoma incidence was 6.8 per 100,000, and by 2007 the rate increased to 20.1 per 100,000.² The American Cancer Society projects 73,870 new cases of melanoma in 2015, with melanoma as the fifth most common cancer in males and the seventh most common in females.³ Melanoma-related deaths are projected to be 9940. The lifetime probability of developing melanoma is 1 in 34 for males and 1 in 53 for females. Twice as many males are estimated to have melanoma-related deaths compared to females. The 5-year relative survival rate is 93% for white individuals and 75% for black individuals.³

Spindle cell melanoma is a rare variant of melanoma that was originally described by Conley et al⁴ in 1971. The lesion represents 2% to 4% of all melanomas and presents in older patients on sun-exposed skin as a pink or variably pigmented nodule measuring an average of 2 cm.⁵ Males are affected more than females, and prominent neural invasion is present in 30% to 100% of cases.^6-10 Neural invasion can result in nerve palsies and/or dysesthesia. Because half of these lesions are amelanotic, they are often clinically misdiagnosed prior to biopsy.¹¹

Histopathologically, these lesions can be quite challenging. Spindle cell melanoma histologically is an intradermal lesion composed of spindle cells distributed in bundles, fascicles, or nests, or singly between collagen fibers of the dermis. Other spindle tumors such as spindle cell squamous cell carcinoma, atypical fibroxanthoma, dermatofibrosarcoma protuberans, angiosarcoma, and leiomyosarcoma have a similar presentation with hematoxylin and eosin stain. The diagnostic process for spindle cell tumors is greatly aided by immunohistologic analysis. Spindle cell melanoma usually shows immunoreactivity with S-100. Human melanoma black 45, CD57, and neuron-specific enolase usually do not stain, and CD68 has been demonstrated in a minority of cases.

The initial biopsy specimen in our case displayed a dense dermal atypical spindle cell proliferation with hematoxylin and eosin stain. The differential diagnosis of the proliferation included desmoplastic melanoma, spindle cell squamous cell carcinoma, leiomyosarcoma, angiosarcoma, and atypical fibroxanthoma. Immunostains were used to further study the lesional biopsy. Cytokeratin 34bE12, CK5/6, cerium ammonium molybdate 5.2, CK7, epithelial membrane antigen, CK18, high-molecular-weight cytokeratin, S-100, Melan-A, human melanoma black 45, smooth muscle actin, desmin, CD68, CD34, CD10, and p63 were studied. The atypical dermal spindle cells were positive for S-100. S-100 and Melan-A highlighted an increased number of single melanocytes at the dermoepidermal junction. Other markers were negative.

A 1.0-cm wide excision to fascia was performed. Routine hematoxylin and eosin stain showed atypical dermal spindle cells with perineural invasion (Figure 1). The malignant spindle cells were S-100 positive (Figure 2). The spindle cells were negative for high-molecular-weight cytokeratin, CK5/6, p63, Melan-A, A103, microphthalmia, and tyrosinase. These findings confirm melanoma of the spindle cell type.

Figure 1. A routine hematoxylin and eosin section showed an atypical dermal spindle cell infiltrate (A)(original magnification ×40). Higher magnification showed a malignant dermal spindle cell infiltrate with increased mitoses (B)(original magnification ×100), atypical mitoses (C)(original magnification ×100), and spindle cells with perineural invasion (D)(original magnification ×100). Figure 2. Spindle cell infiltrate with S-100 positivity (original magnification ×100).

The lesion was a Clark level V melanoma with a Breslow thickness of at least 12 mm. Perineural invasion was noted and the mitotic index was 7 cells/mm2. Vascular and lymphatic invasion was negative and ulceration was present. Tumor-infiltrating lymphocytes were brisk, resulting in a pathologic staging of pT4NXMX.

On initial histologic study with hematoxylin and eosin stain, spindle cell melanoma lesions tend to be generally quite thick. Manganoni et al¹² reported in their series a Breslow thickness ranging from 2.1 to 12 mm with a mean of 5.8 mm.

Treatment in our case involved a second wide incision to fascia with an additional 2-cm margin. The role of sentinel lymph node biopsy (SLNB) remains undefined. Patients with spindle cell melanoma have a lower frequency of positive sentinel lymph nodes than nondesmoplastic melanomas.¹³ As such, the need to perform SLNB has not been determined.^13-15 Our patient had a history of breast cancer. The lesion appeared on the left side of the back and she pre-viously had a complete axillary lymphadenectomy on the left axillae. She declined SLNB. A systematic workup by the oncology service was negative. Continued follow-up has revealed no recurrent disease and recent workup was negative for metastatic disease.

Many studies report the increased incidence of local recurrence after excision for spindle cell melanoma as compared to non–spindle cell melanoma,^16-18 which is likely related to perineural invasion as in our patient.

Spindle cell melanoma is a rare tumor that is often amelanotic and difficult to diagnose clinically. Routine hematoxylin and eosin staining shows a dermal spindle cell tumor. Immunohistochemical study is of great aid in defining the tumor. The clinician and pathologist must work together to correctly diagnose and treat this lesion.

The Diagnosis: Spindle Cell Malignant Melanoma With Perineural Invasion

The incidence of melanoma has steadily increased in the United States since the 1930s when the incidence was reported at 1.0 per 100,000.¹ In 1973 melanoma incidence was 6.8 per 100,000, and by 2007 the rate increased to 20.1 per 100,000.² The American Cancer Society projects 73,870 new cases of melanoma in 2015, with melanoma as the fifth most common cancer in males and the seventh most common in females.³ Melanoma-related deaths are projected to be 9940. The lifetime probability of developing melanoma is 1 in 34 for males and 1 in 53 for females. Twice as many males are estimated to have melanoma-related deaths compared to females. The 5-year relative survival rate is 93% for white individuals and 75% for black individuals.³

Spindle cell melanoma is a rare variant of melanoma that was originally described by Conley et al⁴ in 1971. The lesion represents 2% to 4% of all melanomas and presents in older patients on sun-exposed skin as a pink or variably pigmented nodule measuring an average of 2 cm.⁵ Males are affected more than females, and prominent neural invasion is present in 30% to 100% of cases.^6-10 Neural invasion can result in nerve palsies and/or dysesthesia. Because half of these lesions are amelanotic, they are often clinically misdiagnosed prior to biopsy.¹¹

Histopathologically, these lesions can be quite challenging. Spindle cell melanoma histologically is an intradermal lesion composed of spindle cells distributed in bundles, fascicles, or nests, or singly between collagen fibers of the dermis. Other spindle tumors such as spindle cell squamous cell carcinoma, atypical fibroxanthoma, dermatofibrosarcoma protuberans, angiosarcoma, and leiomyosarcoma have a similar presentation with hematoxylin and eosin stain. The diagnostic process for spindle cell tumors is greatly aided by immunohistologic analysis. Spindle cell melanoma usually shows immunoreactivity with S-100. Human melanoma black 45, CD57, and neuron-specific enolase usually do not stain, and CD68 has been demonstrated in a minority of cases.

The initial biopsy specimen in our case displayed a dense dermal atypical spindle cell proliferation with hematoxylin and eosin stain. The differential diagnosis of the proliferation included desmoplastic melanoma, spindle cell squamous cell carcinoma, leiomyosarcoma, angiosarcoma, and atypical fibroxanthoma. Immunostains were used to further study the lesional biopsy. Cytokeratin 34bE12, CK5/6, cerium ammonium molybdate 5.2, CK7, epithelial membrane antigen, CK18, high-molecular-weight cytokeratin, S-100, Melan-A, human melanoma black 45, smooth muscle actin, desmin, CD68, CD34, CD10, and p63 were studied. The atypical dermal spindle cells were positive for S-100. S-100 and Melan-A highlighted an increased number of single melanocytes at the dermoepidermal junction. Other markers were negative.

A 1.0-cm wide excision to fascia was performed. Routine hematoxylin and eosin stain showed atypical dermal spindle cells with perineural invasion (Figure 1). The malignant spindle cells were S-100 positive (Figure 2). The spindle cells were negative for high-molecular-weight cytokeratin, CK5/6, p63, Melan-A, A103, microphthalmia, and tyrosinase. These findings confirm melanoma of the spindle cell type.

Figure 1. A routine hematoxylin and eosin section showed an atypical dermal spindle cell infiltrate (A)(original magnification ×40). Higher magnification showed a malignant dermal spindle cell infiltrate with increased mitoses (B)(original magnification ×100), atypical mitoses (C)(original magnification ×100), and spindle cells with perineural invasion (D)(original magnification ×100). Figure 2. Spindle cell infiltrate with S-100 positivity (original magnification ×100).

The lesion was a Clark level V melanoma with a Breslow thickness of at least 12 mm. Perineural invasion was noted and the mitotic index was 7 cells/mm2. Vascular and lymphatic invasion was negative and ulceration was present. Tumor-infiltrating lymphocytes were brisk, resulting in a pathologic staging of pT4NXMX.

On initial histologic study with hematoxylin and eosin stain, spindle cell melanoma lesions tend to be generally quite thick. Manganoni et al¹² reported in their series a Breslow thickness ranging from 2.1 to 12 mm with a mean of 5.8 mm.

Treatment in our case involved a second wide incision to fascia with an additional 2-cm margin. The role of sentinel lymph node biopsy (SLNB) remains undefined. Patients with spindle cell melanoma have a lower frequency of positive sentinel lymph nodes than nondesmoplastic melanomas.¹³ As such, the need to perform SLNB has not been determined.^13-15 Our patient had a history of breast cancer. The lesion appeared on the left side of the back and she pre-viously had a complete axillary lymphadenectomy on the left axillae. She declined SLNB. A systematic workup by the oncology service was negative. Continued follow-up has revealed no recurrent disease and recent workup was negative for metastatic disease.

Many studies report the increased incidence of local recurrence after excision for spindle cell melanoma as compared to non–spindle cell melanoma,^16-18 which is likely related to perineural invasion as in our patient.

Spindle cell melanoma is a rare tumor that is often amelanotic and difficult to diagnose clinically. Routine hematoxylin and eosin staining shows a dermal spindle cell tumor. Immunohistochemical study is of great aid in defining the tumor. The clinician and pathologist must work together to correctly diagnose and treat this lesion.

Among patients with early or advanced melanoma, elevated blood levels of C-reactive protein (CRP) predicted disease recurrence and poorer survival. In a subset of patients who had sequential blood draws, CRP levels indicated melanoma disease progression, according to a study published online March 16 in the Journal of Clinical Oncology.

CRP measurements for 1,144 patients demonstrated that elevated CRP was associated with increased overall risk of death (hazard ratio, 1.44/U increase of logarithmic CRP; 95% confidence interval, 1.30-1.59; P < .001), reported Dr. Shenying Fang of the University of Texas MD Anderson Cancer Center, Houston, and his associates.

“These data provide strong evidence that CRP is an independent prognostic biomarker in patients with melanoma, including those with early-stage disease as well as those with advanced-stage disease. A markedly elevated CRP level in particular seems to identify a subgroup of patients at high risk for disease recurrence and death,” they said (J. Clin. Onc. 2015 March 16 [doi: 10.1200/JCO.2014.58.0209]).

Investigators demonstrated a dose effect by dividing CRP levels into quintiles and showing patients in the highest quintile had significantly poorer overall survival than did those in the lowest quintile (HR, 4.14; 2.58-6.64), and significant trends across quintiles. Recursive partitioning indicated the best CRP cutoff value was 10.94 mg/L, close to the commonly used clinical cutoff of 10 mg/L. CRP levels greater than or equal to 10 mg/L predicted poorer survival and higher rates of recurrence.

For a subset of 115 patients, data from sequential blood draws showed a correlation between increasing CRP levels in an individual and disease progression. Changes in CRP levels were obtained at a median of 17.12 months apart, and increased levels were associated with poorer response to treatment (P < .001), progression of disease (P < .001), increase in cancer stage (P = .0065), and increase vs. no increase in number of metastases (P = .0013).

Dr. Fang and his associates suggest further studies on potential benefits of reducing inflammation and/or CRP on melanoma patients. Statins reduce CRP levels, but their effect on cancer prevention is unclear.

“Although there is as yet no defined role for clinical use of statins in cancer treatment, our data suggest that preclinical evaluation of statin therapy in melanoma models is reasonable to pursue,” they wrote.

Among patients with early or advanced melanoma, elevated blood levels of C-reactive protein (CRP) predicted disease recurrence and poorer survival. In a subset of patients who had sequential blood draws, CRP levels indicated melanoma disease progression, according to a study published online March 16 in the Journal of Clinical Oncology.

CRP measurements for 1,144 patients demonstrated that elevated CRP was associated with increased overall risk of death (hazard ratio, 1.44/U increase of logarithmic CRP; 95% confidence interval, 1.30-1.59; P < .001), reported Dr. Shenying Fang of the University of Texas MD Anderson Cancer Center, Houston, and his associates.

“These data provide strong evidence that CRP is an independent prognostic biomarker in patients with melanoma, including those with early-stage disease as well as those with advanced-stage disease. A markedly elevated CRP level in particular seems to identify a subgroup of patients at high risk for disease recurrence and death,” they said (J. Clin. Onc. 2015 March 16 [doi: 10.1200/JCO.2014.58.0209]).

Investigators demonstrated a dose effect by dividing CRP levels into quintiles and showing patients in the highest quintile had significantly poorer overall survival than did those in the lowest quintile (HR, 4.14; 2.58-6.64), and significant trends across quintiles. Recursive partitioning indicated the best CRP cutoff value was 10.94 mg/L, close to the commonly used clinical cutoff of 10 mg/L. CRP levels greater than or equal to 10 mg/L predicted poorer survival and higher rates of recurrence.

For a subset of 115 patients, data from sequential blood draws showed a correlation between increasing CRP levels in an individual and disease progression. Changes in CRP levels were obtained at a median of 17.12 months apart, and increased levels were associated with poorer response to treatment (P < .001), progression of disease (P < .001), increase in cancer stage (P = .0065), and increase vs. no increase in number of metastases (P = .0013).

Dr. Fang and his associates suggest further studies on potential benefits of reducing inflammation and/or CRP on melanoma patients. Statins reduce CRP levels, but their effect on cancer prevention is unclear.

“Although there is as yet no defined role for clinical use of statins in cancer treatment, our data suggest that preclinical evaluation of statin therapy in melanoma models is reasonable to pursue,” they wrote.

Among patients with early or advanced melanoma, elevated blood levels of C-reactive protein (CRP) predicted disease recurrence and poorer survival. In a subset of patients who had sequential blood draws, CRP levels indicated melanoma disease progression, according to a study published online March 16 in the Journal of Clinical Oncology.

CRP measurements for 1,144 patients demonstrated that elevated CRP was associated with increased overall risk of death (hazard ratio, 1.44/U increase of logarithmic CRP; 95% confidence interval, 1.30-1.59; P < .001), reported Dr. Shenying Fang of the University of Texas MD Anderson Cancer Center, Houston, and his associates.

“These data provide strong evidence that CRP is an independent prognostic biomarker in patients with melanoma, including those with early-stage disease as well as those with advanced-stage disease. A markedly elevated CRP level in particular seems to identify a subgroup of patients at high risk for disease recurrence and death,” they said (J. Clin. Onc. 2015 March 16 [doi: 10.1200/JCO.2014.58.0209]).

Investigators demonstrated a dose effect by dividing CRP levels into quintiles and showing patients in the highest quintile had significantly poorer overall survival than did those in the lowest quintile (HR, 4.14; 2.58-6.64), and significant trends across quintiles. Recursive partitioning indicated the best CRP cutoff value was 10.94 mg/L, close to the commonly used clinical cutoff of 10 mg/L. CRP levels greater than or equal to 10 mg/L predicted poorer survival and higher rates of recurrence.

For a subset of 115 patients, data from sequential blood draws showed a correlation between increasing CRP levels in an individual and disease progression. Changes in CRP levels were obtained at a median of 17.12 months apart, and increased levels were associated with poorer response to treatment (P < .001), progression of disease (P < .001), increase in cancer stage (P = .0065), and increase vs. no increase in number of metastases (P = .0013).

Dr. Fang and his associates suggest further studies on potential benefits of reducing inflammation and/or CRP on melanoma patients. Statins reduce CRP levels, but their effect on cancer prevention is unclear.

“Although there is as yet no defined role for clinical use of statins in cancer treatment, our data suggest that preclinical evaluation of statin therapy in melanoma models is reasonable to pursue,” they wrote.

Nail matrix biopsies are performed to confirm a diagnosis or surgically remove a skin lesion that is affecting the growth of the nail plate. The procedure may be used to identify:

Nail biopsy can lead to complications such as bleeding, infection, or scarring. Postoperative scarring can cause permanent nail splitting, dystrophy, or both.

In a Cosmetic Dermatology article, “Matrix Biopsy of Longitudinal Melanonychia and Longitudinal Erythronychia: A Step-by-Step Approach,” Drs. Siobhan C. Collins and Nathaniel J. Jellinek review 6 techniques used to biopsy the nail matrix.

Techniques used to biopsy the nail matrix. From Cosmet Dermatol. 2009;22:130-136.

In the setting of longitudinal melanonychia (to diagnose nail melanoma or SCC) and longitudinal erythronychia (to diagnose SCC and rarely amelanotic melanoma or basal cell carcinoma), the techniques they describe accomplish 3 fundamental goals of nail surgery:

Dermatologists must be confident when performing nail biopsies and the techniques discussed by the authors will help approach nail surgery with more certainty.

At the 73rd Annual Meeting of the American Academy of Dermatology, Dr. Jellinek provides a hands-on approach to nail surgery. On Saturday, March 21, he will provide tips for nail surgeries at the “Medical and Surgical Management of Nail Disorders” lecture.

For more information, read the Collins and Jellinek article from Cosmetic Dermatology.

Nail matrix biopsies are performed to confirm a diagnosis or surgically remove a skin lesion that is affecting the growth of the nail plate. The procedure may be used to identify:

Nail biopsy can lead to complications such as bleeding, infection, or scarring. Postoperative scarring can cause permanent nail splitting, dystrophy, or both.

In a Cosmetic Dermatology article, “Matrix Biopsy of Longitudinal Melanonychia and Longitudinal Erythronychia: A Step-by-Step Approach,” Drs. Siobhan C. Collins and Nathaniel J. Jellinek review 6 techniques used to biopsy the nail matrix.

Techniques used to biopsy the nail matrix. From Cosmet Dermatol. 2009;22:130-136.

In the setting of longitudinal melanonychia (to diagnose nail melanoma or SCC) and longitudinal erythronychia (to diagnose SCC and rarely amelanotic melanoma or basal cell carcinoma), the techniques they describe accomplish 3 fundamental goals of nail surgery:

Dermatologists must be confident when performing nail biopsies and the techniques discussed by the authors will help approach nail surgery with more certainty.

At the 73rd Annual Meeting of the American Academy of Dermatology, Dr. Jellinek provides a hands-on approach to nail surgery. On Saturday, March 21, he will provide tips for nail surgeries at the “Medical and Surgical Management of Nail Disorders” lecture.

For more information, read the Collins and Jellinek article from Cosmetic Dermatology.

Nail matrix biopsies are performed to confirm a diagnosis or surgically remove a skin lesion that is affecting the growth of the nail plate. The procedure may be used to identify:

Nail biopsy can lead to complications such as bleeding, infection, or scarring. Postoperative scarring can cause permanent nail splitting, dystrophy, or both.

In a Cosmetic Dermatology article, “Matrix Biopsy of Longitudinal Melanonychia and Longitudinal Erythronychia: A Step-by-Step Approach,” Drs. Siobhan C. Collins and Nathaniel J. Jellinek review 6 techniques used to biopsy the nail matrix.

Techniques used to biopsy the nail matrix. From Cosmet Dermatol. 2009;22:130-136.

In the setting of longitudinal melanonychia (to diagnose nail melanoma or SCC) and longitudinal erythronychia (to diagnose SCC and rarely amelanotic melanoma or basal cell carcinoma), the techniques they describe accomplish 3 fundamental goals of nail surgery:

Dermatologists must be confident when performing nail biopsies and the techniques discussed by the authors will help approach nail surgery with more certainty.

At the 73rd Annual Meeting of the American Academy of Dermatology, Dr. Jellinek provides a hands-on approach to nail surgery. On Saturday, March 21, he will provide tips for nail surgeries at the “Medical and Surgical Management of Nail Disorders” lecture.

For more information, read the Collins and Jellinek article from Cosmetic Dermatology.