Megan S. Evans, MD

The Diagnosis: Microcystic Lymphatic Malformation

A punch biopsy demonstrated anastomosing fluidfilled spaces within the papillary and reticular dermal layers (Figure), confirming the diagnosis of microcystic lymphatic malformation (LM)(formerly known as lymphangioma circumscriptum), a congenital vascular malformation composed of slow-flow lymphatic channels.1 The patient underwent serial excisions with improvement of the LM, though the treatment course was complicated by hypertrophic scar formation.

The classic clinical presentation of microcystic LM includes a crop of vesicles containing clear or hemorrhagic fluid with associated oozing or bleeding.² When cutaneous lesions resembling microcystic LM develop in response to lymphatic damage and resulting stasis, such as from prior radiotherapy or surgery, the term lymphangiectasia is used to distinguish this entity from congenital microcystic LM.³

Microcystic LMs are histologically indistinguishable from macrocystic LMs; however, macrocystic LMs typically are clinically evident at birth as ill-defined subcutaneous masses.^2,4-6 Dermatitis herpetiformis, a dermatologic manifestation of gluten sensitivity, causes intensely pruritic vesicles in a symmetric distribution on the elbows, knees, and buttocks. Histopathology shows neutrophilic microabscesses in the dermal papillae with subepidermal blistering. Direct immunofluorescence demonstrates the deposition of IgA along the basement membrane with dermal papillae aggregates.⁶ The underlying dermis also may contain a lymphohistiocytic infiltrate rich in neutrophils. The vesicles of herpes zoster virus are painful and present in a dermatomal distribution. A viral cytopathic effect often is observed in keratinocytes, specifically with multinucleation, molding, and margination of chromatin material. The lesions are accompanied by variable lymphocytic inflammation and epithelial necrosis resulting in intraepidermal blistering.⁷ Extragenital lichen sclerosus presents as polygonal white papules merging to form plaques and may include hemorrhagic blisters in some instances. Histopathology shows hyperkeratosis, epidermal atrophy with flattened rete ridges, vacuolar interface changes, loss of elastic fibers, and hyalinization of the lamina propria with lymphocytic infiltrate.⁸

Endothelial cells in LM exhibit activating mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene, PIK3CA, which may lead to proliferation and overgrowth of the lymphatic vasculature, as well as increased production of cyclic guanosine monophosphate.^9,10 Phosphodiesterase 5 (PDE5) is expressed in the perivascular smooth muscle adjacent to lymphatic spaces in LMs but not in the their vasculature. 10 This pattern of PDE5 expression may cause perilesional vasculature to constrict, preventing lymphatic fluid from draining into the veins.¹¹ It is theorized that the PDE5 inhibitor sildenafil leads to relaxation of the vasculature adjacent to LMs, allowing the outflow of the accumulated lymphatic fluid and thus decompression.^11-13

Management of LM should not only take into account the depth and location of involvement but also any associated symptoms or complications, such as pruritus, pain, bleeding, or secondary infections. Magnetic resonance imaging (MRI) typically has been considered the gold standard for determining the size and depth of involvement of the malformation.^1,3,4 However, ultrasonography with Doppler flow may be considered an initial diagnostic and screening test, as it can distinguish between macrocystic and microcystic components and provide superior images of microcystic lesions, which are below the resolution capacity of MRI.4 Notably, our patient’s LM was undetectable on ultrasonography and was found to be largely superficial in nature on MRI.

Serial excision of the microcystic LM was conducted in our patient, but there currently is no consensus on optimal treatment of LM, and many treatment options are complicated by high recurrence rates or complications.⁵ Procedural approaches may include excision, cryotherapy, radiotherapy, sclerotherapy, or laser therapy, while pharmacologic approaches may include sildenafil for its inhibition of PDE5 or sirolimus (oral or topical) for its inhibition of mammalian target of rapamycin.^5,12-14 Because recurrence is highly likely, patients may require repeat treatments or a combination approach to therapy.^1,5 The development of targeted therapies may lead to a shift in management of LMs in the future, as successful use of the PIK3CA inhibitor alpelisib recently has been reported to lead to clinical improvement of PIK3CA-related LMs, including in patients with PIK3CA-related overgrowth syndromes.¹⁵

The Diagnosis: Microcystic Lymphatic Malformation

A punch biopsy demonstrated anastomosing fluidfilled spaces within the papillary and reticular dermal layers (Figure), confirming the diagnosis of microcystic lymphatic malformation (LM)(formerly known as lymphangioma circumscriptum), a congenital vascular malformation composed of slow-flow lymphatic channels.1 The patient underwent serial excisions with improvement of the LM, though the treatment course was complicated by hypertrophic scar formation.

The classic clinical presentation of microcystic LM includes a crop of vesicles containing clear or hemorrhagic fluid with associated oozing or bleeding.² When cutaneous lesions resembling microcystic LM develop in response to lymphatic damage and resulting stasis, such as from prior radiotherapy or surgery, the term lymphangiectasia is used to distinguish this entity from congenital microcystic LM.³

Microcystic LMs are histologically indistinguishable from macrocystic LMs; however, macrocystic LMs typically are clinically evident at birth as ill-defined subcutaneous masses.^2,4-6 Dermatitis herpetiformis, a dermatologic manifestation of gluten sensitivity, causes intensely pruritic vesicles in a symmetric distribution on the elbows, knees, and buttocks. Histopathology shows neutrophilic microabscesses in the dermal papillae with subepidermal blistering. Direct immunofluorescence demonstrates the deposition of IgA along the basement membrane with dermal papillae aggregates.⁶ The underlying dermis also may contain a lymphohistiocytic infiltrate rich in neutrophils. The vesicles of herpes zoster virus are painful and present in a dermatomal distribution. A viral cytopathic effect often is observed in keratinocytes, specifically with multinucleation, molding, and margination of chromatin material. The lesions are accompanied by variable lymphocytic inflammation and epithelial necrosis resulting in intraepidermal blistering.⁷ Extragenital lichen sclerosus presents as polygonal white papules merging to form plaques and may include hemorrhagic blisters in some instances. Histopathology shows hyperkeratosis, epidermal atrophy with flattened rete ridges, vacuolar interface changes, loss of elastic fibers, and hyalinization of the lamina propria with lymphocytic infiltrate.⁸

Endothelial cells in LM exhibit activating mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene, PIK3CA, which may lead to proliferation and overgrowth of the lymphatic vasculature, as well as increased production of cyclic guanosine monophosphate.^9,10 Phosphodiesterase 5 (PDE5) is expressed in the perivascular smooth muscle adjacent to lymphatic spaces in LMs but not in the their vasculature. 10 This pattern of PDE5 expression may cause perilesional vasculature to constrict, preventing lymphatic fluid from draining into the veins.¹¹ It is theorized that the PDE5 inhibitor sildenafil leads to relaxation of the vasculature adjacent to LMs, allowing the outflow of the accumulated lymphatic fluid and thus decompression.^11-13

Management of LM should not only take into account the depth and location of involvement but also any associated symptoms or complications, such as pruritus, pain, bleeding, or secondary infections. Magnetic resonance imaging (MRI) typically has been considered the gold standard for determining the size and depth of involvement of the malformation.^1,3,4 However, ultrasonography with Doppler flow may be considered an initial diagnostic and screening test, as it can distinguish between macrocystic and microcystic components and provide superior images of microcystic lesions, which are below the resolution capacity of MRI.4 Notably, our patient’s LM was undetectable on ultrasonography and was found to be largely superficial in nature on MRI.

Serial excision of the microcystic LM was conducted in our patient, but there currently is no consensus on optimal treatment of LM, and many treatment options are complicated by high recurrence rates or complications.⁵ Procedural approaches may include excision, cryotherapy, radiotherapy, sclerotherapy, or laser therapy, while pharmacologic approaches may include sildenafil for its inhibition of PDE5 or sirolimus (oral or topical) for its inhibition of mammalian target of rapamycin.^5,12-14 Because recurrence is highly likely, patients may require repeat treatments or a combination approach to therapy.^1,5 The development of targeted therapies may lead to a shift in management of LMs in the future, as successful use of the PIK3CA inhibitor alpelisib recently has been reported to lead to clinical improvement of PIK3CA-related LMs, including in patients with PIK3CA-related overgrowth syndromes.¹⁵

The Diagnosis: Microcystic Lymphatic Malformation

A punch biopsy demonstrated anastomosing fluidfilled spaces within the papillary and reticular dermal layers (Figure), confirming the diagnosis of microcystic lymphatic malformation (LM)(formerly known as lymphangioma circumscriptum), a congenital vascular malformation composed of slow-flow lymphatic channels.1 The patient underwent serial excisions with improvement of the LM, though the treatment course was complicated by hypertrophic scar formation.

The classic clinical presentation of microcystic LM includes a crop of vesicles containing clear or hemorrhagic fluid with associated oozing or bleeding.² When cutaneous lesions resembling microcystic LM develop in response to lymphatic damage and resulting stasis, such as from prior radiotherapy or surgery, the term lymphangiectasia is used to distinguish this entity from congenital microcystic LM.³

Microcystic LMs are histologically indistinguishable from macrocystic LMs; however, macrocystic LMs typically are clinically evident at birth as ill-defined subcutaneous masses.^2,4-6 Dermatitis herpetiformis, a dermatologic manifestation of gluten sensitivity, causes intensely pruritic vesicles in a symmetric distribution on the elbows, knees, and buttocks. Histopathology shows neutrophilic microabscesses in the dermal papillae with subepidermal blistering. Direct immunofluorescence demonstrates the deposition of IgA along the basement membrane with dermal papillae aggregates.⁶ The underlying dermis also may contain a lymphohistiocytic infiltrate rich in neutrophils. The vesicles of herpes zoster virus are painful and present in a dermatomal distribution. A viral cytopathic effect often is observed in keratinocytes, specifically with multinucleation, molding, and margination of chromatin material. The lesions are accompanied by variable lymphocytic inflammation and epithelial necrosis resulting in intraepidermal blistering.⁷ Extragenital lichen sclerosus presents as polygonal white papules merging to form plaques and may include hemorrhagic blisters in some instances. Histopathology shows hyperkeratosis, epidermal atrophy with flattened rete ridges, vacuolar interface changes, loss of elastic fibers, and hyalinization of the lamina propria with lymphocytic infiltrate.⁸

Endothelial cells in LM exhibit activating mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene, PIK3CA, which may lead to proliferation and overgrowth of the lymphatic vasculature, as well as increased production of cyclic guanosine monophosphate.^9,10 Phosphodiesterase 5 (PDE5) is expressed in the perivascular smooth muscle adjacent to lymphatic spaces in LMs but not in the their vasculature. 10 This pattern of PDE5 expression may cause perilesional vasculature to constrict, preventing lymphatic fluid from draining into the veins.¹¹ It is theorized that the PDE5 inhibitor sildenafil leads to relaxation of the vasculature adjacent to LMs, allowing the outflow of the accumulated lymphatic fluid and thus decompression.^11-13

Management of LM should not only take into account the depth and location of involvement but also any associated symptoms or complications, such as pruritus, pain, bleeding, or secondary infections. Magnetic resonance imaging (MRI) typically has been considered the gold standard for determining the size and depth of involvement of the malformation.^1,3,4 However, ultrasonography with Doppler flow may be considered an initial diagnostic and screening test, as it can distinguish between macrocystic and microcystic components and provide superior images of microcystic lesions, which are below the resolution capacity of MRI.4 Notably, our patient’s LM was undetectable on ultrasonography and was found to be largely superficial in nature on MRI.

Serial excision of the microcystic LM was conducted in our patient, but there currently is no consensus on optimal treatment of LM, and many treatment options are complicated by high recurrence rates or complications.⁵ Procedural approaches may include excision, cryotherapy, radiotherapy, sclerotherapy, or laser therapy, while pharmacologic approaches may include sildenafil for its inhibition of PDE5 or sirolimus (oral or topical) for its inhibition of mammalian target of rapamycin.^5,12-14 Because recurrence is highly likely, patients may require repeat treatments or a combination approach to therapy.^1,5 The development of targeted therapies may lead to a shift in management of LMs in the future, as successful use of the PIK3CA inhibitor alpelisib recently has been reported to lead to clinical improvement of PIK3CA-related LMs, including in patients with PIK3CA-related overgrowth syndromes.¹⁵

The Diagnosis: Alopecic and Aseptic Nodule of the Scalp

Alopecic and aseptic nodule of the scalp (AANS) is an underdiagnosed condition presenting with one or few inflammatory nodules on the scalp with overlying nonscarring alopecia. The nodules can be soft, fluctuant, or firm and are characterized by negative fungal and bacterial stains as well as cultures.¹ Trichoscopic features such as black or yellow dots, fine vellus hairs, and broken hairs have been reported.^1-3 Dilated follicular openings may be seen and are termed the Eastern pancake sign, as they resemble the bubble cavities formed during the cooking of atayef.² The histologic features of AANS often are nonspecific but show a nodular or pseudocystic, lymphohistiocytic to acute inflammatory component centered in the dermis.¹ Granulomatous inflammation or isolated giant cells have been reported within the deep dermis.^1,4 In our patient, histopathology revealed admixed acute and granulomatous inflammation within the deep dermis (Figure). Treatment of AANS includes oral antibiotics such as doxycycline, intralesional corticosteroids, or excision.¹

Although the etiology of AANS currently is unclear, a process of follicular plugging or a deep folliculitis sparing the bulge stem cells has been theorized. Young males are disproportionately affected.¹ It is uncertain how much overlap there is, if any, between AANS and pseudocyst of the scalp, the latter of which primarily is reported in the Japanese literature and demonstrates alopecic nodules between the forehead and vertex of the scalp with pseudocystic architecture and granulomatous infiltration on histopathology.^4-7

There are several clinical and histologic differences between AANS and other diagnoses in the differential. Dermoid cysts tend to present at birth, with 70% of cases presenting before the age of 6 years, and without overlying skin changes.⁸ They represent a benign entrapment of ectoderm along embryonic closure lines during development.⁹ Histologic examination typically will show a squamous-lined cyst within the dermis with associated adnexal structures.¹⁰ Cylindromas are benign neoplasms of eccrine sweat glands named after the histologic presentation of cylinder-shaped basaloid cell populations when cross-sectioned.^11,12 When cylindromas coalesce on the scalp, they form a distinctive morphology sometimes loosely resembling a turban, giving them the previously more common name turban tumors.^11,13 Cylindromas appear as slow-growing protuberant tumors that are erythematous or flesh colored. Cylindromas are 9 times more common in females.13 Pilar cysts have a stratified squamous epithelium lining with a palisaded outer layer and are derived from the outer root sheath of hair follicles.¹⁴ Clinically, pilar cysts are smooth mobile cysts that favor skin with a dense concentration of hair follicles.^14,15 On palpation, pilar cysts are firm due to their keratinous contents and typically are nontender unless inflamed.¹⁵ Lipomas are benign mesenchymal tumors with mature adipocytes that often appear as subcutaneous nodules without overlying skin changes, though they can involve deep fascia. On palpation, lipomas generally are soft, mobile, and nontender.¹⁶

The Diagnosis: Alopecic and Aseptic Nodule of the Scalp

Alopecic and aseptic nodule of the scalp (AANS) is an underdiagnosed condition presenting with one or few inflammatory nodules on the scalp with overlying nonscarring alopecia. The nodules can be soft, fluctuant, or firm and are characterized by negative fungal and bacterial stains as well as cultures.¹ Trichoscopic features such as black or yellow dots, fine vellus hairs, and broken hairs have been reported.^1-3 Dilated follicular openings may be seen and are termed the Eastern pancake sign, as they resemble the bubble cavities formed during the cooking of atayef.² The histologic features of AANS often are nonspecific but show a nodular or pseudocystic, lymphohistiocytic to acute inflammatory component centered in the dermis.¹ Granulomatous inflammation or isolated giant cells have been reported within the deep dermis.^1,4 In our patient, histopathology revealed admixed acute and granulomatous inflammation within the deep dermis (Figure). Treatment of AANS includes oral antibiotics such as doxycycline, intralesional corticosteroids, or excision.¹

Although the etiology of AANS currently is unclear, a process of follicular plugging or a deep folliculitis sparing the bulge stem cells has been theorized. Young males are disproportionately affected.¹ It is uncertain how much overlap there is, if any, between AANS and pseudocyst of the scalp, the latter of which primarily is reported in the Japanese literature and demonstrates alopecic nodules between the forehead and vertex of the scalp with pseudocystic architecture and granulomatous infiltration on histopathology.^4-7

There are several clinical and histologic differences between AANS and other diagnoses in the differential. Dermoid cysts tend to present at birth, with 70% of cases presenting before the age of 6 years, and without overlying skin changes.⁸ They represent a benign entrapment of ectoderm along embryonic closure lines during development.⁹ Histologic examination typically will show a squamous-lined cyst within the dermis with associated adnexal structures.¹⁰ Cylindromas are benign neoplasms of eccrine sweat glands named after the histologic presentation of cylinder-shaped basaloid cell populations when cross-sectioned.^11,12 When cylindromas coalesce on the scalp, they form a distinctive morphology sometimes loosely resembling a turban, giving them the previously more common name turban tumors.^11,13 Cylindromas appear as slow-growing protuberant tumors that are erythematous or flesh colored. Cylindromas are 9 times more common in females.13 Pilar cysts have a stratified squamous epithelium lining with a palisaded outer layer and are derived from the outer root sheath of hair follicles.¹⁴ Clinically, pilar cysts are smooth mobile cysts that favor skin with a dense concentration of hair follicles.^14,15 On palpation, pilar cysts are firm due to their keratinous contents and typically are nontender unless inflamed.¹⁵ Lipomas are benign mesenchymal tumors with mature adipocytes that often appear as subcutaneous nodules without overlying skin changes, though they can involve deep fascia. On palpation, lipomas generally are soft, mobile, and nontender.¹⁶

The Diagnosis: Alopecic and Aseptic Nodule of the Scalp

Alopecic and aseptic nodule of the scalp (AANS) is an underdiagnosed condition presenting with one or few inflammatory nodules on the scalp with overlying nonscarring alopecia. The nodules can be soft, fluctuant, or firm and are characterized by negative fungal and bacterial stains as well as cultures.¹ Trichoscopic features such as black or yellow dots, fine vellus hairs, and broken hairs have been reported.^1-3 Dilated follicular openings may be seen and are termed the Eastern pancake sign, as they resemble the bubble cavities formed during the cooking of atayef.² The histologic features of AANS often are nonspecific but show a nodular or pseudocystic, lymphohistiocytic to acute inflammatory component centered in the dermis.¹ Granulomatous inflammation or isolated giant cells have been reported within the deep dermis.^1,4 In our patient, histopathology revealed admixed acute and granulomatous inflammation within the deep dermis (Figure). Treatment of AANS includes oral antibiotics such as doxycycline, intralesional corticosteroids, or excision.¹

Although the etiology of AANS currently is unclear, a process of follicular plugging or a deep folliculitis sparing the bulge stem cells has been theorized. Young males are disproportionately affected.¹ It is uncertain how much overlap there is, if any, between AANS and pseudocyst of the scalp, the latter of which primarily is reported in the Japanese literature and demonstrates alopecic nodules between the forehead and vertex of the scalp with pseudocystic architecture and granulomatous infiltration on histopathology.^4-7

There are several clinical and histologic differences between AANS and other diagnoses in the differential. Dermoid cysts tend to present at birth, with 70% of cases presenting before the age of 6 years, and without overlying skin changes.⁸ They represent a benign entrapment of ectoderm along embryonic closure lines during development.⁹ Histologic examination typically will show a squamous-lined cyst within the dermis with associated adnexal structures.¹⁰ Cylindromas are benign neoplasms of eccrine sweat glands named after the histologic presentation of cylinder-shaped basaloid cell populations when cross-sectioned.^11,12 When cylindromas coalesce on the scalp, they form a distinctive morphology sometimes loosely resembling a turban, giving them the previously more common name turban tumors.^11,13 Cylindromas appear as slow-growing protuberant tumors that are erythematous or flesh colored. Cylindromas are 9 times more common in females.13 Pilar cysts have a stratified squamous epithelium lining with a palisaded outer layer and are derived from the outer root sheath of hair follicles.¹⁴ Clinically, pilar cysts are smooth mobile cysts that favor skin with a dense concentration of hair follicles.^14,15 On palpation, pilar cysts are firm due to their keratinous contents and typically are nontender unless inflamed.¹⁵ Lipomas are benign mesenchymal tumors with mature adipocytes that often appear as subcutaneous nodules without overlying skin changes, though they can involve deep fascia. On palpation, lipomas generally are soft, mobile, and nontender.¹⁶

The Diagnosis: Pigmented Fungiform Papillae of the Tongue

Our patient’s hyperpigmentation was confined to the fungiform papillae, leading to a diagnosis of pigmented fungiform papillae of the tongue (PFPT). A biopsy was not performed, and reassurance was provided regarding the benign nature of this finding, which did not require treatment.

Pigmented fungiform papillae of the tongue is a benign, nonprogressive, asymptomatic pigmentary condition that is most common among patients with skin of color and typically develops within the second or third decade of life.^1,2 The pathogenesis is unclear, but activation of subepithelial melanophages without evidence of inflammation has been implicated.² Although no standard treatment exists, cosmetic improvement with the use of the Q-switched ruby laser has been reported.^3,4 Clinically, PFPT presents as asymptomatic hyperpigmentation confined to the fungiform papillae along the anterior and lateral portions of the tongue.^1,2

Pigmented fungiform papillae of the tongue typically is an isolated finding but rarely can be associated with hyperpigmentation of the nails (as in our patient) or gingiva.² Three different clinical patterns of presentation have been described: (1) a single well-circumscribed collection of pigmented fungiform papillae, (2) few scattered pigmented fungiform papillae admixed with many nonpigmented fungiform papillae, or (3) pigmentation of all fungiform papillae on the dorsal aspect of the tongue.^2,5,6 Pigmented fungiform papillae of the tongue is a clinical diagnosis based on visual recognition. Dermoscopic examination revealing a cobblestonelike or rose petal–like pattern may be helpful in diagnosing PFPT.^2,5-7 Although not typically recommended in the evaluation of PFPT, a biopsy will reveal papillary structures with hyperpigmentation of basilar keratinocytes as well as melanophages in the lamina propria.8 The latter finding suggests a transient inflammatory process despite the hallmark absence of inflammation.⁵ Melanocytic neoplasia and exogenous granules of pigment typically are not seen.⁸

Other conditions that may present with dark-colored macules or papules on the tongue should be considered in the evaluation of a patient with these clinical findings. Black hairy tongue (BHT), or lingua villosa nigra, is a benign finding due to filiform papillae hypertrophy on the dorsum of the tongue.⁹ Food particle debris caught in BHT can lead to porphyrin production by chromogenic bacteria and fungi. These porphyrins result in discoloration ranging from brown-black to yellow and green occurring anteriorly to the circumvallate papillae while usually sparing the tip and lateral sides of the tongue. Dermoscopy can show thin discolored fibers with a hairy appearance. Although normal filiform papillae are less than 1-mm long, 3-mm long papillae are considered diagnostic of BHT.⁹ Treatment includes effective oral hygiene and desquamation measures, which can lead to complete resolution.10

Peutz-Jeghers syndrome is a rare genodermatosis that is characterized by focal hyperpigmentation and multiple gastrointestinal mucosal hamartomatous polyps. Peutz-Jeghers syndrome should be suspected in a patient with discrete, 1- to 5-mm, brown to black macules on the perioral or periocular skin, tongue, genitals, palms, soles, and buccal mucosa with a history of abdominal symptoms.^11,12

Addison disease, or primary adrenal insufficiency, may present with brown hyperpigmentation on chronically sun-exposed areas; regions of friction or pressure; surrounding scar tissue; and mucosal surfaces such as the tongue, inner surface of the lip, and buccal and gingival mucosa.¹³ Addison disease is differentiated from PFPT by a more generalized hyperpigmentation due to increased melanin production as well as the presence of systemic symptoms related to hypocortisolism. The pigmentation seen on the buccal mucosa in Addison disease is patchy and diffuse, and histology reveals basal melanin hyperpigmentation with superficial dermal melanophages.¹³

Hereditary hemorrhagic telangiectasia is an inherited disorder featuring telangiectasia and generally appears in the third decade of life.¹⁴ Telangiectases classically are 1 to 3 mm in diameter with or without slight elevation. Dermoscopic findings include small red clots, lacunae, and serpentine or linear vessels arranged in a radial conformation surrounding a homogenous pink center.¹⁵ These telangiectases typically occur on the skin or mucosa, particularly the face, lips, tongue, nail beds, and nasal mucosa; however, any organ can be affected with arteriovenous malformations. Recurrent epistaxis occurs in more than half of patients with hereditary hemorrhagic telangiectasia.¹⁴ Histopathology reveals dilated vessels and lacunae near the dermoepidermal junction displacing the epidermis and papillary dermis.¹⁵ It is distinguished from PFPT by the vascular nature of the lesions and by the presence of other characteristic symptoms such as recurrent epistaxis and visceral arteriovenous malformations.

The Diagnosis: Pigmented Fungiform Papillae of the Tongue

Our patient’s hyperpigmentation was confined to the fungiform papillae, leading to a diagnosis of pigmented fungiform papillae of the tongue (PFPT). A biopsy was not performed, and reassurance was provided regarding the benign nature of this finding, which did not require treatment.

Pigmented fungiform papillae of the tongue is a benign, nonprogressive, asymptomatic pigmentary condition that is most common among patients with skin of color and typically develops within the second or third decade of life.^1,2 The pathogenesis is unclear, but activation of subepithelial melanophages without evidence of inflammation has been implicated.² Although no standard treatment exists, cosmetic improvement with the use of the Q-switched ruby laser has been reported.^3,4 Clinically, PFPT presents as asymptomatic hyperpigmentation confined to the fungiform papillae along the anterior and lateral portions of the tongue.^1,2

Pigmented fungiform papillae of the tongue typically is an isolated finding but rarely can be associated with hyperpigmentation of the nails (as in our patient) or gingiva.² Three different clinical patterns of presentation have been described: (1) a single well-circumscribed collection of pigmented fungiform papillae, (2) few scattered pigmented fungiform papillae admixed with many nonpigmented fungiform papillae, or (3) pigmentation of all fungiform papillae on the dorsal aspect of the tongue.^2,5,6 Pigmented fungiform papillae of the tongue is a clinical diagnosis based on visual recognition. Dermoscopic examination revealing a cobblestonelike or rose petal–like pattern may be helpful in diagnosing PFPT.^2,5-7 Although not typically recommended in the evaluation of PFPT, a biopsy will reveal papillary structures with hyperpigmentation of basilar keratinocytes as well as melanophages in the lamina propria.8 The latter finding suggests a transient inflammatory process despite the hallmark absence of inflammation.⁵ Melanocytic neoplasia and exogenous granules of pigment typically are not seen.⁸

Other conditions that may present with dark-colored macules or papules on the tongue should be considered in the evaluation of a patient with these clinical findings. Black hairy tongue (BHT), or lingua villosa nigra, is a benign finding due to filiform papillae hypertrophy on the dorsum of the tongue.⁹ Food particle debris caught in BHT can lead to porphyrin production by chromogenic bacteria and fungi. These porphyrins result in discoloration ranging from brown-black to yellow and green occurring anteriorly to the circumvallate papillae while usually sparing the tip and lateral sides of the tongue. Dermoscopy can show thin discolored fibers with a hairy appearance. Although normal filiform papillae are less than 1-mm long, 3-mm long papillae are considered diagnostic of BHT.⁹ Treatment includes effective oral hygiene and desquamation measures, which can lead to complete resolution.10

Peutz-Jeghers syndrome is a rare genodermatosis that is characterized by focal hyperpigmentation and multiple gastrointestinal mucosal hamartomatous polyps. Peutz-Jeghers syndrome should be suspected in a patient with discrete, 1- to 5-mm, brown to black macules on the perioral or periocular skin, tongue, genitals, palms, soles, and buccal mucosa with a history of abdominal symptoms.^11,12

Addison disease, or primary adrenal insufficiency, may present with brown hyperpigmentation on chronically sun-exposed areas; regions of friction or pressure; surrounding scar tissue; and mucosal surfaces such as the tongue, inner surface of the lip, and buccal and gingival mucosa.¹³ Addison disease is differentiated from PFPT by a more generalized hyperpigmentation due to increased melanin production as well as the presence of systemic symptoms related to hypocortisolism. The pigmentation seen on the buccal mucosa in Addison disease is patchy and diffuse, and histology reveals basal melanin hyperpigmentation with superficial dermal melanophages.¹³

Hereditary hemorrhagic telangiectasia is an inherited disorder featuring telangiectasia and generally appears in the third decade of life.¹⁴ Telangiectases classically are 1 to 3 mm in diameter with or without slight elevation. Dermoscopic findings include small red clots, lacunae, and serpentine or linear vessels arranged in a radial conformation surrounding a homogenous pink center.¹⁵ These telangiectases typically occur on the skin or mucosa, particularly the face, lips, tongue, nail beds, and nasal mucosa; however, any organ can be affected with arteriovenous malformations. Recurrent epistaxis occurs in more than half of patients with hereditary hemorrhagic telangiectasia.¹⁴ Histopathology reveals dilated vessels and lacunae near the dermoepidermal junction displacing the epidermis and papillary dermis.¹⁵ It is distinguished from PFPT by the vascular nature of the lesions and by the presence of other characteristic symptoms such as recurrent epistaxis and visceral arteriovenous malformations.

The Diagnosis: Pigmented Fungiform Papillae of the Tongue

Our patient’s hyperpigmentation was confined to the fungiform papillae, leading to a diagnosis of pigmented fungiform papillae of the tongue (PFPT). A biopsy was not performed, and reassurance was provided regarding the benign nature of this finding, which did not require treatment.

Pigmented fungiform papillae of the tongue is a benign, nonprogressive, asymptomatic pigmentary condition that is most common among patients with skin of color and typically develops within the second or third decade of life.^1,2 The pathogenesis is unclear, but activation of subepithelial melanophages without evidence of inflammation has been implicated.² Although no standard treatment exists, cosmetic improvement with the use of the Q-switched ruby laser has been reported.^3,4 Clinically, PFPT presents as asymptomatic hyperpigmentation confined to the fungiform papillae along the anterior and lateral portions of the tongue.^1,2

Pigmented fungiform papillae of the tongue typically is an isolated finding but rarely can be associated with hyperpigmentation of the nails (as in our patient) or gingiva.² Three different clinical patterns of presentation have been described: (1) a single well-circumscribed collection of pigmented fungiform papillae, (2) few scattered pigmented fungiform papillae admixed with many nonpigmented fungiform papillae, or (3) pigmentation of all fungiform papillae on the dorsal aspect of the tongue.^2,5,6 Pigmented fungiform papillae of the tongue is a clinical diagnosis based on visual recognition. Dermoscopic examination revealing a cobblestonelike or rose petal–like pattern may be helpful in diagnosing PFPT.^2,5-7 Although not typically recommended in the evaluation of PFPT, a biopsy will reveal papillary structures with hyperpigmentation of basilar keratinocytes as well as melanophages in the lamina propria.8 The latter finding suggests a transient inflammatory process despite the hallmark absence of inflammation.⁵ Melanocytic neoplasia and exogenous granules of pigment typically are not seen.⁸

Other conditions that may present with dark-colored macules or papules on the tongue should be considered in the evaluation of a patient with these clinical findings. Black hairy tongue (BHT), or lingua villosa nigra, is a benign finding due to filiform papillae hypertrophy on the dorsum of the tongue.⁹ Food particle debris caught in BHT can lead to porphyrin production by chromogenic bacteria and fungi. These porphyrins result in discoloration ranging from brown-black to yellow and green occurring anteriorly to the circumvallate papillae while usually sparing the tip and lateral sides of the tongue. Dermoscopy can show thin discolored fibers with a hairy appearance. Although normal filiform papillae are less than 1-mm long, 3-mm long papillae are considered diagnostic of BHT.⁹ Treatment includes effective oral hygiene and desquamation measures, which can lead to complete resolution.10

Peutz-Jeghers syndrome is a rare genodermatosis that is characterized by focal hyperpigmentation and multiple gastrointestinal mucosal hamartomatous polyps. Peutz-Jeghers syndrome should be suspected in a patient with discrete, 1- to 5-mm, brown to black macules on the perioral or periocular skin, tongue, genitals, palms, soles, and buccal mucosa with a history of abdominal symptoms.^11,12

Addison disease, or primary adrenal insufficiency, may present with brown hyperpigmentation on chronically sun-exposed areas; regions of friction or pressure; surrounding scar tissue; and mucosal surfaces such as the tongue, inner surface of the lip, and buccal and gingival mucosa.¹³ Addison disease is differentiated from PFPT by a more generalized hyperpigmentation due to increased melanin production as well as the presence of systemic symptoms related to hypocortisolism. The pigmentation seen on the buccal mucosa in Addison disease is patchy and diffuse, and histology reveals basal melanin hyperpigmentation with superficial dermal melanophages.¹³

Hereditary hemorrhagic telangiectasia is an inherited disorder featuring telangiectasia and generally appears in the third decade of life.¹⁴ Telangiectases classically are 1 to 3 mm in diameter with or without slight elevation. Dermoscopic findings include small red clots, lacunae, and serpentine or linear vessels arranged in a radial conformation surrounding a homogenous pink center.¹⁵ These telangiectases typically occur on the skin or mucosa, particularly the face, lips, tongue, nail beds, and nasal mucosa; however, any organ can be affected with arteriovenous malformations. Recurrent epistaxis occurs in more than half of patients with hereditary hemorrhagic telangiectasia.¹⁴ Histopathology reveals dilated vessels and lacunae near the dermoepidermal junction displacing the epidermis and papillary dermis.¹⁵ It is distinguished from PFPT by the vascular nature of the lesions and by the presence of other characteristic symptoms such as recurrent epistaxis and visceral arteriovenous malformations.