Vulva & vagina

• Rare benign melanocytic lesion, most commonly involving the vulva of young women with concerning histologic features that may overlap with melanoma but are associated with benign behavior (J Cutan Pathol 2008;35:24)
• Belongs to the general group nevi of special sites
• Commonly also part of pigmented lesions of the vulva (J Cutan Pathol 2008;35:24)

• Compared to other nevi of special sites, AMNGT may have alarming clinical features, including darker pigmentation, irregular borders and size up to 2 cm (median: 0.5 cm) (Am J Surg Pathol 2008;32:51, Hum Pathol 1998;29:S1)
  • Mucosal sites most commonly present with flat lesions and demonstrate atypical foci of hyperpigmentation (Am J Surg Pathol 2008;32:51)
• See table 1

Table 1: Clinical and histologic differences between atypical genital nevus and vulvar melanoma (adapted from Hoang: Melanocytic Lesions - A Case Based Approach, 1st Edition, 2014)

Proposed diagnosis	Atypical genital nevus of special anatomic site	Vulvar melanoma
Age	Premenopausal, young adult	Postmenopausal
Size	< 1 cm	> 1 cm
Delineation	Well circumscribed	Infiltrative
Symmetry	Present	Absent
Lateral extension of junctional component	Focal	Present
Lentiginous junctional component	Focal	Present
Junctional nests	Discohesive	Confluent
Retraction artifact	Present	Absent
Ulceration	Absent or due to trauma	Often present
Pagetoid upward spread	Focal, central, inconspicuous	Prominent
Cytologic atypia	Superficial, mild to moderate	Deep, moderate to severe
Dermal mitosis	Rare and superficial	Conspicuous, atypical, deep
Dermal maturation	Present	Absent
Melanin pigmentation	Coarse, uniform	Fine, irregular
Dermal fibrosis	Broad zone of superficial coarse dermal fibrosis	Regression type

• Dermoscopy for nonmodified mucous membranes is useful (Dermatol Ther 2010;23:449)
  • May have any of the dermoscopic patterns seen in benign nevi
  • Globular / cobblestone, homogenous, structureless or mixed patterns are most common (Dermatology 2011;222:157, Dermatology 2010;221:55)
  • Shiny white streaks (SWS), inverse pigment network and atypical network can be seen in AMNGT in setting of symmetry pattern and absence of melanoma specific dermoscopic features (Dermatology 2011;222:157, Dermatology 2010;221:55)
  • See table 2
• Histologic diagnosis is confirmatory
• For optimal diagnosis, lichen sclerosus should be controlled before excision of the nevus (J Am Acad Dermatol 2004;50:690, Arch Dermatol 2002;138:77)

Table 2: Distinguishing vulvar nevi, melanosis and melanoma (adapted from J Am Acad Dermatol 2014;71:1241)

	Reassuring features suggestive of a benign process	Concerning features for possible malignancy
Clinical	Age at diagnosis < 50 years Symmetric, uniformly pigmented, macular or papular lesion with regular borders Measures < 1 mm in diameter Associated with genodermatoses	Age at diagnosis > 50 years Asymmetric, nonuniformly pigmented, elevated lesion with irregular borders Measures > 0.7 mm in diameter Associated bleeding, pruritus or discharge
Dermoscopy	Variable appearance, including cobblestone, globular, ring-like, reticular-like, homogeneous, parallel or mixed	Variable color (gray, white, or blue) with structureless zones, irregular globules or dots and atypical vessels
Reflectance confocal microscopy	Draped or ringed polycyclic papillae Hyper refractive cells around the papillae Sparse dendritic cells	Increased cellularity with atypical cells and disordered architecture

• Simple excision is usually sufficient

Contributed by José Alberto Fonseca Moutinho, M.D.


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Contributed by Anna Sarah Erem, M.D. and Gulisa Turashvili, M.D., Ph.D.

A 28 year old woman presented to the clinic with a 0.6 cm, flat, dark brown lesion with an irregular border on the labia majora. The histologic findings of the shave biopsy demonstrated a relatively symmetric, broad melanocytic proliferation with large oval nests with retraction perpendicular to the dermal epidermal junction, focal fusion and mild cytologic atypia. Dermal maturation is evident. What is the most likely molecular alteration in this lesion?

1. ALK fusion
2. BRAF mutation
3. Homozygous deletion of CDKN2A
4. PTEN mutation

B. BRAF mutation. The majority of atypical melanocytic nevi of genital type (AMNGT) have a driver mutation in BRAF. Answer A incorrect because ALK fusion is more characteristic of Spitz nevi. Answers C and D are incorrect because those alterations are specific to superficial spreading melanoma.

Comment Here

Reference: Atypical melanocytic nevi of genital type-vulva

A 16 year old girl presented with her parents to the OBGYN clinic with an irregular, dome shaped, dark pigmented papule on the mons pubis. A biopsy demonstrated large, ill defined nests with focal retraction. What is the most likely interpretation of the immunohistochemical stains for this patient's lesion?

1. Diffuse expression of PRAME
2. Gradient pattern of HMB45
3. High Ki67 proliferation index in the dermal component
4. SOX10 highlighting pagetoid and extensive lentiginous growth

B. Gradient pattern of HMB45. The histologic features are consistent with atypical melanocytic nevi of genital type (AMNGT). Although HMB45 expression varies in nevi, the stain can be useful to highlight the maturation (zonation) pattern (diminished or loss of expression from epidermal to dermal component). Answers A, C and D are incorrect because PRAME is usually diffusely positive in melanoma, SOX10 helps to highlight the increase of melanocytes and pagetoid growth in melanoma and Ki67 is expected to be low in the dermal component of genital nevi.

Comment Here

Reference: Atypical melanocytic nevi of genital type-vulva