Vulva & vagina

Melanocytic lesions

Atypical melanocytic nevi of the genital type


Editorial Board Members: C. Blake Gilks, M.D., Stephanie L. Skala, M.D.
Anna Sarah Erem, M.D.
Gulisa Turashvili, M.D., Ph.D.

Last author update: 18 December 2023
Last staff update: 5 February 2024

Copyright: 2002-2024, PathologyOutlines.com, Inc.

PubMed Search: Atypical melanocytic nevi of genital type

Anna Sarah Erem, M.D.
Gulisa Turashvili, M.D., Ph.D.
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Cite this page: Erem AS, Turashvili G. Atypical melanocytic nevi of the genital type. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/vulvaAMNGT.html. Accessed March 28th, 2024.
Definition / general
  • 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)
Essential features
  • Nonmelanoma histologic diagnosis
Terminology
  • Atypical melanocytic nevi of genital type (AMNGT)
  • Atypical genital nevi (AGN)
  • Nevi with site related atypia
  • Nevi of special sites
ICD coding
  • ICD-O
    • 8720/0 - atypical melanocytic nevus of genital type
  • ICD-10
    • D28 - benign neoplasm of other and unspecified female genital organs
    • D39 - neoplasm of uncertain behavior of female genital organs
  • ICD-11
    • EG9Y - skin disorders involving other specific body regions
    • EG9Z - skin disorders involving certain specific body regions, unspecified
    • Specific anatomy (use additional code, if desired)
      • 2F33 - benign neoplasm of other or unspecified female genital organ
      • XA78U5 - vulva
        • XA11L9 - labia of vulva
        • XA1A52 - vulval vestibule
        • XA0565 - posterior fourchette of vulva
          • Frenulum of labia minora
      • XA4851 - clitoris
      • XA10Z0 - mons pubis
Epidemiology
Sites
Etiology
  • Largely unknown but associated with anatomic milk line, including axillae, breasts, periumbilical region and groin (Am J Surg Pathol 2008;32:51)
Clinical features

Table 1: Clinical and histologic differences between atypical genital nevus and vulvar melanoma
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

Table adapted from: Hoang: Melanocytic Lesions - A Case Based Approach, 1st Edition, 2014
Diagnosis

Table 2: Distinguishing vulvar nevi, melanosis and melanoma
Reassuring features suggestive of a benign process Concerning features for possible malignancy
Clinical Patient age < 50 years, symmetric, diameter < 1 cm, uniform pigmentation, regular border, macular or papular rash, associated with genodermatoses Patient age > 50 years, irregular coloration, asymmetric borders, diameter > 0.7 cm, elevated lesion, associated bleeding, pruritus or discharge
Dermoscopy Globular, cobblestone, ring-like, reticular-like, homogeneous, parallel or mixed pattern Gray, white or blue color plus structureless zones, irregular dots or globules, atypical vessels
Reflectance confocal microscopy Hyperrefractive cells around the papillae, ringed or draped polycyclic papillae, sparse dendritic cells Increased cellularity, atypical cells, disturbed architecture

Table adapted from: J Am Acad Dermatol 2014;71:1241
Prognostic factors
Case reports
Treatment
  • Simple excision is usually sufficient
Clinical images

Contributed by José Alberto Fonseca Moutinho, M.D.
Nevus

Nevus



Images hosted on other servers:

Irregular dots on the periphery of the lesion

Pigmented lesion

Microscopic (histologic) description
  • Symmetric lesion with sharp demarcation and dermal maturation (J Cutan Pathol 2008;35:24)
  • 3 histologic patterns described by Clark (Hum Pathol 1998;29:S1)
    • Nested: oval, typically large nests, perpendicular or parallel to dermoepidermal junction
    • Discohesive nests: nearly contiguous, forming a band that separates the epidermis from the mature dermal melanocytes
    • Crowded: closely apposed, ill defined nests and single cells obscuring the dermal epidermal junction
  • Usually mild to moderate uniform cytologic atypia (J Cutan Pathol 2008;35:24)
  • Single cell growth with focal pagetoid spread may be present but is usually located in the center of the lesion (J Cutan Pathol 2008;35:24)
  • Adnexal spread may be present (Hum Pathol 1998;29:S1)
  • Dense eosinophilic fibrosis in the superficial dermis (Hum Pathol 1998;29:S1, J Cutan Pathol 2008;35:24)
  • Intradermal component with maturation is often present (J Cutan Pathol 2008;35:24)
  • Nevi within lichen sclerosus can appear more atypical
  • See table 1
Microscopic (histologic) images

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

Atypical melanocytic proliferation

Atypical melanocytic proliferation Atypical melanocytic proliferation

Atypical melanocytic proliferation

Atypical melanocytic proliferation Atypical melanocytic proliferation

Atypical genital nevi



Positive stains
Negative stains
Molecular / cytogenetics description
  • BRAF mutation is the most common alteration in melanocytic nevi of genital skin but not in vulvar melanomas (N Engl J Med 2015;373:1926, J Invest Dermatol 2016;136:1858)
  • Fluorescence in situ hybridization (FISH) or comparative genomic hybridization (CGH) may be considered in very challenging cases to rule out melanoma
Videos

Atypical nevi and nevi of special sites by Dr. Phillip McKee

Atypical nevi and melanoma by Dr. Steven Wang

Sample pathology report
  • Vulva, labia minora, excisional biopsy:
    • Atypical melanocytic nevus of the genital type, compound pattern, excised entirely
Differential diagnosis
  • Melanoma:
    • May be most challenging to differentiate from superficial spreading subtype of melanoma (SSM)
    • Atypical melanocytes in the epidermis as single cells or forming nests with pagetoid spread
    • Dermal component shows no maturation with cells forming sheets, nests, cords, single cells and rarely fascicles
    • S100, SOX10 and nerve growth factor receptor (NGFR) are the most sensitive markers in visualization of invasive growth
    • PRAME shows diffuse staining
    • Melanomas of vulva usually lack BRAF mutation (Br J Dermatol 2010;162:677)
  • Pigmented epithelioid melanocytoma (PEM) of the vulva:
    • PEM family consists of multiple, usually slow growing, distinct histologic melanocytic entities with potential to metastasize but with a better prognosis than melanoma
    • Infiltrative deep dermal tumor that may involve subcutis
    • Hypercellular tumor with cells ranging from medium sized epithelioid cells to large epithelioid cells and spindled cells
    • Low mitotic activity
    • PRKAR1A loss in 67% of PEMs (Am J Surg Pathol 2017;41:1333, Am J Surg Pathol 2019;43:480)
  • Dysplastic nevus of vulva:
    • Differentiation requires clinical pathologic correlates
    • Presence of junctional shoulders; extension of junctional component at least 3 rete ridges beyond the dermal component
    • Superficial nests are usually very similar and may show focal bridging or coalescence of the nests
    • Elongation and bridging of the rete ridges with nests
    • Melanocytes may scatter suprabasally (confined to the lower epidermal layer and centrally)
    • 2 tier grading of cytologic atypia is recommended by World Health Organization (WHO) classification and is largely based on nuclear features (Hum Pathol 1999;30:500)
Board review style question #1
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
Board review style answer #1
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.

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Reference: Atypical melanocytic nevi of genital type
Board review style question #2

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
Board review style answer #2
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.

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Reference: Atypical melanocytic nevi of genital type
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