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Vulva, vagina & female urethra

Melanocytic lesions

Melanoma


Priya Nagarajan, M.D., Ph.D.
Nat Pernick, M.D.

Last author update: 1 February 2015
Last staff update: 6 January 2023 (update in progress)

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PubMed Search: Melanoma vulva "loattrfree full text"[sb]

Priya Nagarajan, M.D., Ph.D.
Nat Pernick, M.D.
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Table of Contents
Definition / general | Terminology | Epidemiology | Sites | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Cytology images | Positive stains | Negative stains | Molecular / cytogenetics description | Differential diagnosis | Additional references
Cite this page: Nagarajan P, Pernick N. Melanoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/vulvamelanoma.html. Accessed March 30th, 2023.
Definition / general
  • Melanoma constitutes about 4 - 10% of all vulvar malignancies (Int J Gynecol Cancer 2013;23:1118)
  • Second most common malignant vulvar neoplasm after squamous cell carcinoma
  • Melanoma may originate in vaginal wall without involvement of vulva, uterine cervix or other surrounding structures (Gynecol Obstet 2013;3:183)
Terminology
  • Also called primary malignant melanoma of vagina
Epidemiology
Vulva:
Vagina:
  • Melanomas arising from female urogenital tract occur primarily in vulva (95%) and vagina (3%)
  • Primary melanoma of vagina is extremely rare and aggressive
  • Constitutes less than 3% of vaginal cancers and only 0.3 - 0.8% of all melanomas in women (Gynecol Obstet 2013;3:183)
  • Occurs mainly in postmenopausal women, sixth and seventh decades of life (J Chin Med Assoc 2011;74:376)
  • Rare cases in young patients (Int J Pathol 2009;7:102)
Sites
Etiology
Clinical features
Vulva:
  • May be discovered during routine gynecologic examinations
  • Usually present as pigmented and sometimes nonpigmented lesions (macules, patches, nodules)
  • May be ulcerated
  • May present with multiple lesions (satellitosis)

Vagina:
Diagnosis
  • In vulva, histologic examination is essential to diagnosis
  • In vagina, diagnosis is based on biopsy / resection specimen with clinical history and imaging
Laboratory
  • In vulva, serum lactate dehydrogenase levels > 200 to 225 U/L are associated with poor survival
Radiology description
Vulva:
Vagina:
  • Small tumors can be difficult to assess on CT scan
  • Use of fluorodeoxyglucose (FDG) as a glycolytic indicator in tumor altered metabolism in PET / CT study can aid in early diagnosis and staging
Radiology images

Images hosted on other servers:

CT scan, enlarged lymph node

Prognostic factors
Vulva:
  • Age: patients ≤ 68 years at diagnosis have a better prognosis
  • Histologic parameters:
  • Stage:
    • Patients with localized disease (stage 0, I, II) have a better prognosis (Obstet Gynecol 2007;110:296)
    • Higher number of positive lymph nodes is associated with worse prognosis
  • Strong and diffuse c-kit expression may be associated with a worse prognosis (Int J Mol Med 2014;33:784)

Vagina:
  • Common sites of recurrence of vaginal melanoma are vagina, vulva, groin
  • Prognosis poorer than cutaneous melanomas
  • 5 year survival rate of 13 - 19% is poor compared to vulvar and cutaneous melanomas
  • 50% have positive lymph nodes and nearly 20 percent have distant metastases at presentation
  • Mean survival is 8.5 months after recurrence (Gynecol Obstet 2013;3:183)
Case reports
Vulva:
Vagina:
Treatment
Vulva:
  • Surgical resection with adequate margins is the principal management
  • Radiation
  • Chemotherapy
  • Topical imiquimod therapy

Vagina:
  • Many different treatment modalities have been tested but there is no standard therapeutic approach
  • Surgery provides local control; procedures include wide local excision, radical surgery (total vaginectomy with or without vulvectomy), pelvic extenteration
  • Sentinel lymph node biopsy (SLNB) provides important prognostic and staging data with minimal morbidity
  • Routine lymph node dissection is not recommended because morbidity is high and prophylactic lymphadenectomy has not been shown to improve survival (J Chin Med Assoc 2011;74:376)
  • Difficult to get negative surgical margins without pelvic exenteration due to multifocality and anatomic constraints
  • Surgery may be combined with radiotherapy or chemotherapy
  • Cytotoxic chemotherapy, IFNα, IL2, ipilimumab and vemurafenib have been used in some cases (Gynecol Obstet 2013;3:183)
  • IFN is used as adjuvant therapy in patients without disease but at high risk of systemic recurrence (J Chin Med Assoc 2011;74:376)
Clinical images

Images hosted on other servers:

Nodule and ulcer

Large friable, gray white growth

Vulvar melanoma

Missing Image

Nonpigmented primary lesion found in vagina

Gross description
Vulva:
  • Preservation of specimen orientation is critical for thorough evaluation of peripheral and deep tissue margins

Vagina:
  • Can have raised, ulcerated and irregular appearance (Gynecol Obstet 2013;3:183)
  • Can present as polypoid lesion or a nodule
  • Usually pigmented with black to brown gross appearance but 40% cases are amelanotic
Microscopic (histologic) description
Vulva:
  • Vulvar melanomas are evaluated and staged similar to cutaneous melanomas
  • Most of the melanomas involving the cutaneous surface only are traditionally classified based on the histologic type (superficial spreading being the most common type at this site)
  • However, when mucosal surfaces are involved, classifying them as mucosal lentiginous type would be most appropriate (CAP: Cancer Protocol Templates [Accessed 9 October 2017])
  • Following histologic parameters should be included in the report:
    • Histologic type
    • Clark (anatomic) level
    • Breslow thickness (primary tumor thickness, if completely mucosal)
    • Presence of radial or nontumorigenic growth phase
    • Presence of vertical or tumorigenic growth phase
    • Mitotic rate per millimeter squared
    • Presence of ulceration (the microscopic size of ulceration is often included)
      • Must exercise caution in resection specimens as the ulceration might represent prior biopsy site
    • Presence of regression (mention percentage of regression, is associated with a poor prognosis if > 75%)
    • Presence of lymphovascular space invasion (the use of MART1 / MelanA plus D2-40 or CD34 immunostains is more sensitive)
    • Presence of perineural invasion (size of nerves involved should be mentioned)
    • Presence of microscopic satellitosis
    • Presence of tumor infiltrating lymphocytes (presence or absence; brisk vs. nonbrisk)
    • Presence of associated melanocytic nevi
    • Predominant cytology of the tumor cells
    • Status of surgical margins (for in situ and invasive melanoma)
  • Sentinel lymph nodes:
    • Examination of several H&E sections cut at various depth into the paraffin block and the use of immunohistochemistry for melanocytic markers are routinely employed to detect single cell metastases

Vagina:
  • Diffuse infiltration of large, pleomorphic, epithelioid and spindle shaped tumor cells in vaginal mucosa
  • Cells have eosinophilic cytoplasm, large oval or pleomorphic hyperchromatic nuclei, may have multiple nuclei with distinct nucleoli (J Clin Pathol 2004;57:986)
  • Amelanotic melanomas can be difficult to diagnose on histology
  • Junctional activity, if present, raises suspicion for melanoma (Int J Pathol 2009;7:102)
  • Immunohistochemical stains are helpful if no melanin pigment or junctional activity (Gynecol Obstet 2013;3:183)
Microscopic (histologic) images

Contributed by Priya Nagarajan, M.D., Ph.D.
   

Melanoma in situ

Melanoma in situ vs. atypical melanocytic hyperplasia

Mostly in situ, minimal invasive component


Invasive and in situ melanoma

Melanoma with ulceration

   

Polypoid melanoma: low to intermediate magnification


 

High magnification

Heavily pigmented

 

Recurrence in subcutaneous fibroadipose tissue


Isolated nodal metastases

   

MelanA

SOX10



Contributed by Mayank Gupta, M.D.

10x

20x

 

40x


Cytokeratin

HMB45

MelanA

Cytology description
Vagina:
  • Loose aggregates of large, pleomorphic, polygonal to spindle shaped tumor cells with ill defined cytoplasmic borders, granular hyperchromatic nuclei and conspicuous nucleoli
  • Multinucleated tumor cells and mitoses can be seen (J Clin Pathol 2004;57:986)
Cytology images

Images hosted on other servers:
Missing Image

Loose aggregates
of pleomorphic
tumor cells

Positive stains
Vulva:
Vagina:
Negative stains
Vulva:
Vagina:
Molecular / cytogenetics description
Vulva:
Vagina:
  • NRAS mutations and KIT amplifications occur in both vaginal and vulvar melanomas
  • KIT mutations appear to be more specific for vulvar melanoma
  • BRAF mutations are absent in both vaginal and vulvar melanomas originating from the vulva or vagina (Mod Pathol 2014;27:1386)
Differential diagnosis
Vulva:
Vagina:
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