General
=========================================================================

• Melanoma originating in vaginal wall without involvement of vulva, uterine cervix or other surrounding structures (Gynecol Obstet 3:183)

Terminology
=========================================================================

• Also called primary malignant melanoma of vagina

Epidemiology
=========================================================================

• 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 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
=========================================================================

• More commonly in the lower third of vagina and on anterior vaginal wall (Gynecol Obstet 3:183, J Chin Med Assoc 2011;74:376)

Etiology
=========================================================================

• Appears to originate from melanocytes present in vaginal mucosa (Gynecol Obstet 3:183)

Clinical features
=========================================================================

• Vaginal bleeding or discharge (J Chin Med Assoc 2011;74:376)

Diagnosis
=========================================================================

• Based on biopsy/resection specimen with clinical history and imaging

Radiology
=========================================================================

• Small tumors can be difficult to assess on CT scan
• The use of fluorodeoxyglucose (FDG) as a glycolytic indicator in tumor-altered metabolism in PET/CT study can aid in early diagnosis and staging

Prognostic factors
=========================================================================

• Common sites of recurrence of vaginal melanoma are vagina, vulva, groin
• Prognosis poorer than cutaneous melanomas
• Five year survival rate of 13-19% is poor compared to vulvar and cutaneous melanomas
• Fifty percent have positive lymph nodes, and nearly 20 percent have distant metastases at presentation
• Mean survival is 8.5 months after recurrence (Gynecol Obstet 3:183)

Case reports
=========================================================================

• 31 year old woman with primary amelanotic melanoma (Onkologie 2008;31:474)
• Melanoma of vagina (Indian J Pathol Microbiol 2003;46:71)
• Primary amelanotic melanoma (Int J Gynaecol Obstet 1989;29:159)

Treatment
=========================================================================

• 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)
• It is 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 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
=========================================================================

Diffuse black pigmentation

 

Colposcopic findings

Mass in posterior wall

Gross description
=========================================================================

• Can have raised, ulcerated and irregular appearance (Gynecol Obstet 3:183)
• Can present as polypoid lesion or a nodule
• Usually pigmented with black to brown gross appearance, but 40% cases are amelanotic

Gross images
=========================================================================

Nodular mass

Micro description
=========================================================================

• 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 3:183)

Micro images
=========================================================================

 

Atypical tumor cells

Melanin granules

 

H&E, S100, HMB45

 

HMB45+

Cytology description
=========================================================================

• 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
=========================================================================

Loose aggregates of
pleomorphic tumor cells

Positive stains
=========================================================================

• S100, HMB45, vimentin
• Melanin pigment can be demonstrated with Fontana-Masson silver staining (J Clin Pathol 2004;57:986)
• MelanA, tyrosinase, MiTF

Negative stains
=========================================================================

• Cytokeratin, epithelial membrane antigen (EMA), desmin, myoglobin, smooth muscle actin, CD34, CD68
• Amelanotic melanomas are negative for melanin pigment (J Clin Pathol 2004;57:986)

Molecular / cytogenetics description
=========================================================================

• 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 Mar 7 [Epub ahead of print])

Differential diagnosis
=========================================================================

• Hemangioendothelioma
• Malignant fibrous histiocytoma (MFH)
• Malignant peripheral nerve sheath tumor
• Sarcoma (Gynecol Obstet 3:183)
• Undifferentiated carcinoma

Additional references
=========================================================================

• Int J Gynecol Cancer 2014;24:149, J Gynecol Oncol 2013;24:330, Int J Gynecol Cancer 2013;23:1484, Melanoma Res 2013;23:138

This information is intended for physicians and related personnel, who understand that medical information is often imperfect, and must be interpreted in the context of a patient's clinical data using reasonable medical judgment. This website should not be used as a substitute for the advice of a licensed physician.

All information on this website is protected by copyright of PathologyOutlines.com, Inc. Information from third parties may also be protected by copyright. Please contact us at copyrightPathOut@gmail.com with any questions (click here for other contact information).