Vaginal Melanoma - An Overview

Introduction

Malignant melanomas occur in body parts, including the mouth, nasal cavity, skin, esophagus, anal canal, and vulva. Vaginal melanoma constitutes less than three percent of all vaginal carcinomas and is the second most common malignancy after squamous cell carcinoma. The first case of vaginal melanoma was reported in 1887. It primarily affects women in their sixth or seventh decade and rarely affects younger people. Early and accurate diagnosis is essential for preparing a treatment plan. This disease has a poor prognosis, and surgery is one of the effective treatments, and post-operative adjunct therapy is necessary for preventing recurrence.

What Is Vaginal Melanoma?

Melanomas are tumors arising from pigment cells or melanocytes. Vaginal melanomas arise from the melanocytes present in the vaginal epidermal mucosa. It occurs at any age or in any part of the vagina. Primary malignant vaginal melanoma usually occurs at the distal one-third of the anterior wall of the vagina. It happens without the involvement of the uterine cervix, vulva, or other structures.

What Are the Causes and Risk Factors of Vaginal Melanoma?

The exact cause of vaginal melanoma is not known. However, the risk factors associated with vaginal melanoma include the following:

• Intermittent exposure to high-intensity ultraviolet radiation.

• History of sunburns.

• Presence of atypical nevi.

• Use of psoralen or ultraviolet A therapy for a long period.

• Skin phenotype (lightly pigmented skin, light eyes, red hair, and freckles).

• Female gender.

• Age.

• Family history of cutaneous melanoma and ethnicity.

• Lichen sclerosus (precursor lesion of squamous cell carcinoma of the genital area).

What Are the Signs and Symptoms of Vaginal Melanoma?

The clinical features of vaginal melanoma include the following:

• Raised, ulcerated, and irregular appearance.

• Palpable vaginal mass present as polypoid, nodular, or mushroom umbrella.

• Ulcer present on the vaginal mass.

• Usually asymmetrical and pigmented inhomogeneously (blue-black, gray-black, or brown-to-black).

• The pigmented lesions are about seven millimeters in diameter.

• Some vaginal lesions are amelanotic (40% of cases are amelanotic).

• The tumor bleeds on the touch.

• Abnormal and irregular vaginal bleeding (bleeding after menopause or between periods).

• Blood-stained, foul-smelling vaginal discharge.

• Local pain and persistent itching.

• Yellow genital secretions.

• Dyspareunia (persistent genital pain after sexual intercourse).

• Bleeding after sex.

Most people with vaginal melanoma are asymptomatic, found during a routine vaginal or cervical examination.

How to Diagnose Vaginal Melanoma?

Vaginal melanoma is often diagnosed late due to its anatomical location. The diagnostic tests used for the diagnosis of vaginal melanoma include the following:

• Magnetic resonance imaging (MRI).

• Computed tomography (CT) scans.

• Ultrasound scans of the lymph nodes in the groin(present near the vagina).

• Biopsy - resection of the tumor or its contents are aspirated using a needle.

• Blood tests.

The following immunohistochemical, macroscopic, microscopic, cytogenetic, and radiological findings are useful for diagnosing vaginal melanoma.

1. Macroscopic Findings:

• The first step in diagnosing vaginal melanoma is the application of the ABCDE rule on pigmented lesions.

  • Asymmetry - Two non-identical halves.

  • Borders - Irregular blurred or ragged edges.

  • Color - Shades of tan, black, brown, blue, red, or white.

  • Diameter - Lesions greater than six millimeters.

  • Evolution - The lesion evolves in color, size, and contour.

2. Microscopic Findings:

• Vaginal squamous epithelium with areas of ulceration is seen on microscopic examination.

• Tumor cells are organized in nests, fusiform-looking cells in the lamina propria.

• Infiltration of tumor cells - Epithelioid 55%, spindled 17%, and mixed type of cells 28% are seen.

• Tumor cells have eosinophilic cytoplasm and multiple hyperchromatic, large, oval, and pleomorphic nuclei.

• Amelanotic melanomas are difficult to diagnose on histological examination.

3. Radiological Findings:

• Small tumors are difficult to find on CT scans.

• Fluorodeoxyglucose (FDG) is a glycolytic indicator in CT studies for early diagnosis and staging.

4. Immunohistochemical Analysis:

This method is used if the junctional activity or melanin pigment is absent. In this analysis, vaginal melanoma shows positive stains in the following:

• S-100 protein - A marker for differentiation of melanocytes.

• Melan A - Most widely used technique to identify basal metabolic proliferations.

• Human melanoma black 45 (HMB-45) - A marker for the pre-melanosomal cytoplasmic glycoprotein (GP 100).

• Vimentin.

• Fontana-Masson silver staining - Demonstrates melanin pigment.

• Tyrosinase.

Vaginal melanoma shows negative stains in the following:

• Amelanotic melanoma shows a negative for melanin pigment staining.

• Cytokeratin.

• Epithelial membrane antigen (EMA).

• Desmin.

• Myoglobin.

• Smooth muscle action.

• CD34 and CD68.

1. Molecular or Cytogenetic Findings:

• NRAS mutations and KIT amplifications.

• BRAF mutations are absent in vulvar and vaginal melanomas.

2. Staging:

• Staging describes the spread and size of the tumor.

• Clinical staging is based on the guidelines of FIGO (International federation of gynecology and obstetrics).

• Pathological staging is based on the AJCC (American joint committee on cancer’s TNM staging) method.

What Is the Differential Diagnosis for Vaginal Melanoma?

The differential diagnosis for vaginal melanoma includes the following:

• Hemangioendothelioma.

• Sarcoma.

• Undifferentiated carcinoma.

• Malignant fibrous histiocytoma (MFH).

• Malignant peripheral nerve sheath tumor.

What Are the Prognostic Factors for Vaginal Melanoma?

Vaginal melanoma has a poor prognosis compared to cutaneous melanomas. After five years of vaginal melanoma, the survival rate is 13 to 19%. Around half of the people with vaginal melanoma have positive lymph nodes, and 20% of patients have distant metastases. After recurrence, the mean survival is around eight months.

How to Treat Vaginal Melanoma?

The treatment options for vaginal melanoma depends on the tumor's size and spread. There is no standard treatment option for vaginal melanoma. However, the most common treatments include the following:

1. Surgery:

• Surgery is the preferred treatment option for melanomas that can be resected.

• Radical surgery, including hysterectomy, vaginectomy, and vulvectomy, depending on the location of melanomas.

• Lymphadenectomy with adjuvant radio or chemotherapy treats patients with advanced stages of primary malignant vaginal melanomas.

• Lymphadenectomy is not recommended for patients without lymph node involvement.

2. Chemotherapy:

• Palliative chemotherapy treats patients with inoperable tumors.

• Chemotherapy is performed using Dacarbazine, Temozolomide, Nitrosourea, Imatinib, Vincristine, and Nidran.

3. Biochemotherapy:

• It is a combination of chemotherapy and immunotherapy.

• Used in cases of advanced-stage diseases.

4. Post-operative Adjuvant Immunotherapy:

• Interferon alpha-2b is effective in preventing the relapse of the tumor.

• Immunotherapy uses agents such as dendritic cells, interleukin-2, lymphokine-activated killer cells, and bacillus Calmette-Geurin.

5. Radiotherapy:

• It is used as a post-operative adjuvant therapy along with immunotherapy and chemotherapy.

• It is used in incomplete resection of the tumor and tumors that cannot be removed surgically.

Conclusion

Patients with vaginal melanoma should have regular checkups to prevent tumor recurrence after the treatment. The survival rate depends on the distant and nodal metastasis of the tumor. More research is needed to prepare a proper therapeutic regimen for vaginal melanoma.