Locations:
Search IconSearch
January 17, 2020/Cancer

Should You Stage Vulvar and Vaginal Melanomas with Mucosal Guidelines?

Molecular study suggests an update to AJCC guidelines

Metastatic melanoma cells. Image source: National Cancer Institute

The molecular characteristics of melanomas of the female genital tract fit more closely with those of mucosal than those of cutaneous melanoma, according to a recent review of 37 cases led by Shabnam Zarei, MD, Cleveland Clinic pathologist. Current American Joint Committee on Cancer (AJCC) staging guidelines recommend grouping vulvar melanoma with cutaneous melanoma and provide no guidance on staging vaginal melanoma. Dr. Zarei and colleagues’ findings suggest a change in current clinical practices and future guideline development.

Advertisement

Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy

“Historically, we have focused on anatomic distribution alone to fit melanoma into different staging categories — vulvar or vaginal, cutaneous or mucosal,” says Chad Michener, MD, Interim Chair of Cleveland Clinic’s Department of Subspecialty Care for Women’s Health. “Dr. Zarei’s work questions that focus and shifts it to a genomic basis.”

The seventh iteration of the AJCC recommendations for staging vaginal melanomas aligned with Dr. Zarei’s findings. However, in the eighth release, that guideline was removed entirely. “The guidelines changed because we have no staging system that seems to be highly predictive of prognosis, especially in vaginal melanoma, not FIGO [International Federation of Gynecology and Obstetrics] or Clark’s staging or tumor thickness or Breslow’s depth. The data we have favor using the cutaneous melanoma TNM staging system for vulvar melanoma,” says Dr. Michener. “That’s why Dr. Zarei’s data is exciting.”

Next-generation sequencing questions anatomic distribution

The study, published in the International Journal of Gynecological Pathology, evaluated the mutational status of 37 vulvar, vaginal and urethral melanoma patients with clear notation of primary tumor site (vulvar dermal, vulvar mucosal, vaginal and urethral) in their medical records. Thirty percent of patients had tumors of the hair-bearing vulva, 22% from the vagina, 19% from the urethra, 16% from vulvar glabrous skin, 8% from the junction of vulvar dermal and vulvar mucosal tissue and 5% from rectal and rectovaginal mucosa.

The research team used a DNA-targeted next-generation sequencing (NGS) panel analyzing the most common genetic mutations in melanomas to evaluate the cases. The panel provided whole exome coverage of 9 genes and mutational hotspot coverage in another 12 genes, and results were classified as pathogenic, likely pathogenic or variant of unknown significance.

Advertisement

Results showed that the three most common genetic alterations were KIT (32%), TP53 (22%) and NFI (19%). Two-thirds of cases had a pathogenic alteration in one or more of the MAPK pathway genes. Notably, none of the differences among mutation profiles in the primary tumor site groups were statistically significant, and overall survival rates were similar among groups.

“We were able to show that melanomas from different sites in the lower genital tract have similar molecular signatures as well as similar overall survival rates,” says Dr. Zarei. “Thus, we believe that vulvar and vaginal melanomas can be grouped together for staging purposes using AJCC mucosal melanoma guidelines.”

More data are needed

Dr. Zarei’s work challenges existing guidelines for staging melanomas of the lower genital tract and suggests a change in practice is necessary. “These are rare cancers, and we don’t understand enough about their biology to accurately predict outcomes. Our study offers evidence that suggests we need to think about these diseases differently,” says Dr. Zarei.

But the data aren’t there quite yet. “While further studies are needed to show that the mucosal melanoma staging system predicts outcomes for vulvar and vaginal melanomas,” adds Dr. Michener, “Dr. Zarei’s work is an exciting step forward in the use of molecular and genomic data to identify more accurate prognostic indicators in vulvar and vaginal melanomas.”

Image: Metastatic melanoma cells. Image source: National Cancer Institute

Advertisement

Related Articles

Older patients
July 17, 2025/Cancer/News & Insight
CAR T-Cell Therapy Safe & Effective for Octogenarians with B-Cell Lymphoma

Age alone should not rule out patients from potentially curative treatment

Surgeon
June 30, 2025/Cancer/News & Insight
Potential for Deintensification of Surgical Interventions in Low-Risk Breast Cancer

Reconsidering axillary lymph node dissection as well as depth of surgical margins

Dendritic cell
June 26, 2025/Cancer/News & Insight
Avelumab Induces Natural Killer Cell Activation and Dendritic Cell Crosstalk

Researchers uncover profound differences in the mechanism of action between different PD-L1 checkpoint inhibitors

World map
June 19, 2025/Cancer/News & Insight
Breaking Barriers to Cancer Care: Cleveland Clinic’s Global Approach

A multi-pronged strategy for tackling cancer access problems

CAR T-cell therapy illustration
June 12, 2025/Cancer/News & Insight
First-Ever U.S. Trial of CAR T-Cell Therapy for Relapsed/Refractory AL Amyloidosis

Early results show patients experiencing deep and complete response

Genomic profiling
June 10, 2025/Cancer
Cleveland Clinic’s Hemato-Oncology Team Spearheads the Development of Guidelines for Genomic Profiling of MDS to Inform Allo-HCT

Inclusion of genomic profiling and risk factors recommended for treatment planning

scan showing cholangiocarcinoma
June 5, 2025/Cancer/News & Insight
Exploring Novel Therapeutic Avenues in Advanced Cholangiocarcinoma: Lessons from the EA2187 Trial

Collaborative research effort underscores the urgent need for effective second-line therapies in this rare, aggressive cancer

Anticoagulant sign
June 4, 2025/Cancer/News & Insight
Direct-Acting Oral Anticoagulants Safe for Patients with Brain Metastasis

Largest study to date comparing direct-acting oral anticoagulants to low-molecular-weight heparin

Ad