Genitourinary melanoma: An overview for the clinician

doi:10.1016/j.ajur.2022.01.003

Asian Journal of Urology, 2022, 9 (4): 407-422 doi: 10.1016/j.ajur.2022.01.003

Special Issue on Advancing the Field of Rare Genitourinary Tumors: Challenges and Opportunities: Reviews

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Genitourinary melanoma: An overview for the clinician

Danielle K. DePalo^a,Kelly M. Elleson^a,Michael J. Carr^b,Philippe E. Spiess^c,Jonathan S. Zager^a,*(

)

^aDepartment of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA
^bDepartment of Surgery, University of Louisville, Louisville, KY, USA
^cDepartment of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL, USA

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Abstract

Genitourinary (GU) melanoma is a rare presentation of melanoma accounting for approximately 0.5% of all melanomas. GU melanomas include primary melanomas of the vulva, vagina, uterine cervix, ovary, penis, scrotum, urethra, bladder, ureter, and kidney. These melanomas are often diagnosed in advanced stages and stigma is thought to contribute to delays in presentation. As the likely diagnosing provider, it is imperative that dermatologists, urologists, and gynecologists are aware of these uncommon sites of presentation. While there have been major advances in the treatment of melanomas as a whole in the last 10 years, their applications to GU melanomas have often been overlooked. GU melanomas have not been included in many of the major phase III clinical trials which brought contemporary advanced treatments to market and the prognoses for GU melanomas remain poor. Due to the rarity of GU melanomas, much of the literature provides generalized recommendations across multiple different organs affected by GU melanomas or omits certain topics, making it difficult to appreciate the fundamentals of the individual presentations. This review aimed to provide background information on the pathogenesis and epidemiology of the different sites of GU melanomas and categorize data specific to the presentation, staging, treatment, and prognosis of each type of GU melanoma to guide the clinician. It was also meant to encourage a multidisciplinary approach to the management of these patients as it spans the expertise of surgical oncologists, medical oncologists, radiation oncologist, dermatologists, urologists, and gynecologists.

Key words： Genitalia Female Male Melanoma Rare diseases Staging Treatment Urinary tract

Received: 02 October 2021 Available online: 20 October 2022

Corresponding Authors: Jonathan S. Zager E-mail: jonathan.zager@moffitt.org

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Danielle K. DePalo,Kelly M. Elleson,Michael J. Carr, et al. Genitourinary melanoma: An overview for the clinician[J]. Asian Journal of Urology, 2022, 9(4): 407-422.

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http://www.ajurology.com/EN/10.1016/j.ajur.2022.01.003 OR http://www.ajurology.com/EN/Y2022/V9/I4/407

Melanoma of the left labium minus with clinically and radiographically node-negative disease undergoing modified radical left vulvectomy with lymphoscintigraphy-guided sentinel lymph node biopsy. (A) Vulvar melanoma visible only after retraction of the labia majora; (B) Margins of resection; (C) Specimen for pathology; (D) Closure of modified radical left vulvectomy (images courtesy of Mitchel S. Hoffman, M.D. and Jonathan S. Zager, M.D.).

Alternative staging system	Description
(A) Staging system proposed by Nagarajan et al.[44] (adjunct to TNM staging in vulvar melanoma)
Stage T1	≤2.0 with mitotic rate <2 per mm²
Stage T2	>2.0 and/or mitotic rate ≥2 per mm²
(B) 2018 FIGO staging for carcinoma of the cervix uteri[81] (applied to cervical melanoma)
Stage I	Carcinoma is strictly confined to the cervix uteri (extension to the corpus should be disregarded)
IA	Invasive carcinoma that can be diagnosed only by microscopy with maximum depth of invasion <5 mm
IA1	Measured stromal invasion <3 mm in depth
IA2	Measured stromal invasion ≥3 mm and <5 mm in depth
IB	Invasive carcinoma with deepest measured invasion ≥5 mm, lesion limited to the cervix uteri
IB1	Invasive carcinoma ≥5 mm in depth of stromal invasion and <2 cm in greatest dimension
IB2	Invasive carcinoma ≥2 cm and <4 cm in greatest dimension
IB3	Invasive carcinoma ≥4 cm in greatest dimension
Stage II	Carcinoma invades beyond the uterus, but has not extended to the lower 1/3 of the vagina or to the pelvic wall
IIA	Involvement limited to the upper 2/3 of the vagina without parametrial involvement
IIA1	Invasive carcinoma <4 cm in greatest dimension
IIA2	Invasive carcinoma ≥4 cm in greatest dimension
IIB	Parametrial involvement not up to the pelvic wall
Stage III	Carcinoma involves the lower 1/3 of the vagina and/or extends to the pelvic wall and/or causes hydronephrosis or non-functioning kidney and/or involves pelvic and/or involves paraaortic lymph nodes
IIIA	Carcinoma involves the lower 1/3 of the vagina with no extension to the pelvic wall
IIIB	Extension to the pelvic wall and/or hydronephrosis or non-functioning kidney (unless known to from another cause)
IIIC	Involvement of pelvic and paraaortic lymph nodes, irrespective of tumor size and extent
IIIC1	Pelvic lymph node metastasis only
IIIC2	Paraaortic lymph node metastasis
Stage IV	Carcinoma has extended beyond the true pelvis or has biopsy-proven involvement of the bladder or rectal mucosa.
IVA	Spread of the growth to adjacent organs
IVB	Spread to distant organs
(C) 2014 FIGO ovarian, fallopian tube, and peritoneal cancer staging system[90] (applied to ovarian melanoma)
Stage I	Tumor confined to ovaries or fallopian tubes
IA	Tumor limited to one ovary (capsule intact) or fallopian tube; no tumor on ovarian or fallopian tube surface; no malignant cells in ascites or peritoneal washings
IB	Tumor limited to both ovaries (capsules intact) or fallopian tubes; no tumor on ovarian or fallopian tube surface; no malignant cells in the ascites or peritoneal washings
IC	Tumor limited to one or both ovaries or fallopian tubes, with any of the following:
IC1	Surgical spill
IC2	Capsule ruptured before surgery or tumor on ovarian or fallopian tube surface
IC3	Malignant cells in the ascites or peritoneal washings
Stage II	Tumor involves one or both ovaries or fallopian tubes with pelvic extension (below pelvic brim) or primary peritoneal cancer
IIA	Extension and/or implants on uterus and/or fallopian tubes and/or ovaries
IIB	Extension to other pelvic intraperitoneal tissue
Stage III	Tumor involves one or both ovaries or fallopian tubes, or primary peritoneal cancer, with cytologically or histologically confirmed spread to the peritoneum outside the pelvis and/or metastasis to the retroperitoneal lymph nodes
IIIA
IIIA1	Positive retroperitoneal lymph nodes only (cytologically or histologically proven):
IIIA1 (i)	Metastasis up to 10 mm in greatest dimension
IIIA1 (ii)	Metastasis more than 10 mm in greatest dimension
IIIA2	Microscopic extrapelvic (above the pelvic brim) peritoneal involvement with or without positive retroperitoneal lymph nodes
IIIB	Macroscopic peritoneal metastasis beyond the pelvis up to 2 cm in greatest dimension, with or without metastasis to the retroperitoneal lymph nodes
IIIC	Macroscopic peritoneal metastasis beyond the pelvis more than 2 cm in greatest dimension, with or without metastasis to the retroperitoneal lymph nodes (including extension of tumor to capsule of liver and spleen without parenchymal involvement)
Stage IV	Distant metastasis excluding peritoneal metastases
IVA	Pleural effusion with positive cytology
IVB	Parenchymal metastases and metastases to extra-abdominal organs (including inguinal lymph nodes and lymph nodes outside of the abdominal cavity)
(D) Staging system as proposed by Bracken and Diokno[101] (applied to penile melanoma)
Stage I	Melanoma confined to the penis
Stage II	Melanoma with regional lymph node metastases
Stage III	Melanoma with distant metastases
(E) Staging system as proposed by Levine[121] (applied to urethral melanoma)
Stage A	Tumor confined to submucosa
Stage B	Tumor infiltrating periurethral muscle in females and corpus spongiosum in males
Stage C	Periurethral invasion including vagina, bladder, labia or clitoris in females and extending beyond the corpus spongiosum in males
Stage D	Metastasis to lymph nodes

Alternative staging systems applied to genitourinary melanoma.

Melanoma of the glans penis with biopsy-proven right inguinal nodal involvement undergoing partial penectomy with ventral phalloplasty and right inguinal complete lymph node dissection. (A and B) Penile melanoma presentation after retraction of the foreskin; (C and D) margins of resection; (E) specimen for pathology; (F) closure of partial penectomy with ventral phalloplasty and right inguinal lymphadenectomy (images courtesy of Philippe E. Spiess, M.D. and Jonathan S. Zager, M.D.).

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