Aaron M Udager1, Nora K Frisch1, Linda J Hong2, Marina Stasenko2, Carolyn M Johnston2, J Rebecca Liu2, May P Chan3, Paul W Harms3, Douglas R Fullen3, Amy Orsini4, Dafydd G Thomas1, Lori Lowe3, Rajiv M Patel5. 1. Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, United States. 2. Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, MI, United States. 3. Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, United States; Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, United States. 4. Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, United States. 5. Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, United States; Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, United States. Electronic address: rajivpat@med.umich.edu.
Abstract
OBJECTIVE: Melanoma originating from gynecologic sites (MOGS), including the vulva, vagina, and cervix, is a rare and aggressive form of melanoma with poor long-term clinical outcome. The clinicopathologic features of vulvar and non-vulvar tumors remain relatively understudied, and in contrast to cutaneous melanomas at non-sun-exposed sites, MOGS typically do not harbor BRAF mutations. Thus, we sought to analyze the clinicopathologic and molecular features of MOGS. METHODS: A large retrospective cohort of patients with MOGS (n=59) at a single large academic institution over a 28-year period was identified. Associations among clinicopathologic characteristics were assessed via standard statistical approaches, and clinical outcome was examined using Cox regression analysis. Sanger sequencing was utilized to identify mutations in hotspot regions of BRAF, KIT, NRAS, and CTNNB1. RESULTS: Tumors involving the vagina and/or cervix (non-vulvar) are significantly associated with high-risk clinicopathologic features, including increased tumor thickness, ulceration, positive resection margins, lymph node metastasis, and poor long-term clinical outcome (with increased risk of death due to disease). The aggressive clinical behavior of non-vulvar tumors is independent of advanced clinical stage and lymph node metastasis in multivariate analysis. Targeted molecular analysis confirms an overall low rate of oncogenic mutations in our MOGS cohort, although KIT mutations (particularly in exon 11) are relatively enriched. CONCLUSIONS: Overall, our results show that non-vulvar MOGS are aggressive tumors with poor long-term clinical outcome and indicate that few targeted therapeutic options are currently available to patients with MOGS.
OBJECTIVE:Melanoma originating from gynecologic sites (MOGS), including the vulva, vagina, and cervix, is a rare and aggressive form of melanoma with poor long-term clinical outcome. The clinicopathologic features of vulvar and non-vulvar tumors remain relatively understudied, and in contrast to cutaneous melanomas at non-sun-exposed sites, MOGS typically do not harbor BRAF mutations. Thus, we sought to analyze the clinicopathologic and molecular features of MOGS. METHODS: A large retrospective cohort of patients with MOGS (n=59) at a single large academic institution over a 28-year period was identified. Associations among clinicopathologic characteristics were assessed via standard statistical approaches, and clinical outcome was examined using Cox regression analysis. Sanger sequencing was utilized to identify mutations in hotspot regions of BRAF, KIT, NRAS, and CTNNB1. RESULTS:Tumors involving the vagina and/or cervix (non-vulvar) are significantly associated with high-risk clinicopathologic features, including increased tumor thickness, ulceration, positive resection margins, lymph node metastasis, and poor long-term clinical outcome (with increased risk of death due to disease). The aggressive clinical behavior of non-vulvar tumors is independent of advanced clinical stage and lymph node metastasis in multivariate analysis. Targeted molecular analysis confirms an overall low rate of oncogenic mutations in our MOGS cohort, although KIT mutations (particularly in exon 11) are relatively enriched. CONCLUSIONS: Overall, our results show that non-vulvar MOGS are aggressive tumors with poor long-term clinical outcome and indicate that few targeted therapeutic options are currently available to patients with MOGS.
Authors: Ozlen Saglam; Syeda M H Naqvi; Yonghong Zhang; Tania Mesa; Jamie K Teer; Sean Yoder; Jae Lee; Jane Messina Journal: Melanoma Res Date: 2018-12 Impact factor: 3.599
Authors: Michail Diakosavvas; Zacharias N Fasoulakis; Maria Kouroupi; Marianna Theodora; Lola Inagamova; Georgios Tsatsaris; Panagiotis Nikolaou; Konstantina Frangia-Tsivou; Alexandra Giatromanolaki; Emmanuel N Kontomanolis Journal: Case Rep Oncol Med Date: 2020-09-03