Primary malignant melanoma of esophagus: clinicopathologic characterization of 20 cases including molecular genetic profiling of 15 tumors

Abstract

Primary malignant melanoma of esophagus is very rare, and its clinicopathologic and genetic features have not been extensively investigated. In this study, 20 tumors from 14 male and 6 female patients (40-79 years old) were evaluated. Dysphagia, chest pain, and weight loss were frequent symptoms. Thirteen melanomas, including two with multiple lesions, involved the distal third of esophagus. The median tumor diameter was 6 cm. Epithelioid morphology, moderate atypia, and pigmentation were typical findings. None of the patients had melanoma elsewhere, and all tumors exhibited a junctional periepithelial component consistent with a primary lesion. The median mitotic activity was 11 per 10 high-power fields (range, 0-31). Nine patients died of tumor within 4-22 months, however, two showed long-term (96 and 104 months) survival. In 15 cases, tissue for further immunohistochemical and molecular studies were available. BRAF, KIT, and NRAS mutation status was assessed by Sanger sequencing in all 15 tumors. The next-generation sequencing of 50 or 409 genes was performed in five and three cases, respectively. IGF1R expression indicating activation of the IGF axis was seen in 82% (9/11) of tumors. However, no BRAF mutations were identified. In 33% (5/15) of tumors, NRAS mutations were detected. KIT expression was seen in 50% (7/14) of melanomas including single KIT mutant. Two of three tumors evaluated with 409 genes panel revealed multiple driver mutations indicating sub-clonal expansion, whereas a single mutation (TSC1 p.H371Q) was the sole change in the third case. SF3B1 p.K666T and p.R625C mutations were detected in two cases. However, no cooccurrence of SF3B1 and GNAQ or GNA11 mutations, seen in uveal melanoma, was detected. FBXW7 p.R465C and p. R479G mutations, linked to cancer progression, were found in two of eight tumors. In summary, esophageal melanoma mutation profile indicates complexity of molecular mechanisms underlying its pathogenesis.

Pulmonary melanocytic nevus – A case report with a mutation analysis of common driver oncogenes

“…The (V600E) BRAF mutation is the most common gene mutation found in cutaneous melanocytic nevi; i.e., it is detected in 55–88% of all cutaneous melanocytic nevi (and 57–75% of extracutaneous melanocytic nevi) and about 50% of cutaneous malignant melanomas (and 7% of extracutaneous malignant melanomas) (Table ) . It is considered that at least in the skin some melanocytic nevi with BRAF (V600E) mutations could progress to become malignant melanomas with the same mutations.…”

Histopathological landscape of rare oesophageal neoplasms

“…Background: Oesophageal melanomas (OMs) have an estimated incidence of 0.03 cases per million in the United States, accounting for 3% of all melanomas and for 0.2% of all collective oesophageal malignancies[ 84 , 85 ]. Both the risk factors and the pathogenesis of OMs are still debated.…”

“…Both the risk factors and the pathogenesis of OMs are still debated. Although melanocytes may encase the oesophageal mucosa as a consequence of aberrant early migration of melanoblasts from the neural crest[ 86 ], individual and environmental drivers of malignant degeneration of these cells are still unclear[ 85 , 86 ]. Moreover, the multiphasic molecular pathway underlying the development of OMs is still uncharacterised.…”

Primary malignant melanoma of the esophagus. Literature review and clinical case

“…Крайне важным для проведения дифференциальной диагностики первичной меланомы пищевода является выполнение иммуногистохимического исследования [4,5,23,24]. Положительные HMB-45, белок S-100, Vimentin, Melan A, нейроспецифичная енолаза и отрицательные цитокератин, р 63, CEA подтверждают наличие меланомы и исключают карциному [4,5,9].…”

“…Согласно данным различных авторов, 2-х летняя безрецидивная выживаемость после радикального лечения первичной опухоли составляет около 40 %, а общая выживаемость -около 50 -60 %. Медиана выживаемости может достигать 34,5 месяцев [23,28,40].…”