Soft Tissue Sarcoma Mimicking Melanoma: A Systematic Review

SIMPLE SUMMARY: Sarcoma may show similarities to malignant melanoma, making it difficult to differentiate between these two neoplasms. This systematic review summarizes evidence on cases of sarcoma that were initially diagnosed as melanoma to help clinicians in the diagnostic process. A comprehensive search of key databases identified 23 case reports and 4 case series with a total of 34 patients. Heterogeneous clinical presentation and frequent immunohistochemistry positivity contributed to the initial misdiagnosis. The second assessment was performed due to unusual presentation or uncertain diagnosis, and the final diagnosis was clear cell sarcoma (50%) or other soft tissue sarcomas (50%). EWSR1 translocation was investigated in 50% of cases, among which 94% were found to be positive. This systematic review suggests that a second diagnosis should be considered in cases of atypical lesions, and ESWR1 translocation should be investigated. ABSTRACT: Background: Sarcoma may show similarities to malignant melanoma in terms of morphologic and immunohistochemical aspects, making it difficult to differentiate between these two neoplasms during the diagnostic process. This systematic review aims to summarize available evidence on cases of sarcoma that were initially diagnosed as melanoma. Methods: A comprehensive search of the MEDLINE/Pubmed, EMBASE, and SCOPUS databases was conducted through March 2023. We included case series and case reports of sarcoma patients that were initially diagnosed as malignant melanoma. PRISMA guidelines were followed. Results: Twenty-three case reports and four case series with a total of 34 patients were included. The clinical presentation was heterogeneous, and the most involved anatomical regions were lower limbs (24%), head/neck (24%), and upper limbs (21%). IHC positivity was reported for S100 (69%), HMB45 (63%), MelanA (31%), and MiTF (3%). The main reasons for a second assessment were unusual presentation (48%) and uncertain diagnosis (28%). EWSR1 translocation was investigated in 17/34 patients (50%) and found to be positive in 16/17 (94%). The final diagnosis was clear cell sarcoma (50%) or other soft tissue sarcomas (50%). Conclusions: Melanoma and some histotypes of sarcoma share many similarities. In cases of atypical lesions, a second diagnosis should be considered, and ESWR1 translocation should be investigated.