Extraordinary Case ReportUndifferentiated Sarcoma as Intermediate Step in the Progression of Malignant Melanoma to Rhabdomyosarcoma: Histologic, Immunohistochemical, and Molecular Studies of a New Case of Malignant Melanoma With Rhabdomyosarcomatous DifferentiationTran, Tien Anh N. MD*; Linos, Konstantinos MD†; de Abreu, Francine B. PhD†; Carlson, John Andrew MD, FRCPC‡Author Information *Department of Pathology, Florida Orlando Hospital, Orlando, FL; †Dermatopathology, Bone & Soft Tissue, and Molecular Pathology Divisions, Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Geisel School of Medicine at Dartmouth, Lebanon, NH; and ‡Department of Pathology and Dermatopathology, Albany Medical College, Albany, NY. Correspondence: Tien Anh N. Tran, MD, Department of Pathology, Florida Orlando Hospital, 601 East Rollins Street, Orlando, FL 32803 (e-mail: email@example.com). The authors declare no conflicts of interest. The American Journal of Dermatopathology: March 2019 - Volume 41 - Issue 3 - p 221-229 doi: 10.1097/DAD.0000000000001236 Buy Metrics Abstract Malignant melanoma (MM) may display highly variable phenotypic diversity, sometimes associated with loss of immunohistochemical melanocytic markers and acquisition of nonmelanocytic lineage of differentiation. Primary cutaneous MM with rhabdomyosarcomatous differentiation is extremely rare with only 5 reported cases in the literature. To date, a chronological progression of a MM to rhabdomyosarcoma has not been conclusively documented. A 96-year-old man underwent a re-excision of an “atypical fibroxanthoma” of the forearm, which revealed a small lentigo maligna melanoma associated with a dominant dermal high-grade spindle cell nodule admixed with a population of malignant polygonal epithelioid cells. On immunohistochemical studies, the spindle cells were completely negative for all melanocytic markers, whereas a small population of polygonal neoplastic cells at the periphery was positive for Desmin and Myo-D1, supporting early rhabdomyosarcomatous transformation. Several subsequent re-excisions demonstrated merely nodules of malignant pleomorphic epithelioid cells with rhabdomyosarcomatous differentiation and devoid of melanocytic markers. In addition, both rhabdomyosarcomatous component and original MM displayed identical mutations. Therefore, the histologic, immunohistochemical, and molecular findings documented for the first time a chronological progression from an invasive MM to a pleomorphic rhabdomyosarcoma through an intermediate stage of undifferentiated sarcoma/atypical fibroxanthoma. Interestingly, subsequent recurrences of pure rhabdomyosarcomatous component displayed skip lesions/microsatellitosis, marked tumor-infiltrative lymphocytes, and rare junctional nests of rhabdomyosarcomatous cells in the epidermis, histologic features that were not described in primary cutaneous rhabdomyosarcoma and therefore could serve as morphologic clues to the diagnosis of rhabdomyosarcomatous transformation in an MM. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.