Abstract

Superficial ALK-rearranged myxoid spindle cell neoplasm (SAMS) is a recently described entity which coexpresses ALK, CD34, and S100. These neoplasms are morphologically characterized by concentric whorls and cords of bland spindle cells, set in myxoid to myxo-collagenous stroma. Such neoplasms show ALK gene rearrangement with partner genes such as (FLNA, MYH10, FMR1 and HMBOX1), detected by next-generation sequencing (NGS). Herein we present a 46-year-old female patient with no past medical history, presenting with a great toe papule for two months. A punch skin biopsy demonstrated bland spindle to ovoid cell proliferation arranged in loose fascicles and vague reticular pattern. The lesional cells were ovoid to spindled with fine chromatin, small nucleoli, and variable pale cytoplasm, in a myxocollagenous stroma with scattered admixed lymphocytes. Mitotic activity reached up to 1 per 10 HPF. Immunohistochemical studies revealed the lesional cells were diffusely positive for ALK and patchy positive for S100, SMA, and CK AE1/AE3, while were negative for CD34, Melan A, SOX10, PRAME, desmin, P63, and EMA. Subsequent flourescence in situ hybridization studies revealed ALK gene rearrangement. NGS-based RNA sequencing demonstrated PRKAR1A::ALK fusion. The histopathological features, immunophenotype, and molecular studies supported a diagnosis of SAMS with aberrant keratin expression and novel gene fusion partner. SAMS has unique morphology, immunophenotype, and ALK gene fusions, mimicking perineurioma and hybrid nerve sheath tumors morphologically, which could be a pitfall. To our knowledge, our case is the first case of SAMS with aberrant keratin expression. Moreover, it is the first case with such PRKAR1A::ALK fusion.