Distinctive Near-Haploid Fibromyxoid Neoplasm: A Clinicopathologic and Molecular Genetic Study of a Unique,...

Despite advances in molecular genetics that have helped elucidate the pathogenesis of many soft tissue neoplasms, subsets of fibromyxoid tumors remain difficult to subclassify because of their nonspecific morphologic and immunohistochemical features, and lack of discrete molecular alterations. We report 7 cases of a distinctive fibromyxoid soft tissue neoplasm characterized at the cytogenomic level by massive loss of heterozygosity, resulting in a near-haploid or pseudohyperdiploid cytogenome. The tumors occurred in superficial and deep soft tissue locations (mesentery, mediastinum, thigh, pelvis, leg, orbit, and head) of 5 males and 2 females (median age, 45 years). They ranged in size from 2.6 to 14 cm (median, 5 cm) and were composed of small, bland spindled cells in a variably vascularized, fibromyxoid stroma with abundant wiry collagen. Mitotic activity was low, and necrosis was absent in all but 1 case, which demonstrated foci of infarct-type necrosis. One tumor showed infiltrative growth into surrounding tissue while all others were circumscribed and noninfiltrative. Immunohistochemistry demonstrated CD34 (5/5) and desmin (3/5) expression; S100 protein, SOX10, MUC4, and GLUT1 were negative, among others. All tumors demonstrated massive loss of heterozygosity with copy number gain and retained heterozygosity of selected chromosomes, including chromosomes 8 and 19, evaluated with OncoScan single-nucleotide polymorphism array. Biallelic inactivation of NF1 was seen in 2 cases, including 1 in a patient with neurofibromatosis type 1. Three patients showed possible evidence of stable locally recurrent/residual disease following incomplete resection while all other patients were free of disease (median follow-up, 17 months). The tumors presented in this study are essentially identical to those of a very recently reported series of 5 cases, strongly suggesting that these collectively represent a novel entity, which we propose terming distinctive near-haploid fibromyxoid neoplasm.