Dedifferentiated Solitary Fibrous Tumor

Dedifferentiated solitary fibrous tumor (DDSFT) is a rare and clinically aggressive malignancy with a poor prognosis. It represents the progression of solitary fibrous tumor to a high-grade, morphologically nondistinctive sarcoma. This study characterizes the clinicopathologic and molecular features of 25 DDSFT. The study cohort comprised 13 males and 12 females with a median age of 63 years (range 31 to 84). Tumors were most common in the pelvic cavity (8/25), thoracic cavity (6/25), and trunk (4/25). Histologically, DDSFT demonstrated remarkably variable morphology, including pleomorphic, epithelioid, spindle cell, and round cell features. Heterologous elements were present in 4/25 (16%). Immunohistochemical expression of STAT6 was completely lost in 8/22 (36%) tumors. Targeted DNA sequencing demonstrated that in most tumors (10/13; 77%), the NAB2 :: STAT6 fusion variant resulted in a truncated STAT6 (STAT6-TAD) in the fusion protein. Recurrent secondary alterations involved TP53 (10/14; 71%), TERT (8/14; 57%), and RB1 (3/14; 21%). Statistical analysis of the study cohort and 55 cases reported in the literature demonstrated that complete loss of STAT6 in DDSFT is associated with shorter disease-specific survival (HR 12.69, P =0.023).