Solitary fibrous tumor with neuroendocrine and squamous dedifferentiation: a potential diagnostic pitfall

Summary Solitary fibrous tumor (SFT) is a ubiquitous mesenchymal neoplasm of deep soft tissue with variable and often unpredictable biological behavior. The lineage is presumed to be fibroblastic and histological features range from benign to overtly malignant with rare tumors showing "dedifferentiation" or transformation to undifferentiated pleomorphic sarcoma. Dedifferentiation in mesenchymal neoplasms is a phenomenon of histologic progression of a well-differentiated neoplasm to a high-grade sarcoma which can differentiate along divergent lines. It is extremely uncommon to encounter "transdifferentiation" to non-mesenchymal lineage and still maintaining the driver genetic event of the primary tumor. Herein we report two diagnostically challenging SFTs with transformation to neuroendocrine and squamous phenotypes. The index case is a pelvic malignant SFT which metastasized to the liver as a high grade neuroendocrine carcinoma. The second case is a recurrent brain tumor initially presenting as a typical SFT and evolving into a dedifferentiated SFT with foci of squamous differentiation. Positive immunohistochemical stains for CD34 and STAT6 and the detection of NAB2-STAT6 fusion supported the diagnosis of dedifferentiated SFT in both cases. In the first case, molecular study demonstrated that both the pelvic primary and liver metastasis harbored the same NAB2-STAT6 fusion. Dedifferentiation to a non-mesenchymal lineage/lineage infidelity can be a potential diagnostic pitfall in these tumors.