TGCT Case Study Highlights Importance of Molecular Testing for Sarcomas

Findings from a case study and review of treatments for patients with malignant tenosynovial giant cell tumor (TGCT) suggest that although novel therapies targeting molecular pathway seem to have activity TGCT, cytotoxic drugs remain the most effective (Anticancer Drugs. 2020;31[1]:80-84). However, malignant TGCT remains “an orphan disease with unmet medical needs.”

Robert Maki, MD, PhD, Northwell Health Cancer Center Institute, New York, provides a brief commentary on the review and its significance regarding the treatment of patients with TGCT.

This is a case report of a patient purportedly with TGCT, who developed metastatic disease, and never responded to any systemic treatment, despite half a dozen types of therapy being used.

While immunohistochemistry was used to diagnose the tumor, and limited molecular testing was done, the definitive translocation was never demonstrated by FISH or RNA sequencing, and thus it will be impossible to know if this was an extremely rare and hyper-aggressive version of TGCT, or whether this was another form of sarcoma, such as undifferentiated pleomorphic sarcoma, angiomatoid fibrous histiocytoma, rhabdomyosarcoma, or histiocytic sarcoma.

In a large series of >250 TGCT, there were no metastases seen, underscoring the unusual nature of this scenario if this were indeed a TGCT. It is unlikely rhabdomyosarcoma, since those tumors generally respond then recur, rather than demonstrating primary resistance.

These are strong data that experts in pathology of soft tissues should review material for most, if not all, cases of soft tissue sarcoma, especially when the clinical scenario does not fit the diagnosis.

This case report also provides data that molecular testing, such as RNA sequencing to identify specific translocations, should be considered for a number of sarcomas, in particular when a rare diagnosis is going to be made.

These data make me hopeful that all sarcomas and connective tissue tumors are reviewed in expert centers, since an incorrect diagnosis means incorrect treatment.