Diagnostic Algorithm For Gastrointestinal Stromal Tumor (Gist) Using Patient Registry Data Impacts Pathology Guidelines.

e23519 Background: The Life Raft Group (LRG) identified that succinate dehydrogenase (SDH) deficient GISTs are under-recognized. In the LRG Registry only 30% of KIT/PDGFRA wildtype patients had received the advanced mutational testing (or SDHB staining) required to identify this unique subtype of GIST with a different natural history and response to treatment, and very strong familial associations. We proposed that two changes would significantly increase the diagnosis of SDH-deficient GIST patients: 1. SDHB staining for all GIST patients with a stomach primary tumor at initial biopsy, 2. Initial pathology report should contain strong recommendations for specific mutational testing. Methods: The LRG collaborated with key medical opinion leaders on a diagnostic algorithm that illustrated the need for wider use of targeted diagnostic procedures and submitted the algorithm to the College of American Pathologists (CAP) GIST editorial board. Results: Because SDH-deficient GISTs require germline genetic analysis and, if mutation related, subsequent surveillance for paragangliomas/pheochromocytomas, and cascade genetic testing for family members, it is necessary to screen all gastric GISTs for loss of SDH by immunohistochemistry. This is best accomplished by immunohistochemical staining for SDHB, which is lost in all genetic subtypes of SDH-deficient GISTs. If SDHB is absent, additional staining for SDHA may be performed, as this protein is selectively lost in SDHA-mutant GISTs and this may help focus genetic analysis. All patients with SDH-deficient GIST should be referred to a genetic counselor. The CAP incorporated both SDHB and SDHA testing paradigms into the updated GIST protocols which were published in August 2019. Conclusions: We believe this will result in significantly better diagnosis and treatment for SDH-deficient GIST patients. We encourage other groups that advise on guidelines to develop similar recommendations. This is a great example of a patient advocacy group utilizing real world evidence derived from a patient registry to influence protocols for treatments that affect GIST patients on a large scale.