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18 January 2023 - Case of the Month #523

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Thanks to Dr. Raul Gonzalez, Emory University School of Medicine, Atlanta, Georgia, USA for contributing this case and discussion and to Dr. Aaron R. Huber, University of Rochester Medical Center, Rochester, New York, USA, for reviewing the discussion.

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Case of the Month #523

Clinical history:
A 25 year old man complaining of abdominal pain is found to have a 4 cm gastric mass, which is resected.

Histopathology images:

What is your diagnosis?

Click here for diagnosis, test question and discussion:

Diagnosis: SDH deficient gastrointestinal stromal tumor (GIST)

Test question (answer at the end):
Which of the following is true about succinate dehydrogenase deficient gastrointestinal stromal tumors (SDH deficient GISTs)?

A. They almost always arise in the colon
B. They are negative for KIT by immunohistochemistry
C. They have a very poor prognosis
D. They sometimes metastasize to lymph nodes




Gastrointestinal stromal tumor (GIST) is the most common mesenchymal malignancy of the gastrointestinal tract. The majority are characterized by mutations in KIT or PDGFRA. However, roughly 5 - 10% of GISTs result from mutations in SDHA, SDHB, SDHC or SDHD genes that encode protein subunits in the succinate dehydrogenase complex.

SDH deficient GISTs, which were previously known as wild type GISTs or pediatric GISTs, have several unique characteristics (Arch Pathol Lab Med 2020;144:655). They almost always occur in the stomach, with extremely rare reports of extragastric examples. Patients tend to be under the age of 50. Histologically, these GISTs are often epithelioid and plexiform / multinodular. Immunohistochemistry shows loss of staining for SDHB (Am J Surg Pathol 2010;34:636), regardless of which gene mutation is present in the tumor. These GISTs remain positive for KIT and DOG1, like other GISTs, allowing the diagnosis to be established. Patients with SDH deficient GISTs often have Carney-Stratakis syndrome (GIST and paraganglioma, due to an autosomal dominant SDH subunit gene germline mutation) or Carney complex (GIST, paraganglioma and pulmonary chondroma, with no known familial link).

While GISTs overall rarely metastasize to lymph nodes, this behavior occurs in up to 18% of SDH deficient GISTs (Am J Surg Pathol 2016;40:1616). Patients often present with metastases to distant sites, such as the liver (JAMA Oncol 2016;2:922). Additionally, traditional risk stratification for GIST (using size and mitotic rate) does not seem to accurately predict risk of disease progression (Am J Surg Pathol 2016;40:1616). Furthermore, imatinib does not appear to be effective against SDH deficient GISTs, though sunitinib has shown some efficacy. Patients with this form of GIST have a moderate prognosis overall and may experience a protracted clinical course.

Test question answer:
D. They sometimes metastasize to lymph nodes. SDH deficient GISTs may metastasize to lymph nodes, which almost never happens in GISTs that arise through other molecular pathways. Despite this behavior, they have a relatively good prognosis. SDH deficient GISTs almost always arise in the stomach, not the colon. They are positive for KIT and DOG1 by immunohistochemistry, facilitating the diagnosis of GIST. They have a moderate prognosis, and patients often have a protracted clinical course with metastases to lymph nodes and distant organs.

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