A Duodenal SDH-Deficient Gastrointestinal Stromal Tumor in a Patient With a Germline SDHB Mutation

Elston, Marianne S.; Sehgal, Shekhar; Dray, Michael; Phillips, Elizabeth A.; Conaglen, John V.; Clifton‐Bligh, Roderick; Gill, Anthony J.

doi:10.1210/jc.2017-00165

Cited by 16 publications

(10 citation statements)

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“…The reported frequency of SDH‐deficient GIST ranges between 40% and 88% of wild‐type GIST 25,27 . With the exception of a single case of small bowel SDH‐deficient GIST reported to date, SDH‐deficient GIST occurs in the stomach 28 . Patients often present with multifocal tumours along the stomach wall and SDH‐deficient GIST have a characteristic histological epithelioid appearance (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

“…25,27 With the exception of a single case of small bowel SDHdeficient GIST reported to date, SDH-deficient GIST occurs in the stomach. 28 Patients often present with multifocal tumours along the stomach wall and SDH-deficient GIST have a characteristic histological epithelioid appearance (Figure 1). 28 SDH-deficient GIST has a high tendency to metastatic spread both locally and to distant sites.…”

Section: Sdh-deficient Gastrointestinal Stromal Tumours (Gist)mentioning

confidence: 99%

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A review of the tumour spectrum of germline succinate dehydrogenase gene mutations: Beyond phaeochromocytoma and paraganglioma

MacFarlane

Seong

Bisambar

et al. 2020

Clinical Endocrinology

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The citric acid cycle, also known as the Krebs cycle, plays an integral role in cellular metabolism and aerobic respiration. Mutations in genes encoding the citric acid cycle enzymes succinate dehydrogenase, fumarate hydratase and malate dehydrogenase all predispose to hereditary tumour syndromes. The succinate dehydrogenase enzyme complex (SDH) couples the oxidation of succinate to fumarate in the citric acid cycle and the reduction of ubiquinone to ubiquinol in the electron transport chain. A loss of function in the succinate dehydrogenase (SDH) enzyme complex is most commonly caused by an inherited mutation in one of the four SDHx genes (SDHA, SDHB, SDHC and SDHD). This mechanism was first implicated in familial phaeochromocytoma and paraganglioma. However, over the past two decades the spectrum of tumours associated with SDH deficiency has been extended to include gastrointestinal stromal tumours (GIST), renal cell carcinoma (RCC) and pituitary adenomas. The aim of this review is to describe the extended tumour spectrum associated with SDHx gene mutations and to consider how functional tests may help to establish the role of SDHx mutations in new or unexpected tumour phenotypes.

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Section: Resultsmentioning

confidence: 99%

Section: Sdh-deficient Gastrointestinal Stromal Tumours (Gist)mentioning

confidence: 99%

A review of the tumour spectrum of germline succinate dehydrogenase gene mutations: Beyond phaeochromocytoma and paraganglioma

MacFarlane

Seong

Bisambar

et al. 2020

Clinical Endocrinology

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“…Duodenal GISTs originate from Cajal interstitial cells or more primitive mesoderm-derived mesen- chymal stem cells [12]. GISTs account for 1-3% of all gastrointestinal tumors and are the most common mesenchymal tumors arising in the gastrointestinal tract [13][14][15][16].…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological Characteristics, Surgical Treatments, and Survival Outcomes of Patients with Duodenal Gastrointestinal Stromal Tumor

et al. 2018

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Background: Duodenal gastrointestinal stromal tumors (GISTs) are rare and their clinicopathological features have not been completely described. In this retrospective study, we examined the characteristics and long-term outcomes of patients who underwent surgical treatment for duodenal GISTs. Methods: We examined patients surgically treated for duodenal GISTs from 1999 to 2016 at the China National Cancer Center. We analyzed patient characteristics, treatments, histological examinations, and survival outcomes. Results: The 52 surgeries performed included 14 pancreaticoduodenectomies (26.9%), 37 limited resections (71.2%), and one palliative bypass procedure (1.9%). No surgery-related death occurred. The complication rate in patients who underwent pancreaticoduodenectomy was slightly higher than that in patients who underwent limited resection. The 5-year overall survival and progression-free survival rates for patients with duodenal adenocarcinoma were 89.1 and 72.9%, respectively. The overall survival and progression-free survival rates were not significantly related to surgical methods. Large tumor size and high mitotic rate were associated with poor overall survival outcomes. However, no independent factor was associated with prognosis, which may be due to the small sample size. Conclusion: The prognosis of duodenal gastrointestinal stromal tumors was good. Limited resection seems to be oncologically feasible, with outcomes being less worse than those of pancreaticoduodenectomy.

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“…SDH‐deficient GISTs are defined by loss of immunohistochemical expression of SDHB . To date, only a single case of SDH‐deficient GIST has been reported in the duodenum, with all other reported cases having arisen in the stomach . From a practical viewpoint, unless there are extraordinary circumstances we only consider the diagnosis of SDH deficiency in gastric GISTS.…”

Section: Sdh‐deficient Gastrointestinal Stromal Tumour (Gist)mentioning

confidence: 99%

“… To date, a single succinate dehydrogenase (SDH)‐deficient gastrointestinal stromal tumour (GIST) arising in the duodenum has been reported …”

Section: Sdh‐deficient Gastrointestinal Stromal Tumour (Gist)mentioning

confidence: 99%

Succinate dehydrogenase (SDH)‐deficient neoplasia

2017

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Gill A J (2018) Histopathology 72, 106-116. https://doi.org/10.1111/his.13277 Succinate dehydrogenase (SDH)-deficient neoplasiaThe succinate dehydrogenase (SDH) complex is a key respiratory enzyme composed of four subunits: SDHA, SDHB, SDHC and SDHD. Remarkably, immunohistochemistry for SDHB becomes negative whenever there is bi-alleic inactivation of any component of SDH, which is very rare in the absence of syndromic disease. Therefore, loss of SDHB immunohistochemistry serves as a marker of syndromic disease, usually germline mutation of one of the SDH subunits. Tumours which show loss of SDHB expression are termed succinate dehydrogenase-deficient. In addition to loss of SDHB, tumours associated with SDHA mutation also show loss of SDHA expression. Fifteen per cent of pheochromocytoma and paraganglioma (PHEO/PGL) are associated with germline SDH mutation, and therefore SDH-deficient. We recommend screening SDHB immunohistochemistry for all PHEO/ PGL. SDH-deficient gastrointestinal stromal tumours (GISTs) show distinctive features, including absent KIT proto-oncogene receptor tyrosine kinase/plateletderived growth factor receptor A (KIT/PDGFRA) mutations [but positive staining for cKIT and DOG1], virtually exclusive gastric location, lobulated growth, multi-focality, a prognosis not predicted by size and mitotic rate, frequent metastasis to lymph nodes and primary resistance to imatinib therapy. Thirty per cent are associated with SDHA germline mutation and 50% are associated with SDHC epimutation (post-zygotic promoter hypermethylation) -the hallmark of the syndromic but non-hereditary Carney triad (SDH-deficient GIST, SDH-deficient paraganglioma and pulmonary chondroma). SDH-deficient renal carcinoma is newly recognized under the World Health Organization (WHO) 2016 classification and shows vacuolated eosinophilic cytoplasmic and cytoplasmic inclusions. It is particularly associated with SDHB mutation, although SDHC and SDHA mutation occur. SDH-deficient pituitary adenomas are recognized, but appear to be the least common SDH-deficient neoplasm.

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A Duodenal SDH-Deficient Gastrointestinal Stromal Tumor in a Patient With a Germline SDHB Mutation

Abstract: We describe an SDH-deficient GIST occurring outside of the stomach. This case indicates that SDH-deficient GISTs may also arise in the small intestine.

Cited by 16 publications

References 10 publications

A review of the tumour spectrum of germline succinate dehydrogenase gene mutations: Beyond phaeochromocytoma and paraganglioma

A review of the tumour spectrum of germline succinate dehydrogenase gene mutations: Beyond phaeochromocytoma and paraganglioma

Clinicopathological Characteristics, Surgical Treatments, and Survival Outcomes of Patients with Duodenal Gastrointestinal Stromal Tumor

Succinate dehydrogenase (SDH)‐deficient neoplasia

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