Succinate Dehydrogenase (SDH)-deficient Renal Carcinoma

Gill, Anthony J.; Hes, Ondřej; Papathomas, Thomas; Sedivcova, Monika; Tan, Puay Hoon; Agaimy, Abbas; Andresen, Per Arne; Kedziora, Andrew; Clarkson, Adele; Toon, Christopher W.; Sioson, Loretta; Watson, Nicole; Chou, Angela; Paik, Julie; Clifton‐Bligh, Roderick; Robinson, Bruce G.; Benn, Diana E.; Hills, Kirsten; Maclean, Fiona; Niemeijer, Nicolasine D; Vlatkovic, Ljiljana; Hartmann, Arndt; Corssmit, Eleonora P M; Leenders, Geert J.L.H. van; Przybycin, Christopher G.; McKenney, Jesse K.; Magi‐Galluzzi, Cristina; Yilmaz, Aslı; Yu, Darryl C W; Nicoll, Katherine D.; Yong, Jim; Sibony, Mathilde; Yakirevich, Evgeny; Fleming, Stewart; Chow, C. W.; Miettinen, Markku; Michal, Michal; Trpkov, Kiril

doi:10.1097/pas.0000000000000292

Cited by 270 publications

(122 citation statements)

References 42 publications

(69 reference statements)

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“…Collectively, these changes are thought to drive tumorigenesis in the multiple organ systems that demonstrate increased incidence of neoplasia in individuals harboring germline SDHx mutations, which include paragangliomas/pheochromocytomas, GISTs and, among a subset, a histologically distinctive type of renal cell carcinoma (Gill et al 2014, Williamson et al 2015. Importantly, with regard to GISTs, SDH-deficient GISTs can be due to either genetic (SDHA, B, C or D mutations) or epigenetic (SDHC promoter methylation) changes.…”

Section: Sdh-deficient Gists (Sdha B C D Mutations Sdhc Epimutants)mentioning

confidence: 99%

Classification of gastrointestinal stromal tumor syndromes

Gopie

Faber

et al. 2018

Endocrine-Related Cancer

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Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, thought to derive from neoplastic outgrowth of the interstitial cells of Cajal. Building on recent advances in recognition, classification and diagnosis, the past two decades have seen a changing paradigm with molecular diagnostics and targeted therapies. KIT and PDGFRA mutations account for 85-90% of GIST carcinogenesis. However, the remaining 10-15% of GISTs, which until recently were called KIT/PDGFRA wild-type GISTs, have been found to have one of the several mutations, including in the SDHA, B, C, D, BRAF and NF1 genes. Though most of such GISTs are sporadic, a number of families with high incidence rates of GISTs and other associated clinical manifestations have been reported and found to harbor germline mutations in KIT, PDGFRA, SDH subunits and NF1. The goal of this review is to describe the mutations, clinical manifestations and therapeutic implications of syndromic and inherited GISTs in light of recent studies of their clinicopathologic range and pathogenesis.

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Section: Sdh-deficient Gists (Sdha B C D Mutations Sdhc Epimutants)mentioning

confidence: 99%

Classification of gastrointestinal stromal tumor syndromes

Gopie

Faber

et al. 2018

Endocrine-Related Cancer

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“…SDH-deficient RCC has been recognized as novel entity in the 2016 WHO classification of renal tumors (44,45). It may show a morphologic spectrum wider than has been previously described (46) and some cases may be essentially indistinguishable from other non-SDH-related RCCs at histology.…”

Section: Renal Cell Carcinomas (Rccs)mentioning

confidence: 98%

“…In a more recent paper, Gill et al evaluated the morphology of 36 SDH-deficient RCCs from 27 patients and concluded that the most distinctive histologic feature was the presence of cytoplasmic vacuoles and inclusionlike spaces containing either pale eosinophilic fluid or flocculent material (42). Nonetheless, in some cases, these inclusions were focal and not easy to identify.…”

Section: Renal Cell Carcinomas (Rccs)mentioning

confidence: 99%

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DIAGNOSIS of ENDOCRINE DISEASE: SDHx mutations: beyond pheochromocytomas and paragangliomas

Mannelli¹,

Canu²,

Ercolino³

et al. 2018

European Journal of Endocrinology

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Mutations in one of the five genes encoding the succinate dehydrogenase (SDHx) or mitochondrial complex II cause the corresponding family syndromes characterized by the occurrence of pheochromocytomas (PHEO) and paragangliomas (PGL). Recently, other solid growths, such as gastrointestinal stromal tumors (GISTs), renal cell carcinomas (RCCs) and pituitary adenomas (PAs) have been associated with these syndromes. In the absence of prospective studies assessing their frequency, at present, their occurrence seems too infrequent to suggest systematic screening for SDHx mutation carriers. However, SDHB immunohistochemistry (IHC) on tumor tissues or SDHx genetic testing on blood or tumor samples should be performed in patients affected by GISTs, RCCs or PAs with clinicopathologic phenotypes suggesting an etiologic role of SDHx genes.

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“…Nextgeneration sequencing of DNA extracted from paraffinembedded tissue showed an SDHB mutation and loss of the second in 5 of 6 tumors studied. A recent report by Gill et al 54 described 36 cases of succinate dehydrogenase-deficient RCCs, 21 of which were previously unreported. This study demonstrated the presence of the described morphologic features in 94% of the tumors studied and estimated that 0.05% to 0.2% of all RCCs are SDH deficient with a slight male predominance, bilaterality in 26%, and a strong association between high-grade nuclei and subsequent metastasis.…”

mentioning

confidence: 99%

Biomarker, Molecular, and Technologic Advances in Urologic Pathology, Oncology, and Imaging

Ellis

Harik

Cohen

et al. 2017

Archives of Pathology &Amp; Laboratory Medicine

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Urologic pathology is evolving rapidly. Emerging trends include the expanded diagnostic utility of biomarkers and molecular testing, as well as adapting to the plethora of technical advances occurring in genitourinary oncology, surgical practice, and imaging. We illustrate those trends by highlighting our approach to the diagnostic workup of a few selected disease entities that pathologists may encounter, including newly recognized subtypes of renal cell carcinoma, pheochromocytoma, and prostate cancer, some of which harbor a distinctive chromosomal translocation, gene loss, or mutation. We illustrate applications of immunohistochemistry for differential diagnosis of needle core renal biopsies, intraductal carcinoma of the prostate, and amyloidosis and cite encouraging results from early studies using targeted gene expression panels to predict recurrence after prostate cancer surgery. At our institution, pathologists are working closely with urologic surgeons and interventional radiologists to explore the use of intraoperative frozen sections for margins and nerve sparing during robotic prostatectomy, to pioneer minimally invasive videoscopic inguinal lymphadenectomy, and to refine image-guided needle core biopsies and cryotherapy of prostate cancer as well as blue-light/fluorescence cystoscopy. This collaborative, multidisciplinary approach enhances clinical management and research, and optimizes the care of patients with urologic disorders. (Arch Pathol Lab Med. 2017;141:499-516; doi: 10.5858.arpa.2016-0263-SA) I n this review, we summarize the effect of a number of biomarker, molecular, and technologic advances in urologic pathology, oncology, and imaging on routine, day-to-day practice and research at our institution. The objective of this review is not to cover the entire gamut of all advances that we have and use at our institution but, rather, to highlight a few pertinent concepts in our field. Topics that will be covered include biomarkers, molecular testing of selected malignancies (eg, transcription factor E3 [TFE3]/ Xp11.2 translocation-associated renal cell carcinoma; p63, high-molecular-weight cytokeratin and racemase cocktail [PIN4]/phosphatase and tensin homolog [PTEN] for some cases of intraductal carcinoma of the prostate; and succinate dehydrogenase subunit B in renal cell carcinoma and pheochromocytoma), amyloidosis of the genitourinary tract, and workup of neoplastic needle core kidney biopsies. In addition, we will report the effect of pathologic, oncologic, and radiologic technologic advances (ie, global transcriptome analysis and RNA biomarkers of prostate cancer; robotic-assisted radical prostatectomy; minimally invasive videoscopic inguinal lymphadenectomy; targeted magnetic resonance imaging [MRI]-guided prostate needle core biopsies; anti-1-amino-3-fluorine 18-fluorocyclobutane-1-carboxylic acid in prostate cancer; cryotherapy for prostate cancer; and blue-light/white-light cystoscopy for bladder lesions) performed at our institution.

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Succinate Dehydrogenase (SDH)-deficient Renal Carcinoma

Abstract: Supplemental Digital Content is available in the text.

Cited by 270 publications

References 42 publications

Classification of gastrointestinal stromal tumor syndromes

Classification of gastrointestinal stromal tumor syndromes

DIAGNOSIS of ENDOCRINE DISEASE: SDHx mutations: beyond pheochromocytomas and paragangliomas

Biomarker, Molecular, and Technologic Advances in Urologic Pathology, Oncology, and Imaging

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