The Triad of Gastric Leiomyosarcoma, Functioning Extra-Adrenal Paraganglioma and Pulmonary Chondroma

Carney, J. Aidan; Sheps, Sheldon G.; Go, Vay Liang W.; Gordon, Hymie

doi:10.1056/nejm197706302962609

Cited by 388 publications

(206 citation statements)

References 1 publication

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“…Carney triad was first described in 1977, as a triad of gastric leiomyosarcomas (now understood to be GISTs), paragangliomas and pulmonary chondromas (Carney et al 1977). Carney triad has also been reported to be associated with esophageal leiomyoma and adrenal cortical adenoma; the overall course in affected individuals tends to be indolent (Carney 1999).…”

Section: Carney Triadmentioning

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: Carney Triadmentioning

confidence: 99%

Classification of gastrointestinal stromal tumor syndromes

Gopie

Faber

et al. 2018

Endocrine-Related Cancer

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“…1,2 CTr is a nonhereditary, sporadic condition, primarily seen in young women. 3 Most CTr patients present with GIST and pulmonary CHO; PGL/ PHEO is rarely the presenting tumor but most often found at screening, in addition to other lesions, such as adrenocortical tumors.…”

Section: Introductionmentioning

confidence: 99%

Carney triad can be (rarely) associated with germline succinate dehydrogenase defects

et al. 2015

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Carney triad, the association of paragangliomas/pheochromocytomas, gastrointestinal stromal tumors and pulmonary chondromas, is a sporadic condition that is significantly more frequent in females; its genetic etiology remains unknown. Carney triad is distinct from the dyad of paragangliomas/pheochromocytomas and gastrointestinal stromal tumors, known as Carney-Stratakis syndrome, which is inherited in an autosomal-dominant manner and is almost always caused by succinate dehydrogenase subunit mutations. In the present study, we investigated the largest cohort of Carney triad patients that is available internationally: 63 unrelated patients. Six patients (9.5%) were found to have germline variants in the SDHA, SDHB or SDHC genes. All six patients, except one, had multifocal gastrointestinal stromal tumors, chondromas and/or paragangliomas. A patient with Carney triad and SDHC variant had a ganglioneuroma. One of the patients with Carney triad and SDHB mutation had a nephew with the same sequence defect, who developed a neuroblastoma. Other relatives, carriers of the identified SDHA, SDHB or SDHC mutations, have not developed any of the components of Carney triad or Carney-Stratakis syndrome. None of the other 57 Carney triad patients had any genomic defects of SDHA, SDHB or SDHC genes. We conclude that, in rare occasions, Carney triad can be allelic to Carney-Stratakis syndrome. Although for the vast majority of patients with Carney triad the causative defect(s) remain(s) unknown, testing for SDHA, SDHB or SDHC variations should be offered, as carriers may develop isolated paragangliomas/pheochromocytomas and occasionally other tumors.

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“…25,27 The Carney triad is a non-familial condition characterized by GISTs, PGLs and pulmonary chondroma. 30,39 So far, no somatic or germline KIT/PDGFRA mutations, SDHB, SDHC and SDHD mutations, have been described in this triad. 31,32 None of our patients presenting GISTs with loss of SDHB or SDHB/SDHA expression revealed clinical-imaging evidence of other tumors (eg, pulmonary chondromas and/or PGLs).…”

Section: Discussionmentioning

confidence: 99%

Molecular alterations and expression of succinate dehydrogenase complex in wild-type KIT/PDGFRA/BRAF gastrointestinal stromal tumors

et al. 2012

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Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, disclosing somatic KIT, PDGFRA and BRAF mutations. Loss of function of succinate dehydrogenase (SDH) complex is an alternative molecular mechanism in GISTs, namely in carriers of germline mutations of the SDH complex that develop Carney-Stratakis dyad characterized by multifocal GISTs and multicentric paragangliomas (PGLs). We studied a series of 25 apparently sporadic primary wild-type (WT) KIT/PDGFRA/BRAF GISTs occurring in patients without personal or familial history of PGLs, re-evaluated clinicopathological features and analyzed molecular alterations and immunohistochemistry expression of SDH complex. As control, we used a series of well characterized 49 KIT/PDGFRA/BRAF-mutated GISTs. SDHB expression was absent in 20% and SDHB germline mutations were detected in 12% of WT GISTs. Germline SDHB mutations were significantly associated to younger age at diagnosis. A significant reduction in SDHB expression in WT GISTs was found when compared with KIT/ PDGFRA/BRAF-mutated GISTs. No significant differences were found when comparing DOG-1 and c-KIT expression in WT, SDHB-mutated and KIT/PDGFRA/BRAF-mutated GISTs. Our results confirm the occurrence of germline SDH genes mutations in isolated, apparently sporadic WT GISTs. WT KIT/PDGFRA/BRAF GISTs without SDHB or SDHA/SDHB expression may correspond to Carney-Stratakis dyad or Carney triad. Most importantly, the possibility of PGLs (Carney-Stratakis dyad) and/or pulmonary chondroma (Carney triad) should be addressed in these patients and their kindred.

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The Triad of Gastric Leiomyosarcoma, Functioning Extra-Adrenal Paraganglioma and Pulmonary Chondroma

Cited by 388 publications

References 1 publication

Classification of gastrointestinal stromal tumor syndromes

Classification of gastrointestinal stromal tumor syndromes

Carney triad can be (rarely) associated with germline succinate dehydrogenase defects

Molecular alterations and expression of succinate dehydrogenase complex in wild-type KIT/PDGFRA/BRAF gastrointestinal stromal tumors

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