Carney triad explained

Carney triad (CT) is characterized by the coexistence of three types of neoplasms, mainly in young women,^[1] including gastric gastrointestinal stromal tumor, pulmonary chondroma, and extra-adrenal paraganglioma.^[2] The underlying genetic defect remains elusive. CT is distinct from Carney complex and Carney-Stratakis syndrome.

Background

Carney triad (CT), named for J Aidan Carney, is considered to be a specific type of multiple endocrine neoplasia (MEN). The three classically associated tumors are a subset of gastric epithelioid leiomyosarcoma (it is now known that this subset is actually gastrointestinal stromal tumor arising from the interstitial cells of Cajal), pulmonary chondroma, and extra-adrenal paraganglioma.

The condition manifests more commonly in females. Multiple tumors in multiple organs in young patients, with occasional sibling involvement, suggested an inherited disorder, but the underlying genetic basis has not been identified.

In addition to these three classical tumors, there is an increased incidence of pheochromocytoma, esophageal leiomyoma and adrenocortical adenoma.^[3]

The original description employed the then-prevailing terminology of gastric epithelioid leiomyosarcoma. Subsequent advances in molecular biology have led to the current terminology of gastrointestinal stromal tumors (GISTs).^[4] However, there is limited evidence to suggest that the gastrointestinal stromal tumors (GIST) in Carney triad lack CD117 (c-kit) mutations (i.e., they are wild-type), and hence these GISTs may prove unresponsive to Imatinib.^[5]

Taxonomy

Carney triad is distinct from two other multiple neoplasia syndromes, also described by J. Aidan Carney.

Carney complex

The Carney complex is a distinct entity,^[6] characterized by myxomatous neoplasms (cardiac, endocrine, cutaneous and neural), and a host of pigmented lesions of the skin and mucosae, including the rarely occurring epitheloid blue nevus.^{[7] [8]}

Carney–Stratakis syndrome

A third condition, the Carney–Stratakis syndrome (CSS), describes the dyad of hereditary gastrointestinal stromal tumor (GIST) and paraganglioma, that is caused by germline mutations in the mitochondrial tumor suppressor gene pathway involving the succinate dehydrogenase subunits SDHD, SDHC and SDHB.

Notes and References

1. OMIM - Online Mendelian Inheritance in Man. Carney Triad (OMIM 604287) https://web.archive.org/web/20150924060442/http://www.omim.org/entry/604287
2. Carney JA. "The triad of gastric epithelioid leiomyosarcoma, pulmonary chondroma, and functioning extra-adrenal paraganglioma: a five-year review." Medicine (Baltimore). 1983;62(3): 159-169.
3. Stratakis CA, Carney JA. The triad of paragangliomas, gastric stromal tumours and pulmonary chondromas (Carney triad), and the dyad of paragangliomas and gastric stromal sarcomas (Carney-Stratakis syndrome): molecular genetics and clinical implications. J Intern Med. 2009;266(1):43.
4. Boccon-Gibod L, Boman F, Boudjemaa S, Fabre M, Leverger G, Carney AJ. "Separate occurrence of extra-adrenal paraganglioma and gastrointestinal stromal tumor in monozygotic twins: probable familial Carney syndrome." Pediatr Dev Pathol. 2004;7(4):380-4.
5. Diment J, Tamborini E, Casali P, Gronchi A, Carney JA, Colecchia M. "Carney triad: case report and molecular analysis of gastric tumor." Hum Pathol. 2005;36(1):112-6.
6. Gaissmaier et al. (letter and response) Carney Complex. Circulation 1999;100 (25); e150 http://circ.ahajournals.org/cgi/reprint/100/25/e150
7. Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine (Baltimore). 1985;64(4):270-83.
8. Iglesias C, Torrelo A, Colmenero I, Mediero IG, Zambrano A, Requenca L. Isolated multiple congential epithelioid blue naevus. British Journal of Dermatology 2005;152:391-393.