Carney syndrome

CARNEY SYNDROME (CARNEY TRIAD):

Carney syndrome (Carney Triad) was originally proposed to describe cases involving the coexistence of several neoplasms, including: gastric epithelioid leiomyosarcoma, pulmonary chondroma, and extra-adrenal paraganglioma.(1)

Recent advances in molecular biology have demonstrated that the so-called gastric epithelioid leiomyosarcomas, in fact, represent gastrointestinal stromal tumours (GISTs).(2) This distinction is important amongst physicians. Pathologists, in addition to examining the conventional morphology of the tumour using a microscope, will use a special diagnostic technique called immunohistochemistry to detect the expression of the molecule CD117 (c-kit) to confirm the diagnosis. Clinicians, in turn, typically treat these tumours with a drug that specifically targets mutations in c-kit, called Gleevec; however, there is limited evidence to suggest that GISTs in Carney Syndrome lack c-kit mutations (i.e., they are wild-type), hence may prove unresponsive to this medication.(3)

Occasionally Carney syndrome is erroneously used by physicians to describe Carney Complex, or vice versa;(4,5,6) however, these terms represent two entirely distinct entities. Carney Complex, simply stated, describes a multiple neoplasia syndrome that is generally 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 naevus.(7,8)

Differential Diagnosis

Carney syndrome must be differentiated from other diseases causing multiple polyps, such as:

Diseases	History and Symptoms			Physical Examination			Laboratory Findings			Other Findings
	Abdominal Pain	Rectal Bleeding	Fatigue	Abdominal Tenderness	Hyperpigmentation	Anemia	Gene(s)	Gastrointestinal Tumors	Cancers
Carney Syndrome	–	–	–	–	Facial+ Mucosal+	–	PRKAR1A		Thyroid Sertoli Cell	Myxoma of skin Myxoma of heart
Familial Adenomatous Polyposis	+	+	+	+/–	–	+	APC gene MUTYH gene	Adenoma+++	Colon Brain Thyroid	Desmoid tumor Osteoma
Peutz–Jeghers syndrome	+	+	+	+	+	+	STK11 (LBK1) gene	Adenoma+ Hamartoma+++	Breast Lung Pancreas Ovaries Sertoli cells Uterine
Juvenile Polyposis Syndrome	+		+	–	–	–	SMAD4 BMPR1A	Adenoma+  Hamartoma+++	Colon
Cowden Syndrome	–	–	–	–	Axillary+ Inguinal+ Facial+	–	PTEN	Adenoma+  Hamartoma+++	Breast Thyroid Endometrium	Trichilemmoma Skin hamartoma Hyperplastic polyp Macrocephaly Breast fibrosis
Hereditary Non–Polyposis Colon Cancer	–	+	+	+/–	–	+	MLH1 MSH2 MSH3 MSH6 PMS1 PMS2	Adenoma+	Endometrium Stomach Kidneys Ureter Ovaries	Sebaceous adenoma

REFERENCES

1. 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.

2. 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.

3. 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.

4. http://www.emedicine.com/derm/topic805.htm

5. Rosai J. Surgical Pathology, 9th Ed. Mosby: China. 2004; p.117.

6. Nwokoro NA, Korytkowski MT, Rose S, Gorin MB, Penles Stadler M, Witchel SF, Mulvihill JJ. Spectrum of malignancy and premalignancy in Carney syndrome. Am J Med Genet. 1997;73(4):369-77.

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.

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