Tumors Associated with Carney Complex, Carney Triad and Carney

Tumors Associated with Carney Complex, Carney Triad and Carney

Tumors Associated with Carney
Complex, Carney Triad and
Carney-Stratakis Syndrome
Ricardo V. Lloyd MD, PhD
Adrenal Primary Pigmented
Nodular Adrenocortical Disease
Adrenal PPNAD – Cortical
Nodules
Brown-black nodules 0.1 to 0.5 cm in
cortex
Nodules usually at cortico-medullary
junction
Large eosinophilic cells with lipofuscin
Myelolipomatous change
Carney Complex Pituitary Adenoma
Pituitary Lesions
• GH Pituitary adenomas
• PRL or mixed GH/PRL adenomas
• GH Pituitary hyperplasia
Carney Complex Cardiac Myxoma
Carney Complex - Lentigenes
Carney Complex
Blue nevi
(epithelioid)
Pigmented
schwannoma
Myxomas
Sertoli cell
tumor
Carney et al -NEJM 296:1517,1977
• Gastric (epithelioid) leiomyosarcoma
• Funtioning extra-adrenal paraganglioma
• Pulmonary chondroma
Carney Triad
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All unrelated young female patients
Two patients had all three tumors
Five other patients with2 of 3 tumors
One patient also with a non-funtioning
adrenocortical adenoma
• Tumor pattern of multifocal lesions in multiple
organs in young patients—suggested an
inherited disorder.
Carney Triad
• Gastrointestinal stromal tumors
• Paragangliomas
• Pulmonary chondromas
Molecular Abnormalities
• Sporadic GISTs—14q, 22q, 1p
• Carney Triad GISTs—1p loss
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(14q, 22q loss uncommon)
Familial Paraganglioma and Gastric
Stromal Tumors(Carney-Stratakis)
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Twelve patients (7M/5F)
Average age 23
Autosomal dominant inheritance
7 Paragangliomas (4 Pg and GIST, 1 GIST)
Paragangliomas multicentric
GIST multifocal
Zhang et al Am J Surg Pathol 34: 53,2010
GISTs in Carney Triad
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Female predilection
Young patient age
Epithelioid cell predominance
Frequent lymph node metastasis
Serial tumor recurrence
Unpredictable behavior
Zhang et al Am J Surg Pathol 34:53,2010
Gill et al AM J Surg Pathol, 2010
• Subtypes of GISTs
Type I—Most GISTs—occurs mainly in adults
Spindle cell morphology
KIT- or PDGFRA-mutant tumors
Type 2—Mainly in children and young adults.
Epithelioid morphology
Not associated with KIT or PDGFRA
mutations-exclusively in stomach
Gill et al Am J Surg Pathol 34:636,2010
Gill et al Am J Surg Pathol 34:636, 2010
Gill et al Am J Surg Pathol 34:636, 2010
Gaal et al Modern Pathol 24:147,2011
Gaal et al Modern Pathol 24:147, 2011
Succinate dehydrogenase-deficient GISTs
are characterized by IGF1R overexpression
Angela Chou1, Jason Chen2, Adele Clarkson2, Jaswinder S Samra3,4,
Roderick J Clifton-Bligh4,5, Thomas J Hugh3,4 and Anthony J Gill2,4,6
Chou et al Modern Pathol 22, 2222, 2012
Summary
• Carney Complex represent a broad
constellation of disorders involving the
adrenal cortex, heart and many other organs
• Carney Triad (CT) includes GISTs,
Paragangliomas and Pulmonary Chondromas
• Carney –Stratakis Dyad (C-S D) includes GISTs
and Paragangliomas
• Some GISTs associated with CT and C-S D
involve mutations of mitochondrial SDH genes
References
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Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas,
spotty pigmentation, and endocrine overactivity. Medicine (Baltimore) 64: 270-83,
1985.
Carney JA, Stratakis CA. Familial paraganglioma and gastric stromal sarcoma: a
new syndrome distinct from the Carney triad. Am J Med Genet 108: 132-9, 2002.
Zhang L, Smyrk TC, Young WF Jr, Stratakis CA, Carney JA. Gastric stromal tumors in
Carney triad are different clinically, pathologically, and behaviorally from sporadic
gastric gastrointestinal stromal tumors: findings in 104 cases. Am J Surg Pathol 34:
53-64, 2010.
Gaal J, Stratakis CA, Carney JA, Ball ER, Korpershoek E, Lodish MB, Levy I, Xekouki
P, van Nederveen FH, den Bakker MA, O’Sullivan M, Dinjens WN, de Krijger RR.
SDHB immunohistochemistry: a useful tool in the diagnosis of Carney-Stratakis
and Carney triad gastrointestinal stromal tumors. Mod Pathol 24: 147-51, 2011.