Carney complex

Carney complex (not to be confused with the Carney triad) is a rare multiple endocrine neoplasia syndrome.

Epidemiology

Collectively there have been >750 cases of Carney complex reported worldwide (c. 2022), however, the exact prevalence is unknown ^6,7,10. The median age of diagnosis has been reported at 20 years old ^9,10. There appears to be no sex predilection ¹⁰.

Clinical presentation

Clinical presentation is highly variable, even among family members with Carney complex, and includes ^8,10:

• skin lesions

• acromegaly: from growth-hormone secreting pituitary adenomas

• Cushing syndrome: most common endocrine presentation; related to primary pigmented nodular adrenocortical disease (PPNAD)

• pain/radiculopathy: related to schwannomas

• hyperthyroidism

Pathology

Carney complex is characterized by:

• skin lesions (>80%) ¹⁰

  • lentigines, blue nevi, cutaneous myxoma

  • especially of the face, trunk, lips, and sclera ^1-4

• cardiac myxoma (~45%; range 20-67%): often multiple ^1-4,10

Multiple other features are also well recognized including:

• pituitary adenoma (up to 80%): excess growth hormone, IGF-1, prolactin ¹⁰

• testicular tumors (up to 75%): large cell-calcifying Sertoli cell tumors ^8,10

• ovarian masses (common): ovarian cyst, cystadenoma, cystic teratoma ¹⁰

• primary pigmented nodular adrenocortical disease (~40%) ^8-10

• breast masses: myxoid fibroadenomas, ductal adenomas ^8,10

• thyroid disease

  • papillary and follicular thyroid cancers in ~10% ^8-10

  • multinodular goiter ⁹

• malignant melanotic nerve sheath tumor (up to 10%) ⁸

• osteochondromyxoma (~1%) ^8,10

Genetics

Carney complex can be familial (70%) or as a sporadic de novo mutation (30%) ^8-10. When familial, Carney complex has autosomal dominant inheritance with ~85% (range 70-100%) penetrance ^5,6,8. Carney complex is related to inactivating mutations or large deletions of the PRKAR1A tumor suppressor gene on chromosome 17q22-24 ^5,6 or chromosome 2p16 ⁸. 

Treatment and prognosis

The most common cause of death in Carney complex patients are complications related to cardiac myxomas (e.g. arrythmia, emboli) ^9,10. Patients are at increased risk of various cancers (e.g. adrenocortical carcinoma, thyroid, colorectal, liver, pancreatic) although with surveillance, life expectancy can be expected to be normal ¹⁰.

History and etymology

Carney complex is named for J. Aidan Carney, who first described a "complex of myxomas, spotty pigmentation, and endocrine overactivity" in 1985 ^9,10.