Random Dermatology MCQ - Carney complex

A 25-year-old man presents with multiple, small, dark brown to black macules on his face, lips, and conjunctivae. He also has a history of recurrent cardiac myxomas requiring surgical resection and evidence of adrenal overactivity. A biopsy of a hyperpigmented macule on the lip would most likely reveal which of the following?

A. Melanocytic hyperplasia with elongation of the rete ridges.
B. Increased basal layer melanin without an increase in the number of melanocytes.
C. Nests of benign melanocytes at the dermo-epidermal junction.
D. Clonal proliferation of atypical melanocytes with pagetoid spread.
E. Deposits of hemosiderin within dermal macrophages.

Correct Answer: B. Increased basal layer melanin without an increase in the number of melanocytes.

Answer and Explanation

The correct answer is B. This question describes the classic features of Carney complex. The triad includes: 1) spotty skin pigmentation (lentigines, blue nevi), 2) cardiac myxomas, and 3) endocrine overactivity (e.g., Cushing's syndrome from primary pigmented nodular adrenocortical disease - PPNAD, acromegaly). The pigmented macules on the face, lips, and conjunctivae are lentigines. The histopathological hallmark of a lentigo, including those in Carney complex, is hyperpigmentation of the basal keratinocytes with a normal or only slightly increased number of melanocytes. This differentiates it from a melanocytic nevus (which has nests) or melanoma (which has atypia).

Why the Other Options are Incorrect:

• A. Melanocytic hyperplasia with elongation of the rete ridges: This describes a solar lentigo. While the clinical lesions in Carney complex are lentigines, they are not induced by sun exposure and do not typically show the marked elongation of rete ridges seen in solar lentigines. The key feature is the pigment, not the epidermal architecture.

• C. Nests of benign melanocytes...: This describes a melanocytic nevus (mole). Lentigines are characterized by increased melanin production, not a proliferation of melanocytes forming nests.

• D. Clonal proliferation of atypical melanocytes...: This describes melanoma in situ. The pigmented lesions in Carney complex are benign lentigines.

• E. Deposits of hemosiderin...: This describes post-inflammatory hyperpigmentation or a stain from hemorrhage, not the primary melanin-based pigmentation of a lentigo.

Additional High-Yield Information for Exams:

• Clinical Features (Major Diagnostic Criteria):

  • Spotty Mucocutaneous Pigmentation: Lentigines (face, lips, conjunctiva, genital mucosa), blue nevi (common, often multiple and epithelioid).

  • Cardiac Myxoma: Can be recurrent, multiple, and in any chamber. They are a major cause of morbidity/mortality (stroke, heart failure).

  • PPNAD: A unique cause of ACTH-independent Cushing's syndrome.

  • Other: Psammomatous melanotic schwannoma (a rare, pigmented nerve sheath tumor), acromegaly, testicular Sertoli cell tumors.

• Genetics: Approximately 70% of cases are due to inactivating mutations in the PRKAR1A gene, a tumor suppressor gene on chromosome 17q22-24. Inheritance is autosomal dominant.

• Differential Diagnosis: The combination of lentigines and cardiac tumors should immediately suggest Carney complex. Other lentiginosis syndromes (e.g., LEOPARD, Peutz-Jeghers) have different systemic associations.

• Prognosis: Prognosis depends on the complications, particularly from cardiac myxomas (embolic stroke, obstruction) and malignancies (e.g., from melanotic schwannoma, thyroid cancer). Lifelong surveillance is critical.

• Management & Rationale:

  • Rationale: Management is multidisciplinary, focusing on surveillance for and early intervention of the potentially life-threatening components of the syndrome.

  • Key Surveillance Protocols:

    • Cardiac: Annual echocardiogram (or more frequent if history of myxoma) to screen for recurrent or new cardiac myxomas.

    • Endocrine: Regular screening for Cushing's syndrome (urinary free cortisol, dexamethasone suppression test) and acromegaly (IGF-1).

    • Oncologic: Annual testicular ultrasound in men (for Sertoli cell tumors), thyroid ultrasound, and neurologic/imaging evaluation if symptoms suggest melanotic schwannoma.

  • Treatment: Surgical resection of myxomas and other tumors as indicated. Adrenalectomy for PPNAD.