History
Patients may present with symptoms of congestive heart failure, transient ischemic attack, or stroke.
Manifestations of Carney complex can also include Cushing syndrome (symptoms of which may develop in young patients) and skin changes associated with pigmentation, with spotty cutaneous pigmentation being a major clue to the diagnosis of Carney complex. [29] The presence of subtle buccal and perioral lentigines may also be an important clue. [30] Other symptoms include the following:
-
The skin is fragile and thin
-
Patients bruise easily and heal poorly
-
The bones are weakened, and routine activities such as bending, lifting, or rising from a chair may lead to backaches and rib and spinal column fractures
-
Severe fatigue, muscle weakness, high blood pressure, and high blood sugar levels may be present
-
Irritability, anxiety, and depression are common
-
Women may have menstrual periods that become irregular or stop
-
Men have decreased fertility, with a diminished or absent desire for sex
Associated prolactin-secreting tumors, acromegaly, and hyperparathyroidism can produce the following symptoms:
-
Prolactin-secreting tumor: Hypogonadism (eg, amenorrhea, impotence) associated with symptoms of increased prolactin levels (eg, galactorrhea) in female patients
-
Acromegaly: Headaches and visual abnormalities
-
Hyperparathyroidism: Fatigue, anemia, muscle weakness, joint pain, constipation with nausea, frequent urination (sometimes bloody), mood change with confusion, abdominal pain due to ulcers, flank or back pain due to stones, bone pain due to bone erosions or fractures, and hypertension
Cardiac myxomas may create ball-valve obstructions that cause unexpected syncopal attacks, cardiac insufficiency, and sudden death in apparently healthy young children and adults.
Right-sided myxomas with extramedullary hematopoiesis and ossification in Carney complex have been described in a patient who also had a tiny eyelid cutaneous myxoma, multiple hypoechoic thyroid follicular adenomas, and multiple small testicular tumors. [31]
Family history in patients with Carney complex may include cardiac myxomas and/or spotty pigmentation.
Physical Examination
Cutaneous
Cutaneous findings in Carney complex can include the following:
-
Pigmentation, including blue nevi of face, lips, sclera, trunk, or genital mucosa
-
Cutaneous myxomas
-
Generalized hyperpigmentation, obesity, striae, or cushingoid appearance
Masses
The following types of growths may be found:
-
Cutaneous
-
Thyroid
-
Breast
-
Testis mass/enlargement (secondary to myxoma)
Neurologic
Patients may exhibit neurologic deficits secondary to tumor emboli.
Cardiac
Cardiologic findings can include the following:
-
Accentuated first heart sound and opening snap
-
Diastolic apical rumbling murmur (mimicking mitral stenosis)
-
Holosystolic murmur best heard at apex and radiating to axilla (mitral regurgitation)
-
Diastolic tumor "plop"
Systemic
Systemic findings can include the following:
-
Fever
-
Clinical signs of anemia
-
Weight loss
-
Arthralgia
Atrial and ventricular myxomas
Upon physical examination, an accentuated first heart sound can be appreciated in patients with cardiac myxomas.
In adults, myxomas are the most common primary tumor of the heart. They arise in any of the 4 chambers or on the heart valves; however, about 90% are located in the atria. Myxomas in the atria have a left-to-right ratio of approximately 4:1.
Myxomas are mostly single and rarely multiple in several chambers. The tumors may be 1-10 cm or larger in diameter and can be pedunculated or sessile. Pedunculated atrial myxomas are often sufficiently mobile to move into or sometimes through the atrioventricular valves during diastole. Sometimes, such mobility exerts a wrecking-ball effect on the valve leaflets.
Multiple nevi, diffuse facial lentigines, and mucosal labial pigmentation
The classic presentation of Carney complex is a spotty pigmentation on the face, chest, and shoulders and on the vermilion border of the lips and conjunctiva. The pigmentation can be tan or dark brown to black.
The lesions can be irregularly shaped or sharply delineated, and they can be small or several millimeters in diameter.
Subcutaneous myxoid neurofibromas and mammary myxoid fibroadenomas
Cutaneous myxomas have a predilection for the eyelids and external ear canals, although they may affect any part of the skin.
The mammary myxoid fibroadenomas in the complex are often multiple and bilateral. These fibroadenomas are an unusual finding in an otherwise normal breast.
Acromegaly
Signs of acromegaly can include the following:
-
Macroglossia
-
Prominent jaw and frontal bossing
-
Large, spadelike hands.
-
Skin tags
-
Hyperhidrosis
Cushing syndrome
Signs of Cushing syndrome can include the following:
-
Thin, fragile skin
-
Easy bruising and poor healing
-
Purplish pink stretch marks on the abdomen, thighs, buttocks, arms, and breasts
-
Upper-body obesity, a rounded face, increased fat around the neck, and thin arms and legs
-
Tendency toward obesity, with slowed growth rates, in children
-
Usually, excessive hair growth in women on the face, neck, chest, abdomen, and thighs
Endocrine involvement
Endocrine involvement in Carney complex includes the following types of testicular tumors:
-
Large-cell calcifying Sertoli-cell tumor (one of the rarest testicular neoplasms)
-
Adrenal rest tumors
-
Leydig-cell tumor
These tumors appear with testicular masses; about one third of affected male patients have them.
Large-cell calcifying Sertoli-cell tumors may also appear as bilateral masses, but in this setting when not associated with other Carney complex findings, may reflect isolated disease unrelated to Carney complex. [32] They can also secrete estrogens, resulting in precocious puberty, gynecomastia, or both.
As many as 75% of patients with Carney complex may have multiple thyroid nodules. The nodules can appear as a goiter or thyroid mass when palpated on physical examination. Patients can also present with symptoms of hyperthyroidism or hypothyroidism.
Psammomatous melanotic schwannomas most frequently occur in the gastrointestinal tract (esophagus and stomach) and paraspinal sympathetic chain. Masses can be palpated on abdominal or paraspinal examination.
-
Transthoracic echocardiogram of a left atrial myxoma in an individual with Carney complex. A 42-year-old woman with a history of spotty pigmentation on the face and cutaneous myxomas presented for annual surveillance echocardiography. Findings from previous echocardiograms were normal. Echocardiography now revealed a 1.0 X 1.3-cm mass (arrow) in the left atrium (LA) arising from the interatrial septum above the mitral valve. No prolapse was seen into the left ventricle (LV). Histopathology upon surgical excision demonstrated that the lesion was a myxoma.
-
A pedunculated, flesh-colored cutaneous myxoma that is 1.5 cm in diameter on trunk. Courtesy of Dermatology, NYU, and Ann Stoecker, medical photographer.
-
Polypoid neoplasm of fibrillary collagen and uniform stellate cells within abundant connective tissue mucin. Note telangiectasia and ramification of tumor as strands through a myxoid dermis (hematoxylin-eosin). Courtesy of Dermatology, NYU School of Medicine; photography by Anca Croitoru, MD, and Scott Sanders, MD.
