Page 244 - The Netter Collection of Medical Illustrations - Integumentary System_ Volume 4 ( PDFDrive )

Plate 9-4 Integumentary System
CARNEY COMPLEX

Carney complex, also known as NAME syndrome
(nevi, atrial myxomas, myxoid neurofibromas, epheli-
des) or LAMB syndrome (lentigines, atrial myxomas,
mucocutaneous myxomas, blue nevi), is an autosomal
dominantly inherited disorder that affects the integu-
mentary, endocrine, cardiovascular, and central nervous
systems. This rare disorder is primarily caused by a
genetic mutation in the tumor suppressor gene,
PRKAR1A. Approximately 20% of patients have defects
in an undescribed gene located at 2p16. Various geno-
types and phenotypes exist, and the diagnosis is based
on a complex list of major, supplemental, and minor Mucocutaneous manifestations
criteria. of Carney complex characterized
Clinical Findings: The phenotypic expression of the
disease is variable, and research has shown the pheno- by pigmented lentigines,
blue nevi, myxomas, common
type to be related to the underlying genotype of the acquired nevi, and subcutaneous
disease. Cutaneous findings are often the first signs of myxomas
the disease, and they are typically noticed in the first
few months of life. Five prominent skin effects can be Additional features of
seen in isolation or, more commonly, in conjunction Carney complex can include:
with one another. Multiple lentigines and common
acquired nevi are the two most frequent skin findings. Myxomas: cardiac atrium,
Multiple blue nevi are also seen. The blue nevi, lentigi- mucocutaneous myxoma
nes, and nevi tend to group together on the head and
neck region, lips, and sclerae. Mucocutaneous myxomas Testicular large-cell
may be found at any location and appear as flesh- calcifying Sertoli cell tumors
colored to slightly translucent, pedunculated papules
that are soft and easily compressed. They vary widely Growth hormone–
in number, from a few to hundreds. Subcutaneous secreting pituitary adenomas
myxomas are often found on the margin of the tarsal
plate and can have a slightly pink-red to somewhat Psammomatous melanotic
translucent appearance. They are not as soft to the schwannomas (found along
touch as the mucocutaneous myxomas. Ephelides are the sympathetic nerve chain)
also found in abundance, primarily in the head and neck
region.
Cardiac myxomas are the leading cause of morbidity
and mortality, and each patient diagnosed with Carney
complex needs routine echocardiography and follow-
up with cardiology. Male patients should be screened
for testicular tumors with physical and ultrasound
evaluations. Pituitary adenomas may lead to a growth
hormone–producing adenoma and subsequent evidence
of acromegaly. Cushing’s syndrome may result from
excessive cortisol production by the adrenal glands.
This is a multisystem disorder with great variation in
potential organ system involvement. Carney complex is
best treated and monitored with a multidisciplinary
approach.
Pathogenesis: The PRKAR1A gene encodes a regula-
tory subunit of a protein kinase A. Protein kinase A
belongs to a family of regulatory proteins that are
dependent on cyclic adenosine monophosphate (cAMP)
for proper functioning. Many different mutations in Primary pigmented nodular adrenocortical disease (PPNAD).
PRKAR1A have been discovered, including missense, Adrenal glands are usually of normal size and most are studded
frame-shift, and nonsense mutations, all leading to with black, brown, or red nodules. Most of the pigmented nodules
defects in the encoded protein. Because of the many are less than 4 mm in diameter and interspersed in the adjacent
unique mutations in this gene, researchers have been atrophic cortex.
able to show that the type of genetic mutation corre-
lates with the phenotype of the disease. As an example,
mutations in the exon portions of the gene (compared gland characteristically show varying amounts of nodu- Treatment: Therapy for skin myxomas includes
with the intron portions) are much more likely to clini- lar pigmented regions; this has been termed primary observation or excision of individual lesions. Lentigines
cally express lentigines and cardiac myxomas. pigmented nodular adrenocortical disease (PPNAD). and blue nevi can be removed for cosmetic purposes.
Histology: Skin biopsies by themselves are not diag- Adrenal disease may lead to increased production of Atrial myxomas are the leading cause of morbidity
nostic, and the lentigines, myxomas, and blue nevi cortisol and ultimately to the signs and symptoms of and mortality, and they require removal by cardio-
found in patients with this syndrome are not different Cushing’s syndrome. A unique tumor, almost always thoracic surgery. Patients need to be monitored by
histologically than those found outside the Carney seen in conjunction with Carney complex, is the psam- cardiology and endocrinology specialists for their
complex. Testicular tumors usually show a Leydig cell momatous melanotic schwannoma. These are not cuta- entire lifetime. Routine screening evaluations of the
or Sertoli cell tumor with various amounts of calcifica- neous tumors but are most likely to be found along the heart, pituitary, adrenal gland, and testicles must be
tion. Histological findings on biopsy of the adrenal paraspinal sympathetic chain. performed.

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