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Carney Syndrome: Differential Diagnoses & Workup

Author: Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Coauthor(s): Santiago A Centurion, MD, Staff Physician, Department of Dermatology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey; Manuel A Cruz, MA, Adjunct Assistant Professor, Department of Pathology, UMDNJ-New Jersey Medical School; Walter HC Burgdorf, MD, Clinical Lecturer, Department of Dermatology, Ludwig Maximilian University, Munich, Germany
Contributor Information and Disclosures

Updated: Oct 7, 2009

Differential Diagnoses

Ephelides (Freckles)
Lentigo
Nevi, Melanocytic

Other Problems to Be Considered

Adrenal adenoma
Adrenal carcinoma
Rhabdomyomas
Intracardiac thrombus
Metastatic neoplasm to the heart
Breast adenoma
Breast carcinoma
Testicular adenoma
Testicular carcinoma

Workup

Laboratory Studies

  • A 24-hour urinary cortisol excretion test and a dexamethasone stimulation test should be performed to evaluate for primary pigmented nodular adrenocortical disease (PPNAD) as part of Carney complex (CNC).
  • Plasma somatomedin C levels should be measured to evaluate possible growth hormone excess.
  • Thyrotropin hormone levels should be obtained.
  • Corticotropin hormone levels should be determined.

Imaging Studies

  • Echocardiography should be performed to evaluate cardiac myxomas.
  • Transesophageal echocardiography may be helpful.
  • Testicular sonography can be used to assess large-cell calcifying Sertoli-cell tumor of the testes.
  • Computed tomography or MRI may depict extrathoracic tumors.

Other Tests

  • ECGs may reflect the presence of left atrial enlargement or pulmonary hypertension.
  • Mutational analysis of the PRKAR1A gene may be a useful adjunctive diagnostic test, but such DNA-based testing currently remains the province of research laboratories.

Histologic Findings

Myxomas

In general, myxomas are globular, hard, and mottled lesions with hemorrhage. Histologically, they are composed of stellate or globular myxoma cells, endothelial cells, macrophages, mature or immature smooth muscle cells, and a variety of intermediate forms embedded in an abundant acid mucopolysaccharide ground substance.

Freckles
Freckles are small (1- to 10-mm), tan-red or light brown macules that first appear in early childhood after sun exposure. Once present, they fade and reappear in a cyclic fashion with winter and summer. The observed hyperpigmentation of the freckle is the result of increased amounts of melanin pigment in the basal keratinocytes. Melanocytes are relatively normal in number, although they may be slightly enlarged.

Lentigo
The term lentigo refers to a common benign hyperplasia of the melanocytes. Lentigo can occur in individuals of all ages, but often occurs in infants and children. Unlike freckles, lentigines do not darken when exposed to sunlight. The essential histologic feature of the lentigo is melanocytic hyperplasia that produces a hyperpigmented basal cell layer in the epidermis in a linear fashion. Elongation and thinning of the rete ridges are also common in a lentigo.

Blue nevi
Blue nevi are characterized by highly dendritic nevus cells (as opposed to the rounded cell typical of most melanocytic nevi) that are heavily pigmented. When these cells are in the middle-to-deep dermis, they are blue to gray-blue at clinical examination. Carney described an additional histopathologic variant of the blue nevus that is called an epithelioid blue nevus. It is a heavily pigmented dermal lesion composed of 2 types of melanocytes: One type is intensely pigmented, globular, and fusiform, whereas the other type is lightly pigmented and polygonal with large amounts of cytoplasm. Most patients with an epithelioid blue nevus have Carney complex. However, cases of epithelioid blue nevi are also reported in children and adults with no evidence of Carney complex.

Schwannomas
Schwannomas are typically solitary, circumscribed, and encapsulated tumors that are eccentrically located on the proximal nerves or spinal nerve roots. Microscopically, the tumors have regions of high and low cellularity called Antoni A and Antoni B areas, respectively. In the Antoni A tissue, foci of palisaded nuclei called Verocay bodies may be present, and the blood vessels in schwannomas often have hyaline thickening around them, indicating that pseudopalisading of the tumor nuclei may be present. Psammomatous melanotic schwannoma is a particular schwannoma in Carney syndrome that is distinctive because of its heavy melanotic pigmentation and calcification. Multicentricity also frequently occurs in this tumor.

Sertoli-cell tumors
Sertoli-cell tumors may be composed of entirely Sertoli cells, or they may have a component of granulosa cells. These neoplasms may appear as firm, small nodules or, rarely, as bulky masses that cause considerable testicular enlargement. On cross sections, the surface is homogeneously gray-white to yellow. On histologic examination, the cells in the classic form are distinctive and tall, columnar, or polyhedral, with abundant and usually vacuolated cytoplasm. The tendency for these cells to grow in cords that are highly reminiscent of spermatic tubules is distinctive.

Primary pigmented nodular adrenocortical tumors
Primary pigmented nodular adrenocortical disease (PPNAD) tumors are characterized by lipofuscin-containing, autonomously functioning, cortisol-producing nodules surrounded by mostly atrophic adrenocortical and normal adrenomedullary tissue. The nature and origin of the tumors are unclear. On gross examination, the surfaces show multiple small nodules, usually with a black-to-brown discoloration. In addition, the extranodular cortex is atrophic. On histologic examination, multiple nodules are observed deep in the cortex. The cells in these nodules stain positively with periodic acid-Schiff. Outside the cortex, intense disorganization is present without normal zonation.

Polypoid neoplasm of fibrillary collagen and unif...

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.

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Polypoid neoplasm of fibrillary collagen and unif...

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.


More on Carney Syndrome

Overview: Carney Syndrome
Differential Diagnoses & Workup: Carney Syndrome
Treatment & Medication: Carney Syndrome
Follow-up: Carney Syndrome
Multimedia: Carney Syndrome
References
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Further Reading

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Keywords

Carney CNC, Carney complex, Carney's complex, Carney's syndrome, CNC type I, CNC type II, Carney myxoma-endocrine complex, lentigines, blue nevi syndrome, LAMB syndrome, nevi, atrial myxoma, myxoid neurofibromata, ephelides, NAME syndrome, complex of myxomas, spotty pigmentation, endocrine overactivity, multiple neoplasia and lentiginosis syndrome, primary pigmented nodular adrenocortical disease, PPNAD, hypercortisolism, nonendocrine tumors, endocrine tumors,

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Contributor Information and Disclosures

Author

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

Coauthor(s)

Santiago A Centurion, MD, Staff Physician, Department of Dermatology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey
Santiago A Centurion, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, and Sigma Xi
Disclosure: Nothing to disclose.

Manuel A Cruz, MA, Adjunct Assistant Professor, Department of Pathology, UMDNJ-New Jersey Medical School
Manuel A Cruz, MA is a member of the following medical societies: Sigma Xi
Disclosure: Nothing to disclose.

Walter HC Burgdorf, MD, Clinical Lecturer, Department of Dermatology, Ludwig Maximilian University, Munich, Germany
Walter HC Burgdorf, MD is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, American Society of Dermatopathology, International Society of Dermatopathology, and Society for Pediatric Dermatology
Disclosure: Nothing to disclose.

Medical Editor

R Stan Taylor, MD, Professor of Dermatology, University of Texas Southwestern Medical School; Director of Skin Surgery and Oncology Clinic, Department of Dermatology, University of Texas Southwestern Medical Center
R Stan Taylor, MD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Surgery, American Dermatological Association, American Medical Association, American Society for Dermatologic Surgery, Christian Medical & Dental Society, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Christen M Mowad, MD, Associate Professor, Department of Dermatology, Geisinger Medical Center
Christen M Mowad, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and Phi Beta Kappa
Disclosure: Nothing to disclose.

CME Editor

Glen H Crawford, MD, Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital
Glen H Crawford, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Phi Beta Kappa, and Society of USAF Flight Surgeons
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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