Which histologic findings are characteristic of McCune-Albright syndrome (MAS)?

Updated: Jan 17, 2019
  • Author: Gabriel I Uwaifo, MD; Chief Editor: George T Griffing, MD  more...
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Answer

The café-au-lait spots seen in MAS are large, melanotic macules (café-au-lait macules [CALMs]). Except for hyperpigmentation of the basal layer, no abnormal pathology is apparent. The melanocytes are normal in both number and size. Some specimens show giant melanosomes, but this finding is by no means diagnostic. Giant melanosomes can also be found in CALMs of patients with neurofibromatosis (NF) and in healthy patients.

That MAS is a disease of excess abnormal and imperfect bone formation helps elucidate its mechanisms. [44] The bone affected by PFD has areas of fibrous metaplasia within flat and tubular bones. The basic anomaly in FD lesions is a progressively expanding fibrous lesion of bone-forming mesenchyme. The lesions typically expand concentrically from the medullary cavity outwards (ie, toward the cortex). The bony lesions are well defined, though invariably, they are not encapsulated.

The bony lesions are rich in spindle-shaped fibroblasts, with a swirled appearance within the marrow space and erratically arranged “tongues” of woven bone. Islands of cartilaginous tissue also may be interspersed within the lesions. Some parts of the affected bones may have cystic lesions lined by multinucleated giant cells, akin to osteitis fibrosa cystica (of severe hyperparathyroidism) but with a paucity of osteoblasts.

Thyroid findings in individuals with hyperthyroidism secondary to MAS can range from a single adenoma to a goiter. The histologic appearance has been reported to range from multinodular hyperplasia to colloid goiter. Single nodules have the appearance of follicular adenomas.

Cushing syndrome in MAS is associated with bilateral nonpigmented adrenocortical hyperplasia with nodular elements (see the image below). Multiple micronodules can be found in the adrenal cortex surrounded by normal tissue. Only the nodules contain DNA coding for the activating Gs alpha mutation; the surrounding normal tissue does not contain the activating mutation, a finding that supports the mosaic nature of this genetic disorder.

Somatotroph adenomas take on the character of typical pituitary adenomas. Somatotroph tumors lack true capsules, with the margins of the adenoma containing normal cells interspersed with adenomatous cells. These adenomatous cells can be confirmed as somatotrophs by means of immunostaining. Although technically not malignant, somatotroph adenomas may be locally invasive into the surrounding bony architecture and vasculature.

Liver histology in individuals with elevated hepatic enzymes can range from the presence of normal hepatocytes with some fatty infiltration to focal nodular hyperplasia with bridging fibrosis and chronic cholestasis. Detailed study of liver biopsy specimens has detected mild biliary abnormalities in many of the specimens, with extramedullary hematopoiesis in a few.

Examination of the ovary in MAS generally reveals large unilateral ovarian cysts, which are follicular in nature.


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