Psammomatous Melanotic Schwannoma
Psammomatous melanotic schwannoma (PMS) consists of Schwann cell-like spindled and polygonal cells arranged in fascicles and syncytial sheets. The nuclei are hyperchromatic and show prominent nucleoli. The nuclear detail may be obscured by heavy melanin pigmentation which can be coarsely clumped or finely granular. Psammoma bodies are usually present (several can be seen in this image). In some foci, there may be whorled structures or vague nuclear palisading creating resemblance to schwannoma. The tumor cells are positive for S-100 protein as well as melanoma markers such as HMB-45, Melan-A, and tyrosinase. Association with Carney Syndrome: PMS is associated with Carney syndrome in about 50% of cases. Carney syndrome is an autosomal dominant disorder consisting of 1) myxomas of heart, skin, and breast; 2) skin pigmentation around lips, eyes, and genitalia caused by lentigines; and 3) endocrine overactivity secondary to tumors, including primary pigmented nodular adrenocortical disease causing Cushing syndrome, pituitary adenoma causing acromegaly, and Sertoli cell tumor causing sexual precocity. Molecular Genetics: Carney complex occurs due to mutations in PRKAR1A tumor suppressor gene on 17q23-24 which codes for type 1 alpha subunit of protein kinase A. The abnormal subunit leads to upregulation of protein kinase A activity which drives uncontrolled cell proliferation. Some individuals with Carney complex donít show this mutation and instead carry abnormalities in the 2p16 region.