Pituitary pathology in Carney complex patients.

Carney complex (CNC) is a familial multiple neoplasia syndrome with features overlapping those of McCune-Albright syndrome (MAS) and multiple endocrine neoplasia (MEN) type 1 (MEN 1). Like MAS and MEN 1 patients, patients with CNC develop growth hormone (GH)-producing pituitary tumors. Occasionally, these tumors are also prolactin-producing, but there are no isolated prolactinomas or other types of pituitary tumors. In at least some patients with CNC, the pituitary gland is characterized by hyperplastic areas; hyperplasia appears to involve somatomammotrophs only. Hyperplasia most likely precedes the formation of GH-producing adenomas in CNC, as has been suggested in MAS-related somatotropinomas, but has never been seen in MEN 1 patients. In at least one case of a patient with CNC and advanced acromegaly, a GH-producing macroadenoma showed extensive genetic changes at the chromosomal level. So far, half of the patients with CNC have germline inactivating mutations in the PRKAR1A gene; in their pituitary tumors, the normal allele of the PRKAR1A gene is lost. Loss-of-hererozygosity suggests that PRKAR1A, which codes for the regulatory subunit type 1alpha of the cAMP-dependent protein kinase A (PKA) may act as a tumor-suppressor gene in CNC somatomammotrophs. These data provide evidence for a PRKAR1A-induced somatomammotroph hyperpasia in the pituitary tissue of CNC patients; hyperplasia, in turn may lead to additional genetic changes at the somatic level, which then cause the formation of adenomas in some, but not all, patients.

Spindle-cell thymic carcinoid occurring in multiple endocrine neoplasia I: fine-needle aspiration findings in a case.

Thymic carcinoid tumors are important to distinguish from thymomas because of their worse prognosis. These rare tumors occasionally occur in the setting of multiple endocrine neoplasia (MEN). A needle biopsy was performed on a 57-yr-old woman with MEN I and a newly-discovered anterior mediastinal mass. Aspiration smears were cellular and contained polygonal-to-spindled cells with high nucleocytoplasmic ratios and evenly-dispersed pattern. Occasional nuclear molding and rosette-like arrangements were present. A synaptophysin immunostain was positive on cell-block preparation. A diagnosis of thymic carcinoid was made. Subsequent excision of the mass confirmed the diagnosis of thymic carcinoid. Thymic carcinoids are cytologically similar to carcinoid tumors elsewhere. They should be distinguished from epithelial thymoma and substernal medullary carcinoma of the thyroid.

Large clear cell adenoma of the parathyroid in a patient with MEN-1 syndrome. Ultrastructural study of the tumour exhibiting unusual RER formations.

A 48 year old man presented with hyperparathyroidism and acromegaly. Although pancreatic tumour was not demonstrated, the diagnosis of MEN-1 syndrome was made. The parathyroid adenoma was removed surgically and investigated by histology and transmission electron microscopy and was diagnosed as large clear cell adenoma with extensive deposition of glycogen. Much of the endoplasmic reticulum was present in two special forms: annulate lamellae and the rare rail-like configurations both of which showed continuity with the conventional RER as well as with each other. No obvious correlation was apparent between presence of special RER formations and growth rate or endocrine activity of tumour; they may be regarded as signs of cellular dedifferentiation.