OSU Department of Pathology

Anatomical Pathology Interesting Case Conference

Microscopic description and IHC:

The adrenal mass is grossly a well circumscribed orange medullary lesion composed of nests of basophilic, polygonal shaped cells each bordered by fibrous bands connected to vascular networks. Periadrenal, capsular, or vascular invasions are not seen. Mitotic figures are rare and no areas of necrosis are identified. There no significant other morphologic patterns and the cells are not significantly pleomorphic.

The adrenal mass is positive for synaptophysin and chromogranin.

The thyroid mass is composed of small nests of round cells separated by fibrous bands and scattered vessels. The individual cells have a granular cytoplasm. Scattered pink amorphous are present.

The cell within the thyroid mass are positive for synaptophysin and calcitonin. The pink amorphous material are positive for Congo red (slide not available to polarize).

Discussion:

It turns out this particular patient has a family history of multiple endocrine neoplasm (MEN) 2A. The two lesions are pheochromocytoma in the adrenal gland and medullary thyroid carcinoma, all from the same patient. However, both MEN 2A or 2B can present this way.

MEN is a syndrome that features tumors of endocrine glands. It is an autosomal dominant disorder. There are three main subtypes.

MEN1 can be remembered with the three Ps, pituitary, parathyroid, and pancreatic tumors. The MEN1 gene on chromosome 11 is responsible for the presentation. Up to 60 percent of the patients will develop pituitary adenomas. Multiple parathyroid tumors can cause hyperparathyroidism and the syndrome has almost 100 percent penetrance for all patients by their middle age. Pancreatic neuroendocrine tumors can manifest as pancreatic islet cell or gastrointestinal adenoma. They can have malignant potential and is the primary life-threatening complication of MEN 1 syndrome.

Both MEN 2A and 2B are linked with RET proto-oncogene on chromosome 10. MEN 2A can be remembered with the two Ps and one M, pheochromocytoma, parathyroid, and medullary thyroid carcinoma. Pheochromocytoma can occur in approximately half of the patients with MEN 2 and is usually not the first manifestation of the syndrome. Hyperparathyroidism in MEN 2A is usually multiglandular and occurs to up to 25 percent of the patient. The clinical presentation is usually mild or asymptomatic. The medullary thyroid carcinoma (MTC) is a neuroendocrine tumor of the parafollicular C cells of the thyroid gland. Virtually all patients with MEN 2 develop MTC early in life.

MEN 2B can be remembered with the one P (pheochromocytoma) and three Ms, MTC, Marfanoid habitus, and mucosal neuroma. The mucosal neuromas typically involve the lips, tongue, and intestine.

References:

Rosai, Juan. Rosai and Ackerman's Surgical Pathology 10e. Elsevier Health Sciences, 2011.

Padberg, B., et al. "Multiple endocrine neoplasia type 1 (MEN 1) revisited."Virchows Archiv 426.6 (1995): 541-548.

Skogseid, Britt, Jonas Rastad, and Kjell Oberg. "Multiple endocrine neoplasia type 1. Clinical features and screening." Endocrinology and metabolism clinics of North America 23.1 (1994): 1-18.

Case Images