Answer: Metastatic medullary carcinoma of the thyroid

Histology: The biopsy shows cords and nests of cells dispersed in a dense eosinophilic background. The tumor cells occur in distinct clusters or nest and have very finely powdered nuclear chromatin. The background stroma has dense acellular material, which was positive on Congo Red staining. The tumor cells, and the background amyloid stroma were both positive for stains directed against calcitonin. There was no reported family history of thyroid carcinoma, or disorders to suggest multiple endocrine neoplasia syndromes. By report, testing for ret oncogene was negative in the patient’s serum. This patient appears to have sporadic medullary thyroid carcinoma.

Discussion: Medullary carcinoma is a malignant thyroid neoplasma composed of cells with C-cell differentiation. The tumor occurs in both sporadic, and familial forms, and medullary carcinoma also occurs in association with multiple endocrine neoplasia (MEN) types 2 A or B. The sporadic form of disease is, as in this patient, primarily a tumor of middle-aged adults. Most sporadic and familial medullary carcinomas are non-encapsulated tumors with a solid pattern of growth, but they may exhibit a wide spectrum of histologic patterns, and can mimic other types of primary thyroid malignancy, including follicular, papillary and undifferentiated carcinoma. Some of the small cell variants may mimic oat cell carcinoma. Stromal amyloid deposits, as seen here, have been identified in a large proportion of cases of medullary carcinoma. As suggested by the immunocytochemical findings, that amyloid is most likely derived from calcitonin or one of its precursors.

The differential diagnosis is concerned primarily with usual histologic variants of the disease. Some medullary carcinomas may consist predominately of stroma and amyloid, and may be difficult to distinguish from so-called “amyloid” goiters associated with primary plasma cell dyscrasia On the other hand, some papillary thyroid carcinomas may contain dense areas of collagen stroma that mimic amyloid. In both types of cases, special stains and immunocytochemical techniques will usually resolve the problems. Medullary carcinomas may contain follicular structures, and must be distinguished from follicular carcinoma. Furthermore, one may find entrapped normal thyroid follicles in medullary carcinoma. Again, immunocytochemical staining should resolve the issue. Insular carcinoma of the thyroid is a poorly differentiated tumor that is characterized by solid islands of tumor cells containing occasional small follicles. The stroma of instular carcinoma is typically negative for amyloid, and the tumor cells are thyroglobulin positive, but calcitonin negative. Spindled and giant cell forms of medullary carcinoma may be distinguished from undifferentiated carcinomas, and from sarcomas, using immunocytochemical staining. Often, both the spindle and giant cell forms of medullary carcinoma show foci of more typical medullary carcinoma, found by extensive sectioning of the tumor. Metastatic small cell carcinoma of the lung and thyroid and metastasis from carcinoid tumors may be difficult to distinguish from primary medullary carcinoma because all may be positive for calcitonin.