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Presented by William Westra, M.D. and prepared by Carla Ellis, M.D.
Case 1: 60 year-old man with hypercalcemia.
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1. Question
Week 456: Case 1
60 year-old man with hypercalcemiaimages/1Alex/10252010case1image1.jpg
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images/1Alex/10252010case1image4.jpgCorrect
Answer: Parathyroid carcinoma
Histology: The tumor is composed of sheets of uniform cells. The cellular sheets are compartmentalized by intersecting bands of collagen. Hemosiderin deposition within the fibrous bands is not a conspicuous feature. The tumor does not appear to be confined by a capsule. Instead it demonstrates irregular infiltration into the adjacent fat. Along this infiltrative front, tumor extends into and fills small to medium-caliber vascular spaces. The tumor cells have pink cytoplasm, relatively uniform nuclei, and small nucleoli. Mitotic figures are not readily identified.
Discussion: The primary differential diagnosis of primary hyperparathyroidism is chief cell hyperplasia, parathyroid adenoma, and parathyroid carcinoma. Among these, parathyroid carcinoma is by far the least common, accounting for only about 1% of cases. In many instances the diagnosis is suspected before an opinion is rendered by the surgical pathologist. Patients tend to be symptomatic due to highly elevated serum calcium levels, patients tend to present with palpable neck masses, and the surgeon often reports difficulty in removing the effected gland due to invasion of surrounding structures.
The histologic recognition of malignancy is notoriously difficult. Indeed, the diagnosis of parathyroid carcinoma is often made retrospectively upon re-excision of a recurrent tumor. Helpful morphologic alterations that tend to be associated with carcinomas include dissecting bands of collagen, increased mitotic activity, invasion beyond the capsule of the gland, and vascular invasion. The presence of thick fibrous bands is the least specific and may occur as a degenerative change in benign adenomas, or may simply represent surgical scarring in an adenoma that has locally recurred. In these cases, the fibrous banding is often accompanied by heavy hemosiderin deposition. This case underscores the problem in diagnosing parathyroid carcinoma on the basis of overt cytologic atypia or by the presence of brisk mitotic activity. Neither of these features are well developed in the present case. The most reliable feature of malignancy is invasive tumor growth, either into blood vessels (angio-invasion) or into local structures of the neck. Documentation of these findings provides more unequivocal proof of malignancy.
By most standards, parathyroid carcinomas are rather indolent tumors. They are slow growing and generally do not overwhelm the patient with widespread dissemination. Nonetheless, as functionally active tumors they can be fatal as a result of uncontrollable hypercalcemia. The primary goal of initial treatment is complete en bloc tumor removal.
Incorrect
Answer: Parathyroid carcinoma
Histology: The tumor is composed of sheets of uniform cells. The cellular sheets are compartmentalized by intersecting bands of collagen. Hemosiderin deposition within the fibrous bands is not a conspicuous feature. The tumor does not appear to be confined by a capsule. Instead it demonstrates irregular infiltration into the adjacent fat. Along this infiltrative front, tumor extends into and fills small to medium-caliber vascular spaces. The tumor cells have pink cytoplasm, relatively uniform nuclei, and small nucleoli. Mitotic figures are not readily identified.
Discussion: The primary differential diagnosis of primary hyperparathyroidism is chief cell hyperplasia, parathyroid adenoma, and parathyroid carcinoma. Among these, parathyroid carcinoma is by far the least common, accounting for only about 1% of cases. In many instances the diagnosis is suspected before an opinion is rendered by the surgical pathologist. Patients tend to be symptomatic due to highly elevated serum calcium levels, patients tend to present with palpable neck masses, and the surgeon often reports difficulty in removing the effected gland due to invasion of surrounding structures.
The histologic recognition of malignancy is notoriously difficult. Indeed, the diagnosis of parathyroid carcinoma is often made retrospectively upon re-excision of a recurrent tumor. Helpful morphologic alterations that tend to be associated with carcinomas include dissecting bands of collagen, increased mitotic activity, invasion beyond the capsule of the gland, and vascular invasion. The presence of thick fibrous bands is the least specific and may occur as a degenerative change in benign adenomas, or may simply represent surgical scarring in an adenoma that has locally recurred. In these cases, the fibrous banding is often accompanied by heavy hemosiderin deposition. This case underscores the problem in diagnosing parathyroid carcinoma on the basis of overt cytologic atypia or by the presence of brisk mitotic activity. Neither of these features are well developed in the present case. The most reliable feature of malignancy is invasive tumor growth, either into blood vessels (angio-invasion) or into local structures of the neck. Documentation of these findings provides more unequivocal proof of malignancy.
By most standards, parathyroid carcinomas are rather indolent tumors. They are slow growing and generally do not overwhelm the patient with widespread dissemination. Nonetheless, as functionally active tumors they can be fatal as a result of uncontrollable hypercalcemia. The primary goal of initial treatment is complete en bloc tumor removal.