Pathology of Parathyroid Carcinoma

The morphological criteria for Parathyroid Carcinoma include:

Capsular and blood vessel invasion, desmoplastic stroma with fibrous bands, trabecular growth pattern, thickening and hyalinization of the capsule, spindle shaped tumour cells, elevated mitotic count and aberrant mitoses.

Of these features, the presence of fibrous bands stands out as the most helpful for the diagnosis of malignancy, being present in 90% of 67 cases studies (Schantz & Castleman 1973).

Caution should be exercised in the interpretation of fibrous bands since these may sometimes occur as part of regressive phenomenon in adenomas, in which case they may be associated with deposition of hemosiderin and surrounded by chronic inflammatory cells.

Assessment of mitotic activity either by mitotic counts, flow cytometry, or by immunohistochemistry has been proposed as a means of predicting malignancy in parathyroid neoplasia.

While there is a statistical tendency for the carcinoma, particularly those with aggressive behaviour, to have higher proliferative activity than adenomas, overlap in the result ranges limits diagnostic utility in the individual case.

The main problem appears to be that some parathyroid adenomas, increasingly recognized to be clonal and a true neoplasm, have high proliferative indices.

In one interesting study, nuclear chromatin texture, even when subject to detailed image analysis, failed to distinguish benign and malignant parathyroid neoplasms.

Capsular invasion is an important distinguishing feature for parathyroid adenocarcinoma, being present in approximately two thirds of cases, often associated with a capsule which itself is thicker than that encountered in parathyroid adenomas.

However, care should be taken not to confuse occasional entrapped clusters of cells, particularly in the capsules of adenomas which have undergone cystic degeneration, for true invasion.

While clear-cut vascular invasion is only encountered in 10-15% of parathyroid adenocarcinomas, when present it is a useful sign of malignancy.

The growth pattern in parathyroid carcinoma may be trabecular, rosette-like or sheet-like. Nuclear palisading may be present. While the tumour cells are generally larger than those in adenomas, there may be little nuclear pleomorphism.

Electron microscopic studies have failed to show any unique features correlating with malignancy in parathyroid neoplasms.

Analysis of the p53 gene mutation is of uncertain value in the prediction of malignancy in parathyroid neoplasia. In one study it was demonstrated in neither adenomas nor carcinomas. In another study two out of nine carcinomas were p53 immunopositive of which one had p53 allelic loss while the other was genetically non-informative, while none of the adenomas had allelic loss.

Loss of Retinoblastoma (Rb) protein has been reported in some parathyroid carcinomas while adenomas appear to be Rb positive.

A number of benign and malignant lesions can mimic parathyroid carcinoma.

The clear cells in the wall of parathyroid cyst, atypical oxyphil parathyroid adenoma, various metastatic tumours particularly of clear cell type, and implantation of parathyroid tissue at previous surgery for benign conditions may mimic parathyroid carcinoma.

The presence of mitotic figures within a parathyroid adenoma, (provided that they are not atypical) is not in itself as indicator of malignancy.

Groups of large atypical cells in parathyroid neoplasms, particularly close to foci of hemorrhage, do not indicate malignancy and are, paradoxically, more common in adenomas.

When a diagnosis of parathyroid carcinoma is established, the prognosis is poor with an approximate 50% 10 year survival, with more patients dying from severe hypercalcemia than the physical effects of metastatic disease.