Histopathologic Varieties of PHPT

A variety of pathologic conditions cause PHPT (Fig. 49-1). The most common cause of PHPT (85% to 90%) is a solitary benign parathyroid adenoma. Malignant tumors of the parathyroid gland are extremely unusual, occurring in less than 1% of cases; parathyroid cancers are sometimes difficult to distinguish from atypical adenomas. Parathyroid tumor metastases are certainly a sign of malignancy. Chief cell

Hyperplasia

Primary

Hyperplasia

Multiple adenoma

Double adenoma^

Familial

FIGURE 49-1. Various forms of hyperparathyroidism encountered in the surgical practice. MEN = multiple endocrine neoplasia.

hyperplasia (four-gland parathyroid hyperplasia) constitutes about 10% to 15% of all cases of PHPT. It affects all glands, but the hyperplasias may vary considerably in size, color, and configuration. Findings of microscopic areas of nodular hyperplasia have been described by Harrison and colleagues,7 and their biologic significance seems to be minimal. Hyperplasia is identified as primary when there is no obvious reason for it to occur. Secondary hyperparathyroidism (HPT) is usually caused by end-stage renal disease. Secondary HPT usually resolves after successful kidney transplantation.

Sporadic multiple adenomas can occur synchronously or metachronously. Multiple adenomas occur much more frequently in patients with multiple endocrine neoplasia (MEN) 1 or 2 and in patients with familial HPT without other endocrinopathies.

Oil red O staining of parathyroid tissue, as introduced by Roth and Gallagher8 and modified by Ljungberg and Tibblin,9 has helped pathologists distinguish between normal and abnormal parathyroid tissue and between solitary adenoma and hyperplasia. True solitary adenomas often have a compressed rim of normal parathyroid tissue. Characteristically, the red stain is taken up by the suppressed chief cells, whereas the hyperactive adenomatous cells do not take up this fat stain. In the normal parathyroid, there is a homogeneous picture of chief cells stained red by the oil red O as an expression of the suppression. These criteria help differentiate between a solitary adenoma and a hyperplastic gland, although some pathologists believe that it is impossible to differentiate between a hyperplastic gland and an adenomatous gland without histologic evidence of another normal gland. The advantage of giving the pathologist a whole normal-appearing parathyroid gland is to eliminate the possibility of four-gland parathyroid hyperplasia as a cause of PHPT.

The cooperation of an experienced pathologist is essential. It is a great advantage for the pathologist if the suppressed rim of normal parathyroid cells can be identified. The surgeon can help the pathologist by tying a suture around the vascular pedicle of the gland because the vessels often first enter the normal compressed tissue of the adenoma. Intraoperative oil red O staining is performed as a complement to the conventional hematoxylin-eosin method. Although this technique improves the diagnostic accuracy and microscopic interpretation in some cases, it is still difficult to be completely sure of this diagnosis. Thus, among 165 consecutive patients with PHPT, all of whom had their parathyroid stained by hematoxylin-eosin and oil red O intraoperatively, 8% were judged equivocal.10

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