Operative Findings and Histopathologic Characteristics

Some macroscopic features are valuable in the intraoperative assessment of a potentially malignant tumor. These include color and findings by palpation. A grayish white tumor that is hard and grossly adherent to adjacent structures is highly suggestive of malignancy. Nonetheless, in a series of 95 cases of parathyroid carcinoma collected from centers with much experience in endocrine surgery, there was no correlation between macroscopic and microscopic findings. Invasiveness was recorded at histopathologic re-evaluation in only half of the tumors.2 Twenty percent of the patients were initially operated on for a benign diagnosis. Other studies have also confirmed the discrepancies in the gross appearance of the lesions.26 Glandular weight is more likely to be prominent, but again size alone cannot discriminate between benign and malignant tumors. The median glandular weight, available for evaluation in 35 of 95 cases, was greater than 4 g (range, 1 to 40 g).2

A major reason for the differences in incidence among centers can be the histologic criteria used. This has probably led to overdiagnosis of carcinoma in some series.26"28 If only variables such as invasive growth pattern and metastases are used, the incidence is lower. Of 20 patients of Smith and Coombs,5 at least 5 had no evidence of local infiltration, recurrence, or metastases. In Shane and Bilezikian's review, 10 of 62 patients did not have these findings of malignancy.4,5 In the previously mentioned series of 95 cases, presence or absence of local infiltrative growth pattern and metastases were used as absolute diagnostic criteria.2 Two distinct groups could be separated. Fifty-six cases fulfilled these criteria, and 39 were called equivocal because these findings were absent. In the latter group, the tumors exhibited combinations of features such as fibrous bands, trabeculae, cellular atypia, and mitotic figures. None of these recurred during a median follow-up of 7 years (range, 0 to 22 years).

In a second study, a more detailed histopathologic evaluation was undertaken, and a cytometric assessment of the crude DNA content of the tumor cell nuclei was also performed.29 There were significant differences between the carcinomas and the equivocal tumors in that the carcinomas predominantly showed a solid growth pattern with marked fibrosis. Even acinar and follicular structures were noted in tumors that eventually recurred. Among the cytologic features, the carcinoma cells were markedly atypical with macronucleoli (Fig. 63-1). These cells showed great variations in size and shape. In one third of the tumors that metastasized, no nuclear atypia could be demonstrated. Mitotic rate as a cell cycle marker has been one of the classic features for diagnosing parathyroid carcinoma. There was a significant difference in mitotic rate between carcinomas and the equivocal cases. Also, metastasizing tumors had a significantly elevated mitotic rate compared with nonrecurrent invasive tumors. Nevertheless, in 20% of the carcinomas, no mitosis was found in available sections analyzed. Necrosis has not been frequently described previously but was found in 30% of the carcinomas. In Table 63-2, a comparison of the histologic and cytologic features for both tumor groups is given. The aggressiveness of the tumors correlated with the histocytologic appearance, whereas nuclear atypia, necrosis, and mitotic activity were more frequent in metastasizing tumors than in invasive but nonrecurrent tumors.

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