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Parathyroid carcinoma, as a malignant tumour of an endocrine gland, is a rare entity. This causes difficulties in the diagnosis as well in the therapeutic approach. Some clinical courses of this malignant disease are demonstrated. The therapeutic options--surgically and medically--are reported and analysed.
BACKGROUND: The incidence of endocrine carcinomas is about 5.3 persons per 100,000 population. Most frequent are malignancies of the thyroid gland (about 89%). THERAPY: Because of low incidences and missing prospective studies as well as radiotherapy and chemotherapy resistance, general accepted therapy guidelines for endocrine carcinomas are still missing. Surgery and radionucleotide treatment is generally the first-line therapy. Hormonal active carcinomas can be additionally treated with special substances such as octreotide and mitotane. Chemotherapy is frequently not effective. Widely used substances are cyclophosphamide, cisplatin, doxorubicine, dacarbazine, vincristine and etoposide. This first part of the review will present medical therapies of thyroid carcinomas, adrenal carcinomas and parathyroid carcinomas. The second part in one of the next issues will focus on less frequent endocrine carcinomas of the gastrointestinal tract.
BACKGROUND: A parathyroid adenoma demonstrating intranuclear holes on aspiration cytology prompted a review of parathyroid neoplasms to determine the frequency of this phenomenon. METHODS: Aspiration cytology slides from 30 parathyroid adenomas and 1 parathyroid carcinoma were reviewed. In addition, histologic slides from 136 parathyroid adenomas and 7 parathyroid carcinomas were reviewed. Twenty-two cases had both cytologic and histologic slides available for review. The presence and approximate frequency of intranuclear holes were recorded. RESULTS: On cytologic smears, intranuclear holes were found in 3 of the 31 cases reviewed (2 adenomas and 1 carcinoma). The holes were frequent in only one adenoma (the index case) and moderate-rare in the other two cases. Review of tissue slides showed holes in 9 of 136 adenomas and 3 of 7 carcinomas; 2 adenomas and 2 carcinomas had frequent holes, whereas the remainder had holes infrequently. CONCLUSIONS: Intranuclear holes do occur in parathyroid neoplasia, in rare cases with considerable frequency. When intranuclear holes are observed in aspiration cytology specimens from the thyroid region, various thyroid and parathyroid conditions must be considered.
1. Immunochemical cross-reactivity, but not identity, has been demonstrated between bovine parathyroid hormone and an antigen in biologically active extracts of human parathyroid tissue by quantitative C' fixation and C' fixation inhibition. 2. An antigen that fixes C' with rabbit antibody to bovine parathyroid hormone has been found in urea extracts of six human non-parathyroid neoplasms associated with a hypercalcemic syndrome mimicking primary hyperparathyroidism. Comparable extracts of control tissues and other tumors were serologically negative. 3. It is concluded that the tumor antigen is parathyroid hormone or a very closely related protein, and that its production by these neoplasms was the cause of the hypercalcemic syndrome in these six patients.
Between 1982 and 1989, 145 patients underwent operations for persistent or recurrent primary hyperparathyroidism (HPT). At re-exploration, 15 patients (10.3%) were found to have locally recurrent parathyroid tumors (11 patients with adenoma and 4 with carcinoma). These 15 patients had 28 previous operations at outside institutions for HPT. Patients with locally recurrent HPT secondary to adenoma had a longer disease-free interval than patients with locally recurrent carcinoma. At the time of evaluation at the National Institutes of Health (NIH) for recurrent or persistent HPT, each patient was symptomatic and patients with carcinoma had significantly more symptoms and higher serum levels of calcium and parathyroid hormone than patients with adenoma. Locally recurrent parathyroid neoplasm was correctly localized by preoperative testing in 14 of 15 patients. These 15 patients underwent 18 reoperations at NIH for excision of locally recurrent parathyroid tumors. Following the final reoperation (two patients had more than one procedure), each patient had normal serum levels of calcium. In addition each patient remains biochemically cured (based on normal serum calcium level), with a median follow-up interval of 21 months. Local recurrence of parathyroid adenoma comprises a small but significant proportion of cases of recurrent or persistent HPT and can be indistinguishable from parathyroid carcinoma. Findings suggestive of carcinoma include shorter disease-free interval, higher serum levels of calcium and parathyroid hormone, and histologic appearance. Whether the locally recurrent parathyroid neoplasm is benign or malignant, aggressive surgery can control serum levels of calcium in these patients with acceptable rates of morbidity.
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The sonographic textures of 10 parathyroid tumors in nine patients were examined and compared with their histologic features, particularly with the amount of fibrous trabeculae. The carcinomas containing a large amount of fibrous trabeculae, which is the most frequent finding in parathyroid cancer, were very echogenic. On the other hand, the adenomas without fibrous trabeculae showed a low echogenicity. These data suggest that the possibility of malignancy is high when the parathyroid tumor is found to be very echogenic.
Over a 25-year period, two carcinomas of the parathyroid were observed in 67 cases of primary hyperparathyroidism. The most important signs and symptoms were bone disease, palpable neck metastases, renal stones, and hypercalceamia with high blood levels of parathyroid hormone. Histology revealed that in principle parathyroid carcinoma can be distinguished from adenoma by a trabecular pattern and thick fibrous bands. The presence of cellular atypia and variation or mitotic figures (regressive polymorphia) was not a useful criteria for carcinoma. Local recurrence occurred in both cases.
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The paper presents current diagnostic and therapeutic approach in parathyroid cancer. The suspicion of parathyroid cancer should be taken into account in patients with primary hyperparathyroidism symptoms (and elevated total and ionised calcium blood level and PTH blood level), present palpable cervical mass and enlarged cervical lymph nodes. Further diagnosis should be based on ultrasound of the neck (including power-Doppler ultrasound), subtraction 99mTc-MIBI and 123J scintigraphy, ultrasound-guided fine needle aspiration, and CT or MRI if necessary to assess the stage of the process. The elective surgical procedure should be primary 'en block' excision of the tumour with the unilateral thyroid lobe and the following loco-regional adjuvant radiotherapy. Patients who underwent surgical treatment due to parathyroid cancer require long-term follow-up as the risk of local recurrence or distant metastases (mostly into lungs or bones) remains high even many years after initial operation. Patients with dissemination usually suffer from severe hypercalcemia leading to death if untreated correctly. Thus, so crucial is effective treatment of hypercalcemia (diuresis, biphosphonates, calcitonine, oktreotide).
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The Authors after a review of literature and on the basis of their direct experience, emphasize the importance of right protocol for diagnosis of parathyroid tumors. The techniques investigated, continuously evolving and with different sensitivity, permit improving diagnosis in order to right surgery.
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The importance of superselective catheterization of the small jugular veins for PTH-radioimmunoassay is shown as an improvement of the preoperative localization technique. Since May 1976 in 20 patients the diagnosis of pHPT could be established. Our own experiences with the method of small vein sampling combined with the radioimmunoassay demonstrate that a reliable localization of overactive parathyroid tumours is possible.