Chronic parathyroiditis associated with parathyroid hyperplasia and hyperparathyroidism.

Two cases of chronic parathyroiditis associated with parathyroid hyperplasia and hyperparathyroidism are described. There was no evidence of an underlying infectious disease, a developmental anomaly, or a drug reaction that could explain the inflammatory component. It is suggested that an autoimmune process might have been involved in the pathogenesis of this previously unreported clinicopathologic entity.

Differentiated thyroid carcinoma, intermediate type: a new tumor entity with features of follicular and parafollicular cell carcinoma.

A group of differentiated thyroid carcinomas with morphologic and immunohistochemical traits of both follicular and medullary carcinoma is described. This group consists of tumors characterized by a solid and/or cribriform histologic pattern with a more or less pronounced admixture of follicular structures, immunohistochemical evidence for the production of thyroglobulin and one or more of the three neurohormonal peptides neurotensin, somatostatin, and calcitonin, and absence of amyloid. These tumors were selected from thyroid carcinomas that had been diagnosed, according to current histopathologic criteria, as differentiated follicular carcinomas. A series of pure follicular carcinomas, devoid of solid or cribriform structures, was found to contain thyroglobulin immunoreactive tumor cells only, whereas a series of classic medullary carcinoma with amyloid stroma revealed specific staining for all three neurohormonal peptides but not for thyroglobulin. The results suggest that differentiated thyroid carcinoma can be regarded as a continuous spectrum of tumor types, with pure follicular carcinomas and classic medullary carcinoma representing the two extremes and the tumors with biphasic features representing a broad intermediate group. The authors suggest that this group be designated "differentiated thyroid carcinoma, intermediate type."

Fat staining in parathyroid disease--diagnostic value and impact on surgical strategy: clinicopathologic analysis of 191 cases.

The study comprised 191 cases of surgically treated hyperparathyroidism, with all principal types of parathyroid disease represented. At least two complete glands stained with a modified isopropanol oil red O method for fat, in addition to sections stained with hematoxylin-eosin, were available in each case. On the basis of the morphologic evaluation and the clinical follow-up data, it is concluded that access to two complete glands and the use of fat staining allow highly reliable intraoperative distinction between adenoma and hyperplasia. Of 105 patients followed up for at least one year (mean, 20 months) in whom adenomas were diagnosed, a single possible error was identified. In each of 68 cases classified as hyperplasia on the basis of two abnormal glands, every additional complete gland available (total, 182 glands) was at least partially abnormal, with distinct signs of hyperactivity, irrespective of size. The rate of equivocal findings for cases in which two glands were available (probably adenoma but hyperplasia not excluded) was 8 per cent in 165 cases of primary hyperparathyroidism. These results justify limitation of surgery to one side of the neck in patients in whom adenoma is diagnosed on the basis of a complete, functionally normal (inactive) gland in addition to the presumed adenoma. Thus, the methods described provide a basis for optimal utilization of imaging techniques that allow preoperative localization of parathyroid adenomas.

Papillary carcinoma of the thyroid with mucoepidermoid features.

The significance and differential diagnoses of signet-ring cells found in the fine-needle aspirate of metastatic mucoepidermoid carcinoma from the thyroid are reported and discussed. The primary tumor occurred in a 35-year-old man, who had a history of neck irradiation during his childhood. Despite postoperative treatment with 60 Gy external radiation and 1,200 mCi 131I, the patient has at present--12 years after the initial operation--progressive disease with local recurrence in the neck as well as lung metastases.

Hyperparathyroidism after treatment with radioactive iodine: not only a coincidence?

Review of medical records in 600 consecutive cases of primary hyperparathyroidism revealed 10 patients with a documented history of iodine 131 (131I) treatment. In seven cases 131I had been given because of Graves' disease and in three cases for ablation of thyroid remnants after tumor operations. All but one of the patients were women. Their age at the time of 131I treatment ranged from 21 to 72 years, and the interval to detection of hypercalcemia was between 3 and 27 years. It is noteworthy that all patients treated for Graves' disease had absorbed radiation doses large enough to cause permanent hypothyroidism, and half of them showed complete absence of the thyroid gland at subsequent operation for hyperparathyroidism. Furthermore, parathyroid adenomas had developed at the sites of thyroid remnants in cases with 131I ablation after tumor operations. Our findings support other observations indicating that not only external radiation but also radiation from 131I is a risk factor for development of hyperparathyroidism, and it is emphasized that age at the time of radiation treatment may be of decisive importance in this context.

The surgical treatment of gastrinoma in MEN I syndrome patients.

The pancreatic component of the multiple endocrine neoplasia type I (MEN I) syndrome is a difficult and controversial problem because the entire endocrine pancreas is diffusely involved with varying degrees of islet-cell hyperplasia, microadenomatosis, and nesidioblastosis. In addition, in patients with functional syndromes, islet-cell tumors usually develop, and these may or may not be malignant. Because of the presumed inability to alleviate or cure the Zollinger-Ellison syndrome (ZES) in MEN patients, total gastrectomy was the treatment of choice before the introduction of H2 antagonists and omeprazole. At present, many physicians and surgeons consider H2 antagonists the best treatment and advise pancreatic exploration only when a gross pancreatic tumor is demonstrated on imaging studies. During the past 10 years we have studied all MEN I patients with ZES without hepatic metastases or gross pancreatic tumors using percutaneous transhepatic selective venous gastrin samplings. Two patterns of gastrin secretion were identified: (1) diffuse from multiple pancreatic sites and (2) localized regional secretion. Four patients from the latter group were selected for attempted surgical "cure" without gastrectomy or total pancreatectomy. Two additional patients are included who had resection of gastrinomas and have maintained basal serum gastrin levels within the normal range for extended periods. The follow-up on these patients ranges from 5 months to 12 years. All six patients have normal basal gastrin values, and those with remaining stomachs require no drug therapy.

ABO blood group antigens in parathyroid adenoma and hyperplasia.

Immunohistochemical determination of ABO blood group antigens was performed on parathyroid tissue to see if the presence or absence of such antigens could be used as an aid to distinguish adenoma from hyperplasia in primary hyperparathyroidism. Material from nine cases of solitary adenoma and seven cases of hyperplasia fixed in formalin and embedded in paraffin was studied using monoclonal antibodies and avidin-biotin-peroxidase complex technique. The two categories of tissue did not show any consistent differences in the extent or intensity of immunoreactivity, and the method tested did not permit distinction between adenomatous and hyperplastic disease of the parathyroid glands.

Surgical strategy in nonfamilial primary parathyroid hyperplasia: long-term follow-up of thirty-nine cases.

The extent and result of surgery in 39 cases of nonfamilial primary parathyroid hyperplasia followed from 2 to 20 years are reported. Thirteen patients had been subjected to subtotal parathyroidectomy leaving no gland intact, while 26 had undergone less extensive surgery leaving at least one grossly normal or near-normal gland intact without biopsy. In the former group two patients (15%) developed permanent hypoparathyroidism requiring vitamin D treatment. In the latter group there were two patients (8%) with persistent hypercalcemia, which might have been avoided with a subtotal parathyroidectomy. Judging from these results, we believe that an individualized surgical approach is justifiable in nonfamilial primary parathyroid hyperplasia. Subtotal parathyroidectomy, leaving no gland intact, is advocated as the method of choice only when all four glands are enlarged. If one or more glands are grossly normal or near normal, factors such as degree of hypercalcemia, symptoms, age, general condition, and life expectancy should be taken into consideration when the extent of the operation is decided. A more conservative operation leaving at least one grossly normal gland intact without biopsy appears to be sufficient for cure in most of these cases and minimizes the risk for development of permanent hypoparathyroidism.

Sub-clinical Cushing's syndrome in patients with adrenal gland incidentalomas. Pitfalls in diagnosis and management.

Widespread use of contemporary imaging techniques (ultrasound, computerized axial tomography, and magnetic resonance imaging scans) have led to the incidental discovery of asymptomatic adrenal neoplasms with increasing frequency. Patients with such adrenal "incidentalomas" typically have no clinical manifestations of adrenal cortical hyperfunction at the time of discovery. We have studied 122 patients with asymptomatic adrenal masses ranging in size from 2 to 7 cm in diameter from 1978 to 1988. Selected patients, after adrenal metastases, pheochromocytoma, myelolipomas, and cysts were ruled out, were further evaluated for adrenal cortical hyperfunction by measuring urinary 17-hydroxysteroids, 17-ketosteroids, and free cortisol, serum A.M., P.M. cortisol, and plasma ACTH levels. These values were also measured before and after dexamethasone suppression. NP-59 adrenal scintiscans were performed on all patients. Six patients were identified with sub-clinical Cushing's syndrome. Baseline cortisol levels were normal in each of these patients. Loss of diurnal rhythm appeared to be the most sensitive indicator of abnormal adrenal cortical function. When adrenalectomy is performed in such patients, especially when contralateral adrenal gland suppression is evidenced by NP-59 scanning or other biochemical assessment, perioperative steroids should be administered in a manner similar to that used for patients with symptomatic Cushing's syndrome. Unilateral adrenalectomy in a patient with an asymptomatic adrenal adenoma, insufficiently studied, may result in Addisonian crisis.

Cytologic features in fine-needle aspirates from a sclerosing mucoepidermoid thyroid carcinoma with eosinophilia.

Fine-needle aspirates from a sclerosing mucoepidermoid thyroid carcinoma with eosinophilia showed peculiar but nonspecific features. The overall picture seems more important than individual elements in recognizing this rare entity cytologically, since the predominant type of malignant cells has a deceptively bland appearance. The differential diagnoses include other primary thyroid malignancies, as well as metastatic growth and Hashimoto's thyroiditis.

Clue helping to distinguish hyalinizing trabecular adenoma from carcinoma of the thyroid in fine-needle aspirates.

Fine-needle aspirates from four hyalinizing trabecular thyroid adenomas stained with May-Grünwald-Giemsa showed a distinctive component of purplish red stromal deposits corresponding to accumulations of basement membrane material occurring in such tumors. Recognition of these deposits helps to prevent cytologic overdiagnosis of malignancy in this rare benign tumor, which has a number of traits in common with both papillary and medullary carcinoma of the thyroid.

Cytopathological variables in parathyroid lesions: a study based on 1,600 cases of hyperparathyroidism.

Fine-needle aspirates and tissue sections from 120 surgically treated parathyroid (PT) lesions and histologic archive material from PT lesions in 1,500 additional cases of hyperparathyroidism were reviewed to assess the importance of various features in distinguishing PT disease from other types of lesions by aspiration cytology. We conclude that the morphologic variation shown by PT lesions is so many-sided that this distinction cannot be based on the presence or absence of a single feature only. Instead the cytologic picture as a whole must be taken into account and evaluated with full knowledge of the anatomical conditions pertaining to the lesion examined. If still in doubt, the diagnosis can be substantiated by supplementary immunocytochemical examinations.

Morphometric studies on nuclei in smears of fine needle aspirates from oxyphilic tumors of the thyroid.

Morphometry was applied to smears of fine needle aspirates from 26 oxyphilic thyroid neoplasms. Thirteen tumors were considered benign as judged from histologic findings and clinical follow-up for 2 to 20 years after the operation. Thirteen tumors were considered malignant histologically; four of these had proven metastases. In each case the mean and standard deviation of the projected nuclear area were calculated from 200 nuclei in the smear. Our results indicate that morphometric estimation of mean nuclear size and/or degree of anisokaryosis is of no practical value in distinguishing between benign and malignant thyroid neoplasms of the oxyphilic type.

Aspiration cytology of a rare solid and papillary epithelial neoplasm of the pancreas. Light and electron microscopic study of a case.

The light and electron microscopic appearance of fine needle aspirates from a case of a solid and papillary neoplasm of the pancreas is described. This rare type of tumor, which is often large when detected and usually occurs in young women, has a favorable prognosis if treated surgically. Thus, it is important to distinguish this lesion from other pancreatic neoplasms with regard to the choice of therapy. Possible cytologic differential diagnoses and the aid of electron microscopy in this context are discussed.

Oncocytic tumor of the pancreas. Report of a case with aspiration cytology.

The fine needle aspiration (FNA) cytologic findings in a case of pancreatic oncocytoma are reported, and the differential diagnoses are discussed. The FNA picture was consistent with an oncocytic, acinar or islet cell neoplasm; electron microscopy was required to make the definitive diagnosis. The partially cystic tumor measured 7 cm and occurred in the head of the pancreas in a 63-year-old man with symptoms related to compression of the common bile duct. The clinical findings in this and a few other known cases indicate that the malignant potential of pancreatic oncocytoma may be low. Thus, it is important to distinguish this type of tumor from the cytologically similar acinar carcinoma of the pancreas, which has a poor prognosis in general.

Clinicopathological peculiarities in parathyroid disease with hypercalcaemic crisis.

OBJECTIVE: To draw attention to some hitherto unnoticed clinicopathological aspects of primary hyperparathyroidism in patients who develop hypercalcaemic crisis. DESIGN: Retrospective review of records and histopathological archive material. SETTING: University hospital. SUBJECTS: 54 patients treated for primary hyperparathyroidism with hypercalcaemic crisis between 1961 and 1988. MAIN OUTCOME MEASURES: Correlation of age, serum calcium concentration, histopathological appearance and size of tumours associated with hypercalcaemic crisis. RESULTS: 11/54 (20%) of the patients with hypercalcaemic crisis were younger than 40 years of age. Among 460 patients treated at the same hospital for primary hyperparathyroidism without hypercalcaemic crisis, 23 (5%) belonged to the same age category (p less than 0.001). There was no difference between the two groups of patients regarding histopathological characteristics, with the exception of mitotic activity which was remarkably high in some benign lesions causing hypercalcaemic crisis. The correlation between tumour size and degree of hypercalcaemia was poor, and one-third of the adenomas did not exceed 2 cm in diameter. CONCLUSIONS: Young age is a risk factor regarding the development of hypercalcaemic crisis in primary hyperparathyroidism; the proportions of the pathological entities causing hypercalcaemic crisis do not differ markedly from other cases of primary hyperparathyroidism; the correlation between adenoma size and degree of hypercalcaemia is poor; oxyphil adenomas are as likely to be associated with hypercalcaemic crisis as other types of parathyroid adenoma; and some benign parathyroid lesions associated with hypercalcaemic crisis (hyperplastic glands as well as adenomas) show high mitotic activity.

Surgical strategy in hyperparathyroidism due to solitary adenoma.

Based on the postulate that parathyroid adenoma is practically always a solitary lesion, unilateral parathyroidectomy including the homolateral normal parathyroid was applied as a principle in the treatment of this form of primary hyperparathyroidism. The exploration was confined to the adenoma side if this was the first to be explored. Intraoperative oil-red-O staining of frozen sections was used to exclude the possibility of a multiglandular involvement. This principle was applied in a consecutive series of 102 patients operated for hyperparathyroidism from 1977 to 1981 and diagnosed as parathyroid adenoma. In 43 patients where the abnormal gland was found on the side explored first, unilateral parathyroidectomy was performed on that side, avoiding exploration of the contralateral side. In 45 patients where normal glands were found on the side first explored, unilateral parathyroidectomy was performed on the contralateral side. In 14 patients other types of operations were performed as the above-mentioned principle could not be achieved. At follow-up 1 to 5 years after surgery, no cases of hypocalcemia were recorded. The results of the different operations were compared as to early and late hypocalcemia. Early hypercalcemia was more pronounced after a bilateral exploration. Two of the patients who had an atypical operation had a permanent need for vitamin D in order to maintain an adequate serum calcium level. Surgical principles for various possible exploratory findings are outlined. These are based upon the idea of performing a unilateral parathyroidectomy whenever intraoperative oil-red-O staining excludes multiglandular involvement as a cause for the hyperparathyroidism.

Unilateral parathyroidectomy in hyperparathyroidism due to single adenoma.

As a general principle in the treatment of primary hyperparathyroidism due to single adenoma, unilateral parathyroidectomy was applied to 50 patients and compared with another group of 50 conventionally explored patients. Twenty-five patients were explored only on the "adenoma" side. The other 25 patients were explored on both sides, avoiding biopsies at the first. In the conventionally explored patients, the adenoma was removed and one to three normal glands were biopsied. Oil-red-O technique was used in the intraoperative microscopical examination. The patients in whom the operation could be limited to the "adenoma" side had a statistically more favorable situation concerning early postoperative hypocalcemia, length of operation time, and need for calcium and vitamin D substitution. The principle of unilateral parathyroidectomy in conjunction with intraoperative oil-red-O staining technique is advocated in hyperparathyroidism due to single adenoma because it offers more reliable peroperative distinction between uni- and multi-glandular involvement, reduced operation time, decreased risk for complication, reduced early hypocalcemia, and more favorable technical conditions for reoperation.