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Primary hyperparathyroidism ( PHPT) is one of the most common of all endocrine disorders encountered by the practising histopathologist. The vast majority of lesions are sporadic in nature, approximately 85% of which are parathyroid adenomas, while hyperplasia and carcinoma account for 10-15% and fewer than 1%, of cases, respectively. Heritable forms of PHPT are much less common and present challenges both to clinicians and pathologists, particularly when they are the presenting feature of an endocrine syndrome. In such instances, pathologists play a key role in alerting physicians to the possibility of an underlying heritable endocrine syndrome and the potential for extra-endocrine manifestations. Therefore, a working knowledge of these disorders is essential for providing guidance to treating physicians. The aim of this update is to review the clinicopathological features, genetic bases and current management for patients with PHPT associated with multiple endocrine neoplasia ( MEN) types 1, 2A and 4 and hyperparathyroidism-jaw tumour ( HPT- JT) syndrome in the context of the 2017 World Health Organization ( WHO) Classification of Tumours of the Endocrine Organs. Additionally, familial isolated hyperparathyroidism, familial hypocalciuric hypercalcaemia and neonatal severe hyperparathyroidism are discussed. [ABSTRACT FROM AUTHOR]

Context.-Primary hyperparathyroidism (P-HPT) is one of the most common of all endocrine disorders. Eighty percent to 85% of cases are due to parathyroid adenomas while hyperplasia and carcinoma account for 10% to 15% and less than 1%, of cases, respectively. The past decade has witnessed remarkable advances in the understanding of the molecular basis of parathyroid hyperplasia and neoplasia. Additionally, imaging studies and the development of the intraoperative assay for parathyroid hormone have transformed the diagnosis and management of patients with these disorders. Objective.-To review the pathology of parathyroid lesions associated with P-HPT, their molecular and genetic bases, including heritable hyperparathyroidism syndromes, and their clinical diagnosis and management. Data Sources.-Review of pertinent epidemiology, pathology, radiology, and surgery literature on the diagnosis, classification, and treatment of P-HPT. Conclusions.-Although heritable causes of P-HPT including multiple endocrine neoplasia 1 and 2A and hyperparathyroidism-jaw tumor syndrome account for a minority of cases of P-HPT, advances in the characterization of the affected genes have provided insights into the genetic basis of sporadic parathyroid neoplasms. Alterations in cyclin D1 and loss of heterozygosity of chromosome 11q in adenomas and hyperplasias have provided support for clonality of these lesions. Parafibromin, the protein product of the HRPT2 gene responsible for hyperparathyroidism-jaw tumor syndrome, has been implicated in the development of sporadic parathyroid carcinomas and loss of immunohistochemical expression of this protein has been suggested to be of value in making the diagnosis of parathyroid carcinoma. Sestamibi scanning and ultrasound have revolutionized the planning of surgical approaches and the intraoperative parathyroid hormone assay has become the standard in guiding completion or extension of surgery. [ABSTRACT FROM AUTHOR]

Background: The NEK serine/threonine protein kinases are involved in cell cycle checkpoints, DNA damage repair, and apoptosis. Alterations in these pathways are frequently associated with cell malignant cellular transformations. Thyroid cancer is the most common malignant tumour in the endocrine system. Despite good treatment methods, the number of cases has increased significantly in recent years. Here, we studied the expression of NEK1, NEK2, NEK3, and NEK5 in different types of normal and malignant tissues, using tissue microarray analysis, and identified NEKs as potential markers in thyroid malignancy.Methods: The studied cases comprised multiple cancer tissue microarrays, including breast, colon, esophagus, kidney, lung, pancreas, prostate, stomach, thyroid and uterine cervix, as well as 281 patients who underwent thyroid resection for thyroid cancer or thyroid nodules. The expression of NEK1, NEK2, NEK3, and NEK5 was analyzed by immunohistochemistry. The expression pattern was evaluated in terms of intensity by two methods, semiquantitative and quantitative, and was compared between normal and cancer tissue.Results: We analysed the expression of each member of the NEK family in a tissue-dependent manner. Compared to normal tissue, most of the evaluated proteins showed lower expression in lung tumour. However, in the thyroid, the expression was higher in malignant tissue, especially for NEK 1, NEK3 and NEK5. Concerning characteristics of the thyroid tumour, such as aggressiveness, NEK1 expression was higher in tumours with multifocality and in patients with lymph node metastasis. NEK3 expression was stronger in patients with stage II, that involved metastasis. NEK5, on the other hand, showed high expression in patients with invasion and metastasis and in patients with tumour size > 4 cm. Furthermore, this work, demonstrated for the first time a high specificity and sensitivity of over-expression of NEK1 in classical and follicular variants of papillary thyroid cancer and NEK3 in tall-cell papillary thyroid cancer.Conclusion: Taken together, the NEK protein kinases emerge as important proteins in thyroid cancer development and may help to identify malignancy and aggressiveness features during diagnosis.Trial Registration: This study was retrospectively registered.  www.accamargo.org.br/cientistas-pesquisadores/comite-de-etica-em-pequisa-cep. [ABSTRACT FROM AUTHOR]

BACKGROUND OR CONTEXT: Pituitary adenoma (PA) is the most common pathology of the pituitary gland. Pituitary tumors were historically considered benign, however, from recent advances in pathological and molecular analyses, numerous prognostic markers have been identified, allowing a better characterization of tumor behavior and prediction of response to treatment and recurrences. AIMS AND OBJECTIVES: Evaluation of the epidemiological occurrence of pituitary tumors in our center and prediction of the benign, aggressive, or malignant nature of the tumor with the help of immunohistochemical markers (IHC) Ki-67, P53, and O-6-methylguanine-DNA methyltransferase (MGMT) along with radiology. MATERIALS AND METHODS: A prospective study was done in 33 cases. Patients with clinically suspected pituitary tumors and related symptoms and signs are referred from the endocrine outpatient department and subsequently operated at the neurosurgery department were selected. We have studied the clinical features, radiology, histopathology, and IHC with the help of Ki-67, P53, and MGMT of PA over 2 years. RESULTS: We have 94% (31/33) cases of PA among them 94% (29/31) cases are macroadenoma. The IHC was conducted on 30 cases (excluding 1 case of pituitary apoplexy) where Ki-67, p53, and MGMT have been used for IHC in order to analyze the prognosis of the PA, irrespective of the immunological subtype of the PA. In our study, only 13% (4 patients) had MGMT score 0 and 2 patients, among these 4 patients having above cutoff level of Ki-67 and p53 value, considered as aggressive (in case of Ki-67 >3% and >50% in case of p53). When comparing MGMT expression with recurrence, a high degree of significance was found (Mann–Whitney U-test, P = 0.0038). Most of the recurrent tumors (6/9) had MGMT score 1 or below and most of the nonrecurring tumor had MGMT score 2 or above. When comparing MGMT expression with aggressiveness, a high degree of significance was found (Mann–Whitney U-test, P < 0.0001). Finally, combining the radiological Ki-67, p53, and MGMT values, two cases of aggressive adenoma have been seen in our study, the remaining being benign adenomas (WHO classification 2004). We did not encounter any case of pituitary carcinoma. MGMT did not show any significant correlation with radiological grading and histology. CONCLUSION: The benign, aggressive, or malignant nature of PA can be effectively predicted with the help of IHC, such as Ki-67, p53, and MGMT. This helps in better patient management and predicts recurrences and prognosis. [ABSTRACT FROM AUTHOR]