Endocrine Pathology最新文献

The introduction of Ki67 immunohistochemistry in the work-up of neuroendocrine neoplasms (NENs) has opened a new approach for their diagnosis and prognostic evaluation. Since the first demonstration of the prognostic role of Ki67 proliferative index in pancreatic NENs in 1996, several studies have been performed to explore its prognostic, diagnostic, and predictive role in other neuroendocrine and endocrine neoplasms. A large amount of information is now available and published results globally indicate that Ki67 proliferative index is useful to this scope, although some differences exist in relation to tumor site and type. In gut and pancreatic NENs, the Ki67 proliferative index has a well-documented and accepted diagnostic and prognostic role and its evaluation is mandatory in their diagnostic work-up. In the lung, the Ki67 index is recommended for the diagnosis of NENs on biopsy specimens, but its diagnostic role in surgical specimens still remains to be officially accepted, although its prognostic role is now well documented. In other organs, such as the pituitary, parathyroid, thyroid (follicular cell-derived neoplasms), and adrenal medulla, the Ki67 index does not play a diagnostic role and its prognostic value still remains a controversial issue. In medullary thyroid carcinoma, the Ki67 labelling index is used to define the tumor grade together with other morphological parameters, while in the adrenal cortical carcinoma, it is useful to select patients to treated with mitotane therapy. In the present review, the most important information on the diagnostic, prognostic, and predictive role of Ki67 proliferative index is presented discussing the current knowledge. In addition, technical issues related to the evaluation of Ki67 proliferative index and the future perspectives of the application of Ki67 immunostaining in endocrine and neuroendocrine neoplasms is discussed.

Thorough gross examination and appropriate sampling of the thyroidectomy specimens are fundamental to the diagnosis and clinical risk management of patients. This study aims to investigate the frequency and clinical significance of initially unsampled microscopic thyroid carcinomas in total thyroidectomy specimens with presumed benign multinodular thyroid disease. Seventy-two total thyroidectomy specimens belonging to multinodular goiter patients were randomly selected and included in this prospectively designed study. Inclusion criteria were set as no suspicion of malignancy before surgery as well as lack of intra-parenchymal primary thyroid carcinoma after histopathological evaluation of slides generated from initial sampling. Subsequently, the remaining thyroidectomy specimens were submitted for microscopic examination and sign-outs were finalized following the microscopic examination of the entire thyroid tissue. Microcarcinomas, with a maximum diameter of 3.5 mm, were detected in 29 cases (40.2%) after the whole gland sampling. Although most of these tumors were low-risk papillary microcarcinomas confined to the thyroid, one specimen also showed a medullary microcarcinoma measuring 1.5 mm. Three had micrometastatic nodal disease. There was no local recurrence or distant metastatic disease during the follow-up (mean 51.4 months). This study further supports microscopic carcinomas, including papillary microcarcinoma, and medullary microcarcinoma might stay hidden in thyroidectomy specimens. Increased glandular weight, male gender, and advanced age were significant risk factors in the detection of microcarcinomas in this series. While each multinodular thyroidectomy specimen is unique, we recommend dynamic extensive sampling (rather than bare-minimum approach) strategy based on careful gross and initial histologic examination findings as well as by taking into consideration risk factors.

Hereditary pituitary tumorigenesis is seen in a relatively small proportion (around 5%) of patients with pituitary neuroendocrine tumors (PitNETs). The aim of the current review is to describe the main clinical and molecular features of such pituitary tumors associated with hereditary or familial characteristics, many of which have now been genetically identified. The genetic patterns of inheritance are classified into isolated familial PitNETs and the syndromic tumors. In general, the established genetic causes of familial tumorigenesis tend to present at a younger age, often pursue a more aggressive course, and are more frequently associated with growth hormone hypersecretion compared to sporadic tumors. The mostly studied molecular pathways implicated are the protein kinase A and phosphatidyl-inositol pathways, which are in the main related to mutations in the syndromes of familial isolated pituitary adenoma (FIPA), Carney complex syndrome, and X-linked acrogigantism. Another well-documented mechanism consists of the regulation of p27 or p21 proteins, with further acceleration of the pituitary cell cycle through the check points G1/S and M/G1, mostly documented in multiple endocrine neoplasia type 4. In conclusion, PitNETs may occur in relation to well-established familial germline mutations which may determine the clinical phenotype and the response to treatment, and may require family screening.

The past decade has brought significant advances in our understanding of the molecular mechanisms of thyroid carcinogenesis. Among thyroid carcinomas, the most successful class of targeted therapeutics appears to be selective kinase inhibitors. Actionable kinase fusions arise in around 10-15% of cases of thyroid cancer, a significant subset. A cohort of molecular testing platforms, both commercial and laboratory-derived, has been introduced into clinical practice to identify patients with targetable tumors, requiring pathologists to develop an integrative approach that utilizes traditional diagnostic cytopathology and histopathology, immunohistochemistry, and cutting-edge molecular assays for optimal diagnostic, prognostic, and therapeutic efficiency. Furthermore, there has been increasing scrutiny of the clinical behavior of kinase fusion-driven thyroid carcinoma (KFTC), still regarded as papillary thyroid carcinomas, and in characterizing molecular predictors of kinase inhibitor resistance with an aim to establish standardized, evidence-based treatment regimens. This review presents an overview of the current literature on the clinicopathologic and molecular features of KFTC as well as the latest investigational progress and encountered challenges for this unique subset of thyroid neoplasias.