Endocrine Pathology最新文献

Tall cell papillary thyroid carcinoma (TC-PTC) is considered adverse histology. However, previous studies are confounded by inconsistent criteria and strong associations with other adverse features. It is therefore still unclear if TC-PTC represents an independent prognostic factor in multivariate analysis and, if it does, what criteria should be employed for the diagnosis. We retrospectively reviewed 487 PTCs from our institution (where we have historically avoided the prospective diagnosis of TC-PTC) for both the height of tall cells (that is if the cells were two, or three, times as tall as wide) and the percentage of tall cells. On univariate analysis, there was significantly better disease free survival (DFS) in PTCs with no significant tall cell component (< 30%) compared to PTCs with cells two times tall as wide (p = 0.005). The proportion of tall cells (30-50% and > 50%) was significantly associated with DFS (p = 0.012). In a multivariate model including age, size, vascular space invasion, and lymph node metastasis, the current WHO tall cell criteria, met by 7.8% of PTCs, lacked statistical significance for DFS (p = 0.519). However, in the subset of tumours otherwise similar to the American Thyroid Association (ATA) guidelines low-risk category, WHO TC-PTC demonstrated a highly significant reduction in DFS (p = 0.004). In contrast, in intermediate to high-risk tumours, TC-PTC by WHO criteria lacked statistical significance (p = 0.384). We conclude that it may be simplistic to think of tall cell features as being present or absent, as both the height of the cells (two times versus three times) and the percentage of cells that are tall have different clinical significances in different contexts. Most importantly, the primary clinical significance of TC-PTC is restricted to PTCs that are otherwise low risk by ATA guidelines.

Endocrine pathology comprises a spectrum of disorders originating in various sites throughout the body. Some disorders affect endocrine glands, and others arise from endocrine cells that are dispersed in non-endocrine tissues. Endocrine cells can broadly be classified as neuroendocrine, steroidogenic, or thyroid follicular cells; these three families have distinct embryologic origins, morphologic structure, and biochemical hormone synthetic pathways. Lesions affecting the endocrine system include developmental abnormalities, inflammatory processes that can be infectious or autoimmune, hypofunction with atrophy or hyperfunction caused by hyperplasia secondary to pathology in other sites, and neoplasia of many types. Understanding endocrine pathology requires knowledge of both structure and function, including the biochemical signaling pathways that regulate hormone synthesis and secretion. Molecular genetics has clarified sporadic and hereditary disease that is common in this field.

A variety of inflammatory conditions may directly involve the endocrine glands, leading to endocrine dysfunction that can cause severe consequences on patients' health, if left untreated. Inflammation of the endocrine system may be caused by either infectious agents or other mechanisms, including autoimmune and other immune-mediated processes. Not infrequently, inflammatory and infectious diseases may appear as tumor-like lesions of endocrine organs and simulate neoplastic processes. These diseases may be clinically under-recognized and not infrequently the diagnosis is suggested on pathological samples. Thus, the pathologist should be aware of the basic principles of their pathogenesis, as well as of their morphological features, clinicopathological correlates, and differential diagnosis. Interestingly, several systemic inflammatory conditions show a peculiar tropism to the endocrine system as a whole. In turn, organ-specific inflammatory disorders are observed in endocrine glands. This review will focus on the morphological aspects and clinicopathological features of infectious diseases, autoimmune disorders, drug-induced inflammatory reactions, IgG4-related disease, and other inflammatory disorders involving the endocrine system. A mixed entity-based and organ-based approach will be used, with the aim to provide the practicing pathologist with a comprehensive and practical guide to the diagnosis of infectious and inflammatory disorders of the endocrine system.

Struma ovarii is a well-known ovarian teratoma made up of benign thyroid tissue. These lesions demonstrate variable, normal architecture and normal thyroid immunohistochemical staining with positivity for TTF1, PAX8, and thyroglobulin. Though most are benign, some of these lesions can also present with a malignant component. Within this article, we review the most common diagnostic malignancies including papillary thyroid carcinoma, strumal carcinoid, highly differentiated follicular thyroid carcinoma, and other thyroid carcinomas. We additionally review the use of TTF1 staining to assist in differentiating these lesions from surrounding gynecologic epithelium, which is imperative in making such diagnoses. In highlighting these entities, we hope to provide practicing pathologists with an effective and concise review of these lesions to assist in more challenging cases of struma ovarii.

Anaplastic thyroid carcinoma (ATC) demonstrates a wide variety of morphologies and is characteristically associated with a differentiated thyroid carcinoma component. Heterologous differentiation is a rare, potentially challenging phenomenon in ATC, mostly observed as osteosarcomatous or chondrosarcomatous differentiation. We now describe a novel 'glomangiosarcoma-like' differentiation, review our archival experience from two institutions (UPMC, CC), and perform a systematic review for the prevalence of heterologous elements in ATC. The patient is a 57-year-old female who presented with 4.5 cm left thyroid, and 3.4 cm neck masses. Histologically, the thyroid demonstrated a differentiated high grade papillary thyroid carcinoma, tall cell and hobnail/micropapillary subtypes transitioning into an anaplastic component with spindled to ovoid cells with hemangiopericytoma-like vasculature showing CD34 positivity, variable muscle marker expression and pericellular lace-like type IV collagen deposition. The neck mass consisted solely of the latter morphology. Targeted next-generation sequencing was performed on high grade DTC and adjacent ATC from the thyroid as well as ATC from the neck metastasis. All three components shared BRAF^V600E, TERT promoter, and PIK3CA mutations confirming a clonal origin. Archival (UPMC: n = 150, CC: n = 74) and literature review showed no prior examples. Systematic review and meta-analysis of prevalence showed a baseline pooled prevalence (generalized linear mixed model) of heterologous elements of any type to be 1.6% (95% confidence interval: 1.0-2.6%) for studies where this was specifically addressed. ATC with glomangiosarcoma-like heterologous differentiation is a rarity among an already rare morphologic category with unique diagnostic pitfalls.

The assessment of cell differentiation in endocrine neoplasms involves not only the identification of a cell's structure and expression of specific transcription factors which regulate that cell, but also the identification of hormones and/or enzymes involved in hormone synthesis. The importance of this functional characterization is emphasized by the fact that the hormones serve as biomarkers for clinical surveillance to identify persistence, recurrence, or progression of disease. Sometimes, unusual patterns of hormone expression lead to unexpected clinical signs and symptoms. Loss of differentiated hormone production can be a sign of dedifferentiation as a tumor becomes more aggressive. In addition to prognostic information, cell differentiation can be predictive, since differentiated endocrine cells express targets for therapy, such as the sodium iodide symporter in thyroid cancers and somatostatin receptors in neuroendocrine tumors. The salient features of differentiation in the three main types of endocrine cells can be used to determine prognosis and to tailor management of patients with endocrine neoplasms.

Endocrine neoplasia represents an increasingly broad spectrum of disorders. Endocrine neoplasms range from incidental findings to potentially lethal malignancies. In this paper, we cover the impact of pathology in the interpretation of the clinic-pathological, genetic, and radiographic features underpinning these neoplasms. We highlight the critical role of multidisciplinary interactions in structuring a rational diagnostic and efficient therapeutic plan and emphasize the role of histopathological input in decision-making. In this context, standardized pathology reporting and second opinion endocrine pathology review represent relevant tools to improve the overall diagnostic workup of patients affected by endocrine tumors in every specific scenario. In fact, although a relevant proportion of cases may be correctly identified based on clinical presentation and biochemical/imaging investigations, a subset of cases presents with atypical findings that may lead to an inappropriate diagnosis and treatment plan based on a wrong pathological diagnosis if all pieces of the puzzle are not correctly considered. Pathologists have a responsibility to actively guide clinicians before and during surgical procedures to prevent unnecessary interventions. In all areas of endocrine pathology, pathologists must understand the complexity of tissue preservation and assay sensitivities and specificities to ensure the optimal quality and interpretation of diagnostic material. Finally, pathologists are central actors in tumor tissue biobanking, which is an expanding field in oncology that should be promoted while adhering to strict ethical and methodological standards.