Endocrine Pathology最新文献

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.

The pathology of neoplasia tends to focus on the tumor that requires characterization, grading, and staging. However, nontumorous tissue surrounding the lesion can also provide information, particularly about pathogenetic mechanisms. In endocrine tissues, this takes the form of precursor lesions that characterize several genetic predisposition syndromes. In addition, because of the unique functional aspects of endocrine neoplasia, the nontumorous tissue provides evidence of hormone excess, with hyperplasia and/or atrophy and other involutional changes allowing the pathologist to confirm both hormone function by the tumor and the effects of medical therapies. In this article, we review the various clinically relevant features that should be assessed and reported to enhance clinical management of patients with endocrine neoplasms. For example, in thyroid there may be inflammatory thyroiditis or goiter of various etiologies; there may be C-cell hyperplasia either as a preneoplastic lesion in patients with genetic predisposition to medullary thyroid carcinoma or as a reactive phenomenon. Drug-induced changes can be seen in thyroid and adrenal cortex. In neuroendocrine tissues, the nontumorous tissues may show precursor lesions such as endocrine cell hyperplasia/dysplasia; there may be related or unrelated hyperplastic or neoplastic lesions. Some tissues, such as pituitary corticotrophs and adrenal cortex, develop changes that reflect feedback suppression by hormone excess that can serve as biomarkers of tumor functionality and provide enhanced clinicopathologic correlates.

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a low-risk thyroid tumor with a favorable prognosis. Nonetheless, differentiating NIFTP from other thyroid tumors remains challenging, necessitating reliable diagnostic markers. This study is aimed at discovering NIFTP-specific mRNA markers through RNA sequencing analysis of thyroid tumor tissues. We performed mRNA expression profiling for 74 fresh frozen thyroid tissue samples, including NIFTP and benign and malignant follicular-cell-derived tumors. NIFTP/malignant tumors showed 255 downregulated genes and 737 upregulated genes compared to benign tumors. Venn diagram analysis revealed 19 significantly upregulated and 7 downregulated mRNAs in NIFTP. Akaike information criterion analysis allowed us to select OCLN, ZNF423, LYG1, and AQP5 mRNA markers. We subsequently developed a predictive model based on logistic regression analysis using these four mRNAs, which we validated in independent samples (n = 90) using a qRT-PCR assay. This model demonstrated high accuracy in predicting NIFTP in discovery dataset (AUC (area under the receiver operating characteristic) = 0.960) and the validation dataset (AUC = 0.757). Our results suggest that OCLN, ZNF423, LYG1, and AQP5 mRNA markers might serve as reliable molecular markers for identifying NIFTP among other thyroid tumors, ultimately aiding in accurate diagnosis and management of NIFTP patients.

Amphicrine carcinomas are epithelial neoplasms composed of cells with co-existing exocrine-neuroendocrine phenotype and are challenging lesions from both diagnostic and therapeutic perspectives.Here, we report the case of a 63-year-old male patient with a gastric nodule that was endoscopically biopsied, revealing histological features of a type 3 well-differentiated gastric neuroendocrine tumor (NET). At imaging, the lesion was single and limited to the stomach, but did not present ^In-111Octreotide uptake, despite SSTR2A immunohistochemical expression. The patient underwent a wedge resection of the gastric wall, with a final pathological diagnosis of amphicrine carcinoma with pancreatic acinar cell and neuroendocrine features (pT1b). Predictive immunohistochemistry showed microsatellite stability and negative HER2 status. Hotspot targeted deep sequencing of 57 genes showed no somatic mutation, in agreement with the low mutational burden reported for gastric amphicrine carcinomas. Due to a low stage of the tumor and the poor performance status of the patient, no additional oncological treatment was administered. The patient was disease-free after 18 months.This unusual case highlights the importance of considering amphicrine carcinoma in the diagnostic work-up of gastric type 3 NET. This can be done by including in the immunohistochemical panel non-neuroendocrine markers, such as the pancreatic acinar cell and glandular ones. Correct pathological diagnosis is pivotal to determine the appropriate staging (NET vs exocrine one) for surgical and oncological management.