Endocrine Pathology最新文献

Unlike somatotroph tumors, the data on correlates of tumor granulation patterns in functional TPIT lineage pituitary neuroendocrine tumors (corticotroph tumors) have been less uniformly documented in most clinical series. This study evaluated characteristics of 41 well-characterized functional corticotroph tumors consisting of 28 densely granulated corticotroph tumors (DGCTs) and 13 sparsely granulated corticotroph tumors (SGCTs) with respect to preoperative clinical and radiological findings, tumor proliferative activity (including mitotic count and Ki-67 labeling index), and postoperative early biochemical remission rates. The median (interquartile range (IQR)) tumor size was significantly larger in the SGCT group [16.00 (16.00) mm in SGCT vs 8.5 (9.75) mm in DGCT, p = 0.049]. T2-weighted signal intensity and T2 intensity (quantitative) did not yield statistical significance based on tumor granulation; however, the T2 intensity-to-white matter ratio was significantly higher in SGCTs (p = 0.049). The median (IQR) Ki-67 labeling index was 2.00% (IQR 1.00%) in the DGCT group and 4.00% (IQR 7.00%) in the SGCT group (p = 0.043). The mitotic count per 2 mm² was higher in the SGCT group (p = 0.001). In the multivariate analysis, the sparse granulation pattern (SGCT) remained an independent predictor of a lower probability of early biochemical remission irrespective of the tumor size and proliferative activity (p = 0.012). The current study further supports the impact of tumor granulation pattern as a biologic variable and warrants the detailed histological subtyping of functional corticotroph tumors as indicated in the WHO classification of pituitary neuroendocrine tumors. More importantly, the assessment of the quantitative T2 intensity-to-white matter ratio may serve as a preoperative radiological harbinger of SGCTs.

Bilateral macronodular adrenocortical disease (BMAD) is an uncommon cause of Cushing's syndrome leading to bilateral macronodules. Isolated BMAD has been classified into three molecular groups: patients with ARMC5 alteration, KDM1A alteration, and patients without known genetic cause. The aim of this study was to identify by NGS, in a cohort of 26 patients with BMAD, the somatic alterations acquired in different nodules after macrodissection from patients with germline ARMC5 or KDM1A alterations and to analyze potential somatic alterations in a panel of five other genes involved in adrenal pathology (GNAS, PDE8B, PDE11A, PRKAR1A, and PRKACA). Twenty-three patients (7 ARMC5, 3 KDM1A, and 13 BMAD with unknown genetic cause) were analyzable. Somatic ARMC5 or KDM1A events were exclusively observed in patients with germline ARMC5 and KDM1A alterations, respectively. Six out of 7 ARMC5 patients have a high heterogeneity in identified somatic events, whereas one ARMC5 and all KDM1A patients show a loss of heterozygosity (LOH) in all nodules. Except for passenger alterations of GNAS, no genetic alteration susceptible to causing the disease was detected in the BMAD with unknown genetic cause. Our study reinforces our knowledge of the somatic genetic heterogeneity of ARMC5 and the somatic homogeneity of KDM1A. It reveals the absence of purely somatic events in these two genes and provides a new tool for detecting KDM1A alterations by FISH 1p36/1q25.

The classification of thyroid nodules, particularly those with a follicular growth pattern, has significantly evolved. These tumors, enriched with RAS or RAS-like mutations, remain challenging for pathologists due to variables such as nuclear atypia, invasion, mitotic activity, and tumor necrosis. This review addresses the histological correlates of benign, low-risk, and malignant RAS-mutant thyroid tumors, as well as some difficult-to-classify follicular nodules with worrisome features. One prototypical RAS-mutant nodule is non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). The assessment of nuclear characteristics in encapsulated/well-demarcated non-invasive RAS-mutant follicular-patterned tumors helps distinguish between follicular thyroid adenoma (FTA) and NIFTP. Despite this straightforward concept, questions about the degree of nuclear atypia necessary for the diagnosis of NIFTP are common in clinical practice. The nomenclature of follicular nodules lacking clear invasive features with increased mitotic activity, tumor necrosis, and/or high-risk mutations (e.g., TERT promoter or TP53) remains debated. Invasion, particularly angioinvasion, is the current hallmark of malignancy in RAS-mutant follicular-patterned neoplasms, with follicular thyroid carcinoma (FTC) as the model. Assessing the tumor interface is critical, though full capsule evaluation can be challenging. Multiple levels and NRASQ61R-specific immunohistochemistry can aid in identifying invasion. Controversies around vascular invasion persist, with ancillary stains like CD31, ERG, and CD61 aiding in its evaluation. Moreover, the review highlights that invasive encapsulated follicular variant papillary thyroid carcinoma (IEFVPTC) is closely associated with FTC, suggesting the need for better nomenclature. The concept of "high-grade" differentiated carcinomas, applicable to FTC or IEFVPTC with necrosis and/or high mitotic activity, is also discussed.

Ileal (I) and pancreatic (Pan) neuroendocrine tumors (NETs) are among the most common digestive neuroendocrine neoplasms (NENs). Coexisting NETs at both sites are rare, and establishing the primary or metastatic nature of the two lesions may be crucial for the appropriate treatment. We reviewed all the clinical reports of patients with INETs or PanNETs, diagnosed and treated in our ENETS Center of Excellence between 2012 and 2022. We selected patients with a history of synchronous or metachronous neuroendocrine (NE) lesions at the ileum and pancreas. For those with available histological samples from both sites, an immunohistochemistry (IHC) analysis for CDX2, Islet1, and serotonin has been performed. We found seven patients with NET in both the ileum and pancreas. F to M ratio was 4:3, and the median age at first diagnosis was 54 years (42-79). Five cases had synchronous lesions; in 2 cases, PanNETs were diagnosed respectively 8 and 56 months, after INETs. In four patients, with available histological samples from both the sites, a pathologic review and the IHC analysis have been performed, identifying three different scenarios: (i) primary INET metastatic to the pancreas, (ii) primary PanNET metastatic to the ileum, and (iii) synchronous primary PanNET and INET. In our experience, coexisting ileal and pancreatic NENs are rare occurrences. A multidisciplinary evaluation case-by-case and, whenever feasible, a comprehensive histopathological examination are needed to distinguish between metastatic and primary disease, in order to properly treat the patient.

Fatty acid-binding protein 4 (FABP4), a fatty acid transporter that coordinates lipid metabolism, is reported to exert a tumorigenic role in certain cancers. We investigated the effects of FABP4 in the carcinogenesis of thyroid cancer. Bioinformatics data about FABP4 in thyroid cancer were collected from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Sixteen paired papillary thyroid cancer (PTC) tissues from Taipei Medical University (TMU) were gathered, and commercial thyroid cancer complementary (c)DNA and tissue arrays were purchased to measure FABP4 messenger (m)RNA and protein levels. By analyzing data from the GEO and TCGA, we showed that FABP4 mRNA was reduced in PTC and follicular thyroid carcinoma (FTC). In addition, a lower FABP4 mRNA level in PTC was associated with poor clinical parameters and outcomes in the TCGA database. Moreover, FABP4 transcripts and proteins were downregulated in PTC and FTC, and its mRNA expression was associated with PTC staging in clinical specimens. In the TCGA database and TMU cohort, FABP4 mRNA levels were associated with thyroglobulin (r = 0.511 and r = 0.656, respectively), thyroid peroxidase (r = 0.612 and r = 0.909, respectively), and sodium iodide symporter (r = 0.485 and r = 0.637, respectively) transcripts. In conclusion, FABP4 mRNA and protein levels were reduced in PTC and FTC, and may be used as a potential indicator for thyroid cancer evolution in clinical settings. Further, well-designed research to dissect the molecular mechanism of FABP4 in modulating thyroid carcinogenesis is needed.