Virchows Archiv最新文献

This report documents the first case of a conventional (bone-type) giant cell tumor of the larynx, in which the diagnosis was confirmed by molecular genetic analysis. A 50-year-old non-smoking man experienced progressive hoarseness lasting for 3 months. Imaging showed a 40-mm tumor arising from the right thyroid cartilage. The total laryngectomy was performed. Grossly, the tumor was solid and whitish, with areas of hemorrhage. Microscopically, the tumor consisted of a biphasic population with mononuclear cells with round to oval nuclei, small nucleoli, and pale eosinophilic cytoplasm admixed with evenly distributed dispersed osteoclast-like giant cells. Immunohistochemically, the neoplastic mononuclear cells expressed diffusely vimentin and p63 and focally SATB2. Admixed mononuclear histiocytes coexpressed CD68 and CD163, while the osteoclast-like giant cells showed only CD68 expression. Most importantly, all mononuclear tumor cells showed strong nuclear expression of anti-histone H3.3 G34W antibody. Subsequent next-generation sequencing confirmed the missense mutation of gene H3-3A: c.103G>T (p.Gly35Trp).

The majority of mastocytosis cases are characterized by an activating mutation in the KIT gene in codon 816. The detection of this alteration is of importance for proper diagnostic workup. Therefore, reliable and sensitive methods for the detection of KIT Codon 816 hotspot mutations in various types of patient samples are required. Since mutated cancer genes are often overexpressed, we evaluated the feasibility and sensitivity of KIT p.D816V detection by analysing mRNA/cDNA instead of genomic DNA. From 80 bone marrow trephines harboring a KIT p.D816 mutation, seven were only mutated by mRNA/cDNA pyrosequencing and 11 only by digital PCR analysis of genomic DNA. These results clearly demonstrate that detection of clinically relevant mutations in mRNA extracted from routinely processed decalcified archival bone marrow trephines is not only possible in a reliable fashion but under many circumstances advantageous. This enables the direct correlation of genomic data with high-quality morphological evaluation.

Sclerosing mucoepidermoid carcinoma (SMEC) of the salivary glands is a rare variant of low-grade mucoepidermoid carcinoma with scanty cellular atypia characterized by marked fibrosis/sclerosis and a rich inflammatory infiltrate. Herein, we report 25 unpublished cases of SMEC, two of them with prominent eosinophilia (2/25; 8%) and three with abundant IgG4-positive plasma cells (3/25; 12%). In our series of salivary SMEC, molecular analysis using fluorescence in situ hybridization (FISH) and/or next-generation sequencing (NGS) provided evidence of MAML2 gene rearrangement in 18 cases of the 21 analyzable cases tested (86%), while this gene locus was intact in 3 cases (14%). This study focuses on the diagnostic criteria of salivary SMEC given its challenge of abundant collagenous stroma, minimal residual neoplastic areas, and inconspicuous mucous cells. Follow-up data of our cases indicate that salivary SMECs have favorable outcomes. Molecular analysis for MAML2 gene rearrangement suggests that SMECs of salivary glands represent a rare variant of conventional low-grade MECs of salivary glands. In contrast, SMECs of the thyroid gland are genetically distinct from salivary-type thyroid MECs.

This review article focuses on the various primary osseous tumors of the orbit. Due to overlapping clinical, radiologic, and histologic features, differentiating these entities can pose significant challenges diagnostically. In this review, emphasis is placed on key distinguishing clinical, morphologic, immunophenotypic, and molecular characteristics. Also described are important prognostic details, recurrence risks, and the gold standard treatment methods for each entity. Relevant genetic syndrome associations are additionally covered. Orbital bone entities discussed include osteoma, osteoid osteoma, osteoblastoma, ossifying fibroma, fibrous dysplasia, aneurysmal bone cyst, osteosarcoma, Ewing sarcoma, and mesenchymal chondrosarcoma.

The classification of TFEB-altered renal cell carcinoma (RCC) has been revised to include TFEB-rearranged RCC and TFEB-amplified RCC in the 2022 World Health Organization (WHO) Classification of Tumors of the Urinary System. Given the wide spectrum of TFEB-altered RCC in terms of morphology and clinical behavior, an accurate diagnosis is challenging yet crucial, particularly in aggressive cases. Moreover, the concurrence of TFEB gene rearrangement and amplification/gene copy number (GCN) gains was also observed, but there was limited knowledge of these cases. We presented three TFEB-rearranged RCC cases, one TFEB-amplified RCC case, and one case of concomitant TFEB-rearranged and -amplified RCC, comparing the similarities and differences among these three subgroups. Furthermore, we summarized the clinicopathological and molecular features of TFEB-rearranged RCC concomitant with TFEB amplification/GCN gains from the literature and the present study. TFEB-altered RCCs exhibit significant heterogeneity in morphology and clinical behavior while displaying similar immunohistochemical profiles, including positive staining for Melan-A, PAX8, and CD117, and negative staining for CK7. A typical biphasic "rosette-like" morphology has been observed in a proportion of TFEB-rearranged RCC concomitant with TFEB amplification/GCN gains, which has been noted in TFEB-rearranged RCC, but not in cases with only TFEB amplification. Notably, TFEB-rearranged RCCs concomitant with TFEB amplification/GCN gains tend to be aggressive, in contrast to the often indolent nature of TFEB-rearranged cases, irrespective of the extent of TFEB gene copy increase. Therefore, a TFEB FISH assay is essential for unclassified RCC cases that exhibit melanocytic marker expression, and fluorescent signals should be counted and interpreted acurrately.

Ki-67 index (Ki-67i) is integral to the grading of many tumours. There remains considerable variability across pathologists in methods used to determine Ki-67i and in their results. Manual counting (or "eyeballing") is widely used, but digital pathology tools such as web-based image analysis and artificial intelligence-assisted cell detection software have become available in daily pathology practice. This study aims to compare the accuracy and efficiency of manual and two digital methods of Ki-67i determination. H&E and Ki-67 immunohistochemical (IHC) slides/images of 12 gastrointestinal neuroendocrine tumours (GI-NETs) were provided to 8 pathologists to evaluate Ki-67i via manual estimation (ME; the "past"), web-based image analysis using cellular segmentation (AI4Path.ca; the "present"), and software-based image analysis with built-in AI algorithms (QuPath; the "future"). Data collected include Ki67i, time expended, total cells counted, and pathologists' confidence level in the reported result. Deviation of Ki-67i from a gold standard result (GS) was analyzed using multiple linear regression, and results were compared via paired t test. Our results found no statistically significant differences in Ki-67i deviation from GS when comparing ME and AI4P methods for all 12 cases. The QP Ki-67i detection accuracy varied significantly. ME was the method with the least time expenditure. Junior pathologists are less confident in ME. Grading consensus was comparable among all three methods. These findings suggest that while digital pathology can confer increased Ki-67i accuracy in some cases of GI-NETs, higher time expenditure and proper hotspot selection may represent barriers to the adoption of digital pathology methods in the future.

In autopsy practice, the thickness of ventricular walls is one of the parameters used to identify cardiac hypertrophy. The presented study aimed to compare ante- and postmortem measurements of ventricular wall thickness, (i) to determine a postmortem standardized localization and dissection method for ventricular wall measurements, and (ii) to determine the ability of postmortem measurements in recognition of antemortem hypertrophy. A single-center prospective study was conducted at the Institute of Legal Medicine in Hamburg, Germany. Sixty hearts were dissected alternating by the inflow-outflow or short-axis method, and the ventricular walls were measured at different locations and compared with the echocardiographic values of the end-diastolic phase during life of these individuals. The results showed measurement differences between the autoptic and echocardiographic values-for the left ventricle between 3.3 and 5.2 mm, for the right ventricle between 0.2 and 1.1 mm, and for the septum between 1.3 and 1.4 mm. Diagnostic performance of recognizing antemortem hypertrophy with postmortem measurement was poor, except for measuring the right ventricle and septum with the short-axis method (area under the ROC curve of 0.72 and 0.82, respectively). According to the results, cardiac changes may occur postmortem and need to be considered when used for diagnosing cardiac pathology. The postmortem diagnosis of left or right ventricular hypertrophy should always be made in conjunction with other, particularly cardiac, autopsy findings. An autoptic diagnosis of hypertrophy solely by a ventricular wall thickness > 15 mm or > 5 mm alone is not sufficient.