Secondary Genetic Alterations in Extraskeletal Myxoid Chondrosarcoma.

Extraskeletal myxoid chondrosarcoma (EMC) is a rare mesenchymal neoplasm of uncertain histogenesis, characterized by recurrent gene fusions involving NR4A3 with various gene partners (EWSR1, TAF15, FUS, etc.). Although the impact of fusion variants has been linked to histology and prognosis, no study to date has comprehensively investigated the incidence and spectrum of secondary genetic alterations (SGAs) in EMC with regard to their association with fusion type and clinical impact.

Overlapping Morphologic and Immunophenotypic Features of Plasmacytoid Urothelial Carcinoma and Urothelial Carcinoma With Osteoclast-Like Giant Cells.

Osteoclast-rich undifferentiated carcinoma of the urinary tract, herein referred to as urothelial carcinoma with osteoclast-like giant cells (UCOGC), is an uncommon tumor currently classified under "poorly differentiated" urothelial carcinoma subtype composed of osteoclast-like giant cells intermixed with abundant mononuclear cells. Not infrequently, the mononuclear component exhibits eccentric nuclear localization reminiscent of plasmacytoid urothelial carcinoma. Given an index tumor where the mononuclear component of UCOGC showed prominent plasmacytoid histology and concomitant plasmacytoid urothelial carcinoma immunophenotype (aberrant loss of membranous E-cadherin with cytoplasmic p120 expression), herein we explore E-cadherin/p120 immunoreactivity in 14 UCOGC with sequencing performed on 4 tumors.

Lymphocytic myocarditis: A histopathologic definition and classification from the Society for Cardiovascular Pathology and Association for European Cardiovascular Pathology. I: Endomyocardial biopsy.

Background And Aim: Lymphocytic myocarditis has long been appreciated as a lymphocyte-predominant myocardial inflammation with resultant myocyte injury. However, current methods of diagnosis on endomyocardial biopsy (EMB) lead to inconsistent diagnoses. To improve patient care, the criteria for the diagnosis of lymphocytic myocarditis on endomyocardial biopsies have been revised to address shortcomings of the Dallas Criteria and European Society of Cardiology (ESC) criteria.

Indolent pediatric lymphomas/lymphoproliferative disorders: a report of the 2024 EA4HP/SH lymphoma workshop.

The boundaries between indolent neoplastic and reactive lymphoproliferations were discussed during the 2024 European Association for Haematopathology/Society for Hematopathology workshop in Dubrovnik, Croatia. Session 4 focused on the revision of indolent pediatric lymphoid neoplasms/lymphoproliferations. Forty-one cases were submitted, representing good examples of indolent pediatric lymphomas/lymphoproliferations and their diagnostic challenges.

Increased exacerbations and hospitalizations among PI*MZ compared to PI*MM individuals: an electronic health record analysis.

Background: The best described endotype of COPD is alpha-1 antitrypsin (AAT) deficiency, due to a genetic abnormality in the SERPINA1 gene. Common deficient PI variants are the Z and S variants. Homozygotes for the Z allele (PI*ZZ individuals) carry the genotype most commonly associated with severe AAT deficiency (AATD), but a highly prevalent endotype is the heterozygous state (PI*MZ individuals).

The morphological spectrum of Castleman disease and related disorders: a report from the Lymphoma Workshop of the 22nd Meeting of the European Association of Hematopathology.

Castleman disease (CD) is an intriguing and complicated group of local and systemic disorders mainly affecting lymph nodes with heterogeneous presentation and therapeutic needs. These disorders were the topic of Session 1 of the Lymphoma Workshop at the 2024 EA4HP in Dubrovnik, Croatia. In this report, we summarize the features of the 85 submitted cases and review the differential diagnosis, pitfalls, and advances for all CD subtypes.

Transcriptomic Profiling of Relapsed Rhabdomyosarcoma: Pre- and Post-Treatment Tissue Analysis Reveals Molecular Characteristics of Treatment Failure.

Background: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. Historically classified based on histology, advances in molecular profiling have allowed further sub-classification, which has improved risk stratification. Although molecular profiling has improved our understanding of disease progression and risk, the molecular evolution of therapy resistance in RMS remains poorly characterized.

Cytological Assessment of Metastatic Gastrointestinal Stromal Tumor in Ascitic Fluid.

Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms typically arising in the stomach and small intestine and rarely involving extra-gastrointestinal organs. While fine-needle aspiration (FNA) offers reliable diagnosis, exfoliation of GIST cells into body fluids is exceedingly rare and diagnostically challenging. We report a case of a 69-year-old male with metastatic GIST in ascitic fluid.

Artificial Intelligence-Based Digital Histologic Classifier for Prostate Cancer Risk Stratification: Independent Blinded Validation in Patients Treated With Radical Prostatectomy.

Purpose: Artificial intelligence (AI) tools that identify pathologic features from digitized whole-slide images (WSIs) of prostate cancer (CaP) generate data to predict outcomes. The objective of this study was to evaluate the clinical validity of an AI-enabled prognostic test, PATHOMIQ_PRAD, using a clinical cohort from the Cleveland Clinic.

Methods: We conducted a retrospective analysis of PATHOMIQ_PRAD using CaP WSIs from patients who underwent radical prostatectomy (RP) between 2009 and 2022 and did not receive adjuvant therapy.

Reactivity of carbonic anhydrase IX (CA IX) across the spectrum of renal cell carcinomas with sarcomatoid differentiation.

Carbonic anhydrase IX (CA IX) is traditionally considered to be an immunomarker of clear cell renal cell carcinoma (RCC). However, CA IX expression has also been documented in other RCCs subtypes. Discrimination between clear cell RCC and non-clear cell RCC is crucial for further patient management.

Urothelial carcinoma with osteoclast-like giant cells: An expanded immunohistochemical and molecular profile.

Objective: Osteoclast-rich undifferentiated carcinoma of the urinary tract, herein referred to as urothelial carcinoma with osteoclast-like giant cells (UCOGC), is a rare tumor currently classified under the "poorly differentiated urothelial carcinoma" subtype. This study aimed to evaluate the clinicopathologic, immunophenotypic, and molecular features of UCOGC to better characterize its origin and support its classification as a unique subtype.

Methods: There were 14 UCOGCs studied with immunohistochemistry/in situ hybridization and compared to urothelial carcinomas with trophoblastic differentiation (n = 6) and giant cell urothelial carcinomas (n = 5).

Soft tissue sarcoma with MN1 gene fusions: a report of three cases with aggressive clinical behavior.

Canonical MN1 fusions with either BEND2 or CXXC5 gene partners represent the molecular hallmark of astroblastoma, a stand-alone group among central nervous system (CNS) high-grade neuroepithelial tumors based on their distinct methylation profile. Outside the CNS, MN1 fusions have been rarely reported, mostly with nonrecurrent gene partners. Herein, we present three cases of soft tissue sarcomas harboring MN1 gene rearrangements, two of which had MN1 (exon 1)::CXXC5 (exon 2) gene fusion and the last had MN1 (exon 1)::ZFP64 (exon 2) gene fusion.

YAP, TAZ, and Hippo-Dysregulating Fusion Proteins in Cancer.

Gene fusions are well-known drivers of cancer and are potent targets for molecular therapy. An emerging spectrum of human tumors harbors recurrent and pathognomonic gene fusions that involve the transcriptional coactivator (which encodes the protein YAP) or its paralog (which encodes the protein TAZ). YAP and TAZ are frequently activated in cancer and are the transcriptional effectors of the Hippo pathway, a highly conserved kinase cascade that regulates diverse functions such as organ size, development, and homeostasis.

Genetic landscapes of breast tumors by next-generation sequencing with focus on less common types and genotype-phenotype correlations.

Next-generation sequencing (NGS) has transformed our understanding of oncogenic pathways and mutational processes underlying many breast tumors. Although large-scale NGS studies included mostly common invasive breast carcinomas, the genetic landscapes of several less common or rare special histologic types and other breast tumors have now also been elucidated. Many of these lesions harbor highly specific types of mutations or rearrangements/gene fusions, including invasive lobular carcinoma, tall cell carcinoma with reversed polarity, most salivary gland-like neoplasms, fibroepithelial neoplasms, and mesenchymal tumors such as fibromatosis, nodular fasciitis, and dermatofibrosarcoma protuberans.

Gut microbial conversion of dietary elderberry extract to hydrocinnamic acid improves obesity-associated metabolic disorders.

Obesity-associated metabolic disorders such as type 2 diabetes mellitus and metabolic dysfunction associated fatty liver disease are major global health concerns, yet current pharmacological treatments often present with major side-effects. Dietary interventions including polyphenol-rich foods offer a promising complementary option for obesity amelioration, but their efficacy is dependent on specific gut microbial metabolism and the underlying molecular mechanisms mostly remain elusive. Here, we demonstrated that dietary elderberry (Eld) extract abrogates the effects of an obesogenic diet in a gut microbiota-dependent manner, by preventing insulin resistance and reducing hepatic steatosis in mice.

Primary Ewing Sarcoma of the Kidney: Clinicopathologic and Molecular Study of 24 Patients Including a Rare EWSR1::ETV4 Fusion.

Primary Ewing sarcoma (ES) of the kidney is rare. We describe the clinicopathologic features of primary renal ES with emphasis on gene fusion partners. A multi-institutional study was conducted to obtain clinicopathologic data on primary ES of the kidney.

Responses to checkpoint inhibition in metastatic triple negative breast cancer driven by divergent myeloid phenotypes.

Background: Given the scarcity of effective therapeutic targets, metastatic triple negative breast cancer (mTNBC) has shorter survival times compared to other advanced breast cancer subtypes. Although chemo-immunotherapy with immune checkpoint inhibitors (ICIs) in PD-L1 mTNBC has shown promise, survival benefit remains modest. Therefore, it is crucial to gain improved insight into the mechanisms underlying response and resistance to checkpoint inhibition in mTNBC.

Germline pathogenic variants in DNA repair pathways: a key feature in a significant subset of translocation-associated sarcomas.

Translocation-associated sarcomas (TAS) are rare, phenotypically heterogeneous, with predisposition for young adults. We aimed to investigate the clinical impact of germline pathogenic/likely pathogenic (P/LP) variants in a diverse group of TAS and to conduct a comprehensive comparative analysis of clinicopathologic features, genomic alterations, and survival outcomes. A retrospective cohort of 426 TAS patients with both tumor and germline DNA sequencing was investigated for clinical actionability of P/LP variants, and potential impact on current screening guidelines and clinical interventions.

In vivo virulence of in native versus prosthetic left-sided valve endocarditis.

Objectives: infective endocarditis is commonly associated with invasive pathology and is worse in prosthetic valve endocarditis. In this study, we aim to examine virulence and pathological features of native and prosthetic valve infective endocarditis.

Methods: Between 2002 and 2020, 438 patients underwent surgery for left-sided endocarditis caused by at our center (59% native and 41% prosthetic valve endocarditis).

Magnetic Resonance Imaging at Second Surveillance Biopsy After Diagnosis in Patients With Grade Group 1 Prostate Cancer in the Canary Prostate Active Surveillance Study.

Purpose: No clear guidelines exist regarding MRI use after confirmatory biopsy during active surveillance. Our objective was to evaluate MRI performance after confirmatory biopsy in patients with vs without prior MRI-informed biopsy.

Materials And Methods: Patients in the Canary Prostate Active Surveillance Study with Gleason Grade Group (GG) 1 disease undergoing MRI-informed Biopsy 2, defined as second surveillance biopsy after diagnosis, were separated into prior vs no prior MRI-informed biopsy groups.