Benign metastasizing fumarate hydratase (FH)-deficient uterine leiomyomas: clinicopathological and molecular study with first documentation of multi-organ metastases
AbstractLeiomyoma is the most prevalent benign tumor of the female reproductive system. Benign metastasizing leiomyoma (BML) is a rare phenomenon that presents at distant sites, typically the lungs, exhibiting histopathological features similar to the primary uterine tumor in the absence of malignancy features in both. Fumarate hydratase-deficient uterine leiomyoma (FH-d UL) is an uncommon subtype among uterine smooth muscle tumors (0.5 –2%), showing distinctive histomorphology andFH inactivation. The majority of FH-d ULs are sporadic, caused by somaticFH inactivation, while a minority of cases occur in the context of th...
Source: Virchows Archiv - April 20, 2024 Category: Pathology Source Type: research

Atrophic changes in thyroid tumors are strong indicators of underlying DICER1 mutations: a bi-institutional genotype –phenotype correlation study
AbstractSomatic and biallelicDICER1 mutations are reported in subsets of thyroid tumors, supporting the role of this gene in thyroid tumor development. As recent studies have brought attention to macrofollicular patterns, atrophic changes, and papillary structures as being associated withDICER1 mutations, we sought to explore these observations in a bi-institutional cohort. A total of 61 thyroid lesions (54 tumors and 7 cases of thyroid follicular nodular disease; TFND), including 26DICER1 mutated and 35DICER1 wildtype controls were subjected to histological re-investigation and clinical follow-up.DICER1-mutated lesions sh...
Source: Virchows Archiv - April 19, 2024 Category: Pathology Source Type: research

Correction to: Multicenter evaluation of an automated, multiplex, RNA-based molecular assay for detection of ALK, ROS1, RET fusions and MET exon 14 skipping in NSCLC
(Source: Virchows Archiv)
Source: Virchows Archiv - April 19, 2024 Category: Pathology Source Type: research

Metastatic cutaneous squamous cell carcinoma accounts for nearly all squamous cell carcinomas of the parotid gland
AbstractPrimary squamous cell carcinoma of the parotid gland (pSCCP) has long been recognized as a separate entity and is included in the WHO classifications of salivary gland tumors. However, it is widely accepted among head and neck pathologists that pSCCP is exceptionally rare. Yet, there are many publications describing series of pSCCP and data from SEER and other cancer register databases indicate erroneously an increasing incidence of pSCCP. Importantly, pSCCP and metastatic (secondary) squamous cell carcinoma to the parotid gland (mSCCP) have nearly identical histological features, and the diagnosis of pSCCP should ...
Source: Virchows Archiv - April 17, 2024 Category: Pathology Source Type: research

Evaluation of the prognostic potential of histopathological subtyping in high-grade serous ovarian carcinoma
AbstractHigh-grade serous ovarian carcinoma (HGSOC) can be categorized into four gene expression-based subtypes, with supposedly distinct prognoses and treatment responses. Murakami et al. translated these gene expression-based subtypes into the histopathological mesenchymal, immunoreactive, solid and proliferative, and papilloglandular subtypes, showing differences in survival outcomes. Miyagawa et al. refined these criteria to improve the interobserver concordance. The current retrospective study evaluated the interobserver variability and the prognostic differences between the histopathologic subtypes using the criteria...
Source: Virchows Archiv - April 16, 2024 Category: Pathology Source Type: research

Familial syndromes associated with testicular and paratesticular neoplasms: a comprehensive review
AbstractA syndromic association between a subset of testicular/paratesticular neoplasms is well established. Such examples include Carney complex and large cell calcifying Sertoli cell tumor, Peutz-Jeghers syndrome and intratubular large cell hyalinizing Sertoli cell neoplasia, and VHL syndrome and clear cell papillary cystadenoma of the epididymis.However, recent studies proposed potential novel links between some testicular and paratesticular neoplasms with certain tumor syndromes. While more studies are still needed to solidify these associations, recent research suggests that a subset of Leydig cell tumors may arise in...
Source: Virchows Archiv - April 15, 2024 Category: Pathology Source Type: research

CCN2/CTGF expression does not correlate with fibrosis in myeloproliferative neoplasms, consistent with noncanonical TGF- β signaling driving myelofibrosis
AbstractThe classicalBCR::ABL1-negative myeloproliferative neoplasms (MPN) form a group of bone marrow (BM) diseases with the potential to progress to acute myeloid leukemia or develop marrow fibrosis and subsequent BM failure. The mechanism by which BM fibrosis develops and the factors that drive stromal activation and fibrosis are not well understood. Cellular Communication Network 2 (CCN2), also known as CTGF (Connective Tissue Growth Factor), is a profibrotic matricellular protein functioning as an important driver and biomarker of fibrosis in a wide range of diseases outside the marrow. CCN2 can promote fibrosis direc...
Source: Virchows Archiv - April 11, 2024 Category: Pathology Source Type: research

POU2F3-expressing intraepithelial small-cell carcinoma with mixed small-cell carcinoma and conventional-type urothelial carcinoma of the urinary bladder
AbstractBased on lineage-specific transcription factors, small-cell neuroendocrine carcinoma (SmCC) of the urinary bladder has recently been subtyped into three molecular subtypes: ASCL1, NEUROD1 and POU2F3. The latter is a master transcriptional regulator of tuft cells (TCs) which are rare solitary cells found in various mucosal epithelia such as the gastrointestinal tract, but which have not been reported in the bladder. The POU2F3 subtype shows low or absent neuroendocrine marker expression. A case of mixed SmCC and conventional-type urothelial carcinoma (CUC) of the urinary bladder with POU2F3-expressing intraepithelia...
Source: Virchows Archiv - April 11, 2024 Category: Pathology Source Type: research

Determining the clinical significance of pathological findings in prostate cancer
(Source: Virchows Archiv)
Source: Virchows Archiv - April 11, 2024 Category: Pathology Source Type: research

Scoring PD-L1 Expression in Urothelial Carcinoma: An International Multi-Institutional Study on Comparison of Manual and Artificial Intelligence Measurement Model (AIM-PD-L1) Pathology Assessments
AbstractAssessing programmed death ligand 1 (PD-L1) expression on tumor cells (TCs) using Food and Drug Administration-approved, validated immunoassays can guide the use of immune checkpoint inhibitor (ICI) therapy in cancer treatment. However, substantial interobserver variability has been reported using these immunoassays. Artificial intelligence (AI) has the potential to accurately measure biomarker expression in tissue samples, but its reliability and comparability to standard manual scoring remain to be evaluated. This multinational study sought to compare the %TC scoring of PD-L1 expression in advanced urothelial car...
Source: Virchows Archiv - April 4, 2024 Category: Pathology Source Type: research

N-myc downstream –regulated gene 1 can promote vasculogenic mimicry and angiogenesis in urothelial carcinoma
This study aims to evaluate the role of intra-tumor microvessel density (MVD) (as a surrogate measure of angiogenesis), VM, and NDRG1 in UC and their correlation with different clinicopathologic features, then assess the correlation between them in UC. Sixty specimens of UC of the bladder were included. PAS-CD31 immunohistochemical double staining method was used to evaluate the intra-tumor MVD and VM. Immunohistochemical expression of NDRG1 was also examined. VM and NDRG1 expression were detected in 41.7% and 83.3% of UC specimens respectively. The mean of intr a-tumor MVD, VM area, and NDRG1 was significantly higher in t...
Source: Virchows Archiv - April 2, 2024 Category: Pathology Source Type: research

Nuclear morphological atypia in biopsy accurately reflects the prognosis of myxoid liposarcoma
In this study, we determined whether nuclear morphology may be used to predict the prognosis of MLS in primary biopsy specimens. Two pathologists evaluated nuclear morphology using the modified WHO/ISUP and Fuhrman grades. Survival analyses were performed by grouping nuclear high- and low-grades. We examined 53 MLS cases, which included 29 (54.7%) male and 24 (45.3%) female patients with a median age of 46  years (interquartile range, 37 − 60). In total, 7 (13.2%) and 16 (30.2%) cases were assigned to the high nuclear grade group based on the modified WHO/ISUP and Fuhrman gradings, respectively. Survival analyses re...
Source: Virchows Archiv - March 28, 2024 Category: Pathology Source Type: research

Expression of fibroblast growth factor receptor 2 (FGFR2) in combined hepatocellular-cholangiocarcinoma and intrahepatic cholangiocarcinoma: clinicopathological study
We examined a prevalence of FGFR2 genetic alterations and their clinicopathological significance in combined hepatocellular–cholangiocarcinoma (cHCC-CCA). FGFR2 expression, which is a su rrogate marker for FGFR2 genetic alterations, was immunohistochemically assessed in the liver sections from 75 patients with cHCC-CCA, 35 with small duct-type iCCA, 30 with large duct-type iCCA, and 35 with hepatocellular carcinoma (HCC). FGFR2 genetic alterations were detected by reverse transcript ion-PCR and direct sequence. An association of FGFR2 expression with clinicopathological features was investigated in cHCC-CCAs. FGFR2 expre...
Source: Virchows Archiv - March 27, 2024 Category: Pathology Source Type: research

Digital counting of tissue cells for molecular analysis: the QuANTUM pipeline
AbstractThe estimation of tumor cellular fraction (TCF) is a crucial step in predictive molecular pathology, representing an entry adequacy criterion also in the next-generation sequencing (NGS) era. However, heterogeneity of quantification practices and inter-pathologist variability hamper the robustness of its evaluation, stressing the need for more reliable results. Here, 121 routine histological samples from non-small cell lung cancer (NSCLC) cases with complete NGS profiling were used to evaluate TCF interobserver variability among three different pathologists (pTCF), developing a computational tool (cTCF) and assessi...
Source: Virchows Archiv - March 26, 2024 Category: Pathology Source Type: research

Primary mismatch repair –deficient prostate cancer can be identified prospectively in prostate biopsies and radical prostatectomies
(Source: Virchows Archiv)
Source: Virchows Archiv - March 26, 2024 Category: Pathology Source Type: research