Virchows

The 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 assessing its reliability vs ground truth (GT) tumor cellularity and potential impact on the final molecular results...

We report on two cases of orthotopic liver transplantation (OLTX) due to SARS-Cov2-associated secondary sclerosing cholangitis (SSC) following long-term artificial respiration and extra-corporal membrane oxygenation in intensive care. Under these conditions, SSC is a rapidly progredient biliary disease featuring degenerative cholangiopathy, loss of bile ducts, ductular and parenchymal cholestasis, biliary fibrosis, and finally cirrhosis. Reduced perfusion and oxygenation of the peribiliary plexus, severe concurrent infections, and secondary medico-toxic effects appear to play a crucial role in the pathogenesis of the disease...

No abstract text is available yet for this article.

Mutations in the TP53 gene, most commonly observed in colorectal cancer (CRC), play an essential role in colorectal carcinogenesis. Although p53 immunohistochemical (IHC) expression patterns have been argued to serve as an excellent surrogate marker for TP53 mutations, its performance has not been confirmed in CRC. We aimed to determine whether p53 IHC expression patterns accurately predict TP53 mutation status as examined by next-generation sequencing (NGS). We performed p53 IHC and sequencing of TP53 by NGS in 92 CRC cases with a microsatellite stable phenotype to investigate the correlation between TP53 mutation status and p53 IHC expression...

Research on the DNA methylation status of gastric cancer (GC) has primarily focused on identifying invasive GC to develop biomarkers for diagnostic. However, DNA methylation in noninvasive GC remains unclear. We conducted a comprehensive DNA methylation profiling study of differentiated-type intramucosal GCs (IMCs). Illumina 850K microarrays were utilized to assess the DNA methylation profiles of formalin-fixed paraffin-embedded tissues from eight patients who were Epstein-Barr virus-negative and DNA mismatch repair proficient, including IMCs and paired adjacent nontumor mucosa...

New generation ultra-fast fluorescence confocal microscopy (UFCM) allows to image histological architecture of fresh breast tissue and may be used for ex vivo intraoperative analysis for margin status. The criteria to identify breast tumoral and non-tumoral tissues in UFCM images are still objects of investigation. The objective of the study was to create an atlas of ex vivo UFCM images of breast tissues and breast carcinomas based on the first extensive collection of large field-of-view UFCM breast images...

Diagnosis of desmoid-type fibromatosis (DF) may be challenging on biopsy due to morphologic overlap with reactive fibrosis (scar) and other uniform spindle cell neoplasms. Evaluation of nuclear β-catenin, a surrogate of Wnt pathway activation, is often difficult in DF due to weak nuclear expression and high background membranous/cytoplasmic staining. Lymphoid enhancer-factor 1 (LEF1) is a recently characterized effector partner of β-catenin which activates the transcription of target genes. We investigated the performance of LEF1 and β-catenin immunohistochemistry in a retrospective series of 156 soft tissue tumors, including 35 DF, 3 superficial fibromatosis, and 121 histologic mimics (19 soft tissue perineurioma, 8 colorectal perineurioma, 4 intraneural perineurioma, 26 scars, 23 nodular fasciitis, 6 low-grade fibromyxoid sarcomas, 6 angioleiomyomas, 5 neurofibromas, 5 dermatofibrosarcoma protuberans, 3 low-grade myofibroblastic sarcomas, 3 synovial sarcomas, 3 inflammatory myofibroblastic tumors, 2 schwannomas, and 1 each of Gardner-associated fibroma, radiation-associated spindle cell sarcoma, sclerotic fibroma, dermatofibroma, and glomus tumor)...

Neuroplacentology is an expanding field of interest that addresses the placental influence on fetal and neonatal brain lesions and on further neurodevelopment. The objective of this study was to clarify the link between placental pathology and perinatal arterial ischemic stroke (PAIS). Prior publications have reported different types of perinatal stroke with diverse methodologies precluding firm conclusions. We report here the histological placental findings in a series of 16 neonates with radiologically confirmed PAIS...

Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignant neoplasm. Certain histologic features and the tumor microenvironment may impact disease progression. We aim to characterize the clinicopathologic features of ICC to identify prognostic factors. A total of 50 surgically resected ICC (partial or transplant) cases were analyzed. The cohort included 26 men and 24 women with a median age of 62 years. Eighteen (36%) cases were multifocal ICC with a mean largest tumor size of 6.5 cm. Neoadjuvant and adjuvant chemotherapy was done in eight (16%) and 33 (66%) patients, respectively...

Vasculogenic mesenchymal lesions (VMLs) of germ cell tumor origin are thought to originate in postpubertal-type yolk sac tumor components and include a spectrum of lesions from teratoma with vasculogenic stroma (TVS), to low and high-grade vasculogenic mesenchymal tumors (VMTs). VMLs exhibit rudimentary to well-developed neoplastic vessels within primitive mesenchyme, being considered a neoplastic reiteration of embryonic vasculogenesis in the splanchnic mesoderm of the yolk sac. They occur in patients with primary mediastinal germ cell tumors after chemotherapy, and a subset progresses to "somatic-type" sarcomas [including angiosarcoma (AS)], with high-grade VMTs likely portending a higher risk...

No abstract text is available yet for this article.

The current study assessed the performance of the fully automated RT-PCR-based Idylla™ GeneFusion Assay, which simultaneously covers the advanced non-small cell lung carcinoma (aNSCLC) actionable ALK, ROS1, RET, and MET exon 14 rearrangements, in a routine clinical setting involving 12 European clinical centers. The Idylla™ GeneFusion Assay detects fusions using fusion-specific as well as expression imbalance detection, the latter enabling detection of uncommon fusions not covered by fusion-specific assays...

Classification of tumors of the head and neck has evolved in recent decades including a widespread application of molecular testing in tumors of the sinonasal tract, salivary glands, and soft tissues with a predilection for the head and neck. The availability of new molecular techniques has allowed for the definition of multiple novel tumor types unique to head and neck sites. Moreover, an expanding spectrum of immunohistochemical markers specific to genetic alterations facilitates rapid identification of diagnostic molecular abnormalities...

The clinical impact of site-specific perineural invasion (PNI) in prostate cancer remains poorly understood. We compared radical prostatectomy findings and oncologic outcomes in 434 patients with single-site PNI on systematic sextant biopsy. PNI was present in the right apex (n = 62; 14%), right mid (n = 70; 16%), right base (n = 89; 21%), left apex (n = 64; 15%), left mid (n = 58; 13%), and left base (n = 91; 21%). There were no significant differences in biopsy or prostatectomy findings, when comparing apex vs...

Most tumors are caused by inherited or acquired genetic changes. However, a subset of tumors is driven by viral infection including Kaposi sarcoma, nasopharyngeal carcinoma, and others. Human papillomavirus (HPV) is an especially common cause of epithelial cancers and hyperplasias. Epidermodysplasia verruciformis (EDV) is a rare type of HPV infection with characteristic histopathologic features and a unique spectrum of HPV subtypes. We report here a distinctive form of EDV-associated eccrine neoplasia. Seven tumors from two patients were analyzed and show highly uniform features including multiple clustered clinical lesions, multifocal epidermal origin, eccrine differentiation with close association with the acrosyringium, an anastomosing growth pattern, and a bland monotonous poroid-to-basaloid cytomorphology...

EWSR1::NFATC2 sarcoma, a rare round cell sarcoma constituting the majority of EWSR1::non-ETS sarcomas, has recently been defined in the latest WHO classification. To date, the cytological findings of EWSR1::NFATC2 sarcoma remain undocumented. We present the case of a 25-year-old man with a history of polyostotic fibrous dysplasia in the right leg, referred to our hospital with left thigh pain. Cytological findings included metachromasia, minimally pleomorphic round cells, and eosinophilic infiltration. There was no precursor fibrous dysplasia and the initial diagnosis was undifferentiated pleomorphic sarcoma...

Immunological mechanisms through the activation of CD4-positive T-cells have been assumed to be involved in the pathogenesis of giant cell arteritis (GCA). Many studies employing frozen tissues of temporal artery biopsy, peripheral blood lymphocytes, and plasma of GCA patients have revealed the contribution of interferon-γ and interleukin-17 in both protein and mRNA levels. However, the analyses using formalin-fixed and paraffin-embedded (FFPE) tissue specimens, in which the correlation between histopathologic pictures and immunological circumstances would be elucidated, have been limited...

The Condensed Protocol (CP) was originally developed for the evaluation of Alzheimer's Disease (AD) and other neurodegenerative diseases as a workable alternative to the complex and costly established autopsy guidelines. The study objective is to examine the degree of implementation of the CP in the pathology department of a third level university hospital in a period of 5 years. Clinical autopsies performed between 2016 and 2021 on patients aged 65 years or over and did not require a specific neuropathological examination were reviewed...

Thyroid carcinomas exhibit various genetic alterations, including the RET and NTRK fusion genes that are targets for molecular therapies. Thus, detecting fusion genes is crucial for devising effective treatment plans. This study characterized the pathological findings associated with these genes to identify the specimens suitable for genetic analysis. Thyroid carcinoma cases positive for the fusion genes were analyzed using the Oncomine Dx Target Test. Clinicopathological data were collected and assessed. Among the 74 patients tested, 8 had RET and 1 had NTRK3 fusion gene...

The objective of this study was to determine Salmonella contamination levels, presence and serovar distribution in broiler carcasses before and after chilling, as well as to evaluate the effectiveness of chilling process. A total of 96 pooled neck skin samples (PNSS) of 48 prechill (PreC) and 48 postchill (PosC) carcasses, representing 480 broilers collected in 6 mo' period were analyzed using ISO 6579-2:2012 Miniaturized Most Probable Number (ISO-mMPN) technique. Species confirmation and serovar identification was performed by Salmonella-specific real-time PCR (Salm-PCR) and conventional serotyping, respectively...