Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology

INTRODUCTION: Many patients with locally advanced breast cancer are proposed to neoadjuvant chemotherapy (NAT) before surgery. Only some of them achieve a pathological complete response (pCR). The determination of gene somatic alterations using Next Generation Sequencing (NGS) in the non-pCR tumors is important, in order to identify potential opportunities of treatment for the patients, if targeted therapies are available. METHODS: Breast cancer tissue samples of 31 patients, collected before NAT, were analyzed by NGS using the Oncomine™ Comprehensive Assay Plus (OCA-Plus) panel...

INTRODUCTION: Tubo-ovarian carcinomas (OCs) are highly sensitive to platinum-based neoadjuvant chemotherapy (NACT) but almost never demonstrate complete pathologic response. METHODS: We analyzed paired primary and residual tumor tissues from 30 patients with hereditary BRCA1/2-driven OCs (BRCA1: 17; BRCA2: 13), who were treated by carboplatin/paclitaxel NACT (median number of cycles: 3, range 3-6). BRCA1/2 and TP53 genes were analyzed by the next-generation sequencing (NGS)...

Transcriptomic data on bronchoalveolar lavage (BAL) from COVID-19 patients are currently scarce. This case series seeks to characterize the intraalveolar immunopathology of COVID-19. BALs were performed on 14 patients (5 COVID-19, of which 3 mild and 2 largely asymptomatic, 9 controls). Controls included asthma (n=1), unremarkable BALs (n=3), infections with respiratory syncytial virus (n=1), influenza B (n=1), and infections with other coronaviruses (n=3). SARS-CoV-2 RNA load was measured by quantitative nucleic acid testing (QNAT), while the detection of other pathogens was performed by immunofluorescence or multiplex NAT...

INTRODUCTION: A variety of gene rearrangements and molecular alterations are key drivers in the pathobiology of acute leukemia and myeloid disorders; current classification systems increasingly incorporate these findings in diagnostic algorithms. Therefore, clinical laboratories require versatile tools, which can detect an increasing number and variety of molecular and cytogenetic alterations of clinical significance. METHODS: We validated an RNA-based NGS assay that enables the detection of: i) numerous hybrid fusion transcripts (including rare/novel gene partners), ii) aberrantly expressed EVI1(MECOM) and IKZF1 (Del Exons 4-7) transcripts, and iii) hotspot variants in KIT, ABL1, NPM1 (relevant in the context of gene rearrangement status)...

INTRODUCTION: Primary mediastinal large B-cell lymphoma (PMBL) is a rarely occurring lymphoid malignancy, which typically affects young adults and presents itself as an anterior mediastinal mass. Gene expression profiling, as well as somatic genetic analysis revealed that it is closely related to classical Hodgkin lymphoma, whereas morphologically it tends to resemble diffuse large B-cell lymphoma. Familial clustering of PMBL is rare - only two reports have been published to date. While generally accepted that positive family history is associated with increased risk of developing a lymphoma, genetic risk factors, which might predispose to PMBL are largely unknown...

INTRODUCTION: The clinical course of prostate cancer (PCa) is highly variable, ranging from indolent behavior to rapid metastatic progression. The Gleason score is widely accepted as the primary histologic assessment tool with significant prognostic value. However, additional biomarkers are required to better stratify patients, particularly those at intermediate risk. METHODS: In this study, we analyzed the expression of 86 cancer hallmark genes in 171 patients with PCa who underwent radical prostatectomy and focused on the outcome of the 137 patients with postoperative R0-PSA0 status...

Introduction The characterization of tumor microenvironment (TME) related-factors and their impact on tumor progression have attracted much interest. We investigated cancer cells and CAFs to evaluate biomarkers that are associated with neoplastic progression, observing them in different interface zones of colorectal cancer. Methods On 357 CRC tissue microarrays, using immunohistochemistry, we examined the associations of podoplanin and α-SMA expressed in cancer cells and CAFs and evaluated them in different areas: tumor core, invasive front, tumor budding, tumor-stroma ratio (TSR) scoring, and desmoplastic stroma...

AIMS: Diabetes mellitus (DM), especially type 2, is strongly associated with non-alcoholic fatty liver disease (NAFLD). Recent studies indicate that particularly in DM patients, "simple" liver steatosis can progress into more severe disease. However, little is known about putative hepatic histopathological changes in DM patients without NAFLD. In this study we therefore analysed fat content and inflammatory cell infiltration in the livers of deceased DM and non-DM patients without NAFLD, and analysed age/sex effects hereon...

Pediatric hematologic malignancies often show genetic features distinct from their adult counterparts, which reflects the differences in their pathogenesis. Advances in the molecular diagnostics including the wide use of next-generation sequencing (NGS) technology have revolutionized the diagnostic workup for hematologic disorders and led to the identification of new disease subgroups as well as prognostic information that impacts the clinical treatment. The increasing recognition of the importance of germline predisposition in various hematologic malignancies also shapes the disease models and management...

Recent studies have highlighted the presence of hepatic progenitor cells (HPCs) in metastatic liver carcinomas. We provide further evidence of this phenomenon, presenting a case of a gastrointestinal stromal tumour (GIST) liver metastasis with evidence of intra- and peritumoral HPC. A 64-year-old man presented with a gastric mass diagnosed as a high-risk KIT-mutated GIST. The patient was treated with Imatinib, recurring five years later with a liver mass. Liver biopsy disclosed a GIST metastasis, hallmarked by a proliferation of ductular structures without cytological atypia intermingled with the tumour cells, with a CK7/CK19/CD56-positive immunophenotype and rare CD44 positivity...

INTRODUCTION: Introduction: Microsatellite instability (MSI) is an important prognostic molecular biomarker for gastric cancer (GC). MSI status may be detected by immunohistochemistry (IHC) for mismatch repair (MMR) proteins and polymerase chain reaction (PCR). Idylla MSI assay has not been validated for GC but may prove to be a valid alternative. METHODS: In a series of 140 GC cases, MSI status was evaluated by IHC for MLH1, PMS2, MSH2, and MSH6; gold-standard pentaplex PCR panel (PPP) (BAT-25, BAT-26, NR-21, NR-24, and NR-27); and Idylla...

Disease progression in myelodysplastic syndromes (MDS), myelodysplastic-myeloproliferative neoplasms (MDS/MPN), and myeloproliferative neoplasms (MPN), altogether referred to as myeloid neoplasms (MN), is a major source of mortality. Apart from transformation to acute myeloid leukemia, the clinical progression of MN is mostly due to the overgrowth of pre-existing hematopoiesis by the MN without an additional transforming event. Still, MN may evolve along other recurrent yet less well-known scenarios: (1) acquisition of MPN features in MDS or (2) MDS features in MPN, (3) progressive myelofibrosis (MF), (4) acquisition of chronic myelomonocytic leukemia (CMML)-like characteristics in MPN or MDS, (5) development of myeloid sarcoma (MS), (6) lymphoblastic (LB) transformation, (7) histiocytic/dendritic outgrowths...

INTRODUCTION: Genomic variants of the human papillomavirus type 16 (HPV16) are thought to play differential roles in the susceptibility to head and neck squamous cell carcinomas (HNSCC) and its biological behaviour. This study aims to establish the prevalence of HPV16 variants in an HNSCC cohort and associate them with clinical-pathological characteristics and patient survival. METHODS: We retrieved samples and clinical data from 68 HNSCC patients. DNA samples were available from tumour biopsy at the time of the primary diagnosis...

INTRODUCTION: TP53 is the most frequently mutated gene in lung tumors, but its prognostic role in admixed populations, such as Brazilians, remains unclear. In this study, we aimed to evaluate the frequency and clinicopathological impact of TP53 mutations in non-small cell lung cancer (NSCLC) patients in Brazil. METHODS: We analyzed 446 NSCLC patients from Barretos Cancer Hospital. TP53 mutational status was evaluated through targeted next-generation sequencing (NGS) and the variants were biologically classified as disruptive/nondisruptive, and as truncating/non-truncating...

BACKGROUND: Inner centromere protein (INCENP) is a member of the chromosomal passenger complex (CPC) and plays a key role in mitosis and cell proliferation. This study aims to evaluate the clinical and prognostic significance of INCENP in invasive breast cancer (BC). MATERIAL AND METHODS: INCENP protein expression was evaluated on a tissue microarray of a large BC cohort (n=1295) using immunohistochemistry. At the mRNA level, INCENP expression was assessed using the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (n=1980) and Cancer Genome Atlas (TCGA) BC cohorts (n=854)...

INTRODUCTION: Local tumor invasion is a critical factor for the outcome of men with prostate cancer. In particular seminal vesicle invasion (SVI) has been reported to be associated with a more unfavorable prognosis. A better understanding of the functional state of invading prostate cancer cells is crucial to develop novel therapeutic strategies for patients with locally advanced disease. METHODS:  The prognostic impact of local tumor progression was ascertained in over 1,000 men with prostate cancer...

OBJECTIVES: The incidence of myelodysplastic syndrome and acute myeloid leukemia is significantly increased in children with Down syndrome (DS). Within the revised 2016 WHO edition, these entities are jointly classified as myeloid leukemia associated with DS (ML-DS). Additionally, infants with DS may develop transient abnormal myelopoiesis (TAM) which is histomorphologically identical to ML-DS. While TAM is self-limiting, it is associated with an increased risk of subsequently developing ML-DS...

INTRODUCTION: Primary effusion lymphoma (PEL) is a malignant lymphomatous effusion, which by definition is Kaposi sarcoma herpesvirus/human herpesvirus 8-positive. PEL typically occurs in HIV-infected patients, but can also occur in HIV-negative individuals, including in organ transplant recipients. Tyrosine kinase inhibitors (TKIs) are currently the standard of care for patients with chronic myeloid leukemia (CML), BCR::ABL1-positive. Although TKIs are extremely effective in treating CML, they alter T-cell function by inhibiting peripheral T-cell migration and altering T-cell trafficking and have been associated with the development of pleural effusions...

Somatic mutations in the nucleophosmin (NPM1) gene occur in approximately 30% of de novo acute myeloid leukemias (AML), and are relatively enriched in normal karyotype (NK) AMLs. Earlier World Health Organization (WHO) classification schema recognized NPM1-mutated AMLs as a unique subtype of AML, while the latest WHO and International Consensus Classification (ICC) now consider NPM1 mutations as AML-defining, albeit at different blast count thresholds. NPM1 mutational load correlates closely with disease status, particularly in the post-therapy setting, and therefore high sensitivity-based methods for detection of the mutant allele have proven useful for minimal/measurable residual disease (MRD) monitoring...

The expanding digitalization of routine diagnostic histological slides holds a potential to apply artificial intelligence (AI) to pathology, including bone marrow (BM) histology. In this perspective we describe potential tasks in diagnostics that can be supported, investigations that can be guided and questions that can be answered by the future application of AI on whole slide images of BM biopsies. These range from characterization of cell lineages and quantification of cells and stromal structures to disease prediction...