Head and neck hematolymphoid proliferations: what is new?

In 2024, the World Health Organization published its 5th edition of tumor classification, which comprises several updates and modifications in the "blue book" focused on head and neck tumors. These changes feature a systematized and expanded discussion on haematolymphoid proliferations using a multi-parameter approach that comprises clinical features, morphology, immunophenotype, and genetic data, with the latter becoming an essential characteristic for classification. Moreover, for the first time, the World Health Organization has included non-neoplastic diseases, such as reactive lymphoid proliferations, alongside several recognized independent disorders, including Epstein-Barr Virus positive mucocutaneous ulcers and IgG4-related diseases.

Annexin A1 Is Involved in the Antitumor Effects of 5-Azacytidine in Human Oral Squamous Carcinoma Cells.

the treatment of squamous cell carcinomas of the oral cavity (OSCCs) is limited by the lack of reliable diagnostic/prognostic, and predictive markers, as well as by intrinsic tumor cell heterogeneity. 5-azacytidine (5-AZA) offers opportunities for cancer cell reprogramming to develop new target-specific treatments. The protein annexin A1 (ANXA1) is downregulated in head and neck squamous cell carcinoma (HNSCC), correlated with pathological differentiation grade.

An Optimized NGS Workflow Defines Genetically Based Prognostic Categories for Patients with Uveal Melanoma.

Background: Despite advances in uveal melanoma (UM) diagnosis and treatment, about 50% of patients develop distant metastases, thereby displaying poor overall survival. Molecular profiling has identified several genetic alterations that can stratify patients with UM into different risk categories. However, these genetic alterations are currently dispersed over multiple studies and several methodologies, emphasizing the need for a defined workflow that will allow standardized and reproducible molecular analyses.

Spleen volume assessment in Ph-negative chronic myeloproliferative neoplasms: a real-life study comparing ultrasonography vs. magnetic resonance imaging scans.

Splenomegaly is a quite common clinical feature of Philadelphia (Ph) negative chronic myeloproliferative neoplasms (MPNs) and its presence may, in some cases, drives treatment decision. Most importantly, palpable splenomegaly is a minor criterion for both pre-fibrotic/early primary myelofibrosis and primary myelofibrosis (PMF) diagnosis, even if clinical assessment by physical examination is poorly reliable and accurate. On the other hand, despite the International Working Group-Myeloproliferative Neoplasms Research and Treatment and European LeukemiaNet guidelines defined spleen response criteria by palpation, they also recognized the highly subjective nature of spleen size assessment by physical examination, and recommended objective confirmation of volume reduction via computed tomography or magnetic resonance imaging (MRI).

Early assessment of IL8 and PD1+ Treg predicts response and guides treatment monitoring in cemiplimab-treated cutaneous squamous cell carcinoma.

Purpose: Anti-programmed cell death 1 (PD1) is the first-choice treatment in patients with advanced cutaneous squamous cell carcinoma (cSCC), when curative options are unavailable. However, reliable biomarkers for patient selection are still lacking.

Experimental Design: In this translational study, clinical annotations, tissue and liquid biopsies were acquired to investigate the association between sustained objective responses and transcriptional profiles, immune cell dynamics in tumor tissue and peripheral blood samples, as well as circulating cytokine levels.

A Digital Workflow for Automated Assessment of Tumor-Infiltrating Lymphocytes in Oral Squamous Cell Carcinoma Using QuPath and a StarDist-Based Model.

The search for reliable prognostic markers in oral squamous cell carcinoma (OSCC) remains a critical need. Tumor-infiltrating lymphocytes (TILs), particularly T lymphocytes, play a pivotal role in the immune response against tumors and are strongly correlated with favorable prognoses. Computational pathology has proven highly effective for histopathological image analysis, automating tasks such as cell detection, classification, and segmentation.

A machine learning approach to predict HPV positivity of oropharyngeal squamous cell carcinoma.

HPV status is an important prognostic factor in oropharyngeal squamous cell carcinoma (OPSCC), with HPV-positive tumors associated with better overall survival. To determine HPV status, we rely on the immunohistochemical investigation for expression of the P16 protein, which must be associated with molecular investigation for the presence of viral DNA. We aim to define a criterion based on image analysis and machine learning to predict HPV status from hematoxylin/eosin stain.

The oral microbiome and its role in oral squamous cell carcinoma: a systematic review of microbial alterations and potential biomarkers.

Background: Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide. Despite advances in diagnosis and treatment, the incidence of OSCC is increasing, and the mortality rate remains high. This systematic review aims to examine the potential association between the composition of the oral microbiota and OSCC.

RNA-Based Next-Generation Sequencing in Non-Small Cell Lung Cancer patients: data from Campania, Italy.

Objective: ALK, ROS1, NTRK, and RET gene fusions and MET exon 14 skipping alterations represent fundamental predictive biomarkers for advanced non-small cell lung cancer (NSCLC) patients to ensure the best treatment choice. In this scenario, RNA-based NGS approach has emerged as an extremely useful tool for detecting these alterations. In this study, we report our NGS molecular records on ALK, ROS1, NTRK, and RET gene fusions and MET exon 14 skipping alterations detected by using a narrow RNA-based NGS panel, namely SiRe fusion.

Leveraging deep learning for identification and segmentation of "CAF-1/p60-positive" nuclei in oral squamous cell carcinoma tissue samples.

In the current study, we introduced a unique method for identifying and segmenting oral squamous cell carcinoma (OSCC) nuclei, concentrating on those predicted to have significant CAF-1/p60 protein expression. Our suggested model uses the StarDist architecture, a deep-learning framework designed for biomedical image segmentation tasks. The training dataset comprises painstakingly annotated masks created from tissue sections previously stained with hematoxylin and eosin (H&E) and then restained with immunohistochemistry (IHC) for p60 protein.

Case report: Potential role of immunotherapy in thymic malignancies: a unique case of a durable and complete response upon an immune checkpoint inhibitor.

Thymic epithelial tumors are rare malignancies with an incidence of 1.7 cases per million people per year. They pose significant management challenges due to their association with autoimmune disorders.

A deep learning model to predict Ki-67 positivity in oral squamous cell carcinoma.

Anatomical pathology is undergoing its third revolution, transitioning from analogical to digital pathology and incorporating new artificial intelligence technologies into clinical practice. Aside from classification, detection, and segmentation models, predictive models are gaining traction since they can impact diagnostic processes and laboratory activity, lowering consumable usage and turnaround time. Our research aimed to create a deep-learning model to generate synthetic Ki-67 immunohistochemistry from Haematoxylin and Eosin (H&E) stained images.

Ultrasonography-guided core-needle biopsy of lymphadenopathies suspected of lymphoma: Analysis on diagnostic efficacy and safety of 1000 front-line biopsies in a multicenter Italian study.

The reliability and safety of front-line ultrasonography guided core needle biopsy (UG-CNB) performed with specific uniform approach have never been evaluated in a large series of patients with lymphadenopathies suspected of lymphoma. The aim of this study was to assess the overall accuracy of UG-CNB in the lymph node histological diagnosis, using a standard reference based on pathologist consensus, molecular biology, and/or surgery. We retrospectively checked the findings concerning the application of lymph node UG-CNB from four Italian clinical units that routinely utilized 16-gauge diameter modified Menghini needle under power-Doppler ultrasonographic guidance.

Immunohistochemical expression of PRAME is a marker of poor prognosis in uveal melanoma: A clinico-pathologic and immunohistochemical study on a series of 85 cases.

PReferentially expressed Antigen in Melanoma (PRAME) is a cancer testis antigen, first isolated in tumor-reactive T-cell clones from a metastatic melanoma patient. It has been widely studied in skin pathology as an immunohistochemical marker capable of distinguishing between benign nevi and malignant melanomas. PRAME has been found to be also expressed in non-melanocytic tumors, including lung, breast, kidney and ovarian cancer.

Granuloma annulare after SARS-CoV-2 vaccination: A case report and a literature review.

Introduction: During the Cov-19 pandemic, many studies reported a broad spectrum of cutaneous reactions presenting as erythematous rashes or pernio-like, urticaria-like or vesicular/bullous patterns associated with Cov-19-infection and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination.

Methods: The authors documented the clinical and histopathological features of an unexpected case of granuloma annulare (GA) arising a few days after the SARS-CoV-2 vaccination and reviewed all GAs reported in the literature following the SARS-CoV-2 vaccination and Cov-19-infection.

Case Report: A 69-year-old woman developed a single reddish lesion on the left deltoid region, where the SARS-CoV-2 vaccine seven days earlier was injected.

Diagnostic accuracy of HIK1083 and MUC6 as immunohistochemical markers of endocervical gastric-type adenocarcinoma: A systematic review and meta-analysis.

Introduction: HIK1083 and MUC6 have been used as immunohistochemical markers to differentiate gastric-type adenocarcinoma (GTAC) from other endocervical adenocarcinomas. We aimed to assess their diagnostic accuracy through a systematic review and meta-analysis.

Methods: Three electronic databases were searched from their inception to July 2022 for all studies assessing the expression in endocervical GTAC vs other endocervical adenocarcinomas.

TCGA Molecular Prognostic Groups of Endometrial Carcinoma: Current Knowledge and Future Perspectives.

The four TCGA-based molecular prognostic groups of endometrial carcinoma (EC), i.e., POLE-mutant, mismatch repair (MMR)-deficient, p53-abnormal, and “no specific molecular profile” (NSMP), have recently been integrated into ESGO-ESTRO-ESP guidelines.

The disruption of the CCDC6 - PP4 axis induces a BRCAness like phenotype and sensitivity to PARP inhibitors in high-grade serous ovarian carcinoma.

Background: Treatment with PARP inhibitors (PARPi) is primarily effective against high-grade serous ovarian cancers (HGSOC) with BRCA1/2 mutations or other deficiencies in homologous recombination (HR) repair mechanisms. However, resistance to PARPi frequently develops, mostly as a result of BRCA1/2 reversion mutations. The tumour suppressor CCDC6 is involved in HR repair by regulating the PP4c phosphatase activity on γH2AX.

Prognostic value of Bcl2 and Bcl6 in primary cutaneous large B-cell lymphoma: A systematic review and meta-analysis.

Aims: To assess the prognostic value of Bcl2 and Bcl6 in primary cutaneous diffuse large B-cell lymphoma (pcDLBCL), through a systematic review and meta-analysis.

Methods: Electronic databases were searched from their inception to April 2021 for studies reporting Bcl2 and Bcl6 expression and survival outcomes in pcDLBCL series. Kaplan-Meier and Cox regression survival analyses with hazard ratio calculation were performed for overall survival (OS), with a significant p-value< 0.

Neuropilin-1 Expression Associates with Poor Prognosis in HNSCC and Elicits EGFR Activation upon CDDP-Induced Cytotoxic Stress.

Head and neck squamous cell carcinoma (HNSCC) includes a group of aggressive malignancies characterized by the overexpression of the epidermal growth factor receptor (EGFR) in 90% of cases. Neuropilin-1 (NRP-1) acts as an EGFR co-receptor, enhancing, upon ligand stimulation, EGFR signaling in several cellular models. However, NRP-1 remains poorly characterized in HNSCC.

Detection of CAF-1/p60 in peripheral blood as a potential biomarker of HNSCC tumors.

To date, a very small number of serum biomarkers have been identified for clinical use in squamous carcinomas of the head and neck region. Chromatin Assembly Factor-1 (CAF-1) heterotrimeric complex subunit CAF1/p60 expression levels have been reported to be of prognostic value in Oral Squamous Cell Carcinoma (OSCC), as well as in other human solid tumors. Here our aim was to detect and quantify CAF1/p60 in the peripheral blood of Head and Neck Squamous Cell Carcinoma (HNSCC) patients, and to investigate the possible associations between serum concentration of CAF-1/p60 and HNSCC tumors.