Plexiform fibromyxoma (PF), also referred to as plexiform angiomyxoid myofibroblast tumor, is an exceedingly rare mesenchymal neoplasm primarily affecting the stomach. Herein, we present a case of PF diagnosed in a 71-year-old male with a history of lung cancer, initially suspected to have a gastrointestinal stromal tumor (GIST) of the stomach, who subsequently underwent subtotal gastrectomy. The histopathological and molecular features of the tumor, including mutations in ABL1, CCND1, CSF1R, FGFR4, KDR, and MALAT1-GLI1 fusion, are elucidated and discussed in the context of diagnostic, prognostic, and therapeutic considerations.

Chemical, physical, and infectious agents may induce carcinogenesis, and in the latter case, viruses are involved in most cases. The occurrence of virus-induced carcinogenesis is a complex process caused by an interaction across multiple genes, mainly depending by the type of the virus. Molecular mechanisms at the basis of viral carcinogenesis, mainly suggest the involvement of a dysregulation of the cell cycle. Among the virus-inducing carcinogenesis, Epstein Barr Virus (EBV) plays a major role in the development of both hematological and oncological malignancies and importantly, several lines of evidence demonstrated that nasopharyngeal carcinoma (NPC) is consistently associated with EBV infection. Cancerogenesis in NPC may be induced by the activation of different EBV “oncoproteins” which are produced during the so called “latency phase” of EBV in the host cells. Moreover, EBV presence in NPC does affect the tumor microenvironment (TME) leading to a strongly immunosuppressed status. Translational implications of the above-mentioned statements are that EBV-infected NPC cells can express proteins potentially recognized by immune cells in order to elicit a host immune response (tumor associated antigens). Three immunotherapeutic approaches have been implemented for the treatment of NPC including active, adoptive immunotherapy, and modulation of immune regulatory molecules by use of the so-called checkpoint inhibitors. In this review, we will highlight the role of EBV infection in NPC development and analyze its possible implications on therapy strategies.

Neoadjuvant strategies in head and neck squamous cell carcinoma (HNSCC) are reshaping therapeutic paradigms by shifting emphasis from anatomical staging toward biology-driven response stratification. The transition from induction chemotherapy to immune checkpoint–based and combination regimens has transformed the perioperative setting into a translational platform that enables interrogation of tumor–immune interactions and clonal selection under therapeutic pressure prior to surgery. In this context, pathological response assessment has emerged as a robust surrogate endpoint, overcoming the limitations of radiologic evaluation, which often fails to capture immune-mediated pseudoprogression and spatially heterogeneous regression. Quantification of residual viable tumor (RVT) provides a reproducible metric of therapeutic efficacy, while characterization of immune-related regression beds, tertiary lymphoid structures, macrophage polarization states, and compartment-specific nodal responses offers mechanistic insight into tumor clearance and resistance evolution. Evidence from phase II trials, single-cell sequencing, spatial transcriptomics, and multiplex immune profiling supports the prognostic relevance of pathology-driven endpoints. Integration of digital pathology and artificial intelligence–assisted image analysis further enhances reproducibility and enables high-resolution mapping of residual disease and immune architecture. Within this modern oncologic framework, the neoadjuvant-treated specimen functions as a dynamic biomarker platform guiding response-adapted surgical strategies and biomarker-driven clinical trial design. This study was designed as a narrative review. A structured literature search was performed using PubMed and major oncology journals to identify relevant studies on pathology-driven response assessment in neoadjuvant-treated head and neck squamous cell carcinoma. The review focused on publications addressing histopathological response criteria, immune microenvironment remodeling, spatial profiling technologies, and computational pathology approaches.

Gastric adenocarcinomas with yolk sac tumor (YST) differentiation represent an exceptionally rare and poorly understood phenotype, characterized by the emergence of extraembryonic features within an epithelial malignancy. Their histogenesis remains debated, with increasing evidence supporting somatic lineage plasticity rather than germ cell origin. Here, we performed an integrated histopathologic and genomic characterization of three gastric adenocarcinomas with YST differentiation surgically treated at a tertiary cancer center. Histologically, all tumors showed a predominant adenocarcinoma component associated with variable YST differentiation, displaying reticular/microcystic and papillary patterns and expression of oncofetal markers, including alpha-fetoprotein (AFP) and Glypican-3. Targeted next-generation sequencing using a 523-gene panel revealed microsatellite-stable profiles with intermediate tumor mutational burden and substantial intertumoral heterogeneity. Despite gene-level variability, the detected alterations involved signaling pathways commonly implicated in epithelial tumorigenesis, including PI3K-AKT and RTK/RAS-MAPK signaling. Several recurrent alterations were identified across cases, including CCND3 variants and MDM2 copy number gains; however, their biological significance requires validation in larger cohorts. Functional enrichment analysis identified alterations involving developmental and proliferative signaling programs. Overall, these findings suggest that YST differentiation may represent a phenotypic manifestation of epithelial tumor plasticity arising within gastric adenocarcinoma and is associated with epithelial-related oncogenic programs, although broader genomic and comparative studies are required to clarify its histogenesis. This study provides preliminary molecular and histopathologic insights into this rare entity and supports the integration of molecular profiling into its diagnostic and translational management.