The invasive tumor front (ITF) of colorectal carcinoma (CRC) is a biologically active interface where epithelial dissociation, stromal activation, immune remodeling, and angiogenesis converge. This retrospective histopathological association study examined whether tumor budding combined with selected ITF microenvironmental markers could better characterize aggressive clinicopathological features of non-metastatic CRC. Fifty-two surgically resected primary CRCs were analyzed after exclusion of patients with distant metastatic disease at diagnosis or surgery. Tumor budding was scored according to ITBCC 2016 criteria. Immunohistochemistry evaluated stromal podoplanin (D2-40) expression, CD34-based microvessel density, the CD163/CD68 ratio, and CD117-positive mast cell density. An unweighted integrated ITF microenvironment score (0–4) was generated by summing high values for these four parameters. High histological grade, lymphovascular invasion, high tumor budding, and node-positive disease were significantly associated with multiple microenvironment-related alterations. The integrated ITF score was significantly higher in high-grade, lymphovascular invasion-positive, node-positive, and high-budding CRCs, suggesting cumulative stromal, immune, and vascular remodeling at the invasive front. These findings support the ITF as an integrated histopathological compartment in CRC progression. However, the score remains hypothesis-generating and requires validation in larger, independent, molecularly and outcome-annotated cohorts before prognostic or clinical use.

Background: Triple-negative breast carcinoma (TNBC) comprises several histological entities with different molecular alterations and clinical behaviour. Recognising these entities is important for accurate classification and for choosing appropriate immunohistochemical and molecular tests. Methods: We conducted a narrative review of English-language literature identified through PubMed/MEDLINE, Scopus, Web of Science Core Collection, citation searching and a Scopus publication list. Journal publications available through 24 August 2026 were eligible. Current reporting and regulatory guidance was obtained from official websites. Findings were synthesised qualitatively, without statistical pooling. Results: The review included 93 journal publications and two official documents. Secretory carcinoma, adenoid cystic carcinoma, tall cell carcinoma with reversed polarity and metaplastic carcinoma require a different diagnostic approach from conventional high-grade invasive breast carcinoma of no special type. Architectural, cytological and stromal findings guide the differential diagnosis and the selection of immunohistochemical stains and molecular assays. Limited sampling, tumour heterogeneity and treatment-related changes can affect tissue selection and interpretation. Conclusions: Pathology reports should specify the histological type and clearly state any remaining diagnostic uncertainty. Morphology should guide diagnostic testing, while validated predictive biomarkers and clinical criteria determine treatment eligibility.

Background and Clinical Significance: Inflammatory fibroid polyp (IFP), also known as Vanek’s tumor, is a rare, benign mesenchymal lesion of the gastrointestinal (GI) tract that frequently mimics neoplastic conditions due to its submucosal location and radiologic appearance. Although most commonly found in the gastric antrum, IFPs may occur throughout the GI tract and present with a range of symptoms, from incidental findings to obstruction or bleeding, depending on size and location. Case Presentation: This article presents two distinct cases of gastric IFP managed at the University Hospital of Messina: one endoscopically resected polyp in a 70-year-old man and one surgically excised infiltrative lesion in a 64-year-old woman with high-grade obstruction. Histological analysis in both cases confirmed the diagnosis of IFP, demonstrating spindle cell proliferation with eosinophilic infiltrates and a characteristic perivascular “onion-skin” pattern. Immunohistochemical staining showed strong CD34 positivity and absence of CD117 and DOG1, aiding in differentiation from gastrointestinal stromal tumors (GISTs). Conclusions: Recent evidence suggests a neoplastic origin for IFPs, supported by the presence of PDGFRA mutations and telocyte involvement, prompting a reevaluation of their pathogenesis. These cases underscore the diagnostic challenges posed by IFPs and highlight the importance of histological and immunohistochemical analysis in guiding appropriate treatment. While endoscopic resection is preferred for localized lesions, surgical intervention remains necessary in complex or obstructive cases. Understanding IFPs’ molecular profile and cellular origin may refine future diagnostic and therapeutic approaches.

Sequestosome 1 (SQSTM1/p62) links autophagy to cellular stress responses and can be assessed by immunohistochemistry. In triple-negative breast cancer (TNBC), however, its staining has no single biological interpretation. This selective narrative review examines human tissue studies alongside experimental evidence, focusing on the pathological assessment of mitochondrial stress. Human evidence remains limited—retrospective cohorts report inconsistent prognostic associations, and treatment-related changes are poorly characterized. Increased p62 can reflect enhanced synthesis or impaired degradation; mitochondrial clearance can also proceed without it. These observations explain why p62 staining alone cannot measure mitophagic flux. We propose assessing p62 distribution and abundance alongside mitochondrial content, oxidative damage and autophagy–lysosomal markers to describe exploratory tissue profiles. Each profile is linked to a proposed mechanism and to findings that would support or challenge that explanation. We consider baseline response associations separately from changes in residual disease, because complete responders lack residual invasive tumor for paired analysis. Mitochondrial turnover, respiratory function and genetic perturbation with rescue offer complementary ways to test the proposed dependencies. This framework provides a basis for investigating the relationship between mitochondrial damage, clearance, recovery and treatment persistence; its clinical relevance remains to be established.