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Gastric cancer (GC) is a common malignant neoplasm worldwide and one of the main cause of cancer-related deaths. Despite some advances in therapies, long-term survival of patients with advanced disease remains poor. Different types of classification have been used to stratify patients with GC for shaping prognosis and treatment planning. Based on new knowledge of molecular pathways associated with different aspect of GC, new pathogenetic classifications for GC have been and continue to be proposed. These novel classifications create a new paradigm in the definition of cancer biology and allow the identification of relevant GC genomic subsets by using different techniques such as genomic screenings, functional studies and molecular or epigenetic characterization. An improved prognostic classification for GC is essential for the development of a proper therapy for a proper patient population. The aim of this review is to discuss the state-of-the-art on combining histological and molecular classifications of GC to give an overview of the emerging therapeutic possibilities connected to the latest discoveries regarding GC.

Despite refinements to diagnostic and therapeutic approaches over the last two decades, the outcome of patients with head and neck squamous cell carcinoma (HNSCC) has not shown substantial improvements, especially regarding those with advanced-stage disease. Angiogenesis is believed to be a turning point in the development of solid tumors, being a premise for mass growth and potential distant dissemination. Cancer-induced angiogenesis is a result of increased expression of angiogenic factors, decreased expression of anti-angiogenic factors, or a combination of both. The assessment of angiogenesis has also emerged as a potentially useful biological prognostic and predictive factor in HNSCC. The aim of this review is to assess the level of current knowledge on the neo-angiogenesis markers involved in the biology, behavior, and prognosis of HNSCC. A search (between 1 January 2012 and 10 October 2022) was run in PubMed, Scopus, and Web of Science electronic databases. After full-text screening and application of inclusion/exclusion criteria, 84 articles are included. The current knowledge and debate on angiogenesis in HNSCC presented in the eligible articles are stratified as follows: (i) diagnostic markers; (ii) prognostic markers; (iii) predictive markers; and (iv) markers with a potential therapeutic role. Angiogenesis is a biological and pathological indicator of malignancies progression and has negative implications in prognosis of some solid tumors; several signals capable of tripping the “angiogenic switch” have also been identified in HNSCC. Although several studies suggested that antiangiogenic agents might be a valuable adjunct to conventional chemo-radiation of HNSCC, their long-term therapeutic value remains uncertain. Further investigations are required on combinations of antiangiogenic agents with conventional chemotherapeutic ones, immunotherapeutic and molecularly targeted agents in HNSCC. Additional data are necessary to pinpoint which patients could benefit most from these treatments.

Temporal bone squamous cell carcinoma (TBSCC) is an uncommon malignancy with a poor prognosis in advanced cases. The dismal outcome of advanced TBSSC cases is largely due to the cancer’s local aggressiveness and the complex anatomy of this region, as well as to persistent pitfalls in diagnosis and treatment. Molecular changes occur in malignancies before any morphological changes become visible, and are responsible for the disease’s clinical behavior. The main purpose of this critical systematic review is to assess the level of knowledge on the molecular markers involved in the biology, behavior, and prognosis of TBSCC. A search (updated to March 2022) was run in PubMed, Scopus, and Web of Science electronic databases without publication date limits for studies investigating molecular markers in cohorts of patients with primary TBSCC. The search terms used were: “temporal bone” OR “external auditory canal” OR “ear”, AND “cancer” OR “carcinoma” OR “malignancy”. We preliminarily decided not to consider series with less than five cases. Twenty-four case series of TBSCC were found in which different analytical techniques had been used to study the role of several biomarkers. In conclusion, only very limited information on the prognostic role of molecular markers in TBSCC are currently available; prospective, multi-institutional, international prognostic studies should be planned to identify the molecular markers involved in the clinical behavior and prognosis of TBSCC. A further, more ambitious goal would be to find targets for therapeutic agents able to improve disease-specific survival in patients with advanced TBSCC.

Introduction/objectivesThe histopathological study of inflammatory cells and their tendency to form aggregates in chronic rhinosinusitis with nasal polyps (CRSwNP) has shown promising results in determining the pathogenesis and predicting clinical outcome. Bilateral nasal polyps also occur in over 70% of patients with eosinophilic granulomatosis with polyangiitis (EGPA). The study aim was to investigate neutrophil infiltrates and eosinophil aggregates in CRSwNP and EGPA tissues of Caucasian patients.MethodA histopathological study was performed on surgical specimens of nasal polyps from 144 adults (15 with allergic fungal rhinosinusitis; 19 with nonsteroidal anti-inflammatory drugs-exacerbated respiratory disease (NERD); 16 with intrinsic asthma; 21 with extrinsic asthma; 21 with allergy; 22 with eosinophil CRSwNP (ECRSwNP); 17 with non-ECRSwNP; 13 with EGPA).ResultsFocusing on the presence of tissue eosinophil aggregates, NERD and ECRSwNP were the sub-cohorts with the highest rate. Neutrophil infiltrate rate was significantly higher in EGPA sub-cohort than in all CRSwNP sub-cohorts apart from non-ECRSwNP.ConclusionsStructured histopathology is increasingly identifying the different histotypes of CRSwNP. This analysis can be used to better understand CRSwNP endotypes and develop targeted therapies. The response to therapy and therefore control of CRSwNP relapses definitely depends on our ability to act on the underlying inflammatory pattern.Key points• Systematic analysis of how neutrophil infiltrates and eosinophilic aggregates are distributed in the different phenotypes of CRSwNP and EGPA.• Neutrophil infiltrates and eosinophil aggregates are strong risk factors for nasal polyps’ refractoriness.• NERD and ECRSwNP are the sub-cohorts of CRSwNP with the highest rate of tissue eosinophil aggregates.• Neutrophil infiltrates are significantly higher in EGPA.

Background Extra-mammary Paget’s disease of the vulva (EMPDV) is an infrequent chronic disease that often recurs. The aim of the study was to assess the presence of neoangiogenesis and the expression of epithelial-mesenchymal transition (EMT) markers in EMPDV, and their potential correlation with stromal invasion. Methods All the women consecutively treated for EMPDV at our Institute, between January 2011 and December 2014, were studied for neoangiogenesis, analysed by microvessel density (MVD) using antibodies against CD31 and CD34. Immunohistochemical expression of E- / N-cadherin, β-catenin and SLUG was also evaluated. In each slide, three fields with the highest number of capillaries and small venules were identified at low power. In these three fields, the highest vessel density (HVD) and the average vessel density (AVD) at 200× and 400× magnification were counted. Immunohistochemical reactions for non-vascular markers were semiquantitatively scored by two pathologists, using a three-tier scale. Results Seventeen cases of EMPDV (including 10 cases of invasive disease) were included. The AVD at 200× and 400× and the HVD at 400× magnification were significantly associated with invasive EMPDV ( p  = 0.02, 0.03, 0.03 respectively). No significant correlation between MVD, EMT-markers expression and risk of recurrence was detected. Conclusion These results indicate that MVD, as a measure of neoangiogenesis, may be associated with histological progression of EMPDV. EMT could also be linked to an invasive potential of EMPDV but larger series are required to confirm this hypothesis.

An increased odontogenic chronic rhinosinusitis (oCRS) occurrence rate has quite recently been reported, likely due to an intensification of conservative dental surgery and implantology. The main aim of the study was to report for the first time the structured histopathological characteristics of the surgical specimens of oCRS. Possible associations between histopathological features and oCRS patho-physiological mechanisms were also evaluated. Structured histopathology features were investigated in the sinonasal mucosa tissue of 42 consecutive oCRS patients. Mean tissue eosinophil counts were significantly different between oCRS with radicular cysts, dental implants, or other dental diseases (p = 0.0118): mean tissue eosinophil count was higher in oCRS with dental implants. Sub-epithelial edema score and squamous metaplasia presence were significantly different when comparing the above-mentioned sub-cohorts of oCRS (p = 0.0099 and p = 0.0258). In particular, squamous metaplasia was more present in oCRS cases with radicular cysts than in those with a dental implant (p = 0.0423). Fibrosis presence was significantly different comparing the three sub-cohorts of oCRS (p = 0.0408), too. This preliminary evidence supports the hypothesis that: (i) structural histopathology can become a useful tool for clinic-pathological practice in diagnostic, therapeutic, and prognostic terms in CRS; (ii) that oCRS, as CRS in general, is a histo-pathologically heterogeneous disease; (iii) oCRS resulting from dental implants disorders can frequently be characterized as a CRS with a rich tissue eosinophilic component.

Background Endometrial stromal sarcomas arising in extrauterine and extraovarian sites, in the absence of a primary uterine lesion are quite rare, especially in the absence of endometriosis. They usually present as an abdominal or pelvic mass lesion. Case presentation In 2007, a 45-year-old woman underwent total hysterectomy for in situ squamous cell carcinoma of the cervix. In 2014, an upper left pulmonary lobectomy was performed for a mass, which was provisionally diagnosed as primary carcinosarcoma of the lung. A second histological revision of the lung surgical specimen was performed in the Pathology Unit of our Institute. After extensive immunohistochemical analyses, the preferred diagnosis was spindle-cell sarcoma, consistent with high-grade extragenital endometrial stromal sarcoma (EESS). A review of all slides of the hysterectomy specimen confirms the original diagnosis: no evidence of stromal tumor was found. Afterwards, the patient developed multiple and metachronous pulmonary lesions and a scapular soft tissue mass, which showed the same morphophenotypic features of the first lung mass. The patient was treated with antiblastic therapy, surgical resection and radioablation, when appropriate. To date, the patient has no signs or symptoms. Conclusions The authors present the first case of primary EESS arising in the lung with no association with endometriosis published to date. Detailed clinical history and follow-up are also described. Moreover, extensive literature review is reported, along with differential diagnoses, immunohistochemical and molecular findings, pathogenetic hypotheses and treatment options. The knowledge of EESS potential extrauterine location and of its peculiar morphophenotypic aspects are required for a correct diagnosis, and for choosing the most suitable treatment.

Programmed cell death ligand 1 (PD-L1) seems to rely on close relations between neoplastic and immune cells in the tumor microenvironment. Tumor to stroma ratio (TSR) has been associated with prognosis in different malignancies. The aims of this exploratory investigation were to analyze for the first time the: (i) association between TSR, PD-L1 expression and other clinical–pathological features in laryngeal squamous cell carcinoma (LSCC) biopsies and paired surgical specimens; (ii) prognostic and predictive role of TSR and PD-L1. TSR, PD-L1 expression (in terms of combined positive score [CPS]), and other clinical–pathological features were analyzed in biopsies and surgical specimens of 43 consecutive LSCC cases. A CPS < 1 evaluated on surgical specimens was associated with a low TSR (stroma rich) on both biopsies and surgical specimens (p = 0.0143 and p = 0.0063). Low TSR showed a significant negative prognostic value when evaluated on both biopsies and surgical specimens (HR = 8.808, p = 0.0003 and HR = 11.207, p = 0.0002). CPS ≥ 1 appeared to be a favorable prognostic factor (HR = 0.100, p = 0.0265). The association between bioptic and surgical specimen TSR and PD-L1 expression should be further investigated for a potential impact on targeted treatments, also with regard to immunotherapeutic protocols.

Gastric cancer (GC) is a deadly disease with poor prognosis that is characterized by heterogeneity. New classifications based on histologic features, genotypes, and molecular phenotypes, for example, the Cancer Genome Atlas subtypes and those by the Asian Cancer Research Group, help understand the carcinogenic differences in GC and have led to the identification of an Epstein–Barr virus (EBV)-related GC subtype (EBVaGC), providing new indications for tailored treatment and prognostic factors. This article provides a review of the features of EBVaGC and an update on the latest insights from EBV-related research with a particular focus on the strict interaction between EBV infection and the gastric tumor environment, including the host immune response. This information may help increase our knowledge of EBVaGC pathogenesis and the mechanisms that sustain the immune response of patients since this mechanism has been demonstrated to offer a survival advantage in a proportion of patients with GC.

Small pretreatment laryngeal biopsies may not fully represent a tumor’s biological profile. This study on laryngeal squamous cell carcinoma (LSCC) aimed to investigate the prognostic role of CD105- and CD31-assessed microvessel density (MVD) in paired biopsies and surgical specimens and the association and discrepancy between CD105- and CD31-assessed MVD in biopsies and surgical specimens. CD105- and CD31-assessed MVD was analyzed in paired biopsies and surgical specimens of 45 consecutive cases of LSCC. In the LSCC biopsies and surgical specimens, median CD105-assessed MVD was significantly higher in N+ than in N0 cases (p = 0.0008, and p = 0.0002, respectively). Disease-free survival (DFS) was associated with CD105- and CD31-assessed MVD in both biopsies and surgical specimens (p < 0.0001 for all specimens). Multivariable Cox’s regression showed that pathological grade (p < 0.0001) and CD105-assessed MVD in LSCC biopsies (p = 0.0209) predicted DFS. Lin’s concordance coefficient showed that CD31 overestimated MVD compared with CD105 in LSCC biopsies and surgical specimens. CD105-assessed MVD should be further investigated in larger LSCC series as a potential prognostic marker for identifying: patients at higher risk of recurrence who might warrant more aggressive therapy; and cN0 patients requiring elective neck dissection for a significant risk of regional metastasis.