Neuroendocrine Small Cell Carcinoma of the Cervix: A case report

Merkel cell polyomavirus (MCPyV) has been found in patients with Merkel cell carcinoma and respiratory tract infections. Merkel cell carcinoma is a primary aggressive neuroendocrine carcinoma of the skin. It has been demonstrated that MCPyV can be transmitted during sexual activity and may be present in the oral and anogenital mucosa. The aim of the present study was to evaluate whether MCPyV coexisted with HPV in three cases of neuroendocrine small cell carcinoma of the cervix using PCR and immunohistochemical analysis Three cases of NSC of the cervix were identified in the pathology archives of Parma University (Italy). Of these, two cases were associated with an adenocarcinomatous component. A set of general primers from the L1 region (forward, L1C1 and reverse, L1C2 or L1C2M) was PCR amplified to detect the broad‑spectrum DNA of genital HPV. The presence of MCPyV was investigated via immunohistochemistry using a mouse monoclonal antibody against the MCPyV LT antigen and through PCR analysis to separate viral DNA. HPV DNA was present in all three neuroendocrine carcinomas and in the adenocarcinoma component of the two mixed cases. None of the cases were immunoreactive to CM2B4 and did not contain viral DNA in either their neuroendocrine or adenocarcinomatous component. Whilst it is difficult to draw definitive conclusions from such a small sample size, these data suggested that MCPyV does not coexist with HPV in the cervix. However, in the present study, the absence of detectable MCPyV may have been due to the presence of a genotype that was not detected by the primers used in the PCR analysis or by the antibody used for the immunohistochemical study. MCPyV microRNA may also have been present, inhibiting LT expression. Additional studies with larger cohorts and more advanced molecular biology techniques are required to confirm the hypothesis of the current study

COVID-19 in pregnancy: placental pathological patterns and effect on perinatal outcome in five cases.

Introduction COVID-19, the disease caused by the novel coronavirus SARS-CoV-2, is a severe systemic thrombotic syndrome that emerged in 2019, with an ensuing pandemic. To evaluate the impact of this disease on placental tissue and perinatal outcome, histological, immunohistochemical and ultrastructural analyses of placental tissue were performed for five cases of pregnant women with COVID-19. Case reports All five pregnant women in this series developed COVID-19 in late pregnancy. Two patients experienced respiratory distress, and computed tomography revealed signs of pneumonia, with bilateral involvement, multiple lobular and subsegmental areas of consolidation and ground-glass opacities. Histological studies of placental tissue revealed the presence of slight signs of maternal vascular underperfusion (MVUs) or foetal vascular underperfusion (FVUs) lesions and mild inflammatory lesions. CD15 immunoreactivity in the placental tissue was low in all cases, demonstrating that in these cases there was not severe foetal hypoxia/asphyxia risk for newborns or distal vascular immaturity. In all cases examined, ultrastructural analyses showed spherical-like coronavirus particles with an electron intermediate-density core as well as projections from the surface as spike-like structures in the syncytiotrophoblasts. At term, all of the women delivered newborns who were negative for SARS-CoV-2 by nasopharyngeal testing in their first day of life. All newborns were exclusively breastfed and were discharged on the 3rd day of life. Conclusions In conclusion, placental patterns in pregnancy due to COVID-19 in the late stage of gestation indicate no evidence of vertical trans-placental SARS-CoV-2 transmission or a significant impact on the perinatal outcome of newborns, in both mild and more severe cases

Phase- and Stage-Related Proportions of T Cells Bearing the Transcription Factor FOXP3 Infiltrate Primary Melanoma

Although tumor-infiltrating lymphocytes (TILs) of primary cutaneous melanoma (PCM) include cytolytic T cells able to exert anti-PCM immunity, progression of PCM most frequently occurs, raising the hypothesis that the PCM microenvironment may also exert suppressive forces, for example, possibly developed by regulatory T (TREG) lymphocytes. The aim of this study was to investigate whether TILs of PCMs include lymphocytes bearing the transcription factor forkhead box protein P3 (FOXP3), which is the TREG lineage specification molecule in mice, and is debated to have a similar role in humans. Fourteen patients with PCM were selected, of which four had radial growth phase (RGP) stage I melanoma, five had vertical growth phase (VGP) stage I melanoma, and five had VGP stage III–IV melanoma. Formalin-fixed, paraffin-embedded sections were utilized for immunohistochemical single and double stainings. TILs of PCMs included FOXP3-bearing lymphocytes, which predominantly were CD20- and CD8-negative, but CD3-, CD4-, and CD25-positive, thus consistent with the standard immunophenotypical characteristics of “natural” TREG cells. Further, the proportions of FOXP3-bearing lymphocytes were higher in vertical than in RGP (P=0.001), as well as in late than in early melanoma stages (P<0.001). Should these FOXP3-bearing lymphocytes actually exert regulatory capabilities within the PCM microenvironment, they may suppress “in vivo” the local anti-PCM immune response, thus favoring melanoma progression

Bovine pestivirus is a new alternative virus for multiple myeloma oncolytic virotherapy

The oncolytic viruses have shown promising results for the treatment of multiple myeloma. However, the use of human viruses is limited by the patients' antiviral immune response. In this study, we investigated an alternative oncolytic strategy using non-human pathogen viruses as the bovine viral diarrhea virus (BVDV) that were able to interact with CD46

Retrospective immunophenotypical evaluation of MET, PD-1/PD-L1, and mTOR pathways in primary tumors and pulmonary metastases of renal cell carcinoma: the RIVELATOR study addresses the issue of biomarkers heterogeneity

Aim: In renal cell carcinoma (RCC), tumor heterogeneity generated challenges to biomarker development and therapeutic management, often becoming responsible for primary and acquired drug resistance. This study aimed to assess the inter-tumoral, intra-tumoral, and intra-lesional heterogeneity of known druggable targets in metastatic RCC (mRCC). Methods: The RIVELATOR study was a monocenter retrospective analysis of biological samples from 25 cases of primary RCC and their paired pulmonary metastases. The biomarkers analyzed included MET, mTOR, PD-1/PD-L1 pathways and the immune context. Results: High multi-level heterogeneity was demonstrated. MET was the most reliable biomarker, with the lowest intratumor heterogeneity: the positive mutual correlation between MET expression in primary tumors and their metastases had a significantly proportional intensity (P = 0.038). The intratumor heterogeneity grade was significantly higher for the mTOR pathway proteins. Combined immunophenotypical expression patterns and their correlations with the immune context were uncovered [i.e., mTOR expression in the metastases positively correlated with PD-L1 expression in tumor-infiltrating lymphocytes (TILs), P = 0.019; MET expression was related to PD-1 expression on TILs (P = 0.041, ρ = 0.41) and peritumoral lymphocytes (RILs; P = 0.013, ρ = 0.49)], suggesting the possibility of predicting drug response or resistance to tyrosine kinase, mTOR, or immune checkpoint inhibitors. Conclusions: In mRCC, multiple and multi-level assays of potentially predictive biomarkers are needed for their reliable translation into clinical practice. The easy-to-use immunohistochemical method of the present study allowed the identification of different combined expression patterns, providing cues for planning the management of systemic treatment combinations and sequences in an mRCC patient population. The quantitative heterogeneity of the investigated biomarkers suggests that multiple intralesional assays are needed to consider the assessment reliable for clinical considerations

Immunological and Molecular Correlates of Disease Recurrence after Liver Resection for Hepatocellular Carcinoma

The definition of the risk of hepatocellular carcinoma (HCC) recurrence after resection represents a central issue to improve the clinical management of patients. In this study we examined the prognostic relevance of infiltrating immune cell subsets in the tumor (TIL) and in nontumorous (NT) liver (LIL), and the expression of immune-related and lineage-specific mRNAs in HCC and NT liver derived from 42 patients. The phenotype of infiltrating cells was analyzed by flow cytometry, and mRNA expression in liver tissue was examined by real-time reverse transcription (RT)-PCR. The tumor immune microenvironment was enriched in inhibitory and dysfunctional cell subsets. Enrichment in CD4+ T-cells and in particular CD4 and CD8+ memory subsets within TIL was predictive of better overall survival (OS) and time to recurrence (TTR). Increased programmed death ligand 1 (PDL1) mRNA content and higher prevalence of invariant NKT (iNKT) cells were associated with shorter OS and TTR, respectively. By combined evaluation of infiltrating cell subsets along with mRNA profiling of immune and tumor related genes, we identified the intratumoral frequency of memory T-cells and iNKT-cells as well as PDL1 expression as the best predictors of clinical outcome. HCC infiltrate is characterized by the expression of molecules with negative regulatory function that may favor tumor recurrence and poor survival

Immunohistochemical expression of Napsin A in normal human foetal lungs and congenital and acquired pathologic conditions

Background&amp;Objective: Surfactant protein B (SP-B) is a key component of pulmonary surfactant. SP-B is processed to mature surface-active protein from a pro-peptide by two distinct cleavages at its N-terminal and C-terminal portions. Napsin A is the protease, expressed in type-II pneumocytes, involved in the N-terminal cleavage of this pro-peptide. In this paper, for the first time, we evaluate the immunohistochemical expression of Napsin A in normal human fetal lungs at different gestational ages, and in examples of congenital and acquired pulmonary pathological conditions. Method: Samples of lungs were collected at the Department ofMedicine and Surgery of Parma University, (Italy) from fetal and neonatal autopsies. The immunohistochemical study was performed using primary monoclonal antibody anti-Napsin A (clone MRQ-60). A section of lung adenocarcinoma was used as an external positive control. Results: The results reveal that Napsin A is expressed early in normal fetal lungs and in the entire epitheliumof distal pseudoglandular tracts. At 30 weeks’ gestation and in the newborn at term of pregnancy, immunoreactivity to Napsin A already presents the same distribution as that in adult subjects, affecting isolated cells of the alveolar epithelium. In pathological conditions, such as inflammatory diseases and pulmonary hypoplasia, both in the fetus and in the newborn, this study demonstrates an increase in the expression of Napsin A compared to a control group. Conclusion: In conclusion, this study demonstrates that Napsin A is produced early during fetal life and its production increases in many diseases in the effort to resolve a functional pulmonary deficiency

Is CD10 a reliable marker of invasive colorectal cancer?

AIM: Previous studies reported that CD10 positive Colorectal Cancer Cells (CRC) characterized by deeply invasive neoplasia.  MATERIALS AND METHODS: We have examined 50 pts surgically treated for colorectal cancer on at least 5 years follow up. TNM, grading score and survival have been compared to CD10 expression.  RESULTS: Thirty-four out of fifty cases have been analyzed (18 males and 16 female) of whom nineteen were CD10 positive and fifteen were CD10 negative. The remaining 16 cases were droping out. No difference in survival rate between CD10 positive and negative in N0, N1, N2. No difference on survival rate and grading 1, 2, 3. We have then analyzed CD10 positive and CD10 negative cases, according to neoplasia grading, in patients with positive linphonodes N1 and N2. We showed a statistical difference between the CD10 positive/N2 (grading 1.66 +/- 0.5) and the CD10 negative/N2 (grading 3) (p < 0.005).  CONCLUSIONS: We can hypothesize that CD10 positive neoplasia display a more invasive behaviour, independently from the N score and the G score, compared to CD10 negative neoplasia

Immunohistochemical expression of Mesothelin in a series of high grade tubal-ovarian serous carcinoma

Objectives In the current study, the immunohistochemical expression of Mesothelin (MSLN) in a series of high grade tubal-ovarian serous carcinoma (HGSC), was analysed and correlated with BRCA mutation, the stage of development at diagnosis, recurrences, and survival, in order to establish whether the expression of this marker could be useful for predicting the mutational aspects and clinical outcome of this severe malignancy. Material and Methods HGSCs were collected from 73 patients who had been surgically treated at Parma University, from 2001 and 2021. For immunohistochemical study, tissue sections from primary, metastatic and recurrences were incubated with a mouse monoclonal antibody against mesothelin (clone SP74, ready to use, Ventana-Roche). The proportion of mesothelin expression was evaluated according to this percentage of positive cells: 0, 0%, +1&lt;10%, +2, with positivity between 51 and 75%, +3, with positivity between 75% and 95%, +4 with positivity &gt;95%. The scores + 3 and +4 were considered as intense positivity, the scores +2 and +1 instead as weak positivity. A pattern of intense immunoreactivity mixed with weak positivity was defined as heterogeneous. Chi-square test and Fisher’s exact test were performed to investigate the relationship between MSLN expression and clinicopathological data. We compared disease-free survival (DFS), overall survival (OS) and progression-free survival (PFS) differences among groups of MSLN expression and disease stages using the Kaplan–Meier method and log-rank tests. P&lt;0.05 was taken as a level of significance. Results We did not find any significant statistical differences in the MSLN expression between cases with and without BRCA mutation, nor were differences observed between low stages (stage I/II) and higher stages of development (stage III/IV) and metastatic tissue. Some tissue of recurrences and post-chemotherapy showed statistical differences, with a reduction in expression of MSLN compared with the primary neoplasm (respectively p Value: 0.023 and 0.0156). On the contrary, the follow-up revealed that the survival of HGSCs seems to be independent of MSLN expression. Conclusions To summarize, the present study demonstrates that MSLN expression is an independent prognostic factor and it could be used particularly as a potential target for targeting therapy in primary and metastatic neoplasms