Background: Pancreatic ductal adenocarcinoma (PDAC) is resistant to single-agent immunotherapies. To understand the mechanisms leading to the poor response to this treatment, a better understanding of the PDAC immune landscape is required. The present work aims to study the immune profile in PDAC in relationship to spatial heterogeneity of the tissue microenvironment (TME) in intact tissues. Methods: Serial section and multiplex in situ analysis were performed in 42 PDAC samples to assess gene and protein expression at single-cell resolution in the: (a) tumor center (TC), (b) invasive front (IF), (c) normal parenchyma adjacent to the tumor, and (d) tumor positive and negative draining lymph nodes (LNs). Results: We observed: (a) enrichment of T cell subpopulations with exhausted and senescent phenotype in the TC, IF and tumor positive LNs; (b) a dominant type 2 immune response in the TME, which is more pronounced in the TC; (c) an emerging role of CD47-SIRPα axis; and (d) a similar immune cell topography independently of the neoadjuvant chemotherapy. Conclusion: This study reveals the existence of dysfunctional T lymphocytes with specific spatial distribution, thus opening a new dimension both conceptually and mechanistically in tumor-stroma interaction in PDAC with potential impact on the efficacy of immune-regulatory therapeutic modalities.
Background: Malignant Brenner tumors are rare ovarian tumors, accounting for less than 1% of malignant ovarian neoplasms. The aim of this manuscript is to systematically review the current literature concerning malignant Brenner tumors. Methods: We searched three medical databases (PubMed, Scopus, and Web of Science) for relevant articles published until 15 September 2023. Results: After applying inclusion and exclusion criteria, 48 manuscripts describing 115 cases were included in this study from the English literature. Conclusions: We analyzed the demographic, clinical, pathological, and oncological characteristics of 115 patients with malignant Brenner tumors. The statistical analysis showed that recurrence was marginally statistically significantly related to tumor stage and was more common in patients with ascites and in women with abnormal CA-125 levels; patients that were treated with lymphadenectomy had better disease-specific survival.
Breast carcinoma is the most common cancer in women. Nineteen different subtypes of breast carcinomas are recognized in the current WHO classification of breast tumors. Except for these subtypes, there are a number of carcinomas with special morphologic and immunohistochemical features that are not included in the 5th WHO classification, while others are considered special morphologic patterns of invasive breast carcinoma of no special type. In this manuscript, we systematically review the literature on four different subtypes of invasive breast carcinoma, namely lymphoepithelioma-like breast carcinoma, breast carcinoma with osteoclast-like giant cells, signet-ring breast carcinoma, and metaplastic breast carcinoma with melanocytic differentiation. We describe their clinicopathological characteristics, focusing on the differential diagnosis, treatment, and prognosis.
Persistent high-risk human papillomavirus (HPV) infection is a pivotal factor in the progression of cervical cancer. In recent years, an increasing interest has emerged in comprehending the influence of HPV on head and neck squamous cell carcinoma (HNSCC). Notably, it is well established that HPV-associated HNSCC show cases with distinct molecular and clinical attributes compared to HPV-negative cases. The present study delves into the epigenetic landscape of HPV16, specifically its L1 gene and untranslated region (UTR), through pyrosequencing, while the HPV16 DNA physical status was evaluated using E2/E6 ratio analysis in HPV16-positive HNSCC FFPE biopsies. Our findings reveal substantial methylation across six sites within the HPV16 L1 gene and seven sites in the UTR. Specifically, methylation percentages of two L1 CpG sites (7136, 7145) exhibit significant associations with tumor histological grade (p < 0.01), while proving concurrent methylation across multiple sites. The HPV16 DNA physical status was not correlated with the methylation of viral genome or tumor characteristics. This is the first study that examines epigenetic modifications and the HPV16 DNA physical status in Greek HNSCC patients. Our findings suggest an orchestrated epigenetic modulation among specific sites, impacting viral gene expression and intricate virus–host interactions.
Background: Axillary lymph node metastasis is a rare stage IV ovarian carcinoma manifestation. This manuscript aims to systematically review the literature regarding axillary lymph node metastasis from ovarian carcinoma. Methods: We searched three medical internet databases (PubMed, Scopus, and Web of Science) for relevant articles published until 22 July 2023. Cases describing supraclavicular or intramammary lymph node metastases and concurrent metastasis to the breast were excluded. Results: After applying eligibility/inclusion and exclusion criteria, twenty-one manuscripts describing twenty-five cases were included from the English literature. Data were collected and analyzed regarding demographic, clinical, laboratory, radiological, histopathological, and oncological characteristics. Conclusions: We analyzed the clinical and oncological characteristics of patients with axillary lymph node metastasis from ovarian carcinoma, presented either as an initial diagnosis of the disease or as a recurrent disease. The analysis we performed showed a significant difference only in the serum CA-125 level (p = 0.004) between the two groups. There was no observed difference in womens’ survival.
Invasive lobular carcinoma (ILC) is the most common special type of breast carcinoma, accounting for 5–15% of all breast carcinoma cases. Its metastatic pattern differs from that of invasive breast carcinoma of no special type, with ILC metastases to the peritoneum, gastrointestinal tract, and female genital tract being more frequent. This literature review focuses on ILC cases with metastasis to the female genital tract (FGT). Searches were conducted in medical databases including PubMed, Scopus, and Web of Science, using specific keywords. Inclusion criteria centered on studies presenting one or more cases of patients with ILC metastasis to the FGT and English language publications. Exclusion criteria included articles that did not present original research findings, studies with insufficient data, and publications in languages other than English. A thorough analysis of 154 results from PubMed, 56 from Scopus, and 173 from Web of Science after the application of inclusion and exclusion criteria resulted in the inclusion of 54 manuscripts describing 61 cases. The demographic, clinicopathological, and therapeutic aspects of ILC metastases to the FGT were reviewed and the differential diagnosis and prognosis for each anatomic location in the FGT were discussed separately. Our analysis of the data showed that the restricted mean survival time was 186 ± 30.7 months and that a negative ER on a secondary tumor was found to be linked to worse patient survival rates. Also of note is the fact that in 37.7% of cases there was involvement of multiple FGT anatomic locations and in 36% of cases there were metastases in organs or anatomic locations other than the FGT. To our knowledge, our study is the only one to describe the features of patients with secondary FGT involvement from ILC.