Inflammation of the Pleural Cavity: A Review on Pathogenesis, Diagnosis and Implications in Tumor Pathophysiology

Pleural effusions are a common respiratory condition with many etiologies. Nonmalignant etiologies explain most pleural effusions and despite being nonmalignant, they can be associated with poor survival; thus, it is important to understand their pathophysiology. Furthermore, diagnosing a benign pleural pathology always harbors the uncertainty of a false-negative diagnosis for physicians and pathologists, especially for the group of non-specific pleuritis. This review aims to present the role of the inflammation in the development of benign pleural effusions, with a special interest in their pathophysiology and their association with malignancy

Immune Escape Is an Early Event in Pre-Invasive Lesions of Lung Squamous Cell Carcinoma

Bronchial dysplasia is the pre-neoplastic lesion recognized for invasive squamous cell carcinoma. The mechanisms leading to invasive squamous cell carcinoma for this lesion are not fully known. Programmed Death-Ligand 1 (PD-L1) expression by the bronchial dysplasia neoplastic epithelium might suggest a response to immunotherapy. The objective of this work is to further characterize PD-L1 and CD8 expression in bronchial dysplasia and bronchial metaplasia compared to normal bronchial epithelium. Immunohistochemical analysis of PD-L1 and CD8 staining were characterized in bronchial dysplasia of 24 patients and correlated with clinical data. We also compared PD-L1 expression in dysplasia samples to 30 normal epithelium and 20 samples with squamous bronchial metaplasia. PD-L1 was never expressed in normal epithelium and in metaplastic epithelium whereas 37.5% of patients with bronchial dysplasia were stained by PD-L1 (p < 0.001). PD-L1 expression was not related to the degree of dysplasia or a medical history of invasive squamous cell carcinoma, while CD8 expression and its localization were related to medical history of squamous cell carcinoma (p = 0.044). Our results show that PD-L1 is expressed in roughly one third of patients with bronchial dysplasia and is not expressed in normal and metaplastic epithelium. This suggests that PD-L1 is expressed in preneoplastic lesions of squamous cell carcinoma

The Premetastatic Lymph Node Niche in Gynecologic Cancer

It has been suggested that a primary tumor can “prepare” the draining of lymph nodes to “better accommodate” future metastatic cells, thus implying the presence of a premetastatic lymph node niche. However, this phenomenon remains unclear in gynecological cancers. The aim of this study was to evaluate lymph-node draining in gynecological cancers for premetastatic niche factors, such as myeloid-derived suppressor cells (MDSCs), immunosuppressive macrophages, cytotoxic T cells, immuno-modulatory molecules, and factors of the extracellular matrix. This is a monocentric retrospective study of patients who underwent lymph-node excision during their gynecological-cancer treatment. In all, 63 non-metastatic pelvic or inguinal lymph nodes, 25 non-metastatic para-aortic lymph nodes, 13 metastatic lymph nodes, and 21 non-cancer-associated lymph nodes (normal controls) were compared for the immunohistochemical presence of CD8 cytotoxic T cells, CD163 M2 macrophages, S100A8/A9 MDSCs, PD-L1+ immune cells, and tenascin-C, which is a matrix remodeling factor. PD-L1-positive immune cells were significantly higher in the control group, in comparison to the regional and distant cancer-draining lymph nodes. Tenascin-C was higher in metastatic lymph nodes than in both non-metastatic nodes and control lymph nodes. Vulvar cancer-draining lymph nodes showed higher PD-L1 values than endometrial cancer and cervical cancer-draining lymph nodes. Endometrial cancer-draining nodes had higher CD163 values and lower CD8 values, compared to vulvar cancer-draining nodes. Regarding regional draining nodes in low- and high-grade endometrial tumors, the former showed lower S100A8/A9 and CD163 values. Gynecological cancer-draining lymph nodes are generally immunocompetent, but vulvar cancer draining nodes, as well as high-grade endometrial cancer draining nodes, are more susceptible to harboring premetastatic niche factors

Prognostic value of CXCR4 expression in patients with clear cell renal cell carcinoma

Introduction: The expression of CXCR4 is implicated in the metastatic dissemination of different cancers. The information on its prognostic value has been very limited in clear cell renal cell carcinoma (ccRCC). Our objective was to explore the prognostic value of CXCR4 in ccRCC. Materials and methods: 104 patients with a ccRCC were studied. There were 69 men and 35 women with an average age of 64.5 years old (range: 34-86 years). The CXCR4 expression was evaluated by immunohistochemistry. The follow-up varied from 12 to 184 months with a mean of 79.5 months. Kaplan-Meier with a log rank test was performed to compare overall survival and cancerspecific survival after surgery. Univariate and multivariate analyses were performed according to the Cox regression model. Results: CXCR4 expression was found in 68/104 (65.4%) of tumor samples. CXCR4 expression was located in the nucleus in 55/68 (80.8%) cases while cytoplasm or membrane location was found in 13/68 (19.2%) cases. High expression was found in 25/68 (36.8%) cases. During follow-up, 39 patients died, of which 26 died of cancer. Kaplan-Meier analysis revealed that a high expression of CXCR4 was associated with a reduced overall survival (p=0.017) and cancer-specific survival (p=0.022). Univariate analysis indicated that a high expression of CXCR4 was a significant factor for a poorer overall survival (p=0.020) and cancer-specific survival (p=0.027). By multivariate analysis, a high expression of CXCR4 appeared to be an independent factor of overall survival (p=0.024) and cancer-specific survival (p=0.028). Conclusion: This study suggested that a high CXCR4 expression was correlated with a worse outcome for ccRCC patients

Autophagic Markers in Chordomas: Immunohistochemical Analysis and Comparison with the Immune Microenvironment of Chordoma Tissues

International audienceChordomas are notably resistant to chemotherapy. One of the cytoprotective mechanisms implicated in chemoresistance is autophagy. There are indirect data that autophagy could be implicated in chordomas, but its presence has not been studied in chordoma tissues. Sixty-one (61) chordomas were immunohistochemically studied for autophagic markers and their expression was compared with the expression in notochords, clinicopathological data, as well as the tumor immune microenvironment. All chordomas strongly and diffusely expressed cytoplasmic p62 (sequestosome 1, SQSTM1/p62), whereas 16 (26.2%) tumors also showed nuclear p62 expression. LC3B (Microtubule-associated protein 1A/1B-light chain 3B) tumor cell expression was found in 44 (72.1%) tumors. Autophagy-related 16‑like 1 (ATG16L1) was also expressed by most tumors. All tumors expressed mannose-6-phosphate/insulin-like growth factor 2 receptor (M6PR/IGF2R). LC3B tumor cell expression was negatively associated with tumor size, while no other parameters, such as age, sex, localization, or survival, were associated with the immunohistochemical factors studied. LC3B immune cell expression showed a significant positive association with programmed death-ligand 1 (PD-L1)+ immune cells and with a higher vascular density. ATG16L1 expression was also positively associated with higher vascular density. Notochords (n = 5) showed different immunostaining with a very weak LC3B and M6PR expression, and no p62 expression. In contrast to normal notochords, autophagic factors such as LC3B and ATG16L1 are often present in chordomas, associated with a strong and diffuse expression of p62, suggesting a blocked autophagic flow. Furthermore, PD-L1+ immune cells also express LC3B, suggesting the need for further investigations between autophagy and the immune microenvironment

Crystal-Storing Histiocytosis: The Iceberg of More Serious Conditions

Crystal-storing histiocytosis is a rare condition that is histologically characterized by intracellular cytoplasmic crystalline inclusions. It usually presents monoclonal immunoglobulins that deposit within histiocytes, which accumulate and affect different organs of the human body and are commonly associated with lymphoproliferative conditions, especially those with plasmacytic differentiation. The prognosis of this condition is variable and related to the underlying clinical disease. In this review article, we aim to describe and discuss the clinical and pathological characteristics of crystal-storing histiocytosis based on the available literature and to provide a thorough differential diagnosis

The Immune Microenvironment of Chordomas: An Immunohistochemical Analysis

International audienceChordomas are rare sarcomas that are usually treated by surgery and/or radiotherapy since these are chemo-resistant tumors, but immunotherapy could be a possible option for chordoma patients. However, few reports investigating the composition of the chordoma immune microenvironment exist. We immunohistochemically studied 81 chordomas regarding their immune microenvironment factors and compared them with clinicopathological data. Macrophages and CD4 cells were the most prominent inflammatory cell populations, followed by CD8 T cells, while CD20 B cells and high endothelial venules (MECA-79+) were less frequently found. PD-L1 (22C3) expression by inflammatory cells was found in 21 (26%) tumors and was associated with a larger tumor size. None of the cases showed the expression of PD-L1 by tumor cells. Survival analysis showed that younger patients had a better overall survival. Considering the immunohistochemical factors studied, higher CD8, the presence of PD-L1+ immune cells, and higher vascular density were adverse prognostic factors, but in multivariate analysis, only PD-L1+ immune cells retained prognostic significance. To conclude, chordoma tumor cells do not express PD-L1, but PD-L1+ immune cells seem to play a negative prognostic role, supporting the need for further studies in this field and the possible beneficial role of immunotherapy in these patients