High Intraepithelial Mast Cell Density in Warthin's Tumor.

BACKGROUND/AIM: Warthin's tumor, the second most frequent neoplasia of the parotid gland, is characterized by a proliferation of both epithelial and lymphoid components. In addition to epithelial and lymphoid cells, various other cell types are implicated to varying degrees in the immune response. Notably, mast cells have long been recognized as a consistent cell population within this tumor. Despite the historical acknowledgment of mast cell presence, their true distribution and significance within Warthin's tumor remain unclear. In this study, we aimed to elucidate the distribution and significance of mast cells in Warthin's tumor. MATERIALS AND METHODS: Histochemical and immunohistochemical methods were employed for the evaluation of mast cells within tumor specimens. RESULTS: Our study revealed a notable concentration of mast cells in the epithelial component of Warthin's tumor. Microscopic examination showed predominant lymphoid and epithelial elements with occasional cystic formations. Immunohistochemical analysis identified mast cells in both components, emphasizing their role in the tumor microenvironment. Double immunostaining (mast cell tryptase and CD34) revealed no significant correlation between mast cells and blood vessels. Intraepithelial mast cells (IEMCs) had a significantly higher density in the epithelial component, suggesting a potential association with the tumor's benign nature. The relationship between IEMCs and epithelial cells, especially in the presence of cystic structures, offers valuable insights into the unique features of Warthin's tumor. CONCLUSION: Our study contributes to the understanding of mast cells in Warthin's tumor, highlighting a substantial concentration within the epithelial component. This knowledge may pave the way for further investigations into the roles of mast cells in the pathogenesis and treatment of Warthin's tumor.

Rutin Linoleate Triggers Oxidative Stress-Mediated Cytoplasmic Vacuolation in Non-Small Cell Lung Cancer Cells.

Lung cancer (LC) represents one of the most prevalent health issues globally and is a leading cause of tumor-related mortality. Despite being one the most attractive compounds of plant origin due to its numerous biological properties, the therapeutic applications of rutin (RUT) are limited by its disadvantageous pharmacokinetics. Thus, the present study aimed to evaluate in vitro the application of two RUT fatty acids bioconjugates, rutin oleate (RUT-O) and rutin linoleate (RUT-L), as potential improved RUT-based chemotherapeutics in non-small cell lung cancer (NSCLC) treatment. The results indicate that both compounds lacked cytotoxic potential in EpiAirway™ tissues at concentrations up to 125 µM. However, only RUT-L exerted anti-tumorigenic activity in NCI-H23 NSCLC cells after 24 h of treatment by reducing cell viability (up to 47%), proliferation, and neutral red uptake, causing cell membrane damage and lactate dehydrogenase (LDH) leakage, affecting cytoskeletal distribution, inducing cytoplasmic vacuolation, and increasing oxidative stress. The cytopathic effects triggered by RUT-L at 100 and 125 µM are indicators of a non-apoptotic cell death pathway that resembles the characteristics of paraptosis. The novel findings of this study stand as a basis for further investigations on the anti-cancer properties of RUT-L and their underlying mechanisms.

Mast Cell: A Mysterious Character in Skin Cancer.

Cutaneous malignancies represent a real concern and burden for the healthcare system, not only due to their increased frequency, but also due to the significant number of deaths attributed to these types of cancer. The genesis of tumors, their progression and metastasis are highly complex and researched subjects; apparently, mast cells (MCs) constitute an important piece in the complicated jigsaw puzzle of cancer. This article reviews the current knowledge of the roles MCs might play in the development of cutaneous malignancies. Besides their well-known and studied role in allergic reactions, MCs are linked to multiple and various disorders, including cancer. MCs exhibit incredible heterogeneity, being able to secrete numerous mediators that influence the tumor microenvironment and tumor cells. They are involved in many physiological and pathological processes, such as inflammation and angiogenesis. In this context, it is paramount to explore the advancements made so far in elucidating the roles that MCs have in skin cancer because they might provide valuable therapeutic targets in the future. Controversial and conflicting results were obtained across the studies examined.

The mast cell reaction in premalignant and malignant lesions of the head and neck.

Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent and aggressive neoplasms of this anatomical region. Many studies evaluated the neoplastic cells, but few works focused on the tumor microenvironment. In the present study, we investigated the distribution and mast cell density (MCD) in malignant and premalignant lesions of the oral cavity, tongue, pharynx, and larynx. There were analyzed 52 specimens of HNSCC, and 15 biopsies taken from patients with dysplasia. Results were compared with those found in a control group of 10 biopsies of oral mucosa from patients with inflammatory diseases. Slides stained with Hematoxylin-Eosin were used for the histopathological diagnosis and grade, and mast cells (MCs) were identified by immunohistochemistry, using anti-MC tryptase. MCs were counted using a method similar to that proposed for microvessel density. We found a significant increase in the number of MCs from the normal oral mucosa until overt carcinoma. Unlike normal tissues, in HNSCC, many MCs were found between tumor cells. We found no relationship between MCs and blood vessels in the tumor area. A significant statistical correlation was found between dysplastic and malignant tumors, but not between tumors with a different grade. Also, it was not found relationship between MCD and the anatomical location of the tumor. Based on these results, we believe that MCD evaluated by anti-MC tryptase is an independent factor of prognosis and reflects an unfavorable outcome.

The molecular profile of breast cancer: primary tumor versus corresponding lymph node metastases.

Breast cancer (BrCa) is the most frequent malignancy in female, and lymph node metastases (LNM) is an important prognostic and therapeutic parameter. The molecular classification is nowadays largely applied to characterize the primary tumors, but few studies focused on the comparison between the molecular profiles of the primary with corresponding LNM. In the current work, we investigated the expression of conventional markers used by molecular classification in both primary tumors and axillary LNM. A series of 156 patients with BrCa was investigated, and from these 80 cases showed LNM. After routine pathological investigation, including the histopathological form and grade, we performed additional step sections from the primary and lymph nodes for immunohistochemistry. All procedures for hormone receptors, human epidermal growth factor receptor 2 (HER2), Ki67, cytokeratin 5 (CK5), epidermal growth factor receptor (EGFR), p53, E-cadherin, and B-cell leukemia∕lymphoma-2 (Bcl-2) were performed using the standard automated procedures. We found significant differences between the primary tumors and corresponding LNM in luminal A, luminal B, and basal-like carcinoma. No phenotypical interconversions were noticed in HER2 and unclassified BrCa. Our data demonstrate that in almost 20% of the cases the molecular profile of the primary does not overlap with aspects found in the lymph nodes. Our results strongly suggest performing the molecular classification in both primary tumors and in LNM. Current data suggest that the application of this diagnostic procedure will significantly influence the therapeutic strategy.

Mast cell density in the primary tumor predicts lymph node metastases in patients with breast cancer.

Breast cancer (BrCa) is the most frequent neoplastic disease in female, with high morbidity and mortality. Most of the researches were focused on tumor cells concerning their natural evolution, molecular profile, and potential response to therapy. Few and uncertain data are available about the tumor microenvironment and its impact on the progression of the disease. Mast cells (MCs) associated to BrCa have been reported many years ago, but their real and specific role in the biology of this disease remained elusive. In the current study, we have investigated the predictive role of MCs from the primary tumor on lymph node metastasis on patients stratified based on the molecular classification. We investigated 156 patients with BrCa, stratified as luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) type, basal-like, and unclassified. MCs were identified with anti-MC tryptase antibody in a double immunohistochemical reaction combined with anti-cluster of differentiation 34 (CD34) antibody. Mast cell density (MCD) was calculated based on the hot-spot method, on three fields with maximum density of MCs in each case. The final result was the arithmetic media that was compared with the molecular profile and lymph node metastases. We found no significant correlation between MCD and the molecular profile of the primary tumor, but we noticed a strong correlation between intratumor MCD and lymph node metastases, regardless of the molecular type.

Oral squamous cell carcinomas: a histopathological review of multiple cases from Western Romania.

Malignant tumors of the oral cavity have a growing incidence, most being squamous cell carcinomas, generally called oral cancers (OCs), clinically detected at various stages of natural evolution. The increased incidence in Romania in recent years and the lack of conclusive data have led to the development of this study. The main purpose of this study was to assess the molecular profile of tumors, the types of blood vessels associated with the tumor, and expression of tumor immunomarkers. Regarding morphological findings, focal epithelial hyperplasia, dysplastic lesions, typical mitoses, perineural invasion, parakeratosis and keratosis beads, intracytoplasmic keratinization were observed. Microvascular density was higher in the tumor area compared to the peritumoral area. Lymphovascular invasion was identified in 13% of cases, which also presented regional lymph node metastases. Podoplanin expression was identified in 79% of cases which were tested positive for the D2-40 immunomarker. All p53-positive cases co-expressed epidermal growth factor receptor (EGFR), half of the EGFR-positive cases co-expressed p53, and co-expression of CD117 and p63 was identified in 80% of EGFR-positive∕cytokeratin 5 (CK5)-positive cases being proposed the basal-like subtype of OCs, defined as EGFR-positive∕CK5-positive, CD117-positive and p63-positive. Results support the need for molecular classification of OCs based on of tumor immunomarker expression and gene analysis.