Thymolipoma is an uncommon, non-malignant mediastinal mass characterized by a mixture of mature fat and normal thymic tissue. It typically grows slowly and is often asymptomatic until it reaches a large size, causing compressive symptoms. We report on a 19-year-old woman who sought medical attention for chest pain, dyspnoea, and anterior chest swelling. Imaging revealed a well-defined anterior mediastinal mass, and surgical excision was performed. Histopathological examination showed a well-encapsulated lesion with mature adipose tissue admixed with normal thymic parenchyma containing Hassall's corpuscles, confirming the diagnosis of thymolipoma. Complete surgical resection is both diagnostic and curative, with an excellent prognosis and negligible recurrence risk. Our findings underscore the importance of recognizing thymolipoma as a potential cause of anterior mediastinal masses, thereby preventing unnecessary radical treatment.
Immunotherapy with programmed death cell ligand-1 (PD-L1) antibodies is an essential treatment for non-small cell lung cancer (NSCLC), and immunohistochemical assessment of PD-L1 expression is required for therapeutic stratification. This study analyzed PD-L1 expression in paired small biopsy and surgical specimens from patients with NSCLC, including adenocarcinoma and squamous cell carcinoma. Associations with the histological type, pathological stage, and clinicopathological parameters were evaluated, and concordance between biopsies and corresponding resections was assessed. A five-year retrospective-prospective study included 102 patients. Programmed death cell ligand-1 expression was determined by immunohistochemistry using monoclonal antibody clone 28-8. Membranous staining in more than 1% of tumour cells was considered positive. No statistically significant difference in PD-L1 expression was found between small biopsy and surgical specimens (p = 0.790). Expression showed no significant association with patient age or gender. A significant association was observed between PD-L1 expression and smoking status in both specimen types (p = 0.012 and p = 0.019). Programmed death cell ligand-1 expression was not significantly related to the T descriptor (p = 0.548) or N descriptor (p = 0.617). A statistically significant correlation was identified between PD-L1 positivity and disease stage (p = 0.012). The high concordance of PD-L1 expression between biopsy and surgical material supports use of biopsies for immunotherapy planning in ineligible patients and confirms reliability of resection specimens for adjuvant treatment decisions.
Bcl-2/adenovirus E1B 19-kDa interacting protein 3 (BNIP3), a pro-apoptotic protein, regulates autophagy. BNIP3 is induced in hypoxic cells, being regulated by hypoxia-inducible factor 1-α (HIF1-α). The role of hypoxia-induced autophagy in surface epithelial ovarian carcinomas (EOC) is not well established. This work aimed to evaluate BNIP3 and HIF1-α immunohistochemical expression and study the relation between their expression and patients' survival in EOC patients. High BNIP3 and HIF1-α expressions were associated with a high tumuor grade (p = 0.012 and 0.013), stage III tumuors (p = 0.031 and 0.035), presence of omental deposits (p = 0.029 and 0.004), presence of capsular invasion (p = 0.010 and 0.019), and presence of vascular invasion (p = 0.033 and 0.007). High BNIP3 and HIF1-α expressions were associated with shortened overall survival (OS) (p = 0.021 and 0.029) and poor disease-free survival (DFS) (p = 0.002 and 0.005). The relation between BNIP3 and HIF1-α immunohistochemical expression was statistically significant (p < 0.001). High BNIP3 and HIF1-α expressions are related to unfavorable clinicopathological parameters in terms of higher tumuor grade, advanced tumuors, presence of omental deposits, capsular and vascular invasion, together with poor OS and DFS in malignant surface epithelial ovarian tumuor patients.
Kikuchi-Fujimoto disease (KFD) is a rare, benign condition that often mimics infectious or malignant disorders. We report the case of a 36-year-old woman with atypical lymphadenopathy involving axillary, supraclavicular, and infraclavicular lymph nodes, without cervical involvement. Initial treatment with antibiotics and acetaminophen was ineffective. Laboratory tests excluded infection and other under- lying diseases, while ultrasonography confirmed lymphadenopathy. Excisional biopsy revealed histopathological findings consistent with KFD. Surgical removal of the affected lymph nodes resulted in complete symptom resolution. This case highlights the importance of considering KFD in unexplained lymphadenopathy and the diagnostic value of excisional biopsy.
Classical Hodgkin lymphoma (cHL) diagnosis occasionally requires clonality assessment. However, the paucity of neoplastic Hodgkin and Reed-Sternberg cells among abundant reactive elements dramatically reduces the sensitivity of standard polymerase chain reaction (PCR)-based BIOMED-2/EuroClonality protocols, which fail to detect clonality in approximately one-third of cases. Next-generation sequencing (NGS)-based approaches have been proposed to overcome this limitation, but their performance in routine diagnostics for cHL remains insufficiently evaluated. We analyzed seven cHL cases and five follicular lymphoid hyperplasia (FLH) controls, all showing polyclonal patterns by standard PCR/capillary electrophoresis. DNA extracted from formalin-fixed paraffin-embedded lymph node biopsies was subjected to immunoglobulin heavy chain (IGH) gene rearrangement analysis using the commercially available LymphoTrack® IGH assay on the MiSeq platform. Next-generation sequencing identified clonal IGH rearrangements in 3 of 7 (43%) cHL cases previously undetectable by conventional methods. Clonal cases exhibited a dominant rearrangement representing > 2.5% of total reads, with the second most frequent rearrangement being less than half of the first. The remaining cHL cases and all FLH controls displayed polyclonal patterns. The LymphoTrack® IGH NGS assay demonstrated superior sensitivity over standard PCR-based protocols for detecting clonality in cHL, supporting its implementation in routine diagnostic workflows for challenging cases.
Spread through air spaces (STAS) represents an independent prognostic factor for poor overall survival (OS) in patients with colorectal carcinoma who underwent pulmonary metastasectomy. This study aims to evaluate the prognostic impact of STAS and explore its associations with histopathologic features and KRAS mutation status/subtypes.We retrospectively analyzed 61 consecutive patients with colorectal cancer (CRC) who underwent pulmonary metastasectomy at a single tertiary center (May 2016 - July 2024). Histopathologic review assessed STAS and other histopathologic features. KRAS mutations were tested using a real-time polymerase chain reaction assay detecting 19 variants (codons 12, 13, 59, 61, 117, 146). Spread through air spaces was present in 37/61 cases (60.7%). Median OS was 1702 days (95% CI: 1495-NA) in STAS-negative and 1288 days (95% CI: 523-NA) in STAS-positive patients (log-rank p = 0.041). In univariable analysis, STAS remained an independent predictor of poorer OS in multivariable modeling (hazard ratio: 2.37; 95% CI: 1.17-4.80; p = 0.017). KRAS mutations (present in 44.3% of tested cases; common subtypes G12V and G12D) showed no significant association with STAS (p = 0.34) or with OS. Spread through air spaces is an independent poor prognostic factor in resected CRC pulmonary metastases, whereas KRAS mutation status and subtypes were not prognostic in this cohort.
The tumour microenvironment plays an important role in the progression of gastric adenocarcinoma, but the prognostic value of its histopathological and immunological components in intestinal-type tumours remains unclear. This retrospective study included 100 patients who underwent gastrectomy for intestinal-type gastric adenocarcinoma. Tumour budding, stromal phenotype, tumour-stroma ratio, and lymphocytic infiltration were assessed on haematoxylin-eosin-stained sections, and immunohistochemical analyses of CD68, CD163, L-caldesmon, and periostin were performed at the invasive front. Tumour budding was associated with invasion depth and tumour stage but showed no independent prognostic significance. A myxoid stromal phenotype was independently associated with improved overall survival and reduced recurrence risk. CD163-positive macrophage density exceeded CD68 density and was independently linked to better survival. L-caldesmon expression was rare and not associated with clinicopathological parameters. Periostin expression correlated with macrophage infiltration but not with survival outcomes. These findings suggest that stromal phenotype and tumour-associated macrophages, particularly CD163-positive cells, have prognostic relevance in intestinal- type gastric adenocarcinoma.
The aim of this study was to investigate the immunohistochemical expression of METTL3 and SERPINE2 in urothelial carcinoma and to assess their individual and combined associations with clinicopathological features and possible correlation. This study included 126 cases of urothelial carcinoma. Immunohistochemical staining was used to evaluate METTL3 and SERPINE2 expression in tumour tissues. Clinico- pathological data including age, sex, bilharziasis, tumour grade and stage, lymph node status, lymphovascular invasion, soft tissue surgical margins, and tumour- infiltrating lymphocytes (TIL) were collected. Statistical analysis was performed to determine associations between marker expression and clinicopathological parameters. High nuclear METTL3 expression was significantly associated with a higher tumour grade, advanced stage, increased TIL, and lymphovascular invasion, with no significant association with age, sex, bilharziasis, nodal stage, or surgical margins. High cytoplasmic SERPINE2 expression was significantly associated with an advanced stage, lymph node metastasis, and positive soft tissue margins, while no association was found with age, sex, bilharziasis, grade, TIL, or lymphovascular invasion. Combined high METTL3/high SERPINE2 expression correlated significantly with a high grade, advanced tumour and nodal stages, low TIL, and positive surgical margins, indicating a more aggressive tumour phenotype. METTL3 and SERPINE2 are associated with adverse pathological features in urothelial carcinoma, and their combined overexpression may serve as a potential prognostic biomarker.
Pumilio proteins (PUM1 and PUM2) are evolutionarily conserved RNA-binding proteins that regulate gene expression at the post-transcriptional level and have been implicated in tumourigenesis in various cancers. However, their role in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) has not been previously investigated. This study aimed to evaluate the expression of PUM1 and PUM2 in GEP-NENs and determine their association with tumour grade and metastatic status. Transcriptomic data (GSE98894) were analyzed using GEO2R to assess differential gene expression in primary tumours, lymph node metastases, and distant meta- stases. Additionally, immunohistochemical analyses were performed on formalin- fixed paraffin-embedded samples, and protein expression was quantified using digital image analysis. Statistical comparisons were conducted across tumour sites and grades (G1-G3). At the mRNA level, PUM2 was significantly upregulated in distant metastases compared with primary tumours (log2FC = 0.151; adjusted p = 0.024), whereas PUM1 showed no significant difference. Protein-level analyses confirmed expression of both proteins in all samples; however, only PUM2 was significantly elevated in high-grade (G3) tumours compared to G1/G2. These findings suggest that PUM2, but not PUM1, is associated with tumour progression in GEP-NENs, although a causal role remains to be established.
Dicer is known to engage in regulating micro (mi)RNA biosynthesis. However, the role in driving thyroid carcinogenesis is unknown. In this study, we explored the role of Dicer in the carcinogenesis of well-differentiated thyroid carcinoma (WDTC). Thyroid cancer complementary (c)DNA and tissue arrays were purchased to measure Dicer messenger (m)RNA and protein levels. Additionally, research into silencing Dicer1 in papillary thyroid cancer (PTC) (TPC-1), follicular thyroid cancer (FTC), and normal thyroid (Nthy-ori 3-1) cell lines was also applied to evaluate its effects on tumour behaviors. Dicer1 mRNA was upregulated in PTC, while the Dicer protein was overexpressed in PTC and FTC tissues. Suppressing Dicer led to inhibition of cell proliferation in all cell lines, and repression of cell-cycle progression signatures in TPC-1 cells. Furthermore, p21 expression consistently increased in response to compromising Dicer in all four cell lines. Finally, Dicer1-knockdown TPC-1 and Nthy-ori 3-1 cells demonstrated nuclear phospho-H2AX staining, reduced bromodeoxyuridine incorporation ability, and G1 phase arrest of the cell cycle. Collectively, Dicer expression is increased in WDTC clinical samples, and Dicer regulates the proliferative ability of normal and WDTC cells, at least in part, through p21-dependent modulation of a cell-senescence mechanism linked to genomic instability.
A granular cell tumor (GCT) is a soft tissue neoplasm of rare occurrence in the lung. A 44-year-old male asphalt worker had interstitial lung disease. Incidentally, a 7 mm polypoid nodule was observed at the entrance of the right upper lobe bronchus. Tumor cells were characterized by a large granular eosinophilic cytoplasm and small, uniform nuclei. The neoplastic cells were diffuse positive for S-100, CD-68, NSE, vimentin, and SOX-10, and focal positive for calretinin and inhibin A. This case is unique in its distinction as the second literature case of pulmonary GCT coexisting with interstitial lung disease.
The BRAF mutation has been observed in 32-73% of papillary thyroid carcinomas. Despite the superiority of genetic tests for detecting BRAF mutations, they have inherent disadvantages. The objective of this study was to analyze the specificity and sensitivity of BRAF immunohistochemistry (IHC) that has been used in recent years and may serve as an alternative to genetic testing, in papillary thyroid carcinoma. A total of 103 cases of papillary thyroid carcinoma were analyzed for BRAF V600E mutation by real-time polymerase chain reaction (PCR) and IHC. The results demonstrated that the BRAF V600E mutation was identified in 55 (53.3%) of 103 cases by real-time PCR, while BRAF IHC positivity was observed in 65 (63.1%) of 103 cases. The study found that the specificity of BRAF IHC was 79.2%, while the sensitivity was 100%. The real-time PCR analysis identified 10 cases that were positive for BRAF IHC and exhibited wild-type BRAF. BRAF IHC can be utilized as a screening test and as a partial alternative to genetic tests. This is due to its low cost, straightforward routine application, moderate to high specificity, and high sensitivity.
Odontogenic keratocysts (OKC) are locally aggressive jaw lesions characterized by a high recurrence rate. Vimentin 3 (VIM3), a truncated splice variant of full-length vimentin (VIMFL), has recently emerged as a potential biomarker in odontogenic tumors. However, its role in OKC and association with recurrence remain unexplored. Formalin-fixed paraffin-embedded samples from OKC (n = 25) and dentigerous cysts (DC) (n = 25) were analyzed. Immunohistochemical staining for VIM3, VIMFL, p53, and Ki-67 was performed. In parallel, reverse transcription-quantitative polymerase chain reaction was used to assess mRNA expression levels of VIM3, VIMFL, and p53. While VIM3 expression did not significantly differ between OKC and DC, recurrent OKC exhibited significantly higher VIM3 labeling indices compared to non-recurrent cases (p = 0.040). This study demonstrates, for the first time, the expression of VIM3 in OKC. Although the findings are promising, further research with larger cohorts and functional validation is required to clarify the mechanistic role of VIM3 in odontogenic cyst biology.
Programmed death-ligand 1 (PD-L1) expression is a critical predictive biomarker for immune checkpoint inhibitor therapies in non-small cell lung cancer (NSCLC). Although various antibody clones are used for immunohistochemical (IHC) detection, differences in platforms and scoring algorithms raise concerns regarding analytical agreement at clinically relevant thresholds. This study evaluated the analytical concordance between VENTANA SP142, VENTANA 22C3, and DAKO 22C3 PD-L1 IHC assays in NSCLC, focusing on therapeutic decision-making thresholds. Non-small cell lung cancer samples from 205 patients were stained using VENTANA SP142, VENTANA 22C3, and DAKO 22C3 assays. Programmed death-ligand 1 expression was assessed in tumor cells using predefined thresholds (< 1%, 1–49%, ≥ 50%). Inter-assay agreement was evaluated using intraclass correlation coefficients (ICC). Strong analytical agreement (ICC > 0.90) was observed between SP142 and both DAKO and VENTANA 22C3 assays in the < 1% and 1–49% expression groups. Agreement decreased between VENTANA SP142 and DAKO 22C3 at the ≥ 50% threshold (ICC = 0.704). Conversely, concordance between VENTANA and DAKO 22C3 was high across all thresholds, particularly in the < 1% and ≥ 50% subgroups (ICC = 1.0 and 0.867, respectively). VENTANA and DAKO 22C3 assays demonstrate high analytical agreement. While SP142 is comparable at low expression levels, its reliability declines at higher thresholds. These findings underscore the necessity of standardized assay selection for accurate immunotherapy stratification in NSCLC.
