Dm Loos

Background: Preventing metastasis is important for improving the survival rates of patients with non-small-cell lung cancer (NSCLC). Our previous investigation suggested that premalignant epithelial changes in small bronchi distant from the primary tumor serve as predictive markers of NSCLC metastasis. Specifically, isolated basal cell hyperplasia (iBCH) is associated with a high risk of distant metastasis, whereas basal cell hyperplasia combined with squamous metaplasia (BCH + SM) correlates with a low risk of distant metastasis. Methods: This exploratory study included patients enrolled both retrospectively and prospectively. A total of 83 NSCLC patients were stratified into two groups: iBCH (high metastatic risk, n = 59, including 37 metastatic events) and BCH + SM (low metastatic risk, n = 24, including 6 metastatic events). Paired peripheral blood and tumor samples from NSCLC patients with iBCH and BCH + SM were subjected to whole exome sequencing. Bioinformatic analysis included tumor mutation quantification, detection of regions with enriched mutations, mutational signatures profiling, and evaluation of metastasis-free survival and hazard ratio modeling. Results: Patients with iBCH were characterized by a higher prevalence of single nucleotide variants and a lower frequency of frameshift mutations. Single-nucleotide indels (mainly insertions) were more frequent in patients with BCH + SM. Additionally, ID1, ID3, ID11, and ID13 mutational signatures were significantly enriched in patients with BCH + SM. Moreover, the combination of SBS3, SBS4, DBS1, DBS2, DBS6, ID8, and ID23 signatures was linked to distant metastasis in NSCLC patients. Finally, a multivariable logistic regression model for assessing the probability of distant metastasis in NSCLC was developed based on the histological subtype, the bronchial lesion, and mutational signature. Conclusions: NSCLC with high and low risk of distant metastasis defined by bronchial lesions have specific mutational landscapes.

Trophoblast cell surface antigen 2 (TROP2) has emerged as a promising therapeutic target in non-small cell lung cancer (NSCLC) in the context of the development of antibody-drug conjugates. In this setting, reproducible and biologically meaningful immunohistochemical assessment of TROP2 expression, taking into account its intracellular localization, is of particular importance. Objective. To characterize TROP2 expression in lung adenocarcinomas and squamous cell carcinomas and to evaluate its association with clinicopathological parameters using different immunohistochemical assessment methods. Material and methods. This retrospective single-center study included 60 cases of NSCLC (30 adenocarcinomas and 30 squamous cell carcinomas) diagnosed between 2019 and 2023. TROP2 expression was evaluated by immunohistochemistry using the semi-quantitative H-score and the normalized membrane ratio (NMR), reflecting the relative contribution of membranous and cytoplasmic expression. Associations between TROP2 expression and clinicopathological characteristics were analyzed. Results. TROP2 expression was detected in all examined NSCLC samples. TROP2 expression assessed by H-score was significantly higher in squamous cell carcinoma compared with lung adenocarcinoma (p=0.0001), whereas NMR values did not differ between histological subtypes. No associations were observed between H-score and clinicopathological parameters. In contrast, NMR demonstrated histotype-dependent associations: with tumor stage in lung adenocarcinoma (p=0.0483) and with lymphovascular invasion in squamous cell carcinoma (p=0.0139). The proportion of cases meeting the NMR-based criteria for TROP2 positivity was low. Conclusion. The results indicate that the choice of TROP2 assessment method substantially influences data interpretation. Consideration of intracellular protein localization using the NMR appears to be more informative than conventional semi-quantitative approaches and may reflect biological features of tumor progression in NSCLC.

Background: Fibroblast activation protein (FAP) is a promising target for cancer diagnosis and therapy, but the specificity and sensitivity of anti-FAP antibodies used for immunohistochemistry (IHC) vary considerably. A head-to-head comparison of commercially available clones is needed to guide antibody selection, thereby standardizing FAP IHC protocols and ensuring reliable patient stratification for FAP-directed therapies. Methods: We evaluated three anti-FAP clones—FAP/4851 (mouse monoclonal), JA56-11 (recombinant rabbit), and EPR20021 (rabbit monoclonal)—in formalin-fixed, paraffin-embedded tissues from 137 patients with breast (n = 29), colorectal (n = 27), lung (n = 42), and head and neck squamous cell carcinoma (n = 39). FAP expression was assessed by manual semiquantitative scoring (H-score and percentage of positive cells) and, for a validation subset, by QuPath-based digital image analysis. The study included negative (normal liver/skeletal muscle) and positive (WI-38 cell block) controls. Results: Clones JA56-11 and EPR20021 showed specific stromal staining, whereas FAP/4851 exhibited intense non-specific reactivity and was excluded from quantitative analysis. EPR20021 demonstrated significantly higher H-scores than JA56-11 in all four cancer types (Wilcoxon test, p ≤ 0.0179), resulting in a higher overall detection rate under the tested conditions. Aberrant tumor cell expression was detected almost exclusively by EPR20021 in head and neck (59% of cases) and colorectal (59%) cancers. QuPath validation showed good correlation with manual scoring for EPR20021 in the tumor compartment of lung cancer (Spearman’s ρ = 0.701, p = 0.024) with small bias (Bland–Altman). Conclusions: Under the conditions tested, EPR20021 (Abcam) demonstrated higher staining intensity and detection rates than JA56-11 across several tumor types. Clone FAP/4851 showed nonspecific staining under the conditions used in this study and was therefore not suitable for quantitative analysis in the present experimental setting. Consequently, careful selection of well-validated antibody clones is essential for ensuring reproducible and reliable FAP immunohistochemical analysis.

Benign neoplasms of the tracheobronchial tree are rare, accounting for approximately 7-10 % of all primary lung tumors. Endobronchial lipoma is an extremely uncommon benign tumor, comprising approximately 0.5 % of all bronchial tumors. These benign tumors typically have a rounded shape, a distinct capsule, and an elastic consistency. Morphologically, lipomas appear as mature adipose tissue separated by connective tissue septa. Intrabronchial location within the tracheobronchial tree is the most common; this type of tumor growth is observed 4-5 times more often than perior exobronchial lesions. The absence of pathognomonic symptoms and clinical manifestations, coupled with the slow growth of the tumor, often leads to late diagnosis. The primary goal in treating endobronchial lipomas is to eliminate bronchial obstruction and prevent irreversible changes to lung tissue. For large tumors obstructing the bronchial lumen or the presence of significant secondary changes to the lung tissue, endoscopic removal is not advisable. Surgical treatment, including segmentectomy or lobectomy, is the optimal option. Here we present a case of successful combined diagnostic approaches for rare endobronchial lipoma. Case presentation . A 79-year-old man presented with benign tumor in the left bronchial tree, with minimal respiratory symptoms. A chest computed tomography revealed a fat-density lesion within the lumen of the left lower lobe bronchus with partial obstruction of the bronchial lumen. Bronchoscopy demonstrated a mass lesion extending into the lower third of the left main bronchus. Conclusion. The presented clinical case demonstrates the challenges associated with the timely diagnosis of endobronchial lipomas and highlights the importance of the multidisciplinary approach utilizing imaging, endoscopic, and histopathological examination for diagnostic verification and treatment planning.

Background. Breast cancer is the most common cancer and the leading cause of cancer mortality among women. Determination of the molecular subtype is a key step in selecting the appropriate treatment strategy. Despite the standardization of current diagnostic methods, the risk of diagnostic errors remains significant, highlighting the need for noninvasive technologies that enable simultaneous assessment of tumor extent and HER2 expression. The purpose of study was to evaluate the feasibility of anatomical visualization and determination of the HER2 receptor status of primary breast tumors and malignant axillary lymph nodes (mAlN) using [ ^99m Tc]Tc-ADAPT6. Material and Methods . The study included 40 patients with T2−4N1−3M0 breast cancer before starting systemic treatment. All patients underwent morphological and iHC studies of HER2 expression in tumors and mAlN (25 patients with positive and 15 patients with negative HER2 status). The patients were injected with 500 µg of [ ^99m Tc]Tc-ADAPT6 followed by SPECT/CT imaging 2 hours after injection. The accumulation of [ ^99m Tc]Tc-ADAPT6 was assessed by measuring the SUV _max in the primary breast tumor and the contralateral breast (background), as well as in mAlN and contralateral axillary region (background), the liver, the latissimus dorsi muscle (lDM) and the spleen. Tumor-to-reference organ and mAlN-to-reference organ ratios were also measured. Statistical data was calculated using Prism 10.2 for Windows. Results. The findings demonstrated the feasibility of assessing locoregional disease extent and HER2 receptor status in the primary breast tumor and metastatic axillary lymph nodes using the radiopharmaceutical [ ^99m Tc]Tc-ADAPT6. The tumor-to-lDM ratio ≥11.46 relative units was the most informative parameter for differentiating HER2-positive from HER2-negative status in primary tumors (80 % sensitivity and 86 % specificity, pConclusion . The use of [ ^99m Tc]Tc-ADAPT6 in breast cancer patients enables assessment of locoregional disease extent and discrimination between HER2-positive and HER2-negative status in the primary tumor and metastatic axillary lymph nodes.

Introduction : Solitary fibrous tumor (SFT) — a rare mesenchymal tumor of fibroblastic origin. Solitary fibrous tumor is not a tumor of the pleura itself, unlike diffuse mesothelioma. The SFT was first described by E. Wagner in 1870. Non-specific clinical manifestations of solitary fibrous tumor complicate the diagnostic search and significantly expand the differential diagnostic range. Purpose : To demonstrate a rare case of solitary fibrous tumor of the pleura and to show, using a clinical case as an example, the difficulties of its diagnosis. Materials and methods : Multislice computed tomography (MSCT) of the chest organs performed to the patient with complaints of cough and shortness of breath during intense physical activity. Formation was detected with clear contours, a heterogeneous structure, located subpleurally was revealed. Results : The presented observation demonstrates non-specific radiological manifestations of a solitary fibrous tumor and illustrates the importance of correct interpretation of data and choice of diagnostic algorithm.

Understanding the molecular mechanisms of carcinogenesis, including disruptions in the homologous recombination system, is fundamental to understanding malignant transformation. Dysfunction of homologous recombination genes, such as BRCA1 and BRCA2, contributes to genomic instability and the development of more aggressive tumor clones. The use of chemical carcinogens enables the modeling of tumor formation and the monitoring of changes in molecular genetic parameters. This approach is important for understanding how tumor cells adapt to genotoxic stress and for advancing the development of personalized cancer therapies. The objective of this study was to evaluate the expression of key homologous recombination system genes in a model of chemically induced carcinogenesis in mice. Materials and Methods: Male outbred ICR (CD-1) laboratory mice (n = 40) were used to study chemically induced carcinogenesis. The animals were divided into four groups: two control groups and two experimental groups, which received 3-methylcholanthrene (MC) or trichloroacetic acid (TCA). Tumor cells were identified by histological analysis of autopsy material using light microscopy after standard hematoxylin and eosin staining. RNA and DNA were extracted from cell suspensions using the RNeasy Plus Mini Kit and QIAamp DNA Mini Kit (Qiagen, Hilden, Germany), respectively. The expression levels of homologous recombination genes were assessed by RT-PCR and microarray analysis. Digital PCR was performed to assess chromosomal aberrations in the Brca1 gene. Results: Tumor formations were identified in laboratory animals two months after 3-methylcholanthrene. Histological analysis revealed morphological changes in a pleomorphic cell tumor, forming diverse, multidirectional fascicular and swirling structures, as well as large solid foci composed of markedly polymorphic spindle-shaped and epithelioid cells. Analysis of copy number aberrations in the examined samples showed that the frequency of Brca1 deletions was 60%, while 40% of animals had normal gene copy number. To further characterize the molecular changes, we assessed gene expression levels through expression microarray analysis. A total of 14 genes were hypoexpressed in the tumor compared to the normal tissue, with p < 0.05. A high level of differential expression was characteristic for Rad50, Rad51, Brca1, Brca2, and Pold4. Two genes, Rad52 and Bard1, exhibited increased expression levels. It was shown that as the tumor mass increased, so did the frequency of homologous recombination genes with hypoexpression. Conclusions: Our findings confirm that MC and TCA influence tumor formation and reveal that suppression of homologous recombination genes may contribute to this process. In addition, it has been established that as tumors progress, the expression of DNA repair genes declines and aberrant gene states accumulate. These data emphasize the importance of studying the state of DNA repair genes for the development of more effective strategies for cancer diagnosis and therapy.

Cellular plasticity, a critical feature of embryonic development, is often reactivated in cancer, enabling tumor cells to acquire stem-like properties and facilitate uncontrolled growth. This study compares cellular plasticity in cancer and early human development by integrating single-cell data from three cancers and embryoid bodies. The analysis identifies a shared, highly proliferative progenitor-like state, driven by an E2F-TFDP transcriptional axis and enriched in key cell-cycle regulators UBE2C , TOP2A , BIRC5 , and NUSAP1 . Functionally linked to cell-cycle progression and DNA repair, this state acts as a lineage hub within tumors. Spatial transcriptomics revealed that this state is enriched in lung adenocarcinoma and in lung tissue with basal cell hyperplasia, a potential precursor to squamous cell carcinoma. Validation across eight cancer types demonstrates a prevalence of this program in tumors versus normal cells. Collectively, these findings define a conserved mechanism of tumor plasticity with potential for early detection and targeted therapy. Abstract Figure:

Aim of the study : to provide a contemporary overview of the nomenclature and terminology of Recklinghausen– Engel syndrome (parathyroid osteodystrophy), its pathogenesis, and characteristic morphological and radiological manifestations. Special attention is paid to the differential diagnosis between brown tumor and skeletal giant cell tumor. The study aims to present the clinical and morphological criteria for distinguishing these conditions, systematized in a comparative table. Material and Methods . A literature search was conducted in the Medline, PubMed, Elibrary, and other databases. Of the 100 identified publications, 30 were included in this systematic review. We report a case of a resected brown tumor of the femur in a 58-year-old man with previously undiagnosed hyperparathyroidism, detailing the morphological diagnostic features and the disease course. Results. Recklinghausen-Engel syndrome (parathyroid osteodystrophy) is a rare but clinically significant metabolic skeletal disorder that develops in the setting of hyperparathyroidism. It is characterized by marked osteoclastic activity, the formation of cystic lesions, subperiosteal resorption, and so-called brown tumors. Despite its benign nature, this syndrome often mimics aggressive giant cell bone tumors, which complicates the interpretation of clinical, radiological, and morphological data and increases the risk of diagnostic errors. Conclusion. This article discusses the diagnostic challenges in the absence of overt clinical symptoms of hyperparathyroidism and emphasizes the key role of the pathomorphologist within a multidisciplinary team. Timely detection of parathyroid hormone hypersecretion and radical removal of the hyperplastic or neoplastic parathyroid gland lead to the regression of bone lesions and a favorable prognosis.

Objective. To study the microenvironment features of MMR-proficient (pMMR) and MMR-deficient (dMMR) endometrial cancer. Material and methods. The study included 34 patients with pMMR endometrial cancer and 10 patients with dMMR endometrial cancer. Using the method of multiplex TSA-associated (tyramide signal amplification) immunofluorescence, phenotyping of the tumor microenvironment was performed with an assessment of stromal and intratumor cell localization and PD-1 expression. Results. In pMMR endometrial tumors, the predominant cell population was CD163+ macrophages, and in tumors with dMMR, CD163+ macrophages were found equally with CD8+ T lymphocytes and CD20+ B lymphocytes. In dMMR tumors, the number of CD8+ T lymphocytes and CD20+ B lymphocytes (as well as CD20+ B lymphocytes expressing PD-1) is higher compared to pMMR tumors, while the number of FoxP3+ T lymphocytes was significantly lower. The number of CD163+ macrophages did not differ depending on the MMR status, while the number of CD163+ macrophages was higher in the stroma compared to the number of these cells located intraepithelially. In patients with dMMR tumors, the number of CD8+ T lymphocytes was higher in the stroma, and did not differ in pMMR tumors. Conclusion. In this study, it was found that dMMR endometrial tumors are characterized by an increase in the proportion of CD8+ T lymphocytes and CD20+ B lymphocytes, which may be associated with a better response to immunotherapy. The differences in spatial distribution of CD8+ T lymphocytes and CD163+ macrophages confirmed the importance of immune cell localization for prognosis and treatment efficacy. These results highlight the need for further study of the endometrial cancer microenvironment in order to personalize therapy.