Pathology & Oncology Research最新文献

Background: Follicular lymphoma (FL) is an indolent yet incurable B-cell lymphoma subtype commonly treated with a combination of bendamustine and anti-CD20 antibodies such as rituximab. While the standard administration involves a 2-day dosing schedule, the COVID-19 pandemic prompted the exploration of a 1-day regimen to reduce hospital visits for immunocompromised patients. This study aimed to compare the efficacy and safety of 1-day versus 2-day bendamustine regimens.

Methods: We conducted a retrospective analysis of 144 patients with FL, marginal zone lymphoma, mantle cell lymphoma, or Waldenström macroglobulinemia treated at the Department of Internal Medicine and Hematology, Semmelweis University between 2015 and 2023. All patients received bendamustine combined with either rituximab or obinutuzumab. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS) and toxicity. Kaplan-Meier survival analysis and appropriate statistical tests were applied.

Results: The median PFS for the cohort was 69.47 months; OS was not reached. Despite receiving a significantly lower cumulative dose, and being significantly older, patients on the 1-day regimen had similar PFS (not reached vs. 69.47 months; p = 0.885) and no significant difference in OS (p = 0.147) compared to the 2-day group. Adverse events were more frequent in the 2-day regimen group, including severe side effects, such as neutropenia (p = 0.044).

Conclusion: A 1-day bendamustine regimen may offer comparable efficacy to the standard 2-day schedule, with a potentially more favorable toxicity profile and better convenience, especially in older or more vulnerable patient populations. These findings warrant further investigation in prospective randomized trials to establish optimal dosing strategies.

Cancer metastasis, driven by cell migration, remains the leading cause of cancer-related deaths. In breast cancer, its high metastatic potential underscores the need for better preclinical models to bridge the gap between laboratory findings and clinical outcomes. However, studying migration in vitro remains challenging due to the complexity of tumour invasion and the difficulty of replicating physiologically relevant conditions. Traditional two-dimensional (2D) models, such as the scratch assay and transwell migration assay, offer simplicity and reproducibility but fail to capture the tumour microenvironment and dynamic migration behaviours. Advanced three-dimensional (3D) models, including spheroids, organoids, microfluidic systems, and organ-on-a-chip platforms, provide more physiologically relevant conditions but are often limited by cost and technical complexity. This mini-review provides an overview of widely used in vitro models for studying breast cancer migration and evaluates their respective advantages, limitations, and future potential. While no single system currently achieves the ideal balance between physiological relevance and practical accessibility, combining complementary tools remains the most effective strategy for investigating the metastatic cascade. Continued innovation in in vitro platforms is essential for improving translational accuracy and supporting the development of more effective anti-metastatic therapies.

Sarcomas are a heterogeneous group of rare and aggressive malignancies and have a propensity to metastasize to the thoracic cavity. While sarcoma lung metastasectomy is an established modality, only scarce information is available about potential prognostic factors for sarcoma patients with pleural dissemination. Accordingly, all consecutive sarcoma patients treated at our thoracic surgery department between 2010 and 2023 with pleural sarcomatosis and/or malignant pleural effusion were retrospectively analyzed. Preoperative circulating biomarker values were collected at the time of first pleural involvement. Overall survival was calculated from the first sarcoma diagnosis as well as from the first diagnosis of pleural dissemination. 98 patients (42 female) were included in the cohort with a median age of 54.6 years (range: 15.9-84.3 years) at the time of pleural involvement. 77 patients had soft tissue sarcoma, while 21 patients had primary sarcoma in the bone including 4 chondrosarcoma. Among the 19 different sarcoma types, synovial sarcoma (13%), liposarcoma (11%), undifferentiated pleomorphic sarcoma (11%), Ewing (like) sarcoma (10%) and leiomyosarcoma (9%) were the most frequent. Pleural dissemination was mostly metachronous, while only 7 cases were synchronous. The median pleural dissemination-free interval was 17.1 months after sarcoma diagnosis. The median overall survival after pleural dissemination was 12 months. WBC values outside the normal range had no significant impact on overall survival. High LDH (>250 U/L) and CRP (>1 mg/dL) conferred significantly lower overall survival (8.6 months vs. 19.1 months (p < 0.0001) and 4.9 months vs. 29 months (p < 0.0001), respectively). Albumin alone showed no prognostic impact, however, the modified Glasgow prognostic score (0, 1, and 2) was a strong prognosticator (20.4 vs. 8.6 vs. 1.7 months (p < 0.0001). In a multivariable analysis, CRP remained a significant prognostic factor. In conclusion, routine circulating biomarkers carry prognostic information for sarcoma patients with pleural dissemination and should be considered for risk stratification and personalized therapeutic decisions.

Recognition of unusual histological features can augment and hasten a diagnosis but also stimulate ideas about physiological and pathological cellular interactions. Osteoclasts resorb mineralised tissue and therefore can be found at sites of heterotopic bone formation. However, multinucleated giant cells with morphological features of osteoclasts, so called 'osteoclast-like cells' can also be encountered in a variety of soft tissue tumours unrelated to ossification and calcification. Prompted by the presence of osteoclast-like cells in undifferentiated pleomorphic sarcoma while undertaking our Artificial Intelligence project for classifying sarcoma, we reviewed the English literature for these cells in soft tissue tumours and we found that this was poorly documented, and much was published before the release of the WHO essential diagnostic criteria in 2020. There were numerous single case reports and small series of a broad range of soft tissue tumours with osteoclast-like cells but only a limited number of diagnoses in which these cells were reported recurrently. We provide a comprehensive update of osteoclast-like cells and mineralisation in soft tissue tumours from the literature. We also present real-world incidence of osteoclast-like cells from selected tumour types in our Whole Slide Image (WSI) library of soft tissue tumours. Assessment of WSI from 1100 different patients showed that osteoclast-like cells were relatively common and under-recognised in nodular fasciitis (18.5 of 200), angiomatoid fibrous histiocytoma (17.5% of 40), undifferentiated pleomorphic sarcoma (15% of 261) and epithelioid sarcoma (9% of 68) while they were never encountered in myxofibrosarcoma (0/250) and clear cell sarcoma of soft tissue (0/80). Awareness of this phenomenon not only helps shape the differential diagnosis but also can be used to stimulate pathobiological questions and to enhance the performance of AI models for classifying disease.

Objective: We aimed to analyze the relationship between the quantitative and qualitative parameters of three-dimensional computed tomography (CT), epidermal growth factor receptor (EGFR), and anaplastic lymphoma kinase (ALK) in ground-glass opacity (GGO)-associated lung adenocarcinoma and determine their prognostic value.

Methods: In total, 208 patients with GGO-associated lung adenocarcinoma admitted to our hospital from January 2019 to September 2021 were selected as study subjects. All participants underwent EGFR gene mutation and ALK gene rearrangement tests. The quantitative and qualitative parameters of three-dimensional CT scans were compared among patients with different EGFR gene mutations and ALK gene rearrangements. Multivariate analysis was conducted to investigate the association of these parameters with EGFR gene mutation and ALK gene rearrangement in patients with GGO-associated lung adenocarcinoma. Furthermore, the quantitative and qualitative parameters of three-dimensional CT scans were compared among patients with different prognoses, and the value of these parameters in predicting patients' prognoses was analyzed.

Results: There were significant differences between patients with wild-type EGFR and patients with mutant EGFR in terms of the bronchial sign (BS), pleural indentation sign (PIS), vascular bundle sign (VBS), maximum nodule diameter (MND), nodule volume (NV), average CT value (ACTV), and solid compartment proportion (SCP) (P < 0.05). There were significant differences between patients with and without ALK gene rearrangement in terms of the BS, PIS, VBS, ACTV, and SCP (P < 0.05). There was a significant difference in BS, PIS, VBS, MND, NV, ACTV, and solidity between patients with favorable prognosis and those with poor prognosis (P < 0.05). The AUC of the combination of BS, PIS, VBS, MND, NV, ACTV, and SCP for predicting patients' prognosis was the highest, significantly higher than the AUC value of individual parameters (P < 0.05).

Conclusion: The quantitative and qualitative parameters of three-dimensional CT are closely associated with EGFR gene mutations, ALK gene rearrangements, and prognosis in patients with GGO-associated lung adenocarcinoma. Moreover, each parameter holds a high value in predicting the prognosis of patients with GGO-associated lung adenocarcinoma.

Introduction: Solid papillary carcinoma (SPC) is a rare type of breast cancer that accounts for approximately 1% of all breast cancers. Although SPC is considered an indolent tumor, metastasis occurs in a few cases. The biological behavior and genomic characteristics of invasive SPC (ISPC) need to be further explored.

Case presentation: A 44-year-old woman presented with a mass in her right breast in 2016 and ultrasound-guided mammotome (MMT) vacuum-assisted biopsy (VAB) pathology indicated an invasive lobular carcinoma (ILC). The patient subsequently underwent right partial mastectomy and axillary lymph node dissection, followed by radiotherapy and hormonal therapy. Eight years later, in 2024, ultrasonography revealed a 1.3 cm*1.0 cm mixed echogenic mass in her right breast, and biopsy pathology showed solid tumor nests with mucus secretion and thin fibrovascular cores. The pathological diagnosis was SPC with positive expression of the neuroendocrine marker synaptophysin (syn). The patient underwent right subcutaneous mastectomy with prosthesis implantation, followed by hormonal therapy. Four months later, multiple masses were found in her liver by ultrasonography and contrast-enhanced magnetic resonance imaging (MRI), which were eventually confirmed as metastatic SPC by pathology. A comprehensive next-generation sequencing (NGS) panel test was performed, and more genetic changes were identified including CCND1, FGF19, GATA3, KMT2C, MEN1, TP53, BRCA2, PI3KC3, and ERCC2::KLC3 fusion. The patient was treated with hormonal therapy combined with CDK4/6 inhibitors and so far no new lesions have appeared.

Conclusion: We report a case of ISPC with liver metastasis in a patient with a history of ILC. Some meaningful genetic variations were identified by NGS. Further studies are needed to elucidate the molecular characteristics of SPC and explore the best therapeutic strategies.

Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide. Despite advances in various treatment approaches, outcomes for patients with metastatic CRC (mCRC) remain poor, and treatment-associated side effects significantly impact quality of life. While immunotherapy has shown promise in certain malignancies, its efficacy in CRC is limited to a minority of patients, highlighting the urgent need for novel therapeutic targets to improve treatment efficacy while minimizing off-target effects. B7-H3 (CD276) has emerged as a promising immunotherapeutic target due to its selective expression on tumor cells and neovasculature, with minimal presence in healthy tissues. A novel IgG-based bispecific antibody targeting B7-H3 and CD3, CC-3, has demonstrated strong preclinical efficacy in stimulating T cell-mediated antitumor responses and is currently being evaluated in a first-in-human trial including patients with mCRC (NCT05999396). In this study, we investigated B7-H3 expression in a cohort of n = 55 mCRC patients and assessed its correlation with demographic, pathological, and molecular factors, as well as clinical outcomes. Additionally, to evaluate the stability of B7-H3 expression over time, we analyzed sequential biopsies from metastatic lesions from n = 7 patients at subsequent time points. Our findings demonstrate that B7-H3 is consistently overexpressed in mCRC, independent of demographic factors, primary tumor localization (right vs. left colon), common molecular and genetic alterations (HER2, MSI, KRAS, NRAS, BRAF, PIK3CA, p53), and serum tumor markers. Longitudinal analysis showed that B7-H3 expression was comparable or increased over time in sequential metastatic specimens. No significant association was observed between B7-H3 expression and overall survival or progression-free survival, and prior chemotherapy treatment did not influence B7-H3 expression levels. In conclusion, B7-H3 is stably and ubiquitously expressed in mCRC, reinforcing its potential as a robust target for immunotherapeutic strategies, including bispecific antibodies. The lack of variability across patient subgroups suggests that routine pre-treatment assessment of B7-H3 may not be necessary. These findings provide a strong rationale for the continued clinical evaluation of B7-H3-targeted therapies, such as CC-3 (NCT05999396), in mCRC patients.

Conjunctival melanoma (CoM) is a rare and aggressive ocular surface malignancy, characterised by increasing incidence, clinical complexity, and substantial challenges in diagnosis and treatment. This review consolidates current knowledge on epidemiology, clinical presentation, genetic and epigenetic foundations, molecular mechanisms, emerging therapeutic strategies, and prognostic factors for localised and metastatic CoM. CoM exhibits distinct biological behaviours, sharing molecular traits with cutaneous and mucosal melanomas, while significantly diverging from uveal melanoma. Key genetic alterations include mutations in BRAF, NF1, and PTEN, elevated mTOR expression, and specific miRNA profiles, which influence tumour progression and response to therapy. Recent advances in treatment, especially immune checkpoint inhibitors such as CTLA-4 and PD-1 receptor inhibitors, along with targeted therapies like BRAF and MEK inhibitors, have led to marked improvements in outcomes for advanced cases. Emerging strategies, including dendritic cell vaccines and epigenetic therapies, hold considerable promise in addressing ongoing clinical challenges. This review integrates case studies and clinical research to demonstrate the practical application of these therapies, highlighting their efficacy and limitations. Combining clinical expertise, genetic insights, and the latest therapeutic developments, offers a comprehensive overview of CoM, underscoring the critical role of a multidisciplinary approach in optimising diagnosis, management, and prognosis to improve patient outcomes.

Purpose: Traditional markers have various limitations in recognizing the breast origin of distant metastatic breast carcinoma (DMBC), especially in ER-negative or low expression cases. In recent years, TRPS1 has been reported as a breast marker with satisfactory sensitivity and specificity in triple-negative breast cancers (TNBC). We aimed to compare the expression of TRPS1, GATA3, and GCDFP-15 in ER-negative or low-ER-expressing DMBC, and to further evaluate the diagnostic value of TRPS1.

Methods: Immunohistochemical staining for TRPS1, GATA3, and GCDFP-15 was performed in 107 cases of ER-negative or low expression DMBC specimens. Nuclear staining was considered positive for TRPS1 and GATA3, and cytoplasmic staining was considered positive for GCDFP-15.

Results: The positive rates for TRPS1, GATA3, and GCDFP-15 were 90.65% (97/107), 91.59% (98/107), and 42.99% (46/107), respectively. There was no significant difference in the expression rate and intensity between the first two markers (p = 0.929), but both rates were significantly higher than that of GCDFP-15 (p < 0.05). Among these, 6 cases showed positive expression for TRPS1 while GATA3 and GCDFP-15 were negative; 8 cases showed positive expression for GATA3 while TRPS1 and GCDFP-15 were negative.

Conclusion: TRPS1 is as effective as GATA3 in confirming breast origin for ER-negative or low expression DMBC, and the two markers exhibit excellent complementary effects, both outperforming GCDFP-15. The combined application of TRPS1 and GATA3 is the optimal method to confirm that ER-negative or low-expression distant metastatic carcinoma originates from the breast.

This study provides a comprehensive analysis of early-stage resectable non-small cell lung cancer (NSCLC) in Hungary, investigating incidence rates, demographic trends, treatment patterns and survival outcomes. We used data from the National Health Insurance Fund (NHIF) spanning 2013-2022, and we analyzed 6,571 patients with available NSCLC histology and no metastasis, who underwent curative surgery within 6 months of diagnosis, and evaluated epidemiological trends and the use of neoadjuvant and adjuvant therapies. For the efficacy analysis, we narrowed the patient cohort to 5,494 patients diagnosed and treated between 2013 and 2019 with at least three-year follow-up data. Key endpoints included overall survival (OS) and disease-free survival (DFS), inferred via time to first subsequent therapy (TFST). Our results revealed a gradual decline in early-stage resectable NSCLC diagnoses, with a significant drop in 2020, likely linked to COVID-19 restrictions. Older age groups (66-75 years) represented a growing proportion of cases, reflecting shifting demographic trends. Among patients with EGFR mutations receiving EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy, OS significantly improved compared to those not receiving EGFR-TKI therapy, who are assumed to have wild-type EGFR status (HR = 0.58 (95% CI: 0.47-0.72), p < 0.0001). These findings underscore the importance of early detection, comprehensive biomarker testing and targeted therapies in improving outcomes for resectable NSCLC patients. Future studies with extended follow-up and integration of broader clinical data, including staging and patient comorbidities, are warranted to optimize therapeutic strategies.