Pathobiology最新文献

Introduction: Prostate cancer (PCa) is the most common malignant tumor in men, with acinar adenocarcinoma as the predominant subtype. While PCa metastases typically affect bones, penile metastases are exceedingly rare. Penile tumors are generally squamous cell carcinoma (SCC), with p16 overexpression often used as a surrogate marker for oncogenic human papillomavirus (HPV) infection.

Case presentation: We report the case of an 85-year-old male with a history of PCa (grade group 5) treated with irradiation and hormonal therapy, who presented with a progressive penile lesion initially misdiagnosed as HPV-associated SCC. Immunohistochemistry revealed diffuse panCK, p16, NKX3.1, androgen receptor, and ERG positivity, with Rb1 protein loss confirming metastatic PCa. Prostate-specific antigen levels remained within the normal range, complicating the diagnosis.

Conclusion: This case emphasizes the importance of thorough clinicopathological correlation in unusual metastatic presentations and highlights that p16 overexpression, even in penile tumors, may indicate Rb1 inactivation rather than HPV-related SCC.

Introduction: Keratin (KRT) 24 is a cytoskeletal protein that plays a major role in the formation of intermediate filaments to provide mechanical stability. KRT24 overexpression facilitates tumour cell migration, invasion, and metastasis in several types of cancers. This study evaluates the clinicopathological significance of KRT24 expression in large breast cancer (BC) cohorts with long-term follow-up.

Methods: KRT24 mRNA expression was assessed in publicly available BC datasets (n = 13,025). KRT24 protein expression was evaluated immunohistochemically using well-characterised operable BC cohort (n = 832), and associations with clinicopathological features and patients' outcomes were evaluated.

Results: The KRT24 expression, at both transcriptomic and protein levels, was associated with features indicative of poor prognosis, including high histological grade, ER negativity, and HER2 positivity, and with poor patient outcomes. High KRT24 protein expression in chemotherapy-treated patients was significantly correlated with a shorter survival, a higher risk of distant metastases, and BC-related deaths. Additionally, patients with high KRT24 mRNA expression exhibited dysregulation of several differentially expressed genes and enriched pathways, including the cytokine-cytokine receptor interaction pathway, IL-17 signalling pathway, and oestrogen signalling pathway.

Conclusion: KRT24 expression is associated with poor prognosis in BC. It also plays a predictive role in advanced BC and may represent a potential therapeutic target for patients with this aggressive disease.

Introduction: We report a case of relapse and refractory acute B-lymphoblastic leukemia (r/r B-ALL) apparently turned into acute myeloid leukemia, which is occasional and fatal during CAR-T treatment. There are still limited data to clarify the molecular mechanism of myeloid blast populations proliferation during CAR-T treatment.

Case presentation: A 21-year-old man with an established history of r/r B-ALL with a complex chromosome karyotype and renal extramedullary infiltration presented to our institution. He exhibited a rapid relapse with acute monocytic leukemia 19 days after CD19 CAR-T cell infusion with extensive infiltration of skin and brain. Salvage chemotherapy was ineffective, and he subsequently succumbed to the uncontrolled invasion and infiltration of leukemia cells and hemorrhage. RNA velocity analysis predicted that HSCs differentiated into GMPs and then GMPs differentiated into myeloid lineage cells. The ANXA1-FPR1/2 axis expression was significantly increased post-treatment, which promotes tumor cell proliferation, invasion, and angiogenesis. 6q deletion (6q-) was the common genetic abnormality across all cell populations, indicating that 6q- conferred a survival ability to HSCs during CAR-T cell therapy.

Conclusions: This case demonstrates potential mechanisms of clone evolution molecular events that CD19 CAR-T cell infusion accelerated the existing myeloid lineage evolution via ANXA1-FPR1/2 axis expression from HSCs with 6q-. (Cyto-)genetic aberrations and/or pathways previously not included in the risk stratification of B-ALL might well be predictive for response and outcome in the era of immunotherapy.

Background: Type 1 diabetes mellitus (T1D) is an autoimmune disease marked by the destruction of pancreatic β cells, necessitating lifelong management. Current therapies, such as insulin injections and pancreas transplants, are effective but impose significant burdens, driving the need for innovative solutions. Among these, the bioartificial pancreas (BAP) stands out as a promising approach. By integrating living insulin-producing cells with synthetic matrices, BAP technology aims to replicate natural pancreatic function, offering the potential for more physiologically relevant and patient-friendly treatment. Summary: This review highlights recent advancements in BAP technology, emphasizing innovations in design, materials, and encapsulation techniques that enhance cell viability and function. Key developments include the use of biocompatible materials for cell encapsulation, continuous glucose monitoring systems, and closed-loop control algorithms, which collectively enable real-time glucose regulation. These breakthroughs address critical challenges such as immune rejection and suboptimal device performance, paving the way for clinical translation. Key Messages: BAP technology represents a paradigm shift in T1D treatment, with the potential to alleviate the daily burdens of insulin management. However, challenges remain, including improving device longevity, bolstering immune protection, and reducing production costs to ensure broader accessibility. Future advancements may emerge from integrating BAP systems with cell-protective therapies, further enhancing their efficacy. While hurdles persist, the BAP signifies a transformative step toward simplifying diabetes management and improving the quality of life for millions worldwide.

Introduction: Duodenal adenomas are most commonly associated with polyposis syndromes. Foveolar adenoma is an especially rare entity with an unknown aetiology. We present a case of duodenal foveolar adenoma with coexisting metaplasia, whole exome sequencing results, and the first literature review. Case Presentation: Hereby, we present the case of a 58-year-old man, whose polypectomy specimen revealed a lesion composed of mainly foveolar cells with low-grade dysplasia and was concluded as foveolar adenoma. Due to the incomplete resection, polypectomy was repeated; this time, foveolar adenoma was diagnosed with high-grade dysplasia. Foveolar differentiation was proved with MUC5AC immunohistochemistry; in addition, KRAS and SMAD4 pathogenic mutations were identified. Discussion: Duodenal foveolar adenoma remains a controversial and an enigmatic entity. Our paper presents such a lesion with first low-grade, then high-grade dysplasia, and KRAS mutation, identical to gastric manifestations. The further sample of our patient suggests foveolar metaplasia as an aetiological factor that supports the literature data.

Introduction: Defining the origin of metastatic cancer is crucial for establishing an optimal treatment strategy, especially when obtaining sufficient tissue from secondary malignancies is limited. While cytological examination is often used in this diagnostic setting, morphologic analysis alone often fails to differentiate metastases derived from the breast from other primaries. The hormone receptor, human epidermal growth factor receptor-2, gross cystic disease fluid protein 15, and mammaglobin immunohistochemistry are often used to diagnose metastatic breast cancer. However, their effectiveness decreases in estrogen receptor (ER)-negative breast cancers, including the triple-negative breast cancer (TNBC) subtype.

Methods: We conducted a comprehensive evaluation of GATA-binding protein 3 (GATA-3), trichorhinophalangeal syndrome type 1 (TRPS-1), and Matrix Gla Protein (MGP) immunochemistry across 140 effusion cytology specimens with metastatic adenocarcinoma derived from various primaries, including the breast, colon, pancreaticobiliary, lung, tubo-ovarian, and stomach.

Results: The expression rates of these immunomarkers were significantly higher in metastatic cancers originating from the breast than other primaries. In TNBC, TRPS-1 (80.00%) and MGP (65.00%) exhibited higher positivity rates compared to GATA-3 (40.00%). Additionally, our data suggest that an immunohistochemical panel comprising MGP, GATA-3, and TRPS-1 significantly enhances the detection of metastatic breast cancer in effusion cytology specimens, including TNBC in particular. When considering dual-marker positivity, the diagnostic accuracy was found to be 89.29% across all breast cancer subtypes and 92.93% for TNBC.

Conclusions: MGP appears to be a robust marker for identifying metastatic breast cancer in malignant effusions, especially TNBC. MGP notably enhances diagnostic accuracy when incorporated together with GATA-3 and TRPS-1 in an immunohistochemical panel.