Malignant melanoma demonstrates strikingly varied clinical presentations, on account of which it is often challenging to diagnose. We describe herein a rare case of amelanotic malignant melanoma (AMM) in the buccinator muscle presenting as a solitary mass. A middle-aged woman presented with a non-pigmented swelling under the right buccal mucosa. Magnetic resonance imaging (MRI) revealed a well-circumscribed lesion without local invasion. A needle biopsy did not establish the diagnosis and was instead interpreted as suggestive of a salivary gland tumor, reinforcing an initial impression of myoepithelioma. Histopathological analysis of an excised specimen revealed poorly defined, pleomorphic tumor cells and a scattering of melanin-containing cells. The diagnosis of AMM was established by integrating these histopathological features with the clinico-radiological findings and the immunohistochemical results, which were positive for HMB-45, S-100, and SOX10 and negative for cytokeratin. Whole-body positron-emission tomography-computed tomography found no primary lesion. Because tumor nests suggesting possible residual disease were observed near the resection margin, a wider, secondary excision including the affected portion of the buccal mucosa and overlying skin was performed together with neck dissection. Histopathological examination of the re-resection specimen showed no residual tumor, indicating that no malignant cells were identified in the adjacent oral mucosa or facial skin. The patient has remained disease-free for three years.

Cervical cancer remains a major global health challenge and a leading cause of gynecological cancer-related mortality, particularly in developing countries. Although persistent human papillomavirus infection is the primary driver of cervical carcinogenesis, host factors such as immune dysregulation and microbiome dysbiosis may contribute to disease progression. Corisin is a microbiota-derived peptide implicated in epithelial injury and fibrosis, but its role in cervical neoplasia is unknown. To investigate its potential involvement, circulating corisin levels were measured in 27 women with cervical intraepithelial neoplasia (CIN) or cervical cancer and compared with those in 15 healthy women. Corisin localization in cervical carcinoma tissues was examined by immunohistochemistry, and its biological effects were evaluated in HeLa cells. Circulating corisin levels were significantly elevated in patients with CIN and cervical cancer, with the highest levels observed in CIN3 and cervical squamous cell carcinoma. Corisin was detected within cervical carcinoma tissues in intracellular and extracellular compartments adjacent to tumor cells. In HeLa cells, corisin accumulated in mitochondria, impaired cell-cycle progression, induced apoptosis, increased p21 expression, and promoted epithelial-mesenchymal transition-like morphological changes. These findings suggest that corisin is elevated from the early stages of cervical neoplasia, is present within the cervical tumor microenvironment, and may contribute to pathogenic cellular processes associated with cervical cancer progression.

Background Primary care is the main route to diagnosis for patients with prostate cancer, either following asymptomatic Prostate Specific Antigen (PSA) testing or investigating prostate-related symptoms. Whilst previous primary care studies suggest an association between symptoms and prostate cancer diagnosis, it remains unknown whether outcomes differ based on the presence or absence of symptoms. Aim To compare prostate cancer stage, grade, and mortality amongst symptomatic patients presenting to primary care with asymptomatic patients. Design and setting Retrospective cohort study using Clinical Practice Research Datalink (CPRD) Aurum. Included adult males aged 50 years and above with first presentation to primary care for coded lower urinary tract symptoms (LUTS), haematuria, or erectile dysfunction between 01/01/2011 and 31/12/2016 with up to two asymptomatic males matched by age, ethnicity, and GP practice. Method Main outcomes: Clinically significant prostate cancer (Gleason Grade Group ≥ 3); Early-stage prostate cancer; Cambridge Prognostic Group; prostate cancer mortality; all-cause mortality. Mixed effect logistic regression modelling was performed. Results 722,597 males were included (262,178 [36.3%] had coded symptoms). Mean age was 64.4 years (SD 9.76). 90.68% identified as White ethnicity. 12,297 new prostate cancer diagnoses within 24 months of index consultation (8,101 [65.88%] in symptomatic group). Clinically significant prostate cancer (Adjusted OR 1.14 95% CI 1.07, 1.23) was more likely in the symptomatic group. No difference was found in stage at diagnosis (aOR 1.02 95% CI 0.95,1.09). Conclusion Investigating symptomatic patients in primary care is more likely to detect clinically significant prostate cancer with no difference in stage at diagnosis.

Nasopharyngeal carcinoma (NPC) is a head and neck cancer characterized by highly locoregionally invasive behavior attributable to the latent infection with Epstein-Barr virus (EBV) and genomic instability. It is well established that EBV-encoded oncogenic molecules actively contribute to the malignant behavior of NPC cells. However, the mechanism by which aberrant genomic alterations enable NPC cells to become aggressive remains largely unknown. In the present study, whole-exome sequencing (WES) revealed that the gene encoding the baculoviral IAP repeat-containing 3 (BIRC3) protein was frequently mutated in circulating tumor cells (CTCs) but not in paired primary tumor cells from patients with metastatic NPC. A minigene assay indicated that the c.637 A > G mutation disrupted normal mRNA splicing, resulting in the partial deletion of Exons 2 and 3 and altered stability of BIRC3 mRNA. In vitro experiments demonstrated that ectopic expression of the BIRC3[c.637A>G] mutant enhanced NPC cell invasive properties, including proliferation, resistance to apoptosis, migration, and invasion. Furthermore, overexpression of wild-type BIRC3 promoted invasive characteristics in NPC cells through the TRAF2-NF-κB signaling axis. In summary, BIRC3 acts as a regulator of the malignant features of NPC cells. Frequent BIRC3 mutations in CTCs, such as the c.637 A > G mutation, further enhance the metastatic potential of disseminated NPC cells by inducing aberrant alternative splicing. These findings suggest the therapeutic feasibility of targeting the BIRC3/TRAF2/NF-κB axis in the treatment of NPC.

SMARCB1/INI1-deficient carcinomas are rare and aggressive, and their responses to immune checkpoint inhibitors remain incompletely characterized. A 38-year-old woman presented with massive bilobar liver metastasis, ascites, bone lesions, and a small pancreatic tail lesion without an identifiable primary tumor. Liver biopsy revealed an undifferentiated carcinoma with rhabdoid features and complete loss of INI1. Comprehensive genomic profiling revealed microsatellite stability, low tumor mutational burden (TMB), and SMARCB1 copy number loss. The programmed death ligand 1 combined positive score was 18. Chemotherapy plus nivolumab induced transient regression of the hepatic lesions; however, progression occurred and the patient died 8 months after presentation.

A 72-year-old man was diagnosed with advanced gastric cancer with severe gastric stenosis, lymph node metastasis, and portal vein invasion. He underwent ileo-gastrostomy, then received chemotherapy using 4 cycles of S-1 and 2 cycles of SOX. The response to this therapy was judged PD; thus, second-line therapy of wPTX + RAM was introduced, although icterus and ascites were recognized then. After a single injection of wPTX + RAM, G4 neutropenia, anorexia, and severe ascites were observed. Thus, the chemotherapy was discontinued. At that point, he had been diagnosed with severe liver cirrhosis, and internal treatment was introduced. Six weeks after the last injection of anti-cancer drugs, CT revealed tumor shrinkage and highly reduced serum CEA, although ascites increased. Subsequently, ascites and general condition gradually recovered without anti-cancer therapy. One year after the last injection of anti-cancer drugs, the primary tumor, lymph node metastasis, and portal vein invasion were not observed on CT and endoscopy, and the patient was judged cCR. This rare case demonstrated prolonged effect of wPTX + RAM that caused the depression of liver metabolism. Therefore, anti-cancer immune response has been induced by an unknown mechanism.

We previously generated a global bulk-level proteogenomic atlas of metastatic colorectal cancer (CRC) in a Chinese cohort (CCRC). Using formalin-fixed paraffin-embedded tissues from this cohort, we identified 2095 ectopic lymphoid-like structures (ELSs) across 132 primary tumors. Both lymphoid aggregates (Aggs) and tertiary lymphoid structures (TLSs) were significantly associated with metastasis and clinical outcomes in CRC, in which the spatial and compositional heterogeneity of ELSs and their clinical relevance remain unknown. Here, we upgraded our LCM-MTA platform to version 2.0 for deep spatial proteomics and profiled spatial proteomic landscapes from matched mCRC and non-mCRC cases with comparable baseline clinical features. This analysis revealed pronounced spatial heterogeneity in protein expression, distinguishing ELSs from parenchymal regions in paired tumor and para-carcinoma tissues. Notably, TLSs displayed distinct functional states: mCRC-associated TLSs showed enrichment of anti-tumor immune activation pathways, whereas non-mCRC TLSs were enriched in acute inflammatory response pathways. Based on these findings, we developed a 13-protein TLS signature and scoring system to predict metastasis and prognosis in the CCRC cohort, validated in two independent CPTAC cohorts. We present a comprehensive spatial proteomic map of ELSs in metastatic CRC and identify a TLS-based signature with strong potential for predicting metastasis and clinical outcomes.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors exert pleiotropic effects beyond glucose lowering, including potential anticancer properties. Whether SGLT2 inhibitor use is associated with reduced distant metastasis risk in patients with breast cancer and type 2 diabetes remains unknown.