Melanoma Research最新文献

Peritoneal carcinomatosis represents an exceptionally rare metastatic pattern of cutaneous malignant melanoma, occurring in fewer than 1% of cases with distant spread and typically within the first few years after primary treatment. This report presents an unusual case with a markedly prolonged disease-free interval, clinically mimicking advanced ovarian carcinoma. We report the case of a 53-year-old woman treated more than 10 years ago for stage IIB nodular melanoma with surgery and adjuvant therapy. The patient presented with progressive abdominal bloating. Imaging revealed bilateral adnexal masses, ascites, peritoneal carcinomatosis, and multiple pulmonary nodules, initially suggestive of advanced ovarian cancer. Diagnostic laparoscopy demonstrated diffuse peritoneal lesions with an atypical yellowish, soft, and nonpigmented appearance. Histology and immunohistochemistry confirmed metastatic melanoma. This case is among the few reports of peritoneal carcinomatosis from melanoma after more than a decade of remission. The prolonged disease-free interval and atypical presentation underline the heterogeneous behavior of melanoma and the need for long-term vigilance and multidisciplinary evaluation.

Wide local excision (WLE) is the standing surgical choice for acral lentiginous melanoma (ALM), yet research is scarce in evaluating other surgical options for ALM and its recurrence rates remain two to five times more likely than other melanoma subtypes. This study evaluates the overall survival outcomes associated with different surgical modalities in patients with stage 0-II ALM. This retrospective cohort study surveyed the National Cancer Database from 2004 to 2021 for International Classification of Diseases-10 codes specific for all skin structures with histologically confirmed ALM for stage 0-II patients. Using IBM SPSS, statistical analyses were conducted via variable frequency with crosstabulations and Chi-squared tests, Kaplan-Meier survival curves with log-rank pairwise comparisons, and Cox proportional hazards regression models. Data for 6737 patients showed significantly greater overall survival for biopsy followed by gross excision (BFGE) than WLE [median overall survival = 204.8 months ( P  < 0.001); hazard ratio = 0.77 (95% confidence interval, 0.68-0.87)]. Median overall survival for WLE was 181.6 months. Cross analysis of Breslow depth (BD) with surgical procedures revealed the majority (21.8%) of WLEs were completed for lesions with a BD of 0.1-5 mm followed by 16.8% for lesions greater than 3 cm ( P  < 0.001). Crossanalysis of surgical margins of the primary site with surgical procedures, showed no residual tumor in 92.1% of all BFGE patients, which is 3.7% and 3.3% less patients than major amputation and WLE. This study highlights significant differences across ALM surgery options, suggesting each modality has their own niche and BFGE should be investigated further.

The surfactant protein-C (SFTPC) gene encodes a hydrophobic pulmonary surfactant protein essential for lung function and homeostasis. While primarily associated with lung diseases, emerging evidence suggests its potential involvement in human cancers. In addition, SFTPC expression was also found in human skin cells, however, its expression profile in cutaneous melanoma is unknown. In this study, we analyzed expression profiles of SFTP family genes including SFTPA1/2 , SFTPB , SFTPC , and SFTPD in human skin melanoma tissues. Our analysis revealed that SFTPC expression was the predominant SFTP gene and was associated with disease progression, including tumor stage, Clark level, and Breslow depth. High levels of SFTPC expression in skin melanoma tissues were significantly associated with patient survival outcomes including overall and disease-specific survival. The associations were specifically dictated in aggressive tumors, suggesting a potential role of SFTPC expression in melanoma progression. Interestingly, SFTPC expression was negatively correlated with T-helper cell infiltration in skin melanoma tissues. Gene enrichment analysis also indicated that SFTPC expression was in parallel with elevated expressions of mitochondrial energy biosynthesis-related genes and reduced IgE/IgG-mediated immunity-related genes. In conclusion, SFTPC upregulation is associated with disease progression and patient survival outcomes, possibly through enhancing ATP overproduction and suppressing antitumor immunity.

Programmed death ligand-1 (PD-L1) is an inducible protein heterogeneously expressed in melanoma. Assessment of PD-L1 expression is challenging and standard immunohistochemistry (IHC) requires biopsies and cannot capture heterogeneity of expression. Noninvasive imaging methods provide evaluation of expression across lesions in the body. We conducted a prospective pilot trial with PD-L1 PET imaging with [ 18 F]-BMS-986229 as a noninvasive approach to assess PD-L1 expression across lesions, in 10 patients with advanced melanoma, longitudinally during treatment with nivolumab and ipilimumab. PET imaging was performed at baseline and at 6 weeks after initiation of treatment. We examined the relationship of PD-L1 PET uptake to radiographic clinical response. [ 18 F]-BMS-986229 uptake was variably seen across lesions in patients at baseline. All patients showed positive uptake in lesions at baseline PET with a median SUV max of 3.6 (range: 1.7-8.6). PD-L1 PET SUV max decreased in all but two lesions 6 weeks after treatment initiation. Four of five patients had a mean (SUV max ) greater than or equal to 3.00 in Response Evaluation Criteria in Solid Tumors (RECIST) evaluable lesions at baseline, and all had a RECIST response while all progressors ( n  = 3) had baseline PD-L1 mean SUV max less than or equal to 2.60. A higher lesional baseline SUV max was associated with greater individual lesion reduction during treatment. The PD-L1 uptake in lesions showed a low correlation with baseline PD-L1 by IHC. In this small pilot study, PD-L1 PET imaging using [ 18 F]-BMS-986229 showed feasibility in noninvasively assessing lesion uptake and PD-L1 heterogeneity in patients receiving combination immunotherapy. Future exploration of this tracer in larger patient cohorts is necessary to delineate its use in managing immunotherapy treatments.

Surgical stress is gaining increasing focus in surgical oncology due to its impact on complications, prognosis, and survival. The neutrophil-to-lymphocyte ratio (NLR) is a recognized biomarker reflecting inflammation and immune response, key aspects of surgical stress. Sentinel lymph node biopsy (SLNB) and wide local excision (WLE) are considered minimally invasive procedures used in the management of melanoma. Yet, the surgical stress response of WLE and SLNB remains unexplored. This study aims to investigate perioperative changes in the NLR as a marker of surgical stress in patients with melanoma undergoing WLE and SLNB. This prospective pilot study investigated NLR as a marker of surgical stress in patients ( n = 20) with melanoma undergoing WLE and SLNB. NLR was calculated from the plasma differential count and measured preoperatively and at 2 and 6 h postoperatively. Surgical stress was categorized into four groups according to the NLR values: No stress, mild, moderate, and severe stress. Paired t -tests tested differences between time points. Mean NLR increases from 1.94 (±0.86) preoperatively to 9.5 (±4.39) at 2 h ( P < 0.001) and further increases to 16.04 (±11.11) at 6 h ( P = 0.02) postoperatively. This increase reflects a shift from no systemic stress (NLR: 1-3) to a moderate (NLR: 8-18) response, approaching severe thresholds. Changes in NLR are driven by significant neutrophilia and lymphocytopenia. Despite minor procedures, WLE and SLNB elicit a substantial surgical stress response. NLR may serve as a valuable biomarker for monitoring surgical stress in melanoma surgery, with potential implications for surgical and oncologic outcomes.

Pembrolizumab is an immune checkpoint inhibitor targeting programmed cell death protein 1 , used for stage IIB/IIC melanoma. While effective, pembrolizumab can lead to immune-mediated toxicities in various systems; however, nervous system effects are less well-documented. We report the case of a 34-year-old man who developed delayed immune-mediated encephalomyelitis with antiglial fibrillary acidic protein (GFAP) antibodies after completing nine cycles of adjuvant pembrolizumab for stage IIC melanoma. Four months posttreatment, he presented with neurological symptoms, including ataxic gait, sensory deficits in the lower limbs, and urinary retention. Imaging revealed extensive myelitis and encephalitis in the spinal cord and posterior fossa. The etiological evaluation was negative except for the presence of anti-GFAP antibodies in the cerebrospinal fluid. Treatment with high-dose corticosteroids led to significant improvement. This case represents the first reported instance of postimmunotherapy encephalomyelitis with anti-GFAP antibodies following pembrolizumab treatment. Although rare, this is a serious adverse event requiring careful monitoring and early multidisciplinary management.

Phosphodiesterase type 5 (PDE5) inhibitors are the first-line treatment for erectile dysfunction, with modest adverse effects. Since 2011, concerns have arisen about increased melanoma risk in PDE5 inhibitor users. PDE5 inhibitors affect the rat sarcoma virus oncogene-rapidly accelerated fibrosarcoma-mitogen-activated protein kinase-extracellular signal-regulated kinase signaling cascade, which is involved in melanoma formation. This systematic review and meta-analysis investigates melanoma risk in PDE5 inhibitor users. PubMed, Cochrane, and Embase were searched to examine the relationship between PDE5 inhibitors and melanoma. A random-effects model estimated pooled odds ratios (ORs) and hazard ratios (HRs), with the I ² statistic assessing heterogeneity. RStudio v4.4.2 was used for the meta-analysis, and a P value less than 0.05 was deemed significant. Eight studies including 7 620 765 patients were analyzed, with 2 123 165 (27.86%) comprising the PDE5 inhibitor-exposed group. The meta-analysis found a relationship between PDE5 inhibitor use and increased melanoma risk [OR: 1.60, 95% confidence interval (CI): 1.13-2.27, P = 0.009, I ² = 98%] and [HR: 1.10, 95% CI: 1.03-1.17, P = 0.005, I ² = 43%]. When each PDE5 inhibitor was examined separately, increased melanoma incidence was observed, though not statistically significant. The OR for sildenafil was 1.85 (95% CI: 0.97-3.51, P = 0.059, I ² = 99%), tadalafil 1.54 (95% CI: 0.79-3.00, P = 0.203, I ² = 96%), and vardenafil 1.16 (95% CI: 0.82-1.64, P = 0.391, I ² = 89%). This study suggests PDE5 inhibitor users have a higher chance of developing potentially fatal melanoma. Patients with a history of skin cancer, a family history of melanoma, or other risk factors should avoid these medications.

To explore the functional role of thrombospondin 2 (THBS2) in the metastasis of skin cutaneous melanoma (SKCM), with a focus on its regulation of angiogenesis and extracellular matrix (ECM) remodeling. THBS2 expression was assessed in normal melanocytes and SKCM cell lines with varying metastatic potential. Functional analyses were conducted after THBS2 knockdown in A375 cells and overexpression in G-361 cells. Effects on migration, invasion, endothelial tube formation, and angiogenesis- and ECM-related factors were evaluated. Tumor IMmune Estimation Resource database was used for correlation analyses in SKCM samples. A liver metastasis model was established by intrasplenic injection of B16-F10 cells into Thbs2 knockout and wild-type mice, followed by quantification of hepatic metastases and molecular analysis of peritumoral liver tissue. THBS2 was highly expressed in invasive melanoma cell lines and was positively associated with VEGFA, PECAM1, and MMPs in both databases and experimental models. Knockdown of THBS2 significantly suppressed VEGFA, PECAM1, FGF2, FLT1, MMP2, MMP9, and ECM components (LAMA4, COL1A1, and COL4A1) at mRNA and protein levels, inhibited melanoma cell migration and invasion, and reduced tube formation in human umbilical vein endothelial cells. Overexpression had opposite effects. In vivo , Thbs2 knockout mice exhibited significantly fewer hepatic metastases and reduced metastatic area compared with wild-type controls. Expression of Lama4, Pecam1, Vegfa, Mmp2, and Mmp9 was markedly lower in peritumoral liver tissue of knockout mice. THBS2 promotes SKCM metastasis by enhancing angiogenesis and ECM remodeling. Targeting THBS2 may represent a promising strategy for inhibiting melanoma progression and distant organ colonization.