Survival outcomes in patients with de novo metastatic Merkel cell carcinoma according to site of metastases.

Introduction: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine malignancy of the skin with a predilection for metastases. This study investigates the clinical outcomes in patients presenting with de novo Stage IV MCC according to the metastatic site(s) at presentation. Materials and methods: Patients who presented with one or more sites of distant metastatic MCC at initial diagnosis between 2009 and 2023 were identified. The presence or absence of one or more metastases in each organ was categorized for each patient at the time of diagnosis. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Competing risk analysis was used to estimate the cumulative occurrence risk of MCC-specific death. Fisher's exact test was used for response rate analysis. Results were considered statically significant if p < 0.05. Results: Thirty-four patients presented with de novo distant metastatic MCC. There was no association between the number of metastatic sites at diagnosis and OS (p= 0.58), PFS (p=0.79), or response rates (p=0.53). However, the presence of bone metastases was associated with significantly shorter OS (8.2 versus 25.2 months, HR: 2.4, 95% CI 1.01-5.7, p= 0.04). MCC-specific death in patients with lymph node metastases was significantly lower than in patients without (HR: 0.28, 95% CI: 0.09-0.87, p= 0.013). The presence of bone metastases tended to associate with an increased risk of MCC-specific death, although not statistically significant. The location of metastases was not associated with the response rate to first-line treatment. There was no significant association between site of metastases and PFS. Conclusion: In this cohort of patients with de novo metastatic MCC, the presence of bone metastases, but not the number of organs involved, was associated with significantly worse OS. The presence of lymph node metastases was associated with lower MCC-specific death. Further research is warranted in larger cohorts to investigate the impact of the location of metastases on clinical outcomes.

Patterns of initial distant metastases in 151 patients undergoing surveillance for treated Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is associated with high rates of recurrence and distant metastatic progression. Current guidelines for surveillance imaging are not evidence based. Better characterization of the pattern of distant metastatic spread will better inform surveillance and facilitate earlier detection of metastases. OBJECTIVES: This retrospective study aimed to assess potential relationships between primary tumour site and site of initial distant metastasis, time to distant metastasis, overall survival (OS) and MCC-specific death (MSD). METHODS: Patients with local or regional (Stage I-III) disease who were treated with curative intent and progressed to Stage IV were included in this study (n = 151). Fisher's exact test was used to assess differences in patterns of initial distant metastases based on primary tumour site. Time to initial distant metastasis was calculated from date of MCC diagnosis. OS and MSD were calculated from date of initial distant metastasis to date of death from any or MCC-related causes, respectively. RESULTS: Of 151 patients included in analysis, 89 (58.9%) had a single initial distant metastatic site, and 62 (41.1%) had multiple sites. Patients with upper limb primary tumours were significantly less likely to develop distant lymph node or liver metastases (p = 0.02 and 0.04, respectively). Median time to distant metastasis was 11 months (IQR 6.7-17.9 months). Median OS was 15.3 months, and was shorter for patients with liver (7.0 months, p = 0.0004) or bone metastases (8.9 months, p < 0.0001). Using skin/soft tissue metastasis as a reference group, patients with multiple metastatic sites had significantly higher hazards of MSD (HR = 3.46 univariate, 3.77 multivariate analysis). Time to distant metastasis, OS and MSD did not differ by viral status. CONCLUSION: Sites of initial distant metastasis are related to primary tumour sites and survival outcomes. Because patients often have multiple initial metastases, full-body cross-sectional rather than region-specific imaging may facilitate earlier detection of metastatic disease.

Unprecedented coexistence of autoinflammatory myositis and chronic thrombosis with heterozygotic M694V mutation: An atypical presentation of familial Mediterranean fever.

Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disorder predominantly characterised by periodic fever, abdominal pain, and joint manifestations. It can exhibit various atypical presentations. However, cases of FMF concurrently presenting with chronic thrombosis and myositis have not been previously reported. A 41-year-old male presented with alternating severe bilateral leg pain, stiffness, and localised swellings without fever or abdominal symptoms. His history included inflammatory joint pain treated with prednisolone. Physical examination revealed leg pain, limited ankle joint movement, and tender swellings in thighs, forearms, and feet. Collateral abdominal veins were also observed. Unresponsive to prednisolone and colchicine, the patient underwent MRI, revealing muscle inflammation in both legs and thighs and chronic thrombosis in the infrarenal inferior vena cava. Genetic testing confirmed the heterozygotic M694V mutation, diagnosing an atypical FMF. This case uniquely showcases coexisting myositis and chronic thrombosis in FMF. Myalgia is common in FMF, with M694V mutation associated with severe muscular symptoms. The lack of fever and myositis findings differentiate our case from protracted febrile myalgia syndrome. FMF's chronic inflammatory state is known to influence thrombosis risk, and our findings align with this association. Chronic thromboembolism and myositis together signify an unusual clinical presentation of FMF. This case highlights the potential for FMF to present with complex manifestations beyond the conventional symptoms. Myositis and vascular involvement should prompt consideration of FMF diagnosis when combined with patient history, clinical features, and laboratory results. These rare associations underscore the need for further research to enhance understanding of FMF's diverse clinical spectrum.