Merkel Cell Carcinoma: An Updated Review Focused on Bone and Bone Marrow Metastases

Background/objectives: Despite advancements in early diagnosis and clinical practices guided by standardized care protocols, Merkel cell carcinoma (MCC) is still marked by an unfavorable prognosis with a 5-year relative survival rate of 65%. Indeed, regional nodal metastases affect 40-50% of MCC patients, while approximately 33% experience distant dissemination. Among these, bone and bone marrow metastases are particularly notable, although the characteristics and clinical implications of this metastatic disease in MCC remain poorly understood. Methods: A comprehensive review was conducted using the Medline database (via PubMed) up to January 2024. The search strategy included the string “(Merkel cell carcinoma AND (bone OR marrow))”. Results: A total of 1,133 (69.3% male and 30.7% female) patients diagnosed with advanced MCC were collected. The median (IQR) age at diagnosis was 67.5 (12.65) years old. 201 (20.8%) cases of bone and/or bone marrow metastases were identified and linked to a primary known MCC in 75.7% of cases. Bone metastases (BMs) appear as the third most common metastatic site, following the liver (2nd) and lymph nodes (1st). They show a mixed biological and radiological behavior, with a marked preference for the axial skeleton over the appendicular one. Addressing characteristics of bone metastatic disease, neurological symptoms were the most documented, whereas bone marrow involvement and leukemic spread seemed to be primarily related to immunosuppression. Multimodal treatment including platinum-based chemotherapy and radiotherapy represented the primary approach for effective management. Conclusions: The pattern of metastatic spread in MCC differ among studies, with the bones resulting as the third most common site of distant spread. Excluding head and neck MCC, which seems to be more regularly associated with liver metastases, the relationship between the primary tumor site and the development of bone or bone marrow metastases appears inconsistent. Overall, BMs mostly correlated with advanced MCC stages and poorer survival outcomes, with a median OS of 8 months (range 12.75-4). The integration of international guidelines alongside the ongoing findings from clinical trials will contribute to improve systemic disease control and enhance patient care.