Scotti Biagio, Broseghini Elisabetta, Ricci Costantino, Corti Barbara, Viola Costanza, Misciali Cosimo, Baraldi Carlotta, Vaccari Sabina, Lambertini Martina, Venturi Federico, Magnaterra Elisabetta, Alessandrini Aurora, Ferrari Tiziano, Lepri Massimo, Argenziano Gabriele, Melotti Barbara, Campione Elena, Campana Davide, Ferracin Manuela, Dika Emi
Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy.
Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.
Cancers (Basel). 2025 Jul 6;17(13):2253. doi: 10.3390/cancers17132253.
BACKGROUND/OBJECTIVES: Despite advancements in early diagnosis and clinical practices guided by standardized care protocols, Merkel cell carcinoma (MCC) is marked by an unfavorable prognosis with a 5-year relative survival rate of 65%, based primarily on data collected prior to the introduction of immunotherapy. 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.
A comprehensive review was conducted using the Medline database (via PubMed) up to January 2025. The search strategy included the string "(Merkel cell carcinoma AND (bone OR marrow))".
A total of 1133 (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. Overall, 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 (second) and lymph nodes (first). They show mixed biological and radiological behavior, with a marked preference for the axial skeleton over the appendicular one. Addressing the characteristics of metastatic bone disease, neurological symptoms were the most documented, whereas bone marrow involvement and leukemic spread seemed to be primarily related to immunosuppression. Multimodal treatment strategies, including platinum-based chemotherapy and radiotherapy, were the primary approaches adopted, reflecting therapeutic practices from the pre-immunotherapy era.
The pattern of metastatic spread in MCC differs 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 overall survival (OS) of 8 months (range 12.75-4). The integration of international guidelines, evolving evidence from clinical trials, and the expanding role of immune checkpoint inhibitors (ICIs) will contribute to improving systemic disease control and enhance patient care.
背景/目的：尽管早期诊断和基于标准化护理方案的临床实践取得了进展，但默克尔细胞癌（MCC）的预后仍然不佳，5年相对生存率为65%，这主要基于免疫疗法引入之前收集的数据。区域淋巴结转移影响40%-50%的MCC患者，约33%的患者发生远处转移。其中，骨和骨髓转移尤为显著，尽管MCC中这种转移性疾病的特征和临床意义仍知之甚少。
截至2025年1月，使用Medline数据库（通过PubMed）进行了全面综述。检索策略包括字符串“（默克尔细胞癌AND（骨或骨髓））”。
共收集了1133例（男性69.3%，女性30.7%）诊断为晚期MCC的患者。诊断时的中位（IQR）年龄为67.5（12.65）岁。总体而言，共识别出201例（20.8%）骨和/或骨髓转移病例，75.7%的病例与已知的原发性MCC相关。骨转移（BMs）是第三大最常见的转移部位，仅次于肝脏（第二）和淋巴结（第一）。它们表现出混合的生物学和放射学行为，明显更倾向于轴向骨骼而非附属骨骼。针对转移性骨病的特征，神经症状记录最多，而骨髓受累和白血病扩散似乎主要与免疫抑制有关。多模式治疗策略，包括铂类化疗和放疗，是主要采用的方法，反映了免疫疗法前时代的治疗实践。
MCC的转移扩散模式在不同研究中有所不同，骨是远处转移的第三大最常见部位。排除似乎更常与肝转移相关的头颈部MCC，原发性肿瘤部位与骨或骨髓转移发生之间的关系似乎并不一致。总体而言，BMs大多与晚期MCC阶段和较差的生存结果相关，中位总生存期（OS）为8个月（范围12.75-4）。国际指南的整合、来自临床试验的不断演变的证据以及免疫检查点抑制剂（ICIs）作用的扩大将有助于改善全身疾病控制并加强患者护理。
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