Department of Pathology and Laboratory Medicine, Queen Elizabeth II Health Sciences Centre, Nova Scotia Health Authority (Central Zone), Halifax, Nova Scotia, B3H 1V8, Canada; Department of Pathology, Dalhousie University, Halifax, Nova Scotia, B3H 1V8, Canada.
Department of Pathology and Laboratory Medicine, Queen Elizabeth II Health Sciences Centre, Nova Scotia Health Authority (Central Zone), Halifax, Nova Scotia, B3H 1V8, Canada; Department of Pathology, Dalhousie University, Halifax, Nova Scotia, B3H 1V8, Canada; Department of Medicine, Dalhousie University, Halifax, Nova Scotia, B3H 1V8, Canada.
Hum Pathol. 2022 Nov;129:47-55. doi: 10.1016/j.humpath.2022.07.021. Epub 2022 Aug 6.
Combined Merkel cell carcinomas are hybrid tumors composed of neuroendocrine and other phenotypic (usually squamous) elements. They form a minority of Merkel cell carcinomas (MCCs) as a whole, are usually Merkel cell polyomavirus-negative, and have rarely been segregated for specific study. Sporadic reports have indicated that metastases from these tumors can show a combined phenotype. We retrospectively studied 38 cases (24 men [63%], 14 women [37%], mean age 78 years [range, 46-99 years]) of combined MCC. Metastases occurred in 20 patients (53%) (at presentation and/or in follow-up [mean 38 months (range, 0.6-185 months)]). Those from 17 individuals (45%) were examined microscopically. These were mainly nodal in distribution. In 12 patients (71%), the secondary deposits were of pure neuroendocrine type, whereas in 5 (29%), combined deposits were identified. Squamous elements were the most common divergent component, in the primary and secondary tumors. The combined metastases varied from obvious squamous nests in a neuroendocrine background to scattered bizarre tumor giant cells expressing CK5/6 on immunohistochemistry. In one case, individual nodes within a single basin displayed purely squamous or purely neuroendocrine deposits. The mean overall survival in the cohort was 48 months (range, 30-67 months) and the mortality was 82%. Our work sheds light on the frequency and patterns of metastases in combined MCCs. In concert with the poor outcome data documented by others, it also raises a question as to the potential prognostic significance of a combined phenotype per se, independent of a virus-negative status and other variables. This issue deserves further study.
混合性 Merkel 细胞癌是由神经内分泌和其他表型（通常为鳞状）成分组成的混合性肿瘤。它们构成了 Merkel 细胞癌（MCC）的一小部分（整体而言），通常 Merkel 细胞多瘤病毒阴性，并且很少被分离出来进行专门研究。零星报告表明，这些肿瘤的转移可能表现出混合表型。我们回顾性研究了 38 例（24 例男性[63%]，14 例女性[37%]，平均年龄 78 岁[范围，46-99 岁]）混合性 MCC 患者。20 例患者（53%）发生转移（在初次就诊时和/或随访时[平均 38 个月（范围，0.6-185 个月）]）。对 17 例患者（45%）的转移灶进行了显微镜检查。这些转移灶主要分布在淋巴结。在 12 例患者（71%）中，继发性沉积物为纯神经内分泌型，而在 5 例患者（29%）中，鉴定出混合性沉积物。鳞状成分是原发性和继发性肿瘤中最常见的分化成分。混合性转移灶从神经内分泌背景下明显的鳞状巢到散在的表达 CK5/6 的奇异肿瘤巨细胞不等。在 1 例患者中，单个淋巴结内显示出单纯的鳞状或单纯的神经内分泌沉积物。该队列的总生存率为 48 个月（范围，30-67 个月），死亡率为 82%。我们的工作阐明了混合性 Merkel 细胞癌转移的频率和模式。与其他人记录的不良预后数据一致，它还提出了一个问题，即混合表型本身是否具有潜在的预后意义，而与病毒阴性状态和其他变量无关。这个问题值得进一步研究。
