Ura Ayako, Moser Elisa, Evert Matthias, Evert Katja, Märkl Bruno, Sipos Eva, Kremer Marcus, Sasano Hironobu, Okada Yoshinori, Steiger Katja, Mogler Carolin, Hoffmann Hans, von Werder Alexander, Kaemmerer Daniel, Uccella Silvia, La Rosa Stefano, Klöppel Günter, Kasajima Atsuko
Department of Pathology, Technical University of Munich, TUM School of Medicine and Health, Munich, Germany.
Institute of Pathology, University of Regensburg, Regensburg, Germany.
Endocr Pathol. 2025 May 2;36(1):16. doi: 10.1007/s12022-025-09860-5.
The literature emphasizes that pulmonary ectopic Cushing syndrome (ECS) is associated not only with neuroendocrine tumors (NETs), but also with small cell lung carcinomas (SCLCs). This statement is debatable, because extrapulmonary ECS is associated with NETs in the vast majority of cases and very rarely with neuroendocrine carcinomas (NECs). Therefore, we critically reviewed the literature on SCLCs associated with ECS (ECS-SCLC) and performed immunohistochemical analysis of ACTH expression in 155 resected SCLCs and 158 pulmonary NETs. The literature search revealed that 90% of the 205 ECS-SCLC patients identified between 1952 and 2023 had no or poor-quality histologic images, so the diagnosis of SCLC could not be confirmed. Review of the 20 reports (10%) with histologic images revealed that 18/20 (90%) had to be reclassified as "probable NET", of which 5/18 (28%) showed spindle cell morphology, while only 2 cases were qualified as "SCLC compatible" due to their pleomorphic cell features. Immunohistochemically, 5/155 (3%) resected SCLCs, all without ECS, showed weak single cell ACTH expression, whereas in the NET cohort, 61/158 (39%) tumors expressed ACTH, of which 4 (3%) were associated with ECS. Both observations, the literature review, which casts doubt on previously reported data regarding the frequency of SCLC in ECS, and the immunohistochemical study, suggest that there is limited evidence that SCLC is the cause of ECS.
文献强调，肺异位库欣综合征（ECS）不仅与神经内分泌肿瘤（NETs）有关，还与小细胞肺癌（SCLCs）有关。这一说法存在争议，因为肺外ECS在绝大多数情况下与NETs相关，很少与神经内分泌癌（NECs）相关。因此，我们严格审查了与ECS相关的小细胞肺癌（ECS-SCLC）的文献，并对155例切除的小细胞肺癌和158例肺NETs进行了促肾上腺皮质激素（ACTH）表达的免疫组织化学分析。文献检索发现，在1952年至2023年期间确定的205例ECS-SCLC患者中，90%没有或仅有质量不佳的组织学图像，因此无法确诊为小细胞肺癌。对有组织学图像的20篇报告（10%）进行回顾发现，其中18/20（90%）必须重新分类为“可能的NET”，其中5/18（28%）表现为梭形细胞形态，而只有2例因其多形性细胞特征而符合“小细胞肺癌兼容”标准。免疫组织化学分析显示，155例切除的小细胞肺癌中有5例（3%），均无ECS，显示出弱的单细胞ACTH表达，而在NET队列中，158例肿瘤中有61例（39%）表达ACTH，其中4例（3%）与ECS相关。文献综述对先前报道的ECS中小细胞肺癌发生率的数据提出了质疑，免疫组织化学研究这两项观察结果均表明，仅有有限的证据表明小细胞肺癌是ECS的病因。
