Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Mod Pathol. 2019 Sep;32(9):1271-1280. doi: 10.1038/s41379-019-0275-z. Epub 2019 Apr 25.
Trophoblastic differentiation has been previously described in somatic carcinomas at different primary sites, including the lung. Lung carcinomas with trophoblastic morphology presenting in women during the reproductive years pose a unique diagnostic challenge due to their overlapping microscopical and immunophenotypical features with metastatic choriocarcinoma of gestational origin. Distinction between the two entities is paramount as they require different chemotherapeutic regimens and have a markedly different prognostic outlook. Here we report a series of three female patients (ages 37-48 years) presenting with lung masses. Two of the three patients were noted to have elevated serum beta-hCG levels at the time of their presentation, while serum beta-hCG was not evaluated preoperatively in the third patient. None of them had a clinical history of molar pregnancy or gestational trophoblastic neoplasia. Core biopsies of the lung masses were performed in two patients and one patient underwent a wedge resection, showing poorly differentiated carcinoma in all cases with scattered multinucleated giant cells, hemorrhage, and necrosis. Beta-hCG immunostain was performed in two cases and showed diffuse immunoreactivity. Clinical history and imaging studies were not conclusive in any of the cases to rule out a gestational origin. Short tandem repeat genotyping analysis was performed to compare the allelic patterns between tumor and normal tissues and revealed identical profiles in one case, consistent with somatic origin, and unique paternal alleles in two cases, confirming metastatic gestational choriocarcinoma. The patient with primary somatic lung carcinoma died of disease within 15 months despite chemotherapy, while both patients with gestational choriocarcinoma responded well to chemotherapy and are alive without evidence of disease. Our cases illustrate the diagnostic pitfalls of lung tumors with trophoblastic differentiation in young women. Genotyping analysis offers precise diagnostic distinction between primary lung carcinoma and gestational choriocarcinoma with major therapeutic and prognostic implications for the patients.
滋养细胞分化已在不同原发部位的体癌中得到描述，包括肺。在生育期女性中出现具有滋养细胞形态的肺腺癌，由于其与妊娠来源的转移性绒毛膜癌在显微镜和免疫表型特征上存在重叠，因此构成独特的诊断挑战。区分这两种实体至关重要，因为它们需要不同的化疗方案，并且预后明显不同。在这里，我们报告了三例女性患者（年龄 37-48 岁）出现肺肿块的系列病例。其中两例患者在就诊时发现血清β-HCG 水平升高，而第三例患者术前未评估血清β-HCG。她们均无葡萄胎或妊娠滋养细胞肿瘤的临床病史。两例患者进行了肺肿块的核心活检，一例患者进行了楔形切除，所有病例均显示低分化癌，伴有散在多核巨细胞、出血和坏死。两例患者均进行了β-HCG 免疫组化染色，显示弥漫性免疫反应。任何病例的临床病史和影像学研究均不明确，无法排除妊娠来源。短串联重复基因分型分析用于比较肿瘤和正常组织之间的等位基因模式，其中一例显示一致的模式，与体细胞起源一致，两例显示独特的父系等位基因，证实转移性妊娠性绒毛膜癌。尽管接受了化疗，原发性肺腺癌患者在 15 个月内死于疾病，而两例妊娠性绒毛膜癌患者对化疗反应良好，且无疾病证据。我们的病例说明了年轻女性具有滋养细胞分化的肺肿瘤的诊断陷阱。基因分型分析可在原发性肺癌和妊娠性绒毛膜癌之间提供精确的诊断区分，对患者具有重要的治疗和预后意义。
