Department of Pathology, Yokohama City University Hospital, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Department of Pathology, Yokohama Minami Kyousai Hospital, 1-21-1 Mutsuura-higashi, Kanazawa-ku, Yokohama, 236-0037, Japan.
Diagn Pathol. 2020 Feb 7;15(1):11. doi: 10.1186/s13000-020-0928-8.
Primary malignant melanoma of the lung (PML) is extremely rare. No precursor lesions of PML have been identified, and little is known about the genetic mutations associated with the disease. Typically, 15-20% of malignant melanomas possess NRAS gene mutations, but no cases of NRAS-mutated PML have been reported in the English literature. We present a case of PML involving an NRAS mutation.
Clinical summary A 74-year-old Japanese female presented with worsening dyspnea and was admitted to hospital. Computed tomography (CT) revealed a right lung (S10) mass and pleural dissemination. Cytology of the pleural effusion in the right lung was performed, and malignant melanoma or clear cell sarcoma was suspected. A dermatological examination and gallium scintigraphy were conducted to determine the primary tumor site, but no suspicious lesions, expect for the right lung mass, were found. After admission, CT showed complicating bilateral pneumonia, and an antibiotic drug was administered, but the pleural effusion got worse. About 2 weeks later, the patient died of respiratory failure and cardiac arrest. An autopsy was performed to determine the histological diagnosis. Autopsy findings A 26x15x20-mm black and pale yellow mass was found in the right lower lobe. Many disseminated nodules were found in the right lobe. The tumor had invaded the right diaphragm. Subcarinal lymph node metastasis was also detected. Immunohistochemically, the tumor cells exhibited positivity for S-100 and HMB45 staining. The patient was diagnosed with malignant melanoma. Sanger sequencing of the tumor detected an NRAS mutation.
We found an NRAS D54N mutation in PML, which has not been reported previously anywhere in the world. Previous reports indicated that most cases of PML can be classified into the triple-wild-type, but BRAF mutation status was only analyzed in a few cases. We should analyze the mutation patterns of PML to determine whether any subtypes other than the triple-wild-type exist. PML might be a form of de novo cancer.
原发性肺恶性黑色素瘤（PML）极为罕见。目前尚未发现 PML 的前体病变，对与该疾病相关的基因突变更知之甚少。通常，15-20%的恶性黑色素瘤存在 NRAS 基因突变，但在英文文献中尚未报道过 NRAS 突变型 PML 病例。我们报告了一例涉及 NRAS 突变的 PML 病例。
临床概要一名 74 岁的日本女性因呼吸困难加重而就诊，并被收入院。计算机断层扫描（CT）显示右肺（S10）肿块和胸膜播散。对右侧胸腔积液进行细胞学检查，怀疑为恶性黑色素瘤或透明细胞肉瘤。进行了皮肤科检查和镓闪烁显像以确定原发肿瘤部位，但除了右肺肿块外，未发现可疑病变。入院后，CT 显示并发双侧肺炎，并给予抗生素治疗，但胸腔积液恶化。约 2 周后，患者因呼吸衰竭和心脏骤停死亡。进行了尸检以确定组织学诊断。
尸检发现右肺下叶发现一个 26x15x20-mm 的黑色和苍黄色肿块。右叶有许多播散性结节。肿瘤已侵犯右膈肌。也检测到隆突下淋巴结转移。免疫组化染色显示肿瘤细胞对 S-100 和 HMB45 染色呈阳性。患者被诊断为恶性黑色素瘤。肿瘤的 Sanger 测序检测到 NRAS D54N 突变，这在世界范围内尚无报道。先前的报告表明，大多数 PML 病例可分为三野生型，但仅对少数病例分析了 BRAF 突变状态。我们应该分析 PML 的突变模式，以确定是否存在除三野生型以外的任何亚型。PML 可能是一种新发癌症。
