Clinical Characteristics, MAML2 Gene Rearrangement and Prognosis of Pulmonary Mucoepidermoid Carcinoma

TL;DR

This study examines the clinical features, MAML2 gene rearrangements, and survival outcomes of a rare lung cancer called pulmonary mucoepidermoid carcinoma.

Contribution

The study identifies MAML2 gene rearrangements in about half of the cases and highlights lymph node metastasis as a key predictor of poor prognosis.

Findings

Approximately 52.4% of PMEC cases showed MAML2 gene rearrangements.

High-grade PMEC and lymph node metastasis were strongly associated with worse survival outcomes.

Lymph node metastasis was identified as an independent poor prognostic factor.

Abstract

背景与目的 原发性肺黏液表皮样癌（pulmonary mucoepidermoid carcinoma, PMEC）是起源于支气管黏液腺的罕见恶性肿瘤，占肺癌比例不足0.2%。其病理特征为黏液细胞、表皮样细胞及中间细胞混合构成，可分为低级别与高级别亚型，后者预后较差。本研究旨在探讨PMEC的临床病理特征及预后影响因素。方法 回顾性分析26例PMEC患者的临床资料、影像学表现、病理特征（含免疫组化及MAML2重排检测）及生存数据，结合文献进行总结。结果 26例患者中男性14例、女性12例，平均年龄55.6岁。吸烟者8例（30.8%），有症状者19例（73.1%）。中央型肿块19例（73.1%），周围型7例（26.9%）。计算机断层扫描（computed tomography, CT）均表现为低-中等密度团块/结节。病理分型：低级别19例，高级别7例。免疫组化示CK7、P40、P63、CK5/6阳性，Ki-67指数2%-70%。MAML2重排检出率52.4%（11/21）。临床分期：I期14例，II期8例，III期3例，IV期1例。治疗方式：根治手术13例，手术+辅助化疗11例，放化疗1例，保守治疗1例。中位随访57个月，6例（23.1%）死亡。预后分析显示：（1）高级别组生存率显著低于低级别组（P<0.05）；（2）淋巴结转移、晚期分期、Ki-67>20%及高级别与总生存期缩短有关联（P<0.05）；（3）淋巴结转移是独立不良预后因素（HR=12.73, 95%CI: 1.22-132.96）。结论 PMEC具有独特的临床病理特征，约半数存在MAML2重排。淋巴结转移、晚期分期、高Ki-67指数及高级别是预后不良的影响因素，其中淋巴结转移为独立危险因素。

A-B: Case 5, a-66-year-old-female, showed a mass of soft tissue density (22 mm×16 mm) in the left upper lobe of the lung on CT plain scan (Fig 1A), enhanced CT (Fig 1B) showed enhancement, and postoperative pathological evaluation showed low-grade PMEC; C-D: Case 9, a 58-year-old male, showed a mass of soft tissue density (41 mm×37 mm) in the posterior segment of the left upper lobe on CT plain scan (Fig 1C). Within the mass, there were small low-density lesions with well-defined boundaries, uneven margins, lobulated shape, and spiculation; Enhanced CT (Fig 1D) showed uneven and obvious enhancement. Postoperative pathological evaluation showed high-grade PMEC. CT: computed tomography.

A: HE of low-grade PMEC: Well-differentiated mucinous cells can be seen forming glandular cavities or cystic cavities, with low cell atypia; B: HE of high-grade PMEC: Poorly differentiated epidermoid cells and intermediate-type cells can be observed to be distributed in sheet-like and island-like patterns, with obvious cell atypia, significant nucleolus, and visible mitosis; C: Ki-67 in low-grade PMEC (approximately 5%); D: Ki-67 in high-grade PMEC (approximately 30%) ; E: CK7 is positive in low-grade PMEC, marking the glandular tubule-like area of the tumor tissue; F: CK7 is positive in high-grade PMEC, marking diffuse patchy areas of tumor tissue; G: PAS staining of low-grade PMEC marked a large number of mucous cells; H: PAS staining of high-grade PMEC, which marks mucinous cells in small focal areas; I: Schematic diagram of positive cases of low-grade PMEC FISH (×1000); J: Schematic diagram of positive cases of high-grade PMEC FISH (×1000). FISH: fluorescence in situ hybridization; PAS: periodic acid-schiff stain; HE: hematoxylin-eosin.

Results of univariate and multivariate Cox proportional hazards models for PMEC

Figures