Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Mod Pathol. 2018 Jan;31(1):122-131. doi: 10.1038/modpathol.2017.108. Epub 2017 Sep 8.
Pleural diffuse malignant mesothelioma typically presents during the seventh decade of life and has poor prognosis. Recent epidemiologic studies have shown differences between young and older mesothelioma patients, but the biology of pleural mesothelioma in young patients is poorly understood. We studied the clinicopathologic and genetic characteristics in pleural mesothelioma patients aged 35 years and younger. Thirty-six consecutive pleural mesothelioma patients aged 35 years and younger were compared with 48 older patients. We examined demographic and clinical characteristics, histologic type, growth patterns, mitotic index, and nuclear grade on hematoxylin and eosin-stained slides, BAP1 protein expression by immunohistochemistry, and CDKN2A and NF2 deletions by fluorescence in situ hybridization. Clinicopathologic and cytogenetic results were compared between young and older groups, and correlated with overall survival. Young patients were more frequently women, reported less asbestos exposure, and had a greater frequency of prior therapeutic radiation and family history of breast cancer than older patients (P<0.05 each). There were no histologic differences between young and older patients (all P>0.05). CDKN2A deletion was less prevalent in young patients (P=0.01), loss of BAP1 protein expression less frequent in young patients (P=0.06), and NF2 deletion rates similar between groups (P>0.05 each). Median overall survival was 40 vs 26 months (P=0.10) in young and older patients, respectively, and 47 vs 31 months (P=0.04) when comparing patients with epithelioid histology only. High mitotic index and non-epithelioid histology were the only characteristics associated with a poor overall survival in young patients. Young patients with pleural mesothelioma have an equal sex distribution and are more likely to have a history of mantle radiation, family history of breast cancer, and lower rates of CDKN2A deletion than older patients. Our results suggest that pleural mesothelioma in young patients has distinctive clinical and genetic characteristics, despite some similarities to pleural mesothelioma in older patients.
弥漫性胸膜恶性间皮瘤通常发生在 70 岁左右，预后较差。最近的流行病学研究表明，年轻和老年间皮瘤患者之间存在差异，但年轻患者胸膜间皮瘤的生物学特性尚未得到很好的理解。我们研究了年龄在 35 岁及以下的胸膜间皮瘤患者的临床病理和遗传特征。将 36 例连续的年龄在 35 岁及以下的胸膜间皮瘤患者与 48 例年龄较大的患者进行比较。我们检查了苏木精和伊红染色切片上的组织学类型、生长模式、有丝分裂指数和核级、BAP1 蛋白免疫组化表达以及荧光原位杂交的 CDKN2A 和 NF2 缺失。比较了年轻和老年组的临床病理和细胞遗传学结果，并与总生存相关。年轻患者更多为女性，报告的石棉暴露较少，且既往治疗性放疗和乳腺癌家族史的发生率高于老年患者（均 P<0.05）。年轻和老年患者之间的组织学差异无统计学意义（均 P>0.05）。年轻患者中 CDKN2A 缺失的发生率较低（P=0.01），年轻患者中 BAP1 蛋白表达缺失的频率较低（P=0.06），两组 NF2 缺失率相似（均 P>0.05）。年轻和老年患者的中位总生存时间分别为 40 个月和 26 个月（P=0.10），仅比较上皮样组织学的患者分别为 47 个月和 31 个月（P=0.04）。年轻患者中高有丝分裂指数和非上皮样组织学是总生存不良的唯一特征。与老年患者相比，年轻患者的胸膜间皮瘤具有性别分布均等、更有可能接受斗篷放疗、乳腺癌家族史和 CDKN2A 缺失率较低的特点。我们的研究结果表明，尽管年轻患者的胸膜间皮瘤与老年患者的胸膜间皮瘤有一些相似之处，但年轻患者的胸膜间皮瘤具有独特的临床和遗传特征。
