Department of Pathology, The University of Chicago Medicine, Chicago, IL, USA.
Department of Public Health Sciences, The University of Chicago, Chicago, IL, USA.
Mod Pathol. 2018 Apr;31(4):598-606. doi: 10.1038/modpathol.2017.170. Epub 2018 Jan 12.
A recently described nuclear grading system predicted survival in patients with epithelioid malignant pleural mesothelioma. The current study was undertaken to validate the grading system and to identify additional prognostic factors. We analyzed cases of epithelioid malignant pleural mesothelioma from 17 institutions across the globe from 1998 to 2014. Nuclear grade was computed combining nuclear atypia and mitotic count into a grade of I-III using the published system. Nuclear grade was assessed by one pathologist for three institutions, the remaining were scored independently. The presence or absence of necrosis and predominant growth pattern were also evaluated. Two additional scoring systems were evaluated, one combining nuclear grade and necrosis and the other mitotic count and necrosis. Median overall survival was the primary endpoint. A total of 776 cases were identified including 301 (39%) nuclear grade I tumors, 354 (45%) grade II tumors and 121 (16%) grade III tumors. The overall survival was 16 months, and correlated independently with age (P=0.006), sex (0.015), necrosis (0.030), mitotic count (0.001), nuclear atypia (0.009), nuclear grade (<0.0001), and mitosis and necrosis score (<0.0001). The addition of necrosis to nuclear grade further stratified overall survival, allowing classification of epithelioid malignant pleural mesothelioma into four distinct prognostic groups: nuclear grade I tumors without necrosis (29 months), nuclear grade I tumors with necrosis and grade II tumors without necrosis (16 months), nuclear grade II tumors with necrosis (10 months) and nuclear grade III tumors (8 months). The mitosis-necrosis score stratified patients by survival, but not as well as the combination of necrosis and nuclear grade. This study confirms that nuclear grade predicts survival in epithelioid malignant pleural mesothelioma, identifies necrosis as factor that further stratifies overall survival, and validates the grading system across multiple institutions and among both biopsy and resection specimens. An alternative scoring system, the mitosis-necrosis score is also proposed.
最近描述的核分级系统预测了上皮样恶性胸膜间皮瘤患者的生存情况。本研究旨在验证该分级系统，并确定其他预后因素。我们分析了来自全球 17 个机构的上皮样恶性胸膜间皮瘤病例，这些病例来自 1998 年至 2014 年。核分级通过使用发表的系统，将核异型性和有丝分裂计数结合起来，计算为 I-III 级。核分级由一名病理学家为三个机构进行评估，其余机构则独立评分。还评估了坏死和主要生长模式的存在与否。评估了另外两种评分系统，一种是将核分级和坏死结合起来，另一种是将有丝分裂计数和坏死结合起来。中位总生存期是主要终点。共确定了 776 例病例，其中 301 例（39%）为核 I 级肿瘤，354 例（45%）为核 II 级肿瘤，121 例（16%）为核 III 级肿瘤。总生存率为 16 个月，与年龄（P=0.006）、性别（0.015）、坏死（0.030）、有丝分裂计数（0.001）、核异型性（0.009）、核分级（<0.0001）和有丝分裂与坏死评分（<0.0001）独立相关。将坏死与核分级相结合，进一步分层了总生存率，使上皮样恶性胸膜间皮瘤分为四个不同的预后组：无坏死的核 I 级肿瘤（29 个月）、有坏死的核 I 级肿瘤和无坏死的核 II 级肿瘤（16 个月）、有坏死的核 II 级肿瘤（10 个月）和核 III 级肿瘤（8 个月）。有丝分裂-坏死评分按生存情况对患者进行分层，但不如坏死与核分级相结合的效果好。本研究证实核分级可预测上皮样恶性胸膜间皮瘤的生存情况，确定坏死是进一步分层总生存率的因素，并在多个机构以及活检和切除标本中验证了该分级系统。还提出了另一种评分系统，即有丝分裂-坏死评分。
