Although there is early support for schemes based on nuclear grade, necrosis and mitotic rate, there is currently no widely implemented grading system for diffuse pleural mesothelioma (DPM). We investigated current systems and propose a novel Mesothelioma Weighted Grading Scheme (MWGS). The MWGS assigns weighted scores from 0 to 10 based on age (≤74, >74 yrs: 0,1); histologic type (epithelioid, biphasic, sarcomatoid: 0,1,2); necrosis (absent, present: 0,2); mitotic count per 2 mm² (≤1, 2 to 4, ≥5: 0,1,2); nuclear atypia (mild, moderate, severe: 0,1,2); and BRCA1-associated protein 1 (BAP1) expression (lost, retained: 0,1). A score of 0 to 3 is low grade, 4 to 6 intermediate grade, and 7 to 10 high grade. In 369 consecutive DPMs, median survival was 17.1, 10.1, and 4.1 months for low, intermediate, and high grades (P<0.0001). A progressive increase in score correlated with worsening overall survival (P<0.0001). Interobserver concordance was substantial (κ=0.588), with assessment of nuclear grade being the most subjective parameter (κ=0.195). We compared the MWGS to the 2-tiered system discussed in the World Health Organization (WHO) fifth edition. The WHO system predicted median survival in epithelioid (median 18.0 vs. 11.3 mo, P=0.003) and biphasic (16.2 vs. 4.2 mo, P=0.002), but not sarcomatoid DPM (5.4 vs. 4.7 mo, P=0.407). Interestingly, the WHO grading system was prognostic in cases with BAP1 loss (median survival 18.7 vs. 10.4 mo, P<0.0001), but not retained BAP1 expression (8.9 vs. 6.2 mo, P=0.061). In conclusion, the WHO scheme has merit in epithelioid/biphasic and BAP1-deficient DPM, however, the MWGS can be used for risk stratification of all DPMs, regardless of histologic subtype and BAP1 status.

虽然早期支持基于核分级、坏死和有丝分裂率的方案，但目前还没有广泛实施的弥漫性胸膜间皮瘤 (DPM) 分级系统。我们调查了当前系统并提出了一种新颖的间皮瘤加权分级方案 ( MWGS )。MWGS根据年龄（≤74，>74 岁：0,1）分配从 0 到 10 的加权分数；组织学类型（上皮样、双相、肉瘤样：0、1、2）；坏死（不存在，存在：0,2）；^{每 2 mm 2}的有丝分裂计数(≤1, 2 至 4, ≥5: 0,1,2)；核异型（轻度、中度、重度：0、1、2）；和BRCA1 相关蛋白 1(BAP1) 表达（丢失，保留：0,1）。0 到 3 分是低等级，4 到 6 分是中等等级，7 到 10 分是高等级。在 369 次连续 DPM 中，低、中和高等级的中位生存期分别为 17.1、10.1 和 4.1 个月（P <0.0001）。分数的逐渐增加与总生存期恶化相关（P <0.0001）。观察者间的一致性是显着的（κ=0.588），核分级的评估是最主观的参数（κ=0.195）。我们将MWGS与世界卫生组织 (WHO) 第五版中讨论的 2 层系统进行了比较。WHO 系统预测上皮样（中位 18.0 对 11.3 个月，P = 0.003）和双相（16.2 对 4.2 个月，P= 0.002），但不是肉瘤样 DPM（5.4 对 4.7 个月，P = 0.407）。有趣的是，WHO 分级系统对 BAP1 缺失的病例具有预后意义（中位生存期 18.7 对 10.4 个月，P <0.0001），但未保留 BAP1 表达（8.9 对 6.2 个月，P = 0.061）。总之，WHO 方案在上皮样/双相和 BAP1 缺陷型 DPM 方面具有优势，然而，MWGS可用于所有 DPM 的风险分层，无论组织学亚型和 BAP1 状态如何。