Turashvili Gulisa, Ding Qingqing, Liu Yi, Peng Limin, Mrkonjic Miralem, Mejbel Haider, Wang Yihong, Zhang Huina, Zhang Gloria, Wang Jigang, Wei Shi, Li Xiaoxian
Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, GA, USA.
Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Am J Surg Pathol. 2023 Nov 1;47(11):1195-1206. doi: 10.1097/PAS.0000000000002109. Epub 2023 Sep 9.
The latest World Health Organization classification of breast tumors recommends diagnosing malignant phyllodes tumors (MPTs) when all 5 morphologic features are present: permeative borders, marked stromal cellularity, marked stromal cytologic atypia, ≥10 mitoses per 10 high-power fields (HPF), and stromal overgrowth. We assessed the performance of this recommendation to capture MPTs and features predictive of distant metastasis in a multi-institutional retrospective study. Of 65 MPTs, most cases had at least focally permeative borders (58, 89%), with marked stromal cellularity in 40 (61.5%), marked atypia in 38 (58.5%), ≥10 mitoses per 10 HPF in 50 (77%), and stromal overgrowth in 56 (86%). Distant metastases were observed in 20 (31%) patients (median follow-up 24.5 mo, 1 to 204). Only 13 of 65 (20%) cases had all 5 morphologic features, while only 7 of 20 (35%) cases with distant metastases had all 5 features. In univariate analysis, only marked stromal atypia ( P =0.004) and cellularity ( P =0.017) were associated with decreased distant metastasis-free survival. In multivariate Cox regression, the combination of stromal overgrowth, marked stromal cellularity, and atypia (C-index 0.721, 95% CI: 0.578, 0.863) was associated with decreased distant metastasis-free survival. The current World Health Organization recommendation will miss a significant number of MPTs with distant metastases. We propose refined diagnostic criteria for MPTs: (1) stromal overgrowth combined with ≥1 feature(s) (marked cellularity, marked atypia, or ≥10 mitoses per 10 HPF), or (2) in the absence of stromal overgrowth, marked cellularity combined with ≥1 feature(s) (permeative borders, marked atypia, or ≥10 mitoses per 10 HPF).
世界卫生组织最新的乳腺肿瘤分类建议，当具备以下所有5种形态学特征时，可诊断为恶性叶状肿瘤（MPT）：浸润性边界、显著的间质细胞增多、显著的间质细胞学异型性、每10个高倍视野（HPF）有≥10个核分裂象以及间质过度生长。我们在一项多机构回顾性研究中评估了该诊断建议对于识别MPT以及预测远处转移特征的效能。在65例MPT中，大多数病例至少有局灶性浸润性边界（58例，89%），40例（61.5%）有显著的间质细胞增多，38例（58.5%）有显著异型性，50例（77%）每10个HPF有≥10个核分裂象，56例（86%）有间质过度生长。20例（31%）患者出现远处转移（中位随访24.5个月，1至204个月）。65例中只有13例（20%）具备所有5种形态学特征，而20例有远处转移的病例中只有7例（35%）具备所有5种特征。单因素分析中，只有显著的间质异型性（P =0.004）和细胞增多（P =0.017）与远处无转移生存期缩短相关。多因素Cox回归分析显示，间质过度生长、显著的间质细胞增多和异型性的组合（C指数0.721，95%CI：0.578，0.863）与远处无转移生存期缩短相关。世界卫生组织当前的诊断建议会遗漏大量伴有远处转移的MPT。我们提出了MPT的细化诊断标准：（1）间质过度生长并伴有≥1项特征（显著的细胞增多、显著的异型性或每10个HPF有≥10个核分裂象），或（2）在无间质过度生长的情况下，显著的细胞增多并伴有≥1项特征（浸润性边界、显著的异型性或每10个HPF有≥10个核分裂象）。
