To understand how malignant tumors develop, we tracked cell membrane, nuclear membrane, spindle, and cell cycle dynamics in polyploid giant cancer cells (PGCCs) during the formation of high-grade serous carcinoma organoids using long-term time-lapse imaging. Single cells underwent traditional mitosis to generate tissue with uniform nuclear size, while others formed PGCCs via asymmetric mitosis, endoreplication, multipolar endomitosis, nuclear fusion, and karyokinesis without cytokinesis. PGCCs underwent restitution multipolar endomitosis, nuclear fragmentation, and micronuclei formation to increase nuclear contents and heterogeneity. At the cellular level, the development of PGCCs was associated with forming transient intracellular cells, termed fecundity cells. The fecundity cells can be decellularized to facilitate nuclear fusion and synchronized with other nuclei for subsequent nuclear replication. PGCCs can undergo several rounds of entosis to form complex tissue structures, termed fecundity structures. The formation of PGCCs via multiple modes of nuclear replication in the absence of cytokinesis leads to an increase in the nuclear-to-cytoplasmic (N/C) ratio and intracellular cell reproduction, which is remarkably similar to the mode of nuclear division during pre-embryogenesis. Our data support that PGCCs may represent a central regulator in malignant histogenesis, intratumoral heterogeneity, immune escape, and macroevolution via the de-repression of suppressed pre-embryogenic program in somatic cells.

Background: The impact of chemotherapy response score (CRS) on prognosis has varied among studies. We addressed the prognostic significance of CRS and the prognostic value of previously undescribed histologic features using a cohort of 245 patients. Methods: Retrospective study in patients with advanced extrauterine high-grade serous carcinomas treated with neoadjuvant chemotherapy followed by interval tumor reductive surgery from 1990 to 2018 in our hospital. Gynecologic pathologists assessed tumor CRS and other histologic features. Clinical information was collected, and multivariate analyses were conducted. Results: A modified 2 tier CRS (CRS 1/2 versus CRS 3) was significantly associated, independent of scoring site (omental versus adnexal), with overall survival (OS) (omentum, p = 0.018; adnexa, p = 0.042; entire cohort, p = 0.002) and progression-free survival (PFS) (p = 0.021, p = 0.035, and p = 0.001, respectively). On multivariate survival analysis, 2 tier CRS, oncocytic change, inflammation, and desmoplasia were significant for OS (p = 0.034, p = 0.020, p = 0.007, and p = 0.010, respectively). Likewise, 2 tier CRS, inflammation, and desmoplasia were significant for PFS (p = 0.012, p = 0.003, p = 0.011, respectively). Conclusions: The modified 2 tier CRS was significantly associated with survival, independent of scoring site. Additional histologic features including oncocytic change, inflammation, and desmoplasia can also predict patient outcomes.

评价国产苯达莫司汀联合利妥昔单抗一线治疗惰性B细胞淋巴瘤（B-iNHL）和老年套细胞淋巴瘤（MCL）的有效性和安全性。 于2020年12月1日至2022年9月10日在山东省内10家三甲医院多中心前瞻性研究国产苯达莫司汀联合利妥昔单抗治疗初诊B-iNHL和老年MCL患者的疗效和安全性，所有患者均已完成至少4个周期诱导治疗。 共入组B-iNHL与年MCL患者72例，中位年龄为55（24～74）岁，美国东部肿瘤协作组体能状态评分（ECOG评分）0～1分者占76.4％，ECOG 2分者占23.6％。滤泡淋巴瘤（FL）占51.4％，边缘区淋巴瘤（MZL）占33.3％，老年MCL占11.1％，不能分类占4.2％。Ann Arbor分期：Ⅲ期占16.7％、Ⅳ期占65.3％。4个周期诱导治疗后，总有效率为98.6％，其中完全缓解（CR）率为83.3％，部分缓解（PR）率为15.3％。仅1例MCL患者治疗中进展，1例FL患者复发。考虑到PET/CT评估与CT评估的差异，即使按照CT评估，其CR率为63.9％。中位随访11（4～22）个月，无进展生存（PFS）率为96.8％，总生存（OS）率为100.0％。主要血液学不良反应包括：3～4级白细胞减少（27.8％，其中8.3％的患者出现粒细胞缺乏伴发热），3～4级淋巴细胞减少（23.6％），3～4级贫血（5.6％）及3～4级血小板减少（4.2％）。非血液学不良反应主要为乏力、恶心/呕吐、皮疹、感染，发生率均低于20.0％。 国产苯达莫司汀联合利妥昔单抗一线治疗B-iNHL和老年MCL患者安全有效。