Objective To discuss the clinical pathological features,diagnosis and differential diagnosis,therapy and prognosis of primary breast diffuse large B-cell lymphoma(PB-DLBCL).Methods The clinical manifestations,pathological features,immunophenotypic characteristics of 4 cases of PB-DLBCL were retrospectively reviewed,and related literatures were reviewed.Results All of the 4 patients were women,aged 45 to 69 years,with the median 58.5 years.There were 3 cases of lesions involving the left breast and 1 case of the right breast.Microscopic observation showed that the normal structure of the mammary gland was destroyed,and no capsule was seen.There was a large number of large-to medium-sized heterotypic lymphoid cells which characterized as diffuse infiltration between the remaining ducts or lobules of mammary gland.Tumor cells infiltrated adipose tissue,mainly as central blast-like cells (3 cases) and immunoblast-like cells (1 case).No lymphatic epithelial lesions were observed.The immunophenotype showed 4 cases were non-GCB type.Immunostaining showed that the neoplastic cells were LCA,CD20,CD79a and MUM-1 positive.Ki67 index were from 50％ to 80％.The follow-up time of these cases was until Dec.2017.There was one recurrence during the follow-up period.The patient died 13 months later.One patient was alive and had survived for 66 months.Two patients were lost to follow-up.Conclusions PB-DLBCL is extremely rare,mainly found in women.Most of the cell origin types are non-GCB type,which is often misdiagnosed as breast cancer.The diagnosis of PB-DLBCL is confirmed by pathological biopsy and immunohistochemical markers.The treatment is not clear,and a comprehensive treatment plan such as R-CHOP/ CHOP chemotherapy combined with radiotherapy is recommended.

Objective:The residual cancer burden (RCB) evaluation system was used to analyze the influencing factors of the efficacy of neoadjuvant therapy in breast cancer, and to explore the prognostic value of RCB evaluation in neoadjuvant therapy.Methods:Clinicopathologic data and postoperative RCB grading of 364 breast cancer patients who underwent neoadjuvant therapy in Renmin Hospital of Wuhan University from Nov. 2019 to Nov. 2022 were collected. Chi-square test was used to analyze the relationship between RCB grading and clinicopathological parameters, and Spearman’s rank correlation analysis was performed to evaluate the correlation between RCB grading and clinicopathological characteristics. Factors influencing pathologic complete response (pCR) were analyzed by Logistic regression. Kaplan-Meier survival analysis and log-rank test were used to evaluate cumulative survival.Results:Among the 364 patients who underwent neoadjuvant therapy, 129 cases of RCB grade 0 and 235 cases of RCB gradeⅠ-Ⅲ (including 46 cases of RCB gradeⅠ, 109 cases of RCB grade Ⅱ and 80 cases of RCB grade Ⅲ) were obtained after surgery. Histological classification ( χ 2=21.757, P=0.000), estrogen receptor (ER) ( χ 2=52.837, P=0.000), progesterone receptor (PR) ( χ 2=55.658, P=0.000), human epidermal growth factor receptor-2 (HER2) ( χ2=89.040, P=0.000), Ki67 expression ( χ2=12.927, P=0.005), molecular typing ( χ 2=80.793, P=0.000) and preoperative lymph node status ( χ 2=25.764, P=0.000) were all associated with postoperative RCB grading. Further correlation analysis showed that histological grade ( r=-0.229, P=0.000), HER2 expression ( r=-0.465, P=0.000) and Ki67 expression ( r=-0.179, P=0.000) were negatively correlated with RCB grading, while ER ( r=0.352, P=0.000), PR ( r=0.379, P=0.000) and lymph node metastasis ( r=0.214, P=0.000) were positively correlated with RCB grading. Logistic regression analysis showed that high histological grade, negative expression of ER, PR and AR, positive expression of HER2, high proliferation index of Ki67 and no lymph node metastasis were favorable factors for postoperative pCR, and PR, AR and HER2 were independent predictors of postoperative pCR. Kaplan-Meier survival analysis showed significant differences in postoperative cumulative survival among patients with different RCB grades ( P=0.004) . Conclusions:Postoperative RCB grading of breast cancer is closely related to many clinicopathological features before neoadjuvant therapy and survival prognosis. Clinicopathological factors closely related to RCB grading are also important influencing factors affecting the pCR of patients with neoadjuvant therapy. Therefors, RCB grading has a high prognostic value.

Objective:To investigate the role of Caspase-1/gasdermin D (GSDMD) -mediated cell pyroptosis in anti-tumor effect of cisplatin (DDP) in triple-negative breast cancer (TNBC) .Methods:HE staining and immunohistochemical staining were performed to detect the morphological changes and the expression of pyroptosis/apoptosis pathway related proteins in TNBC tissues before and after DDP-based neoadjuvant chemotherapy (NACT) . The TNBC cell line MDA-MB-231 was treated with DDP and the morphological changes were observed. The type of cell death induced by DDP was analyzed by Annexin V-FITC/PI double staining and flow cytometry. Lactate dehydrogenase (LDH) release assay and ELISA were performed to detect the release of LDH and inflammatory factors (IL-18 and IL-1β) in cell culture supernatant after DDP treatment. Western blot (WB) was performed to detect the expression of pyroptosis/apoptosis pathway related proteins in cells after DDP treatment. MDA-MB-231 cells treated with DDP were co-treated with caspase-1 specific inhibitor to inhibit pyroptois or co-treated with caspase-3 specific inhibitor to inhibit apoptosis. The effect of caspase-1 inhibitor or caspase-3 inhibitor on the anti-tumor effect of DDP was detected by MTT assay, clone formation assay, transwell assay and would healing test.Results:Reactive changes in the breast surgical specimen after DDP-based NACT included cell swelling and inflammatory cell aggregation around the tumor bed, which were more similar to pyroptosis. The up-regulation of key molecules of pyroptosis pathway post-NACT was significantly higher than that of key molecules of apoptosis pathway. Further experiments in vitro showed that DDP could induce MDA-MB-231 cells to show pyroptosis-like changes characterized by large bubbles blowing from the cellular membrane. Flow-cytometry analyses showed that the death type of MDA-MB-231 cells caused by DDP was mainly Annexin V +PI + cells (mainly lytic cells, such as pyroptosis) . Additionally, DDP treatment induced significant activation of caspase-1 and GSDMD, increased the release of LDH, IL-18 and IL-1β, however, the activation level of caspase-3, which dominates the apoptosis pathway, was significantly lower than that of caspase-1/GSDMD. Moreover, caspase-1 inhibitors (blocking the classical pyroptosis pathway) had a significantly greater inhibitory effect on the anti-tumor effect of DDP than caspase-3 inhibitors (blocking the apoptosis pathway) . Conclusion:Caspase-1/GSDMD mediated pyroptosis may play a leading role in the anti-tumor effect of DDP in triple-negative breast cancer.