Malignant phyllode tumor metastatic to the duodenum

Phyllode tumor （PT） is extremely rare tumor of the breast. Distant metastasis occurs in 10-20% of patients with malignant phyllode tumor. The most common sites of metastases are the lungs and bones. Although theoretically any organ may have metastasis, an isolated duodenum metastasis has not been documented as yet in the English-language literature. We report herein a case with a isolated duodenal metastasis from PT of breast in a 31 year-old-woman who underwent right mastectomy 4 years before because of the recurrent malignant PT. She presented to our hospital with massive upper gastrointestinal bleeding. Clinical evaluation revealed a huge mass originated from duodenum. Urgent laparotomy and pancreaticoduodenectomy were carried out in order to remove the bleeding duodenal mass. The pathologic examination of the resected specimen showed a malignant spindle cell tumor consistent with metastatic malignant PT. Our case of gastrointestinal bleeding due to an isolated duodenal metastasis as a result of hematogenous spread from malignant phyllode tumor of breast is unique in the English literature and pancreaticoduodenectomy is a curative treatment for patients with isolated duodenal involvement.

Giant phyllodes tumor of the breast:a case report

Objective： The aim of the study was to report a case with a giant phyllodes tumor of the left breast and discuss the diagnostic and management challenges. Methods： A 47-year-old female patient was admitted to our center （Department of General Surgery, the First Affiliated Hospital, Luzhou Medical College, China） due to a large left breast mass for about 2.5 years. Core tissue biopsy showed mixed epithelial-stromal proliferation suggestive of a phyllodes tumor. Left modified radical mastectomy with dissection of level Ⅰ and level Ⅱ lymph nodes was performed. Results： The pathologic findings of this proce- dure were consistent with borderline phyllodes tumor. The tumor measured 47.5 cm× 37,0 cm× 28.0 cm and weighed 9.79 kg ex vivo. Conclusion： To our knowledge, this patient presented one of the biggest phyllodes tumors of breast in all cases reported in English-language publications so far.

LncRNA ZFPM2-AS1 promotes phyllodes tumor progression by binding to CDC42 and inhibiting STAT1 activation

Breast phyllodes tumor(PT)is a rare fibroepithelial neoplasm with potential malignant behavior.Long non-coding RNAs(lncRNAs)play multifaceted roles in various cancers,but their involvement in breast PT remains largely unexplored.In this study,microarray was leveraged for the first time to investigate the role of lncRNA in PT.We identified lncRNA ZFPM2-AS1 was significantly upregulated in malignant PT,and its overexpression endowed PT with high tumor grade and adverse prognosis.Furthermore,we elucidated that ZFPM2-AS1 promotes the proliferation,migration,and invasion of malignant PT in vitro.Targeting ZFPM2-AS1 through nanomaterial-mediated siRNA delivery in patient-derived xenograft(PDX)model could effectively inhibit tumor progression in vivo.Mechanistically,our findings showed that ZFPM2-AS1 is competitively bound to CDC42,inhibiting ACK1 and STAT1 activation,thereby launching the transcription of TNFRSF19.In conclusion,our study provides evidence that ZFPM2-AS1 plays a pivotal role in the pathogenesis of breast PT,and suggests that ZFPM2-AS1 could serve as a prognostic indicator for patients with PT as well as a promising novel therapeutic target.

CD146 promotes malignant progression of breast phyllodes tumor through suppressing DCBLD2 degradation and activating the AKT pathway

Background As a rapid-progressing tumor,breast malignant phyllodes tumors(PTs)are challenged by the lack of effective therapeutic strategies and suitable prognostic markers.This study aimed to clarify the role and mechanism of CD146 on promoting PTs malignant progression,and to identify a novel prognosis marker and treatment target of breast malignant PTs.Methods The expression and prognostic significance of CD146 in PTs was detected through single-cell RNA-sequencing(scRNA-seq),immunostaining,real-time PCR and other methodologies.Functional experiments including proliferation assay,colony formation assay,transwell assay,and collagen contraction assay were conducted to validate the role of CD146 in malignant progression of PTs.The efficacy of anti-CD146 monoclonal antibody AA98 against malignant PTs was corroborated by a malignant PT organoid model and a PT patient-derived xenograft(PDX)model.Transcriptome sequencing,proteomic analysis,co-immunoprecipitation,and pull-down assay was employed to identify the modulating pathway and additional molecular mechanism.Results In this study,the scRNA-seq analysis of PTs disclosed a CD146-positive characteristic in theα-SMA+fibroblast subset.Furthermore,a progressive elevation in the level of CD146 was observed with the malignant progression of PTs.More importantly,CD146 was found to serve as an independent predictor for recurrence in PT patients.Furthermore,CD146 was found to augment the viability and invasion of PTs.Mechanistically,CD146 acted as a protective“shield”to prevent the degradation of Discoidin,CUB,and LCCL domain-containing protein 2(DCBLD2),thereby activating the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway and enhancing malignant behaviors of PT cells.In the malignant PT organoid and PDX model,a significant suppression of malignant PT growth was observed after the application of AA98.Conclusions These findings suggested that CD146 served as an efficacious marker for predicting PT malignant progression and showed promise as a prognosis marker and treatment target of breast malignant PTs.The study further unveiled the essential role of the CD146-DCBLD2/PI3K/AKT axis in the malignant progression of PTs.

Pulmonary metastases 12 years after a mastectomy for borderline phyllodes tumor

Phyllodes tumor is a rare breast tumor. A 45-year-old woman who underwent left mastectomy 12 years ago was found to have infiltrates in both lungs in a health examination. Combining histological examinations of the lung and breast samples the diagnosis of borderline phyllodes tumor metastases to the lung was made. It is the longest interval to our knowledge that the metastases occurred 12 years after primary phyllodes tumor.