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Histology and Histopathology Jun 2024Breast phyllodes tumors (BPTs) are difficult to differentiate from other tumor types. In-depth research is needed due to the insufficient description of the amine...
BACGROUND
Breast phyllodes tumors (BPTs) are difficult to differentiate from other tumor types. In-depth research is needed due to the insufficient description of the amine oxidase protein family, particularly in BPTs.
OBJECTIVE
This study investigated the expression and clinical implications of amine oxidase-related proteins in BPTs.
METHODS
Tissue microarrays were constructed (n=181), and amine oxidase-related proteins of monoamine oxidase (MAO) A, MAOB, lysyl oxidase (LOX), and primary-amine oxidase 3 (AOC3) were assessed using immunohistochemical staining. Staining patterns of these proteins were compared and analyzed with clinicopathologic parameters.
RESULTS
In all, 149, 27, and 5 cases were classified as benign, borderline, and malignant, respectively. A higher grade of BPT was associated with increased MAOB (<0.001), LOX (=0.035), and AOC3 (<0.001) expression. BPT cases with tumor recurrence and distant metastasis had higher proportions of MAOB positivity in stromal components (=0.002 and 0.018, respectively). During follow-up, there was a significant association between MAOB positivity in the stromal component and shorter disease-free survival (DFS) (=0.001) as well as overall survival (=0.003). Moreover, MAOB positivity emerged as an independent factor for shorter DFS (hazard ratio: 4.253, 95% confidence interval: 1.034-17.49, =0.045).
CONCLUSIONS
Higher MAOB, LOX, and AOC3 expression were observed in higher-grade BPTs, and MAOB expression was identified as a significant prognostic factor.
PubMed: 38887035
DOI: 10.14670/HH-18-773 -
Journal of Cancer Research and... 2023Phyllodes tumors are rare biphasic fibroepithelial lesions of the breast and account for 0.3%-0.5% of primary breast tumors. Malignant phyllodes tumor has a 10%-26% risk...
Phyllodes tumors are rare biphasic fibroepithelial lesions of the breast and account for 0.3%-0.5% of primary breast tumors. Malignant phyllodes tumor has a 10%-26% risk of distant metastasis. The most common site of metastasis is lungs followed by bone and soft tissue. This is a rare case of a 42-year-old female with a previous history of malignant phyllodes tumor breast. She presented after 10 years with metastases to multiple sites including lung, abdominal wall, retroperitoneum, bone, and brain. These tumors have a poor overall survival. Accurate diagnosis and aggressive management of malignant phyllodes tumors can help in effective treatment at diagnosis and for close follow-up of the patients.
Topics: Female; Humans; Adult; Phyllodes Tumor; Breast; Treatment Outcome; Lung Neoplasms; Breast Neoplasms
PubMed: 37787325
DOI: 10.4103/jcrt.jcrt_715_21 -
Cancer Reports (Hoboken, N.J.) Sep 2023Phyllodes tumor (PT) is a solid fibroepithelial breast lesion with proliferation of stromal and epithelial elements, usually presents with a rapidly expanding feature....
BACKGROUND
Phyllodes tumor (PT) is a solid fibroepithelial breast lesion with proliferation of stromal and epithelial elements, usually presents with a rapidly expanding feature. Venous thromboembolism (VTE) have been reported to increase the burden in terms of mortality and morbidity of malignant tumor, and associate with worsened survival. However, benign PTs with silent thromboembolism that have not yet been reported, we report an unusual case of massive benign PT that grew on the left side of the breast in a cauliflower-shaped form and presented severe chronic blood loss and deep VTE.
CASE
A 37-year-old woman with uncontrolled pain presented a rapidly enlarging left breast mass, measuring approximately 30 × 20 × 15 cm that first started 25 years ago. color Doppler ultrasound showed a large mass lesion on the left breast and deep VTE, several enlarged lymph nodes in the left axilla and mediastinum, which presented a malignant character. However, the biopsies of the mass did not show evidence of malignancy and the pathology result was considered to be benign PT. The patient was treated with an inferior vena cava and anticoagulation, the operation was arranged according to the surgical procedure, the patient recovered very well after mastectomy.
CONCLUSION
This case is unique in that the giant breast mass presented with malignant character, was eventually pathologically confirmed to be benign PT, and it's rare that the benign tumor accompanied with silent thromboembolism. This finding describes the atypia features of giant benign PT and reminds the surgeon to consider the factor of VTE and risk when encountering ulcerative benign breast tumor and avoid excessive treatment.
Topics: Female; Humans; Adult; Breast Neoplasms; Mastectomy; Phyllodes Tumor; Venous Thromboembolism; Breast
PubMed: 37580942
DOI: 10.1002/cnr2.1865 -
European Journal of Cancer (Oxford,... Apr 2024The aim of our study is to analyze patterns in treatment and outcome in a population-based series of patients with borderline and malignant phyllodes tumors (PT).
AIM
The aim of our study is to analyze patterns in treatment and outcome in a population-based series of patients with borderline and malignant phyllodes tumors (PT).
MATERIAL AND METHODS
Data on all patients with a borderline or malignant PT (1989-2020) were extracted from the Netherlands Cancer Registry and the Dutch nationwide pathology databank (Palga) and retrospectively analyzed.
RESULTS
We included 921 patients (borderline PT n = 452 and malignant PT n = 469). Borderline PT patients more often had breast-conserving surgery (BCS) as final surgery (81 vs. 46%). BCS rates for borderline PT increased over time (OR 1.08 per year, 95%CI 1.04 - 1.13, P < 0.001). In malignant PT adjuvant radiotherapy was given in 14.7%; this rate increased over time (OR 1.07 per year, 95%CI 1.02 - 1.13, P = 0.012). Local recurrence rate (5-year estimate of cumulative incidence) was 8.7% (95%CI 6.0-11.4) for borderline PT and 11.7% (95%CI 8.6-14.8) for malignant PT (P = 0.187) and was related to tumor size ≥ 20 mm (HR 10.6 (95%CI 1.5-76.8) and positive margin (HR 3.0 (95%CI 1.6-5.6), p < 0.001), but not to negative margin width (HR 1.3 ( 95%CI 0.7-2.3), p = 0.350)). Distant metastasis occurred only in malignant PT with a 5-year cumulative incidence of 4.7% (95%CI 3.3 - 6.1).
CONCLUSION
This population-based series showed an increase in BCS in borderline PT and an increase in adjuvant radiotherapy in malignant PT over time. We identified malignant PT, BCS, larger tumor size and positive final margins as possible risk factors for local recurrence. Small but negative margins can be accepted.
Topics: Humans; Female; Mastectomy; Phyllodes Tumor; Retrospective Studies; Netherlands; Follow-Up Studies; Neoplasm Recurrence, Local; Margins of Excision; Breast Neoplasms
PubMed: 38364628
DOI: 10.1016/j.ejca.2024.113924 -
Pathology, Research and Practice Jul 2024A female in her 60's presented with a left-sided breast mass. A core needle biopsy specimen showed diffuse proliferation of a round cell tumor, which was positive for...
A female in her 60's presented with a left-sided breast mass. A core needle biopsy specimen showed diffuse proliferation of a round cell tumor, which was positive for vimentin, NKX2.2, BCOR, and focal CD99 on immunohistochemistry (IHC). No fusion genes of the Ewing family sarcomas were detected. With a tentative diagnosis of primary breast sarcoma (PBS), total mastectomy was performed after chemotherapy. The resected tissues showed proliferation of round or spindle-shaped tumor cells with a high nuclear-to-cytoplasmic ratio, exhibiting solid and fascicular arrangements but no epithelial component or organoid pattern. While IHC indicated no particular histological diagnosis, genomic examination revealed gene alterations in MED12 p.G44D, MLL2 (KMT2D) p.T1496fs*27, and EGFR variant III (vIII). Moreover, a retrospective IHC study showed overexpression of EGFRvIII. A malignant phyllodes tumor (PT) with extensive sarcomatous overgrowth was indicated as an integrative diagnosis. This is a rare case of a malignant PT harboring EGFRvIII. The present case provides an importance of accurate diagnosis and genomic analysis of rare breast tumors, as malignant PT and PBS are different in its treatment strategy and prognosis.
Topics: Humans; Female; Phyllodes Tumor; Breast Neoplasms; Middle Aged; ErbB Receptors; Immunohistochemistry; Mutation; Biomarkers, Tumor; Homeobox Protein Nkx-2.2; DNA-Binding Proteins; Homeodomain Proteins; Nuclear Proteins; Mediator Complex; Transcription Factors; Neoplasm Proteins
PubMed: 38850845
DOI: 10.1016/j.prp.2024.155389 -
Cancers Dec 2023Epidermal growth factor receptor variant III (EGFRvIII, the deletion of exons 2-7) is a recurrent intragenic .E1E8 fusion that occurs in high-grade gliomas. The presence...
Epidermal growth factor receptor variant III (EGFRvIII, the deletion of exons 2-7) is a recurrent intragenic .E1E8 fusion that occurs in high-grade gliomas. The presence of EGFRvIII in other solid tumors has not been well characterized. We retrospectively reviewed advanced malignant solid tumor cases tested by a custom hybrid capture 610-gene next-generation sequencing platform from 2021 to 2022. EGFRvIII was identified in 17 of 4331 (0.4%) cases, including 16 of 238 (7%) brain tumors and 1/301 (0.3%) breast tumors. EGFRvIII-positive brain tumors were all glioblastoma IDH-wildtype, most with concurrent promoter mutation (14 of 16), amplification (13 of 16), and mutation (8 of 16). The only EGFRvIII-positive breast lesion was a sarcomatoid neoplasm in a young female patient. A separate breast case tested outside our institution with reported EGFRvIII was noted in a young female patient with a malignant phyllodes tumor with stromal overgrowth. Microscopically, both EGFRvIII-positive breast tumors showed high-grade sarcomatoid morphology with brisk mitotic activity. In summary, EGFRvIII is rare, occurring primarily in glioblastoma and rarely in breast sarcomatoid neoplasm, with no instances identified in other tumor types in our series. This select group of patients may benefit from chemotherapy and/or targeted anti-EGFR therapy.
PubMed: 38201434
DOI: 10.3390/cancers16010006 -
Heliyon Jan 2024Proliferation of both stromal and epithelial components is a characteristic of fibroepithelial cancers of the breast. Certain fibroepithelial tumors of the breast, such...
Proliferation of both stromal and epithelial components is a characteristic of fibroepithelial cancers of the breast. Certain fibroepithelial tumors of the breast, such as fibradenomas and phyllodes tumors, are challenging to distinguish and categorize. To find biomarkers for early diagnosis and improved disease management, it is crucial to deepen our understanding of the molecular pathogenesis pathways and tumor biology of PTs. It has been demonstrated that microRNAs (miRNAs) have significant roles in cancers; the expression pattern of miRNAs can help with cancer categorization and treatment. In contrast, little is understood about miRNAs in breast fibroepithelial cancers. This study was conducted retrospectively with the goal of assessing the expression of six mature miRNAs (hsa-miR-21, hsa-miR-155, hsa-miR-182, hsa-miR-34a, hsa-miR-148a, and hsa-miR-205) in breast fibroepithelial cancers using real-time PCR and predicting these miRNAs' targets using computational techniques. This study comprised 64 patients in total-55 with phyllodes tumors and 9 with fibroadenoma. The research was carried out at the Farhat Hached University Hospital's pathology department in Tunisia. These particular miRNAs expression levels were evaluated via qRT-PCR, and in silico techniques were utilized to predict potential miRNA targets. Analysis of miRNA expression in fibroadenoma and phyllodes tumor tissues revealed that miR-21, miR-155 and miR-182 were upregulated in PTs compared to fibroadenoma and normal tissues. We reported that miR-34a, miR-148a and miR-205 were downregulated in both borderline and malignant PTs compared to fibroadenoma and normal tissue. In silico miRNA target prediction suggested the involvement of these molecules in a wide context of cell signaling pathways.
PubMed: 38312609
DOI: 10.1016/j.heliyon.2024.e24803 -
International Journal of Surgical... Feb 2024
PubMed: 38303558
DOI: 10.1177/10668969241228287 -
Clinical Breast Cancer May 2024To investigate whether a radiomics model based on mammography (MG) and magnetic resonance imaging (MRI) can be used to predict disease-free survival (DFS) after...
PURPOSE
To investigate whether a radiomics model based on mammography (MG) and magnetic resonance imaging (MRI) can be used to predict disease-free survival (DFS) after phyllodes tumor (PT) surgery.
METHOD
About 131 PT patients who underwent MG and MRI before surgery between January 2010 and December 2020 were retrospectively enrolled, including 15 patients with recurrence and metastasis and 116 without recurrence. 884 and 3138 radiomic features were extracted from MG and MR images, respectively. Then, multiple radiomics models were established to predict the recurrence risk of the patients by applying a support vector machine classifier. The area under the ROC curve (AUC) was calculated to evaluate model performance. After dividing the patients into high- and low-risk groups based on the predicted radiomics scores, survival analysis was conducted to compare differences between the groups.
RESULTS
In total, 3 MG-related and 5 MRI-related radiomic models were established; the prediction performance of the T1WI feature fusion model was the best, with an AUC value of 0.93. After combining the features of MG and MRI, the AUC increased to 0.95. Furthermore, the MG, MRI and all-image radiomic models had statistically significant differences in survival between the high- and low-risk groups (P < .001). All-image radiomics model showed higher survival performance than the MG and MRI radiomics models alone.
CONCLUSIONS
Radiomics features based on preoperative MG and MR images can predict DFS after PT surgery, and the prediction score of the image radiomics model can be used as a potential indicator of recurrence risk.
PubMed: 38839461
DOI: 10.1016/j.clbc.2024.05.006 -
Clinical and Translational Medicine Mar 2024Breast phyllodes tumours (PTs) are a unique type of fibroepithelial neoplasms with metastatic potential and recurrence tendency. However, the precise nature of...
BACKGROUND
Breast phyllodes tumours (PTs) are a unique type of fibroepithelial neoplasms with metastatic potential and recurrence tendency. However, the precise nature of heterogeneity in breast PTs remains poorly understood. This study aimed to elucidate the cell subpopulations composition and spatial structure and investigate diagnostic markers in the pathogenesis of PTs.
METHODS
We applied single-cell RNA sequencing and spatial transcriptomes on tumours and adjacent normal tissues for integration analysis. Immunofluorescence experiments were conducted to verify the tissue distribution of cells. Tumour cells from patients with PTs were cultured to validate the function of genes. To validate the heterogeneity, the epithelial and stromal components of tumour tissues were separated using laser capture microdissection, and microproteomics data were obtained using data-independent acquisition mass spectrometry. The diagnostic value of genes was assessed using immunohistochemistry staining.
RESULTS
Tumour stromal cells harboured seven subpopulations. Among them, a population of widely distributed cancer-associated fibroblast-like stroma cells exhibited strong communications with epithelial progenitors which underwent a mesenchymal transition. We identified two stromal subpopulations sharing epithelial progenitors and mesenchymal markers. They were inferred to further differentiate into transcriptionally active stromal subpopulations continuously expressing COL4A1/2. The binding of COL4A1/2 with ITGA1/B1 facilitated a growth pattern from the stroma towards the surrounding glands. Furthermore, we found consistent transcriptional changes between intratumoural heterogeneity and inter-patient heterogeneity by performing microproteomics studies on 30 samples from 11 PTs. The immunohistochemical assessment of 97 independent cohorts identified that COL4A1/2 and CSRP1 could aid in accurate diagnosis and grading.
CONCLUSIONS
Our study demonstrates that COL4A1/2 shapes the spatial structure of stromal cell differentiation and has important clinical implications for accurate diagnosis of breast PTs.
Topics: Humans; Female; Phyllodes Tumor; Transcriptome; Stromal Cells; Cell Differentiation; Breast Neoplasms; Collagen Type IV
PubMed: 38481388
DOI: 10.1002/ctm2.1611