Phyllodes Tumor Research Articles

Clinicopathological Study of Patients with Non-inflammatory Benign Breast Disease at Combined Military Hospital (CMH) Chattogram

Introduction: Breast lump is a very common problem among females attending surgical outpatient department. Its development and growth are under the control of various hormones and various physiological statuses like menstruation, pregnancy, lactation and menopause. Objectives: To evaluate the clinicopathological status of patients with non-inflammatory benign breast disease (NIBBD). Methods: This clinical study was conducted at the department of surgery, CMH Chattogram, this study was done during January 2018 to May 2019. Patient presented with breast lump, nipple discharge, sinus and mastalgia in whom histopathology revealed any type of non-malignant BBD were included in the study. Patient treated on outdoor patient basis were excluded and patient with malignant breast lesions or acute breast abscess requiring incision and drainage were excluded from the study. Results: Majority of the patients, 41(74.5%) had breast lump followed by 10(18.2%) had breast pain, 6(10.9%) had nipple discharge and 3(5.5%) had enlargement of breast. Most of the site was found unilaterally 54(98.2%). Majority of the patients, 27(49.1%) had fibroadenoma, 14(25.5%) had fibrocystic diseases, 10(18.2%) had fibroadenosis, 2(3.6%) had duct ectasia, 1(1.8%) had cystosarcoma Phyllodes and 1(1.8%) had Lipoma. Conclusion: Maximum age group was 3rd to 4th decade. Most of the patients clinically presented with lumps in the breast followed by pain, enlargement of breast, fever and nipple discharge. Mostly encountered breast lesion was fibroadenoma other common lesion were found fibrocystic diseases, fibroadenosis, duct ectasia, cystosarcomaphyllodes and Lipoma. JAFMC Bangladesh. Vol 19, No 1 (June) 2023: 27-30

Integrating single-cell and spatial transcriptomes reveals COL4A1/2 facilitates the spatial organisation of stromal cells differentiation in breast phyllodes tumours.

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. 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. 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. 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.

213 (PB-120) Poster - Management of Phyllodes tumors: a Dutch population-based retrospective cohort between 1989 and 2022

213 (PB-120) Poster - Management of Phyllodes tumors: a Dutch population-based retrospective cohort between 1989 and 2022

Malignant Phyllodes Tumor of the Right Breast with Sacral Bone Metastasis- A Clinical Case from our Practice with A Literature Review

Phyllodes breast neoplasms are rarely diagnosed biphasic tumors that are benign, borderline, or malignant. We present a rare malignant phyllodes tumor in a 62-year-old woman with bone metastasis in the sacrum, presented 4 months after radical breast tumor surgery. Because of a severe pain syndrome, we performed intensity modulated radiotherapy with a high single dose of 8 Gy in two fractions, once a week. In this article we emphasize the difficult histopathological diagnosis, as well as the differential diagnosis, requiring immunohistochemistry of the two tumor components / epithelial and stromal/, as well as the clinical and pathological characteristics determining the malignant nature of the disease. In the presence of a soft tissue component of the bone metastasis, a biopsy with immunohistochemistry is required to prove the histopathological diagnosis of the distant metastasis. Distant metastases require complex treatment, including chemotherapy and palliative radiation therapy

A Recurrent Giant Phyllodes Tumor with Review of Literatures

Phyllodes tumors are rare breast tumors accounting for less than 1% Unlike breast cancers where they started from ducts and glands, phyllodes tumors start in the connective tissue of the breast. They are fast growing tumors with a large spectrum of behavior and most of them are benign with resemble of fibroadenoma with small number of borderline and malignant tumors. The correct diagnosis is mostly through core needle biopsy and it is also important to decide whether surgical management has to be done. Here we had a case of 38 year-old woman having recurrent fast growing lump to her right breast with distorted nipple with irregular border. MRI showed mass lesion measuring 9.5cm×14cm×20cm at right breast with few cystic areas with subtle chest wall infiltration especially underling muscles. After diagnosed to have phyllodes tumor total mastectomy involving partially the pectorals’ major with latissimus Dorsi myocutaneous flap reconstruction was done.

Cytoplasmic Expression of p16 Is Associated with Carcinoma Breast: It Is Not an Artifact.

p16 has different roles in the nuclear and cytoplasmic locations. The nuclear localization of the p16 protein explains its role in cell cycle regulation. Cytoplasmic expression was considered an artifact in the initial years, but there is evidence to prove that cytoplasmic localization is real and that p16 has different roles in the nuclear and cytoplasmic locations. We aimed to study the immunoexpression of p16 protein in the nuclear and cytoplasmic locations of the epithelial and stromal compartments of fibroadenoma, invasive breast carcinoma, and a select number of phyllodes tumors. The study included a total of 107 patients, comprising 51 cases of invasive breast carcinoma, 51 cases of fibroadenoma, 4 cases of benign phyllodes tumors, and 1 case of lobular carcinoma in situ (LCIS). The p16 immunohistochemistry was evaluated for nuclear and cytoplasmic localization in the epithelial and stromal compartments of the tumors. Of the 51 fibroadenoma cases, 23 showed strong nuclear p16 epithelial expression, but no case showed cytoplasmic expression. In 19/51 cases, stromal cells also showed strong p16 nuclear expression. Moderate stromal p16 expression was observed in 3 out of 4 cases of benign phyllodes. Out of the 51 cases of invasive carcinoma, 31 showed moderate to strong nuclear p16 immunopositivity, while 27 cases exhibited cytoplasmic p16 expression. We found a statistically significant correlation between moderate to strong nuclear p16 immunoexpression and the molecular subtype of breast carcinoma. The cytoplasmic localization of p16 immunohistochemistry is not seen in epithelial components of fibroadenoma, while it is seen frequently in breast carcinoma. Nuclear p16 expression has a statistically significant correlation with molecular subtypes of breast carcinoma.

Real-world data on malignant and borderline phyllodes tumors of the breast: A population-based study of all 921 cases in the Netherlands (1989 −2020)

AimThe 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 methodsData 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. ResultsWe 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). ConclusionThis 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.

Case series on phyllodes tumour of breast in young females: Unusual clinico-radiological presentations in unusual age group—Thinking beyond fibroadenomas!

BackgroundPhyllodes tumours (PT) of the breast are rare primary breast neoplasms, mostly seen in fourth to fifth decades of life. These tumours are exceptionally rare in children and young females. The clinico-radiological features often overlap with fibroadenoma. Though imaging plays a pivotal role in providing an initial diagnostic approach, the final confirmation is dispensed on histopathology, which further classifies PT into either benign, low-grade malignant (borderline), or high-grade malignant. On reviewing the literature, only 20 cases have been reported so far in young females, with majority of them being benign and very few numbers of malignant PT.Case presentationHerein, we report the clinical and imaging features of PT in four young females, of benign, borderline and high-grade malignant categories as confirmed on histopathology, thereby adding few more numbers to the already existing cases. Additionally, our fourth case depicts rare presentation of high-grade malignant recurrent PT in adolescent female with nodal and unilateral ovarian metastases.ConclusionsIn conclusion, a possibility of PT should be considered in differential diagnosis in a large rapidly enlarging breast mass even in young females with characteristic imaging features, as it alters the plan of management.

Detailed DNA methylation characterisation of phyllodes tumours identifies a signature of malignancy and distinguishes phyllodes from metaplastic breast carcinoma.

Phyllodes tumours (PTs) are rare fibroepithelial lesions of the breast that are classified as benign, borderline, or malignant. As little is known about the molecular underpinnings of PTs, current diagnosis relies on histological examination. However, accurate classification is often difficult, particularly for distinguishing borderline from malignant PTs. Furthermore, PTs can be misdiagnosed as other tumour types with shared histological features, such as fibroadenoma and metaplastic breast cancers. As DNA methylation is a recognised hallmark of many cancers, we hypothesised that DNA methylation could provide novel biomarkers for diagnosis and tumour stratification in PTs, whilst also allowing insight into the molecular aetiology of this otherwise understudied tumour. We generated whole-genome methylation data using the Illumina EPIC microarray in a novel PT cohort (n = 33) and curated methylation microarray data from published datasets including PTs and other potentially histopathologically similar tumours (total n = 817 samples). Analyses revealed that PTs have a unique methylome compared to normal breast tissue and to potentially histopathologically similar tumours (metaplastic breast cancer, fibroadenoma and sarcomas), with PT-specific methylation changes enriched in gene sets involved in KRAS signalling and epithelial-mesenchymal transition. Next, we identified 53 differentially methylated regions (DMRs) (false discovery rate < 0.05) that specifically delineated malignant from non-malignant PTs. The top DMR in both discovery and validation cohorts was hypermethylation at the HSD17B8 CpG island promoter. Matched PT single-cell expression data showed that HSD17B8 had minimal expression in fibroblast (putative tumour) cells. Finally, we created a methylation classifier to distinguish PTs from metaplastic breast cancer samples, where we revealed a likely misdiagnosis for two TCGA metaplastic breast cancer samples. In conclusion, DNA methylation alterations are associated with PT histopathology and hold the potential to improve our understanding of PT molecular aetiology, diagnostics, and risk stratification. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

The Feasibility of Chest Wall Resection and Reconstruction during an Operation in Breast Cancer, Phyllodes Tumor, and Osteoradionecrosis

Background: The effectiveness and safety of chest wall surgery for various breast conditions remain unclear. Previous studies have reported a high risk of morbidity. We hypothesized that the limited chest wall resection can be performed under safe and good technique and aim to identify the extent of safe surgery. Methods: A retrospective study analyzed patients who underwent chest wall resection for chest wall recurrence breast cancer, locally advanced breast cancer, phyllodes, fibromatosis breast tumor, and osteoradionecrosis from January 1, 2008, to April 10, 2023. The primary objectives were the extent of safe chest wall surgery and performance status postoperatively. Results: Thirteen chest wall resections with an average of two to three ribs removed were performed. Patients who had two or more rib resections underwent mesh stabilization; nevertheless, paradoxical chest without deteriorating oxygenation remained. Anterolateral thigh-free flap, pedicled-TRAM or latissimus dorsi flap, pectoralis major myocutaneous flap, and local fasciocutaneous bilateral advancement flap were performed on five, four, three, and one patient, respectively. Patients with a maximum of three ribs removed had an ECOG score of 0–1 postoperatively. Hematoma and wound dehiscence affected two patients. In a small series of chest wall recurrence cases (N = 7), R0 resection had better disease-free survival of 13 months. Conclusions: The procedure of chest wall resection and reconstruction can be performed safely with a maximum of three ribs removed, using mesh and myocutaneous flaps in two or more rib resections. Further studies with larger sample sizes will provide better understanding.

Detailed DNA methylation characterisation of phyllodes tumours identifies a signature of malignancy and distinguishes phyllodes from metaplastic breast carcinoma

Detailed DNA methylation characterisation of phyllodes tumours identifies a signature of malignancy and distinguishes phyllodes from metaplastic breast carcinoma

Management of Benign Phyllodes Tumors: a Dutch Population-Based Retrospective Cohort between 1989 and 2022.

Management of Benign Phyllodes Tumors: a Dutch Population-Based Retrospective Cohort between 1989 and 2022.

Benign Phyllodes Tumor with Extensive Cystic Squamous Metaplasia, Clinically Presenting as Malignant Phyllodes

Abstract Phyllodes tumor are very rare fibroepithelial lesions which comprises 0.3%–1% of all primary breast tumors with peak age around 40–50 years. Phyllodes tumor are classified ino three types: Benign, borderline and malignant tumors. Metaplastic change is very rare in these tumors and can involve both epithelial or stromal components. Stromal metaplastic changes include cartilage, bony or fatty change. Epithelial metaplastic changes include apocrine or squamous change. About 10% of phyllodes tumor show squamous metaplasia. We report a case of 47-year-old patient presenting with large lump in right breast measuring 16 cm × 15 cm × 11 cm, occupying all four quadrants. Clinically, it appeared as malignant phyllodes. But, microscopically, it was benign phyllodes tumor having extensive cystic squamous metaplasia.

Assessment of Ki-67 expression in Phyllodes tumor of breast: An Indian study

Phyllodes tumor (PT) accounts for 0.3-1% of all breast tumors and classified into benign (BP), borderline (BLP) and malignant (MP). However, grading system is somewhat subjective and diagnosis remains challenging. Ancillary techniques may help in classification and prognostication of the tumor.Evaluation of the proliferative activity by Ki-67 index in Indian scenario.50 PTs received from January 2014 to December 2018 were graded using WHO criteria 2019. Ki-67 labelling index (LI) was calculated and graded 1+ (1-35%), 2+ (35-70%), 3+ (70-100%). Relevant statistical analysis was applied. P value of &amp;#60;0.05 was considered significant.70% (35) were BP, 26% (13) BLP and 4% (2) MP. Infiltrative margin, increased stromal cellularity, overgrowth, nuclear atypia and mitotic index were significantly associated with higher grade (P&amp;#60;0.000). The proportion of Ki-67 positive stromal cells in MP (mean76%) was higher than in BLP (mean 56.2%) and BP (mean 23.1%). Increasing Ki-67 index was significantly associated with infiltrative margin, presence of stromal overgrowth, increasing stromal cellularity, nuclear atypia, mitotic index and histological grade (P&amp;#60;0.000). Ki-67 statistically distinguished BP from BLP and MP (P&amp;#60;0.000, P&amp;#60;0.001 respectively), but not between BLP and MP (P&amp;#60;0.329). As a prognostic feature, high Ki-67 index expression did not predict local recurrence and due to fewer recurrent cases, the statistical correlation with any parameter could not be done.Histopathologic characteristics correlated with Ki-67 index. However, it was uncertain whether Ki-67 could provide independent prognostic information beyond histopathological typing. Continued follow-up with greater number of significant episodes may yield more informative correlations.

Surgical margins and prognosis of borderline and malignant phyllodes tumors.

To investigate the optimal surgical margin and prognostic risk factors for borderline and malignant phyllodes tumors (PTs). A retrospective analysis was conducted on patients with borderline and malignant PTs at our hospital from 2011 to 2022. Univariate and multivariate Cox proportional hazard models were employed to analyze the effects of various variables on local recurrence-free survival (LRFS) and disease-free survival (DFS). This study comprised 150 patients, 85 classified as borderline and 65 as malignant. During a median follow-up of 66months (range: 3-146months), 34 cases (22.7%) experienced local recurrence, 9 cases (6.0%) exhibited distant metastasis, and 7 cases (4.7%) resulted in death. Irrespective of the histological subtypes, patients with surgical margins ≥ 1cm exhibit significantly higher 5-year LRFS and 5-year DFS rates compared to those with margins < 1cm. Among patients with initial margins < 1cm, LRFS (P = 0.004) and DFS (P = 0.003) were improved in patients reoperated to achieve margins ≥ 1cm. Surgical margin < 1cm (HR = 2.567, 95%CI 1.137-5.793, P = 0.023) and age < 45years (HR = 2.079, 95%CI 1.033-4.184, P = 0.040) were identified as independent risk factors for LRFS. Additionally, surgical margin < 1cm (HR = 3.074, 95%CI 1.622-5.826, P = 0.001) and tumor size > 5cm (HR = 2.719, 95%CI 1.307-5.656, P = 0.007) were determined to be independent risk factors for DFS. A negative surgical margin of at least 1cm (with secondary resection if necessary) should be achieved for borderline and malignant PTs. Tumor size > 5cm and age < 45years were predictive of recurrence, suggesting multiple therapy modalities may be considered for these high-risk patients.

Margin status impact on recurrence of phyllodes tumors in high-risk groups: a retrospective observational study

BackgroundPhyllodes tumor (PT) is an fibroepithelial tumor with potential for local recurrence. The optimal margin for surgical resection of PT is still debated, particularly in cases of positive margins. This study aimed to identify the risk factors for phyllodes tumor recurrence and the effect of a free margin on tumor recurrence by considering these risk factors.Materials and methodsThis is a retrospective observational study of patients diagnosed with PT who had undergone surgical management. The data were collected from medical records from 2001 to 2020 in the breast clinic of Shahid Motahhari Clinic of Shiraz. Patients were followed up for at least 3 years after the operation to be checked for local recurrence or distant metastasis at regular intervals.ResultsThis retrospective study included 319 patients with PT who underwent surgical management. Of these patients, 83.9% (n = 267), 7.6% (n = 24), and 8.5% (n = 27) were classified as benign, borderline, and malignant, respectively. 8.8% of all patients and 7.6% of non-malignant cases experienced local recurrence, and risk factors for recurrence included oral contraceptive use, smoking, size > 4 cm, stromal overgrowth, and stromal cell atypia. A negative surgical margin decreased the prevalence of recurrence in tumors > 4 cm and with stromal overgrowth significantly.ConclusionThe study found that a negative margin in all patients did not reduce the recurrence rate in benign and borderline phyllodes tumors, suggesting close follow up as a reasonable alternative. However, a negative margin may be effective in reducing recurrence in certain high-risk groups.

Differentiation Between Phyllodes Tumor and Fibroadenoma of the Breast: A Radiomics Prediction Model Based on Full-Field Digital Mammography & Digital Tomosynthesis.

To assess the diagnostic performance of FFDM-based and DBT-based radiomics models to differentiate breast phyllodes tumors from fibroadenomas. 192 patients (93 phyllodes tumors and 99 fibroadenomas) who underwent mammography were retrospectively enrolled. Radiomic features were respectively extracted from FFDM and the clearest slice of DBT images. A least absolute shrinkage and selection operator (LASSO) regression was used to select radiomics features. A combined model was constructed by radiomics and radiological signatures. Machine learning classification was done using logistic regression based on radiomics or radiological signatures (clinical model). Four radiologists were tested on phyllodes tumors and fibroadenomas with and without optimal model assistance. The area under the receiver operating characteristic (ROC) curve (AUC) was computed to assess the performance of each model or radiologist. The Delong test and McNemar's test were performed to compare the performance. The combined model yielded the highest performance with an AUC of 0.948 (95%CI: 0.889-1.000) in the testing set, slightly higher than the FFDM-radiomics model (AUC of 0.937, 95%CI: 0.841-0.984) and the DBT-radiomics model (AUC of 0.860, 95%CI: 0.742-0.936) and significantly superior to the clinical model (AUC of 0.719, 95%CI: 0.585-0.829). With the combined model aid, the AUCs of four radiologists were improved from 0.808 to 0.914 (p=0.079), 0.759 to 0.888 (p=0.015), 0.717 to 0.846 (p=0.004), and 0.629 to 0.803 (p=0.001). Radiomics analysis based on FFDM and DBT shows promise in differentiating phyllodes tumors from fibroadenomas.

A Case Report of Two Malignancies in Breast with Short Review of Literature: Phyllodes and Ductal Type

A 54-year-old female presented with a recurrent mass in the right breast for eight months, associated with pain and discolouration of the skin for two weeks. Past history revealed a wide local excision of a tumour in the same breast 10 months ago, which was reported as a benign phyllodes tumour. Local examination revealed a bosselated mass of size 20×20×10 cm occupying all four quadrants of the right breast, along with another firm lump of size 3×3 cm in the lower inner quadrant. Magnetic Resonance Imaging (MRI) of the breast showed two separate lumps: the large lump involved all four quadrants of the right breast and was suggestive of malignant transformation of a recurrent phyllodes tumour-BIRADS V (Breast Imaging-Reporting and Data System), and another smaller lump was noted in the lower inner quadrant. A Tru-cut biopsy of the larger lesion was reported as a possibility of a phyllodes tumour with mild nuclear atypia. The total mastectomy specimen showed both solid and cystic areas with necrotic material, haemorrhagic fluid, and blood clots in the larger lump. A separate lump from the lower inner quadrant of the ipsilateral breast showed a firm, solid lesion. Microscopic examination of both lesions revealed the simultaneous presentation of a malignant phyllodes tumour with chondrosarcomatous differentiation and infiltrating ductal carcinoma. This case highlights the unpredictable co-existence of two separate malignant lumps in the ipsilateral breast, which is an extremely rare event.

The variable histogenesis and biology of selected bland fibroblastic lesions of the breast - pitfalls in the differential diagnostics and optimal therapeutic approach (three case reports).

Presented are three casuistics of seemingly identical breast lesions which even by adopting advanced laboratory techniques may represent diagnostic challenge. Microscopic features of some bland spindle cell lesions of different histogenesis (epithelial or mesenchymal) are misleading and a potential source of unaware errors, which might affect optimal therapeutic strategy. In the setting of three diverse entities (low-grade spindle cell metaplastic carcinoma, desmoid fibromatosis and phyllodes tumor) is documented both demanding diagnostic algorithm and revealing molecular landscape on one side as well as evolving predictive/prognostic parameters on the other one. Close interdisciplinary cooperation is inevitable for accurate interpretation/understanding of revealed diagnostic facts which is required for adjustment of competent rational and individualized therapy.

Benign phyllodes tumor arising from accessory breast tissue of the axilla: An inquisitive rarity

Abstract Accessory breast tissue is the superfluous tissue that persists from normal embryological development. The pathological involvement of this tissue is quite uncommon and can be diagnostically challenging. Phyllodes tumor is a rare mammary fibroepithelial lesion that has been seldom reported to originate from the accessory breast tissue. This article describes an extremely rare case of a benign phyllodes tumor arising from the accessory breast tissue of the left axilla in a 40-year-old female so as to create awareness about rare tumors occurring within rare anomalies.