Phyllodes Tumor Research Articles

Osseous Metaplasia of the Breast: A Series of Rare Cases

Osseous metaplasia is a reversible condition in which non-osseous soft tissue is replaced by bone. This is most commonly seen in musculoskeletal system and central nervous system. Osseous metaplasia in breast is a rare event. In this case series, we have reported 4 cases of osseous metaplasia of breast. 1 case of Osseous metaplasia in benign phyllodes tumor, 1 case of Osseous metaplasia in fibroadenoma, 1 case of Osseous metaplasia in invasive breast carcinoma and 1 extremely rare case of Osseous metaplasia of breast presenting as breast lump without any other associated pathology. Since osseous metaplasia of breast is a rare phenomenon, this entity specially in association with benign breast disease conditions pose a great challenge for accurate diagnosis.

Review of Two Cases of Borderline Phyllodes Tumor of the Breast with Metastasis

Abstract The case series outlines two cases of borderline phyllodes tumor which later on transformed into malignant phyllodes with metastasis. Malignant phyllodes tumors, although rare, exhibit unique clinicopathological features that necessitate prompt and accurate diagnosis to mitigate their higher recurrence rates. The current lack of consensus on optimal surgical techniques and the appropriate application of radiation and chemotherapy underscores the critical need for a standardized treatment protocol. This is particularly crucial in palliative care settings, where a standardized approach will play a vital role in reducing tumor recurrence and improving patient outcomes.

Corrigendum: A Retrospective Review of Phyllodes Tumor of Breast Treated with Multimodality Approach

Corrigendum: A Retrospective Review of Phyllodes Tumor of Breast Treated with Multimodality Approach

Using the DNA Integrity Number to Analyze DNA Quality in Specimens Collected from Liquid-Based Cytology after Fine-Needle Aspiration of Breast Tumors and Lesions

Introduction: Cancer genome analysis using next-generation sequencing requires adequate and high-quality DNA samples. Genomic analyses were conventionally performed using formalin-fixed paraffin-embedded sections rather than cytology samples such as cell block or smear specimens. Specimens collected from liquid-based cytology (LBC) have the potential to be sources of high-quality DNA suitable for genetic analysis even after long-term storage. Methods: We collected breast tumor/lesion fractions from 92 residual LBC specimens using fine-needle aspiration (FNA) biopsy, including breast carcinoma (1 invasive carcinoma and 4 ductal carcinomas in situ), papillomatous lesion (5 intraductal papillomas), and fibroepithelial lesion (19 phyllodes tumors and 53 fibroadenomas) samples, and others (1 ductal adenoma, 1 hamartoma, 1 fibrocystic disease, and 7 unknown). DNA was extracted from all samples and subjected to DNA integrity number (DIN) score analysis. Results: Average DIN score collected from 92 LBC specimens was significantly higher score. In addition, high-quality DNA with high DIN values (7.39 ± 0.80) was successfully extracted more than 12 months after storage of residual LBC specimens. Conclusion: Residual LBC specimens collected from FNA of the breast were verified to carry high-quality DNA and could serve as an alternate source for genetic analysis.

Clinical presentation and radiologic imaging findings of phyllodes tumors: benign and borderline/malignant phyllodes tumors

Background Phyllodes tumor is a rare fibroepithelial neoplasm of the breast, which is classified histologically as benign, borderline, or malignant. Accurate preoperative diagnosis allows the correct surgical planning and reoperation avoidance. Objective To describe the clinical presentation and radiologic features of phyllodes tumors and differentiate between benign and non-benign (borderline and malignant) groups. Methods A retrospective study of 57 patients with a diagnosis of phyllodes tumor who had preoperative imaging (mammography, ultrasound, or CT chest) and histological confirmation. The data was collected from 1 June 2011 to 30 September 2021. The imaging features of the phyllodes tumors were described according to the 5th edition of the ACR BI-RADS lexicon. For comparing between two groups, the student t-test, Wilcoxon rank sum test, Chi-square test, and Fisher’s exact test were used for statistical analyses. The logistic regression analysis was calculated for non-benign phyllodes tumor prediction. Results From 57 patients, the pathologic results were benign for 43 cases and non-benign phyllodes tumors for 14 cases. There was no differentiation of mammographic and CT features between benign and non-benign groups. Non-benign phyllodes tumors had the statistical significance of menopausal status, entire breast involvement, tumor size larger than 10 cm, and heterogeneous echo on univariable analysis. After multivariable analysis, menopausal status (odd ratios=13.79, p=0.04) and presence of vessels in the rim (odd ratios=16.51, p=0.019) or absent vascularity (odd ratios=8.45, p=0.047) on doppler ultrasound were significantly increased possibility of non-benign phyllodes tumor. Conclusions Menopausal status and presence of vessels in the rim or absent vascularity on Doppler ultrasound were important predictors for the diagnosis of non-benign phyllodes tumor.

Phyllodes Tumors of the Breast-Experience in a Tertiary Care Center.

Phyllodes tumors (PTs) are rare neoplasms of the breast that are a challenge in clinical practice. Though mostly benign, they are notorious for local recurrence, requiring adjuvant treatments. This study was planned to report the clinicopathological features and outcomes of patients with PT treated at our center. Details of all patients who underwent surgery for PT in the last 6 years (December 2017-December 2023) were obtained from our prospectively maintained database. The demographic, clinical, radiological, pathological, and follow-up details were recorded and analyzed. Statistical analyses were carried out with Jamovi version 2.3.18. Out of 61 suspected PTs by triple assessment, 9 were excluded due to a non-phyllodes diagnosis on histopathology. We included 52 women with a mean age of 38.2 ± 11.0 years, most of whom were premenopausal (57.7%). BI-RADS 4 was the most common finding on radiological assessment (65.4%). Core needle biopsy (CNB) was the most frequently employed modality for histological diagnosis preoperatively (65.4% of cases). Wide local excisions (WLE) and mastectomies were done in 63.5% and 36.5% of patients, respectively. Benign, borderline, and malignant phyllodes constituted 67.3%, 15.4%, and 17.3% of tumors, respectively. Patients undergoing breast conservation surgery (BCS) had a significantly smaller mean tumor diameter than those who underwent a mastectomy (p < 0.001). Overall, the margin positivity rate was 34.6%. Patients undergoing mastectomy developed more local recurrence compared to WLE, although the difference was not significant (p = 0.400). The outcome following surgical excisions of large PTs in terms of margin positivity and local recurrence is the same, irrespective of whether BCS or mastectomy is done. A negative pathological margin width of > 1 mm appears acceptable. Malignant phyllodes with positive margins are associated with a higher rate of recurrence but positive margins in patients with other subtypes may not translate into recurrence, at least in the short term.

Study of diagnostic accuracy of non-aspiration cytology in solid tumors

Fine needle aspiration cytology (FNAC) is widely accepted as a primary method for the diagnosis of thyroid lesions. An alternative to FNAC is fine-needle sampling without aspiration (FNNAC). FNAC is easy to perform, quickly and has a high degree of sensitivity and specificity and avoid unnecessary surgery. Hence the present study was performed to study the diagnostic accuracy of FNNAC with FNAC technique in solid tumors.: An observational study was carried out on 325 patients with swellings in the breast, thyroid, and soft tissues and enlarged lymph nodes in the Department of surgical oncology, Regional Cancer Centre, Government Coimbatore Medical college hospital, Coimbatore, India. A single pathologist was responsible for all cytological and histological reports. Slides of both approaches were analysed and compared using Mair et al grading methodology, which depends on five factors. The number of smears with superior quality and diagnostic accuracy is compared and analysed statistically using the 'z' test for two proportions.: FNNAC produced better smears with less haemorrhage in vascular organs like the thyroid. FNAC performed better in breast fibrous lesions such as fibroadenoma and phyllodes tumour. For malignant lumps of breast and lymph nodes, FNAC yields better material than FNNAC.: The current research shows that FNNAC is the superior approach for highly vascular organs such as the thyroid because it yields high-quality smears with less blood admixtures. Although FNAC smears were more often diagnostic, they typically yielded acceptable rather than excellent grade smears.

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.