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.

Malignant phyllodes tumour with lymph node metastasis: a diagnostic conundrum resolved by next generation DNA sequencing.

A malignant neoplasm with spindle cell and chondroid differentiation in the breast, metastatic to lymph node. In this context, a metaplastic carcinoma is typically favored given the exceptional nature of lymph node metastases in malignant phyllodes tumors (MPT). However, we demonstrate pathognomonic hotspot mutations in MED12 and the promoter of the TERT gene by targeted next-generation DNA sequencing, supporting a diagnosis of MPT.

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

BACKGROUND: Phyllodes 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 METHODS: This 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. RESULTS: This 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. CONCLUSION: The 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.

Phyllodes tumour evidence gaps mapped from the 5th edition of the WHO classification of tumours of the breast.

AIMS: Breast phyllodes tumours (PTs) are a rare subset of fibroepithelial neoplasms categorised into benign, borderline, and malignant grades according to the World Health Organization (WHO) Classification of Tumours (WCTs). In this report, we developed an evidence gap map (EGM) based on the literature cited in the PT chapter of the 5th edition of the breast WCT in order to identify knowledge and research gaps in PT. METHODS: A framework was first established where the dimensions of the EGM were defined as categories of tumour descriptors, tumour types, and evidence levels. Citations were collected into a Microsoft Excel form and imported into EPPI-reviewer to produce the EGM. RESULTS: The EGM showed that the "Histopathology" and "Pathogenesis" sections contained the most citations, the majority being of low-level evidence. The highest number of citations considered of moderate-level evidence were found in the "Histopathology" section. There was no high-level evidence cited in this chapter. The "Localisation", "Aetiology", and "Staging" sections had the fewest citations. CONCLUSION: This EGM provides a visual representation of the cited literature in the PT chapter of the breast WCT, revealing the lack of high-level evidence citations. There is an uneven distribution of references, probably due to citation practices. Pockets of low-level evidence are highlighted, possibly related to referencing habits, lack of relevant research, or the belief that the information presented is standard accepted fact, without the need for specific citations. Future work needs to bridge evidence gaps and broaden citations beyond those in the latest WCT.

Fibroepithelial lesions of the breast: A review of recurring diagnostic issues.

Breast fibroepithelial lesions, which are composed of biphasic epithelial and stromal proliferations, comprise the fascinating spectrum of fibroadenomas and phyllodes tumours. Common difficulties surrounding their diagnosis include distinguishing between cellular fibroadenomas and benign phyllodes tumours, grading phyllodes tumours, classifying fibroepithelial lesions in paediatric patients, and handling surgical margins. Recent molecular advances have provided insights into the pathogenesis of fibroepithelial lesions and may offer diagnostic, prognostic, and therapeutic information. In this review, we briefly revisit the pathological features of fibroadenomas and phyllodes tumours, discuss common diagnostic dilemmas and management implications, and examine their key molecular characteristics.

Diagnostic concordance of phyllodes tumour of the breast.

AIMS: Phyllodes tumours (PT) are rare and distinct breast tumours, which span a morphological continuum. Classification into benign, borderline and malignant categories reflects their biology and clinical behaviour and is essential to guide management. This study aims to assess the diagnostic agreement of PT using the UK National Health Service Breast Screening Programme (NHSBSP) breast pathology external quality assurance (EQA) scheme data. METHODS AND RESULTS: Twenty-six PTs were identified in the EQA scheme, which were diagnosed by an average of 607 participants/circulation. Data on diagnostic categories were collected and representative slides were reviewed. The level of concordance between reporting pathologists was assessed. There were 14 benign, six borderline and six malignant PT. The overall rate of diagnosis agreement was 86% when analysed as benign lesions, borderline PT and malignant lesions, which decreased to 79% when diagnosed as PT (irrespective of grade) and to 63% when the diagnosis was further refined to PT categories (benign, borderline and malignant PTs). The highest agreement rate was observed in malignant PT (86%) and the lowest in borderline PT (42%). Malignant heterologous elements, stromal overgrowth and leaf-like architecture are features associated with higher concordance rates. Lower-priority features were stromal expansion, clefting and multinodularity. CONCLUSION: The concordance of PT diagnosis, as an entity, is high, but its classification into benign, borderline and malignant has variable agreement levels, with borderline tumours having the lowest concordance rate. More research to refine the diagnostic criteria for categorisation of PT is warranted to improve concordance between pathologists.

Phyllodes tumours - a retrospective review of 83 clinical cases.

INTRODUCTION: Phyllodes tumours are rare, accounting for 0.3-1.0% of all primary breast tumours. According to biological behaviour, they are divided into three categories: benign, borderline and malignant. Due to the rare incidence, the requirements for the radicality of surgical treatment are not well known. According to respected foreign recommendations, resection with a free margin of 10 mm or more is desirable. METHODS: A retrospective review of patients, who underwent surgical treatment due to phyllodes tumour in the Masaryk Memorial Cancer lnstitute in 2003-2014. RESULTS: 83 patients were evaluated with a median follow-up of 68.0 months. Benign tumours accounted for 62.3%, borderline tumours accounted for 16.9% and malignant accounted for 20.8% of all tumours. Malignant phyllodes tumours reached a bigger average size (84.9 mm) than borderline (41.4 mm) and benign tumours (33.3 mm) and occurred in older patients (mean 56.4 years) than benign (mean 42.5 years). Results from preoperative core-cut biopsy were often inaccurate. In 70 cases, the primary resection was breast preserving, but the free margin above 1 mm was achieved only in 13 cases. The width of the resection edge never exceeded the recommended 10 mm. Nevertheless, there was a relapse in benign tumours in two cases and in the borderline tumours only in one case. Malignant tumours recurred more frequently, even after total mastectomy. Four patients with malignant tumours experienced distant metastases. There has never been a death caused by benign or borderline tumour. CONCLUSION: The 10 mm resection margin is unachievable in our conditions. However, it seems that such radicality is not necessary in benign tumours, because they rarely recur even with close margins. Conversely, neither total mastectomy of the malignant phyllodes tumours will protect against local progression or distant metastasis.

Metaplastic Breast Cancer Masquerading as Liposarcoma of the Breast: A Case Report following Oncoplastic Treatment.

Mammary liposarcoma is among the rarest of breast tumours. Here we report the presentation, macroscopic, microscopic, and immunohistochemical features of an extremely rare case of metaplastic carcinoma with extensive pleomorphic liposarcomatous differentiation. A 47-year-old woman presented with bilateral grade III breast ptosis and a 3 × 4 cm mass in the lower outer quadrant of the left breast. Mammography and ultrasound confirmed a well-defined mass. A core biopsy performed was diagnosed as pleomorphic liposarcoma. Microscopically, this was a well-defined, lobulated tumour comprising solid sheets of large pleomorphic and spindle cells with bizarre forms, vacuolated cytoplasm, and ample mitoses. Atypical lipoblasts were easily identifiable. Due to the strong, though patchy, cytokeratin expression, the diagnosis of metaplastic carcinoma with pleomorphic liposarcomatous differentiation was made. Extensive sampling, careful search for a biphasic pattern, ductal carcinoma in situ, and/or epithelial differentiation, and a panel of broad-spectrum cytokeratins are essential to establish the diagnosis.

Postoperative follow-up practice of phyllodes tumour in the UK: Results from a national survey.

BACKGROUND: Resected phyllodes tumours (PT) of the breast carry a small but significant risk of recurrence. Nevertheless, there are no national guidelines on the postoperative follow-up of these tumours potentially resulting in a wide variation in practice among breast surgeons in the UK. METHODS: A web-based questionnaire was sent to breast surgeons across the UK to assess individual follow-up practices including availability of local guidelines, methods of follow-up and influence of risk factors. RESULTS: Only 38% of 121 responses indicated the availability of local guidelines on PT follow-up. Modal follow-up duration for borderline and malignant disease was 5 years (53.7% and 79.3% of responses respectively), compared to 1 year for benign disease (43%) although 28% of respondents continue to review benign cases for 5 years. Immediate post-operative discharge and self-directed aftercare for benign and borderline cases remains uncommon practice in the UK. Within hospitals represented by more than one respondent in this survey, only around 30% demonstrated consistent practices pertaining to length and frequency of postoperative PT follow-up. Recurrent disease and margin status influenced the follow-up practice of 60% of respondents in our survey. More than 75% indicated that they combine clinical examination with radiological investigations (mammography and/or ultrasound) to follow up PT postoperatively. CONCLUSION: This survey highlights the wide variation in follow-up practice for resected PT. This may affect the detection of disease relapse or, conversely, result in wasted clinical resources and unnecessary patient distress. Evidence-based national guidelines are necessary to resolve this issue and inform best follow-up practice.

Massively parallel sequencing of phyllodes tumours of the breast reveals actionable mutations, and TERT promoter hotspot mutations and TERT gene amplification as likely drivers of progression.

Phyllodes tumours (PTs) are breast fibroepithelial lesions that are graded based on histological criteria as benign, borderline or malignant. PTs may recur locally. Borderline PTs and malignant PTs may metastasize to distant sites. Breast fibroepithelial lesions, including PTs and fibroadenomas, are characterized by recurrent MED12 exon 2 somatic mutations. We sought to define the repertoire of somatic genetic alterations in PTs and whether these may assist in the differential diagnosis of these lesions. We collected 100 fibroadenomas, 40 benign PTs, 14 borderline PTs and 22 malignant PTs; six, six and 13 benign, borderline and malignant PTs, respectively, and their matched normal tissue, were subjected to targeted massively parallel sequencing (MPS) using the MSK-IMPACT sequencing assay. Recurrent MED12 mutations were found in 56% of PTs; in addition, mutations affecting cancer genes (eg TP53, RB1, SETD2 and EGFR) were exclusively detected in borderline and malignant PTs. We found a novel recurrent clonal hotspot mutation in the TERT promoter (-124 C>T) in 52% and TERT gene amplification in 4% of PTs. Laser capture microdissection revealed that these mutations were restricted to the mesenchymal component of PTs. Sequencing analysis of the entire cohort revealed that the frequency of TERT alterations increased from benign (18%) to borderline (57%) and to malignant PTs (68%; p < 0.01), and TERT alterations were associated with increased levels of TERT mRNA (p < 0.001). No TERT alterations were observed in fibroadenomas. An analysis of TERT promoter sequencing and gene amplification distinguished PTs from fibroadenomas with a sensitivity and a positive predictive value of 100% (CI 95.38-100%) and 100% (CI 85.86-100%), respectively, and a sensitivity and a negative predictive value of 39% (CI 28.65-51.36%) and 68% (CI 60.21-75.78%), respectively. Our results suggest that TERT alterations may drive the progression of PTs, and may assist in the differential diagnosis between PTs and fibroadenomas. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Liposarcomatous differentiation in malignant phyllodes tumours is unassociated with MDM2 or CDK4 amplification.

AIMS: Breast sarcomas are rare, usually occurring in the setting of malignant phyllodes tumour (MPT). Heterologous differentiation commonly resembles well-differentiated or pleomorphic liposarcoma. In extramammary sites, these subtypes have different biological behaviours and distinct genetic alterations: MDM2 and CDK4 amplification in well-differentiated liposarcoma, and polyploidy with complex structural rearrangements in pleomorphic liposarcoma. The aim of this study was to investigate foci resembling well-differentiated liposarcoma in MPT for MDM2 and CDK4 amplification. METHODS AND RESULTS: We evaluated the clinicopathological characteristics of MPTs received by the Vanderbilt Breast Consultation Service containing components resembling well-differentiated or pleomorphic liposarcoma. Cases with available tissue blocks were subjected to fluorescence in-situ hybridization with MDM2 and CDK4 probes. Thirty-eight MPTs with liposarcomatous components were available for review. The mean patient age was 49.8 years (range 26-84 years). In addition to well-differentiated liposarcoma, the following components were also present: high-grade undifferentiated sarcoma (n = 9; 23.7%), pleomorphic liposarcoma (n = 4; 10.5%), non-high-grade sarcoma not otherwise specified (n = 22; 57.9%), and malignant peripheral nerve sheath tumour-like (n = 2; 5.2%). Among 10 cases tested, none showed amplification of MDM2 or CDK4. CONCLUSIONS: This study examined molecular changes in the well-differentiated liposarcomatous components of MPT. Despite histological similarity to well-differentiated liposarcoma of soft tissues, liposarcomatous differentiation in MPT lacks the molecular phenotype characteristic of extramammary well-differentiated liposarcoma.

[Malignant phyllodes tumour : a case report]. / Le cas clinique du mois Tumeur phyllode maligne : à propos d'un cas avec composante hétérologue.

A 28 year old woman has suffered over the previous month from a post-traumatic swelling sensation of the left breast. Ultrasonography demonstrates a 9 cm, sharply-cut, rounded, hypo-echogenic lesion. Surgery is performed, with the hypothesis of an haematoma. The pathological analysis of the lesion shows a malignant phyllodes tumour with heterologous rhabdomyosarcomatous features. No metastasis is found. A radical mastectomy is performed and the patient benefits from an adjuvant radio-chemotherapy. Phyllodes tumours represent up to 1 % of all mammary cancers, with 10-20 % of malignant lesions. These tumours behave differently from usual breast cancers. This atypical case, arising in a traumatic context, provides the opportunity to discuss the treatment and classification of phyllodes tumours of the breast.

Nous rapportons le cas d'une patiente de 28 ans se plaignant d'une sensation de tension mammaire, évoluant depuis un mois et apparue dans le décours d'un traumatisme. L'échographie démontre une lésion arrondie, hypo-échogène, de 9 cm aux contours nets. Après chirurgie réalisée dans l'hypothèse d'un hématome, l'analyse anatomo-pathologique révèle une tumeur phyllode maligne avec composante hétérologue de type rhabdomyosarcome. Le bilan d'extension ne met en évidence aucune métastase. La patiente a bénéficié d'une mastectomie radicale ainsi que d'une radio-chimiothérapie adjuvante. Les tumeurs phyllodes, qui représentent jusqu'à 1 % des tumeurs mammaires, dont 10-20 % sont de nature maligne, constituent une entité rare avec un comportement différent des autres tumeurs malignes mammaires. Ce cas, dont la présentation est atypique, permet de discuter de la classification et du traitement des tumeurs phyllodes du sein.

Diagnostic Maze: Malignant Phyllodes Tumor Mimicking Metaplastic Breast Carcinoma.

Phyllodes tumors (PTs) are uncommon breast tumors. They represent a spectrum of benign to malignant neoplasms. These erratic tumors have traits ranging from fibroadenomas on one end of the spectrum to sarcomas on the other end. The presentation of PT is variable, thus posing a diagnostic difficulty. Malignant PTs are often associated with recurrence, poor prognosis, and adverse disease outcomes. The recent genetic studies produced by genome sequencing offer information about the molecular pathophysiology of PT, aid in enhancing diagnostic precision, and suggest possible therapeutic targets in cases of malignant PT. Planning a treatment modality and prognostication requires meticulous histopathological sampling, as it relies on a correct histopathological diagnosis. There are no definitive guidelines for surgical management and targeted therapy for malignant PTs due to the rarity of these cases and very little available literature on these topics. Here in this article, we address a malignant PT in a 74-year-old female that presented as a breast mass mimicking metaplastic breast carcinoma histologically. This article also illuminates how immunohistochemistry plays a vital role in the diagnosis of this tumor.

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

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.

Surgery for phyllodes tumour of the breast. What should be surgical margins?

BACKGROUNDS: Optimal and tailored surgical treatment of phyllodes tumour(PT) of the breast is controversial. This study aims to determine the appropriate surgical margin in the treatment of PT. METHODOLOGY: The data of 132 patients who underwent breast surgery with the diagnosis of PT at the Breast Unit of Istanbul Faculty of Medicine from 2000 to 2022 were retrospectively reviewed. RESULTS: Median age was 38 and patients with benign PT were younger than others(median age was 34, 44, and 43 for benign, borderline, and malignant, respectively) (P = 0.001). Local recurrence was observed in 7 (5.3%) patients, systemic recurrence was observed in 3 (2.3%) patients, and disease-related death was observed in 2 (1.5%) patients. Local recurrence occurred in 1.4% (n = 1) of benign tumours, 8.3% (n = 2) of borderline tumours, and 10.3% (n = 4) of malignant tumours. All of the systemic recurrences and deaths were seen in the malignant group. The local recurrence rate was found to be higher in borderline and malignant tumours with surgical margins less than 10 mm (44.4% versus 3.7%, P = 0.003), and tumours larger than 5 cm (11.8% versus 1.3%, P = 0.015). In comparison, there was no correlation between the surgical margin proximity, tumour diameter, and local recurrence rates in benign PT (P > 0.05). CONCLUSION: According to our findings, negative surgical margins seem to be sufficient in the treatment of benign phyllodes tumours. Furthermore at least 1 cm negative surgical margins must be achieved for malignant and borderline phyllodes tumours to avoid local recurrence.

Benign Phyllodes Tumour With Cystic Squamous Metaplasia: A Rare Histology Finding.

Phyllodes tumour (PT) comprises 0.3-1% of all breast cancers and 3% of fibroepithelial neoplasm. It occurs more commonly in the fourth and fifth decades of life. Fibroepithelial neoplasms are composed of cell types with two different origins, commonly mesenchymal and epithelial. Histological features are important as this forms the basis of the categorization of PT into benign, borderline and malignant types, thus facilitating management. Metaplasia in any of the two components of PT is rare and the cystic squamous type of metaplasia has even more infrequent histological features. Case: This paper presents the case of a 63-year-old female with a palpable lump in the lower outer quadrant of her left breast. Histology showed a benign Phyllodes tumour with patchy, cystic squamous metaplasia within the lesion, keratin production and foreign-body reaction in response to keratin spillage. The previously done core biopsy was also reviewed, which showed focal stromal cell condensation and features overlapping between benign and borderline phyllodes tumours. Conclusion: The case was presented because of its unique and rare histological picture of Cystic squamous metaplasia in benign PT and a further rarer finding of foreign body reaction to keratin spillage.

Borderline phyllodes tumour of the breast with eosinophilic inclusion bodies: Case report and molecular sequencing.

INTRODUCTION AND IMPORTANCE: The presence of eosinophilic inclusion bodies in the breast is very rare and fewer than 20 cases were described in the literature. Herein we report the first case of borderline phyllodes tumour associated with this kind of cells. To the best of our knowledge, this is also the first time that a molecular sequencing is made targeting the stroma cells with inclusion bodies. CASE PRESENTATION: A 33-yr-old woman presented a large mass in the right breast. Imaging techniques by mammogram and ultrasonographic examination were performed. After multidisciplinary approach, a breast conserving surgery has been decided. Microscopic analysis, immunohistochemical stains and molecular tests were performed on the lesion. The proposed diagnosis is borderline phyllodes tumour with eosinophilic inclusion bodies. CLINICAL DISCUSSION: Inclusion bodies are typically found in the infantile digital fibromatosis. Finding them in extradigital fibromatosis is rare. Their signification is still unclear. Some studies suggest a disturbance in the metabolism of proliferating myofibroblasts. CONCLUSION: The presence of inclusion bodies in breast tumour do not seem to have a prognosis impact. It might be interesting to perform others molecular tests on lesions with eosinophilic inclusion bodies to discover potential mutations.

Clinicopathological Parameters Predicting Malignancy in Phyllodes Tumor of the Breast.

Introduction Phyllodes tumor (PT) is an uncommon fibroepithelial neoplasm of the breast. It is a biphasic tumor with stromal and epithelial components, with a tendency to recur. Because of its wide range of disease manifestations, it has been subclassified into three categories, i.e., benign, borderline, and malignant, based on several histological parameters. This study was conducted to evaluate the clinicopathological features associated with malignancy in breast PTs. Methods We conducted a retrospective study at the Department of Histopathology at Liaquat National Hospital, Karachi, Pakistan. A total of 146 biopsy-proven cases of PTs were enrolled in the study. Clinical data were obtained from the clinical referral forms. Specimens were obtained from either lumpectomy or simple mastectomy. The specimens obtained were received at the laboratory where after gross examination, paraffin-embedded tissue blocks were prepared, which were sectioned, stained, and studied by a senior histopathologist. Pathological features, such as mitotic count, necrosis, stromal atypia, stromal overgrowth, and heterologous elements, were observed. Based on these features, the PTs were classified into benign, borderline, and malignant tumors. Results The mean age of the PTs in our setup was 40.65 ± 12.17 years with a mean size of 9.40 ± 6.49 cm. Malignant PT was found to be the most prevalent in our population, accounting for 63 (43.2%) cases, followed by borderline (51, 34.9%) and benign (32, 21.9%). A significant association was found between the tumor subtype and patient age, i.e., patients diagnosed with malignant and borderline PTs were found to be of older age (mean 42.82 ± 12.94 and 42.05 ± 11.31 years, respectively) than those diagnosed with benign PTs (mean age 34.12 ± 9.75 years). Moreover, malignant PTs were associated with larger tumor size (mean 11.46 ± 6.08) compared with the other two subtypes. Conclusion We found a significant association among patient age, tumor size, and PT subtype. Therefore, apart from the usual histological parameters, patient age and tumor size are important parameters for predicting the behavior of breast PT and should be considered for management.

A Large Phyllodes Tumor With Axillary Lymph Node Involvement: A Case Report.

Malignant phyllodes tumors of the breast are uncommon and complex to treat. This case involves a 39-year-old woman with a rapidly growing mass in her right breast measuring 32cm. The patient underwent a bilateral mastectomy with a right sentinel node biopsy and right chest wall reconstruction. The final pathology of the tumor revealed a malignant phyllodes tumor, with one of two right axillary lymph nodes positive for metastatic phyllodes tumor. Malignant phyllodes tumors should be taken into consideration in any rapidly growing breast mass. Further studies analyzing the treatment of malignant phyllodes tumors are necessary to reduce the risk of tumor recurrence and metastasis.