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Introduction Fibroepithelial lesions of the breast mainly include fibroadenoma and phyllodes tumors with overlapping morphological features and varied clinical behavior. This study aims to determine the histopathological spectrum of fibroepithelial lesions of the breast in a tertiary care hospital. Methods This is a cross-sectional study that was carried out in the pathology department from 1st January 2015 to 31st December 2023. Relevant data of all fibroepithelial lesions reported during the study period were retrieved from the medical records, tabulated, and analyzed. The Pearson chi-square test was used to determine the significant association between the various clinicopathological parameters of fibroepithelial lesions. A p-value of less than 0.05 was taken as statistically significant. Results Out of a total of 195 fibroepithelial lesions, 185 (95%) were fibroadenoma, 07 (3.5%) were phyllodes tumors, and three (1.5%) were fibroadenoma with tubular adenoma. The most common age group was 21 to 40 years, with the majority of phyllodes tumors being more than 5 cm in size compared to fibroadenomas. The association between the clinicopathological characteristics such as age of patients, tumor size, and histological grade was statistically insignificant in this study. Conclusions The implementation and usage of morphological diagnostic criteria will help in diagnosing and categorizing this broad group of fibroepithelial lesions, thereby facilitating appropriate treatment for patients.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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A phyllodes tumour of the vulva is a rare, well-illustrated benign neoplasm having characteristic histo-morphological features similar to a phyllodes tumour of the breast. We report a case of a primary benign phyllodes tumour in a 28-year-old female patient. She was seen in an outpatient clinic presenting with a slow-growing, non-painful lesion on her vulva. Examination revealed a 2 cm cyst located on the labia minora. Complete excision of the cyst was achieved, and pathological examination revealed a benign phyllodes tumour of the vulva. Hallmarks of this rare pathology are classically a leaf-like architectural configuration and fronds projecting into the cystic spaces on a low-power magnification. To date, a grading or classification of these vulva tumours has not been established due to their rarity. There have been very few reported cases of phyllodes tumours occurring on the vulva and fewer still affecting the labia minora. Continued surveillance for recurrence should be adopted.

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We present a case of a giant phyllodes tumor (PT) requiring simple mastectomy with en bloc pectoralis major resection and immediate deep inferior epigastric perforator (DIEP) flap reconstruction. This patient presented with a four-year history of an enlarging breast mass with ultrasound-guided biopsy results consistent with atypical fibroepithelial proliferation that was highly concerning for a borderline phyllodes tumor. In this large, rare breast tumor that required en bloc pectoralis major resection, we describe the novel use of an immediate single pedicled DIEP flap for the resulting chest wall defect. The patient's postoperative course was uncomplicated, and she reported satisfactory cosmetic and functional outcomes at her initial postoperative follow-up visits. Our findings support the use of simple mastectomy with en bloc resection and immediate single-pedicled DIEP flap for the definitive treatment of giant phyllodes tumors. Our experience shows this is a safe and effective technique for achieving adequate oncologic resection while maintaining postoperative function and cosmesis, which are essential for patient quality of life.

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We aim to report on a patient presenting with a rare breast tumor. The tumor was recurrent with the patient having undergone wide local excision twice previously and the diagnosis was inconclusive both times. Under our care, the patient underwent a modified radical mastectomy with a level III dissection and a transverse rectus abdominis myocutaneous (TRAM) flap for reconstruction. The entire procedure was performed in front of a live audience comprising medical students, junior doctors, and consultants, managed with audio-visual feedback enabling a real-time discussion. The final histopathological report showed a spindle-cell tumor of the breast but also mentioned that a Phyllodes tumor could not be ruled out.

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Typical phyllodes tumours (PTs) of the breast are fibroepithelial neoplasms characterised histologically by stromal hypercellularity and leaf-like structures. However, morphological changes may be atypical in some cases, increasing the difficulty of diagnosis and the likelihood of misdiagnosis. To provide more morphological clues for pathological diagnosis of PTs, we retrospectively analysed 52 PT cases with typical morphological features after recurrence, and summarized the clinicopathological characteristics of the paired primary tumours. We found five special histological features in the primary tumours distinct from classic PTs, namely (1) PTs with epithelioid feature (three cases); (2) PTs with gland-rich feature (eight cases); (3) PTs with fibroadenoma-like feature (20 cases); (4) PTs with myxoid fibroadenoma-like feature (five cases); and (5) PTs with pseudohemangiomatoid stromal hyperplasia-like feature (four cases). All the features can exist independently, and a few cases displayed more than two distinctive features at the same time. In this cohort of recurrent PTs, all the primary tumours were absent of recognisable stromal hypercellularity and leaf-like structures that are the critical diagnostic criteria of PTs; however, they showed some other non-classic characteristics which may provide significant clues for the diagnosis of PTs. Particularly, tumours with epithelioid feature displayed high grade at earlier stages, tumours with fibroadenoma-like feature were most likely to be confused with classical fibroadenomas, and tumours with myxoid feature were prone to be neglected because of their hypocellularity.

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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.

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Phyllodes tumours are an uncommon type of biphasic fibroepithelial neoplasm of the breast. We present a case of a 28-year-old, para one lady with no risk of breast cancer presented with painless left breast swelling for three months. Over one month, the swelling suddenly increased in size and became painful with skin changes associated with pus discharge. On physical examination, a huge swelling measuring about 25cm x 30cm occupies the central and lateral aspect of the left breast with surrounding erythema. We proceeded for a tru-cut biopsy, and the histopathological examination (HPE) showed a stromal proliferation with myxoid changes consistent with phyllodes tumour of benign type. The patient underwent a left simple mastectomy, and the histopathological examination (HPE) confirmed the diagnosis of borderline phyllodes tumour with clear margins without lymph nodes involvement. The patient was subsequently referred to the oncology team and was subjected to 40 Gy in 15 fractions of radiotherapy. Given the rarity of the disease and based on current studies, simple mastectomy with negative margins is recommended for giant benign phyllodes tumours.

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This is a case of a woman who presented with a left breast mass that was initially diagnosed as fibroadenoma on core biopsy and, after three years without any surgical intervention, was found to be a malignant phyllodes tumor. Initially, a core needle biopsy of the mass showed probable fibroadenoma. Because of the initial benign seeming diagnosis and the need to treat her tongue cancer, the patient did not recognize the need for a recommended surgical consultation and excision. Three years later, she presented after the mass had enlarged to encompass nearly the whole left breast. Core needle biopsy revealed spindle cell proliferation with scattered benign-looking tubules. Due to the large size of the mass, she underwent a total mastectomy, and the final pathology demonstrated a malignant phyllodes tumor. This case demonstrates a case of progression of a benign-appearing fibroepithelial lesion to a malignant phyllodes tumor three years later.

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INTRODUCTION: A recent Association of Breast Surgery summary statement on fibroadenoma management recommends excision only for cellular fibroepithelial lesions and rapidly growing lesions with a core biopsy diagnosis of fibroadenoma; persistent pain is a relative indication for excision. METHODS: This retrospective study looked at the impact this approach would have on the diagnosis of phyllodes tumours. RESULTS: From 2014 to 2018, there were 1,058 core biopsy diagnoses of fibroadenoma; 112 lesions were excised, of which 98 were fibroadenomas, 4 were hamartomas and 10 were phyllodes tumours. In this group, an excision diagnosis of phyllodes tumour was associated with size more than 40 mm, age more than 40 years and radiological suspicion of phyllodes tumour or carcinoma. One hundred and sixty-six excised fibroepithelial lesions with no previous core biopsy included eight phyllodes tumours; in this group, rapid growth was associated with phyllodes tumour diagnosis. Twelve of the 26 fibroepithelial lesions classified as B3 (cellular fibroepithelial lesion or phyllodes tumour) were diagnosed as phyllodes tumours on excision. Using a combination of radiological, clinical and pathological features it was possible to create an excision policy that would recommend excision of 22 of the 31 phyllodes tumours in this period. Eight of the nine 'missed' phyllodes tumours were benign. CONCLUSION: The Association of Breast Surgery summary statement will reduce the number of fibroadenomas excised, but may also result in delayed diagnosis of some phyllodes tumours. Appropriate safety netting advice should be provided to identify rapidly growing lesions.

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