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Pathologica Apr 2022Phyllodes tumors (PT) are fibroepithelial neoplasms of the breast showing a peculiar leaf-like appearance. They account for 0.3 to 1% of all primary breast tumors and... (Review)
Review
Phyllodes tumors (PT) are fibroepithelial neoplasms of the breast showing a peculiar leaf-like appearance. They account for 0.3 to 1% of all primary breast tumors and 2.5% of all fibroepithelial breast tumors. PT are classified into benign, borderline and malignant based upon their stromal morphology with a distribution of 60%, 20%, and 20%, respectively. Malignant PT of the breast constitute an uncommon challenging group of fibroepithelial neoplasms. They have a relatively high tendency to recur, although distant metastasis is uncommon, and nearly exclusive to malignant PT. Adequate surgical resection remains the standard approach to achieve maximal local control. Giant malignant PT are rare and a pose a diagnostic dilemma for pathologists, especially when comprised of sarcomatous elements. This review highlights the morphological features of PT detected in cytology and histology specimens and discusses diagnostic pitfalls and differential diagnosis.
Topics: Breast; Breast Neoplasms; Female; Humans; Neoplasm Recurrence, Local; Neoplasms, Fibroepithelial; Phyllodes Tumor
PubMed: 35414723
DOI: 10.32074/1591-951X-754 -
Histopathology Jan 2016Phyllodes tumours constitute an uncommon but complex group of mammary fibroepithelial lesions. Accurate and reproducible grading of these tumours has long been... (Review)
Review
Phyllodes tumours constitute an uncommon but complex group of mammary fibroepithelial lesions. Accurate and reproducible grading of these tumours has long been challenging, owing to the need to assess multiple stratified histological parameters, which may be weighted differently by individual pathologists. Distinction of benign phyllodes tumours from cellular fibroadenomas is fraught with difficulty, due to overlapping microscopic features. Similarly, separation of the malignant phyllodes tumour from spindle cell metaplastic carcinoma and primary breast sarcoma can be problematic. Phyllodes tumours are treated by surgical excision. However, there is no consensus on the definition of an appropriate surgical margin to ensure completeness of excision and reduction of recurrence risk. Interpretive subjectivity, overlapping histological diagnostic criteria, suboptimal correlation between histological classification and clinical behaviour and the lack of robust molecular predictors of outcome make further investigation of the pathogenesis of these fascinating tumours a matter of active research. This review consolidates the current understanding of their pathobiology and clinical behaviour, and includes proposals for a rational approach to the classification and management of phyllodes tumours.
Topics: Breast; Breast Neoplasms; Carcinoma; Consensus; Diagnosis, Differential; Female; Fibroadenoma; Humans; Phyllodes Tumor; Sarcoma
PubMed: 26768026
DOI: 10.1111/his.12876 -
Virchows Archiv : An International... Jul 2023The heterogeneous group of B3 lesions in the breast harbors lesions with different malignant potential and progression risk. As several studies about B3 lesions have... (Review)
Review
The heterogeneous group of B3 lesions in the breast harbors lesions with different malignant potential and progression risk. As several studies about B3 lesions have been published since the last Consensus in 2018, the 3rd International Consensus Conference discussed the six most relevant B3 lesions (atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), classical lobular neoplasia (LN), radial scar (RS), papillary lesions (PL) without atypia, and phyllodes tumors (PT)) and made recommendations for diagnostic and therapeutic approaches. Following a presentation of current data of each B3 lesion, the international and interdisciplinary panel of 33 specialists and key opinion leaders voted on the recommendations for further management after core-needle biopsy (CNB) and vacuum-assisted biopsy (VAB). In case of B3 lesion diagnosis on CNB, OE was recommended in ADH and PT, whereas in the other B3 lesions, vacuum-assisted excision was considered an equivalent alternative to OE. In ADH, most panelists (76%) recommended an open excision (OE) after diagnosis on VAB, whereas observation after a complete VAB-removal on imaging was accepted by 34%. In LN, the majority of the panel (90%) preferred observation following complete VAB-removal. Results were similar in RS (82%), PL (100%), and FEA (100%). In benign PT, a slim majority (55%) also recommended an observation after a complete VAB-removal. VAB with subsequent active surveillance can replace an open surgical intervention for most B3 lesions (RS, FEA, PL, PT, and LN). Compared to previous recommendations, there is an increasing trend to a de-escalating strategy in classical LN. Due to the higher risk of upgrade into malignancy, OE remains the preferred approach after the diagnosis of ADH.
Topics: Humans; Female; Breast; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Mammography; Biopsy, Large-Core Needle; Precancerous Conditions; Phyllodes Tumor; Retrospective Studies
PubMed: 37330436
DOI: 10.1007/s00428-023-03566-x -
Archives of Pathology & Laboratory... Jul 2016-Phyllodes tumor (PT) of the breast is a rare fibroepithelial neoplasm with risks of local recurrence and uncommon metastases. The classification proposed by the World... (Review)
Review
CONTEXT
-Phyllodes tumor (PT) of the breast is a rare fibroepithelial neoplasm with risks of local recurrence and uncommon metastases. The classification proposed by the World Health Organization for PTs into benign, borderline, and malignant is based on a combination of several histologic features. The differential diagnosis between PT and fibroadenoma and the histologic grading of PT remain challenging. In addition, the molecular pathogenesis of PT is largely unknown.
OBJECTIVE
-To provide an updated overview of pathologic features, diagnostic terminology, and molecular alterations of PT.
DATA SOURCES
-Current English literature related to PT of the breast.
CONCLUSIONS
-Phyllodes tumor shows a wide spectrum of morphology. There are no clearly distinct boundaries between PT and fibroadenoma. Strict histologic assessment of a combination of histologic features with classification can help to achieve the correct diagnosis and provide useful clinical information. The genomic landscapes of PT generated from genomic sequencing provide insights into the molecular pathogenesis of PT and help to improve diagnostic accuracy and identify potential drug targets in malignant PT.
Topics: Biomarkers, Tumor; Breast; Breast Neoplasms; Diagnosis, Differential; Female; Fibroadenoma; Humans; Immunohistochemistry; Phyllodes Tumor
PubMed: 27362571
DOI: 10.5858/arpa.2016-0042-RA -
Virchows Archiv : An International... Jan 2022Spindle cell lesions of the breast comprise a heterogeneous group of lesions, ranging from reactive and benign processes to aggressive malignant tumours. Despite their... (Review)
Review
Spindle cell lesions of the breast comprise a heterogeneous group of lesions, ranging from reactive and benign processes to aggressive malignant tumours. Despite their rarity, they attract the attention of breast pathologists due to their overlapping morphological features and diagnostic challenges, particularly on core needle biopsy (CNB) specimens. Pathologists should recognise the wide range of differential diagnoses and be familiar with the diverse morphological appearances of these lesions to make an accurate diagnosis and to suggest proper management of the patients. Clinical history, immunohistochemistry, and molecular assays are helpful in making a correct diagnosis in morphologically challenging cases. In this review, we present our approach for the diagnosis of breast spindle cell lesions, highlighting the main features of each entity and the potential pitfalls, particularly on CNB. Breast spindle cell lesions are generally classified into two main categories: bland-appearing and malignant-appearing lesions. Each category includes a distinct list of differential diagnoses and a panel of immunohistochemical markers. In bland-appearing lesions, it is important to distinguish fibromatosis-like spindle cell metaplastic breast carcinoma from other benign entities and to distinguish fibromatosis from scar tissue. The malignant-appearing category includes spindle cell metaplastic carcinoma, stroma rich malignant phyllodes tumour, other primary and metastatic malignant spindle cell tumours of the breast, including angiosarcoma and melanoma, and benign mimics such as florid granulation tissue and nodular fasciitis.
Topics: Breast; Breast Neoplasms; Carcinoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Phyllodes Tumor
PubMed: 34322734
DOI: 10.1007/s00428-021-03162-x -
Breast Cancer Research and Treatment Apr 2019The second International Consensus Conference on B3 lesions was held in Zurich, Switzerland, in March 2018, organized by the International Breast Ultrasound School to... (Review)
Review
PURPOSE
The second International Consensus Conference on B3 lesions was held in Zurich, Switzerland, in March 2018, organized by the International Breast Ultrasound School to re-evaluate the consensus recommendations.
METHODS
This study (1) evaluated how management recommendations of the first Zurich Consensus Conference of 2016 on B3 lesions had influenced daily practice and (2) reviewed current literature towards recommendations to biopsy.
RESULTS
In 2018, the consensus recommendations for management of B3 lesions remained almost unchanged: For flat epithelial atypia (FEA), classical lobular neoplasia (LN), papillary lesions (PL) and radial scars (RS) diagnosed on core-needle biopsy (CNB) or vacuum-assisted biopsy (VAB), excision by VAB in preference to open surgery, and for atypical ductal hyperplasia (ADH) and phyllodes tumors (PT) diagnosed at VAB or CNB, first-line open surgical excision (OE) with follow-up surveillance imaging for 5 years. Analyzing the Database of the Swiss Minimally Invasive Breast Biopsies (MIBB) with more than 30,000 procedures recorded, there was a significant increase in recommending more frequent surveillance of LN [65% in 2018 vs. 51% in 2016 (p = 0.004)], FEA (72% in 2018 vs. 62% in 2016 (p = 0.005)), and PL [(76% in 2018 vs. 70% in 2016 (p = 0.04)] diagnosed on VAB. A trend to more frequent surveillance was also noted also for RS [77% in 2018 vs. 67% in 2016 (p = 0.07)].
CONCLUSIONS
Minimally invasive management of B3 lesions (except ADH and PT) with VAB continues to be appropriate as an alternative to first-line OE in most cases, but with more frequent surveillance, especially for LN.
Topics: Biopsy, Large-Core Needle; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Lobular; Databases, Factual; Female; Humans; Image-Guided Biopsy; Minimally Invasive Surgical Procedures; Phyllodes Tumor; Population Surveillance; Practice Guidelines as Topic
PubMed: 30506111
DOI: 10.1007/s10549-018-05071-1 -
Cancer Communications (London, England) Nov 2023As a rapid-progressing tumor, breast malignant phyllodes tumors (PTs) are challenged by the lack of effective therapeutic strategies and suitable prognostic markers....
BACKGROUND
As a rapid-progressing tumor, breast malignant phyllodes tumors (PTs) are challenged by the lack of effective therapeutic strategies and suitable prognostic markers. This study aimed to clarify the role and mechanism of CD146 on promoting PTs malignant progression, and to identify a novel prognosis marker and treatment target of breast malignant PTs.
METHODS
The expression and prognostic significance of CD146 in PTs was detected through single-cell RNA-sequencing (scRNA-seq), immunostaining, real-time PCR and other methodologies. Functional experiments including proliferation assay, colony formation assay, transwell assay, and collagen contraction assay were conducted to validate the role of CD146 in malignant progression of PTs. The efficacy of anti-CD146 monoclonal antibody AA98 against malignant PTs was corroborated by a malignant PT organoid model and a PT patient-derived xenograft (PDX) model. Transcriptome sequencing, proteomic analysis, co-immunoprecipitation, and pull-down assay was employed to identify the modulating pathway and additional molecular mechanism.
RESULTS
In this study, the scRNA-seq analysis of PTs disclosed a CD146-positive characteristic in the α-SMA fibroblast subset. Furthermore, a progressive elevation in the level of CD146 was observed with the malignant progression of PTs. More importantly, CD146 was found to serve as an independent predictor for recurrence in PT patients. Furthermore, CD146 was found to augment the viability and invasion of PTs. Mechanistically, CD146 acted as a protective "shield" to prevent the degradation of Discoidin, CUB, and LCCL domain-containing protein 2 (DCBLD2), thereby activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and enhancing malignant behaviors of PT cells. In the malignant PT organoid and PDX model, a significant suppression of malignant PT growth was observed after the application of AA98.
CONCLUSIONS
These findings suggested that CD146 served as an efficacious marker for predicting PT malignant progression and showed promise as a prognosis marker and treatment target of breast malignant PTs. The study further unveiled the essential role of the CD146-DCBLD2/PI3K/AKT axis in the malignant progression of PTs.
Topics: Animals; Female; Humans; Breast Neoplasms; CD146 Antigen; Disease Models, Animal; Membrane Proteins; Phosphatidylinositol 3-Kinases; Phyllodes Tumor; Proteomics; Proto-Oncogene Proteins c-akt
PubMed: 37856423
DOI: 10.1002/cac2.12495 -
Biomedica : Revista Del Instituto... Jun 2016The Li-Fraumeni syndrome is characterized clinically by the appearance of tumors in multiple organs generally at an early age. This hereditary condition is caused by...
The Li-Fraumeni syndrome is characterized clinically by the appearance of tumors in multiple organs generally at an early age. This hereditary condition is caused by germinal mutations in the TP53 gene, which codifies for the tumoural suppressor gene p53. We present the case of a patient aged 31 with clinical and molecular diagnosis of Li-Fraumeni syndrome who presented two synchronous tumors: a leiomyosarcoma on the forearm and a phyllodes breast tumour. She had a family history of cancer, including a son diagnosed with a cortical adrenal carcinoma when he was three years old, who died at five from the disease. Furthermore, her maternal grandmother and great-grandmother died of stomach cancer at 56 and 60 years old, respectively, while her other great-grandmother and a great aunt presented with breast cancer at the ages of 60 and 40, respectively. After genetic counseling, complete sequencing and analysis of duplications and deletions in the TP53 gene were ordered prior to diagnosis. The molecular analysis of a DNA sample taken from peripheral blood lymphocytes revealed the germinal mutation c.527G>T (p.Cys176Phe) on exon 5 of the TP53 gene, a deleterious mutation described previously in tumoural tissues. To our knowledge, this is the first published case in Colombia of Li-Fraumeni syndrome with confirmed molecular diagnosis. The diagnosis and management of Li-Fraumeni syndrome should be performed by a multidisciplinary team, and genetic counselling should be offered to patients and their relatives.
Topics: Breast Neoplasms; Exons; Genes, p53; Humans; Li-Fraumeni Syndrome; Mutation; Stomach Neoplasms; Tumor Suppressor Protein p53
PubMed: 27622479
DOI: 10.7705/biomedica.v36i3.2793 -
Autopsy & Case Reports Apr 2021Lactating adenoma is a rare benign breast lesion that most often presents as a small (up to 3 cm), solid, well-circumscribed, solitary, painless, mobile, lobulated mass....
Lactating adenoma is a rare benign breast lesion that most often presents as a small (up to 3 cm), solid, well-circumscribed, solitary, painless, mobile, lobulated mass. The highest incidence occurs in primiparous women (20 to 40 years old) during the third trimester of pregnancy. However, in the rare case presented herein, in addition to its giant size (more than 10 centimeters on palpation), this lactating adenoma is distinctive due to the presence of multiple nodules, poorly defined ultrasonographic margins, worrisome radiologic features, growth since early pregnancy, presence of infarction and association with chronic mastitis. From the clinical-radiologic perspective, the differential diagnoses included abscess associated with puerperal mastitis, phyllodes tumor, and galactocele. Biopsy was performed, and pathologic examination revealed the classic characteristics of lactating adenoma with multiple infarcted areas, leading to an unexpected confirmed case of giant lactating adenoma.
PubMed: 33968827
DOI: 10.4322/acr.2021.252