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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 -
International Journal of Surgery... Nov 2022Phyllodes tumor is rare but has a high recurrence rate. Treatment modalities and clinicopathological prognostic factors for recurrence remain unclear. The synthesis of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Phyllodes tumor is rare but has a high recurrence rate. Treatment modalities and clinicopathological prognostic factors for recurrence remain unclear. The synthesis of real-world data can enable the integration of sufficient evidence on optimal treatment for this population.
METHODS
We searched PubMed, Embase, and Cochrane Library databases for studies focusing on the management of phyllodes tumor including the surgical margin, different clinicopathological prognostic factors, and postoperative adjuvant radiotherapy versus no radiotherapy.
RESULTS
Fifty-two studies were retrieved. The pooled estimated recurrence rates of benign, borderline, and malignant tumors were 7.1%, 16.7%, and 25.1%, respectively. Surgical margins of 1 mm (odds ratio [OR]: 0.4, 95% confidence interval [CI]: 0.27-0.61) and 1 cm (OR: 0.45, 95% CI: 0.15-0.85) resulted in significantly higher recurrence rates. Postoperative adjuvant radiotherapy significantly reduced the recurrence rate of malignant tumors relative to no radiotherapy (P = 0.034) but did not significantly reduce the recurrence rates of overall and borderline tumors. Regarding clinicopathological features, moderate or severe stromal atypia and hypercellularity, stromal overgrowth, mitotic number of 5, tumor necrosis, tumor border, and margin status were determined as independent prognostic factors for recurrence, except a tumor size of 5 cm.
CONCLUSION
The ideal surgical margin for phyllodes tumor incision should be at least 1 cm in width. Adjuvant radiotherapy reduced the recurrence of malignant tumor. By identifying patients with poor clinicopathological risk factors, surgeons may reduce the recurrence rate of phyllodes tumor.
Topics: Humans; Female; Phyllodes Tumor; Margins of Excision; Neoplasm Recurrence, Local; Radiotherapy, Adjuvant; Adjuvants, Immunologic; Breast Neoplasms; Prognosis; Retrospective Studies
PubMed: 36328344
DOI: 10.1016/j.ijsu.2022.106969 -
Virchows Archiv : An International... Jan 2022Fibroepithelial tumours of the breast are biphasic neoplasms composed of both epithelial and stromal elements, including the common fibroadenoma and the infrequent... (Review)
Review
Fibroepithelial tumours of the breast are biphasic neoplasms composed of both epithelial and stromal elements, including the common fibroadenoma and the infrequent phyllodes tumour. The admixture of epithelium and stroma in the fibroadenoma shows intra- and pericanalicular patterns, and may display a variety of histological changes. Fibroadenoma variants include the cellular, juvenile, myxoid and complex forms. The cellular fibroadenoma may be difficult to distinguish from the benign phyllodes tumour. Stromal mitotic activity can be increased in fibroadenomas in the young and pregnant patients. Phyllodes tumours, neoplasms with the potential for recurrence, show an exaggerated intracanalicular growth pattern with broad stromal fronded architecture and stromal hypercellularity. They are graded into benign, borderline and malignant forms based on histological assessment of stromal features of hypercellularity, atypia, mitotic activity, overgrowth and the nature of the tumour borders. Classification of phyllodes tumours is imperfect, compounded by tumour heterogeneity with overlapping microscopic features among the different grades, especially in the borderline category. Malignant phyllodes tumours can metastasise and cause death. Determining which phyllodes tumours may behave aggressively has been difficult. The discovery of MED12 mutations in the pathogenesis of fibroepithelial tumours, together with other gene abnormalities in the progression pathway, has allowed refinements in diagnosis and prognosis.
Topics: Breast; Breast Neoplasms; Female; Fibroadenoma; Humans; Neoplasms, Fibroepithelial; Phyllodes Tumor
PubMed: 34505197
DOI: 10.1007/s00428-021-03175-6 -
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 -
Der Pathologe May 2021The development of the WHO classification of tumors of the breast is driven by new knowledge from research whose translation into daily practice is considered clinically... (Review)
Review
The development of the WHO classification of tumors of the breast is driven by new knowledge from research whose translation into daily practice is considered clinically relevant. The fifth edition represents an update of the fourth edition and essentially follows the previously known systematics. The histologic features of the lesions continue to form the basis of the classification in the update. This also applies to the definition of invasive tumor types. However, several new molecular classifications as well as additional prognostic and predictive factors are presented and discussed, which improve prognosis estimation and therapy decisions. This paper aims to present the main changes in the current WHO classification. These include the revised definition of mixed invasive carcinomas, the introduction of new special invasive entities (tall cell carcinoma with reversed polarity, mucinous cystadenocarcinoma), the deletion of special invasive types and their classification as variants of invasive carcinoma, NST (no special type, including medullary, lipid-rich, glycogen-rich, among others), the typing of primary neuroendocrine neoplasms of the breast by analogy with other organ systems, changes in the dignity criteria of phyllodes tumors, and the revised subtyping of lobular carcinoma in situ (LCIS). In addition to improvements in the fifth edition of the classification, flaws are also highlighted. A section is devoted to new molecular parameters.
Topics: Breast; Breast Neoplasms; Carcinoma; Carcinoma, Lobular; Humans; Prognosis; World Health Organization
PubMed: 33822251
DOI: 10.1007/s00292-021-00934-9 -
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 -
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 -
The Surgical Clinics of North America Dec 2022Breast stromal lesions include fibroadenomas, phyllodes tumors, pseudoangiomatous stromal hyperplasia, periductal stromal tumors, and lipomas. Most of these lesions are... (Review)
Review
Breast stromal lesions include fibroadenomas, phyllodes tumors, pseudoangiomatous stromal hyperplasia, periductal stromal tumors, and lipomas. Most of these lesions are benign and can be managed with observation or surgical excision. Phyllodes tumors, however, are subcategorized into benign, borderline, and malignant. Benign phyllodes tumors may be removed without a margin of breast tissue while borderline and malignant phyllodes tumors need a wide excision with a greater than 1 cm margin. Because malignant phyllodes tumors have a poor prognosis, efforts should be made to discuss their treatment in a multidisciplinary setting and enrollment in a clinical trial should be considered.
Topics: Humans; Female; Phyllodes Tumor; Fibroadenoma; Margins of Excision; Breast Neoplasms
PubMed: 36335922
DOI: 10.1016/j.suc.2022.07.002 -
The Breast Journal Mar 2020
Topics: Breast Neoplasms; Chorionic Gonadotropin, beta Subunit, Human; Female; Humans; Phyllodes Tumor
PubMed: 31605427
DOI: 10.1111/tbj.13562 -
Advances in Experimental Medicine and... 2020Phyllodes tumor constitutes around 1% of all and 2.5% of fibroepithelial breast lumps. Three types including benign, borderline, and malignant tumors have been... (Review)
Review
Phyllodes tumor constitutes around 1% of all and 2.5% of fibroepithelial breast lumps. Three types including benign, borderline, and malignant tumors have been described. The benign variant is the most common, is close to fibroadenoma, but is usually larger and recurs more frequently. The rare malignant type is aggressive. Standard treatment consists of lumpectomy with appropriate margins for benign phyllodes tumor, while the borderline and malignant variants must be treated by wide resection or mastectomy. Phyllodes tumor is a rare tumor in pregnancy and lactation, and the effect of gestational alterations in hormone levels on this tumor have not been discussed in the literature, except for several case reports. In summary and alluding to our recent literature review, large size, fast growth, bilaterality, and probably malignancy are more commonly expected in gestational phyllodes tumors.
Topics: Breast Neoplasms; Female; Humans; Lactation; Mastectomy; Phyllodes Tumor; Pregnancy; Pregnancy Complications, Neoplastic
PubMed: 32816274
DOI: 10.1007/978-3-030-41596-9_19