Fibroepithelial Tumors of the Breast: Pathologic and Immunohistochemical Features and Molecular Mechanisms

Abstract

Context.—The 2 main prototypes of fibroepithelial tumors of the breast include fibroadenoma and phyllodes tumor (PT). Although both tumors share some overlapping histologic features, there are significant differences in their clinical behavior and management. Phyllodes tumors have been further divided into clinically relevant subtypes, and there is more than one classification scheme for PT currently in use, suggesting a lack of consistency within different practices. Accurate differentiation between fibroadenoma and PT, as well as the grading of PT, may sometimes be challenging on preoperative core needle biopsy. Some immunohistochemical markers have been suggested to aid in the pathologic classification of these lesions. Objective.—To discuss the salient histopathologic features of fibroepithelial tumors and review the molecular pathways proposed for the initiation, progression, and metastasis of PTs. Also, to provide an update on immunohistochemical markers that may be useful in their differential diagnosis and outline the practice and experience at our institution from a pathologic perspective. Data Sources.—Sources included published articles from peer-reviewed journals in PubMed (US National Library of Medicine). Conclusions.—Fibroepithelial tumor of the breast is a heterogenous group of lesions ranging from fibroadenoma at the benign end of the spectrum to malignant PT. There are overlapping histologic features among various subtypes, and transformation and progression to a more malignant phenotype may also occur. Given the significant clinical differences within various subtypes, accurate pathologic classification is important for appropriate management. Although some immunohistochemical markers may be useful in this differential diagnosis, histomorphology still remains the gold standard.

Mutational analysis of MED12 in fibroadenomas and phyllodes tumors of the breast by means of targeted next-generation sequencing

“…These results indicate that MED12 mutation is implicated in the pathogenesis of both FA and PT, and that intracanalicular FA is most closely related to PT. The fact that FA occasionally recurs as PT at the site of the FA resection also suggests a common pathogenesis of FA and PT [4][5][6]. It has been suggested that several markers, such as p53 [21][22][23], Ki-67 [23,24], c-kit [25], and CD10 [22], can be useful for differentiation between FA and PT.…”

“…The clinical behavior of FAs is generally benign so that small FAs (\3 cm) are usually followed up without resection and about 16-37 % of FAs reportedly resolve spontaneously [1,2]. However, it has also been reported that a small percentage of FAs progresses to PTs [1,[4][5][6]. Unlike FAs, PTs often grow into large tumors, necessitating resection of the tumor or even the whole breast.…”

Application of Immunohistochemistry in Breast Pathology: A Review and Update

“…Among those, the Ki-67 proliferative index has been reported to be increased in borderline and especially in malignant PT and can be useful in the classification of fibroepithelial tumors. [102][103][104][105][106] The World Health Organization classification of PT 1 requires greater than 10 mitoses per 10 high-power fields for malignant PT; however, no numeric cutoff has been established to define benign and borderline PTs, which were described as ''few if any'' and ''moderate,'' respectively. Some authors 2 classify less than 2 mitoses per 10 high-power fields as benign PT, 2 to 5 mitoses per 10 high-power fields as borderline PT, and more than 5 mitoses per 10 high-power fields as malignant PT.…”

“…Some authors 2 classify less than 2 mitoses per 10 high-power fields as benign PT, 2 to 5 mitoses per 10 high-power fields as borderline PT, and more than 5 mitoses per 10 high-power fields as malignant PT. Several immunomarkers showed increased expression in the stroma of malignant PT compared with that in benign tumors, including p53, 8,103,105,[107][108][109][110][111][112] CD117, 8,103,105,[107][108][109][110][111][112] epithelial growth factor receptor (EGFR), 113 and CD10. 114 However, no significant difference can distinguish between borderline and malignant PT.…”

Transformation of benign phyllodes to malignant phyllodes tumor

“…Foi observado que as recorrências locais não dependem apenas do tipo histológico, mas também de adequada margem cirúr-gica, além da heterogeneidade intratumoral que se encontra em tumores que possuem focos de estroma maligno muito pequenos para serem identificados histologicamente na primeira apresentação. 12 Além disso, mudanças genéticas são adquiridas em recorrências de tumores benignos que são associados ao fenótipo bordeline e maligno e a recorrência desses mostra aquisição de novas mudanças genéticas que podem influenciar o comportamento do tumor. A transformação do tumor filóide envolve interação entre estroma e epitélio.…”