Mammary mesenchymal and fibroepithelial lesions: An illustrated cytomorphologic update with differential diagnoses.

The Uniform Approach to Breast Fine Needle Aspiration Biopsy was put forward by a learned group of breast physicians in 1997. This landmark manuscript focused predominantly on diagnosis and reporting of mammary epithelial lesions. Today, most American practitioners turn initially to core biopsy rather than aspiration biopsy for the first line diagnosis of solid breast lesions; however, recent efforts from the International Academy of Cytology have produced a system called the Standardized Reporting of Breast Fine Needle Aspiration Biopsy Cytology (colloquially labeled in 2017 as the "Yokohama System"), suggesting a new interest in breast fine needle aspiration (FNA), especially in resource limited settings or clinical practice settings with experienced breast cytopathologists. Fibroepithelial lesions of the breast comprise a heterogeneous group of biphasic tumors with epithelial and stromal elements. Mesenchymal lesions of the breast include a variety of neoplasms of fibroblastic, myofibroblastic, endothelial, neural, adipocytic, muscular, and osteo-cartilaginous derivations. The cytology of mesenchymal breast lesions is infrequently described in the literature and is mainly limited to case reports and small series. This illustrated review highlights the cytologic features of fibroepithelial and mesenchymal mammary proliferations and discusses differential diagnoses and histomorphologic correlates.

Biomarkers distinguishing mammary fibroepithelial neoplasms: a tissue microarray study.

AIM: To determine whether any markers in biopsy specimens were useful for distinguishing (1) fibroadenoma (FA) from benign phyllodes tumors (PTs); and (2) from benign borderline PTs of the breast. MATERIALS AND METHODS: Specimens of 80 breast tumors (20 FA, 38 benign, 12 borderline, and 10 malignant PTs) diagnosed at Tri-Service General Hospital from 1986 to 2006 and 10 normal breast tissue were investigated immunohistochemically for the expression of 11 biomarkers including p53, Ki-67, topoisomerase IIα, p16, retinoblastoma protein (pRb), fascin-1, estrogen receptor-ß, CD117, osteopontin, hypoxia-inducible factor-1α, and cyclooxygenase-2. The binary logistic regression method was used to generate functions that discriminate between benign and borderline PT and also between FA and benign PT. RESULTS: On the basis of the most active area of stained stromal cells, the staining intensity, and the immunoscore, the expression of Ki-67, topoisomerase IIα, p16, and pRb was significantly higher in borderline or malignant PTs than in benign PTs. Ki-67 could discriminate benign from borderline PTs singly with a high sensitivity (91.7%), specificity (100%), and accuracy (98%). In addition, expression of Ki-67, p16, and pRb was significantly higher in benign PT than in FA. Binary logistic regression identified p16 and pRb as the only marker combination capable of distinguishing FA from benign PTs with sensitivity (94.7%), specificity (75%), and accuracy (87.9%). CONCLUSION: Ki-67 may be a useful marker for discriminating benign from borderline PTs, and p16 and pRb may be a useful combination of markers for distinguishing FA from benign PTs in core biopsy specimen.

Fibroepithelial tumors of the breast: pathologic and immunohistochemical features and molecular mechanisms.

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.

Expression of androgen receptor by fibroepithelioma of Pinkus: evidence supporting classification as a basal cell carcinoma variant?

The classification of fibroepithelioma of Pinkus as basal cell carcinoma or trichoblastoma remains controversial. Immunohistochemical stains for androgen receptor may be useful in differentiating basal cell carcinoma from trichoepithelioma or trichoblastoma. We studied androgen receptor expression in 13 fibroepitheliomas of Pinkus, 11 basal cell carcinomas, 12 trichoepitheliomas, and 3 trichoblastomas. Androgen receptor expression was present in 77% (10/13) of fibroepitheliomas of Pinkus, 73% (8/11) of basal cell carcinomas, 17% (2/12) of trichoepitheliomas, and 0% (0/3) of trichoblastomas. Androgen receptor expression was significantly higher in fibroepitheliomas of Pinkus compared with trichoepitheliomas and trichoblastomas (P = .0007), but not basal cell carcinoma (P = 1.00). Tumor-associated Merkel cells, a feature of benign follicular tumors, was identified by cytokeratin 20 stains. Merkel cells were identified in 85% (11/13) of fibroepitheliomas of Pinkus, 27% (3/11) of basal cell carcinoma cases, and 73% (11/15) of benign follicular tumors. Cytokeratin 20 expression was significantly higher in fibroepithelioma of Pinkus and benign follicular tumors compared with basal cell carcinomas (P = 0.0111 and P = 0.025, respectively). No significant difference was found between fibroepitheliomas of Pinkus and trichoepitheliomas and trichoblastomas (P = 1.00). Similar to basal cell carcinomas, fibroepitheliomas of Pinkus express androgen receptors, potentially supporting classification as a basal cell carcinoma. Conversely, fibroepithelioma of Pinkus demonstrates retention of Merkel cells, a feature of benign follicular tumors. Immunophenotypic evidence for the classification of fibroepithelioma of Pinkus remains inconclusive. In small, partial biopsy specimens, coexpression of androgen receptor and cytokeratin 20 may aid in the diagnosis of fibroepithelioma of Pinkus.

Fibroepithelioma of pinkus is a fenestrated trichoblastoma.

Pinkus described "pre-malignant fibroepithelioma" as a proliferation that gave rise to many tiny basal cell carcinomas within each lesion. Later authors have generally considered it to be an unusual variant of basal cell carcinoma (BCC). The delineation of trichoblastoma as the general term for the benign counterpart of BCC raises the possibility that the fibroepithelioma of Pinkus (FEP) would be better classified under that rubric. To address this subject, we examined the records of 114 patients with FEP for body site, age and sex distribution, and sections from 75 lesions. All FEP examined show a blunt interface with the underlying dermis (where one could be seen), differentiation toward follicular bulbs and papillae, and large areas of cellular stroma. FEP has a slight female preponderance in contrast to BCC, which is more common in males. Unlike the common types of BCC, FEP has an overwhelming predilection for the trunk and extremities, and only 5% of tumors are set in a dermis with significant amounts of solar elastosis. Next, FEP, BCC, and FEP with BCC-like areas were stained with MIB-1 (to assess proliferation), p53 (an oncogene product), and CK20 (a Merkel cell marker) antisera. FEP shows a low level of staining for p53 and MIB-1, in contrast to conventional BCCs that over-express these markers. FEP also shows retention of Merkel cells, a characteristic of benign neoplasms with follicular germinative differentiation but not in general of BCC. The BCC-like areas in some FEP tumors reflect these staining tendencies with less striking differences. Given the contrast between FEP and BCC with respect to site of occurrence, relationship to sun damage, histopathologic features, and immunohistochemical studies, it appears that FEP more closely resembles trichoblastoma than BCC.