Breast phyllodes tumors with epithelioid features show distinct molecular profiles and a high recurrence rate, raising concern for potential malignant transformation, according to a recent study.
Researchers characterized a rare histologic variant of breast phyllodes tumor (PT) with epithelioid features in a study published in the Journal of Clinical Pathology. The investigation aimed to determine whether epithelioid PT represents a distinct morphological and molecular subtype and to assess its potential for malignant transformation. The study analyzed seven cases classified as borderline PT based on the 2019 WHO criteria, each with stromal epithelioid cell composition exceeding 90 percent.
The Chinese study utilized immunohistochemistry, immunofluorescence, transmission electron microscopy, and transcriptomic and proteomic profiling. Proteomic analysis was performed using data-independent acquisition technology, while RNA sequencing was conducted on formalin-fixed, paraffin-embedded samples. Comparative analyses were performed on six epithelioid PTs and eight classical PTs (one benign, six borderline, one malignant), along with two normal breast tissue samples.
All patients were females aged 17 to 39 years, presenting with unilateral breast masses ranging in size from 2.0 cm to 18.2 cm. Three of the seven patients (43 percent) experienced local recurrence following surgical resection. Histologically, the tumors demonstrated stromal epithelioid cells with moderate to marked atypia, vacuolated nuclei, prominent nucleoli, and frequent mitotic figures. In several cases, sarcomatoid transformation was observed, including pleomorphic liposarcoma features in one tumor.
Transcriptomic and proteomic analyses revealed distinct molecular signatures between epithelioid and classical PTs. Twenty-one proteins were found to be upregulated in both tumor types compared with normal tissue, while four proteins—HAUS1, MAPKAPK2, CDKN2A, and TIMP1—were uniquely elevated in epithelioid PTs. These proteins were associated with pathways involving protein phosphorylation and cell cycle regulation.
Immunohistochemical staining patterns for p16 and retinoblastoma (Rb) proteins in epithelioid PTs were similar to those observed in malignant PTs. Among five evaluable epithelioid cases, three demonstrated diffuse p16+/Rb− expression, one showed diffuse Rb+ only, and one was negative for both. This expression pattern contrasted with benign and borderline PTs, where p16 and Rb were typically negative or weakly positive.
These findings suggest that epithelioid PTs possess unique morphological and molecular characteristics, exhibit a high risk of recurrence, and share immunophenotypic features with malignant PTs, supporting their classification as a distinct and clinically significant subtype.
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