Histopathologic, immunophenotypic, and proteomics characteristics of low-grade phyllodes tumor and fibroadenoma: more similarities than differences

Jeremy L Norris,Nathan H Patterson,Michelle L Reyzer,Horacio M Maluf,Audra M Judd,Richard M Caprioli,Chen Yang,Lingxin Zhang,John D Pfeifer

doi:10.1038/s41523-020-0169-8

Abstract

Distinguishing low-grade phyllodes tumor from fibroadenoma is practically challenging due to their overlapping histologic features. However, the final interpretation is essential to surgeons, who base their management on the final pathology report. Patients who receive a diagnosis of fibroadenoma might not undergo any additional intervention while lumpectomy with wide margins is the standard of care for phyllodes tumor, which can have significant cosmetic consequences. We studied the clinical, immunophenotypic, and proteomics profiles of 31 histologically confirmed low-grade phyllodes tumor and 30 fibroadenomas. Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) and immunohistochemistry for Ki-67, p53, β-catenin, and E-cadherin were performed on all cases. After the mass spectra for all 31 cases of low-grade phyllodes tumor and 30 cases of fibroadenoma were collected, an average peak value for all cases was generated. There was no significant difference in the overall mass spectra pattern in any of the peaks identified. There was also overlap in the percentage of cells staining positive for Ki-67, p53, β-catenin, and E-cadherin. The two groups of patients showed no statistically significant difference in age, tumor size, or disease-free survival. Neither group developed malignant transformation, distant metastases, or disease-related mortality. We have demonstrated low-grade phyllodes tumor and fibroadenoma to show significant overlapping clinical and proteomics features.

Highlights

Fibroepithelial lesions of the breast are a heterogeneous group of biphasic tumors that include the common benign fibroadenomas and the relatively rare phyllodes tumors (2.5% of all fibroepithelial lesions of the breast)
There was a slight trend that show low-grade phyllodes tumor to be more commonly seen in older patients with a median age of 39.0 years and a mean age of 35.5 years, compared to patients with fibroadenoma who had a median age of 24.5 years and a mean age of 27.0 years
Low-grade phyllodes tumors had a median size of 2.8 cm and a mean size of 3.0 cm at the time of resection, only marginally larger than the median size of 2.5 cm and mean size of 2.7 cm of fibroadenomas at the time of surgery

Summary

Introduction

Fibroepithelial lesions of the breast are a heterogeneous group of biphasic tumors that include the common benign fibroadenomas and the relatively rare phyllodes tumors (2.5% of all fibroepithelial lesions of the breast). Many grading systems for phyllodes tumor have been proposed, all based on the assessment of tumor borders, stromal cellularity and atypia, mitotic activity, and stromal overgrowth. AFIP defines low-grade phyllodes tumors as fibroepithelial neoplasms with well-defined borders, uniform leaf-like processes, rare to moderate mitoses (

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