Malignant phyllodes tumor of the breast: a systematic review

Abstract

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.

Keywords: breast disease; breast oncology; fine needle aspiration; malignant phyllodes tumor; pathology; personalized medicine; phyllodes tumor.

Figure 1.

Morphological features of a benign phyllodes tumor (on surgical sample). (A, B, C, D) A surgical sample of a fibro-epithelial biphasic neoplasm constituted by well delimited or pushing margins into the surrounding tissue (A, B, HEx4), marked pericanalicular growth pattern and leaf-like formations (C, D, HEx10). We can observe only a focal increase of the stromal cellularity (D, HE x4). The spindle cell stromal nuclei are monomorphic and bland; mitoses are rare. The sample shows stromal heterogeneity with areas of sparse stromal cellularity and other areas with sclerosis and hyalinization (E, HEx10). A diagnosis of benign phyllodes tumor has been made.

Figure 2.

Morphological features of a borderline phyllodes tumor (on surgical sample). (A, B, C, D, E, F) Breast surgical sample with a borderline phyllodes tumor, characterized by the following features: marked pericanalicular pattern of growth (A, HEx4), stromal heterogeneity with sclerotic, edematous and more cellular areas (B, HEx4), non-uniform increase of stromal cellularity, with a periepithelial or subepithelial accentuation (C, HEx4), moderate stromal nuclear pleomorphism (insert on the right top in image C, HE 40X), with scattered fields with higher mitotic activity (up to 4-5 mitoses/10 HPF of 0.5 mm²), focal areas of stromal overgrowth (D, HEx4) and focally permeative borders with some tumoral buds protruding into the surrounding tissue (E,F HEx4). Epithelial component does not show significant atypia.

Figure 3.

Morphological features of a malignant phyllodes tumor (on VABB and surgical sample).(A, B, C) A biopsy sample of a fibro-epithelial biphasic neoplasm constituted by increase stromal cellularity (an overwiew; A, HE x4). For moderate-severe nuclear atypia (B, HE x20) and presence of elevated mitotic index (C, HE x40), a diagnosis of malignant phyllodes tumor was made. (D) Breast surgical sample with the malignant phyllodes tumor diagnosed on the VABB observed and commented in A-B-C. We can note the following features: permeative margins into the surrounding breast parenchyma (D, HE x4), increased stromal cellularity, being usually diffuse (E, HE x20), with areas of stromal overgrowth and marked stromal nuclear pleomorphism (F, HE 40X), with scattered fields with brisk mitotic activity (up to 18 mitoses/10 HPF of 0.5 mm²). No malignant heterologous elements were observed.

Figure 4.

Vertebral metastasis of a malignant phyllodes tumor: histological and immunohistochemical findings. (A-B) After 1 year from histological diagnosis, the patient (affected from the malignant phyllodes tumor shown in Figure 1), experienced a vertebral metastases (on D3), constituted by a proliferation of spindle atypical cells (A, HE x10; B, HE x20), morphological resembling the primitive breast tumor, with a significant proliferative index (Ki-67: 20%, LSAB-HRP, x20; insert on the right top in image B).