Phyllodes tumours of the breast: a consensus review

Abstract

Phyllodes tumours constitute an uncommon but complex group of mammary fibroepithelial lesions. Accurate and reproducible grading of these tumours has long been challenging, owing to the need to assess multiple stratified histological parameters, which may be weighted differently by individual pathologists. Distinction of benign phyllodes tumours from cellular fibroadenomas is fraught with difficulty, due to overlapping microscopic features. Similarly, separation of the malignant phyllodes tumour from spindle cell metaplastic carcinoma and primary breast sarcoma can be problematic. Phyllodes tumours are treated by surgical excision. However, there is no consensus on the definition of an appropriate surgical margin to ensure completeness of excision and reduction of recurrence risk. Interpretive subjectivity, overlapping histological diagnostic criteria, suboptimal correlation between histological classification and clinical behaviour and the lack of robust molecular predictors of outcome make further investigation of the pathogenesis of these fascinating tumours a matter of active research. This review consolidates the current understanding of their pathobiology and clinical behaviour, and includes proposals for a rational approach to the classification and management of phyllodes tumours.

Keywords: classification; fibroadenoma; malignant; metastasis; phyllodes.

Figure 1

Assessment of stromal cellularity in phyllodes tumours. (A) Mild hypercellularity with slightly increased cellularity, where stromal nuclei are non-overlapping. (B) Moderate hypercellularity with some overlapping stromal nuclei. (C) Marked hypercellularity with many overlapping stromal nuclei.

Figure 2

Assessment of stromal atypia in phyllodes tumours. (A) Mild nuclear atypia shows minimal variation in nuclear size with even chromatin and smooth nuclear contours. (B) Moderate nuclear atypia with more variation in nuclear size and irregular nuclear membranes. (C) Marked nuclear atypia with marked nuclear pleomorphism, hyperchromasia, and irregular nuclear contours.

Figure 3

Phyllodes tumour graded as borderline, as it did not fulfil all criteria of malignancy. (A) Rounded pushing contour of the tumour. (B) Stromal hypercellularity was of moderate degree, accompanied by focally marked nuclear atypia. (C) Higher magnification of atypical stromal cells showed hyperchromatic nuclei, prominent nucleoli, and occasional mitoses (arrow).

Figure 4

Malignant phyllodes tumour with metastasis to the lung. (A) Low magnification of the primary breast phyllodes tumour with a cystic space into which stromal fronds projected. Part of the tumour showed a fibroadenoma-like appearance, whereas the remaining parts were more cellular. (B) Higher magnification of the cellular stromal areas showed sheets of plump spindled cells with enlarged vesicular nuclei with distinct nucleoli and scattered mitoses. Several osteoclastic giant cells were dispersed among the spindled cells. (C) Metastasis to the lung 1 year later showed a similar abnormal spindled population with scattered osteoclastic giant cells. No epithelial component was present in the metastasis.

Figure 5

Cellular fibroepithelial neoplasm that raised the differential diagnosis of a cellular fibroadenoma versus a benign phyllodes tumour. (A) Low magnification showed a few elongated epithelium-lined clefts with stromal mounds. Mild stromal hypercellularity was observed. (B) Higher magnification of a stromal frond pushing into the clefted space that contained blood and haemosiderophages, with accentuation of stromal nuclei in the peri-epithelial zone.

Figure 6

Malignant phyllodes tumour with liposarcoma. (A) Stromal fronds contained cells with marked nuclear pleomorphism with a few bizarre cells. (B) Among the abnormal stromal cells were scattered lipoblasts featuring hyperchromatic scalloped nuclei with vacuolated cytoplasm, indicating a liposarcomatous component.