Malignant phyllodes tumours of the breast: the case for revising WHO's 'full house' diagnostic criteria

Abstract

Phyllodes tumours (PTs) of the breast present diagnostic challenges due to their complex histological features and potential for malignant behaviour. The World Health Organisation (WHO) classification requires the presence of five adverse histological criteria to categorise PTs as malignant, aiming to avoid overdiagnosis and improve diagnostic consistency. However, emerging evidence suggests that these strict criteria may underdiagnose tumours with metastatic potential and histological features that would otherwise be considered malignant in soft tissue tumours, leading to significant implications for prognosis and treatment. Recent studies have highlighted cases where tumours classified as borderline PT by WHO criteria exhibited metastatic behaviour, emphasising the need to refine the diagnostic framework. Microscopic criteria used to classify PT also vary among reporting pathologists, resulting in suboptimal reproducibility. This review examines the histological parameters utilised in the classification of malignant PT, highlights existing evidence gaps and analyses international breast pathologist survey data to propose a pragmatic diagnostic approach. We recommend redefining malignant PTs to include cases meeting four of the five WHO criteria, supplemented by comprehensive sampling and clinical context. This approach balances the risk of underdiagnosis with the need for standardised, reproducible diagnostic practices. Future collaborative efforts should focus upon developing evidence-based, biologically relevant classification systems and leveraging technological advancements to enhance diagnostic precision. These efforts aim to refine classification, improve prognostic accuracy and optimise patient management strategies.

Keywords: breast; grade malignancy; phyllodes tumours.

Figure 1

Pie charts illustrating the responses of breast pathologists within this review (authors of this manuscript) for three scenarios: (A) FEL with marked stromal cellularity, stromal atypia and stromal mitoses ≥ 10 per 10 high‐power fields but with well‐defined margins and no overgrowth. (B) Fibroepithelial lesions (FEL) with marked stromal cellularity, stromal atypia and stromal mitoses ≥ 10 per 10 high‐power fields, and overgrowth but with defined margins. (C) FEL with marked stromal cellularity, atypia and mitoses ≥ 10, and infiltrative margins but without stromal overgrowth.

Figure 2

(A) Phyllodes tumour in a 47‐year‐old female shows well‐defined borders with an area of stromal overgrowth (arrow). (B) Higher magnification of the area of stromal overgrowth shows crowded stromal cells with atypia. (C) Moderate to marked stromal cellularity shows touching and overlapping nuclei. (D) Marked stromal atypia. (E) Mitoses are readily discerned, numbering up to 34 mitoses per 10 high‐power fields. This tumour fulfils four of five histological criteria of malignancy.

Figure 3

Phyllodes tumour with three of five adverse histological parameters, graded as borderline, with a well‐defined border (A), marked stromal cellularity and atypia (B), with mitoses > 10 per 10 high power fields. No stromal overgrowth is present.

Figure 4

Phyllodes tumour in a 53‐year‐old‐female with (A) a characteristic phyllodiform architecture and a focally infiltrative border, (B) focal areas of marked stromal hypercellularity, (C) up to 16 mitoses/10 high‐power fields and nuclear atypia. There is focal well‐differentiated liposarcomatous differentiation (D), but no other heterologous elements are seen. No stromal overgrowth is present (although a number of 10× magnification fields lack an epithelial component). Despite the lack of stromal overgrowth, a diagnosis of malignant phyllodes tumour is favoured in view of the other atypical features. (E) Core biopsy shows focal marked stromal hypercellularity and stromal atypia with (F) the corresponding immunohistochemistry for CD34 displaying positive staining of stromal cells.

Figure 5

Evidence map of malignant phyllodes tumour references in the World Health Organisation (WHO) Classification of Tumours (WCT) of the Breast (5th edition). The colour of each sphere shows the evidence level of a publication; namely, green for level P1 (highest level evidence), red for level P2, blue for level P3, purple for level P4, orange for level P5 (lowest level evidence) and black for unclassifiable. The size of the sphere corresponds to the number of cited publications.