Case 5 -

Malignant Phyllodes Tumor Gary Tse Prince of Wales Hospital Hong Kong, China

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Clinical history A 50 year old lady presented with a 4.7 cm mass in the right breast. There was no nipple discharge. There was also a previous history of breast lump removed from the same breast 2 years ago. Physical examination showed the mass to be hard to palpation, but was not adherent to the skin or underlying tissue. There was no axillary lymphadenopathy. The breast lump was excised and the section is a representative sampling of this breast mass. Case 5 - Figure 1 Case 5 - Figure 2 Case 5 - Figure 3 Case 5 - Figure 4 Case 5 - Figure 5 Case 5 - Figure 6 Case 5 - Figure 7 Case 5 - Figure 8 Differential diagnosis Fibroepithelial Lesions- Fibroadenoma Within the group of fibroepithelial lesions, fibroadenomas and phyllodes tumors share the histologic feature of intimate association of the epithelial and stromal components, the latter being derived exclusively from the interlobular specialized stroma. The usual fibroadenomas are readily recognized and do not pose any diagnostic challenges. Juvenile fibroadenoma may present with a more worrisome clinical history of rapid growth, and histologically it may be endowed with high stromal cellularity, with a predominantly pericanalicular pattern and mitotic figures may be seen among the stromal cells. The relatively uniform stromal proliferation and absence of true sarcomatous stroma or stromal overgrowth help to differentiate juvenile fibroadenoma from phyllodes tumor. The behavior and prognosis of juvenile fibroadenoma is similar to other fibroadenomas [1]. Fibroepithelial Lesions - Phyllodes Tumor Phyllodes tumor is an uncommon breast tumor, and is estimated to account for less than 1% of primary breast tumors [2]. There appears to be ethnical difference, with a higher incidence occurring in Asians. In general the patient's age for phyllodes tumor is about 15-20 years older than that for fibroadenoma. Patient with phyllodes tumor presents with a history of rapidly enlarging breast lump. Microscopically, phyllodes tumor is characterized by variable degree of stromal proliferation, resulting in distortion of the architecture to give a leaf like pattern. In general, there is increased stromal cellularity, particularly in areas that are in close contact with the epithelium. The stromal cells may also show nuclear crowding, atypia and increased mitotic activity. Stromal overgrowth may be present; and the margin of the phyllodes tumor may vary from well delineated to infiltrative. The epithelial cells may occasionally show squamous or apocrine metaplasia or epithelial hyperplasia. Phyllodes tumor are usually graded into benign, borderline and malignant [3]. A malignant phyllodes tumor is characterized by stromal hypercellularity, significant stromal cell atypia or nuclear pleomorphism, the presence of malignant heterologous elements (osteoid or chondroid), increased mitotic activity (3-4 or more mitoses per 10 high power fields) and the presence of infiltrative margin and stromal overgrowth [1, 3, 4]. Sometimes, the stromal overgrowth may be so prominent that the benign epithelial element may only be found after diligent search. In a typically benign phyllodes tumor, the stroma is also cellular, especially when compared to fibroadenoma, and the stromal cell nuclei are monomorphic and mitoses are rare, and the margin is better delineated. Borderline phyllodes tumor tend to show intermediate features. Thus the histomorphology of different grades of phyllodes tumors lie in a continuum. The outcome of phyllodes tumor is recurrence and systemic metastasis. Local recurrence occurs in all grades of phyllodes tumors, and the histology may be similar or may progress to a higher grade lesion. Metastasis tends to be systemic rather than lymph node as phyllodes tumor behaves more like a sarcoma than carcinoma, and the metastasis may only contain the stromal component devoid of epithelium [4]. The frequency of recurrences and metastases differ in different series, but the rate for both events increases from benign to borderline to malignant phyllodes. The differentiation between the various phyllodes tumor and fibroadenoma is particularly problematic in core needle biopsies. The difficulty stems from the intrinsic limited sampling in core biopsy and the heterogeneous stromal cellularity in phyllodes. About 70% of phyllodes tumors at excision were diagnosed as fibroadenoma on core biopsy [5, 6]. Features that were found to be useful for diagnosing phyllodes (over fibroadenoma) in core biopsies include increased stromal cellularity [6, 7], stromal overgrowth, fragmentation, adipose tissue within stroma [6], higher mitotic rate and proliferative index as measured by Ki67 staining [7]. Metaplastic Carcinoma (Spindle Cell Carcinoma) and Sarcoma Metaplastic carcinoma is characterized morphologically by highly pleomorphic malignant cells, with some (monophasic) showing only spindle cell (sarcomatoid) pattern [1]. Primary breast sarcoma also shows proliferation of malignant spindle cells, which can range from spindled to pleomorphic. These entities can be differentiated from malignant phyllodes tumor by the presence of benign epithelial element in phyllodes tumor but not in others. Immunohistochemistry may be helpful, as epithelial markers for cytokeratins like AE1/3 or CAM5.2, and p63 [8] are positive for metaplastic carcinoma, whereas CD34 has been reported to be positive for phyllodes tumor [9]. Final diagnosis Malignant phyllodes tumor. Keywords Breast, phyllodes tumors, sarcoma, metaplastic carcinoma Reference: Pike AM, Oberman HA. Juvenile (cellular) adenofibromas. A clinicopathologic study. Am J Surg Pathol 1985;9:2891-2905. Elston CW, Ellis IO. The breast. In: Systemic pathology, vol. 13, 3rd edn. 1998. Churchhill Livingstone, Edinburgh. WHO Classification of tumors. Tumors of the breast and female genital organs. IARC, Lyon. 2003. Tan PH, Jayabaskar T, Chuah KL, Lee HY, Tan Y, Hilmy M, Hung H, Selvarajan S, Bay BH. Phyllodes tumours of the breast. The role of pathologic parameters. Am J Clin Pathol 2005;123:529-40. Jacklin RK, Ridgway PF, Ziprin P, Healy V, Hadjiminas D, Darzi A. Optimising preoperative diagnosis in phyllodes tumour of the breast. Optimising preoperative diagnosis in phyllodes tumour of the breast. J Clin Pathol 2006;59:454-9. Lee AH, Hodi Z, Ellis IO, Elston CW. Histological features useful in the distinction of phyllodes tumour and fibroadenoma on needle core biopsy of the breast. Histopathology 2007;51:336-44. Jacobs TW, Chen YY, Guinee DG Jr, Holden JA, Cha I, Bauermeister DE, Hashimoto B, Wolverton D, Hartzog G. Fibroepithelial lesions with cellular stroma on breast core needle biopsy: are there predictors of outcome on surgical excision? Am J Clin Pathol 2005;124:342-54 Koker MM, Kleer CG. p63 expression in breast cancer: a highly sensitive and specific marker of metaplastic carcinoma. Am J Surg Pathol. 2004;28:1506-12. Lee AH. Recent developments in the histological diagnosis of spindle cell carcinoma, fibromatosis and phyllodes tumour of the breast. Histopathology 2008;52:45-57.