CASES 1147091-2016, 1144825-2016
The patient is a 51-year old woman who presented with bilateral breast masses. Excisional biopsies were performed on both lesions
Histological sections on both tumors reveal fibroepithelial tumor with a cellular stroma and foci of stromal overgrowth. Moderately increased stromal cellularity and leaf-like architecture is present. Borders of the tumor appear smooth, no infiltrative growth is identified. Nuclear atypia is mild. Rare mitoses are seen (less than 9 per 10 HPF). Ki-67 proliferative index is estimated at 15-20%
DIAGNOSIS: BILATERAL SYNCHRONOUS BORDERLINE PHYLLOIDES TUMORS
Phylloides tumors (PTs) is a group of fibroepithelial neoplasms of the breast. These are rare biphasic tumors that are defined by an overgrowing cellular mesenchymal component surrounding a benign double layered epithelial component (ie, the glandular breast tissue). The stromal component is typically organized in cleft-like spaces that give the tumor its name (“leaf-like”). Rosai believes that the phylloides tumor is a tumor of the specialized mammary stroma that has the capacity to induce epithelial growth. The epithelial glands may have a proliferative appearance but are not neoplastic, while the stromal component is neoplastic and may be either monomorphic, or pleomorphic and reminiscent of fibrosarcoma, liposarcoma, leiomyosarcoma, and/or chondrosarcoma. Therefore, it is the amount and appearance of the stromal component that determines whether a tumor should be called a phylloides tumor or fibroadenoma, and whether it may have an aggressive clinical behavior.
The relationship between PT and fibroadenoma is unclear. The recent whole genome sequencing studies have found that MDM12 mutation is common in both fibroadenoma and PT suggesting that the two entities may be related. In some cases, PT arises in a background of pre-existing fibroadenoma, but not uncommonly it developed de novo. Phylloides tumor occurs in the same age group as breast carcinoma with the median age at diagnosis being 45 years. This is in contrast with the fibroadenoma which usually affects younger women before the age of 25. Malignant PTs tend to occur 2-5 years earlier than benign PT and are more prevalent in Hispanics, especially in women born in Latin America.
Patient who developed phylloides tumor unusually notice a unilateral firm painless mass that is mobile and not attached to the skin. On the imaging, the mass is rounded and sharply defined. Multifocal or bilateral lesions, such as seen in this patient are highly unusual. There are isolated cases in the literature reporting bilateral synchronous malignant and benign tumors, benign lesions developing in contralateral breast a year apart, and phylloides tumor coexisting with an invasive ductal carcinoma, among other. All those are rare occurrences, and their pathogenesis is not well understood.
Phylloides tumor may have areas of necrosis, cystic degeneration, and hemorrhage including complete hemorrhagic infarct that clinically leads to bloody nipple discharge. In its malignant form, PT has marked nuclear atypia, numerous mitoses, and loss of the relationship between glands and stroma whereby the sarcomatous stroma overgrows the glands, and the epithelial elements are no longer identifiable on histologic examination.
The 2012 WHO Classification contains a comprehensive morphologic grading system to categorize the tumor as benign, malignant, or borderine (if it does not fall easily into the two other categories). The histologic parameters that should be evaluated include mitotic activity, stromal overgrowth, stromal cellularity, stromal atypia, intratumoral heterogeneity, tumor margin (well-defined for benign lesions and infiltrative in malignant PT), presence of the leaf-like pattern, stromal fragmentation and subepithelial stromal condensation. Stromal cellularity and atypia are graded as mild, moderate or marked, and as with all morphologic grading systems, there is room for subjectivity. In addition, there may be significant heterogeneity within the same tumor, and benign, borderline, and malignant features may be present within the same neoplasm. Therefore, adequate and representative histologic sampling is very important, and excision is required for accurate grading of the tumor.
It may be challenging to distinguish benign PT from cellular fibroadenoma because both are characterized by prominent stromal cellularity. Focal-leaf like configuration may be present in the cellular fibroadenoma and fibroadenoma-like areas may be seen in PT. The distinction is important because the treatment and prognosis for these two entities are different, and the histologic features should not be used in isolation. If there is no epithelial component identified, the differential diagnosis includes other types of sarcoma. Phylloides tumor express CD34 and BCL-2, similar to other stromal tumors of the breast, but unlike the metaplastic (sarcomatoid) carcinoma. A panel of cytokeratins (AE1/AE3, CK5/6, 34bE12, CAM 5.2) and myoepithelial marker p63 can be further helpful to exclude sarcomatoid carcinoma.
While the histologic grading described in 2012 WHO generally correlates with prognosis, this may not be true in individual patients. Benign phylloides tumor may recur locally, but almost never metastasize. The stromal elements of malignant phylloides tumor have the potential to metastasize, especially to bone and lung. The local recurrence rate of the borderline PT, as in our patient, falls between 14-25%. There are rare reports of metastases in borderline tumors, further supporting their equivocal biological potential and the importance of longitudinal follow-up.
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