Skip to content

Fibroepithelial Tumors of the Breast

May 22, 2014
Bruce A. Britton, M.D.

Bruce A. Britton, M.D.

Fibroepithelial tumors of the breast represent a class of biphasic tumors ranging from benign to highly malignant. These tumors share the histologic feature of proliferation of both epithelium and stroma, the former of which usually consists of benign glandular epithelium while the latter is composed of spindle cells that vary from uniform and benign to anaplastic. The distinction between these tumors has long suffered from variation in histologic criteria, grading schemes, and the limitations of ancillary studies.

Fibroepithelial tumors can be divided into two general categories: fibroadenomas (FA) and phyllodes tumor (PT). FAs are regarded as benign neoplasms while two and three tier grading schemes have been proposed over the years to describe the biologic potential of PTs. Indeed, low grade PTs are often so banal in appearance that separating them from benign fibroadenomas may be difficult. The histologic features most commonly evaluated in the classification of these tumors are growth pattern, stromal cellularity and distribution, atypia, mitotic activity, and tumor margins. The most recent WHO Classification of these tumors (2003) separates them into benign fibroadenoma and low grade, borderline, and malignant phyllodes tumor.

Fibroadenoma: Note the uniformly distributed stromal cells compressing benign epithelial elements.

Fibroadenoma: Note the uniformly distributed stromal cells compressing benign epithelial elements.

Fibroadenomas are thought to result from hyperplasia of the lobular elements while PTs are thought to arise from the interlobular or periductal stroma, thus giving the microscopic appearance of increased stromal volume relative to epithelial elements. It is believed the interaction between epithelium and adjacent stroma is crucial in the development of these tumors. The insulin-like growth factor signalling pathway is thought to be involved, but the interactions are not clear. Both IGF 1 and 2 are overexpressed in the stroma of these tumors.

Fibroadenomas present as painless, slow growing, circumscribed tumors up to 3 cm at all ages, most commonly in women under 30 years. They may attain extreme (up to 20 cm) sizes in adolescents, which may also be known as a “giant fibroadenoma”. They may occur as single, or uncommonly multiple, nodules in one or both breasts. Phyllodes tumors represent 0.3% to 1% of primary breast tumors and 2.5% of fibroepithelial tumors. Phyllodes tumors can occur at all ages, but are most common in middle-aged women. They occur at a younger age in those of Asian descent and are more frequently malignant in those of Central and South American descent. Tumors in men have been reported as well. The clinical presentation is that of a firm, painless breast mass. Large tumors may stretch the overlying skin. A bloody nipple discharge due to autoinfarction may occur. Imaging generally demonstrates a well-defined mass that may contain clefts, cysts, or calcifications. The relative risk of developing the usual type breast cancer in association with a fibroadenoma is low (1.5 to 2).

Benign Phyllodes Tumor: A leaf-like growth pattern is evident with mildly increased stromal cellularity.

Benign Phyllodes Tumor: A leaf-like growth pattern is evident with mildly increased stromal cellularity.

The single most distinctive histologic feature that differentiates PTs from FAs is the leaf-like growth pattern of the former, the result of excess proliferation of stromal cells. The broad bands of cellular stroma usually protrude into clefts lined by benign epithelial cells. These clefts can be identified upon careful gross examination. While some FAs may have hypercellular stroma and attain significant size, they usually lack the quintessential leaf-like pattern. Additionally, PT stroma commonly condenses around the epithelial structures and often demonstrates some degree of mitotic activity; characteristics not generally seen in FAs.

Once a tumor is identified as a PT, it is incumbent upon the pathologist to further grade the biologic potential of the tumor as benign, borderline, or malignant. Stromal hypercellularity and atypia increase with grade, as does the degree of margin irregularity. Key features in the grading of PTs are the heterogeneous distribution of stroma in intermediate grade PTs, and the mitotic activity, which generally exceeds 10 per 10 high power fields in malignant PTs. Heterologous stromal areas are occasionally seen in malignant PTs. PT stroma may predominate over the epithelial component (stromal overgrowth), hiding the biphasic fibroepithelial nature of the tumor. Ancillary techniques have been investigated in an attempt to assist in the differential diagnosis. To date, immunohistochemical stains include CD34, Ki-67, and insulin-dependent growth factor have proven to be of little value. P53 and Ki-67 proliferation antigens may be useful in differentiating benign and malignant PTs, but not FAs from PTs. Benign Phyllodes Tumor: A leaf-like growth pattern is evident with mildly increased stromal cellularity.

Borderline Phyllodes Tumor: The stroma is cellular with moderately atypical nuclei, mitotic activiity, and cellular stroma.

Borderline Phyllodes Tumor: The stroma is cellular with moderately atypical nuclei, mitotic activiity, and cellular stroma.

Care must be exercised by the pathologist and clinician in evaluating any fibroepithelial lesion by core needle biopsy. The clefts and leaf-life structures are often incomplete or inapparent due to limited sampling and fragmentation. A lesion with the previously noted architectural changes or with stromal hypercellularity and condensation of stroma around glands should be considered a potential PT and completely excised. To further complicate the issue, the heterogeneous distribution of stroma in some PTs may result in a core needle biopsy that shows exclusively benign appearing fibrous tissue or pseudoangiomatous stromal hyperplasia; the result of sampling variation. As always, clinical and radiographic correlations are paramount in the final analysis.

Borderline Phyllodes Tumor: There are leaf like projections with condensation of cellular stroma under the benign epithelium and relatively hypocellular stroma mixed in. Sampling of the latter by needle core biopsy could result in the erroneous impression of a benign lesion.

Borderline Phyllodes Tumor: There are leaf like projections with condensation of cellular stroma under the benign epithelium and relatively hypocellular stroma mixed in. Sampling of the latter by needle core biopsy could result in the erroneous impression of a benign lesion.

The treatment for FAs ranges from close follow-up to complete excision. All phyllodes tumors should be completely excised for adequate margins. Any of these lesions can recur if not completely excised and may recur at a higher grade. The rate of local recurrence for benign, borderline, and malignant PTs is 10%, 20%, and 50%. Local recurrence is more common in the lower grade tumors while metastases may develop in the higher grade tumors, more commonly to the lungs and bone. Lymph node metastases are uncommon but do occur.

At Incyte Diagnostics, all benign and malignant fibroepithelial tumors are reviewed by a second pathologist before the final diagnosis is rendered.

 

Advertisements

Comments are closed.