Phyllodes Tumor Of The Breast

Continuing Education Activity

Phyllodes tumor of the breast is a relatively rare fibroepithelial neoplasm that presents a morphologic continuum from benign to malignant. Most phyllodes tumors behave benignly, with local recurrences occurring in a small proportion of cases. Very rarely, the tumor may metastasize. This activity describes the evaluation and treatment of phyllodes tumors and highlights the interprofessional team's role in managing patients with this condition.


  • Identify the etiology of phyllodes breast tumors.
  • Describe the evaluation of phyllodes breast tumors.
  • List the treatment and management options available for phyllodes tumors of the breast.
  • Employ interprofessional team strategies for improving care coordination and communication to advance the management of phyllodes breast tumors and improve outcomes.


Phyllodes tumor of the breast is an infrequently encountered fibroepithelial neoplasm, which accounts for 0.3% to 1% of all tumors.[1] Phyllodes tumor presents a morphologic continuum from benign to malignant. Based on histologic features, including nuclear atypia, stromal cellularity, mitotic activity, tumor margin appearance, and stromal overgrowth, the World Health Organization (WHO) classifies Phyllodes tumors benign, borderline, and malignant.[1] Phyllodes tumors have an inherent recurrence and/or metastatic potential, which varies based on histologic grade. Their diagnosis is mainly established based on histopathological examination. However, the differential diagnosis between benign phyllodes tumors and fibroadenoma remains challenging, especially on core biopsy specimens.


Genetic risk factors of phyllodes tumors are largely unknown, but the literature describes phyllodes tumors in Li-Fraumeni syndrome patients and a mother and daughter pair.[2] Rare cases of phyllodes tumors in men are often associated with gynecomastia, suggesting a role for hormonal imbalance.[3]

Researchers have postulated that stromal induction of phyllodes tumors can occur due to growth factors produced by the breast epithelium. Trauma, pregnancy, increased estrogen activity, and lactation are occasionally implicated as factors stimulating tumor growth. The nature of these factors is not well understood, but endothelin-1, a stimulator of breast fibroblast growth, might be a contributory factor.[4]


Phyllodes tumors occur predominantly in middle-aged women (average age at presentation, 40 to 50 years) about 15 to 20 years later than fibroadenomas.[5]

Phyllodes tumor occurs mainly in women, although there are reports of some cases in men.[6]

Data analysis from the Surveillance, Epidemiology, and End Results Program (SEER) data registry from 2000 to 2004 reported that 500 women are diagnosed with malignant phyllodes tumors in the US annually.[7]


Unlike breast carcinoma, phyllodes tumors start outside of the lobules, and ducts, in the breast’s connective tissue, called the stroma, including the ligaments and fatty tissue surrounding the lobules, ducts, lymph, and blood vessels in the breast. In addition to epithelial cells from the ducts and lobules, phyllodes tumors can also contain stromal cells.[8] They most likely develop de novo, although there have been reports of progression of fibroadenoma to phyllodes tumor.[9]

Molecular Features

Recent studies have focused on defining a molecular classification of phyllodes tumors. Comparative genomic hybridization studies showed recurrent chromosome imbalances, including +1q, −6q, −13q, −9p, −10p, and +5p. Although currently no chromosomal aberrations were found to be specific to phyllodes tumors, some authors reported that low-grade and high-grade (borderline/malignant) phyllodes tumors segregate in two genetic groups based on genomic alterations, with high-grade phyllodes tumors consistently showing 1q gain and 13q loss and low-grade phyllodes tumors showing few or no alterations.[10] Preliminary data from array comparative genomic hybridization (CGH) demonstrate interstitial deletion 9p21 involving the CDKN2A locus and 9p deletion in malignant and some borderline phyllodes tumors.[11]


Macroscopic Examination

Phyllodes tumors form well-circumscribed, firm, protruding masses. When cut, the surface is tan or pink to grey and may present as fleshy and mucoid. The characteristic whorled pattern with curved clefts resembling leaf buds is most evident in large lesions, but smaller lesions may have a homogeneous appearance. Hemorrhage or necrosis may be present in large lesions.[1]

Microscopic Examination

Phyllodes tumors exhibit an enhanced intra-canalicular growth pattern with leaf-like projections into variably dilated elongated lumina. The epithelial component consists of luminal epithelial and myoepithelial cells stretched into arc-like clefts surmounting stromal fronds.[1]


There have been proposals for several grading systems, but the use of the three-tiered system, including benign, borderline, and malignant phyllodes tumor, is preferred because this approach leads to greater certainty at the ends of the spectrum of these fibroepithelial lesions.[1]

Benign Phyllodes Tumors

This variety comprises 60% to 75% of all phyllodes tumors. In benign phyllodes tumors, the stroma is usually more cellular than in fibroadenomas. The spindle-cell stromal nuclei are uniform, and mitoses are rare, generally less than 5 per 10 high-power fields. Areas of sparse stromal cellularity, hyalinization, or myxoid changes are not uncommon, reflecting stromal heterogeneity. The margins are usually well-delimited and pushing.[1]

Borderline Phyllodes Tumors

These tumors are diagnosed when the mass does not possess all the adverse histological characteristics found in malignant phyllodes tumors. 

Borderline phyllodes tumors may have frequent mitoses (5 to 9 per 10 HPF), moderate stromal cellularity, a circumscribed or focally invasive border,  and stromal atypia. Stromal overgrowth is often absent.

Malignant Phyllodes Tumors

Malignant phyllode tumors show a combination of marked nuclear pleomorphism of stromal cells, stromal overgrowth defined as the absence of epithelial elements in one low-power microscopic field containing only stroma, increased mitoses (greater than or equal to 10 per 10 HPF), increased stromal cellularity, which is usually diffuse, and infiltrative borders.[1]


Multiple immunohistochemistry markers have undergone a study in an attempt to improve the classification of PT and predict their outcomes. Studies demonstrate that p53, Ki67, CD117, EGFR, p16, and VEGF (being the lowest in benign phyllodes tumors and the highest in malignant phyllodes tumors) are associated with histologic grades of phyllodes tumors, but none has been proven to be clinically useful.[12][13][14][15]

Among these markers, p53 expression and Ki67 index were reported in some studies to be significantly associated with disease-free and overall survivals,  but other studies found no association with recurrence or clinical behavior.[16][17]

PAX3 and SIX1 expression by immunohistochemistry and gene expression analysis have recently been identified in borderline and malignant phyllodes tumors and correlate with a poor clinical outcome.[18]

History and Physical

Clinically, phyllodes tumors tend to present as unilateral firm, enlarging painless breast masses that stretch the overlying skin with striking distension of superficial veins.

The size may range from 1 to 45 cm and may occupy the entire breast.

Bloody nipple discharge caused by spontaneous infarction of the tumor has been described.

Ulceration and nipple retraction are uncommon.

Although axillary lymphadenopathy is common, nodal metastases are the exception.[19]


The imaging findings on mammography are typically round lobulated dense mass with partially indistinct or circumscribed margins. Calcifications within the mass are rare, but they can be large.[20]

On ultrasound, phyllodes tumor present as a hypoechoic, partially indistinct, or partially circumscribed mass with frequent posterior enhancement. A cystic component is more typical in malignant phyllodes tumors. Frequently phyllodes tumor will show increased vascularity on color or power Doppler.[21] MRI evaluation may be of benefit to evaluate for chest wall invasion in malignant phyllodes tumor. The characteristics present on MRI are typically heterogeneously low signal on T1-weighted images, although areas of T1-hyperintense hemorrhage may be visible. T2-weighted images usually show a lobulated mass with hyperintense fluid in slit-like spaces and sometimes hyperintensity in the surrounding tissues.[22]

Treatment / Management

Complete wide local excision with greater than 1 cm margins is often curative and reduces the risk of local recurrence.[23]  Large tumors require a mastectomy. Despite the higher incidence of local recurrence secondary to breast-conserving surgery, studies have shown no differences between breast-conserving surgery versus mastectomy regarding metastasis-free survival or overall survival. Adjuvant therapy options mainly include radiation therapy, which has been found to reduce local recurrence. Research has not shown a clinical benefit with giving adjuvant chemotherapy.[24]

Differential Diagnosis

  • Fibroadenoma: The principal differential diagnosis for benign phyllodes tumor is fibroadenoma having a pronounced intracanalicular pattern.[25]
  • Sarcomas: malignant phyllodes tumor may be confused with pure sarcomas of the breast.[26]
  • Periductal stromal tumor: the periductal stromal tumor is an entity that histologically overlaps with malignant phyllodes tumor, the main difference being the absence of leaf-like processes. It is non-circumscribed, consisting of spindle-cell proliferation localized around open tubules.[27]
  • Metaplastic carcinoma: carcinoma is also in the differential diagnosis of malignant phyllodes tumor, but the immunohistochemical demonstration of epithelial differentiation helps resolve the problem.


The prognosis of phyllodes tumor is good, with an 87% 10-year survival. The recurrence risk varies with tumor size and surgical approach.

Most phyllodes tumors behave benignly, with local recurrences occurring in a small proportion of cases. Very rarely, the tumor may metastasize, most commonly in the cases of malignant grade tumors. 

Malignant phyllodes tumors carry a poor prognosis.


Local Recurrence

Local recurrences can occur in all phyllodes tumors, at an overall rate of 21%, with ranges of 10% to 17%, 14% to 25%, and 23% to 30% for benign, borderline malignant, and phyllodes tumors, respectively. Local recurrences generally develop within 2 to 3 years.[28]

Distant Metastases

Distant metastases are almost exclusively a feature of malignant phyllodes tumors. The lungs (66%), the bones (28%), and the brain (9%) are the most common sites of spread.[28] Rarely, metastases can involve the liver and heart.


  • Surgical oncologist
  • Oncologist

Deterrence and Patient Education

Patients might be instructed to self-examine their breasts regularly and consult their doctors if any abnormality is detected.

Enhancing Healthcare Team Outcomes

Accurate preoperative pathological diagnosis of phyllodes tumors enables adequate surgical planning and avoidance of reoperation. The distinction between phyllodes tumor and fibroadenoma is important but can be difficult on core biopsy. Management of phyllodes tumor needs an approach involving an interprofessional team that consists of a surgical oncologist, an oncologist, a pathologist, and a radiologist along with oncology specialty-trained nurses, all working together as an interprofessional team to deliver the best clinical results. [Level V]

The primary care provider and nurse practitioner must refer patients with suspected breast masses to an oncologist for further workup. Treatment can be either wide local excision or mastectomy to achieve histologically clear margins. After the treatment of phyllodes tumor, long-term follow-up by the primary care providers/nurse practitioner is necessary to detect local and distant relapse. 

(Click Image to Enlarge)
Phylloides tumor of the breast, benign. H/E 4x
Phylloides tumor of the breast, benign. H/E 4x
Contributed by Fabiola Farci, MD

(Click Image to Enlarge)
Phylloides tumor of the breast, benign. H/E 4x
Phylloides tumor of the breast, benign. H/E 4x
Contributed by Fabiola Farci, MD
Article Details

Article Author

Faten Limaiem

Article Editor:

Sarang Kashyap


11/10/2020 7:43:31 AM



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