Phyllodes Tumor (Cystosarcoma Phyllodes) 

Updated: Jul 23, 2019
Author: Donald R Lannin, MD; Chief Editor: John Geibel, MD, MSc, DSc, AGAF 

Overview

Background

Phyllodes tumor—once more commonly referred to as cystosarcoma phyllodes (from Greek kystis ["sac, bladder"], sarkoma ["fleshy tumor"], and phyllon ["leaf"])—is a rare, predominantly benign tumor that occurs almost exclusively in the female breast.[1, 2] Grossly, the tumor displays characteristics of a large, malignant sarcoma, takes on a leaflike appearance when sectioned, and displays epithelial, cystlike spaces when viewed histologically.

Because most of these tumors are benign, the term cystosarcoma is potentially misleading. Accordingly, the term currently favored is phyllodes tumor.

Pathophysiology and Etiology

Phyllodes tumor is the most commonly occurring nonepithelial neoplasm of the breast, though it represents only about 1% of tumors in the breast.[3]  It has a smooth, sharply demarcated texture and typically is freely movable. It is a relatively large tumor, with an average size of 5 cm (though lesions larger than 30 cm have been reported). The etiology of phyllodes tumors is unknown.

Because of limited data, the relative percentages of benign and malignant phyllodes tumors are not well defined. Reports have suggested, however, that about 85-90% of phyllodes tumors are benign and that approximately 10-15% are malignant.[4]

Although benign phyllodes tumors do not metastasize, they have a tendency to grow aggressively and can recur locally.[3]  Like other sarcomas, malignant phyllodes tumors metastasize hematogenously. Unfortunately, the pathologic appearance of a phyllodes tumor does not always predict the neoplasm's clinical behavior; in some cases, therefore, there is a degree of uncertainty about the lesion's classification.

The characteristics of a malignant phyllodes tumor include the following[5] :

  • Recurrent malignant tumors seem to be more aggressive than the original tumor
  • The lungs are the most common metastatic site, followed by the skeleton, heart, and liver
  • Symptoms of metastatic involvement can arise from as early as a few months to as late as 12 years after the initial therapy
  • Most patients with metastases die within 3 years of the initial treatment [6]
  • No cures for systemic metastases exist
  • Roughly 30% of patients with malignant phyllodes tumors die of the disease

Although most phyllodes tumors are benign, it is nonetheless important not to underestimate the potential of these lesions for malignancy. Moreover, some juvenile fibroadenomas in teenagers can look like phyllodes tumors on histologic examination; however, they behave in a benign fashion similar to that of other fibroadenomas. The difficulty of distinguishing among fibroadenomas, benign phyllodes tumors, and malignant phyllodes tumors may be vexing for even the most experienced pathologist.[7]

Epidemiology

Phyllodes tumors occur almost exclusively in females, though rare cases have been reported in males. The tumors can develop in people of any age; however, the median age is the fifth decade of life.

Prognosis

If a phyllodes tumor is benign, the long-term prognosis is excellent after adequate local excision. However, the possibility for local recurrence after excision always exists, particularly with lesions that display malignant histology.[8, 9, 10] If the tumor recurs locally after excision, further local excision or total mastectomy is typically curative. Metastatic disease is typically observed in the lung, mediastinum, and skeleton.[5]

A study from the British Columbia Cancer Agency analyzed local recurrence, overall survival, and disease-free survival (DFS) in 183 patients with newly diagnosed benign (n = 83), borderline (n = 50), or malignant (n = 49) phyllodes tumors who were followed for a median of 65 months (range, 0.5-197 months).[11]  Overall, 8.7% experienced local recurrence, 4.4% distant metastasis, and 3.8% cause-specific death. With respect to individual subgroups, 5-year outcomes for women with benign, borderline, and malignant phyllodes tumors were as follows:

  • Local recurrence - 6%, 9%, and 21%, resectively
  • Overall survival - 96%, 100%, and 82%, respectively
  • DFS - 94%, 91%, and 67%, respectively

The 5-year local recurrence rates were 8% for women with negative margins, 6% for those with close margins, and 37% for those with positive margins.[11] The corresponding rates for intermediate, pushing, and infiltrative borders were 6%, 6%, and 33%, respectively. Positive margins and infiltrative tumor borders were significantly associated with increased local recurrence.

Patient Education

As for all breast neoplasms, self-examination remains the most important initial detection mechanism for phyllodes tumors. Appropriate teaching of this procedure is vital for early detection of all breast neoplasms.

For patient education information, see the Women's Health Center and the Cancer Center, as well as Breast Cancer and Breast Self-Exam.

 

Presentation

History

Phyllodes tumors generally manifest as larger masses and display rapid growth. A small mass may rapidly increase in size in the few weeks before the patient seeks medical attention. Tumors rarely involve the nipple-areola complex or ulcerate to the skin. Patients with metastases may present with such symptoms as dyspnea, fatigue, and bone pain.

Physical Examination

A firm, mobile, well-circumscribed, nontender breast mass is appreciated. Curiously, phyllodes tumors tend to involve the left breast more commonly than the right. Overlying skin may display a shiny appearance and be translucent enough to reveal underlying breast veins. A very large phyllodes tumor may erode through overlying skin and present as an external fungating breast mass.[12] More typically, physical findings (ie, the occurrence of mobile masses with distinct borders) are similar to those of fibroadenoma.[7]

 

DDx

Diagnostic Considerations

Conditions to consider in the differential diagnosis of phyllodes tumors include the following:

  • Angiosarcoma
  • Breast cancer
  • Juvenile fibroadenoma
  • Giant fibroadenoma
  • Inflammatory carcinoma
  • Sclerosing adenosis
  • Radial scar
  • Fat necrosis
  • Fibrocystic change
  • Breast abscess
  • Adenocarcinoma
  • Mastitis
 

Workup

Laboratory Studies

No specific hematologic tumor markers or other blood tests can be used to diagnose phyllodes tumors, though expression of biologic markers can discriminate between different grades of tumor.[13, 14] The immunohistochemical expression of CD10 can predict the occurrence of distant metastasis.[15] Investigation of a malignant phyllodes tumor with whole genomic and proteomic analysis revealed chromosome mutations, amplifications, and deletions.[16] Further exploration of the biology of phyllodes tumor may lead to the development of targeted treatments.

Imaging Studies

Although mammography and ultrasonography generally are important in the diagnosis of breast lesions, they are notoriously unreliable in differentiating benign phyllodes tumors from malignant phyllodes tumors or from fibroadenomas. (The phyllodes tumor’s mammographic appearance, as a round density with smooth borders, is similar to that of fibroadenoma.) Thus, findings on imaging studies are not definitively diagnostic of phyllodes tumors.[17]

A retrospective study by Kawashima et al suggested that intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) could differentiate phyllodes tumors from fibroadenomas by comparing the apparent diffusion coefficient (ADC) values.[18]  The study included seven fibroadenomas and 15 phyllodes tumors (10 benign, four borderline, and one malignant). The authors found that on IVIM MRI, the ADC was higher in borderline and malignant phyllodes tumors than in fibroadenomas, whereas the opposite was true for the perfusion-related diffusion coefficient (D*).

 

Biopsy

Open excisional breast biopsy for smaller lesions and incisional biopsy for large lesions are the definitive methods for diagnosing phyllodes tumors. Fine-needle aspiration (FNA) for cytologic examination usually is inadequate for the diagnosis of phyllodes tumors. Core biopsy is more reliable,[19, 20]  but sampling errors may still occur, and it may still be difficult to distinguish the lesion from a fibroadenoma.

Histologic Findings

All phyllodes tumors contain a stromal component that can vary significantly in histologic appearance from one lesion to another.[15]  In general, benign phyllodes tumors demonstrate a markedly increased number of regular fusiform fibroblasts in the stroma. Occasionally, highly anaplastic cells with myxoid changes are observed. A high degree of cellular atypia, with increased stromal cellularity and an increased mitotic count, is almost always observed in malignant phyllodes tumors.

Ultrastructurally, in both benign and malignant forms of phyllodes tumors, nucleoli may reveal a coarsely meshed nucleolonema and abundant cisternae in the endoplasmic reticulum.

Staging

The World Health Organization (WHO) divided phyllodes tumors into the following three categories[21] :

  • Benign (grade 1)
  • Borderline (grade 2)
  • Malignant (grade 3)

In a retrospective multicentric cohort study that included 230 patients who underwent breast surgery for grade 1 (benign; n = 144), 2 (borderline; n = 60) or 3 (malignant; n = 26) phyllodes tumor,[22] Adam et al concluded that the surgical margin should be at least 5 mm regardless of tumor grade. On the basis of a finding that moderate-to-severe nuclear stromal pleomorphism identified a grade 1 subgroup with a higher rate of recurrence, they suggested that the WHO classification could be revised by introducing consideration of nuclear stromal pleomorphism.

 

Treatment

Tumor Excision and Mastectomy

Complete excision, with accurate histologic examination and continued follow-up care, is the best way to treat phyllodes tumors. A general surgery specialist should be consulted.

In most cases, wide local excision is indicated, with a rim of normal tissue included.[23, 24, 8]  No absolute rules regarding margin size have been established.[25]  However, a 2-cm margin for small (< 5 cm) tumors and a 5-cm margin for large (>5 cm) tumors have been advocated.

Guidelines on benign breast tumors from the French College of Obstetrics and Gynecology (CNGOF) recommended surgical resection with clear margins for grade 1 (benign) phyllodes tumors and resection with 10-mm margins for grade 2 (borderline) phyllodes tumors.[26]  

The lesion should not be "shelled out," as might be done with a fibroadenoma, or the recurrence rate will be unacceptably high.[6]

If the tumor-to-breast ratio is sufficiently high to preclude a satisfactory cosmetic result with segmental excision, total mastectomy, with or without reconstruction, is an alternative. More radical procedures generally are not warranted.[24]

Axillary lymph node dissection should be performed only for clinically suspicious nodes. However, virtually all of these nodes are reactive and do not contain malignant cells.[27]

There is no proven role for adjuvant chemotherapy or radiation therapy in the treatment of phyllodes tumors. Response to chemotherapy and radiotherapy for recurrences and metastases has been poor, and no success with hormonal manipulation has been documented.

Complications

Surgical treatment of phyllodes tumors, like most surgical procedures of the breast, may have the following complications:

  • Infection
  • Seroma formation
  • Local or distant recurrence

Long-Term Monitoring

Although specific guidelines regarding follow-up care for phyllodes tumors are limited because of the rarity of these lesions, regular, long-term follow-up care should be performed to detect possible local recurrences.

An initial visit 1-2 weeks after surgery to detect any initial complications should be followed by periodic visits as determined by the patient's surgeon. A reasonable schedule might be physical examinations every 6 months and mammograms yearly for at least 5 years. Carefully observe patients for any possible recurrence.

 

Questions & Answers

Overview

What is phyllodes tumor (cystosarcoma phyllodes)?

What is the pathophysiology of phyllodes tumor (cystosarcoma phyllodes)?

What are the characteristics of a malignant phyllodes tumor (cystosarcoma phyllodes)?

How are benign phyllodes tumors (cystosarcoma phyllodes) differentiated from juvenile fibroadenomas?

What is the prevalence of phyllodes tumors (cystosarcoma phyllodes)?

What is the prognosis of phyllodes tumor (cystosarcoma phyllodes)?

What are the rates of recurrence of phyllodes tumors (cystosarcoma phyllodes)?

What is included in patient education about phyllodes tumor (cystosarcoma phyllodes)?

Presentation

Which clinical history findings are characteristic of phyllodes tumor (cystosarcoma phyllodes)?

Which physical findings are characteristic of phyllodes tumor (cystosarcoma phyllodes)?

DDX

Which conditions are included in the differential diagnoses of phyllodes tumor (cystosarcoma phyllodes)?

Workup

What is the role of lab tests in the workup of phyllodes tumor (cystosarcoma phyllodes)?

What is the role of imaging studies in the workup of phyllodes tumor (cystosarcoma phyllodes)?

What is the role of biopsy in the workup of phyllodes tumor (cystosarcoma phyllodes)?

Which histologic findings are characteristic of phyllodes tumor (cystosarcoma phyllodes)?

How are phyllodes tumors (cystosarcoma phyllodes) staged?

Treatment

How are phyllodes tumors (cystosarcoma phyllodes) treated?

What are the possible complications of phyllodes tumor (cystosarcoma phyllodes) surgery?

What is included in the long-term monitoring of phyllodes tumor (cystosarcoma phyllodes)?