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J Radiol Case Rep. 2013 February; 7(2): 24–37.
Published online 2013 February 1. doi:  10.3941/jrcr.v7i2.1430
PMCID: PMC3661309

Unusual Aggressive Breast Cancer: Metastatic Malignant Phyllodes Tumor


For the year of 2012, it has been estimated that breast cancer will account for the greatest number of newly diagnosed cancers and the second highest proportion of cancer related deaths among women. Breast cancer, while often lumped together as one disease, represents a diverse group of malignancies with different imaging findings, histological appearances and behavior. While most invasive primary breast cancers are epithelial derived adenocarcinomas, rare neoplasms such as the phyllodes tumor may arise from mesenchymal tissue. Compared to the breast adenocarcinoma, the phyllodes tumor tends to affect a younger population, follows a different clinical course, is associated with different imaging and histological findings and is managed distinctively. There may be difficulty in differentiating the phyllodes tumor from a large fibroadenoma, but the mammographer plays a key role in reviewing the clinical and imaging data in order to arrive at the correct diagnosis. Early diagnosis with proper surgical management can often cure non-metastatic phyllodes tumors. However, in rare cases where metastasis occurs, prognosis tends to be poor. This report describes the presentation, imaging findings and management of a metastatic malignant phyllodes tumor.

Keywords: phyllodes, cystosarcoma phyllodes, breast cancer, mesenchyal breast tumor, metastatic, enhancing septations


For the year of 2012, it has been estimated that breast cancer will account for the greatest number of newly diagnosed cancers and the second highest proportion of cancer related deaths among women [1]. Breast cancer, while often lumped together as one disease, represents a diverse group of malignancies with different imaging findings, histological appearances and behavior. Most invasive primary breast cancers are epithelial derived adenocarcinomas with the most common histological subtype being the invasive ductal adenocarcinoma accounting for approximately 75% of cases [2]. Overwhelmingly diagnosed in women and arising from mesenchymal tissue, phyllodes tumors (PTs) are rare breast cancers which account for between 0.3 and 1% of primary breast cancers [3,4] (Table 1). Unfortunately, there are similarities between the primary breast adenocarcinoma and the PT which can make differentiation difficult. The PT also shares much in common with the benign fibroadenoma. Therefore, in order to ensure prompt and correct treatment, it is imperative that the mammographer uses all of the available information to make the correct diagnosis.

Table 1
Summary table for phyllodes tumor

The clinical presentation of the PT is different compared to that of the breast adenocarcinoma. First, while both the breast adenocarcinoma and PT can occur at any age, the mean age of diagnosis of breast cancer in general in women is 61 [11]. In contrast, multiple studies have shown that the diagnosis of the PT tends to occur at an earlier age [4,5,8,9,10]. In a review of seventeen studies each describing at least twenty patients or more diagnosed with PTs, Parker et al. determined that the mean age at diagnosis is 45, twenty years older than the typical age range of fibroadenoma proliferation [12]. By contrast, the peak age range of fibroadenoma detection has been described as 20–25 years old [19]. Second, the PT tends to be larger than the adenocarcinoma and is classically characterized by rapid growth. Parker et al. describe cases of tumors becoming as large as forty centimeters (cm) in diameter. While these clinical findings help in making the diagnosis of a PT, they are not specific. The next step in working up such a breast lesion involves imaging. Unfortunately, although there are imaging findings that aid in making the diagnosis of a PT, none are pathognomonic. Unlike other commonly encountered breast lesions, percutaneous biopsy is often not sufficient to arrive at a conclusive diagnosis because there are histopathological similarities between the fibroadenoma and the PT. Moreover, percutaneous biopsy may result in insufficient sampling because the behavior of the tumor is determined by the most malignant cells. Therefore, excisional biopsy is often required to make a definitive diagnosis [19]. The excisional biopsy is also the treatment of choice because even the benign PT is well known for local aggressiveness.

In this manuscript, a patient diagnosed with metastatic malignant PT is described and the multimodality imaging findings of the metastases are characterized. The aims include adding information to the relatively small database of PT imaging findings and to describe imaging findings typical of the PT, the histopathological correlation and current management strategies.


A 43 year old Latin female from Honduras with no significant past medical history presented with a palpable left breast mass which she first noticed five months prior to admission. She noted that over the two months leading up to her admission, this mass had rapidly increased in size and was associated with pain and pruritus. The patient experienced menarche at the age of 12, gave birth to five children starting at the age of 22, did not breast feed and denied prior use of oral contraceptives or hormonal replacement therapy. She had no history of prior chest radiation therapy and had no known family history of PT. Upon initial physical examination, the patient was afebrile with normal vital signs. Examination of the left breast revealed a very large lobulated mass with thinning of the overlying skin, nipple inversion and no palpable axillary or supraclavicular lymphadenopathy. The right breast was normal. The patient could not tolerate mammography due to the size of the tumor. A contrast enhanced computed tomographic (CT) study of the chest, abdomen and pelvis was performed to evaluate the breast mass and for the presence of metastatic disease. A large, heterogeneous left breast mass that measured 19 × 24 × 25 cm was visualized. The mass was mostly cystic (measuring −9.1 Hounsfield units), but contained thick, irregular enhancing septations and was surrounded by a thick enhancing wall (Figure 1). The mass abutted the left pectoralis major muscle. Also identified were bilateral pulmonary nodules, the largest of which measured 6 mm.

Figure 1
43 year old female with malignant phyllodes tumor. Contrast enhanced CT of the chest, abdomen and pelvis. 410 mAs, 120 kVP, 1.5 and 5.0 millimeter (mm) slices.

A percutaneous biopsy of the breast mass was performed which revealed a high grade malignant spindle cell neoplasm representing either a metaplastic sarcomatoid carcinoma or a malignant PT (not shown). Given the bulk of the tumor and the patient’s resultant discomfort, mastectomy was elected. During surgery, the mass was noted to invade the pectoralis major muscle necessitating partial resection. A left pectoralis major flap was utilized for reconstruction. Following resection, the mass weighed 16 pounds. Pathologically, the mass was described as a high grade PT with sarcomatous overgrowth (Figure 2). Immunohistochemistry was positive for CD10 and negative for ER, PR, HER2, CD34, desmin, S100, p63 and CK903. The negative CK903 and p63 excluded the possibility of a myoepithelial or squamous spindle cell carcinoma and the negative S100 and CD34 excluded the possibility of a myofibroblastic or neurogenic sarcoma.

Figure 2
43 year old female with malignant phyllodes tumor.

One month following the surgery, the patient became aware of a soft tissue mass growing at the mastectomy scar. Upon physical examination, there were post surgical changes consistent with a left mastectomy and a new parasternal 10 cm non-mobile, non-tender mass fixed to the medial portion of the scar. There was no palpable axillary lymphadenopathy. A non-enhanced CT of the chest was performed which demonstrated a lobulated soft tissue mass superficial to the sternum that measured 9 × 6 × 8 cm without definite involvement of the sternum, although periosteal reaction was identified. (Figure 3A and C). Bilateral stable pulmonary nodules were again visualized. The patient was started on Adriamycin and ifosfamide. Following two cycles, a contrast enhanced CT of the chest demonstrated that the mass had a cystic component, with a thick, irregular, enhancing wall and enhancing septations and now measured 13 × 7 × 9 cm (Figure 3B). Stable pulmonary nodules and sternal periosteal reaction was identified. Due to progression in spite of therapy, the decision was made to treat with radiation therapy and gemcitabine. After completing chemotherapy and radiation with a total dose of 5000 cGy, the patient underwent resection of the parasternal mass. The mass was removed en bloc with partial resection of the sternum, the bilateral third, fourth and fifth ribs and the bilateral costal cartilages of ribs six and seven. Upon exposure of the lungs, multiple bilateral lung masses were visualized four of which were biopsied. A rectus abdominis free flap was used to reconstruct the anterior chest wall. Histopathologically, the chest wall mass contained pleomorphic tumor cells and areas of treatment related necrosis (Figure 4).

Figure 3
43 year old female with malignant phyllodes tumor. CT of the chest. 76 mAs, 120 kVP, 5.00 mm slices.
Figure 4
43 year old female with malignant phyllodes tumor. Chest wall mass showing metastatic malignant phyllodes tumor with an area of necrosis consistent with treatment effect. H&E section, 10× magnification.

Two months later, the patient noted diminished ability to use her right lower extremity due to worsening right hip pain. A femoral radiograph was obtained and a permeative pattern with associated periosteal reaction was visualized in the proximal femur (Figure 5). These findings were concerning for metastatic disease and a Technetium 99m (Tc99m) labeled methylene diphosphonic acid (MDP) bone scan confirmed new radiotracer uptake in the proximal femur corresponding to the radiographic abnormality, not present on a bone scan obtained eight months previously (Figure 6). Subsequently, a CT guided bone biopsy was performed (Figure 7) which confirmed the presence of a spindle cell tumor consistent with the patient’s known history of malignant PT. Next, magnetic resonance imaging (MRI) of the femur was acquired (Figure 8) to evaluate disease extent and to aid in surgical planning which showed a soft tissue mass adherent to the femur with diffuse infiltration of the cortical and medullary bone. The mass measured 4.0 × 4.4 × 2.1 cm and demonstrated low T1 signal intensity, contrast enhancement and high T2 signal intensity. The increased T2 signal intensity and enhancement both within the soft tissue surrounding the mass and within the vastus lateralis muscle raised suspicion for local invasion. The underlying femoral cortex was thinned and in some places was destroyed. The marrow signal intensity in the involved portion of the proximal femur was markedly abnormal with low T1 signal intensity, high T2 signal intensity and heterogenous areas of enhancement, mostly peripherally. Upon surgical excision, invasion of the vastus lateralis muscle was confirmed necessitating partial resection. The proximal right femur was resected and a megaprosthesis was placed. The gross specimen demonstrated tumor adherent to the femur with diffuse tumor infiltration of the medullary cavity (Figure 9), compatible with the MRI findings. Light microscopy again verified the presence of spindle cell tumor cells confirming the diagnosis of metastatic PT (Figure 10).

Figure 5
43 year old female with malignant phyllodes tumor. Femur radiographs.
Figure 6
43 year old female with malignant phyllodes tumor. Bone scan utilizing 25.5 mCi Tc99m labeled MDP with acquisition of delayed planar and spot images.
Figure 7
43 year old female with malignant phyllodes tumor. CT guided bone biopsy. Coaxial system of bone needles advanced under CT guidance into the intertrochanteric region where the permeative pattern was best visualized.
Figure 8
43 year old female with malignant phyllodes tumor. Contrast enhanced MRI of the right femur (Siemens Avanto 1.5 tesla)
Figure 9
43 year old female with malignant phyllodes tumor. Gross surgical specimen following resection with demonstration of medullary cavity tumor infiltration, cortical destruction and tumor adherent to the external cortical surface.
Figure 10
43 year old female with malignant phyllodes tumor. Metastatic phyllodes tumor infiltration of the right femoral medullary cavity. H&E section, 10× magnification.

One month later, the patient presented to the emergency department with shortness of breath. A CT demonstrated significant progression of disease (Figure 11) with a large necrotic left breast mass invading the chest wall. Additionally, there was a large necrotic right axillary mass that measured 11 × 10 × 9 cm. Also identified were a right breast mass and multiple large pleural based masses, the largest of which measured 13 × 5 cm. There were numerous pulmonary nodules, some of which were new, areas of pulmonary parenchymal consolidation and a left pleural effusion. At this point, the decision was made to transition towards palliative care and the patient was discharged to home hospice.

Figure 11
43 year old female with malignant phyllodes tumor. Non-enhanced chest CT. 305 mAs, 120 kVP, 1.5 mm slices.


With the first reported case in 1838 by Johannes Müller, PTs derive their name from their histological appearance that is characterized by a leaf like architecture containing varying degrees of epithelial and mesenchymal elements. The epithelial component tends to line thin cystic spaces, hence the historical (but no longer used) name cystosarcoma phyllodes. The mesenchymal cells represent the neoplastic portion of the PT. The epithelial component is essential for making the diagnosis of a phyllodes tumor because in its absence, the presence of spindle shaped cells suggests an alternative diagnosis such as a sarcoma [12].

After a patient presents with a breast mass that is clinically concerning for a PT, imaging studies must be performed. Although non-specific, the imaging findings may aid in making the correct and timely diagnosis (table 2). The first step in management should be a mammogram. Mammographically, the PT usually appears as a hyperdense, large, rounded or lobulated mass with distinct margins [8,10,13,19]. In a study of 51 patients with PTs, 96% were non-spiculated masses. In this same study, larger tumor size was shown to correlate with a higher likelihood of malignancy. A size greater than 3 cm had a relative risk of malignancy of 3.87 (p < 0.004) while all tumors larger than 8 cm were malignant. Microcalcifications within a PT are unusual, especially those calcifications more commonly associated with ductal carcinoma in situ or invasive ductal carcinoma such as fine linear branching calcifications. If calcifications are present, they tend to be coarse [8]. Tan et al. speculate that the tendency of PTs to lack microcalcifications is due to the rapid tumor growth. Liberman et al. was able to estimate doubling time in five cases of phyllodes tumors and found that the doubling time for a single case of a malignant PT was 36 days, while the median doubling time of the four benign PTs was 211 days [13]. In another study of 34 PTs, the calculated median growth rate for the combined borderline and malignant tumors was 105% per month and 17% per month for benign tumors [19]. Gordon et al. analyzed a group of 194 breast lesions diagnosed as fibroadenomas by fine needle aspiration that were subsequently followed over time and found that an increase in size of up to 20% over a six month interval was consistent with a lesion that was benign [14]. These authors also stated that a mass with a size greater than 3 cm should be considered for excision because of an increased risk of representing a PT [14]. Percutaneous biopsy, while useful in evaluating epithelial derived neoplasia, may be less accurate when attempting to differentiate a fibroadenoma from a PT. In a group of 17 patients with PTs, Foxcroft et al. were able to make the correct diagnosis utilizing percutaneous core biopsy in 65% of cases. Fine needle aspiration (FNA) fared worse. Among 57 cases of PTs evaluated with FNA, the diagnosis was suggested in 13 cases (22.8%). In this group evaluated by FNA, 22 were diagnosed as fibroadenomas (38.5%). It is also important to note that the pathophysiology of PT proliferation is different than that of ductal and lobular cancer. Since the malignant cells are not associated with epithelial elements, the likelihood of ductal type microcalcifications typically regarded as suspicious is low. However, there are reported cases of epithelial derived breast cancer arising within a PT [16,17]. Therefore, the presence of suspicious microcalcifications in a mass that is otherwise concerning for a PT does not exclude the diagnosis of adenocarcinoma and a concomitant ductal carcinoma should be entertained in the differential.

Table 2
Differential diagnosis based on imaging characteristics for phyllodes tumor

Following mammography, breast ultrasound is the imaging modality of choice to characterize a breast mass and suspected PT. Sonographically, not only is it difficult to differentiate a PT from a fibroadenoma, but the ability to grade a PT with ultrasound is also limited [8]. In a study of the 24 PTs, half were diagnosed by ultrasound preoperatively as fibroadenomas [8]. In this same study, the only characteristic that statistically significantly differentiated between benign and borderline or malignant tumors was an irregular shape (X2 = 5.754, p = 0.039), which the authors speculated was related to different rates of proliferation within the high grade portions of the tumor. An irregular shape was described in 66.7% of malignant PTs, 90.9% of borderline PTs and 25% of benign PTs. One sonographic characteristic all of these tumors had in common was an overall heterogeneous appearance. In general, most authors describe the PT appearance, regardless of grade, as hypoechoic. Authors have described small cystic clefts which are sometimes visible and have been attributed to the cystic areas visualized pathologically. It has been suggested that their presence may indicate higher grade PTs. Clefts with a mean diameter of 8 mm were described in 4/9 and 3/21 malignant and benign PTs, respectively, but the difference between the two grades lacked statistical significance (p = 0.15) [13]. In another study including 78 PTs with available ultrasound examinations, Foxcroft et al. found cystic clefts or macrocysts associated with 4/5 malignant PTs. However, these clefts were found in 18 non-malignant PTs in the same study [19]. In another case, after utilizing mammography, breast ultrasound, breast MRI and percutaneous biopsy, El Khouli et al. described a case of a 25-year-old with an enlarging breast mass that measured 3 × 3 cm which required excisional biopsy to make the diagnosis of a giant fibroadenoma [18]. More recently, breast imagers have been utilizing ultrasound as a method to determine the relative elasticity of tumors. Adamietz et al. found that in eight cases of PTs, all had a relatively elastic center surrounded by an inelastic periphery, which the authors termed the “ring sign” [15].

MRI also may play a role in the evaluation of a suspected PT. In general, PTs are often described as heterogeneous. In one study of 21 PTs and 81 fibroadenomas, 71% of the PTs had a heterogeneous internal structure while only 41% of the fibroadenomas were described similarly [20]. On T1 weighted (T1W) sequences, the mass is usually either isointense or hypointense. However, hemorrhage has been documented to occur within these tumors which will result in foci of increased T1 signal intensity [8]. T2 weighted (T2W) sequences may be hypointense with the exception of focal areas of hyperintensity when there are cystic spaces or clefts present [20]. Necrosis may also result in increased T2 signal intensity. These masses often have internal septations that are hypointense on both T1 and T2 weighted sequences. Following the administration of intravenous contrast, these tumors often demonstrate rapid enhancement although the septations usually do not enhance. However, in the authors’ institution, there was one case of a pathologically proven benign PT with enhancing septations (figure 12). In one study, 33% of the PTs imaged with MR had suspicious enhancement kinetics [20]. Although the sample size is low, Wurdinger et al. finds that focal increased T2 signal around the mass is seen in 21% of PTs, but in only 1.2% of fibroadenomas (p =0.005) [20].

Figure 12
Pathology proven (images not shown) benign phyllodes tumor in a 42 year old female.

The role of CT is usually to assess for the degree of local invasion, recurrence or for the presence of metastasis. Since the workup of a breast mass typically does not include a CT, large studies evaluating the CT appearance of a PT have not been published. Suzuki-Uematsu et al. described a case of a malignant PT evaluated with contrast enhanced CT where the 10 × 10 cm mass was described as having a peripheral enhancing rim which is concordant with the CT findings of the patient described in this manuscript.

Currently, there are few reports describing the imaging appearance of osseous PT metastases. In this report, we describe such findings across four imaging modalities. While metastasis can present as a solid mass adjacent to the involved bone, it appears to rapidly infiltrate the cortex and medulla resulting in a permeative pattern on radiographs and CT. Bone scan may show increased Tc99m-MDP radiotracer uptake. Correspondingly, MRI may show a diffusely infiltrated bone with complete marrow replacement, avid enhancement, cortical destruction and significant surrounding soft tissue edema. More importantly, if surgical resection is to be considered, the MRI may better delineate the metastasis extent into the surrounding tissues which would aid the surgeon in terms of approach.

The PT is classified on the basis of its histological grade as benign, borderline or malignant. Grading is determined by evaluating the frequency of observed mitoses, the characteristics of the tumor margins, the stromal cellularity and the degree of atypia [5,12]. Another histological finding which is worrisome for increased aggressiveness is stromal overgrowth, defined as the presence of stroma without associated epithelial elements over one low power (x 40) field [13]. It has been estimated that 60% are benign, 20% are borderline and the remaining 20% are malignant [3]. With increasing tumor grade, studies have shown that the risk of metastasis increases [5,12]. In addition to grade, specific pathological findings have been shown to correlate to recurrence and metastasis with statistical significance. Chen et al. found that in patients with positive surgical margins, 6/13(46%), recurred locally, while only 13/159 (8%) with negative margins did (p = 0.00018). In terms of risk for metastasis, the same authors found that stromal cellularity, stromal overgrowth, stromal atypia, mitotic activity, tumor margin status and heterologous stromal elements correlated with statistical significance (p = 0.032, 0.00002, 0.004, 0.005 and 0.046, respectively) [5]. These authors also noted that of the three patients with metastases, all three were initially graded as benign and that all three eventually succumbed to their disease.

Regardless of grade, the primary method of treatment is surgical. Options include local excision, wide local excision and mastectomy. Wide excision is recommended because of the strong tendency for local recurrence (up to 20%), even in benign PTs [20]. In a study of 172 patients with PT conducted by Chen et al., local excision was defined as removal of the mass with no more than a 0.5 cm tumor free margin while wide local excision was defined as removal of the mass with at least a 1.0 cm tumor free margin. Of the 172 patients, 76% were benign, 7% were borderline and 17% were malignant. There was a tendency for less aggressive surgical treatment of lower grade tumors with mastectomy performed in 10% of benign cases, 67% of borderline cases and 86% of malignant cases. Local recurrence occurred only in the benign cases treated with local or wide local excision with a rate of approximately 15% [5]. When metastatic, lymph node involvement is rare with authors noting a rate of approximately 10% [4,5]. Among 42 patients who underwent a modified radical mastectomy, none had lymph node involvement [5]. Similarly, in a study with axillary nodal dissection performed in 42 patients with either PT or primary breast sarcoma, 2 patients had lymph node involvement, one of which was from a malignant PT [4]. In a third review, lymph node involvement was noted in 3/15 cases (20%) [3]. Secondary treatments include adjuvant radiotherapy and/or chemotherapy. These adjuvant therapies are rarely utilized and in one study, two received adjuvant radiation therapy and three received adjuvant chemotherapy [5]. Of the two patients that received radiation therapy, one diagnosed with a malignant PT and the other with a borderline PT, neither had recurrence or metastasis. Of the three who received chemotherapy, two began after detection of metastasis and died within six months time. The third, diagnosed with a borderline PT, remained disease free. In another study, survival of six patients diagnosed with either benign or borderline PTs had a 100% survival rate at 3 years, while of the 13 diagnosed with malignant PTs, 3 years survival was 53.8% [4]. However, in this study, some patients received adjuvant therapy although the specifics regarding which patients are unclear. Suzuki-Uematsu et al. reviewed 15 cases of malignant PTs and described a five year survival rate following primary surgery of 10% while the 2.2 year survival rate following detection of metastasis was 11%.

In conclusion, the phyllodes tumor is a rare mixed mesenchymal and epithelial primary breast neoplasm which affects a younger cohort of patients than the more common primary epithelial derived breast adenocarcinoma. Depending on histopathological characteristics, the tumor behavior may range from benign with a similar surgical response compared to that of the fibroadenoma, to local aggressiveness to distant metastasis with associated poor prognosis. A key to the successful management of this tumor may be early detection and resection prior to the development of distant metastasis. Given the low incidence of this tumor and the current lack of specific clinical and imaging characteristics to make this diagnosis, more pooling of data may be beneficial to identify specific findings that increase pre-test probability prior to making a decision whether to observe the mass or proceed to surgery.


The phyllodes tumor is a rare mesenchymal primary breast cancer that occurs in middle aged women, exhibits rapid growth and shares many clinical, imaging and histopathological similarities with the benign fibroadenoma. At a size between 3–5 cm, consideration for excisional biopsy should be entertained.


Thank you to Dr. Isabelle Ray-Coquard and Philippe Cousin for sharing their data with us.


phyllodes tumor
computed tomography
magnetic resonance imaging
methylenediphosphonic acid
technetium 99 metastable
estrogen receptor
progesterone receptor
fine needle aspiration


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