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Phyllodes tumours


Phyllodes tumours are rare fibroepithelial lesions that account for less than 1% of all breast neoplasms. With the non-operative management of fibroadenomas widely adopted, the importance of phyllodes tumours today lies in the need to differentiate them from other benign breast lesions. All breast lumps should be triple assessed and the diagnosis of a phyllodes tumour considered in women, particularly over the age of 35 years, who present with a rapidly growing “benign” breast lump. Treatment can be by either wide excision or mastectomy provided histologically clear specimen margins are ensured. Nodal metastases are rare and routine axillary dissection is not recommended. Few reliable clinical and histological prognostic factors have been identified. Local recurrence occurs in approximately 15% of patients and is more common after incomplete excision. It can usually be controlled by further surgery. Repeated local recurrence has been reported without the development of distant metastases or reduced survival. Approximately 20% of patients with malignant phyllodes tumours develop distant metastases. Long term survival with distant metastases is rare. The role of chemotherapy, radiotherapy, and hormonal manipulation in both the adjuvant and palliative settings remain to be defined.

  • benign breast disease
  • fibroadenoma
  • phyllodes tumour

Statistics from

Phyllodes tumours are rare fibroepithelial lesions that account for less than 1% of all breast neoplasms.1-3 First described by Johannes Müller in 1838,4 he coined the termcystosarcoma phyllodes; a misleading description as the tumours are rarely cystic and the majority follow a benign clinical course. In total, more than 60 synonyms have been reported5 but today, the World Health Organisation regards phyllodes tumour as the most appropriate nomenclature.6Displaying a broad range of clinical and pathological behaviour, phyllodes tumours should be regarded as a spectrum of fibroepithelial neoplasms rather than a single disease entity. At one extreme, malignant phyllodes tumours, if inadequately treated, have a propensity for rapid growth and metastatic spread. In contrast, benign phyllodes tumours on clinical, radiological, and cytological examination are often indistinguishable from fibroadenomas and can be cured by local surgery. With the non-operative management of fibroadenomas widely adopted, the importance of phyllodes tumours today lies in the need to differentiate them from other benign breast lesions.

A Medline search of the English literature published since 1975 was performed using the medical subject heading “phyllodes tumour”. Further articles were identified from the reference lists of papers reviewed. In view of the rarity of these tumours, most reported clinicopathological series are small, retrospective in nature, with limited long term follow up. This review collates the results of larger series and discusses the current status of diagnostic investigations, pathological assessment, aetiological and prognostic factors relating to phyllodes tumours. The management of primary, recurrent, and metastatic disease is outlined.


Triple assessment by clinical, radiological, and cytological or histological examination forms the fundamental basis for the evaluation of all breast lumps. In patients with phyllodes tumours, all three aspects individually have a low sensitivity and, even in combination, the diagnostic accuracy is often poor.7-11


Phyllodes tumours occur over a wide age range. The median age of presentation is 45 years (table 1); 20 years later than that for fibroadenomas.12 Phyllodes tumours are rare in adolescence13-15 and are more prevalent in the Latin American white16 and Asian populations.17 Few cases have been reported in men and these have invariably been associated with the presence of gynaecomastia.18-20 With the earlier presentation today of all breast lesions, most tumours are seen at a smaller size than a decade ago.

Table 1

Patient age, tumour diameter, and histological types reported from all studies of phyllodes tumours with greater than 20 patients published since 1975

Phyllodes tumours usually present as a rapidly growing but clinically benign breast lump.9 21 In some patients a lesion may have been apparent for several years, with clinical presentation precipitated by a sudden increase in size.7 22 23Malignant tumours are often larger and faster growing, but size and growth rate per se are poor predictors of the final histopathological type.8 10 21-25 They are found more commonly in the upper outer quadrant with an equal propensity to occur in either breast.7 8 The skin over large tumours may have dilated veins and a blue discoloration but nipple retraction is rare. Fixation to the skin or the pectoralis muscles has been reported, but ulceration is uncommon, even in patients with histologically malignant tumours.7 Pressure necrosis of the overlying skin can occur.23 Palpable axillary lymphadenopathy can be identified in up to 20% of patients but nodal metastases are uncommon.22 26 27 A significant proportion of patients have previously had a fibroadenoma and in a minority these have been multiple.7 18 28 29Occasionally fibroadenomas present simultaneously with a phyllodes tumour30 31 and synchronous bilateral phyllodes tumours have been reported.32 33 The diagnosis of a phyllodes tumour should be considered in all women, particularly over the age of 35 years, who present with a rapidly growing but clinically benign breast lump.


As with fibroadenomas, phyllodes tumours are mammographically well defined with a smooth and occasionally lobulated border. A radiolucent “halo” may be seen around the lesion, due to compression of the surrounding breast stroma.34 35 Coarse microcalcification has been reported within both fibroadenomas and phyllodes tumours9 36-39 but “malignant” microcalcification is rare.35 38 40 No mammographic indicators have been identified that allow differentiation between benign and malignant tumours.34 39 40 On ultrasound examination, phyllodes tumours often show smooth contours with low level homogenous internal echoes, intramural cysts, and the absence of posterior acoustic enhancement.9 34 41 As with mammography, no reliable ultrasonic indicators have been identified that differentiate between benign and malignant lesions.34 36 The role of magnetic resonance imaging in the assessment of phyllodes tumours and fibroadenomas remains to be defined.42

Box 1: Diagnosis

  • Phyllodes tumours account for less than 1% of breast neoplasms.

  • Median age of presentation is 45 years; 20 years later than that for fibroadenomas.

  • Diagnosis should be considered in all rapidly growing benign breast lesions.

  • No radiological indicators exist to differentiate benign and malignant lesions.

  • Fine needle aspiration cytology specimens require both epithelial and stromal elements to confirm the diagnosis.


As both phyllodes tumours and fibroadenomas belong to a spectrum of fibroepithelial lesions, accurate cytological diagnosis of phyllodes tumours by fine needle aspiration can be difficult.43 44Cytologically, it is often easier to differentiate benign from malignant phyllodes tumours than to separate benign phyllodes tumours from fibroadenomas.45 The presence of cohesive stromal cells (phyllodes fragments), isolated mesenchymal cells, clusters of hyperplastic duct cells, foreign body giant cells, bipolar naked nuclei, and the absence of apocrine metaplasia are highly suggestive of a phyllodes tumour.46 47 In the correct clinical setting, the presence of both epithelial and stromal elements within the cytological smear supports the diagnosis.48 Epithelial cells may, however, be absent from specimens taken from malignant lesions.46 The reporting of C3 (possibly benign) or C4 (possibly malignant) cytology from what appears to be a fibroadenoma should raise clinical suspicion of a phyllodes tumour.8With the increased use of core biopsies, preoperative diagnostic accuracy should improve and confusion with breast carcinomas should rarely occur.44 47


Phyllodes tumours vary greatly in size with most series reporting lesions up to 20 cm in diameter (table 1). Macroscopically, most small tumours have a uniform white consistency with a lobulated surface, similar to that of a fibroadenoma. They are rarely cystic in nature.18 Large tumours often have a red or grey “meaty” consistency with fibrogelatinous, haemorrhagic, and necrotic areas.1 The term cystosarcoma phyllodes was applied by Müller as phyllodedescribed the leaf-like projection of the stroma into cystic spaces while sarcoma referred to the “fleshy” consistency of the tumour.4

Microscopically, phyllodes tumours are characterised by epithelial lined cystic spaces into which projects a hypercellular stroma (fig 1). The presence of both epithelial and stromal elements are necessary to confirm the diagnosis. The stroma is the neoplastic component and determines the pathological behaviour.49 Only the stromal cells have the potential to metastasise.50 Primary tumours of the breast with pure sarcomatous differentiation and the absence of epithelial elements should be regarded as soft tissue sarcomas.51 52 Fibroadenomas are pathologically distinct from phyllodes tumours. They have a hypocellular stroma with few mitoses and little evidence of pleomorphism (fig 2). Unlike phyllodes tumours, fibroadenomas have a true capsule.

Figure 1

Malignant phyllodes tumour. Stroma shows cellular pleomorphism, nuclear atypia, and high mitotic activity (haematoxylin and eosin × 200).

Figure 2

Fibroadenoma. Stroma shows no cellular pleomorphism, nuclear atypia, or mitotic activity (haematoxylin and eosin × 200).

A wide range of histological features are seen within phyllodes tumours with heterogeneity existing between abutting areas within the same lesion. Based on the histological characteristics of the tumour, including its margin (pushing or infiltrating), stromal cellularity (slight or severe), stromal overgrowth (absent, slight, or severe), tumour necrosis (present or absent), cellular atypia (absent, slight, or severe), and the number of mitoses per high power field, they can be classified into “benign”, “borderline”, and “malignant” categories. The widely accepted definitions as proposed by Azzopardi53 and Salvadori et al 54 are shown in table 2. Other pathological classifications have defined similar categories but based on slightly different histopathological features.55 56 Some have regarded the designation of borderline lesions as unnecessary.57

Table 2

Criteria used to classify histological type as proposed by Azzopardi53 and Salvadori et al54

Tumour heterogeneity, sampling errors, and the lack of a standard interpretation of histological features are important factors in determining the relative proportions of benign, borderline, and malignant tumours seen in different series. The percentage of malignant lesions reported ranges from 2% to 45% (table 3). Furthermore, studies in which different pathologists have reported on the same histological slides have shown up to a 25% discordance in the final histopathological typing.58 59

Table 3

Operative treatment, local and distant recurrence rates from all studies of phyllodes tumours with greater than 20 patients published since 1975


The aetiological relationship between fibroadenomas and phyllodes tumours is at present unclear. Many patients develop both lesions either synchronously or metachronously and histological features of both fibroadenomas and phyllodes tumours have been identified in some tumours.55 Whether phyllodes tumours develop from fibroadenomas or arise de novo remains to be defined. Noguchiet al showed that most fibroadenomas have polyclonal elements and should be regarded as hyperplastic rather than neoplastic lesions.60 It has been suggested that, in a proportion of fibroadenomas, a somatic mutation can result in a monoclonal proliferation, histologically indistinguishable from the polyclonal element, but with a propensity to local recurrence and progression to a phyllodes tumour. Clonal analysis performed on histological specimens from patients who sequentially developed fibroadenomas and phyllodes tumours at the same site showed that both lesions were monoclonal and expressed the same inactivated allele, appearing to support this hypothesis.61

It has also been postulated that stromal induction of phyllodes tumours can occur as a result of growth factors produced by the breast epithelium.62 The nature of these factors is unclear but endothelin-1, a stimulator of breast fibroblast growth, may be important. Increased endothelin-1 levels have been demonstrated within phyllodes tumours.63 Endothelin-1 immunoreactive cells has been demonstrated in both the stroma of normal breast tissue64 and the epithelium of phyllodes tumours63 suggesting a possible paracrine mechanism for stromal stimulation.

Box 2: Pathology

  • Tumours can grow to over 20 cm in diameter.

  • Macroscopically small tumours usually resemble fibroadenomas.

  • Large tumours often have a red “meaty” appearance with cystic and necrotic areas.

  • Microscopy shows epithelial lined cystic spaces with hypercellular stroma.

  • On histological appearance tumours are classified as benign, borderline, or malignant.

  • Axillary lymph node metastases occur in approximately 10% of patients.

Prognostic factors

Most malignant phyllodes tumours do not recur or metastasise while some histologically benign tumours can show an usually aggressive clinical course.18 52 65 Consequently, it has been suggested that all phyllodes tumours should be regarded with malignant potential.58 66 Radical surgery for all phyllodes tumours is unnecessary and attempts have been made to identify clinical and histopathological prognostic factors. Little consensus exists regarding their relative importance and different factors appear to be important in predicting for local recurrence and metastatic spread. The local recurrence and distant metastatic rates of large published series are shown in table 3.

No reliable clinical prognostic factors have been identified that predict for local recurrence. Patient age does not appear to be important10 27 56 67 but tumours presenting in adolescence do seem to be less aggressive irrespective of their histological type.13 14 30 The role of tumour size is unclear. While most series have reported low local recurrence rates with tumours less than 2 cm in diameter,10 21 68 no correlation between tumour size and the risk of local recurrence has been demonstrated.8 10 22 30 56 69 70 The size of the tumour in relation to the breast appears important as this usually determines the extent of surgery and the resulting specimen resection margins. The risk of local recurrence is increased in incompletely excised lesions.30 25 70 71 Conversely, low recurrence rates have been reported in patients in which histologically clear margins have been assured.21 22 Whether the risk of local recurrence is increased in histologically malignant phyllodes tumours is unclear.8 10 70 72-74

Most distant metastases develop from borderline or malignant tumours.75 Unlike for local recurrence, tumour size does appear to be an important factor in predicting for metastatic spread.56 67 70 Many histological prognostic factors have been evaluated. Different studies have regarded stromal overgrowth,67 76-78 tumour necrosis,79infiltrating margins,30 56 67 80 mixed mesenchymal components,73 high mitotic rate,30 56 67 79 and stromal atypia56 74as important but in isolation each appears to have a low predictive value. Reinfuss et al, by univariate analysis, identified stromal overgrowth, margin and histological type as key prognostic factors.22 When entered in a multivariate analysis only histological type remained an independent prognostic factor. Similarly, Cohn-Cedermark et al in a univariate analysis identified mitotic activity, stromal overgrowth, cellular atypia, tumour necrosis and stromal elements other than fibromyxoid tissue as significant prognostic factors,79 but in a multivariate analysis only the presence of necrosis and the type of stromal elements remained significant.

As studies of histological prognostic factors have been disappointing, recent interest has been shown in markers of tumour biology. Mutations of the p53 tumour suppresser gene have been identified in human malignancies and are believed to be important in neoplastic progression and malignant potential. Increased p53 stromal immunoreactivity has been detected in malignant phyllodes tumours and p53 immunoreactivity may be valuable in differentiating fibroadenomas from phyllodes tumours.81 82 Furthermore, in phyllodes tumours, p53 immunoreactivity has been shown to correlate with negative prognostic factors but alone fails to predict for local recurrence or survival.83 In flow cytometric studies, correlations between DNA content, cell proliferation, and histological grade have been demonstrated.84-86 Some studies have identified a correlation between these markers of cellular proliferation and clinical outcome,87 however, most have not.84-86 88 Recent small studies have suggested that telomerase, a ribonuceloprotein enzyme that generates telomeres (DNA sequences important in determining cell immortality) may be a useful prognostic factor in phyllodes tumours.89 90

Five year disease-free survival rates of 96%, 74%, and 66% have been reported after surgery for benign, borderline, and malignant phyllodes tumours, respectively.22 Using pooled cancer registry data, Vorherr et al estimated an overall five year survival rate of 80% for malignant phyllodes tumours.27

Box 3: Prognosis

  • Most malignant tumours do not metastasise.

  • Some benign tumours may show an unusually aggressive behaviour.

  • Incomplete excision increases the risk of local recurrence.

  • Histological type is the most important predictor for metastatic spread.

  • The five year survival for benign, borderline, or malignant tumours is 96%, 74%, and 66% respectively.


The natural history of fibroadenomas has recently been clearly defined. With the negligible increased risk of malignancy and the recognition that 40% of fibroadenomas reduce in size over a two year period, non-operative management has been widely adopted.91 With the low prevalence of phyllodes tumours among all benign breast lumps, routine excision of all benign breast lumps cannot be advocated. However, treatment protocols need to be adopted that allow the timely identification of phyllodes tumours. As most phyllodes tumours grow faster than fibroadenomas, histological assessment and possible excision of a benign breast lump should be considered if rapid growth is seen during a period of observation.

Until the late 1970s, mastectomy was the standard surgical treatment for all phyllodes tumours, irrespective of tumour size or histological type.1 23 26 Radical surgery offered no survival advantage79 and today more conservative surgical approaches have been adopted. Directly comparing the outcome of local surgery and mastectomy is difficult as mastectomy has invariably been performed for larger tumours.8 10 Some generalisations regarding the management of these tumours can however be made. Simple intracapsular enucleation or “shelling out” of phyllodes tumours, irrespective of the histological type, results in an unacceptably high rate of local recurrence.58 92 If diagnosed preoperatively, wide excision with a margin of at least 1 cm of normal breast tissue is required, particularly for borderline and malignant tumours.28 For benign phyllodes tumours diagnosed after local excision of what appeared to be a fibroadenoma, a “watch and wait” policy does appear to be safe.93 With such an approach, local recurrence and five year survival rates of 4% and 96% respectively have been reported for benign phyllodes tumours.22 Whether patients with benign phyllodes tumours who have undergone local excision and have histologically positive specimen margins should undergo further surgery7 70 or be entered in a surveillance programme21 is controversial. Re-excision of borderline and malignant phyllodes tumours identified after local excision should be considered. It has been suggested that mastectomy is no longer required, even for malignant phyllodes tumours, provided adequate resection margins can be achieved.58 59With the “benign” course of the disease in adolescents, irrespective of the histological type of the tumour, the breast can invariably be preserved.7 14 94

As malignant phyllodes tumours undergo haematogenous spread, the proportion of patients with lymph node metastases is approximately 10% and routine axillary clearance is not recommended.10 18 22 72 76 The role of adjuvant breast radiotherapy is unclear and has not been the subject of large randomised controlled trials.29 79 95 In those few unselected cases in which it has been used, the dose of radiotherapy given has been higher than that used in the adjuvant setting for patients with breast cancer.

Box 4: Management

  • All rapidly growing benign breast lesions require histological assessment.

  • Wide excision or mastectomy should be performed ensuring histological clear margins.

  • Mastectomy for malignant tumours offers no survival advantage.

  • Axillary nodal dissection is not required.

  • The role of adjuvant radiotherapy is unclear.

Recurrent disease

The potential for phyllodes tumours to recur and metastasise was first recognised in the 1930s.96 97 To date, local recurrence rates ranging from 10% to 40% have been reported with most series averaging 15% (table 3). Local recurrence appears to be related to the extent of the initial surgery and should be regarded as a failure of primary surgical treatment.10 56 76 77 79 92 Whether malignant tumours have an increased risk of recurrence is unclear but when it does occur it is invariably seen earlier than with benign tumours.74 92 98 Local recurrence usually occurs within the first few years of surgery and histologically resembles the original tumour.8 10 25 56 92 99 Occasionally recurrent tumours shows increased cellularity and more aggressive histological features than the original lesion.25 52 67 92 In most patients, local recurrence is isolated and is not associated with the development of distant metastases.79 99 In a minority of patients repeated local recurrence occurs, over a prolonged period with no survival disadvantage.56 92 98 100 101 This is often seen irrespective of either the histological type of the tumour or the extent of the specimen margins.

Local recurrence can usually be controlled by further wide excision7 and mastectomy is not invariably required.56 99 Mastectomy should, however, be considered for local recurrence after local surgery for borderline or malignant tumours.17 22 82 Occasionally aggressive local recurrence can result in widespread chest wall disease with direct invasion of the underlying lung parenchyma.56 Isolated reports of good palliation in this situation with radiotherapy have been published.29 102

Box 5: Recurrent and metastatic disease

  • 15% of patients develop local recurrence.

  • Local recurrence is not associated with distant metastases or reduced survival.

  • Local recurrence can often be controlled with further surgery.

  • 20% of patients with malignant tumours develop distant metastases.

  • The commonest sites are lung, bone, and abdominal viscera.

  • Good palliation can be obtained with single agent or combination chemotherapy.

  • The role of hormonal therapy remains to be defined.

Metastatic disease

Overall, 10% of patients with phyllodes tumours develop distant metastases (table 3) and these eventually occur in approximately 20% of patients with histologically malignant tumours.25 Most distant metastases develop without evidence of local recurrence.99 The commonest sites for distant metastases are the lung, bone, and abdominal viscera.22 55 103 104These often occur in the absence of lymph node metastases24 103 and histologically contain only the stromal element.105 The risk of metastatic disease does not appear to influenced by the extent of the initial surgery56 75 92 104 and appears to be predetermined by tumour biology. Few reports have been published of distant metastases after excision of a benign phyllodes tumour, except when histologically malignant local recurrence occurs.24 29 52 92

Metastatic phyllodes tumours have a poor prognosis and no long term survival has been reported.103 105 Isolated reports have been published of good palliation of metastatic disease from single agent22 106 or combination chemotherapy107-109 but the exact role of chemotherapy in metastatic phyllodes tumours remains to be defined. Up to 40% of phyllodes tumours are oestrogen receptor positive110 and as with fibroadenomas, almost all phyllodes tumours express progesterone receptors.111 Despite these features, the use of endocrine therapy in either the adjuvant or palliative setting has not been extensively studied.


The authors would like to thank Dr Mark Newbold, Consultant Pathologist, Walsgrave Hospitals NHS trust for the photomicrographs in figures 1 and 2.


Medical Anniversary

King Edward VII, 19 July 1897

King Edward VII (1841–1910) was elected honorary FRCP at Malborough House on this day by the President, Sir Samuel Wilks, and in the presence of the Censors, Treasurer, and Registrar. He was presented with a gold headed cane, a replica of the one carried in turn by Radcliffe, Mead, Askew, Pitcairn, and Baillie and presented to the Royal College of Physicians in 1823 by Baillie's widow. During his reign, he showed continued support for medical services by opening a new wing to the London Hospital (1903), King Edward VII Sanatorium, Midhurst (1906), King Edward Hospital, Windsor (1908), and the new King's College Hospital (1909).—D G James

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