Acta Chirurgica Belgica

ISSN: 0001-5458 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/tacb20

Comparison of Predictive Factors For the

Diagnosis and Clinical Course of Phyllodes
Tumours of the Breast

H. Yabanoglu, T. Colakoglu, H. O. Aytac, A. Parlakgumus, F. A. Bolat, A.

Pourbagher & S. Yildirim

To cite this article: H. Yabanoglu, T. Colakoglu, H. O. Aytac, A. Parlakgumus, F. A. Bolat, A.

Pourbagher & S. Yildirim (2015) Comparison of Predictive Factors For the Diagnosis and
Clinical Course of Phyllodes Tumours of the Breast, Acta Chirurgica Belgica, 115:1, 27-32, DOI:
10.1080/00015458.2015.11681063

To link to this article: http://dx.doi.org/10.1080/00015458.2015.11681063

Published online: 11 Mar 2016.

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 Phyllodes Tumours of the Breast 27
Acta Chir Belg, 2015, 115, 27-32

Comparison of Predictive Factors For the Diagnosis and Clinical Course of

Phyllodes Tumours of the Breast
H. Yabanolu1, T. Colakoglu1, H. O. Aytac1, A. Parlakgumus1, F. A. Bolat 2, A. Pourbagher 3, S. Yildirim 1
Department of 1General Surgery, 2Pathology, 3Radiology, Baskent University Faculty of Medicine, Adana, Turkey.

Abstract. Background : To compare predicting factors for the diagnosis and clinical course of benign and malign/
borderline phyllodes tumours (PT) of the breast, and to discuss treatment modalities.
Methods : Clinical and demographic characteristics of the patients with histopathological diagnosis of phyllodes tumour
were examined. Patients were divided into group 1 (benign PT) and group 2 (borderline/malignant PT). Groups were
Downloaded by [University of California Santa Barbara] at 17:15 14 June 2016

compared in terms of demographic and clinical characteristics.

Results : Of the patients studied, 37 (68.5%) had benign, 7 (12.9%) had borderline and 10 (18.5) had malignant histopa-
thology. A statistically significant relationship was detected between the incidence of malignancy and mass diameter
(p = 0.001) and age (p = 0.030) when the two groups were compared. Wide surgical excision was performed on 46
(82.5%) patients, simple mastectomy on 7 (13%) patients and modified radical mastectomy on one (1.9%) patient. Ten
(18.5%) patients were re-operated for surgical margin positivity. Local recurrence was determined only in one (1.9%)
patient. Distant metastasis due to malignant PT developed in two (3.7%) patients.
Conclusion : Among the patients who were considered to have PT, malignancy was likely to be present, especially if the
patients age was over 40 and the diameter of the mass was above 33.5 mm. Therefore, in patients with similar charac-
teristics, surgical margins should be kept slightly wider or wider excisions should be preferred with or without simultane-
ous reconstructive surgery in appropriate cases.

Abbreviations togenous spread (1). Because of this feature, there is no

PT, phyllodes tumours
Introduction
Phyllodes tumours (PT) of the breast are rare fibroepithe-
lial tumours. They constitute 0.3-1% of all breast tu-
mours and 2-3% of fibroepithelial tumours (1). Phyllodes
tumours are divided into subgroups according to histo-
logical features (according to the features such as tumour
margins, stromal overgrowth, tumour necrosis, cellular
atypia, and number of mitosis per high power field) as
benign, borderline and malignant (2-4). Many of these
tumours are benign (35-64%), but approximately 25% of
the cases have malignant features (5-7). In a similar man-
ner to fibroadenomas, phyllodes tumours may show a
benign behaviour or may also tend to metastasize in a
similar way to sarcomas (8-10). No morphological and
radiological finding is fully reliable as a predictor of the
biological behaviour of phyllodes tumours. The main
treatment for phyllodes tumours is surgery. Once the pre-
operative diagnosis is confirmed, wide local excision of
the mass is usually the preferred method of treatment.
After excision, a regional recurrence rate of 14-21% is
observed. In large masses or regional recurrences, simple
mastectomy may be necessary (7, 11-12). PTs can behave
like malignant sarcomatous masses by showing hema-
place in the surgical treatment of axillary dissection.
Surgery is established as the basic method of treat-
ment for PT, but there is no common consensus on the
surgical technique that should be selected, the width of
surgical resection, the group of patients to which adju-
vant therapy (chemotherapy and / or radiotherapy) should
be applied and the treatment algorithm for borderline
malignant phyllodes tumours.
The aims of this study are to compare predicting
factors for the diagnosis and clinical course of benign
and malign/borderline phyllodes tumours of breast, and
also to discuss treatment modalities.
Materials and Methods
This study involved 54 patients diagnosed histopatho-
logically, with phyllodes tumours and treated in the De-
partment of General Surgery, Baskent University Hospi-
tals from 2002 to 2013. The patients medical records
were retrieved from Baskent University Research Hospi-
tals and the data were analyzed retrospectively. This
study was approved by Baskent University Institutional
Review Board and supported by Baskent University Re-
search Fund (KA13/220). All diagnostic and therapeutic
procedures were performed by a single team for all of the
patients. Patients data were analyzed in terms of age,
gender, family history, physical examination findings,

5326-yabanoglu-yildirim-.indd 27 27/01/15 11:23

 28
mass localization, biopsy type, preoperative radiologic
imaging, radiographic imaging preliminary diagnosis,
mass size, concomitant pathologies, presence of multiple
masses, surgery type, surgical margin distance, mitotic
index, histopathologic diagnosis, recurrence, re-excision,
distant organ metastasis, radiotherapy/chemotherapy
treatment, follow-up and mortality.
Diagnosis
Patients were diagnosed both radiologically and patho-
logically. Ultrasonography (USG), mammography (MG)
and magnetic resonance imaging (MRI) were used as im-
aging techniques. Either excisional or core biopsies were
preferred for pathologic diagnosis.
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Surgery
According to the histopathological and radiological diag-
nosis of the patient, wide excision (lumpectomy) ensur-
ing a macroscopic safe margin of one centimetre was
performed. Re-excision, when surgical margin was posi-
tive or closer than one centimetre or mastectomy (with or
without reconstruction) when the entire breast volume
was not suitable for breast conserving surgery was made.
Pathological evaluation
Phyllodes tumours were classified according to the
criteria defined by World Health Organization (WHO) as
follows (2, 13-14).
a) Benign : 0-4 mitoses/10 high power fields, minimal
stromal cellularity and atypia, minimal or moderate
stromal overgrowth, intact surgical margins.
b) Borderline : 5-9 mitoses/10 high power fields, moder-
ate stromal cellularity and atypia, moderate stromal
overgrowth, intact or infiltrated surgical margins.
c) Malignant : > 10 mitoses/10 high power fields, mod-
erate or marked stromal cellularity and atypia, moder-
ate or marked stromal overgrowth, infiltrated surgical
margins.
The safe surgical margin was considered as above one
centimetre for malignant and borderline tumours and two
millimetres for benign tumours (15).
Statistical analysis
Statistical analysis was performed using the statistical
package SPSS v 17.0. For each continuous variable, nor-
mality was checked by Kolmogorov Smirnov and Shap-
iro-Wilk tests. Comparisons between groups were evalu-
ated using Students t-test for the data normally
distributed and using the Mann Whitney U test for the
data that were not normally distributed. The categorical
variables between the groups were analyzed by using the
Chi square test. Values of p < 0.05 were considered sta-
5326-yabanoglu-yildirim-.indd 28
H. Yabanolu et al.
tistically significant. Roc curve analysis was performed
to identify cut-off values.
Results
Results comparing the demographic and clinical charac-
teristics of benign and malignant PTs are summarized in
Table 1.
When comparing the two groups, a statistically sig-
nificant relationship was detected between the incidence
of malignancy and mass diameter (p = 0.001) and age
(p = 0.030). Ultrasound alone in 23 (42.6%) patients, or a
combination of two or more imaging techniques (ultra-
sound, MRI or mammography) in 31 patients, were used
as the diagnostic tool. The most frequent diagnosis was
fibroadenoma (FA, which was observed in 19 (35.1%)
patients, followed by PT shown in 16 (26.6%) patients
and breast cancer in 11 (20.3%). The remaining eight
(14.8%) patients were considered to have more than one
disease as primary diagnosis. In eight of the 12 patients
preliminary diagnosis of PT was made correctly with
MRI (75%). Of these patients, six had malignant and two
had benign PT. Radiological pre-diagnosis was FA and
pathological diagnosis was benign PT for the four pa-
tients who were not accurately diagnosed with MRI.
Pathological diagnoses were done by core biopsy in
51 patients (94.4%) and by surgical biopsy in three
patients (5.5%). No false negativity was determined in
the diagnosis of patients for whom core biopsy was
performed. According to pathological mitotic count,
37 patients (68.5%) had benign, 7 (12.9%) had border-
line and 10 had (18.5%) malignant PT. As a surgical
treatment, wide excision was performed in 46 (85.2%)
patients, simple mastectomy in 7 (13%) patients and
modified radical mastectomy in one (1.9%) patient. Ten
patients (18.5%) were operated on again because of posi-
tive surgical margins, for whom repetitive wide excision
was done in 9 (90%) patients and mastectomy in one
(10%), as the second surgery. Of these patients, three
(30%) had malignant, 5 (50%) had borderline and two
(20%) had benign lesions. When the patients data were
evaluated by the Roc curve, age over 40 and mass dia-
meter of greater than 33.5 mm were found to have higher
malignant potential. Of the patients who underwent
surgery in accordance with the diagnosis of PT, five
(9.3%) were given chemotherapy and two (3.7%) re-
ceived radiotherapy. Only one (1.9%) patient showed
regional recurrence. The patient underwent repeated
wide excision and radiotherapy (RT) was given and has
been followed-up for 29 months without recurrences.
Two patients (3.7%) developed distant metastases due to
malignant PT. Two patients (3.7%) with PT had simulta-
neous infiltrating ductal carcinoma of the breast. The
68 years old first patient had an 80 mm PT and 40 mm of
invasive ductal carcinoma in her left breast. Diagnoses of
27/01/15 11:23
 Phyllodes Tumours of the Breast 29

Table 1. Comparison of demographic and clinical characteristics of benign and borderline / malignant PTs.
Demographic and clinical characteristics Group 1 Group 2 (Borderline/malignant PT) All PTs
(Benign FT)
Number of patients, n (%) 37 (68.5%) 17 (31.5%) 54 (100%)
*Age (years) (median) 33 (15-74) 45 (21-68) 40 (15-74)
(p: 0.030)
Family history, n (%) 3 (8.1%) 1 (5.9%) 4 (7.4%)
Side of tumour (right/left), n (%) 17 (45.9%)/20 (54.1%) 9 (52.9)/8 (47.1%) 26 (48.1%)/28 (51.9%)
The most common initial diagnosis in 17 Phyllodes tumor 8 Breast cancer 19 Fibroadenoma
radiological imaging
*Size of the mass (mm) (median) 29 (10-80) 51 (30-110) 38 (10-110)
(p: 0.001)
Type of biopsy (excisional/core), n (%) 36 (97.2%)/1 (2.7%) 15 (88.2%)/2 (11.7%) 51 (94.4%)/3 (5.5%)
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Presence of multiple simultaneous mass, n 11 (29.7%) 4 (23.5%) 15 (27.7%)

(%)
Type of surgery 36 wide surgical excision, 10 wide surgical excision, 46 wide surgical excision,
1 simple mastectomy 6 simple mastectomy 7 simple mastectomy
1 modified radical mastectomy 1 modified radical mastectomy
Positive surgical margins, n (%) 2 (5.4%) 8 (47.1%) 10 (18.5%)
Number of mitoses In 37 patients; 0-4 mitoses / In 7 patients; 5-9 mitoses/10 high In 37 patients; 0-4 mitoses/
10 high power fields power fields 10 high power fields
In 10 patients; >10mitoses/ 10 high In 7 patients; 5-9 mitoses/
power fields 10 high power fields,
In 10 patients; >10mitoses/
10 high power fields
Histopathologic diagnosis 37 benign histopathology 7 borderline histopathology, 37 benign histopathology,
10 malignant histopathology 7 borderline histopathology,
10 malignant histopathology
Recurrences n (%) No 1 (5.9%) 1 (1.9%)
Re-excision n (%) 2 (5.4%) 8 (47.1%) 10 (18.5%)
Distant organ metastasis n (%) No 2 (11.7%) 2 (3.7%)
Radiotherapy/Chemotherapy n (%) No 2 (11.7%)/5 (29.4%) 2 (3.7%)/5 (9.3%)
Follow-up time (month) (median) 29 (3-150) 21 (3-120) 24 (3-150)
Mortality n (%) No 2 (11.7%) 3 (5.5%) In 2 patients, because
of distant organ metastasis due
to PT
In 1 patient due to metastasis
of invasive ductal carcinoma
*, P < 0.05 ; PT, Phyllodes tumour.

the both masses were done by core needle biopsy and a
modified radical mastectomy was performed which
determined a stage 2 (T2N0M0) cancer. She died on the
77th month of follow-up due to lung and liver metastases
of breast cancer. The second patient was a of 45-year-old
woman with a benign PT of 10 mm in diameter in her
right breast and 40 mm invasive ductal carcinoma in her
left breast. Wide excision to the PT in the right breast and
lumpectomy in conjunction with left axillary lymph node
dissection to the invasive cancer in the left breast was
performed. The stage of the cancer was determined as
T2N1M0 and had been followed-up for 42 months
disease free. As a result, mortality due to distant organ
metastasis was encountered in two patients with PT and
in one patient with infiltrative ductal carcinoma.
Discussion
PTs are rare tumours of the breast with difficult radio-
logical diagnosis, diverse clinical behaviour and contro-
versies regarding the most effective surgical approach
and adjuvant chemotherapy / radiotherapy treatment op-
tions. Serious problems arise during the diagnosis and
treatment of the disease. However, the increasing number
of patients and clinical outcome results contribute toward
re-establishing the diagnosis and treatment algorithms of

5326-yabanoglu-yildirim-.indd 29 27/01/15 11:23

 30 H. Yabanolu et al.

PT. This updated information helps particularly in evalu-

ation of the risk factors affecting prognosis, surgical mo-
dalities and effects adjuvant treatment on survival. Until
now, many studies investigated the prognostic risk fac-
tors without considering the histopathological features of
the disease (benign, borderline and malignant) in all pa-
tient groups. In this study, the PTs were divided into
groups as 1 : benign and 2 : borderline/malignant, ac-
cording to histopathological features. Patients in both
groups were compared across clinical and demographic
characteristics. PT is usually seen in women between the
ages of 35-55 (16). Different results have been reported
in the literature, revealing relationship between age and
malignancy. Whereas in a series of six hundred patients, a
PT was shown as likely to have a significantly higher ten-
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dency to be malignant in patients over the age of 35, in a

series of 65 patients no significant relationship between
age and malignancy has been reported (16-17). In our
study, the median age was found to be significantly high-
er in group two (p : 0.030). Also considering the median
age between groups one and two, PTs were found to have
a much greater malignancy potential in patients aged
over 40.
Preoperative diagnosis of PT is important in order to
determine the best surgical approach. However, despite
all the physical examinations and radiological evalua-
tions, difficulties in differential diagnosis have not been
fully resolved. Primary diagnosis of PTs are often con-
fused with FAs (15, 19). Similarly, in our series, the most b
common radiological diagnosis was FA (35.1%). The
specificity of mammography and/or ultrasound in the di-
agnosis of PT is very limited (15, 20). The specificity of
mammography was found between 6.5-15% and ultra-
sound between 15-30% in various studies (7, 11, 15, 19-
21). Recently, MRI is increasingly gaining popularity,
especially in the diagnosis of malignant PT. Low signal
intensity compared to normal breast tissue, the presence
of irregular cyst wall and low diffusion coefficient are the
findings suggesting malignant PT on T2-weighted MRI
sections (22) (Fig. 1). In our series, MRI accurately pre-
dicted the diagnosis of PT, with a specificity of 66% in
eight of the 12 patients. Of these patients, six had malig-
nant and two had benign PT. It is noteworthy that, for the
four patients who couldnt be accurately diagnosed by
c
MRI, the radiological diagnosis was FA whereas the
pathological diagnosis was benign PT. Figure 1. a. Fronds of stroma covered by a thin layer of epithe-
Core biopsy in the diagnosis of breast mass is increas- lium in benign phylloides tumour (Hematoxylin and Eosin
ing day by day. However, in the literature, the number of 40). b. Borderline phyllodes tumour ; the tumour has an
studies showing the sensitivity of core biopsy in the diag- irregular invasive margins (black arrows) and stromal over-
growth (Hematoxylin and Eosin 40). c. Malignant phyllodes
nosis of FT is limited (23). The false negative rate of core
tumour ; malignant stroma showing a liposarcomatous differ-
biopsy in the diagnosis of PT is between 34-39% (20, entiation (black arrows) (Hematoxylin and Eosin 100).
24). The most important reason for this is the difficulty in
distinguishing microscopic hypercellularity of FA from
benign FT. The pathologists experience and interpreta-
tion is very important in this regard (24). We compared

5326-yabanoglu-yildirim-.indd 30 29/01/15 14:13

 Phyllodes Tumours of the Breast
a Anderson Cancer Centre (28). In cases where the tumour
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b
Figure 2. a. Axial T2-weighted MR image shows a heteroge-
neously hyperintense lobular mass with a smooth margin (open
arrows). b. Axial contrast-enhanced MR image demonstrates
that the mass shows heterogeneous enhancement (open arrows).
the tissue samples of the three patients previously diag-
nosed as PT by core biopsy with the mass removed after
surgery. We have detected that core biopsy correctly pre-
dicted pathological diagnosis of PT in all patients. The
effort of diagnosing a mass in the breast during surgery
usually works out with a limited intervention like inci-
sional biopsy or enucleation. Consequently, in many pa-
tients a subsequent wider intervention is needed due to
margin positivity problems (24). Therefore, those pa-
tients whose diagnoses of PT were obtained with core
biopsy, needed a second surgery with direct surgical mar-
gin positivity to a lesser extent than those directly oper-
ated on.
Surgery is the main treatment for phyllodes tumours
and surgical margins are very important in terms of re-
gional recurrence. Regional recurrence rates range be-
tween 3% and 15% for benign PTs and between 3% and
50% for malignant PTs (12). The presence of positive
surgical margins after excision has been reported as the
main prognostic factor for recurrence (25). In our study,
regional recurrence occurred in one patient (3.4%) after a
48-months follow-up. However, this patient did not have
positive surgical margins. In general, 6.6% to 7.5% of
5326-yabanoglu-yildirim-.indd 31
31
malignant PTs tend to metastasize. Most metastases are
seen in the lung and in the bone tissue. In parallel with
these results, two (3.7%) of our patients with malignant
PT developed distant metastases. One patient had metas-
tases in the lungs and the other in the bones.
Surgery is the only treatment for benign phyllodes
cases. The role of adjuvant therapy after efficient surgery
in high-risk patients with malignant histopathology is
controversial (27). Radiotherapy is recommended only
for cases with positive or close surgical margins or for
those forward operations which cannot be applied in MD
is removed with wide excision, the additional benefit and
survival advantage of radiotherapy is unknown. Like-
wise, adjuvant systemic chemotherapy involving doxo-
rubicin and dacarbazine has been found to be ineffective
on survival rates in malignant tumours in a recent
study (29). There are limited numbers of case reports
showing invasive breast cancer focus in excised malig-
nant PT (30). However, there is only one study showing
simultaneous PT with breast cancer (31). We detected PT
and invasive breast cancer as two simultaneous distinct
masses were in two (3.7%) patients, but we think that it is
a coincidence.
Disease-free survival rate for five years and overall
survival rates were reported as 72% and 86.6% respec-
tively for malignant PTs in the literature (16, 32). In our
study, which has a median follow-up period of 24 (3-
150) months, which, two (3.7%) of our patients with
malignant PTs died.
Conclusion
Due to the problems in both diagnosis and treatment
phases, PTs remain a serious health problem. We think
that diagnosis and appropriate treatment should be deter-
mined according to a proper assessment of prognostic
factors of the disease to reduce these problems. Accord-
ing to the results obtained in our study, among the pa-
tients who were considered to have PT, malignancy was
likely to be present, especially if patients age was over
40 and the diameter of the mass was above 33.5 mm.
Therefore, in patients with similar characteristics,
surgical margins should be kept slightly wider or wider
excisions with or without simultaneous reconstructive
surgery in appropriate cases should be preferred. Further-
more, although larger series are needed to make robust
judgments, we believe that the application of core biopsy
and MRI would be effective in determining the appropri-
ate preoperative treatment protocols and surgical
margins.
Acknowledgments
This study did not receive any specific funding or grants.
27/01/15 11:23
 32
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H. Yabanoglu, M.D.
Bakent niversitesi Aratrma ve Uygulama Hastanesi, Dadalolu
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