Hindawi Publishing Corporation
Volume 2013, Article ID 361469, 10 pages
Phyllodes Tumor of Breast: A Review Article
Shashi Prakash Mishra, Satyendra Kumar Tiwary,
Manjaree Mishra, and Ajay Kumar Khanna
Department of Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Ultar Pradesh 221005, India
Correspondence should be addressed to Ajay Kumar Khanna; email@example.com
Received 19 January 2013; Accepted 11 February 2013
Academic Editors: M. G. Chiofalo, M. Frascio, H. Hirose, K.-E. Kahnberg, and M. Wronski
Copyright © 2013 Shashi Prakash Mishra et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
planning and avoidance of reoperation. Treatment can be either wide local excision or mastectomy to achieve histologically clear
margins. Discussion. The exact aetiology of phyllodes tumour and its relationship with fibroadenoma are unclear. Women aged
between 35 and 55 years are commonly involved. The median tumour size is 4cm but can grow even larger having dilated veins
and a blue discoloration over skin. Palpable axillary lymphadenopathy can be identified in up to 10–15% of patients but <1% had
in phyllodes tumours has been associated with inadequate local excision. The role of adjuvant radiotherapy and chemotherapy
remains uncertain and use of hormonal therapy has not been fully investigated. Conclusion. The preoperative diagnosis and proper
pathological positive nodes. Mammography and ultrasonography are main imaging modalities. Cytologically the presence of both
Phyllodes tumors are rare fibroepithelial lesions. They make
up 0.3 to 0.5% of female breast tumors  and have an
women aged 45 to 49 years [2, 3]. The tumor is rarely found
in adolescents and the elderly. They have been described as
early as 1774, as a giant type of fibroadenoma . Chelius
 in 1827 first described this tumor. Johannes Muller (1838)
was the first person to use the term cystosarcoma phyllodes.
It was believed to be benign until 1943, when Cooper and
Ackerman reported on the malignant biological potential of
the term phyllodes tumor and as described by Rosen 
subclassified them histologically as benign, borderline, or
malignant according to the features such as tumor margins,
stromal overgrowth, tumor necrosis, cellular atypia, and
number of mitosis per high power field. The majority of
phyllodes tumors have been described as benign (35% to
malignant subtypes. The term phyllodes tumor represents a
broad range of fibroepithelial diseases and presence of an
the phyllodes tumor from other stromal sarcomas.
Accurate preoperative pathological diagnosis allows cor-
achieve wider excision or for subsequent tumor recurrence
[8–10]. At one extreme, malignant phyllodes tumors, if
inadequately treated, have a propensity for rapid growth
and metastatic spread. In contrast, benign phyllodes tumors
on clinical, radiological, and cytological examination are
by local surgery. With the nonoperative management of
fibroadenomas widely adopted, the importance of phyllodes
tumors today lies in the need to differentiate them from
other benign breast lesions. Treatment can be either wide
local excision or mastectomy provided histologically clear
specimen margins are ensured [2, 11, 12].
At present time, the exact etiology of phyllodes tumor and
its relationship with fibroadenoma are unclear. Noguchi
2 ISRN Surgery
et al.  showed that most fibroadenomas have polyclonal
elements and should be regarded as hyperplasic rather than
neoplastic lesions. It has been suggested that, in a proportion
of fibroadenomas, a somatic mutation can result in a mono-
clonal proliferation, histologically indistinguishable from the
polyclonal element, but with a propensity to local recurrence
and progression to a phyllodes tumor which has also been
supported by clonal analysis. It has also been postulated
that stromal induction of phyllodes tumors can occur as a
result of growth factors produced by the breast epithelium.
occasionally have been implicated as factors stimulating
tumor growth. The nature of these factors is unclear but
endothelin-1, a stimulator of breast fibroblast growth, may be
Unlike carcinoma breast, phyllodes tumors start outside of
the ducts and lobules, in the breast’s connective tissue, called
the stroma which includes the fatty tissue and ligaments that
surround the ducts, lobules, and blood and lymph vessels in
the breast. In addition to stromal cells, phyllodes tumors can
also contain cells from the ducts and lobules.
4.1. WHO Criteria. World Health Organization divided
phyllodes tumor into benign, borderline, and malignant
categories based on the degree of stromal cellular atypia,
mitotic activity per 10 high power fields, degree of stromal
overgrowth (these three are main), tumor necrosis, and
margin appearance (see Table 1).
4.2. Criteria Proposed by Azzopardi et al.  and Salvadori et
al. . See Table 2.
5.1. ClinicalPresentation. Mostofthetumorarisesinwomen
aged between 35 and 55 years (approximately 20 years
Mitotic rate (per 10hpf)
Figure 1: Giant phyllodes tumor.
later than fibroadenoma), 3, 15, 16 more prevalent in the
Latin American white and Asian populations . Few cases
have been reported in men and these have invariably been
associated with the presence of gynaecomastia. It usually
presents as a rapidly growing but clinically benign breast
lump. In some patients a lesion may have been apparent
for several years, with clinical presentation precipitated by a
sudden increase in size [15, 16].
a blue discoloration but nipple retraction is rare.
(ii) Fixation to skin and pectoralis muscles has been
reported, but ulceration is uncommon.
(iii) More commonly found in upper outer quadrant with
an equal propensity to occur in either breast.
(iv) Rarely presentation may be bilateral.
(v) The median size of phyllodes tumors is around 4cm.
20% of tumors grow larger than 10cm (giant phyl-
lodes tumor). These tumors can reach sizes up to
40cm in diameter (see Figure 1).
(vi) A significant proportion of patients have history of
fibroadenoma and in a minority these have been
(vii) Palpable axillary lymphadenopathy can be identified
in up to 10–15% of patients but <1% had pathological
5.2. Radiological Investigations. Mammography and ultra-
sonography are mainstay of routine imaging of breast lumps.
Wurdinger et al.  show that round or lobulated shape,
well-defined margins, heterogeneous internal structure, and
in phyllodes tumors than in fibroadenomas.
Figure 2: Phyllodes tumor on mammography.
5.2.1. Ultrasonography [18, 19]. Lobulated shape (in some
cases round or oval) well circumscribed with smooth mar-
gins, echogenic rim, and low level homogenous internal
echoes. Fluid-filled clefts in a predominantly solid mass
(highly suggestive of phyllodes tumor) with good thorough
transmission and lack of microcalcification are seen.
5.2.2. Color Doppler Ultrasonography. Features suggesting
malignant behavior are
(i) marked hypoechogenicity,
(ii) posterior acoustic shadowing,
(iii) ill-defined tumor margins.
(iv) higher values of RI (resistance index),
(v) increased PI (pulsatility index),
(vi) increased Vmax (systolic peak flow velocity).
5.2.3. Mammography [18, 20, 21] (see Figure 2)
(i) It shows well circumscribed oval or lobulated mass
with rounded borders.
to compression of the surroundings.
(iii) Coarse calcification (but malignant microcalcifica-
tion is rare) may be present.
5.2.4. Magnetic Resonance Imaging (MRI) [21–28]. The fol-
(i) round or lobulated shape and well-defined margins,
(ii) heterogeneous internal structure/nonenhancing sep-
(iii) exhibits hypointense signals on T1-weighted images,
(iv) exhibits hyper/isointense signals on T2-weighted
(v) contrast enhancement pattern:
(a) benign lesion:
(1) slow initial enhancement with persistent
(b) malignant lesion:
(1) fast initial enhancement with plateau
(2) fast initial enhancement with wash-out
5.3. Pathological/Histological Assessment. As both phyllodes
tumors and fibroadenomas belong to a spectrum of fibroep-
ithelial lesions, accurate cytological diagnosis of phyllodes
tumors by fine needle aspiration can be difficult.
Cytologically, it is often easier to differentiate benign
from malignant phyllodes tumors than to separate benign
setting, the presence of both epithelial and stromal elements
within the cytological smear supports the diagnosis. Epithe-
lial cells may, however, be absent from specimens taken from
malignant lesions. The presence of cohesive stromal cells
hyperplastic duct cells, foreign body giant cells, blood vessels
crossing the stromal fragments, and bipolar naked nuclei
and the absence of apocrine metaplasia are highly suggestive
of a phyllodes tumor. However, the value of FNAC in the
diagnosis of phyllodes tumor remains controversial, with an
overall accuracy of about 63% [29, 30]. Core tissue biopsy
is an attractive alternative to FNAC because of the extra
architectural information provided by histology compared
with cytology. Komenaka et al.  found the sensitivity of
core needle biopsy to be 99% and negative predictive value
and positive predictive value 93% and 83%, respectively, for
5.3.1. Macroscopic Appearance. Macroscopically most small
tumors have a uniform white consistency with a lobulated
surface, similar to that of a fibroadenoma. Large tumors on
cut section often have a red or grey “meaty” consistency with
protrusions into the cystic spaces.
5.3.2. Microscopic Appearance (see Figures 3–6). Fine Needle
Aspiration Cytology. The cytological diagnosis of phyllodes
tumors is mainly suggested by the presence of hypercellular
stroma and the stromal elements on the smears being more
numerous than the epithelial ones. The cells on the smears
were classified by Deen et al.  in 1999, and Jayaram
and Sthaneshwar in 2002 , by comparison with small
(1) short, round/oval cells, two-size smaller than the size
of a lymphocyte: considered to be epithelial cells;
(2) long, spindle cells, three-size larger than the size of a
lymphocyte: considered to be stromal cells.
Many authors considered that the following aspects
should also be taken into consideration in the case of
cytological diagnosis of phyllodes tumors:
(a) the presence of hypercellular stromal fragments;
(b) the cellular composition of the stromal fragments;
(c) the amount of naked nuclei on the background of the
4 ISRN Surgery
Figure 3: Stained slide showing microphotograph of phyllodes
Figure 4: Stained slide showing microphotograph of phyllodes
(d) the morphology of the naked nuclei (especially the
See Table 3.
Core Needle Biopsy. Fibroepithelial lesions with cellular
stroma in breast core needle biopsy (CNB) specimens may
result in either fibroadenoma or phyllodes tumor at exci-
sion. Assessment of stromal cellularity, stromal cell atypia,
mitoses, and relative proportion of stroma to epithelium are
mainly helpful to reach the diagnosis. Phyllodes tumors are
increased stromal cellularity and mitotic activity. However,
benign phyllodes tumor by definition lacks marked atypia
Figure 5: Stained slide showing microphotograph of phyllodes
Figure 6: Stained slide showing microphotograph of phyllodes
and excess mitotic activity in its stromal component, and
juvenile fibroadenoma may also have cellular stroma, pre-
senting a source of increased diagnostic difficulty. Diagnosis
relies on the recognition of the exaggerated intracanalicular
growth pattern in phyllodes tumor. In addition, the stromal
proliferation in juvenile fibroadenoma tends to be relatively
uniform, whereas in phyllodes tumor it is often (though not
always) more prominent in the periductal areas. The stromal
cellularity in phyllodes tumor may be heterogeneous. Con-
sequently, surgical excision is recommended for complete
evaluation of the lesion.
Jacobs et al.  found that 4 stromal features in
CNB specimens (i.e., cellularity, nuclear atypia, mitoses, and
between cases that were fibroadenoma at excision compared
with those that were phyllodes tumor. However, only cases
that had mildly or markedly increased stromal cellularity in
CNB specimens were absolutely predictive of fibroadenoma
or phyllodes tumor, respectively. Among the subset of cases
with moderate stromal cellularity in the CNB specimens, the
Benign phyllodes tumors Borderline phyllodes tumors
(i) There is predominance of the stromal
component as compared to the epithelial
(ii) Frequent hypercellular stromal
fragments, an average of 2 in each
(iii) Frequent large spindle cells and
monomorphic naked stromal nuclei.
Malignant phyllodes tumors
(i) Stromal fragments of variable
dimensions, with moderate cellularity,
made of discohesive spindle cells, with
(ii) Minimal/no epithelial elements found
on the smears.
(iii) Presence of atypical multinucleated
The stromal compound, represented by
stromal fragments, isolated stromal cells,
and naked stromal nuclei are found to be
more numerous than the epithelial one in
most of the cases.
(i) Sudden increase in size in a longstanding breast lesion
(ii) Apparent fibroadenoma>3cm diameter or in patient >35 years
(ii) Attenuation or cystic areas within a solid mass on Ultrasonography
(i) Presence of hypercellular stromal fragments
(ii) Indeterminate features
ANY 2 features mandate core biopsy
(i) Rounded borders/lobulated appearance at mammography
presence of stromal mitoses remained the single histological
feature significantly different between the phyllodes tumor
and fibroadenoma groups.
Sarcomatous stromal elements, including angiosarcoma,
chondrosarcoma, leiomyosarcoma, osteosarcoma, liposar-
coma, and rhabdomyosarcoma, are rarely encountered in
malignant phyllodes tumors.
Paddington Clinicopathological Suspicion Score. This outlines
criteria to assist in the selection of patients for core biopsy,
for use in conjunction with existing local protocols. The aim
diagnosis (see Box 1).
5.3.3. Differential Diagnosis. It includes the following:
(v) juvenile papillomatosis,
(viii) metastatic tumor.
Management. Surgical management is the mainstay but the
type of surgery has been a source of debate over the years.
surgery versus mastectomy in terms of metastasis-free sur-
vival or overall survival, despite the higher incidence of local
recurrence that comes with breast conserving surgery .
If diagnosed preoperatively, tumor should be resected
with at least 1cm margins particularly in the borderline and
malignant phyllodes tumors. This can be accomplished by
either lumpectomy or mastectomy, depending upon the size
of the tumor relative to the breast. For benign phyllodes
tumors diagnosed after local excision of what appeared to
be a fibroadenoma, a “watch and wait” policy does appear
to be safe. With such an approach, local recurrence and five
year survival rates of 4% and 96% respectively have been
benign phyllodes tumors who have undergone local excision
and have histologically positive specimen margins should
undergo further surgery or be entered in a surveillance pro-
phyllodes tumors identified after local excision should be
Twenty percent of tumors grow larger than 10cm, the
arbitrary cutoff point for the designation as giant phyllodes
tumor, an entity that presents the surgeon with several
unique management problems. These tumors can reach sizes
up to 40cm in diameter . Since an excision with the
required margins is often impossible in giant phyllodes
tumors, mastectomy should be reserved for larger tumors
and should be considered in recurrent tumors, especially
of the malignant histotype [2, 36–38]. Local recurrence in
phyllodes tumors has been associated with inadequate local
excision and various histological characteristics, including
mitotic activity, tumor margin, and stromal cellular atypia.
Depending on the size of the breast and the location of
the phyllodes tumor, mastectomy may also be required
for tumors that are between 5 and 10cm in diameter
. While managing a giant phyllodes tumor, emphasis
should be on complete extirpation of all visible tumors and
6 ISRN Surgery
breast tissue during mastectomy to minimize the chances of
As malignant phyllodes tumors undergo mainly hema-
togenous spread, the proportion of patients with lymph
node metastases are <1% (lymph node enlargement in about
for malignant cells.
Chest wall invasion appears to be an uncommon event
with phyllodes tumors , extended excision of involved
pectoralis muscle, followed by reconstruction of the chest
wall with marlex mesh or latissimus dorsi muscular/myocu-
taneous flap been recommended if the fascia or muscle is
infiltrated. Some have recommended the consideration of
postoperative radiation for cases of chest wall infiltration.
Foreknowledge of the location of the tumor’s blood
Jonsson and Libshitz documented the angiographic pattern
of a 25cm phyllodes tumor via one large and several smaller
perforating anterior branches of the internal mammary,
axillary artery . Liang et al.  found that the giant
tumors in the present report derived the majority of their
blood supply from skin collaterals. Thus, the surgeon can
expect the majority of blood loss during resection to come
from the creation of the skin flaps. In this situation, the
surgeon need not routinely obtain an angiogram.
In general, immediate breast reconstruction can be per-
formed at the time of mastectomy for phyllodes tumors .
tectomy was performed for a large phyllodes tumor, followed
by immediate implantation of a breast prosthesis. They cite
minimal interference with the detection of recurrent lesions
and the minimization of emotional distress as advantages to
an adolescent female in which a silicon implant was placed
under the pectoralis major, where it would not impair the
recognition of recurrent disease . Local recurrence rates
for phyllodes tumors are 15 to 20% and are correlated with
positive excision margins, rather than with tumor grade or
size [1, 16, 42, 45]. Other studies have shown a higher risk
of local recurrence in borderline and malignant tumors. In
a series of 21 patients by Salvadori et al., 51 patients were
treated with breast conserving surgery (enucleations, wide
excisions), and 14 of the tumors recurred locally. In contrast,
the 20 patients treated with mastectomy (subcutaneous,
modified radical, or radical) showed no evidence of local
recurrence . Importantly, there is no contraindication to
immediate reconstruction after mastectomy in cases of giant
phyllodes tumor, and this decision can be made solely based
upon patient preference [43, 44].
10%) and routine axillary clearance is not recommended.
Axillary dissection is required, when histologically positive
NCCN Guidelines for the Management of Phyllodes Tumor.
with the intention of obtaining surgical margins ≥1cm.
rence risk, but are not an absolute indication for mastectomy
(see Figure 7).
Role of Adjuvant Therapy. The role of adjuvant radiother-
apy and chemotherapy remains uncertain, but encouraging
results using radiotherapy and chemotherapy for soft-tissue
sarcomas suggest that consideration be given for their use in
cases of malignant phyllodes tumors [46–50].
Chaney et al.  found adjuvant radiotherapy to be ben-
eficial in patients with adverse features (e.g., bulky tumors,
close or positive surgical margins, hypercellular stroma,
high nuclear pleomorphism, high mitotic rate, presence of
necrosis, and increased vascularity within the tumor and
tumor recurrence) but the use is controversial. A study done
by Richard J. Barth Jr demonstrated that margin-negative
therapy for local control of borderline and malignant phyl-
lodes tumors. In MD Anderson Cancer Center, radiotherapy
is recommended only for cases with positive or near-positive
procedures cannot be performed.
Chemotherapy, including anthracyclines, ifosfamide, cis-
platin, and etoposide, has been mentioned in various studies
but with no survival advantage.
The use of hormonal therapy, such as tamoxifen, has not
been fully investigated in cystosarcoma phyllodes. Estrogen
and 84%, respectively, of the epithelium and less than 5% of
the stromal cells. Still, the use of endocrine therapy in either
the adjuvant or palliative setting has not been extensively
Patient age does not appear to be important but tumors
presenting in adolescence do seem to be less aggressive
irrespective of their histological type. The size of the tumor
not as such but in relation to the breast appears important as
specimen resection margins.
Most distant metastases develop from borderline or
malignant tumors. Unlike local recurrence, tumor size does
appear to be an important factor in predicting for metastatic
spread. Many histological prognostic factors have been eval-
uated. Different studies have regarded stromal overgrowth,
tumor necrosis, infiltrating margins, mixed mesenchymal
components, high mitotic rate, and stromal atypia as impor-
tant but in isolation each appears to have a low predictive
5.3.4. Role of Tumor Markers in Phyllodes Tumor. Increased
p53 protein and Ki-67 antigen expression has been detected
in malignant phyllodes tumors and they may be valuable
in differentiating fibroadenomas from phyllodes tumors.
Furthermore, in phyllodes tumors, p53 and Ki-67 expression
has been shown to correlate with negative prognostic factors.
Philip C. W. et al. showed the role of angiogenesis and
found that the higher the microvessel density, the higher the
degree of malignancy for the phyllodes tumor.
by stromal cells in phyllodes tumors is correlated with histo-
logical parameters such as grade, implying a possible role of
Clinical presentation Clinical suspicion of phyllodes tumor
Imaging with ultrasound suggestive of
fibroadenoma except for size and/or
history of growth
Workup History and physical examination
Wide excision (≥1 cm) without
Fibroadenoma Excisional biopsy
including benign, borderline,
Core needle biopsy
Fibroadenoma or indeterminate
Mammogram for women ≥30 yrs
Wide excision (≥1 cm) without
Large size (>2 cm)
is up to 46%. This provides additional strong evidence
that c-kit receptor-mediated tyrosine kinase activity may be
involved early on in the pathogenesis of phyllodes tumors,
and the new therapeutic agent, STI571, Glivec, may be a
useful drug therapy for this disease, particularly in the tumor
recurrences and advanced-stage disease. Marick Lae et al.
showed that chromosomal changes detected by comparative
genomic hybridization (CGH) could be helpful in grading
phyllodes tumors. In flow cytometric studies, correlations
between DNA content, cell proliferation, and histological
grade have been demonstrated. Some studies have identified
a correlation between these markers of cellular proliferation
and clinical outcome, however, most have not. Recent small
studies have suggested that telomerase, a ribonucleoprotein
enzyme that generates telomeres (DNA sequences important
in determining cell immortality), may be a useful prognostic
factor in phyllodes tumors.
Recurrence. To date, local recurrence rates ranging from 10%
to 40% have been reported with most series averaging about
15%. Local recurrence appears to be related to the extent
of the initial surgery and should be regarded as a failure of
primary surgical treatment. Whether malignant tumors have
an increased risk of recurrence is unclear but when it does
occur it is invariably seen earlier than with benign tumors.
In multivariate analysis, the surgical margin is found to be
the only independent predictive factor for local recurrence.
In most patients, local recurrence is isolated and is not
associated with the development of distant metastases.
This is often seen irrespective of either the histological
type of the tumor or the extent of the specimen margins.
Local recurrence can usually be controlled by further wide
excision (with 1cm margins) and mastectomy is not invari-
ably required. Mastectomy should, however, be considered
for local recurrence after local surgery for borderline or
malignant tumors. Occasionally aggressive local recurrence
can result in widespread chest wall disease with direct
of good palliation in this situation with radiotherapy have
NCCN Guidelines for the Management of Recurrence. See
Metastasis. Overall, 10% of patients with phyllodes tumors
develop distant metastases and these eventually occur in
approximately 25% of patients with histologically malignant
8 ISRN Surgery
Locally recurrent breast mass following
excision of phyllodes tumor
History and physical examination
Consider chest imaging
No metastatic disease
Reexcision with wide margins without
Consider postoperative radiotherapy∗∗
Metastatic disease management following
principles of soft tissue sarcoma
∗∗There is no prospective randomized data supporting the use of radiation treatment with phyllodes
tumors. However, in the setting where additional recurrence would create significant morbidity, e.g.,
chest wall recurrence following salvage mastectomy, radiation therapy may be considered, following
the same principles that are applied to the treatment of soft tissue sarcoma.
tumors. Most distant metastases develop without evidence of
local recurrence. The commonest sites for distant metastases
are the lungs (66%), bones (28%), and brain (9%) and in rare
instances, the liver and heart. The risk of metastatic disease
does not appear to be influenced by the extent of the initial
surgery and appears to be predetermined by tumor biology.
Metastatic phyllodes tumors have a poor prognosis and no
especially when not excised with a clear margins and very
essary to follow up the patient regularly at 6-month interval
for the first two years (chances of recurrence are maximum
in the first two years) and then on yearly basis. Patients
must be instructed to self examine her breast regularly and
consult her doctor, if any abnormality detected. In followup,
it should be investigated with USG, mammogram, MRI, or
Phyllodes tumor bears specific clinical characteristic and
can be considered as a differential diagnosis for the breast
lumps. The preoperative diagnosis and proper management
are crucial in phyllodes tumor because of their tendency to
recur and malignant potential in some of these tumors.
Conflict of Interests
The authors declared that they have no conflict of interests.
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