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Review Article
Phyllodes Tumor of Breast: A Review Article
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
cited.
Introduction. Phyllodes tumours are rare fibroepithelial lesions. Accurate preoperative pathological diagnosis allows correct surgical
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 4 cm 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
pathological positive nodes. Mammography and ultrasonography are main imaging modalities. Cytologically the presence of both
epithelial and stromal elements supports the diagnosis. The value of FNAC in diagnosis of phyllodes tumour remains controversial,
but core needle biopsy has high sensitivity and negative predictive value. Surgical management is the mainstay and local recurrence
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
management are crucial in phyllodes tumours because of their tendency to recur and malignant potential in some of these tumours.
Table 1 Table 2
Criteria Benign Borderline Malignant Histological type
Criteria
Stromal Benign Borderline Malignant
cellularity Minimal Moderate Marked Tumor margins Pushing ↔ Infiltrative
and atypia Stroma cellularity Low Moderate High
Stromal Marked Mitotic rate (per 10 hpf) <5 5–9 ≥10
Minimal Moderate
overgrowth Pleomorphism Mild Moderate Severe
Mitoses/10
high power 0–4 5–9 ≥10
fields
Well Zone of
Tumor circumscribed microscopic Infiltrative
margins with pushing invasion around tumor margins
tumor margins tumor margins
Table 3
Benign phyllodes tumors Borderline phyllodes tumors Malignant phyllodes tumors
(i) There is predominance of the stromal (i) Stromal fragments of variable
component as compared to the epithelial dimensions, with moderate cellularity,
The stromal compound, represented by
one. made of discohesive spindle cells, with
stromal fragments, isolated stromal cells,
(ii) Frequent hypercellular stromal atypical nuclei.
and naked stromal nuclei are found to be
fragments, an average of 2 in each (ii) Minimal/no epithelial elements found
more numerous than the epithelial one in
microscopical field. on the smears.
most of the cases.
(iii) Frequent large spindle cells and (iii) Presence of atypical multinucleated
monomorphic naked stromal nuclei. giant cells.
Clinical findings
(i) Sudden increase in size in a longstanding breast lesion
(ii) Apparent fibroadenoma > 3 cm diameter or in patient >35 years
Imaging findings
(i) Rounded borders/lobulated appearance at mammography
(ii) Attenuation or cystic areas within a solid mass on Ultrasonography
FNAC findings
(i) Presence of hypercellular stromal fragments
(ii) Indeterminate features
ANY 2 features mandate core biopsy
Box 1
presence of stromal mitoses remained the single histological If diagnosed preoperatively, tumor should be resected
feature significantly different between the phyllodes tumor with at least 1 cm margins particularly in the borderline and
and fibroadenoma groups. malignant phyllodes tumors. This can be accomplished by
Sarcomatous stromal elements, including angiosarcoma, either lumpectomy or mastectomy, depending upon the size
chondrosarcoma, leiomyosarcoma, osteosarcoma, liposar- of the tumor relative to the breast. For benign phyllodes
coma, and rhabdomyosarcoma, are rarely encountered in tumors diagnosed after local excision of what appeared to
malignant phyllodes tumors. be a fibroadenoma, a “watch and wait” policy does appear
to be safe. With such an approach, local recurrence and five
Paddington Clinicopathological Suspicion Score. This outlines year survival rates of 4% and 96% respectively have been
criteria to assist in the selection of patients for core biopsy, reported for benign phyllodes tumors. Whether patients with
for use in conjunction with existing local protocols. The aim benign phyllodes tumors who have undergone local excision
of developing the score is to improve the rates of preoperative and have histologically positive specimen margins should
diagnosis (see Box 1). undergo further surgery or be entered in a surveillance pro-
gram is controversial. Reexcision of borderline and malignant
5.3.3. Differential Diagnosis. It includes the following: phyllodes tumors identified after local excision should be
considered.
(i) fibroadenoma, Twenty percent of tumors grow larger than 10 cm, the
(ii) adenoma, arbitrary cutoff point for the designation as giant phyllodes
(iii) hamartoma, tumor, an entity that presents the surgeon with several
unique management problems. These tumors can reach sizes
(iv) lipoma, up to 40 cm in diameter [15]. Since an excision with the
(v) juvenile papillomatosis, required margins is often impossible in giant phyllodes
tumors, mastectomy should be reserved for larger tumors
(vi) carcinoma,
and should be considered in recurrent tumors, especially
(vii) sarcomas, of the malignant histotype [2, 36–38]. Local recurrence in
(viii) metastatic tumor. phyllodes tumors has been associated with inadequate local
excision and various histological characteristics, including
Management. Surgical management is the mainstay but the mitotic activity, tumor margin, and stromal cellular atypia.
type of surgery has been a source of debate over the years. Depending on the size of the breast and the location of
Studies have shown no differences between breast conserving the phyllodes tumor, mastectomy may also be required
surgery versus mastectomy in terms of metastasis-free sur- for tumors that are between 5 and 10 cm in diameter
vival or overall survival, despite the higher incidence of local [39]. While managing a giant phyllodes tumor, emphasis
recurrence that comes with breast conserving surgery [35]. should be on complete extirpation of all visible tumors and
6 ISRN Surgery
breast tissue during mastectomy to minimize the chances of Role of Adjuvant Therapy. The role of adjuvant radiother-
recurrence. apy and chemotherapy remains uncertain, but encouraging
As malignant phyllodes tumors undergo mainly hema- results using radiotherapy and chemotherapy for soft-tissue
togenous spread, the proportion of patients with lymph sarcomas suggest that consideration be given for their use in
node metastases are <1% (lymph node enlargement in about cases of malignant phyllodes tumors [46–50].
10%) and routine axillary clearance is not recommended. Chaney et al. [51] found adjuvant radiotherapy to be ben-
Axillary dissection is required, when histologically positive eficial in patients with adverse features (e.g., bulky tumors,
for malignant cells. close or positive surgical margins, hypercellular stroma,
Chest wall invasion appears to be an uncommon event high nuclear pleomorphism, high mitotic rate, presence of
with phyllodes tumors [15], extended excision of involved necrosis, and increased vascularity within the tumor and
pectoralis muscle, followed by reconstruction of the chest tumor recurrence) but the use is controversial. A study done
wall with marlex mesh or latissimus dorsi muscular/myocu- by Richard J. Barth Jr demonstrated that margin-negative
taneous flap been recommended if the fascia or muscle is resection combined with adjuvant radiotherapy is an effective
infiltrated. Some have recommended the consideration of therapy for local control of borderline and malignant phyl-
postoperative radiation for cases of chest wall infiltration. lodes tumors. In MD Anderson Cancer Center, radiotherapy
Foreknowledge of the location of the tumor’s blood is recommended only for cases with positive or near-positive
supply can be vital information when removing large tumors. surgical margins and selected cases for whom further surgical
Jonsson and Libshitz documented the angiographic pattern procedures cannot be performed.
of a 25 cm phyllodes tumor via one large and several smaller Chemotherapy, including anthracyclines, ifosfamide, cis-
perforating anterior branches of the internal mammary, platin, and etoposide, has been mentioned in various studies
lateral thoracic, acromiothoracic arteries, and branches of the but with no survival advantage.
axillary artery [40]. Liang et al. [41] found that the giant The use of hormonal therapy, such as tamoxifen, has not
tumors in the present report derived the majority of their been fully investigated in cystosarcoma phyllodes. Estrogen
blood supply from skin collaterals. Thus, the surgeon can and progesterone receptor expression has been shown in 43%
expect the majority of blood loss during resection to come and 84%, respectively, of the epithelium and less than 5% of
from the creation of the skin flaps. In this situation, the the stromal cells. Still, the use of endocrine therapy in either
surgeon need not routinely obtain an angiogram. the adjuvant or palliative setting has not been extensively
In general, immediate breast reconstruction can be per- studied.
formed at the time of mastectomy for phyllodes tumors [42].
Mendel et al. [43] reported a case in which subcutaneous mas- Prognostic Factors. No reliable clinical prognostic factors have
tectomy was performed for a large phyllodes tumor, followed been identified that predict for local recurrence or metastasis.
by immediate implantation of a breast prosthesis. They cite Patient age does not appear to be important but tumors
minimal interference with the detection of recurrent lesions presenting in adolescence do seem to be less aggressive
and the minimization of emotional distress as advantages to irrespective of their histological type. The size of the tumor
the procedure. Orenstein and Tsur described a similar case in not as such but in relation to the breast appears important as
an adolescent female in which a silicon implant was placed this usually determines the extent of surgery and the resulting
under the pectoralis major, where it would not impair the specimen resection margins.
recognition of recurrent disease [44]. Local recurrence rates Most distant metastases develop from borderline or
for phyllodes tumors are 15 to 20% and are correlated with malignant tumors. Unlike local recurrence, tumor size does
positive excision margins, rather than with tumor grade or appear to be an important factor in predicting for metastatic
size [1, 16, 42, 45]. Other studies have shown a higher risk spread. Many histological prognostic factors have been eval-
of local recurrence in borderline and malignant tumors. In uated. Different studies have regarded stromal overgrowth,
a series of 21 patients by Salvadori et al., 51 patients were tumor necrosis, infiltrating margins, mixed mesenchymal
treated with breast conserving surgery (enucleations, wide components, high mitotic rate, and stromal atypia as impor-
excisions), and 14 of the tumors recurred locally. In contrast, tant but in isolation each appears to have a low predictive
the 20 patients treated with mastectomy (subcutaneous, value.
modified radical, or radical) showed no evidence of local
recurrence [2]. Importantly, there is no contraindication to 5.3.4. Role of Tumor Markers in Phyllodes Tumor. Increased
immediate reconstruction after mastectomy in cases of giant p53 protein and Ki-67 antigen expression has been detected
phyllodes tumor, and this decision can be made solely based in malignant phyllodes tumors and they may be valuable
upon patient preference [43, 44]. in differentiating fibroadenomas from phyllodes tumors.
Furthermore, in phyllodes tumors, p53 and Ki-67 expression
NCCN Guidelines for the Management of Phyllodes Tumor. has been shown to correlate with negative prognostic factors.
According to NCCN guidelines wide excision means excision Philip C. W. et al. showed the role of angiogenesis and
with the intention of obtaining surgical margins ≥1 cm. found that the higher the microvessel density, the higher the
Narrow surgical margins are associated with high local recur- degree of malignancy for the phyllodes tumor.
rence risk, but are not an absolute indication for mastectomy Gary M. K. Tse et al. found that CD117 protein expression
when partial mastectomy fails to achieve margin width ≥1 cm by stromal cells in phyllodes tumors is correlated with histo-
(see Figure 7). logical parameters such as grade, implying a possible role of
ISRN Surgery 7
Findings Treatment
Phyllodes tumors
including benign, borderline, Wide excision (≥1 cm) without
and malignant axillary staging
Figure 7
their being used as adjunctive markers of malignancy in these an increased risk of recurrence is unclear but when it does
tumors. In malignant phyllodes tumors, the rate of expression occur it is invariably seen earlier than with benign tumors.
is up to 46%. This provides additional strong evidence In multivariate analysis, the surgical margin is found to be
that c-kit receptor-mediated tyrosine kinase activity may be the only independent predictive factor for local recurrence.
involved early on in the pathogenesis of phyllodes tumors, In most patients, local recurrence is isolated and is not
and the new therapeutic agent, STI571, Glivec, may be a associated with the development of distant metastases.
useful drug therapy for this disease, particularly in the tumor In a minority of patients repeated local recurrence occurs.
recurrences and advanced-stage disease. Marick Lae et al. This is often seen irrespective of either the histological
showed that chromosomal changes detected by comparative type of the tumor or the extent of the specimen margins.
genomic hybridization (CGH) could be helpful in grading Local recurrence can usually be controlled by further wide
phyllodes tumors. In flow cytometric studies, correlations excision (with 1 cm margins) and mastectomy is not invari-
between DNA content, cell proliferation, and histological ably required. Mastectomy should, however, be considered
grade have been demonstrated. Some studies have identified for local recurrence after local surgery for borderline or
a correlation between these markers of cellular proliferation malignant tumors. Occasionally aggressive local recurrence
and clinical outcome, however, most have not. Recent small can result in widespread chest wall disease with direct
studies have suggested that telomerase, a ribonucleoprotein invasion of the underlying lung parenchyma. Isolated reports
enzyme that generates telomeres (DNA sequences important of good palliation in this situation with radiotherapy have
in determining cell immortality), may be a useful prognostic been published.
factor in phyllodes tumors.
NCCN Guidelines for the Management of Recurrence. See
Recurrence. To date, local recurrence rates ranging from 10% Figure 8.
to 40% have been reported with most series averaging about
15%. Local recurrence appears to be related to the extent Metastasis. Overall, 10% of patients with phyllodes tumors
of the initial surgery and should be regarded as a failure of develop distant metastases and these eventually occur in
primary surgical treatment. Whether malignant tumors have approximately 25% of patients with histologically malignant
8 ISRN Surgery
∗∗
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.
Figure 8
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10 ISRN Surgery