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com
JCP Online First, published on January 4, 2016 as 10.1136/jclinpath-2015-203545
1
Department of General
Surgery, Singapore General
Hospital, Singapore
2
Division of Surgical Oncology,
National Cancer Centre
Singapore, Singapore
3
Department of Pathology,
Singapore General Hospital,
Singapore
Correspondence to
Dr Puay Hoon Tan, Department
of Pathology, Level 7,
Diagnostics Tower, Academia,
Singapore General Hospital,
20 College Road, Singapore
169856, Singapore; tan.puay.
hoon@sgh.com.sg
Received 30 November 2015
Accepted 7 December 2015
To cite: Lim SZ, Ong KW,
Tan BKT, et al. J Clin Pathol
Published Online First:
[please include Day Month
Year] doi:10.1136/jclinpath-
2015-203545
Copyright Article author (or their employer) 2016. Produced by BMJ Publishing Group Ltd under licence.
Sarcoma of the breast: an update on a rare entity
Sue Zann Lim,1 Kong Wee Ong,2 Benita Kiat Tee Tan,1 Sathiyamoorthy Selvarajan,3
Puay Hoon Tan3
ABSTRACT
Breast sarcoma is a rare condition. It consists of a
heterogeneous group of non-epithelial tumours arising
from the mesenchymal tissue of the breast. It has a
distinctly different natural history, treatment response
and prognosis as compared with carcinoma of the
breast. A different diagnostic approach and treatment
strategy have to be defined for this group of tumours.
Due to its rarity, the current understanding on breast
sarcoma is limited and is mostly based on small
retrospective case series or case reports. Hence, the
management generally follows the algorithms derived
from randomised control trials of soft tissue sarcomas in
the extremities and chest wall. Through this review, we
discuss the results of major retrospective studies on
breast sarcomas including data on epidemiology,
aetiology, diagnostic approach, treatment strategies and
outcomes of this challenging and potentially aggressive
condition.
INTRODUCTION
Breast sarcoma is a rare condition. It consists of a
heterogeneous group of non-epithelial tumours
arising from mesenchymal tissues of the breast.
They account for <1% of all breast malignancies
and <5% of all sarcomas.1 2 According to a study
in the USA, the annual incidence of breast sarcomas
is 44.8 new cases per 10 million women and this
has remained constant from 1973 to1986.3 The
initial series of breast sarcomas was reported by
Schmidt in 1887 where he documented 11 cases of
breast angiosarcoma.4 To date, most published arti-
cles are still limited to small retrospective case
series or individual reports, and thus it has been
difficult to draw significant conclusions from them.
The objective of this review is to provide an
updated overview of the current literature on the
epidemiology, aetiology, diagnostic approach, treat-
ment strategies and outcomes of breast sarcomas.
This review will focus on malignant mesenchymal
tumours of the breast, excluding malignant phyl-
lodes tumour, mesenchymal-like metaplastic carcin-
oma and dermatofibrosarcoma protuberans. A
PubMed literature search was conducted for the
terms ‘breast’ and ‘sarcoma’. The key English lan-
guage studies on breast sarcomas following the above
definition were included in this review (table 1).
AETIOLOGY
Primary breast sarcomas are tumours arising de
novo from the mesenchymal tissues of the breast.
The predisposing factors for primary breast sarco-
mas are largely unknown. As with other soft tissue
sarcomas, there are some genetic conditions that
are associated with a higher risk for breast sarco-
mas, including Li–Fraumeni syndrome, familial
Lim SZ, et al. J Clin Pathol 2016;0:1–9. doi:10.1136/jclinpath-2015-203545
Review
adenomatous polyposis and neurofibromatosis type
1.21–23 The development of breast sarcomas is
strongly associated with TP53 mutation in Li–
Fraumeni syndrome.21 There are several environ-
mental exposures that have been suggested as pos-
sible risk factors for breast sarcomas, namely
previous exposure to arsenic compounds, vinyl
chloride and alkylators.23 There are also reports of
Kaposi’s sarcomas secondary to underlying HIV
and human herpes virus infection occurring in the
breast.24–26
Secondary breast sarcomas most often occur fol-
lowing external beam radiation therapy for the
breast or other intrathoracic malignancies. Breast
carcinoma and non-Hodgkin’s lymphoma are the
most common antecedent malignancies in
radiation-induced sarcomas.27–29 The incidence of
radiation-induced breast sarcomas is low, occurring
in about 0.2% of patients with breast carcinoma
treated with radiation.30 The risk of radiation-
induced sarcomas generally increases with higher
dose of radiotherapy, exposure in childhood, con-
current administration of chemotherapy, and
genetic conditions such as ataxia telangiectasia and
BRCA-1 mutation.31 32 The common histological
subtypes in radiation-induced breast sarcoma are
angiosarcoma, undifferentiated pleomorphic
sarcoma, leiomyosarcoma and liposarcoma.33–35
Huang and Mackillop36 demonstrated that patients
with breast cancer treated with radiotherapy had a
15.9 times higher risk of developing angiosarcomas
as compared with controls who received no radi-
ation. They suggested that radiotherapy may
increase the risk of angiosarcomas directly by
causing radiogenetic mutations in the irradiated
field and also indirectly by contributing to the
development of lymphoedema. It was also reported
that the risk of developing radiation-induced
sarcomas started to increase within 5 years after
radiotherapy and peaked at 5–10 years. Radiation-
induced angiosarcomas are genetically different
from primary breast angiosarcomas and are often
associated with high MYC and FLT4 gene amplifi-
cation.37 In a separate study by Blanchard et al,33
angiosarcomas were shown to have a shorter
latency period as compared with other soft tissue
sarcoma histological subtypes. It is still unclear
whether new techniques in accelerated partial
breast irradiation will reduce the risk of
radiation-induced sarcomas since they focus radi-
ation only to the tumour bed and spare the rest of
the breast from radiation. Besides, hypofractionated
regimens for whole breast radiotherapy may also
influence the risk for radiation-induced sarcomas.
The association between lymphangiosarcoma and
chronic lymphoedema is well recognised.38 Stewart
and Treves were the first to report the syndrome of
1
2

Review
Table 1 Patient demographics, tumour characteristics, prognostic factors and clinical outcomes in major breast sarcoma series
Patient Age Age Size Size
Author Year no Female Male (median) (range) (median) (range) Most common histological subtypes Prognostic factors Clinical outcomes

Adem et al 5
2004 25 25 0 43 24–81 5 cm 0.3–12 cm Fibrosarcoma (n=6), angiosarcoma (n=6), pleomorphic Size 1. 5-Year OS 66%

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sarcoma (n=6) 2. 5-Year cause-specific survival 70%
Barnes and 1977 10 10 0 56 26–71 5 cm 3–15 cm Fibrosarcoma (n=5) 1. Tumour border UK
Pietruszka6 2. Cellular pleomorphism
3. Mitosis
4. Histological subtype
Barrow et al7 1999 59 UK UK 45 16–78 UK UK Malignant fibrous histiocytoma, fibrosarcoma or 1. Size 1. Median DFS 18 months
stromal sarcoma (n=32) 2. Margin status 2. Median OS 66 months
3. Histological subtype
Berg et al8 1961 25 24 1 UK 25–64 6 cm UK Stromal sarcoma (n=25) Extent of surgery 5-Year OS 60%
Bousquet et al9 2007 103 UK UK 55 13–86 4.45 cm 0.8–22 cm Angiosarcoma (n=42) 1. Histological subtype 1. 5-Year DFS 44%
2. Margin status 2. 10-Year DFS 36%
3. Grade 3. 5-Year OS 55%
4. 10-Year OS 51%
Fields et al10 2008 13 UK UK 50 32–72 5.5 cm 2–11 cm Leiomyosarcoma (n=3), malignant fibrous histiocytoma Size 5-Year OS 67%
(n=3), fibrosarcoma (n=3)
Gutman et al11 1994 60 UK UK UK UK UK UK UK 1. Size 1. Median OS 67 months
2. Histological subtype 2. Median DFS 18 months
3. Adjuvant therapy
Johnstone et al12 1992 10 10 0 28 15–56 UK UK Angiosarcoma (n=4) UK 1. 5-Year OS 66%
2. 5-Year DFS 68%
Lim SZ, et al. J Clin Pathol 2016;0:1–9. doi:10.1136/jclinpath-2015-203545

Norris and Taylor13 1967 32 UK UK 49 13–84 4 cm 1–19 cm UK 1. Tumour border 5-Year OS 73%
2. Cellular atypism
North et al14 1998 25 24 1 55 UK UK UK Angiosarcoma (n=10) None 5-Year OS 61%
Pandey et al15 2004 19 19 0 36 12–70 10 cm 4–18 cm Angiosarcoma (n=8) Margin status 1. 3-Year DFS 39%
2. Median DFS 33 months
Pollard et al1 1990 25 24 1 UK 24–79 UK 2–13 cm Malignant fibrous histiocytoma (n=11) 1. Tumour border 1. Average DFS 22 months
2. Mitosis 2. Average OS 18.7 months
3. Giant cells
Smola et al16 1993 7 6 1 UK UK 12.8 cm 4.5–26 cm UK UK UK
Stanley et al17 1987 4 4 0 61 43–85 UK UK Angiosarcoma (n=2), malignant fibrous histiocytoma UK UK
(n=2)
Surov et al18 2011 21 21 0 66 27–86 2.5 cm 1–11 cm Fibrosarcoma (n=8) UK UK
Toesca et al19 2012 37 36 1 UK UK UK UK Angiosarcoma (n=34) None 1. 5-Year DFS 29.2%
2. 5-Year OS 56.6%
Zelek et al20 2003 83 UK UK 47 17–89 6.5 cm 1.5–30 cm Malignant fibrous histiocytoma (n=58) 1. Tumour size 1. 10-Year OS 62%
2. Grade 2. 10-Year DFS 50%
3. Histological subtype
DFS, disease-free survival; OS, overall survival; UK, unknown.
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postmastectomy lymphangiosarcomas arising in the upper
extremities, breast and axilla in the presence of longstanding
extensive lymphoedema.39 Factors contributing to chronic lym-
phoedema include mastectomy, axillary dissection and radio-
therapy. Impaired immune responsiveness in anatomical areas
affected by lymphatic obstruction has been suggested to allow
unrestricted sarcomatous tumour growth.40
CLINICAL PRESENTATION
Breast sarcomas occur almost entirely in females, although there
have been rare cases reported in males. In our review, we found
that 97.6% of the patients were female while 2.4% were male
(table 1).1 5 6 8 12 14–19 These are similar to the figures reported
by Al-Benna et al41 previously.
Breast sarcomas are usually diagnosed during the fifth or sixth
decades of life. The median age of diagnosis was 49.5 years
old though the range was fairly wide (12–89 years old;
table 1).1 5–10 12–15 17 18 20 Patients with secondary breast
sarcomas are usually older than those with primary breast sarco-
mas mainly because they develop after treatment for carcinoma of
the breast. Rarely, sarcomatous metastasis to the breast can occur.
Breast sarcomas are generally large, with a median size of 5.25 cm,
ranging from 0.3 to 30 cm (table 1).1 5 6 8–10 13 15 16 18 20
Patients typically present with a firm, well-defined, unilateral
breast mass, which is rapidly growing in size. It is rarely asso-
ciated with pain or overlying skin changes. However, angiosar-
comas can cause blue or purple discolouration of the overlying
skin reflecting haemorrhage or vascularity of the lesion.42 43
The disease process may also involve the cutaneous layer result-
ing in thickening of the skin.43
DIAGNOSIS
Radiological imaging
The appearance of breast sarcomas on radiological imaging is
non-specific. Breast sarcoma most often presents as an opaque
mass on mammogram. It is very rarely associated with spicula-
tion and microcalcification.44 Thus, its mammographic appear-
ance may mimic a benign condition such as fibroadenoma. The
mammogram may appear normal even in the presence of a palp-
able breast sarcoma with skin involvement.45 46 Similarly, there
is no specific diagnostic feature for breast sarcoma on ultrason-
ography, usually appearing as an irregular mass with indistinct
edges and no shadowing.47
MRI has been increasingly used to assess the extent of disease
in breast sarcomas. Malignant tumours characteristically display
rapid contrast enhancement and washout characteristics.47 48
Surov et al18 reported marked inhomogeneous contrast
enhancement on MRI for all breast sarcomas in their study. Due
to the hypervascular nature of angiosarcomas, they typically
have low signal intensity on T1-weighted images, but high
signal intensity on T2-weighted images.45
Histology
As with other non-breast soft tissue sarcomas, breast sarcomas
comprise a diverse mix of histological subtypes (figures 1–3).
Many disparate classification schemes have been used. Some
series have included different entities under the rubric of breast
sarcomas, namely malignant phyllodes tumours, metaplastic car-
cinomas and dermatofibrosarcoma protuberans.2 49–51 However,
malignant phyllodes tumours are considered a distinct entity
from breast sarcomas in view of its epithelial component, which
relegate them with fibroepithelial neoplasms.52 Metaplastic car-
cinoma is clearly different from breast sarcomas since it is of
Lim SZ, et al. J Clin Pathol 2016;0:1–9. doi:10.1136/jclinpath-2015-203545
Review
epithelial origin, often characterised by high-grade features with
heterogeneous and sometimes heterologous metaplastic compo-
nents.53 Despite the presence of a fibrosarcomatous component
in dermatofibrosarcoma protuberans, they differ from breast sar-
comas in their cutaneous derivation.54
From our review, the most common histological subtypes of
breast sarcoma were angiosarcoma, malignant fibrous histiocy-
toma and fibrosarcoma (table 1).1 5–7 9 10 12 14 15 17–20 In com-
parison, for soft tissue sarcomas irrespective of sites, the most
common histological subtypes include malignant fibrous histio-
cytoma, liposarcoma, synovial sarcoma and leiomyosarcoma.55 56
Angiosarcomas occurred more commonly in the breast because
the majority of them are related to radiotherapy and chronic
lymphoedema following breast cancer treatment. As breast-
conserving therapy is becoming the standard of care, the inci-
dence of radiation-induced sarcoma can be expected to rise.
Core biopsy is considered the procedure of choice in obtaining
the diagnosis of sarcomas, though often requiring adjunctive
immunohistochemistry with awareness of issues of sampling and
limited material. There is concern for seeding of malignant cells
along the biopsy tract; thus, it is important to preplan and incorp-
orate the biopsy tract into the resection specimen.57 Fine needle
aspiration has a low diagnostic accuracy for breast sarcomas.
Immunohistochemistry is essential in distinguishing breast sar-
comas from other neoplasms. The lack of diffuse or significant
reactivity for cytokeratin and myoepithelial markers helps to
rule out an epithelial component in the tumours and thereby
exclude the diagnosis of metaplastic carcinoma.
Immunohistochemistry also allows further classification of sarco-
mas into various histological subtypes. Angiosarcomas are often
immunoreactive for factor VIII-related antigen, Ulex europaeus
I lectin, CD34 and CD31.58–61 The cartilaginous component in
osteosarcoma with chondroid elements is usually immunoreac-
tive for epithelial membrane antigen (EMA) and S100.62 63
STAGING
Staging of breast sarcomas is usually performed using the
American Joint Committee on Cancer system for soft tissue sar-
comas. The parameters used in this staging system are tumour
size, grade, nodal and metastatic disease. Tumour grading
follows the French Federation of Cancer Centers System, based
on tumour differentiation, mitotic index and necrosis.64
Following the National Comprehensive Cancer Network guide-
line for soft tissue sarcomas of the extremity, superficial trunk,
head and neck, CT of the thorax is included in the metastatic
workup in view of the propensity of these tumours to metasta-
sise to the lungs. Additional imaging is individualised based on
histological subtypes as they have different tendencies to spread
to various locations. Abdominal and pelvic CT is suggested in
patients with myxoid/round cell liposarcoma, epithelioid
sarcoma, angiosarcoma and leiomyosarcoma. Patients with
angiosarcomas should also have imaging of the central nervous
system. The role of positron emission tomography-CT in the
staging of breast sarcomas is still undefined.
The aim of staging is to better categorise patients into groups
with different prognoses and render appropriate treatment to
improve outcomes. Prognostic factors in breast sarcomas have
been well studied in the major series (table 1). Tumour size
>5 cm, high-grade disease, angiosarcoma histology and positive
resection margins were associated with poorer prognosis.5–7 9–11
15 20
There are authors who suggest that primary sarcomas gen-
erally have a better prognosis than secondary sarcomas.65 Breast
sarcomas appear to share similar prognostic factors as soft tissue
sarcomas arising from other sites.66 There have been attempts to
3
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Figure 1 Postradiation sarcoma of the chest wall with histological features consistent with a myofibroblastic origin. The patient received prior
radiation treatment for breast carcinoma. (A) Low-power magnification shows intersecting fascicles of spindle cells pushing against skeletal muscle of
the chest wall. (B) Higher magnification shows plump spindle cells with vesicular nuclei and occasional mitoses. Immunohistochemistry shows diffuse
reactivity of the spindle cells for smooth muscle actin (C) supporting smooth muscle differentiation and increased proliferative fraction with MIB1 (D).

increase the accuracy of prediction on patients’ outcome by
combining these factors into a nomogram. In 2007, Eilber and
Kattan proposed a Memorial Sloan Kettering Cancer Center
sarcoma nomogram for the prediction of disease-specific death
in patients with soft tissue sarcomas.66 The parameters included
in the nomogram were tumour size, depth, site, histological
subtype and age.
TREATMENT
A multidisciplinary approach is essential in the treatment of
breast sarcomas. The evaluation and management of patients
with breast sarcoma by an experienced and dedicated team
4 Lim SZ, et al. J Clin Pathol 2016;0:1–9. doi:10.1136/jclinpath-2015-203545
consisting of surgical, medical and radiation oncologists is of
utmost importance in securing an optimal outcome. The rarity
of breast sarcomas often precludes prospective studies and limits
the statistical value of retrospective analysis on effectiveness of
therapy. The treatment principles are often extrapolated from
studies of soft tissue sarcomas of the extremities and chest wall
since they are similar in terms of clinical behaviour, histology
and prognosis.
Surgery
Complete surgical resection of tumour with negative margins is
the mainstay of treatment for breast sarcomas. It is the only
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Figure 2 Osteosarcoma in the breast. (A) At low magnification, there
is a haemorrhagic necrotic and cellular tumour impinging the skeletal
muscle of the chest wall. (B) Higher magnification shows osteoclastic
giant cells intermingled with malignant epithelioid and spindle cells
elaborating lacy slender osteoid.
modality, which can potentially offer cure. For many years,
mastectomy has been considered the gold-standard surgical
treatment for breast sarcomas, adopted because of the presumed
aggressive behaviour of the tumours. In 1961, Berg et al8
demonstrated that mastectomy was associated with better local
control as compared with wide excision. However, this
approach was challenged by more recent studies as breast-
conserving surgery gained popularity. In a study involving 25
patients, North et al14 showed that there was no difference in
survival and local control when comparing local excision and
mastectomy. Toesca et al19 demonstrated that the extent of
surgery and type of reconstruction did not significantly influ-
ence local control and survival in patients with breast sarcomas.
Instead of the extent of surgery, margin status has been consist-
ently shown to affect patients’ outcome.7 9 15 The standard rec-
ommendation is to obtain at least a 1 cm clear margin for all
resected breast sarcomas.41 Thus, for small-to-moderate size
breast sarcomas where resection with clear margins can be
achieved with acceptable cosmetic outcome, breast-conserving
surgery should be adequate for oncological clearance. Crosby
et al67 from MD Anderson Cancer Center suggested oncoplastic
reconstruction with parenchymal rearrangement or reconstruc-
tion with local flap (namely intercostal artery perforator flap,
long thoracic artery perforator flap and thoracodorsal artery
perforator flap) for patients with breast sarcoma deemed suit-
able for breast-conserving surgery. This can widen the use of
breast-conserving surgery and improve the cosmetic outcome.
For large tumours, which extend close to the chest wall, even
the pectoralis muscles and ribs may have to be resected en bloc
with the tumours during mastectomy.68 Reconstruction using
myocutaneous flap may be needed to close very large chest wall
defects in order not to compromise patients’ respiratory
Lim SZ, et al. J Clin Pathol 2016;0:1–9. doi:10.1136/jclinpath-2015-203545
Review
function. Since angiosarcomas often have infiltrative cutaneous
disease that extends well beyond the visible tumour, it is recom-
mended to obtain at least a 3 cm clear margin during
surgery.41 69 This approach in breast-conserving surgery often
results in a huge defect with poor cosmetic outcome, thus
simple mastectomy and reconstruction may be a better option
for patients with angiosarcomas. In view of its propensity for
early local recurrence, it is also prudent to perform a delayed
reconstruction for this group of patients.
Lymph node disease is very rare in soft tissue sarcomas. In a
study by Fong et al70 involving 1772 cases of soft tissue sarco-
mas, the rate of nodal metastasis was only 2.6%. Sarcomas pre-
dominantly spread via the haematogenous route. The rarity of
nodal disease is also seen in breast sarcomas, thus routine senti-
nel lymph node biopsy, axillary sampling or clearance is deemed
unnecessary as these may expose patients to additional morbid-
ity.5 11 There may be clinically enlarged axillary lymph nodes in
up to 25% of patients with breast sarcomas, but most of these
lymph nodes show reactive changes instead of malignancy.44 In
a study based on the Surveillance Epidemiology and End Results
database from 1988 to 2002, 333 patients had breast sarcomas,
of which 129 patients underwent lymphadenectomy and only
six patients (4.7%) were found to have nodal metastasis.71
None of these six patients with nodal disease survived beyond
5 years, and examination of nodes did not have an impact on
survival. This reiterates the fact that lymph node metastases are
seen mostly in patients with advanced, disseminated disease;
thus, the benefit of lymphadenectomy in this context is unclear.
Radical dissection of axillary lymph nodes should only be per-
formed in the presence of histologically proven isolated nodal
disease or where the purpose of surgery is local control and
symptom relief.
Radiotherapy
In contrast to surgery, there is no clear evidence on the benefit
of adjuvant radiotherapy in the treatment of breast sarcomas.
There have been studies dedicated to analyse the effect of post-
operative radiotherapy on the clinical outcome of patients with
breast sarcomas. Johnstone et al12 retrospectively analysed 10
patients with non-metastatic primary sarcoma of the breast who
were treated with mastectomy and adjuvant radiotherapy. There
were no local or regional failures. They concluded that adjuvant
radiotherapy allowed excellent local control of disease.
However, the limitation of this study was that there was no
direct comparison with patients who had undergone surgery
alone. Summarising the MD Anderson Cancer Center experi-
ence in breast sarcomas, Gutman et al11 demonstrated that there
was a trend towards improved local control with adjuvant radio-
therapy. In a later study, McGowan et al50 retrospectively ana-
lysed 78 patients with breast sarcoma without distant metastases
at presentation. Patients with malignant phyllodes tumours and
metaplastic carcinomas were included in this series.
Twenty-three patients had adjuvant radiotherapy. They demon-
strated that patients who had received a radiation dose ≥48 Gy
had a lower local relapse rate as compared with those who
received a radiation dose <48 Gy. However, this difference did
not reach statistical significance. They recommended that post-
operative radiation should deliver a microscopic tumouricidal
dose to the whole breast, and at least 60 Gy to the tumour bed.
During the same period, Barrow et al7 also reported a lower
local recurrence rate in patients treated with total or segmental
mastectomy and radiotherapy as compared with patients who
had surgery alone, though this again was not statistically signifi-
cant. In general, adjuvant radiotherapy is recommended for
5
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Figure 3 Primary low-grade angiosarcoma of the breast. (A) Low magnification shows a vasoformative tumour in the breast, accompanied by
haemorrhage. (B) Medium magnification shows anastomosing vascular channels that extend into the adipose septa. (C) The vessels dissect through
a lobule, splaying the acini apart. (D) CD31 immunohistochemistry decorates the endothelial cells lining the neoplastic vessels.

high-grade breast sarcomas >5 cm and for tumours resected
with positive margins.72 However, surgery to obtain clear
margins should be undertaken whenever possible as radiother-
apy cannot compensate for inadequate surgery.
There have been multiple case series describing adjuvant
radiotherapy in cases of radiation-induced sarcomas.73–75
Feigenberg et al74 reported three patients who had no disease
recurrence after adjuvant hyperfractionated radiotherapy for
radiation-induced breast angiosarcomas. Palta et al75 recom-
mended the use of hyperfractionated and accelerated radiother-
apy (HART) for radiation-induced breast angiosarcomas. They
demonstrated a 5-year disease-free survival of 64% in 14
patients following HART. Despite the above encouraging
results, we should still be cautious in the use of adjuvant radio-
therapy in cases of radiation-induced sarcomas for fear of the
potential late effects of a high cumulative radiation dose,
namely rib fractures, lung fibrosis and cardiomyopathy. There is
also lack of evidence to support neoadjuvant radiotherapy in
the management of breast sarcomas.
in general. Pervaiz et al performed a systematic meta-analysis on
randomised controlled trials of adjuvant chemotherapy for loca-
lised resectable soft tissue sarcomas.77 Twenty-two trials were
evaluated, representing 1953 patients in the whole analysis.
They concluded that an ifosfamide plus doxorubicin regimen
conferred a marginal benefit in operable soft tissue sarcomas
with respect to overall survival, local and distant recurrence. A
taxane-based chemotherapy regimen is often used in patients
with angiosarcomas especially in those who had received prior
anthracycline-based chemotherapy for previous malignancy.
Torres et al analysed the long-term outcome in 95 patients who
had radiation-induced angiosarcomas and found that combined
tumour resection and adjuvant chemotherapy significantly
reduced the risk of local recurrence ( p=0.0003).78
The role of chemotherapy as a neoadjuvant treatment for
breast sarcomas is debatable. Since soft tissue sarcomas are rela-
tively insensitive to chemotherapy, with response rates ranging
from 20% to 40%, there is a constant concern of tumour pro-
gression on chemotherapy which may render it unresectable.79

Chemotherapy
The role of adjuvant chemotherapy in the treatment of breast
sarcomas remains undefined. Based on their experience in MD
Anderson Cancer Center, Gutman et al demonstrated that adju-
vant chemotherapy was associated with prolonged disease-free
survival in patients with breast sarcoma.11 Zelek et al20 also
recommended adjuvant chemotherapy for patients with high-
grade tumours exceeding 5 cm in size. In contrast, there are
other retrospective studies, which showed no survival benefit
for patients with breast sarcoma who received adjuvant chemo-
therapy.19 76 At present, there are no prospective clinical trials
investigating the benefit of adjuvant chemotherapy for breast
sarcomas. Thus, we can only extrapolate from randomised con-
trolled trials of adjuvant chemotherapy for soft tissue sarcomas
6 Lim SZ, et al. J Clin Pathol 2016;0:1–9. doi:10.1136/jclinpath-2015-203545
Hyperthermia
Hyperthermia is both an effective complementary treatment
and a strong sensitiser of radiotherapy and chemotherapy. It is
performed through non-invasive selective heating of the tumour
area to temperatures between 40°C and 43°C by the use of an
electromagnetic heating device. Besides direct cytotoxicity,
hyperthermia enhances chemotherapy effect by increasing
chemical reaction and intratumoural drug absorption. The add-
ition of regional hyperthermia to a multimodality treatment of
high-risk soft tissue sarcomas has been shown to improve local
recurrence-free and disease-free survival.80 Focusing on breast
sarcomas, Linthorst et al81 demonstrated that adjuvant radio-
therapy with hyperthermia improved local disease control in
patients with radiation-induced angiosarcomas of the breast and
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chest wall. These are promising results to show that regional
hyperthermia can potentially be an additional standard treat-
ment option for breast sarcomas.
Targeted therapy
Studies have been conducted to identify genetic mutations spe-
cific to breast sarcomas and their corresponding protein pro-
ducts, which could serve as therapeutic targets. Antonescu
et al82 found that about 10% of angiosarcomas have activating
mutations in the kinase insert domain receptor (KDR, also
known as vascular endothelial growth factor receptor 2) gene,
which encodes proteins whose autophosphorylation is inhibited
by KDR antagonists. This specific KDR-positive genotype is
limited to angiosarcomas of the breast. These encouraging
results provide a basis for the use of vascular endothelial growth
factor receptor-directed therapy in the treatment of angiosarco-
mas. Agulnik et al83 conducted a phase II study on the effective-
ness of bevacizumab for the treatment of angiosarcoma and
epithelioid haemangioendotheliomas. Seventeen per cent of the
patients had a partial response while 50% of the patients
showed stable disease with a mean time to progression of
26 weeks. This provided further evidence that directed therapy
against vascular endothelial growth factor can also potentially
benefit patients with angiosarcomas.
CLINICAL OUTCOMES
In general, breast sarcomas have a poorer prognosis than breast
carcinoma (table 1). Based on the major series on breast sarco-
mas, the median 5-year overall survival was 63.5%, ranging
between 55% and 73%.5 8–10 12–14 19 The median 5-year
disease-free survival was 44%, ranging between 29.2% and
68%.9 12 19 The median overall and disease-free survivals were
66.5 months (range 66–67 months) and 18 months (range 18–
33 months), respectively.7 11 15 The variability in the reported
survival figures may be contributed by the small number of
cases in each series, varying proportion of histological subtypes
in each cohort and different treatment regimens in individual
centres. There have been several studies which suggested that
recurrence of disease is more prevalent in the first 5 years after
surgery.9 20 Zelek et al20 showed that the disease-free survival
remained stable at 5, 10 and 15 years (52%, 50% and 48%,
respectively). This was replicated in the series reported by
Bousquet et al9 where there were no significant differences in 5
and 10 years disease-free and overall survivals. Disease recur-
rences were mainly local relapses instead of metastatic disease,
usually treated with tumour re-excision with or without adju-
vant therapy. In metastatic disease, the lung, bone and liver are
the most commonly affected organs.84 There have been reports
of metastasectomy for lung lesions in metastatic soft tissue sar-
comas, but generally patients with metastatic breast sarcomas
have poor prognosis and palliative chemotherapy is offered.85 86
FUTURE DIRECTIONS
Most studies on breast sarcomas to date are retrospective ana-
lyses of either small groups of cases specific to certain histo-
logical subtypes or larger groups of patients with a variety of
sarcoma histological types. It is difficult to generate useful inter-
pretation on the effectiveness of treatment regimens from these
studies. Centralising the referral of breast sarcoma cases to a
high volume centre is important to standardise the multidiscip-
linary management of breast sarcomas and hopefully secure
better outcomes. This will also allow assessment of treatment
effects, patient outcomes and disease biology in a more system-
atic manner to allow formulation of better therapeutic strategies.
Lim SZ, et al. J Clin Pathol 2016;0:1–9. doi:10.1136/jclinpath-2015-203545
Review
With advancement in scientific research, we hope to gain
more insight into the biology of breast sarcomas. Through
molecular profiling, it is possible to identify candidate breast
sarcoma subtype-specific genetic mutations and their corre-
sponding protein products, which could serve as therapeutic
targets. This will allow development of novel therapeutic
approaches in breast sarcomas.
CONCLUSION
Breast sarcoma is a rare entity with a remarkable heterogeneity.
It behaves in an aggressive manner and should be managed by
an experienced multidisciplinary team. Total surgical resection
of tumour with clear margins is the mainstay of treatment.
Breast-conserving surgery confers similar survival as compared
with mastectomy, provided negative margins are obtained.
Routine axillary dissection is unnecessary as nodal metastasis is
rare in breast sarcomas. Adjuvant radiotherapy, chemotherapy
and regional hyperthermia should be reserved for high-grade
and large tumours (exceeding 5 cm). More research is still
needed to define effective therapeutic strategies.
Take home messages
▸ Sarcoma of the breast is a rare entity, comprising diverse
histological tumour subtypes.
▸ Angiosarcoma is the commonest primary breast sarcoma,
arising either de novo or consequent to radiation treatment
of breast carcinoma.
▸ A multidisciplinary approach is important for clinical
management of breast sarcomas.
▸ Complete resection with clear margins is the mainstay of
treatment, while axillary dissection is not indicated due to
the low likelihood of nodal metastasis of breast sarcomas.
Handling editor Cheok Soon Lee
Contributors SZL: performed literature review, drafted and revised the manuscript.
KWO, BKTT and SS: critically reviewed and contributed ideas to the manuscript.
PHT: supervised the literature review, contributed to the conception and design of
article, critically reviewed and provided ideas to the manuscript.
Competing interests None declared.
Provenance and peer review Not commissioned; internally peer reviewed.
REFERENCES
1 Pollard SG, Marks PV, Temple LN, et al. Breast sarcoma. A clinicopathologic review
of 25 cases. Cancer 1990;66:941–4.
2 Terrier P, Terrier-Lacombe MJ, Mouriesse H, et al. Primary breast sarcoma: a review
of 33 cases with immunohistochemistry and prognostic factors. Breast Cancer Res
Treat 1989;13:39–48.
3 May DS, Stroup NE. The incidence of sarcomas of the breast among women in the
United States, 1973–1986. Plast Reconstr Surg 1991;87:193–4.
4 Schmidt GB. Ueber das angiosarkom der mamma. Arch Klin Chir 1887;36:421–7.
5 Adem C, Reynolds C, Ingle JN, et al. Primary breast sarcoma: clinicopathologic
series from the Mayo Clinic and review of the literature. Br J Cancer
2004;91:237–41.
6 Barnes L, Pietruszka M. Sarcomas of the breast: a clinicopathologic analysis of ten
cases. Cancer 1977;40:1577–85.
7 Barrow BJ, Janjan NA, Gutman H, et al. Role of radiotherapy in sarcoma of the
breast – a retrospective review of the M.D. Anderson experience. Radiother Oncol
1999;52:173–8.
8 Berg JW, Decrosse JJ, Fracchia AA, et al. Stromal sarcomas of the breast. A unified
approach to connective tissue sarcomas other than cystosarcoma phyllodes. Cancer
1962;15:418–24.
7
 Downloaded from http://jcp.bmj.com/ on January 18, 2016 - Published by group.bmj.com
Review
9 Bousquet G, Confavreux C, Magné N, et al. Outcome and prognostic factors in
breast sarcoma: a multicenter study from the rare cancer network. Radiother Oncol
2007;85:355–61.
10 Fields RC, Aft RL, Gillanders WE, et al. Treatment and outcomes of patients with
primary breast sarcoma. Am J Surg 2008;196:559–61.
11 Gutman H, Pollock RE, Ross MI, et al. Sarcoma of the breast: implications for extent
of therapy. The M. D. Anderson experience. Surgery 1994;116:505–9.
12 Johnstone PA, Pierce LJ, Merino MJ, et al. Primary soft tissue sarcomas of the
breast: local-regional control with post-operative radiotherapy. Int J Radiat Oncol
Biol Phys 1993;27:671–5.
13 Norris HJ, Taylor HB. Sarcomas and related mesenchymal tumors of the breast.
Cancer 1968;22:22–8.
14 North JH Jr, McPhee M, Arredondo M, et al. Sarcoma of the breast: implications of
the extent of local therapy. Am Surg 1998;64:1059–61.
15 Pandey M, Mathew A, Abraham EK, et al. Primary sarcoma of the breast. J Surg
Oncol 2004;87:121–5.
16 Smola MG, Ratschek M, Amann W, et al. The impact of resection margins in the
treatment of primary sarcomas of the breast. A clinicopathological study of 8 cases
with review of literature. Eur J Surg Oncol 1993;19:61–9.
17 Stanley MW, Tani EM, Horwitz CA, et al. Primary spindle-cell sarcomas of the
breast: diagnosis by fine-needle aspiration. Diagn Cytopathol 1988;4:244–9.
18 Surov A, Holzhausen HJ, Ruschke K, et al. Primary breast sarcoma: prevalence,
clinical signs, and radiological features. Acta Radiol 2011;52:597–601.
19 Toesca A, Spitaleri G, De Pas T, et al. Sarcoma of the breast: outcome and
reconstructive options. Clin Breast Cancer 2012;12:438–44.
20 Zelek L, Llombart-Cussac A, Terrier P, et al. Prognostic factors in primary breast
sarcomas: a series of patients with long-term follow-up. J Clin Oncol
2003;21:2583–8.
21 Birch JM, Alston RD, McNally RJ, et al. Relative frequency and morphology of
cancers in carriers of germline TP53 mutations. Oncogene 2001;20:4621–8.
22 Malkin D, Li FP, Strong LC, et al. Germ line p53 mutations in a familial syndrome of
breast cancer, sarcomas, and other neoplasms. Science 1990;250:1233–8.
23 Lahat G, Lazar A, Lev D. Sarcoma epidemiology and etiology: potential
environmental and genetic factors. Surg Clin North Am 2008;88:451–81.
24 Osmers F, Strunk E, Clemens M, et al. Kaposi sarcoma of the breast with osseous
and pulmonary involvement (author’s transl). Rofo 1978;129:350–2.
25 Ng CS, Taylor CB, O’Donnell PJ, et al. Case report: mammographic and ultrasound
appearances of Kaposi’s sarcoma of the breast. Clin Radiol 1996;51:735–6.
26 Hamed KA, Muller KE, Nawab RA. Kaposi’s sarcoma of the breast. AIDS Patient
Care STDS 2000;14:85–8.
27 Pradniwat K, Ong KW, Sittampalam K, et al. Sarcoma of the breast and chest wall
after radiation treatment for bilateral breast carcinoma. J Clin Pathol
2015;68:491–5.
28 Penel N, Grosjean J, Robin YM, et al. Frequency of certain established risk factors in
soft tissue sarcomas in adults: a prospective descriptive study of 658 cases.
Sarcoma 2008;2008:459386.
29 Laskin WB, Silverman TA, Enzinger FM. Postradiation soft tissue sarcomas. An
analysis of 53 cases. Cancer 1988;62:2330–40.
30 Pierce SM, Recht A, Lingos TI, et al. Long-term radiation complications following
conservative surgery (CS) and radiation therapy (RT) in patients with early stage
breast cancer. Int J Radiat Oncol Biol Phys 1992;23:915–23.
31 Rubino C, Shamsaldin A, Lê MG, et al. Radiation dose and risk of soft tissue and
bone sarcoma after breast cancer treatment. Breast Cancer Res Treat
2005;89:277–88.
32 Karlsson P, Holmberg E, Samuelsson A, et al. Soft tissue sarcoma after treatment
for breast cancer – a Swedish population-based study. Eur J Cancer
1998;34:2068–75.
33 Blanchard DK, Reynolds C, Grant CS, et al. Radiation-induced breast sarcoma.
Am J Surg 2002;184:356–8.
34 Yap J, Chuba PJ, Thomas R, et al. Sarcoma as a second malignancy after treatment
for breast cancer. Int J Radiat Oncol Biol Phys 2002;52:1231–7.
35 Mery CM, George S, Bertagnolli MM, et al. Secondary sarcomas after radiotherapy
for breast cancer: sustained risk and poor survival. Cancer 2009;115:4055–63.
36 Huang J, Mackillop WJ. Increased risk of soft tissue sarcoma after radiotherapy in
women with breast carcinoma. Cancer 2001;92:172–80.
37 Guo T, Zhang L, Chang NE, et al. Consistent MYC and FLT4 gene amplification in
radiation-induced angiosarcoma but not in other radiation-associated atypical
vascular lesions. Genes Chromosomes Cancer 2011;50:25–33.
38 Woodward AH, Ivins JC, Soule EH. Lymphangiosarcoma arising in chronic
lymphedematous extremities. Cancer 1972;30:562–72.
39 Stewart FW, Treves N. Lymphangiosarcoma in postmastectomy lymphedema;
a report of six cases in elephantiasis chirurgica. Cancer 1948;1:64–81.
40 Schreiber H, Barry FM, Russell WC, et al. Stewart-Treves syndrome. A lethal
complication of postmastectomy lymphedema and regional immune deficiency.
Arch Surg 1979;114:82–5.
41 Al-Benna S, Poggemann K, Steinau HU, et al. Diagnosis and management of
primary breast sarcoma. Breast Cancer Res Treat 2010;122:619–26.
8 Lim SZ, et al. J Clin Pathol 2016;0:1–9. doi:10.1136/jclinpath-2015-203545
42 Chen KT, Kirkegaard DD, Bocian JJ. Angiosarcoma of the breast. Cancer
1980;46:368–71.
43 Strobbe LJ, Peterse HL, van Tinteren H, et al. Angiosarcoma of the breast after
conservation therapy for invasive cancer, the incidence and outcome. An unforeseen
sequela. Breast Cancer Res Treat 1998;47:101–9.
44 Elson BC, Ikeda DM, Andersson I, et al. Fibrosarcoma of the breast: mammographic
findings in five cases. AJR Am J Roentgenol 1992;158:993–5.
45 Liberman L, Dershaw DD, Kaufman RJ, et al. Angiosarcoma of the breast. Radiology
1992;183:649–54.
46 Schnarkowski P, Kessler M, Arnholdt H, et al. Angiosarcoma of the breast:
mammographic, sonographic, and pathological findings. Eur J Radiol
1997;24:54–6.
47 Smith TB, Gilcrease MZ, Santiago L, et al. Imaging features of primary breast
sarcoma. AJR Am J Roentgenol 2012;198.
48 Sanders LM, Groves AC, Schaefer S. Cutaneous angiosarcoma of the breast on MRI.
AJR Am J Roentgenol 2006;187.
49 Confavreux C, Lurkin A, Mitton N, et al. Sarcomas and malignant phyllodes
tumours of the breast – a retrospective study. Eur J Cancer 2006;42:2715–21.
50 McGowan TS, Cummings BJ, O’Sullivan B, et al. An analysis of 78 breast sarcoma
patients without distant metastases at presentation. Int J Radiat Oncol Biol Phys
2000;46:383–90.
51 McGregor GI, Knowling MA, Este FA. Sarcoma and cystosarcoma phyllodes
tumors of the breast – a retrospective review of 58 cases. Am J Surg 1994;167:
477–80.
52 Lakhani SR, Ellis IO, Schnitt SJ, et al. World Organization Classification of Tumours
of the Breast. Lyon: IARC Press, 2012:143–7.
53 Lee H, Jung SY, Ro JY, et al. Metaplastic breast cancer: clinicopathological features
and its prognosis. J Clin Pathol 2012;65:441–6.
54 Al-Rahbi S, Al-Lawati T, Al-Kharusi S, et al. Dermatofibrosarcoma protuberans:
a rare malignancy of the breast. Oman Med J 2015;30:378–81.
55 Zagars GK, Ballo MT, Pisters PW, et al. Prognostic factors for patients with localized
soft-tissue sarcoma treated with conservation surgery and radiation therapy: an
analysis of 1225 patients. Cancer 2003;97:2530–43.
56 Coindre JM, Terrier P, Guillou L, et al. Predictive value of grade for metastasis
development in the main histologic types of adult soft tissue sarcomas: a study of
1240 patients from the French Federation of Cancer Centers Sarcoma Group.
Cancer 2001;91:1914–26.
57 Schwartz HS, Spengler DM. Needle tract recurrences after closed biopsy
for sarcoma: three cases and review of the literature. Ann Surg Oncol 1997;4:
228–36.
58 Merino MJ, Carter D, Berman M. Angiosarcoma of the breast. Am J Surg Pathol
1983;7:53–60.
59 Yonezawa S, Maruyama I, Sakae K, et al. Thrombomodulin as a marker for vascular
tumors. Comparative study with factor VIII and Ulex europaeus I lectin. Am J Clin
Pathol 1987;88:405–11.
60 Pai MR, Upadhyaya K, Naik R, et al. Bilateral angiosarcoma breast diagnosed
by fine needle aspiration cytology. Indian J Pathol Microbiol 2008;51:
421–3.
61 Kar A, Mukhopadhyay D, Das SS, et al. Cytodiagnosis of angiosarcoma of breast.
Indian J Pathol Microbiol 2008;51:427–9.
62 Silver SA, Tavassoli FA. Primary osteogenic sarcoma of the breast: a
clinicopathologic analysis of 50 cases. Am J Surg Pathol 1998;22:925–33.
63 Muller AG, Van Zyl JA. Primary osteosarcoma of the breast. J Surg Oncol
1993;52:135–6.
64 Trojani M, Contesso G, Coindre JM, et al. Soft-tissue sarcomas of adults; study of
pathological prognostic variables and definition of a histopathological grading
system. Int J Cancer 1984;33:37–42.
65 Luini A, Gatti G, Diaz J, et al. Angiosarcoma of the breast: the experience of the
European Institute of Oncology and a review of the literature. Breast Cancer Res
Treat 2007;105:81–5.
66 Eilber FC, Kattan MW. Sarcoma nomogram: validation and a model to evaluate
impact of therapy. J Am Coll Surg 2007;205:S90–5.
67 Crosby MA, Chike-Obi CJ, Baumann DP, et al. Reconstructive outcomes in patients
with sarcoma of the breast. Plast Reconstr Surg 2010;126:1805–14.
68 Pencavel T, Allan CP, Thomas JM, et al. Treatment for breast sarcoma: a large,
single-centre series. Eur J Surg Oncol 2011;37:703–8.
69 Pencavel TD, Hayes A. Breast sarcoma – a review of diagnosis and management.
Int J Surg 2009;7:20–3.
70 Fong Y, Coit DG, Woodruff JM, et al. Lymph node metastasis from soft tissue
sarcoma in adults. Analysis of data from a prospective database of 1772 sarcoma
patients. Ann Surg 1993;217:72–7.
71 Gullett NP, Delman K, Folpe AL, et al. National surgical patterns of care: regional
lymphadenectomy of breast sarcomas. Am J Clin Oncol 2007;30:461–5.
72 Lahat G, Lev D, Gerstenhaber F, et al. Sarcomas of the breast. Expert Rev
Anticancer Ther 2012;12:1045–51.
73 Buatti JM, Harari PM, Leigh BR, et al. Radiation-induced angiosarcoma of the
breast. Case report and review of the literature. Am J Clin Oncol 1994;17:444–7.
 Downloaded from http://jcp.bmj.com/ on January 18, 2016 - Published by group.bmj.com
74 Feigenberg SJ, Mendenhall NP, Reith JD, et al. Angiosarcoma after
breast-conserving therapy: experience with hyperfractionated radiotherapy. Int J
Radiat Oncol Biol Phys 2002;52:620–6.
75 Palta M, Morris CG, Grobmyer SR, et al. Angiosarcoma after breast-conserving
therapy: long-term outcomes with hyperfractionated radiotherapy. Cancer
2010;116:1872–8.
76 Shet T, Malaviya A, Nadkarni M, et al. Primary angiosarcoma of the breast:
observations in Asian Indian women. J Surg Oncol 2006;94:368–74.
77 Pervaiz N, Colterjohn N, Farrokhyar F, et al. A systematic meta-analysis of
randomized controlled trials of adjuvant chemotherapy for localized resectable
soft-tissue sarcoma. Cancer 2008;113:573–81.
78 Torres KE, Ravi V, Kin K, et al. Long-term outcomes in patients with
radiation-associated angiosarcomas of the breast following surgery and radiotherapy
for breast cancer. Ann Surg Oncol 2013;20:1267–74.
79 Brennan MF, Singer S, Maki RG, et al. DeVita, Hellman, Rosenberg’s cancer:
principles and practice of oncology. Philadelphia: Lippincott Williams and Wilkins,
2008:1741–89.
Lim SZ, et al. J Clin Pathol 2016;0:1–9. doi:10.1136/jclinpath-2015-203545
Review
80 Lindner LH, Issels RD. Hyperthermia in soft tissue sarcoma. Curr Treat Options
Oncol 2011;12:12–20.
81 Linthorst M, van Geel AN, Baartman EA, et al. Effect of a combined surgery,
re-irradiation and hyperthermia therapy on local control rate in radio-induced
angiosarcoma of the chest wall. Strahlenther Onkol 2013;189:387–93.
82 Antonescu CR, Yoshida A, Guo T, et al. KDR activating mutations in human
angiosarcomas are sensitive to specific kinase inhibitors. Cancer Res 2009;69:7175–9.
83 Agulnik M, Yarber JL, Okuno SH, et al. An open-label, multicenter, phase II study
of bevacizumab for the treatment of angiosarcoma and epithelioid
hemangioendotheliomas. Ann Oncol 2013;24:257–63.
84 Lahat G, Dhuka AR, Lahat S, et al. Outcome of locally recurrent and metastatic
angiosarcoma. Ann Surg Oncol 2009;16:2502–9.
85 Billingsley KG, Burt ME, Jara E, et al. Pulmonary metastases from soft tissue
sarcoma: analysis of patterns of diseases and postmetastasis survival. Ann Surg
1999;229:602–10.
86 Casson AG, Putnam JB, Natarajan G, et al. Five-year survival after pulmonary
metastasectomy for adult soft tissue sarcoma. Cancer 1992;69:662–8.
9
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Sarcoma of the breast: an update on a rare

entity
Sue Zann Lim, Kong Wee Ong, Benita Kiat Tee Tan, Sathiyamoorthy
Selvarajan and Puay Hoon Tan

J Clin Pathol published online January 4, 2016

Updated information and services can be found at:

http://jcp.bmj.com/content/early/2016/01/04/jclinpath-2015-203545

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