Primary sarcomas of the breast are rare, malignant tumours arising from the mesenchymal
tissue of the mammary gland (Oberman, 1965; Barnes and Pietruszka, 1977; Callery et
al, 1985), with an approximate incidence of 17 new cases per million women (Moore
and Kinne, 1996). At the Mayo Clinic, 27 881 malignant breast tumours were seen between
1940 and 1999 (C Adem, personal unpublished data) and 18 breast sarcomas were diagnosed
accounting for 0.0006% of breast malignancies.
Breast sarcomas should be distinguished from metaplastic carcinomas (Adem et al, 2002).
When facing a spindle cell neoplasm in an epithelial organ such as the breast one
should be careful in rendering the diagnosis of sarcoma. In this setting, immunohistochemistry
using the right antibodies is of major input. Berg et al defined stromal sarcomas
of the breast in 1962 as a group of mesenchymal malignant tumours with fibrous, myxoid
and adipose components, excluding malignant cystosarcoma phyllodes, lymphomas and
angiosarcomas (Berg et al, 1962). However, series in the literature have included
many different entities under the rubric of sarcomas such as cystosarcoma phyllodes,
lymphosarcoma and carcinosarcoma (Botham et al, 1958; Donegan, 1967; Fawcett, 1967;
Kennedy and Biggart, 1967; Rissanen and Holsti, 1968; Gogas et al, 1976; Ludgate et
al, 1977; Khanna et al, 1981; Christensen et al, 1988; Terrier et al, 1989; Pitts
et al, 1991; Ciatto et al, 1992; Luna Vega et al, 1992; McGregor et al, 1994; Moore
and Kinne, 1996; McGowan et al, 2000). For this review, we choose to categorise primary
breast sarcomas in histogenic terms, similar to other soft-tissue sarcomas, thus including
angiosarcomas, and excluding malignant cystosarcomas phyllodes, as reported by others
(see Table 1
Table 1
Major breast sarcomas comparable series in the English literature
Author
N cases/period
Median age (years)
Median size (cm)
Diagnosis
Prognostic factors
Barnes and Pietruszka (1977)
10/31 years
51
6.3
5F, 1RMS, 1Le, 2OGS, 1 Li
Tumour contour, atypia, mitosis
Barrow et al (1999)
59/43 years
45
UK
32F, 17A, 1OGS, 7 NOS
Size, margins status, type
Berg et al (1962)
25/UK
48
6.0
Li and F
Positive margins
Callery et al (1985)
25/33 years
54
4.0
9F, 5M, 1HPC, 2Le, 2D, 3Desmoid, 1Li, 2 SS
UK
Gutman et al (1994)
60/51 years
48
6.5
17A, 16SS, 10F, 6M, 3O, 2Li, 2Le, 1R, 3U
Size, multifocal lesions, vascular, lymphatic, skin or chest wall invasion
Johnstone et al (1993)
10/12 years
28
UK
4A, 2M, 1R, 1Li, 1SS, 1Sc
UK
Norris and Taylor (1968)
32/UK
49
4.0
5 OGS, 1 Le/R, 3 Li, 1D, 22F
Size, contour, atypia, mitotic activity
North et al (1998)
25/31 years
55
6.0
10A, 5SS, 3F, 2Li, 2Le, 1M, 1OGS, 1 U
Type of surgery
Oberman (1965)
13/30 y
56
7.1
7f, 3R, 2D, 1MM
Size, type of surgery
Pollard et al (1990)
25/81 years
55.4
5.9
11M, 6Li, 4F, 1CC, 1NS, 1Le, 1ASP
Type of surgery
Smola et al (1993)
8/23 years
56
12.8
2CHS, 1M, 2Li, 2F, 1A
UK
Stanley et al (1988)
4/UK
61
UK
2M, 2A
UK
Zelek et al (2003)
83/37 years
47
6.5
58M, 8A, 7L, 2Sc, 2R, 2OGS, 2Le, 2O
Grade, size
A = angiosarcoma; SS = stromal sarcoma; F = fibrosarcoma; M = malignant fibrous histiocytoma;
Li = liposarcoma; D = dermatofibrosarcoma protuberans; Sc = spindle cell sarcoma;
Cs = carcinosarcoma; Le = leiomyosarcoma; R = rhabdomyosarcoma; U = unspecified; CC
= clear cell sarcoma; ASP = alveolar soft part sarcoma; MM = malignant mesenchymoma;
OGS = osteosarcoma; Others = O.
) (Berg et al, 1962; Oberman, 1965; Norris and Taylor, 1968; Barnes and Pietruszka,
1977; Callery et al, 1985; Stanley et al, 1988; Pollard et al, 1990; Johnstone et
al, 1993; Smola et al, 1993; Gutman et al, 1994; North et al, 1998; Barrow et al,
1999).
MATERIALS AND METHODS
All cases diagnosed pathologically at our institution from 1910 to 2000 as breast
sarcomas and stromal sarcomas were retrieved from Mayo Clinic Surgical Pathology files.
The H&E-stained sections were examined in all cases to confirm the diagnosis. An average
of seven (range, 1–28) H&E slides per case were available. Clinical charts and surgical
notes were retrospectively reviewed and the following information was collected: age,
gender, size of tumour, clinical presentation, duration of symptom, history of radiation,
type of surgery, local recurrences and systemic metastases. Follow-up information
was obtained from patient records and death certificates. Patients with other prior
primary malignancy in the breast, radiation therapy and metastatic disease to the
breast were excluded.
Patients with cystosarcoma phyllodes were excluded, as well as patients with metaplastic
carcinoma. For this purpose, immunoperoxidase studies were performed using two primary
antibodies, vimentin, to determine immunocompetence and wide spectrum screening keratin,
to diagnose a metaplastic carcinoma as reported earlier (Adem et al, 2002). In regards
of the fact that some cases were diagnosed at the beginning of the century, if immunoperoxidase
study with vimentin was negative, another block representative of the tumour was chosen
for further immunostaining. If vimentin staining was still negative, search for an
internal control such as normal or carcinomatous component was done in each case.
Size, diagnosis, infiltrative or nodular pattern, presence of heterologous elements,
grade according to Broders' scheme of grading used at the Mayo Clinic, mitotic index
(in 10 high-power fields, using a Leitz microscope, field diameter 0.45 mm), and necrosis
were assessed.
Overall survival (OS) and cause-specific survival (CSS) following diagnosis were estimated
based on the Kaplan–Meier method, overall and separately for morphological features.
Associations between morphologic features and survival were evaluated univariately
based on fitting Cox proportional hazards models. All calculated P-values were two-sided
and P-values less than 0.05 were considered statistically significant.
RESULTS
In all, 42 patients were retrieved between 1910 and 2000. Six were excluded after
morphological review for the following reasons: cystosarcoma phyllodes (n=4), fibromatosis
(n=1), benign haemangioma (n=1). Totally, 11 cases were also excluded after showing
a positive stain with wide spectrum screening keratin, and being considered metaplastic
carcinoma.
Clinical data
Overall, 25 remaining patients constituted the study group and are summarised in Table
2
Table 2
Patients clinical and pathological characteristics in our series
Age (years)
Diagnosis
Duration
Surgery
Adjuvant therapy
Size
Gross
Margins
Grade
Local recurrence
Metastases
Last follow-up
Case 1
38
MXFS
15 m
R Mast
N
UK
C
N
2
3 y, S
N
DUK, 45 m
Case 2
38
F
UK
R Mast
RT
5
UK
UK
2
N
N
DOC, 5.5 y
Case 3
31
PS
2 m
Excision
N
UK
UK
I
4
1 y, R Mast
N
DOC, 1 y
Case 4
38
A
UK
Excision
N
UK
UK
I
2
5 times, 3 to 6 y, S/RT
L, 6 y
DOD, 84 m
Case 5
72
PS
UK
R Mast
N
3
I
I
4
N
N
Alive, 18 y
Case 6
49
F
1 m
Mast
UK
3
UK
I
3
N
N
DOC, 37 y
Case 7
43
A
1 m
Mast
N
8
C
I
1
N
B/L, 1 y, S/CT
DOD, 16 m
Case 8
48
MXFS
96 m
Mast
RT
5.5
I
I
3
4 m, No TTT
N
AWD, 6 m
Case 9
55
F
2 m
Mast
UK
UK
UK
N
2
Twice, 11 m and 17 m, S
N
DOD, 76 m
Case 10
67
Le
UK
Excision
CT
2
UK
UK
4
N
Li/B/Skin, at presentation, CT
DOD, 7 m
Case 11
39
A
2 m
Excision
N
8
I
I
2
20 m, S
Li/Jejunum, 9 y, None
DOD, 114 m
Case 12
32
PS
2 m
Excision
N
UK
UK
I
4
2 m, S
N
DOD, 23 m
Case 13
52
F
4 m
M R Mast
N
4.5
C
I
3
N
N
Alive, NED, 23.5 y
Case 14
27
A
11 m
S Mast
N
12
I
I
2
11 m, UK
L/Li/S, 22 m, UK
DOD, 32 m
Case 15
63
MXFS
30 y
S Mast
N
4
C
N
2
N
N
DOC, 21 y
Case 16
60
PS
12 m
R Mast
RT
10
C
N
4
N
B/Lu, 6 y, RT
DOD, 88 m
Case 17
55
Le
UK
Mast
N
4
UK
N
4
N
Multiple sites, 6 y, CT
DOD, 77 m
Case 18
33
A
12 m
R Mast
RT
10
C
I
2
10 m, UK
B, 10 m, RT
DOD, 13 m
Case 19
33
HPC
UK
UK
UK
UK
UK
N
4
N
L/Li/Pelvis, UK, RT
DOD, 41 m
Case 20
24
PS
12
S Mast
N
5
C
I
3
N
N
Alive, NED, 11 y
Case 21
32
A
11 m
S Mast
N
UK
UK
I
3
14 m, RT
B/L, 14 m, RT/CT
DOD, 26 m
Case 22
42
F
UK
S Mast
N
3
UK
I
3
8 m, S
N
DOC, 49 y
Case 23
54
F
1 m
M R Mast
N
5
UK
N
2
N
N
Alive, NED, 13 y
Case 24
81
PS
UK
M R Mast
N
0.3
UK
I
4
N
N
Alive, NED, 14 m
Case 25
54
OGS
UK
M R Mast
N
10
C
I
3
N
N
Alive, NED, 4 y
Abbreviations: MXFS = myxofibrosarcoma; F = fibrosarcoma; PS = pleomorphic sarcoma;
AGS = angiosarcoma; Le = leiomyosarcoma; HPC = hemangiopericytoma; OGS = osteosarcoma;
UK = unknown; R = radical; Mast = mastectomy; S = simple; M = modified; RT = radiotherapy;
CT = chemotherapy; C = circumscribed; I = infiltrative; y = year; m = month; DOC =
dead of other causes; DUK = dead of unknown cause; NED = no evidence of disease; DOD
= dead of disease; Lu = lung; B = bone; Li = liver; S = spleen; N = nodular or pushing
margins; I = infiltrative.
. There were 25 women age range 24–81 (mean 45 years). In total, 24 cases presented
with lump, two of them associated with pain. In one case, it presented as an incidental
mammographic finding. Contralateral breast sarcoma had been diagnosed elsewhere 3
years earlier in one case, renal cell carcinoma 5 years later in one case, colon cancer
4 years earlier in one case, skin melanoma and uterine cancer in one case 16 and 27
years earlier, respectively. No history of prior radiation was found in any case,
therefore excluding postradiation sarcoma. The duration of symptoms for 16 patients
ranged between 1 month to 40 years (mean 3.2 years).
Surgical treatment was excision in five cases, mastectomy in 19 cases (modified, four;
simple, five; radical, five; not specified, five), and unknown in one case. Adjuvant
therapy was administered in five cases (radiation, four; chemotherapy, one).
The right breast was affected in 10 cases, while the left was affected in 15 cases.
Pathological data
Gross description was available in 12 cases. Eight tumours were described as well-circumscribed,
four as infiltrative of which two were angiosarcoma. Tumour size was available on
18 patients, and the mean tumour size was 5.7 cm (range 0.3–12.0). Angiosarcomas tended
to be larger in size with a mean of 10 cm (range, 8–12 cm).
After present review, histopathological diagnoses were fibrosarcoma (n=6), angiosarcoma
(n=6), pleomorphic sarcoma (n=6), leiomyosarcoma (n=2), myxofibrosarcoma (n=3), hemangiopericytoma
(n=1) and osteosarcoma (n=1). Tumours were graded as low grade (grade 1, one; grade
2, nine), and high grade (grade 3, seven; grade 4, eight). Necrosis was observed in
four cases (three high-grade tumours). In all, 11 (range, 0–43) mitoses were found
on average in 10 HPF. Heterologous component was seen in one case of osteosarcoma.
Seven had pushing margins while 16 had infiltrative ones.
An in situ ductal carcinoma component was observed in one case. In this case of pleomorphic
sarcoma, keratin staining was negative in neoplastic cells with adequate internal
control (the in situ component as well as benign entrapped ducts).
There was no metastasis in the 15 cases where axillary node dissection was performed.
Follow-up and survival analysis (Figure 1)
Figure 1
Overall survival following surgery, according to tumour size (⩽5 vs >5 cm). The numbers
in parentheses indicate the number of patients still at risk at selected time points.
Overall mean and median follow-up were, respectively, 10.5 and 6.4 years (range, 7
months–41 years). Local recurrence was observed in 11 patients and ranged from 2 to
36 months (mean 15 months), while distant metastasis was observed in 10 patients,
in order of frequency affecting the lungs (n=7), bones (n=6), liver (n=5), spleen
(two) and skin (two). In one case, other sites were also kidney, pancreas, adrenal,
omentum, epicardium and mediastinum. Of the 25 patients, 12 have died of disease and
six of other causes. At the last follow-up, seven patients were still alive with a
mean and median follow-up of 10.2 and 10.9 years, respectively.
Five-year overall (OS) and cause-specific survival (CSS) were 66 and 70%, respectively.
Five-year OS and CSS were both 91% for tumours ⩽5 cm, and 50% for tumours >5 cm. Tumour
size was significantly associated with OS (risk ratio=1.3 per 1 cm increase; 95% CI,
1.02–1.7; P=0.036). There was no significant difference between low- and high-grade
lesions (OS were 60 and 70%, P=0.14, CSS were 70 and 70%, P=0.5, respectively) or
tumours showing infiltrative compared to pushing margins (OS were 65 and 71%, P=0.47,
CSS were 65 and 86%, P=0.94, respectively) in terms of OS or CSS.
Although there was no statistically significant association between tumour size and
metastasis or recurrence, mean tumour size of patients with recurrence or metastasis
was 7.7 cm, compared to 4.9 and 4.3 cm, respectively, for patients without recurrence
or metastasis. Four out of five patients treated with simple excision had recurrence
or metastasis.
By the most common histopathologic types, all but one patient with angiosarcoma (4/5),
one patient with fibrosarcoma, and two patients with pleomorphic sarcoma, died of
disease.
DISCUSSION
Primary breast sarcomas are extremely rare (Moore and Kinne, 1996). In our institution,
they compose 0.0006% of breast malignancies. They constitute a specific clinicopathologic
entity and, therefore should be differentiated from the two main entities in differential
diagnosis, cystosarcoma phyllodes and metaplastic carcinoma. Specific morphological
features (biphasic tumour, with leaf-like architecture and epithelial component) recognise
the former, and extensive sampling of the tumour can help when a stromal overgrowth
is present. The latter is recognised on H&E sections by the presence of a carcinomatous
component, or based on a cytokeratin immunopositivity of the neoplastic spindle cells.
Reported series in the English literature had included all three entities as breast
sarcomas, and include in their reports angiosarcomas, desmoid tumours, and lymphosarcomas
(Botham et al, 1958; Berg et al, 1962; Oberman, 1965; Donegan, 1967; Fawcett, 1967;
Kennedy and Biggart, 1967; Norris and Taylor, 1968; Rissanen and Holsti, 1968; Gogas
et al, 1976; Barnes and Pietruszka, 1977; Ludgate et al, 1977; Khanna et al, 1981;
Callery et al, 1985; Christensen et al, 1988; Stanley et al, 1988; Terrier et al,
1989; Pollard et al, 1990; Pitts et al, 1991; Ciatto et al, 1992; Luna Vega et al,
1992; Johnstone et al, 1993; Smola et al, 1993; Gutman et al, 1994; McGregor et al,
1994; Moore and Kinne, 1996; North et al, 1998; Barrow et al, 1999; McGowan et al,
2000). Therefore, reliable assessments of prognostic factors are difficult to make
based on the published literature. Table 1 depicts comparable major series using soft-tissue
tumours as basis for classification.
Tumour size seems to be the most frequently reliable prognostic factor in many of
these series, as in breast carcinomas and soft-tissue sarcomas (Oberman, 1965; Norris
and Taylor, 1968; Gutman et al, 1994; Barrow et al, 1999; Zelek et al, 2003) Other
reported prognostic factors are the histopathological diagnosis (Barrow et al, 1999),
the infiltrative features (Norris and Taylor, 1968; Barnes and Pietruszka, 1977),
the histopathologic grading (Norris and Taylor, 1968; Barnes and Pietruszka, 1977;
Gutman et al, 1994; Barrow et al, 1999; Zelek et al, 2003), presence of positive margins
(Berg et al, 1962; Barrow et al, 1999), and extent of surgery for local recurrence
(Pollard et al, 1990; North et al, 1998). Some authors found age to be of prognostic
importance (Ludgate et al, 1977). Margins status is a major risk factor for recurrence
as it occurs in any neoplastic entity, and some authors advised adjuvant radiotherapy
for cases with positive margins (Callery et al, 1985; Smola et al, 1993), or less
than 2 cm of clear margins (McGowan et al, 2000). Treatment is generally based on
a wide local excision, without axillary dissection (Barrow et al, 1999). Breast sarcomas
bear different histogenesis than breast carcinomas as shown by cytogenetic studies
(Garcia-Palazzo et al, 1992), and biological behaviour (Berg et al, 1962).
We believe that breast sarcomas are comparable to soft-tissue sarcomas seen elsewhere.
They present mainly as a lump and size is a prognostic marker with 5 cm serving as
a valuable cut point. Tumour grade did not correlate with the outcome in our series
but statistical power was limited and this finding could be related to the small size
of the series. Lymphatic spread is uncommon as shown by the absence of axillary lymph
node metastasis in our cases, and therefore axillary node dissection is not necessary.
When lymph node metastasis is present, the diagnosis of a metaplastic carcinoma should
be considered even in the presence of a pure spindle cell neoplasm.