Keywords
Carcinosarcoma breast - chemotherapy - metaplastic carcinoma
Introduction
Carcinosarcoma (CS) breast is an extremely rare malignancy, accounting for about 0.1%
of all primary breast tumors.[1] CS is defined as tumor exhibiting both carcinomatous and sarcomatous components
(malignant nonepithelial component of mesenchymal origin), without evidence of a transition
zone between the two elements.[2] The exact cell of the origin of CS is not known, but it is believed to be sarcomatoid
metaplasia of carcinoma cells.[3] Herein, we report two rare cases of CS breast, along with the review of literature.
Case Reports
Patient 1
A 50-year-old postmenopausal female presented in August 2012 with lump in the left
breast for 3 months. The patient was diagnosed as carcinoma left breast with clinical
stage T2N1M0 after complete clinicoradiological evaluation. Tru-cut biopsy revealed
CS. The patient underwent left-sided modified radical mastectomy in September 2012.
She was given six cycles of chemotherapy with mesna, ifosfamide, Adriamycin, and dacarbazine
(MAID regimen) followed by external beam radiotherapy to a dose of 50 Gy in 25 fractions
to left-sided chest wall. After 3 years of treatment, the patient presented with breathing
difficulty. Whole-body positron emission tomography-computed tomography (PET-CT) showed
fluorodeoxyglucose avid right-sided suprahilar, hilar, and infrahilar mass lesion
measuring 6.2 cm × 3.1 cm × 5.4 cm suggestive of metastasis [Figure 1]a. After three cycles of docetaxel and gemcitabine chemotherapy, repeat whole-body
PET-CT showed complete remission [Figure 1]b. The patient is currently receiving chemotherapy to complete a total of six cycles.
Figure 1: (a) (Whole-body positron emission tomography-computed tomography) – Fluorodeoxyglucose
avid right-sided suprahilar, hilar, and infrahilar mass lesion measuring 6.2 cm ×
3.1 cm × 5.4 cm (suggestive of metastasis). (b) (Whole-body positron emission tomography-computed
tomography) – No significant fluorodeoxyglucose avid lesion in the body
Patient 2
A female patient presented to us in November 2016 with a chief complaint of lump in
the right breast for 1 year. On local examination, the right breast was enlarged with
the presence of engorged veins and superficial ulceration and was firm in consistency
[Figure 2]. It was fixed to the chest wall. There was no axillary lymphadenopathy. Her general
examination was unremarkable. The lump gave a clinical impression of malignant phyllodes
tumor. Biopsy from the breast lump was suggestive of CS, with tumor cells showing
positivity for both epithelial membrane antigen and vimentin and negativity for ER,
PR, HER2Neu, and CK [Figure 3]a, [Figure 3]b, [Figure 3]c. Contrast-enhanced CT of the neck, thorax, and abdomen was performed which showed
a large heterogeneously enhancing mass, with necrotic and cystic areas measuring 10
cm × 16 cm × 13.5 cm, replacing whole of the right breast along with the presence
of bilateral lung metastasis [Figure 4]. The patient's blood parameters were normal. She was discussed in multidisciplinary
clinic and planned for chemotherapy with MAID regimen. The patient is currently receiving
the same and is tolerating well.
Figure 2: Enlarged right breast with engorged veins and superficial
ulcers (arrow) on the surface
Figure 3: (a) Pleomorphic malignant tumor cells seen infiltrating into fibrocollagenous
tissue (×40). (b and c) Immunohistochemistry: Tumor cells are positive for epithelial
membrane antigen and vimentin
Figure 4: (Contrast-enhanced computed tomography thorax) – Heterogeneously enhancing
mass with necrotic and cystic areas measuring 10 cm × 16 cm × 13.5 cm, replacing whole
of the right breast
Discussion
Breast cancer is currently the most common malignancy seen in females worldwide.[4] The most common histology is that of infiltrating ductal carcinoma (IDC).[5] CS arising in the breast is a rare phenomenon and is aggressive in behavior with
a poor clinical course. CS is a general term used for biphasic tumors showing the
presence of both malignant epithelial and mesenchymal components in the same tumor.
It was first described by Huvos et al. in 1973.[6] They are believed to have a distinct behavior and clinical course that is different
from either carcinoma or sarcoma.[3]
Clinical features of carcinosarcoma breast
Breast CS often presents in a way clinically similar to IDC.[2] The patient commonly presents with painful lump in the breast, while the presence
of nipple discharge, nipple retraction, or skin ulceration is rarely seen in this
entity.[7] It is commonly seen in females of age more than 50 years.[8] The lung is the most common site of visceral metastasis followed by brain, bone,
and liver.[9] Axillary lymph node involvement is seen in about 8%–40% of the cases.[10]
Pathogenesis and histopathological features
The exact etiopathogenesis and origin of CS breast are controversial. It is postulated
that they have myoepithelial cell origin. According to the literature, cystosarcoma
phyllodes, fibroadenoma, and other cystic diseases of breast may be the possible causative
factors.[3],[11] Immunohistochemistry has the prime role in the definitive diagnosis of CS.[12] According to Wargotz et al., the sarcomatous component shows positivity for CK in 55% of cases and vimentin
in 98% of cases.[13] Unlike adenocarcinoma (ductal and lobular carcinoma) breast, the tumor is usually
negative for estrogen, progesterone, and HER2/neu (75%–85%). They show an overexpression
of the epidermal growth factor receptor gene (EGFR/HER1).[14],[15] Like stem cells, tumor cells show positivity for CD44 and negativity for CD24.[16] GATA3-regulated genes are responsible for cell-to-cell adhesion, epithelial-to-mesenchymal
transition, and stem cell-like features. The minimal expression of these GATA3-regulated
genes makes these tumors relatively chemoresistant. The knowledge of various receptors
and genes (therapeutic targets) involved in CS breast can lead to the development
of newer treatment strategies.[17]
Investigations and workup
Like adenocarcinoma breast, mammography, ultrasonography, and magnetic resonance imaging
aid in the diagnosis of CS breast with histopathological examination followed by immunohistochemistry,
being confirmatory also helping in defining the subtypes (epithelial component may
be in the form of undifferentiated carcinoma, adenocarcinoma, in situ carcinoma, IDC, or squamous carcinoma, while mesenchymal component may be composed
of undifferentiated mesenchymal, fibroblastic, chondroblastic, or osteoblastic areas).[7],[10],[18],[19]
Differential diagnosis
[Table 1] is showing the differential diagnoses of CS breast with their differentiating features.[10],[20]
Table 1
Differential diagnoses of carcinosarcoma and their differentiating features
|
Clinical condition and differentiating features
|
CS breast
|
|
CS – Carcinosarcoma
|
|
Adenocarcinoma, breast (infiltrating ductal and lobular carcinoma)[10]
|
More aggressive Lower incidence of axillary node involvement Generally larger tumor
size Mostly triple negative
|
|
Phyllodes tumor
|
|
Mostly benign
|
Malignant tumor
|
|
Benign epithelium with squamous metaplasia
|
Malignant epithelium with squamous differentiation
|
|
Negative for high-molecular-weight keratin and p63[10]
|
Positive for high-molecular-weight keratin and p63
|
|
Primary breast sarcoma - epithelial component absent and negative for keratin and
p63[20]
|
Epithelial component present and positive for keratin and p63
|
|
Pleomorphic adenoma (rare in the breast) Infiltrating margins absent Epithelial
component is not malignant[10]
|
Infiltrating margins with malignant epithelial component
|
|
Nodular fasciitis (proliferative lesion containing fibroblasts and myofibroblasts
in myxoid stroma) Fibromatosis (benign condition with proliferation of fibroblasts)[10]
|
Keratin positivity differentiates it from nodular fasciitis and fibromatosis
|
Treatment
The exact treatment of CS breast is unknown, but surgery remains the main treatment
like that of IDC. The surgical approach shifted from mastectomy to breast conservation
therapy (BCT) in selected patients after NSABP B-06 trial results.[20] Large tumors (≥5 cm) are a relative contraindication to BCT.[21] Surgery with sentinel lymph node biopsy or axillary node dissection followed by
postoperative chemotherapy and radiation therapy in various combinations was used
in different studies.[4] Owing to the aggressive nature of the tumor, the rates of local recurrence and metastasis
are high, so radiation and chemotherapy have a potential role in this entity. According
to Lai et al., postmastectomy adjuvant radiotherapy is beneficial in patients with tumor size
≥5 cm, skin or chest wall invasion, or with more than four metastatic axillary lymph
nodes.[22] Dave et al. treated CS breast with 50–66 Gy of radiotherapy and reported a 10.5% rate of local
recurrence for patients receiving adjuvant radiation after breast conservation surgery
(BCS).[23] The chemotherapy regimen which is recommended is anthracycline/taxane-based therapy.[24] In 2006, Hennessy et al. reported no relapse in three patients who had received adriamycin and ifosfamide
as treatment. Index patient is also receiving the same chemotherapy regimen.[25] According to Bae et al., patients with triple-negative CS breast have poor 3-year disease-free survival
as compared to triple-negative IDC patients receiving the same chemotherapy regimens.[26] Hormone therapy has no role in the management of CS breast.[20] However, HER1/EGFR protein overexpression makes EGFR inhibitors (such as gefitinib
and cetuximab) as potential therapeutic targets.[27],[28] The molecular studies being carried out for the different genetic and epigenetic
aberrations may provide a platform for more targeted and novel treatment options in
future.[29]
Prognosis and survival
CS breast is an aggressive malignant tumor with a poorer prognosis than the classical
breast carcinomas. Tumor size, type of differentiation, histologic grade, atypia,
and presence of active pleomorphic spindle cells play a role in prognosis.[15] Wargotz et al. described 5-year survival rates as 100%, 63%, and 35% for TNM clinical Stages I,
II, and III, respectively.[13] According to Beatty et al., 5-year survival rates range from 49% to 68%.[7] In a retrospective study, 5-year overall survival rate was reported as 0.73, 0.59,
0.44, and 0.00 for at Stages I, II, III, and IV, respectively, by Hennessy et al.[25]
Conclusion
CS is an unusual form of breast malignancy, with only few cases published in the literature.
The usual clinical presentation is similar to that of IDC. However, one of our cases
presented unusually and raised suspicion of phyllodes tumor. It is challenging to
diagnose it preoperatively, even with core needle biopsy and histopathology sometimes.
Triple-negativity or basal-like features make it an aggressive neoplasm. Owing to
its rarity, there is no standard treatment protocol till now. BCS, mastectomy, and
axillary lymph node dissection form the current treatment options similar to IDC.
Regardless of the type of surgery used, adjuvant radiation therapy should always be
considered. Traditional hormone therapy has no role in the treatment while adriamycin-
and taxane-based chemotherapy has some response. The lung lesions in patient 1 responded
significantly to docetaxel and gemcitabine, while patient 2 is receiving chemotherapy
with MAID regimen. Both will be curiously followed up to know the disease course and
response.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms.
In the form the patient(s) has/have given his/her/their consent for his/her/their
images and other clinical information to be reported in the journal. The patients
understand that their names and initials will not be published and due efforts will
be made to conceal their identity, but anonymity cannot be guaranteed.
