Metaplastic carcinoma of breast, previously called as carcinosarcoma, is one rare form of breast cancer. It accounts for less than 1% of all primary breast tumors. It consists of both glandular and nonglandular components admixed with epithelial and mesenchymal tissues. This type of breast cancer usually resembles invasive ductal carcinoma clinically and radiologically. This is a case of a 65-year-old female with painful lump in left breast for 2 months. Lumpectomy of the same showed features of metaplastic carcinoma of breast with chondroid differentiation, which is a rare form of metaplasia with better prognosis than other forms. Immunohistochemistry was helpful in confirming the diagnosis. Overall survival is less with this form of carcinoma as compared to intraductal carcinoma of breast.
Keywords: Metaplastic, epithelial and mesenchymal, breast carcinoma, prognosis
Metaplastic breast carcinoma (MBC) is a rare heterogeneous group of invasive breast carcinomas. Previously termed as carcinosarcoma, it is characterized by differentiation of neoplastic epithelial cells towards squamous and/or mesenchymal looking elements. It accounts for only about 1% of all invasive breast carcinomas.1 This rare histopathological variant of breast malignancy is reported for its correct identification and appropriate management.
A 65-year-old female presented with chief complaints of a lump in left breast for past 2 months. The swelling was insidious in onset and was progressive in nature and associated with pain. There was no nipple discharge. There was no history of fever or trauma or weight loss. Her past medical history was unremarkable with no comorbidities. She had no family history of breast or ovarian cancer.
General physical and systemic examination was unremarkable. On examination, left breast was showing fullness over lower inner quadrant. Skin over swelling was normal and pinchable with no dimpling or ulceration. Nipple areola complex was normal. On palpation, there was a 2 × 1 cm lump felt over lower inner quadrant, hard in consistency, nontender and was moving with breast tissue. Right breast was normal. No palpable lymph nodes were noted in left and right axilla. All baseline investigations were normal. True-cut biopsy was done and was reported as benign breast tissue. After a complete pre-surgery workup, wide local excision under general anesthesia was done.
Histological examination was suggestive of metaplastic carcinoma with heterogeneous mesenchymal differentiation (chondroid) (Fig. 1). The tumor showed <10% of areas with glandular or tubular formation and with marked nuclear pleomorphism, irregular nuclear membrane, vesicular nuclei and prominent nucleoli (Figs. 2 and 3). Mitosis was increased (16/10 hpf) with a Nottingham grade of three. The surgical margins were free of tumor. The tumor conferred to pT1c pNx. By immunohistochemistry, tumor cells were triple negative (estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor 2 [HER2]) and p63 was negative. The tumor cells were strongly positive for S-100 and pan-cytokeratin (pan-CK). Ki-67 labeling index was 40% (Fig. 4). Postoperative period was uneventful.
Figure 1. Breast tissue with multiple lobules of chondroid material (H&E x40).
Figure 2. Invasive mammary carcinoma with <10% glandular formation and marked nuclear pleomorphism with chondroid differentiation (H&E x40).
Figure 3. Higher magnification showing metaplastic carcinoma breast with chondroid differentiation (H&E x100).
Figure 4. Immunohistochemistry showing Ki labeling index (A), CK positivity (B) and S-100 positivity (C).
Most of the benign and malignant tumors of breast originate from glandular epithelium.1 In few instances, glandular epithelium differentiates into nonglandular mesenchymal tissue, known as metaplasia.1 Metaplastic changes in breast include squamous cell, spindle cell and heterogeneous mesenchymal growth. Earlier it was known with different names like carcinosarcoma, sarcomatoid carcinoma, carcinoma with pseudosarcomatous metaplasia, carcinoma with pseudosarcomatous stroma, all of which are not recommended; rather it is known as metaplastic carcinoma not otherwise specified.
Metaplastic breast carcinoma is a rare, aggressive high-grade breast cancer. It accounts for <1% of all breast malignancy.2 Most common age of presentation is around 48-59 years.3 It presents as a rapidly growing mass with size usually larger than 2 cm2. Clinically and radiologically more or less it resembles invasive ductal carcinoma (IDC).4 On ultrasonogram, it may have high density with either circumscribed or irregular and/or spiculated margins. This may appear benign on mammogram.3
The cell of origin for MBC is not clear but many studies suggest that myoepithelial cells will differentiate along mesenchymal lines and produce matrix elements.4 Epidermal growth factor receptor amplification is seen in around 28% of MBC.4 P53 mutation is seen in 61% in MBC.3,5 Presence of transitional areas and epithelial differentiation like tight junctions or desmosomes in heterogeneous sarcomatous component is supportive of a metaplastic process.3 GATA3-regulated genes account for cell-to-cell adhesion, stem cell-like characteristics and epithelial to mesenchymal transition. Decreased expression of these GATA3-regulated genes make any tumor chemoresistant.6 Like stem cells, tumor cells are positive for CD44 and negative for CD24.7
Histologically, MBC is a biphasic tumor containing ductal carcinoma admixed with areas of spindle, squamous, chondroid and osseous elements.3 MBC with chondroid differentiation is a rare phenomenon.8 Differential diagnoses include angiosarcoma, fibromatosis, pleomorphic carcinoma,9 malignant phyllodes tumor, malignant adenomyoepithelial tumor with chondroid matrix and chondrosarcoma. With presence of benign chondroid tissue, chondrolipoma and pleomorphic adenoma are considered.8 Thorough and extensive sampling is necessary for definitive diagnosis. Immunohistochemistry plays a vital role in confirming the diagnosis.
MBC also shows triple negativity in 90% cases, similar to infiltrating ductal carcinomas, because it is associated with poorly differentiated carcinomatous elements.9 Chondroid cells are usually positive for pan-CK and S-100 and negative for epithelial membrane antigen (EMA).5 Axillary lymph node metastasis in MBC is very uncommon. Rather, hematogenous route is preferred with most common distant site of metastasis being pleura, lung, liver and abdominal viscera.9 Presence of axillary lymph node metastasis indicates a poor prognosis.1,3
Prognostic factors of MBC depend on tumor size >5 cm, histological type, degree of differentiation, type and degree of mesenchymal component, presence of axillary lymph node and distant metastasis.1,9 Increased risk of local recurrence has been reported. Basically, MBC has poorer prognosis than other IDC, but MBC with chondroid differentiation exhibits better prognosis than other subtypes.
Surgical radical mastectomy is considered the mainstay of treatment. Conservative surgery with radiotherapy is followed for tumors <5 cm in size.5 And total mastectomy followed by chemotherapy and radiotherapy is followed for tumors >5 cm in size with skin or chest wall involvement or >4 axillary lymph node metastasis. Since local recurrence and metastasis is more common, radiotherapy and chemotherapy play a vital role in treatment.6 Clinical trials on role of targeted gene therapy following genetic profiling have been done.4 Epidermal growth factor receptor inhibitors act as potent therapeutic agents.6 Overall 5-year survival rate is around 43%.1
When a malignant breast tumor with chondroid elements is seen, metaplastic carcinoma with chondroid differentiation is essentially considered, even though epithelial component is minimal or even absent. Extensive sampling and immunohistochemistry will help in differentiating it from other tumors. Surgery with chemotherapy and radiotherapy is considered as most appropriate treatment. Disease-free survival and overall survival is less in metaplastic carcinoma as compared to IDC of breast.
- Bhosale SJ, Kshirsagar AY, Sulhyan SR, Jagtap SV, Nikam YP. Metaplastic carcinoma with predominant chondrosarcoma of the right breast. Case Rep Oncol. 2010;3(2):277-81.
- Kumar M, Nigam JS, Khanna P, Arora A. Metaplastic carcinoma of the breast - Case report and review of literature. Int J Surg Open. 2020;24:43-6.
- Schwartz TL, Mogal H, Papageorgiou C, Veerapong J, Hsueh EC. Metaplastic breast cancer: histologic characteristics, prognostic factors and systemic treatment strategies. Exp Hematol Oncol. 2013;2(1):31.
- Shruti S, Siraj F. Matrix-producing metaplastic breast carcinoma - a rare tumor with heterologous elements. Ger Med Sci. 2017;15:Doc17.
- Taghipour Zahir S, Javannejad M. Metaplastic breast carcinoma with chondroid differentiation: a rare variant of infiltrative carcinoma in a 38-year-old woman. BMJ Case Rep. 2017;2017:bcr2016217687.
- Singh GK, Singh P, Bhowmik KT. Carcinosarcoma (metaplastic carcinoma) breast: a rare and aggressive primary - report of two cases with review of literature. Indian J Med Paediatr Oncol. 2018;39(3):400-4.
- Oon ML, Thike AA, Tan SY, Tan PH. Cancer stem cell and epithelial-mesenchymal transition markers predict worse outcome in metaplastic carcinoma of the breast. Breast Cancer Res Treat. 2015;150(1):31-41.
- Kim YJ, Shim HS, Lee H, Jung WH. Metaplastic carcinoma with extensive chondroid differentiation in the breast (chondroid carcinoma). Yonsei Med J. 2006;47(2):259-63.
- Fernández Pérez MA, Viqueira Rodriguez I, Tello Royloa A, Martínez Guisasola J. Metaplastic breast carcinoma with unusual presentation: review of three cases. Breast Care (Basel). 2015;10(6):404-7.