Mammary liposarcoma is among the rarest of breast tumours. Here we report the presentation, macroscopic, microscopic, and immunohistochemical features of an extremely rare case of metaplastic carcinoma with extensive pleomorphic liposarcomatous differentiation. A 47-year-old woman presented with bilateral grade III breast ptosis and a 3 × 4 cm mass in the lower outer quadrant of the left breast. Mammography and ultrasound confirmed a well-defined mass. A core biopsy performed was diagnosed as pleomorphic liposarcoma. Microscopically, this was a well-defined, lobulated tumour comprising solid sheets of large pleomorphic and spindle cells with bizarre forms, vacuolated cytoplasm, and ample mitoses. Atypical lipoblasts were easily identifiable. Due to the strong, though patchy, cytokeratin expression, the diagnosis of metaplastic carcinoma with pleomorphic liposarcomatous differentiation was made. Extensive sampling, careful search for a biphasic pattern, ductal carcinoma in situ, and/or epithelial differentiation, and a panel of broad-spectrum cytokeratins are essential to establish the diagnosis.
Tumours with liposarcomatous features in the breast are extremely rare. These can represent part of the spectrum of metaplastic carcinomas or malignant phyllodes tumours.
The workup of tumours with heterologous differentiation in the breast should include:
Extensive sampling of the tumour and adjacent tissue.
Histological assessment for the presence of ductal carcinoma in situ and/or epithelial differentiation.
A panel of immunohistochemical markers including broad-spectrum and basal cytokeratins. Note that cytokeratin expression may be focal/patchy and therefore a large panel is essential.
Metaplastic carcinoma of the breast (MCB) is a rare type of breast cancer and accounts for around < 1% of all breast malignancies . According to the 2012 World Health Organisation classification of tumours of the breast, MCB is classified into spindle cell carcinoma, squamous cell carcinoma, low-grade adenosquamous carcinoma, fibromatosis-like metaplastic carcinoma, and mesenchymal and mixed types .
MCB are thought to behave aggressively with poor outcomes (local recurrence and poor overall survival) compared with invasive ductal carcinoma (including triple-negative cases). The histological spectrum is diverse consisting of various combinations of mesenchymal and epithelial components. Typically, presentation occurs between 48 and 59 years of age, usually as a large, rapidly enlarging mass . The 5-year overall survival rate has been reported as 54.5%, considerably lower than the 85.1% survival rate for invasive ductal carcinoma and 73.3% in triple-negative invasive ductal carcinomas (p < 0.001) . There is a limited evidence base to guide therapy. Some studies recommend aggressive treatment modalities such as mastectomy, chemotherapy, and radiotherapy . However, to our knowledge, there are limited data to preclude breast-conserving surgery or to routinely recommend chemotherapy. MBC can be diagnostically challenging and require careful attention to morphological features, adequate sampling, and a panel of immunohistochemical markers.
We report the results of oncoplastic breast-conserving surgery to treat this rare cancer – with the first documented presentation of a metaplastic breast carcinoma with pleomorphic liposarcomatous differentiation. The histological differentials are discussed together with a review of the published literature of potential diagnostic mimics.
A 47-year-old woman presented with a lump in the left breast. She was otherwise well, nulliparous, and with no significant past medical history. She wore a 38D cup bra.
Upon clinical examination, she had bilateral grade III breast ptosis and a 3 × 4 cm mass in the lower outer quadrant above the infra-mammary fold in the 4 o’clock position. A well-defined mass was seen on mammography and ultrasound that was suggestive of a lipoma or mammary hamartoma. The lymph node basin was clear.
Percutaneous core biopsy demonstrated features consistent with a pleomorphic liposarcoma. A staging CT scan confirmed a well-defined left breast mass (Fig. 1a) but did not show other primary tumours or any evidence of metastatic disease. A central pathology review reported features consistent with a pleomorphic liposarcoma.
Consequently, the patient was referred to a sarcoma and oncoplastic breast surgery centre for management. The case was reviewed in both the sarcoma and breast multidisciplinary team meetings, and treatment planned accordingly. Having discussed the options, the patient elected to undergo a therapeutic mammoplasty and a sentinel lymph node biopsy in view of the possibility of a malignant epithelial diagnosis. The mammoplasty was performed using a wise pattern skin incision and a superiomedial dermoglandular pedicle. A contralateral symmetrizing breast reduction was performed at the same time. The specimen was X-rayed at the time of surgery (Fig. 1b).
Macroscopically, the wide local excision included a well- defined greyish white lesion. No clefts or cystic spaces were identified. The lesion was well away from all surgical margins.
Microscopically, this was a well-defined, lobulated tumour comprising solid sheets of large pleomorphic and spindle cells with bizarre forms, vacuolated cytoplasm, and ample mitoses (Fig. 1c). Atypical lipoblasts were easily identifiable (Fig. 1d). No biphasic pattern, glandular differentiation, or ductal carcinoma in situ was noted.
Immunohistochemistry showed few scattered AE1/3 (Fig. 1e), CK7 (Fig. 1f, g), CK8/18 (Fig. 1h), and Cam5.2 (Fig. 1i) strongly stained cells. CK14, p63, S100, Melan A, β-HCG, LCA, ER, PR, and HER2 were all negative. The panel of immunohistochemistry was performed on the diagnostic core biopsy and repeated on excision.
Due to the strong, though patchy, cytokeratin expression, the diagnosis of metaplastic carcinoma with pleomorphic liposarcomatous differentiation was made.
The tumour was excised with clear margins, and the sentinel node was tumour free. She then received adjuvant radiotherapy and chemotherapy. She remains well after 13 months of follow-up.
Metaplastic carcinoma is a group of breast tumours characterized by the presence of adenocarcinoma with areas of squamous, spindle cell, and/or mesenchymal differentiation. Within the mesenchymal type, the WHO classification describes the existence of a variant with liposarcomatous differentiation . However, to our knowledge, this is the first report of this variant within metaplastic carcinoma. The liposarcomatous differentiation includes, in addition to metaplastic carcinoma, malignant phyllodes tumour and primary liposarcoma. Other differentials which may be considered if a low-grade lipomatous lesion is identified include adenolipomas, angiolipomas (in which no lipoblasts would be seen), fibroadenomas with fat cells, pleomorphic lipoma, and silicone implants; the latter may appear to contain lipoblasts which are in fact silicone granulomas.
Liposarcomatous differentiation is more commonly seen in the context of a malignant phyllodes tumour. The presence of a biphasic pattern and negative cytokeratin expression would favour the diagnosis of a malignant phyllodes tumour. Table 1 summarises previous studies showing a phyllodes tumour with liposarcomatous differentiation.
In this particular case, pleomorphic liposarcomatous differentiation was observed, which is defined as a cellular, pleomorphic sarcoma in the presence of multivacuolated lipoblasts .
Metaplastic carcinoma is a rare form of breast cancer that presents both diagnostic and therapeutic challenges. The condition can be difficult to diagnose and requires a high index of suspicion, especially in the context of large or rapidly enlarging breast lumps. Oncoplastic techniques may be appropriate and can afford good excision margins depending on the tumour location.
Extensive sampling, careful search for a biphasic pattern, ductal carcinoma in situ and/or epithelial differentiation and a panel of broad-spectrum cytokeratins are essential to establish the diagnosis. It is important, in the diagnostic workup, to include basal cytokeratin stains such as p63, CK5, and CK14 since those tumours belong to the basal phenotype group of breast cancers. In the current case, the large pleomorphic cells were convincingly and strongly positive for a number of broad-spectrum and basal cytokeratins. No staining was observed in the few lymphocytes enclosed within the tumour. In addition, the tumour was devoid of benign mammary epithelium, which excludes the possibility of benign positive epithelial entrapment. Of note, the expression of cytokeratins can be focal and hence the importance of extensive sampling and the use of more than one marker. On selecting suitable blocks for immunohistochemical testing, areas with epithelial appearances should be favoured as these are likely to express cytokeratins. While S100 positivity would be helpful in confirming the diagnosis of liposarcoma, the positivity is described in less than half of the reported liposarcoma cases according to the WHO Classification of Tumours of Soft Tissue and Bone in 2013 .