Primary breast sarcoma is a rare type of cancer arising from the mesenchymal tissue of the breast and represents less than 1% of all breast malignancies. It includes a heterogeneous group of disease entities. According to the World Health Organization (WHO) classification, malignant fibrous histiocytoma (MFH) is a morphological pattern rather than a distinct clinicopathological entity. Many neoplasms diagnosed as MFH previously are actually classified as pleomorphic subtypes of other sarcomas [2
]. Pleomorphic MFH/undifferentiated pleomorphic sarcoma is defined as a group of pleomorphic, high-grade sarcomas showing no line of differentiation.
Undifferentiated pleomorphic sarcoma has been a diagnosis of exclusion following thorough sampling and critical use of ancillary diagnostic techniques. In the previous reports, it consisted of 10.5-24% of all primary breast sarcomas [4
]. Most undifferentiated pleomorphic sarcomas have appeared in patients who are in their sixth and seventh decade of life [2
]. Neither the symptoms nor the physical findings of undifferentiated pleomorphic sarcoma of the breast present any characteristic pattern that would easily suggest the diagnosis. Immunohistochemistry may be useful to distinguish primary breast sarcomas from non-mesenchymal malignant tumors and to delineate the level of differentiation of primary breast sarcomas [5
]. Desmin, vimentin, smooth muscle antigen, CK, leukocyte common antigen, CD34, HMB-45, SMA, EMA, and S-100 protein should all be analyzed in sarcoma patients.
Undifferentiated pleomorphic sarcomas often grow rapidly and then may be painful. Imaging methods and macroscopy have revealed well-circumscribed masses with heterogeneous composition. Further, they have been identified as pale fibrous and fleshy areas admixed with zones of (cystic) necrosis, hemorrhage, or myxoid features [7
]. Microscopically, lesions exihibits cells showing marked pleomorphism admixed with bizarre giant cells, spindle cells, and variable foamy cells [8
]. A storiform growth pattern and variable chronic inflammatory cells are also common [7
Limited data on undifferentiated pleomophic sarcoma have indicated that this neoplasm has an aggressive clinical course and high incidence of recurrence and metastasis. Overall 5-year survival of patients with undifferentiated pleomophic sarcoma has been roughly 50% [7
]. Local surgical resection is the choice of treatment and negative margins are particularly important, although the extent of the surgery has been controversial. Axillary dissection has been generally thought to be unnecessary for undifferentiated pleomophic sarcoma of the breast, since these tumors rarely metastasize via the lymphatics [9
]. The role of adjuvant chemotherapy and radiation also has been unclear [9
]. In our case, the patient was subjected to wide local excision for recurrent mass without axillary dissection and will undergo simple mastectomy due to involvement of the resected margin.
Differential diagnosis should include metaplastic (saromatoid) carcinoma, malignant phyllodes tumor, inflammatory myofibroblastic tumor (IMT), and myofibrosarcoma.
Metaplastic (sarcomatoid) carcinoma, also called spindle cell carcinoma, is a rare heterogeneous neoplasm generally characterized by a mixture of adenocarcinoma with dominant areas of spindle cells, squamous and other mesenchymal differentiation [11
]. CK positivity of the spindle cells confirms the epithelial origin of this tumor.
Malignant phyllodes tumor consists of malignant mesenchymal cells and a benign epithelial component [5
]. The tumor shows overgrowth of the stroma in relation to the epithelial component, cellular pleomorphism with sarcomatous elements and frequent mitoses, and invasion of the surrounding tissues. The tumor can be differentiated from undifferentiated pleomorphic sarcoma by more extensive sampling for identifying epithelial component.
IMT is a neoplasm of myofibroblastic origin, often admixed with prominent inflammatory infiltrate consisting of lymphocytes, plasma cells, macrophages, eosinophils and histiocytes. An IMT is a low-grade neoplastic lesion showing lack of atypia, hyperchromasia, and abnormal mitotic figures [12
]. Immunohistochemistry of IMT shows strong SMA reactivity within the spindle cells frequently and occasional immunoreactivity for ALK, and negative or focal positivity for pankeratin.
Myofibrosarcomas are malignant tumors of myofibroblasts. Electron microscopy examination has been considered a gold standard for diagnosis of myofibrosarcoma, and ultrastructurally, the neoplastic cells have variable rough endoplasmic reticulum (RER) as well as peripheral filament bundles resembling stress fibers, collagen secretion granules and, rarely fibronectin fibrils and a fibronexus junction [13
]. Most myofibrosarcomas are immunoreactive for SMA and expression of CK, EMA, CD34, desmin or S100 protein is seen sporadically.
Although rare, benign spindle cell lesions of the breast may show malignant progression as in our case; however, breast sarcoma may be misdiagnosed as benign spindle cell lesions such as myofibroblastoma, nodular fasciitis and fibromatosis. The histological criteria for the diagnosis of benign spindle cell neoplasms includes well-circumscribed cells, monomorphic, bland-looking spindle to oval-shaped cells, minimal to moderate cytological atypia, fascicular and/or haphazard growth pattern; absence of epithelial and myoepithelial components; mitotic activity of 2 or less per 10 hpf, and the absence of both atypical mitosis and necrosis [14
Myofibroblastoma is a benign prototypic tumor of mammary stroma [13
]. Currently, it is believed that myofibroblastoma occurs mainly in older men and postmenopausal women. Morphologic features of classic-type myofibroblastoma are purely mesenchymal tumor with no epimyoepithelial components, interspersed thick hyalinized collagen bundles, low mitotic count, lack of marked cytologic atypia, no atypical mitoses, and the absence of necrosis. Most myofibroblastomas are typically positive to vimentin, desmin, and CD34 and immunoreactivity for SMA, bcl-2, and CD99 is frequently obtained [13
Nodular fasciitis is a rapidly growing lesion, which is usually subcutaneous and does not reach a large size. Microscopically, the lesion is fairly well circumscribed. It consists of plump active fibroblasts and myofibroblasts arranged in short, loose and irregular bundles. Nodular fasciitis is less cellular and uniform than undifferentiated pleomorphic sarcoma and does not infiltrate into surrounding tissue. Unlike in undifferentiated pleomorphic sarcoma, nuclear atypia and necrosis are not seen [5
Fibromatosis is non-encapsulated well-differentiated fibroblastic lesion composed of relatively uniform fibroblasts and collagen forming a firm, solitary, or multinodular mass with an infiltrative growth pattern. Immunohistochemically, fibromatosis exhibits positivity for SMA and vimentin and negativity for CK, estrogen, progesterone and androgen receptors [15
In our case, the histological sections of the initially excised tumor showed nodular proliferation of fibrous tissue with focal infiltrating margins; and it was composed of plump to spindle-shaped fibroblasts, eosinophilic infiltrates, many lymphoplasma cells, many keloid-like collagen bundles, a few atypical cells, including multinuclear giant cells and pleomorphic cells. The lack of abnormal mitosis was pointed towards a benign spindle cell lesion, and negative immunoreactivity for desmin, SMA, and S-100 protein was useful to exclude lesions with myofibroblastic components or differentiation such as myofibroblastoma, nodular fasciitis, or fibromatosis. However, the histological sections of the recurrent tumor exhibited different features compared to the initial histological findings; it revealed increased multinucleated giant and atypical tumor cells and abnormal mitosis, and it was suggestive of malignancy. This case did not arise from the epithelial tissue but from the mesenchymal tissue of the breast, being consistent with the negative immunoreactivity for CK, EMA, SMA, desmin and S-100 protein. Histologic findings of many atypical cells and abnormal mitotic activity, a negative immunoreactivity for SMA and ALK helped to exclude IMT from the differential diagnostic consideration. This case was distinguished from myofibroblastoma by negative immunoreactivity for SMA, CK, EMA, CD34, desmin and S100 protein. Although histological features of the recurrent mass were suggestive of a malignant pleomorphic spindle cell tumor, the immunohistochemical results failed to disclose the line of differentiate of the lesion. Hence, the final diagnosis of the tumor was undifferentiated pleomorphic sarcoma.
In conclusion, most breast cancers originate from the epithelium, and mesenchymal breast tumors are rarely seen, especially in men. Also, undifferentiated pleomorphic sarcoma, one subtype of primary breast sarcoma has been uncommon and these lesions represent special diagnostic difficulties. Herein, we reported a case of the undifferentiated pleomorphic sarcoma occurring in the male breast. Initially, it was difficult to classify the lesion as undifferentiated pleomorphic sarcoma; finally, based on histological findings and the immunohistochemical results of the tumor, we diagnosed the recurrent mass as undifferentiated pleomorphic sarcoma. In case of undifferentiated pleomorphic sarcoma of the breast, surgical excision of the tumor with adequate margins seems to be the most significant prognostic factor; therefore, it will be necessary to treat this patient with repeated excision or simple mastectomy to prevent local recurrence and to improve his chances of survival.