Primary mammary sarcomas are very rare, histologically heterogeneous non-epithelial malignant neoplasms. Primary undifferentiated pleomorphic sarcoma is a rare malignant mesenchymal tumor in the breast. It is characterized by marked cellular atypism and pleomorphism. Isolated cases with an aggressive course and poor prognosis have been commonly described in the literature. We present a rare case of a 62-year-old woman with an 18-cm solid tumor of the left breast, 6 months old, which grew rapidly during the last month. Physical examination and mammography revealed no enlarged lymph nodes in the left axilla. A total mastectomy was performed. The diagnosis of undifferentiated pleomorphic sarcoma is challenging due to the lack of specific immunohistochemical markers. It can only be made after excluding other types of soft tissue sarcomas. This report discusses the histopathological and immunohistochemical studies that were conducted. Our case is distinguished from others with the same diagnosis by the atypical clinical presentation, which is painless, and the spontaneous bleeding, as well as the large size of the tumor.

This malignant tumor is a diagnostic and therapeutic challenge for pathologists, surgeons, and oncologists due to the lack of consensus schemes.

breast sarcoma, immunohistochemistry, pleomorphic, undifferentiated

Undifferentiated pleomorphic sarcoma (UPS), formerly known as malignant fibrous histiocytoma (MFH), is a rare malignant soft tissue tumor that mostly affects the extremities, retroperitoneum, and abdominal cavity. Although uncommon, it can also arise in the mammary gland. The literature mentions less than 20 specific examples.^[1]

The cause of undifferentiated pleomorphic sarcomas is unknown. Primary breast sarcomas are rare malignant neoplasms that arise from connective tissue, not from the ductal or acinar epithelium of the gland. They have an aggressive course and account for less than 1% of all malignant mammary tumors and less than 5% of all sarcomas in adults.^[2]

Breast sarcomas typically present as a solid, painless tumor mass that often infiltrates the underlying muscle, fibrous tissue, and occasionally the skin. The diagnosis of undifferentiated pleomorphic sarcoma is made by excluding other groups of sarcomas, as it has no specific immunohistochemical markers for diagnosis.

This report presents a case study of a 62-year-old woman with a slowly growing, painless mammary tumor mass. The tumor was 18 cm in diameter and had been present for 3-4 months. However, it had shown rapid growth and ulceration in the last month. The patient sought medical help and was admitted to hospital due to spontaneous bleeding from skin ulceration in the area of the tumor. After taking her medical history, conducting an outpatient examination and palpation, and performing ultrasound and X-ray examinations of the lungs, the patient was admitted to the Department of Surgery in the PULMED University Hospital in Plovdiv. The patient reported no family history of breast cancer. The last preventive examination was conducted four years ago. Laboratory blood tests and tumor markers were normal. On examination, a superficial ulceration of the skin was found, accompanied by bleeding. No discharge from the nipple or deformation of the areola was described. The tumor covered the entire mammary gland, infiltrating the skin and surrounding fatty tissue. Operative intervention using a frozen section procedure was followed by a total mastectomy and lymphatic dissection. Biopsy examination of permanent preparations and additional immunohistochemical examinations with Vimentin, Cytokeratin, SMA, Desmin, and S-100 confirmed that it was an undifferentiated pleomorphic sarcoma. No metastases were found in the lymph nodes. Despite the poor prognosis of our patient, no metastases were detected in the lymph nodes, brain and lungs 6 months after the operation. The fibrosis of the stroma and the tumor microenvironment may have an impact on the prognosis and evolution of the specific case.

Macroscopic and microscopic examinations

During the physical examination, a painless tumor mass measuring 18 cm in diameter was discovered in the patient’s left mammary gland. The patient reported no family history of breast cancer, and the last preventive examination was 4 years ago. Laboratory blood tests and tumor markers were normal. Additionally, a superficial ulceration of the skin was found during the examination, which was accompanied by bleeding but did not result in any secretion or violation of the integrity of the areola. The tumor had infiltrated the skin, surrounding the fatty tissue, and chest wall, covering the entire mammary gland (Figs 1A, 1B) . The patient underwent surgery, and a total left-sided mastectomy was performed.

Histological examination showed diffuse, irregularly arranged atypical pleomorphic spindle cells intermixed with a few bizarre giant multinucleated tumor cells. Areas of coagulation necrosis were encountered, and mitoses were common (Figs 2, 3) .

Preserved ductal epithelium from the gland was found along with the tumor tissue in a malignant phyllodes tumor that was excluded. Immunohistochemistry revealed negative results for cytokeratin, S100, SMA, CD34, and HMB45, thus excluding metaplastic breast carcinoma, pleomorphic liposarcoma, leiomyosarcoma, and angiosarcoma. The Ki-67 proliferative index was 50%, while immunohistochemistry for ER, PR, and Her2 remained negative. The patient received postoperative radiation and chemotherapy.

Figure 1.

A, B. Macroscopic characteristics of the tumor - unclear borders with the surrounding soft tissues, dimensions 18 cm in diameter, grayish-whitish color, dense consistency. They show areas of necrosis in the center of the tumor.

Figure 2.

A, B. Microscopic presentation of the case, bundles of atypical neoplastic cells arranged in a storiform pattern, spindle-shaped and oval pleomorphic cells with bizarre nuclei, arranged in whorls; HE, ×200.

Figure 3.

IHC examination of the material from the tumor. A. IHC testing with Vimentin - diffuse positive in tumor cells; B. IHC testing with Desmin - focal positive in tumor cells; C. IHC testing with S-100 - negative in tumor cells; D. IHC testing with SMA - negative in tumor cells, positive in blood vessel walls.

Breast sarcoma is a rare and aggressive malignant tumor, accounting for less than 1% of all malignant breast tumors. They can be primary or secondary. Histologically, they exhibit marked cellular atypism and nuclear pleomorphism, with significant mitotic activity (including atypical mitoses) and adjacent fields of spindle cells. It is important to exclude metaplastic carcinoma and malignant phyllodes tumor as differential diagnoses.^[3] Angiosarcoma is the most common type.^[2] Clinically, patients commonly present with a rapidly enlarging unilateral breast mass.^[4] Tumors can grow up to 40 cm in size.^{[1, 5]} In some cases, patients may experience bleeding from the mammary or mammary skin.

The etiology of UPS remains unclear, and accurate diagnostic and therapeutic regimens are yet to be established. As tumor cells do not exhibit a specific differentiation to a particular mesenchymal tissue, the results of the IHC examination must be analyzed. Immunohistochemistry can aid in diagnosis, but it is often used as a tool of exclusion. In the malignant variant of a phyllodes tumor, neoplastic cells will be present alongside preserved mammary parenchyma. Conversely, in metaplastic carcinoma, epithelial markers such as CK will test positive. In relation to other sarcoma subtypes, pleomorphic liposarcomas exhibit positive immunohistochemistry for S-100 and MDM2, while angiosarcoma displays positive vascular endothelial markers such as CD31, CD34, and ERG. Leiomyosarcoma tests positive for SMA, Desmin, and CD10, while fibrosarcoma tests positive for SMA and Vimentin.

Undifferentiated pleomorphic breast sarcoma typically presents as a rapidly growing unilateral tumor.^[6] The diagnosis of sarcomas is not based on characteristic imaging studies.^[7] On mammography, sarcomas often appear as a well-defined tumor with demarcation and, in rare cases, calcification.^{[6, 7]} The pathohistological diagnosis relies on precise microscopic examination of high-quality histological specimens. Previously, undifferentiated pleomorphic sarcomas were classified as malignant fibrous histiocytomas (MFH) by the World Health Organization (WHO).^[8]

However, it was later acknowledged that MFH was a morphological pattern rather than a distinct clinicopathological entity and did not show definite differentiation to a particular type of mesenchymal tissue. Today, many neoplasms that were previously diagnosed as MFH are classified as pleomorphic subtypes of other sarcomas.^[9] Pleomorphic MFH/undifferentiated pleomorphic sarcoma is a group of high-grade sarcomas that lack differentiation. The name reflects this characteristic. In 2013, the World Health Organization (WHO) revised the classification of soft tissue tumors and introduced the concept of undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma (UPS/MFH). UPS is now classified into three groups: high-grade pleomorphic sarcoma, pleomorphic sarcoma with giant cells, and pleomorphic sarcoma with marked inflammation.^[10]

Primary undifferentiated breast sarcoma is a rare condition, and there is currently a lack of established clinicopathological studies and treatment approaches. The standard treatment for patients without distant metastases is surgical treatment with total mastectomy. The most important factor for long-term survival and prognosis is complete resection and absence of tumor infiltration in border areas.^[11] Axillary lymph node dissection is sometimes performed, but its significance for prognosis is not completely clear.^[12] The long-term outcomes of chemotherapy and radiotherapy after surgery are still unclear^[13] A case of UPS in a male breast has been reported.^[14]

Undifferentiated high-grade pleomorphic sarcomas in the breast typically occur in individuals in their sixth and seventh decades of life, as was the case in the example we are describing.^[15] In some instances, these sarcomas have been reported to occur after radiotherapy.^[16] The occurrence of undifferentiated pleomorphic sarcoma with giant cells is exceedingly rare, as is the case we are presenting.‌^[17] Immunohistochemical staining for Vimentin, smooth muscle actin (SMA), CD34, and CD68 may be positive, but their expression is not specific.^[18] Desmin staining may be positive, sometimes focally, as described in our findings. Desmin positivity can be observed in cells with myofibroblastic differentiation. Myofibroblastic tumors should be differentiated from myogenic tumors, which have a worse prognosis and a higher rate of metastases. Differentiating sarcoma subtypes based on molecular characteristics helps to individualize therapy for these patients.

The reasons for the development of sarcomas remain unclear. Diagnosis is difficult due to the lack of specific immunohistochemical markers. Total mastectomy with or without lymph node dissection is the most common treatment, followed by chemo- and radiotherapy. Histological grading of the tumor and assessment of the resection margins are crucial for prognosis. Differentiating between breast sarcoma subtypes based on molecular characteristics can help tailor therapy for individual patients. In such cases, the gold standard for diagnosis is immunohistochemical examination. Effective treatment for these patients requires a multidisciplinary approach.

Primary breast sarcomas are rare malignant neoplasms that grow rapidly and have an aggressive course. The only definitive intervention in these cases is surgery with wide resection of the tumor. Diagnosing mammary sarcomas can be challenging due to their low incidence, long latency period, non-specific imaging findings, and difficulties in clinical and histological detection of these lesions. Rapidly growing breast masses should include consideration of these tumors in the differential diagnosis.

The distinguishing features of our case are the lack of previous radiotherapy, the large size of the tumor and the painless course, as well as the currently favorable evolution of the patient’s follow-up, which we associate with the clear resection lines and the absence of metastases in other organs.

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The authors have declared that no competing interests exist.