Phyllodes tumor (PT), an uncommon fibroepithelial neoplasm, accounts for <1% of all primary tumors of the breast.1 PT is classified as benign, borderline, or malignant based on several histopathologic features, such as stromal cellularity, atypia, overgrowth, tumor border, and mitotic index. Malignant phyllodes tumor (MPT), comprising 8% to 20% of PT cases, exhibits rapid growth and aggressive behavior resulting in local recurrence and distant metastasis.

The presence of a heterologous sarcomatous component is sufficient to diagnose MPT, regardless of all the aforementioned parameters.2 The stromal component may show transformation to liposarcoma, angiosarcoma, chondrosarcoma, or rarely to osteosarcoma. MPT with osseous differentiation is often misdiagnosed on imaging as benign giant calcifications, which can result in treatment delay.3 Timely management and better prognosis for patients depend on a strong clinical and radiologic suspicion and a correct histopathologic diagnosis.

This study describes a patient diagnosed with MPT with heterologous osteosarcomatous differentiation and osteoclast-like giant cells. Only a few cases of MPT exhibiting osteosarcomatous components have been reported in the literature, making this case report valuable.

A 34-year-old woman presented with a painless lump in her right breast that had been rapidly increasing in size over the preceding few months. On physical examination, a large, mobile mass with hard consistency was palpated in the lower outer quadrant of the right mammary tissue. Mammography revealed a partly circumscribed, high-density, irregular mass measuring 55 × 43 × 29 mm with amorphous dense calcification in the retroareolar region, suggestive of a neoplastic etiology (Figure 1A–1B).

A core needle biopsy was performed, and histopathologic examination showed stromal hypercellularity and an abundance of osteoclast-like giant cells, raising the possibility of phyllodes tumor vs giant cell tumor of the breast. For confirmation of the diagnosis, the patient underwent a wide local excision with clear margins.

On gross inspection, the specimen measured 6 × 6 × 5.5 cm in size (Figure 1C–D). The cut section revealed a hard, gray-white tumor measuring 5.5 × 4.5 × 3 cm with large areas of calcification. Microscopy showed the presence of a focally infiltrative stromal tumor exhibiting large areas of eosinophilic, lace-like osteoid matrix with osteoblastic rimming and abundant osteoclastic giant cells. The tumor showed moderate stromal cellularity and cellular atypia with a mitotic rate of >10/10 high-power fields (HPF) (Figure 2A–E). Extensive sampling revealed epithelial components with a leaf-like pattern resembling phyllodes tumor, thereby excluding the possibility of primary osteosarcoma.

A panel of immunohistochemistry markers was ordered to rule out metaplastic carcinoma or carcinosarcoma. On immunohistochemistry, stromal cells were positive for vimentin, CD10, and focally for BCL-2. The osseous component was positive for osteonectin and SATB2 (Figure 3A–D). The tumor cells were negative for pan-CK and p63 (Figure 3E–F).

Thus, a final diagnosis of malignant phyllodes tumor with heterologous osteosarcomatous differentiation and osteoclast-like giant cells was made. All the resected margins were free of tumor. The patient did not undergo axillary lymph node dissection. The tumor was staged as pT2NxM0 according to the American Joint Committee on Cancer (AJCC) 8th edition and the World Health Organization (WHO) recommendations.2,4

MPT is a rare entity that poses several diagnostic and therapeutic challenges. It usually presents as a unilateral mass with an average size of 4 to 5 cm. Larger tumors (>10 cm) may distort the mammary architecture and cause skin ulceration due to pressure effects and ischemia.2 PT is primarily seen in older women (aged 40–50 years), but our patient was 34 years old, which was similar to a case reported by Jha et al.5 Osteosarcomatous transformation of MPTs is extremely uncommon, accounting for 1.3% of breast phyllodes tumors. The proportion of the osseous component is variable and may replace the entire tumor tissue.6

The imaging profile of phyllodes tumors is variable, and the prediction of tumor grade on radiology alone is unreliable. MPT tends to display an irregular shape on radiology as opposed to well-circumscribed borders in the benign category. Calcifications are not a common finding associated with PT. According to a study by Lee et al., coarse and amorphous calcifications suggest a benign process, whereas the presence of linear and branched calcifications is indicative of malignant lesions.7 The mammography findings of our patient showed a partly circumscribed mass and coarse calcifications. A rapidly enlarging mass coupled with suspicious radiologic findings substantiated the need for a confirmatory biopsy.

Correct diagnosis with preoperative tissue biopsy prevents secondary surgical interventions. However, owing to the biphasic nature and marked heterogeneity of MPT, the sensitivity of core needle biopsies is low. Research has reported the use of larger needle diameters and taking at least 3 samples from the lesion to improve accuracy.8 In our patient, biopsy raised the differential diagnosis of phyllodes tumor vs giant cell tumor (GCT) due to the presence of numerous interspersed osteoclast-like giant cells. Due to the heterogeneous nature of phyllodes tumors, surgical excision with clear margins was planned for confirmation of the diagnosis. Primary GCT arising from the soft tissues of the breast is extremely rare. The presence of an epithelial component, stromal hypercellularity, cellular pleomorphism, and an osteoid matrix ruled out the diagnosis of this rare entity in our case.9

Several parameters are used to categorize phyllodes tumors as benign, borderline, and malignant. Despite moderate stromal cellularity and atypia, our case was diagnosed as malignant due to the presence of the osteosarcomatous component, which is consistent with the criteria mentioned in the WHO classification.2 Furthermore, MPT may predominantly comprise sarcomatous components on histopathology, making its diagnosis extremely challenging. In such cases, a thorough sampling of different areas of the tumor is warranted to identify epithelial structures indicative of a phyllodes tumor. Our case showed a preponderance of osteoid matrix with rimmed osteoblasts and numerous osteoclastic giant cells, raising the possibility of primary extraosseous osteosarcoma. Numerous samples were taken to visualize ductal and leaf-like structures and arrive at a correct diagnosis. Metaplastic carcinoma, an important differential consideration of MPT, was excluded using pan-CK and p63 immunohistochemistry markers in our patient.

MPT with osteosarcomatous transformation has been linked to poor clinical outcomes and a biological behavior similar to its soft tissue sarcoma counterpart. These tumors hold a great propensity for local recurrence and distant metastasis.10 The mesenchymal stem cell niche is considered responsible for metastatic spread via the hematogenous route. Distant metastasis has been reported in nearly all internal organs, but the lung is the most common site.10 A comprehensive review conducted by Hall et al. on phyllodes tumors with osteosarcomatous transformation reported metastatic spread in 52% of cases, with the majority exhibiting lung metastases.11 Kapiris et al. found an increased incidence of local recurrence (12% to 65%) and metastatic spread (up to 27%), especially in tumors with large sizes and inadequate surgical margins.12

There is no consensus on the optimal management of MPT. The National Comprehensive Cancer Network (NCCN) 2020 guidelines recommend excision with a margin of ≥10 mm for borderline and malignant phyllodes tumors to reduce the incidence of tumor recurrence.13 Tumor size and a negative margin status are considered to be the most reliable predictors of recurrence.10

Lymph node involvement is relatively uncommon in MPT; thus, axillary lymph node dissection is not routinely performed for such patients, which was also true in our case. The role of adjuvant therapy for cases displaying heterologous sarcomatous elements remains controversial due to limited evidence.10,12 Our patient opted for surgery with regular follow-up using imaging studies and has not reported recurrence or metastasis to date.

A summary of clinicopathological characteristics of cases diagnosed as MPT with osteosarcomatous differentiation in the last 3 years is provided in Table 1.

MPT with osteosarcomatous differentiation is a rare and challenging entity associated with a poor clinical outcome. The aggressive nature of this subtype underscores the importance of a multidisciplinary approach involving breast surgeons, pathologists, and radiologists to optimize patient care and prognosis. A careful histopathologic examination and immunohistochemistry evaluation aid in the accurate diagnosis of high-grade PT. We presented a unique case of MPT with osteosarcomatous differentiation and osteoclast-like giant cells diagnosed on a wide local excision specimen. Close surveillance is crucial in such patients for the timely detection of tumor recurrence and metastasis.

The patient provided written informed consent to publish the information and images contained in the case report.