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

Presence of a heterologous sarcomatous component is sufficient to diagnose malignant phyllodes tumor, regardless of all the above parameters. 2 The stromal component may show transformation to liposarcoma, angiosarcoma, chondrosarcoma or rarely to osteosarcoma. MPT with osseous differentiation often gets misdiagnosed on imaging as benign giant calcifications resulting in treatment delay. 3 Timely management and better prognosis of patients is dependent on a strong clinical and radiological suspicion coupled with correct histopathological diagnosis.

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

A 34-year-old female 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 right mammary tissue. Mammography revealed a partly circumscribed high-density irregular mass measuring 55x43x29mm with amorphous dense calcification in the retroareolar region, suggestive of neoplastic aetiology (Figure Ia-Ib). A core needle biopsy was performed and histopathological examination showed stromal hypercellularity and an abundance of osteoclast-like giant cells raising the possibility of phyllodes tumor versus giant cell tumor of the breast. For confirmation of diagnosis, the patient underwent a wide local excision with clear margins.

On gross inspection, the specimen measured 6x6x5.5cms in size ( Figure Ic

Malignant phyllodes tumor is a rare entity that poses several diagnostic and therapeutic challenges. It usually presents as a unilateral mass with an average size of 4-5 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 (40-50 years), but our patient was aged 34 which was similar to a case reported by Jha N et al. 4 Osteosarcomatous transformation of MPTs is extremely uncommon, accounting for 1.3% of breast phyllodes tumors. The proportion of osseous component is variable and may replace the entire tumor tissue. 5 The imaging profile of phyllodes tumor is variable and prediction of tumor grade on radiology alone is unreliable. MPT tends to display an irregular shape on radiology as opposed to good circumscription in the benign category. Calcifications are not a common finding associated with PT. According to a study by Lee JS et al., coarse and amorphous calcifications suggest a benign process, whereas the presence of linear and branched calcifications is indicative of malignant lesions. 6 The mammography findings of our patient showed a partly circumscribed mass and coarse calcifications. A rapidly increasing mass coupled with suspicious radiology 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, sensitivity of core needle biopsies is low. Research has reported the use of larger needle diameters and taking at least three samples from the lesion to improve accuracy. 7 In our patient, biopsy raised the differential diagnosis of phyllodes tumor versus giant cell tumor (GCT) due to the presence of numerous interspersed osteoclast-like giant cells. Due to the heterogeneous nature of phyllodes tumor, surgical excision with clear margins was planned for confirmation of diagnosis. Primary GCT arising from the soft tissues of breast is extremely rare. Presence of an epithelial component, stromal hypercellularity, cellular pleomorphism and osteoid matrix ruled out the diagnosis of this rare entity in our case. 8 Several parameters are used to categorise phyllodes tumor as benign, borderline and malignant. Despite moderate stromal cellularity and atypia, our case was diagnosed as malignant due to the presence of the ostesarcomatous component, which is according to the criteria mentioned in WHO. 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 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 visualise 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 with 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. 9 The mesenchymal stem cell niche is considered responsible for metastatic spread via hematogenous route. Distant metastasis has been reported in nearly all internal organs, but the lung is the most common site. 9 A comprehensive review conducted by Hall RR. et al. on phyllodes tumor with osteosarcomatous transformation reported metastatic spread in 52% with majority exhibiting lung metastases. 10 Kapiris et al. found an increased incidence of local recurrence (12-65%) and metastatic spread (up to 27%), especially in tumors with large sizes and inadequate surgical margins. 11 There is no consensus on the optimal management of MPT. NCCN 2020 guidelines recommend excision with a margin of ≥10 mm for borderline and malignant phyllodes tumors (MPT) to reduce the incidence of tumor recurrence. 12 Tumor size and a negative margin status are considered to be the most reliable predictors of recurrence. 9 Lymph node involvement is relatively uncommon in MPT; thus, axillary lymph node dissection is not routinely performed for such patients which was similar to our case. The role of adjuvant therapy for cases displaying heterologous sarcomatous elements remains controversial due to limited evidence. 911 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 osteosarcoma differentiation in the last three years is provided in Table 1.

MPT with osteosarcomatous transformation 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 histopathological examination and immunohistochemistry evaluation aid in 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 timely detection of tumor recurrence and metastasis.

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