Malignant phyllodes tumor with heterologous component, aneurysmal bone cyst-like changes and osteoclast-type giant cells
Histopathology:
- Cellular neoplasm composing of pleomorphic epithelioid to spindle-like stromal cells with marked nuclear pleomorphism, vesicular nuclei, prominent nucleoli, and focal areas of necrosis.
- Leaf-like patterns of phyllodes tumor with benign duct epithelium are seen, which are pushed by underlying sheets of giant cells at a few places.
- Sheets of osteoclast-type giant cells are admixed with pleomorphic stromal cells in many areas.
- Some areas show large vascular channels and blood-filled pools with osteoclast-type giant cells, reminiscent of aneurysmal bone cyst-like areas.
- Heterologous cartilaginous components are seen with atypical chondrocytes, suggestive of chondrosarcomatous changes.
- On extensive sectioning, ductal carcinoma in situ or, frankly malignant epithelial cells, anastomosing vascular channels or immature osteoid areas are not seen.
Practical Points of Pathoclinics:
- Diagnostic features of malignant phyllodes tumor are stromal overgrowth, infiltrative border, highly cellular stroma (most often fibrosarcomatous stroma), moderate-to-marked cellular atypia, mitotic activity (≥10 mitoses/10 high-power fields) and areas of tumor necrosis.
- Heterologous areas are not common, and may include liposarcoma, osteosarcoma, chondrosarcoma, rhabdomyosarcoma, and angiosarcoma. Malignant phyllodes tumor with heterologous components should be differentiated from metaplastic/spindle cell carcinomas and primary or metastatic breast sarcomas. Appropriate clinical history and radiological workup are useful to rule metastatic sarcoma.
- The presence of giant cells in malignant phyllodes tumor also bring giant cell tumor of soft tissue and breast carcinoma with osteoclast-like giant cells in the differentials.
- In the present case, the presence of benign epithelial component, forming the leaf-like pattern of benign/low-grade phyllodes tumors, provides evidence of phyllodes tumor. Identification of such areas usually requires extensive sampling. Diagnosis requires clinical inputs and immunohistochemistry work-up in the absence of a typical phyllodes pattern and in breast core biopsies.
- Aneurysmal bone cyst-like areas are very uncommon. Such areas are reactive in origin, and may indicate a previous vascular lesion of the breast.
- Differential diagnostic features of breast mass with heterologous components and giant cells rich lesions:
| Diagnostic features | Metaplastic carcinoma with heterologous differentiation and/or osteoclast-like giant cells | Malignant phyllodes tumors with heterologous differentiation | Primary or metastatic breast sarcomas | Giant cell tumor of the breast |
| Atypical ductal hyperplasia or ductal carcinoma in situ, glandular and tubular pattern or squamous areas | Characteristic features. When present, surely favour carcinoma | Not seen. Uncommon to have additional separate areas of carcinoma. | Not seen | Not seen |
| Benign epithelial component (leaf-like pattern) | Not seen | Highly suggestive of phyllodes tumor | Not seen | Not seen. |
| Heterologous elements | May include chondroid, osseous, or rhabdoid areas. | angiosarcoma, liposarcoma, osteosarcoma, chondrosarcoma, or rhabdomyosarcoma | angiosarcoma, liposarcoma, osteosarcoma, chondrosarcoma, or rhabdomyosarcoma | Uncommon. Osseous and chondroid metaplasia may be seen. |
| Giant cells | Tumor giant cells may be seen but uncommon. Osteoclast type giant cells are also uncommon and admixed with carcinomatous and spindle cell areas | Osteoclast-like giant cells may be seen especially around vascular spaces | Osteosarcoma may contain numerous osteoclast-type giant cells | Numerous osteoclast type giant cells are the predominant component with mononuclear round to ovoid spindled stromal cells in a richly vascularized stroma. |
| Additional features: | Aneurysmal bone cyst-like areas are described in very few reports of malignant phyllodes tumors. | 1. Extraskeletal osteosarcoma may show aneurysmal bone cyst-like areas. 2. lace-like immature osteoid favours osteosarcoma 3. Anastomosing vascular channels with atypical endothelial cells favours angiosarcoma. | Aneurysmal cyst-like changes, extravasated red blood cells, hemosiderin deposits and fibrosis are common | |
| Atypical mitotic figures. | Seen | Seen | Seen | Not seen. Significant nuclear atypia, and pleomorphism are not seen. |
| Immunohistochemistry | Cytokeratin: positive p63: positive CD34: negative GATA3: positive | Cytokeratin: may be focal positive p63: may be focal positive CD34: positive GATA3: negative | GATA3: negative | CD68: positive SMA: positive p63: positive S100: positive SATB2: positive CK: negative H3F3A is negative in breast giant cell tumor, while it is positive in bone counterpart. GATA3, MGB1, and CK OSCAR are negative. |
| Recurrence and metastasis | High risk | High risk | High risk | Approximately 10% cases recur, but metastasis is rare |
Thanks to Dr Manoj Kahar @Bhanumati Clinical Laboratory, Navsari, Gujarat 396445, for submitting the above surgical pathology case for learning and teaching purpose @ https://www.pathoclinics.com/
Additional reading and references:
- Nayak M, Patra S, Mishra P, Sahoo N, Sasmal PK, Mishra TS. Malignant phyllodes tumor with heterologous differentiation: Clinicopathological spectrum of nine cases in a tertiary care institute in Eastern India. Indian J Pathol Microbiol. 2017 Jul-Sep;60(3):371-376. doi: 10.4103/IJPM.IJPM_426_16. PMID: 28937374.
- Liu T, Jiang L, Li J, Sun J, Li H, Gao J, Li S, Li J, Zhao H. A huge malignant phyllodes tumor of the breast with osteoclast-like giant cells: a case report. Gland Surg. 2021 Apr;10(4):1508-1514. doi: 10.21037/gs-20-845. PMID: 33968702; PMCID: PMC8102212.
- Kelten C, Boyaci C, Leblebici C, Behzatoglu K, Trabulus DC, Sari S, Nazli MA, Bozkurt ER. Malignant Phyllodes Tumor Including Aneurysmal Bone Cyst-Like Areas in Pregnancy – a Case Report and Review of the Literature. Breast Care (Basel). 2016 Aug;11(4):291-294. doi: 10.1159/000448236. Epub 2016 Aug 11. PMID: 27721719; PMCID: PMC5040892.