|Year : 2014 | Volume
| Issue : 2 | Page : 124-126
Malignant phyllodes tumor with osteoclastic giant cells
BR Vani, B Deepak Kumar, BN Sandhyalakshmi, K Geethamala, V Srinivasa Murthy, M Radha
Department of Pathology, ESIC Medical College and PGIMSR, Bengaluru, Karnataka, India
|Date of Web Publication||20-Jun-2014|
B R Vani
Department of Pathology, ESIC Medical College and PGIMSR, Rajajinagar, Bengaluru, Karnataka
Source of Support: None, Conflict of Interest: None
Phyllodes tumor (PT) is uncommon biphasic epithelial tumors with exaggerated stromal cellularity, accounting for 0.3-0.9% of primary breast tumors. Malignant PT (MPT) is a rare and potentially aggressive breast neoplasm. Histologically has fibrosarcomatous type of stroma and rarely heterologous mesenchymal differentiation. MPT with osteoclastic giant cells is even rarer, which can be confused for primary malignant fibrous histiocytoma and metaplastic carcinoma. Herein, authors present a 51 year female who presented with right breast mass, clinically and cytological diagnosed as carcinoma of the breast. Histopathology and added immunohistochemistry enabled in arriving at a final definitive diagnosis of MPT with osteoclast giant cells. The diagnosis of this distinct entity is of importance due to their better prognostic implication.
Keywords: Breast carcinoma, immunohistochemistry, metaplastic carcinoma, osteoclastic giant cells, phyllodes tumor
|How to cite this article:|
Vani B R, Kumar B D, Sandhyalakshmi B N, Geethamala K, Murthy V S, Radha M. Malignant phyllodes tumor with osteoclastic giant cells. Saudi J Health Sci 2014;3:124-6
| Introduction|| |
Phyllodes tumor (PT) are uncommon biphasic tumors with exaggerated stromal cellularity, accounting for 0.3-0.9% of primary breast tumors.  Malignant PT (MPT) is aggressive neoplasms with fibrosarcomatous type of stromal histology. Rarely, heterologous mesenchymal differentiation toward liposarcoma, osteosarcoma, chondrosarcoma, rhabdomyosarcoma occurs. MPT with osteoclastic giant cells are even rarer. This can be confused for metaplastic carcinoma and primary malignant fibrous histiocytoma (MFH).  Herein, authors present a 51 year female who presented with right breast mass, clinically and cytologically diagnosed as carcinoma of the breast. Histopathology with immunohistochemistry (IHC) helped us to arrive at the final diagnosis of MPT with osteoclast giant cells.
| Case report|| |
The case we present here is about a 51-year-old female tailor by occupation presented to surgical out-patient block with right breast lump of 2 months duration. Clinical examination revealed right breast mass measuring 6 × 5 cm with restricted mobility in the outer quadrant. There were no skin changes. No other local or systemic complaints. A clinical diagnosis of carcinoma of the breast was made and the patient was subjected to fine-needle aspiration cytology. Aspiration performed from multiple sites yielded cellular smears composed predominantly of bizarre pleomorphic oval to spindle cells showing vesicular nuclei, mitotic figures along with numerous osteoclastic types of multinucleated giant cells against a hemorrhagic background. A diagnosis of carcinoma of the breast with multinucleated giant cells was offered. With prior pre-operative investigations modified radical mastectomy (MRM) with axillary clearance was performed. MRM specimen received measured 26 × 19 × 4 cm, external surface showed a bulge measuring 4 × 4 cm. Serial sections revealed solid fleshy grey tan lesion measuring 6 × 5 × 4 cm with areas of microcysts, nodules and hemorrhage. Adjacent breast tissue was unremarkable. Axillary pad dissection identified 11 lymph nodes of which larger measured 1 × 0.9 cm.
Histopathological examination (HPE) showed cellular neoplasm composed of pleomorphic spindle cells arranged in diffuse sheets. Individual spindle cells have hyperchromatic pleomorphic nucleus, prominent nucleoli and moderate eosinophilic cytoplasm. Numerous osteoclastic type of multinucleated giant cells, tumor giant cells and 4-5 mitosis per high power field (hpf) seen. Secondary changes like calcification and ossification were noted. Adjacent areas showed features of benign PT [Figure 1]a-c. All 11 lymph nodes were free of tumor. Differentials of MFH, metaplastic tumor and MPT were thought of. IHC performed showed strong positivity for vimentin, whereas negative for cytokeratin and epithelial membrane antigen. Ki-67 performed showed (80%) strong positivity in stromal cells; however osteoclastic giant cells were negative. Adjacent benign PT showed positivity of Ki-67 in less than 0.1% of stromal cells [Figure 1]d. Considering HPE and IHC a final diagnosis of MPT with osteoclast giant cells and benign phyllodes in adjacent foci was made-stage 2B (pT3N0Mx). Patient was subjected to the tumor bed radiotherapy and on follow-up, no recurrence till date.
|Figure 1: (a) H and E photomicrograph show spleomorphic spindle cells (×40), (b) H and E photomicrograph sarcoma stroma with osteoclastic giant cells (×40), (c) H and E photomicrograph surrounding foci of benign phyllodes tumor (×10), (d) Ki-67 immunostaining showing strong nuclear positivity (×40)|
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| Discussion|| |
PT is rare biphasic neoplasms originating from intralobular stroma of breast and constitutes 0.3-1.5% of all breast tumors.  Johannes Muller in 1838 was first to describe these fibroepithelial neoplasms.  Clinically, they present as rapidly growing large painless mass. Average age of presentation is 40-50 years, while in Asians it is 25-30 years; though MPT develops 4-5 years later.  Average size of tumor is 4-5 cm, bilaterality is rare. , In the present case, patient was 51 years of age with history of progressively increasing breast lump measuring 6 cm.
In general, these tumors are large round to oval, bosselated, grey white, soft, fleshy, partially encapsulated, sometimes with secondary changes such as cysts, hemorrhage, necrosis and myxoid degeneration.  In the present case, there were cysts filled with mucoid material along with adjacent areas of hemorrhage. PT encompasses the spectrum of benign, borderline, malignant neoplasms depending on the histologic grade. MPT is characterized by infiltrating margins, marked stromal cellularity, mitotic rate >10/10 hpf and severe pleomorphism. Various studies reveal prevalence range of benign PT being 75.6-100%, while that of borderline PT and MPT being 2.3-17.8% and 6.6-20% respectively.  MPTs have overall local recurrence rate of 21% and metastasis of 22%.
Stroma in MPT is of monomorphic spindle cell to pleomorphic fibrosarcomatous areas. Nevertheless heterologous mesenchymal differentiation such as liposarcoma, chondrosarcoma, rhabdomyosarcoma, osteosarcoma and MFH occurs. Secondary stromal changes such as metaplastic cartilage, bone, fat smooth muscle and exceptionally skeletal muscle do occur. ,
Literature search revealed only few case reports with associated osteoclastic giant cells. ,,,, In the present case, osteoclastic giant cells with additionally foci of benign calcification and ossification were seen. These findings were concurrent with the case report by Hemalatha et al.  Multinucleate osteoclastic giant cells are non-neoplastic and considered to be modified histiocytes, occurring as a reaction to extracellular matrix produced by tumor cells. , IHC plays a pivotal role wherein MPTs are positive for vimentin and negative for epithelial markers.
At histology differential include MFH and metaplastic carcinoma. MFH was ruled out due to lack of storiform pattern of cell arrangement and the presence of adjacent benign phyllodes foci. Metaplastic carcinoma needs to have glandular differentiation and by IHC cytokeratin positivity in tumor cells.
In the present case, percentage of Ki-67 positivity in the proliferating stromal cells was as high as up to 60% as against a percentage of <10% in the non-proliferating stroma. All 11 lymph nodes were negative supporting the fact that PT usually spreads by hematogenous route than via lymphatics.  Hematogenous metastasis of only stromal component occurs to lungs, pleura, bone and brain. ,, Overall 5-year survival rates in MPT is more than 91% when compared to metaplastic carcinoma with less than 60%. , This highlights that differentiation from metaplastic carcinoma/epithelial carcinoma plays a vital role for treatment and in prognosis. Surgical options of lumpectomy versus mastectomy depends if women meets the criteria for breast conservation. However, role of adjuvant radiotherapy is uncertain though the decrease in local recurrence reported following treatment.  In the present case, cytology could not subtype the breast carcinoma; hence the patient was subjected to MRM with axillary clearance followed by tumor bed radiotherapy.
| Conclusion|| |
We report a rare entity of MPT with osteoclastic giant cells in 51-year-old lady. Histopathology supplemented with IHC enabled in arriving at a final definitive diagnosis. Since MPT has better prognostic implications in comparison to metaplastic carcinoma or other epithelial malignancy of breast, its distinction is imperative.
| References|| |
|1.||Chan YJ, Chen BF, Chang CL, Yang TL, Fan CC. Expression of p53 protein and Ki-67 antigen in phyllodes tumor of the breast. J Chin Med Assoc 2004;67:3-8. |
|2.||Khurshid A, Kayani N, Bhurgri Y. Phylloides tumors in adolescent girls and young women in Pakistan. Asian Pac J Cancer Prev 2006;7:563-6. |
|3.||Pandit AA, Vora IM, Shenoy SG, Gurjar AM. Bilateral cystosarcoma phylloides with osteogenic sarcomatous stroma (a case report with review of literature). J Postgrad Med 1985;31:215-6. |
|4.||Bellocq JP, Magro G. Fibroepithelial tumors. In: Tavassoli FA, Devilee P, editors. Pathology and Genetics. Tumours of the Breast and Female Genital Organs. WHO Classification of Tumors. Lyon: IARC Press; 2003. p. 99-103. |
|5.||Hemalatha AL, Sindhuram VS, Asha U. MFH mimic in breast: A high-grade malignant phyllodes tumor. Case Rep Pathol 2012;2012:835687. |
|6.||Fernández-Aguilar S, Noël JC. Malignant phyllodes tumor of the breast with osteoclast-like giant cells: A case report. Ann Pathol 2007;27:31-4. |
|7.||Guerrero MA, Ballard BR, Grau AM. Malignant phyllodes tumor of the breast: Review of the literature and case report of stromal overgrowth. Surg Oncol 2003;12:27-37. |
|8.||Rosai J. Breast. In: Rosai and Ackerman′s Surgical Pathology. 10 th ed., Vol. 2. Missouri: Mosby Elsevier; 2011. p. 1764-839. |
|9.||Macdonald OK, Lee CM, Tward JD, Chappel CD, Gaffney DK. Malignant phyllodes tumor of the female breast: Association of primary therapy with cause-specific survival from the Surveillance, Epidemiology, and End Results (SEER) program. Cancer 2006;107:2127-33. |
|10.||Rosen PP. Carcinoma with metaplasia. Rosen′s Breast Pathology. 3 rd ed. Philadelphia: Lippincott, Williams and Wilkins; 2009. p. 500-1. |