|Year : 2015 | Volume
| Issue : 4 | Page : 1035
Cerebellar metastases of recurrent phyllodes tumor breast; a rare phenomenon reflecting the unpredictable outcome
Jyotsna Singh1, Kaushik Majumdar2, Rahul Gupta3, Vineeta Vijay Batra1
1 Department of Pathology, Academic Block, Govind Ballabh Pant Hospital, New Delhi, India
2 Department of Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India
3 Department of Neurosurgery, Fortis Hospital, Noida, Uttar Pradesh, India
|Date of Web Publication||15-Feb-2016|
Vineeta Vijay Batra
Department of Pathology, Academic Block, Govind Ballabh Pant Hospital, Jawaharlal Nehru Marg, New Delhi - 110 002
Source of Support: None, Conflict of Interest: None
Carcinomas of lung, breast, colon, kidney, and malignant melanomas are the most common malignancies that metastasize to the central nervous system (CNS). Phyllodes tumor is a rare fibroepithelial tumor of the breast, often having unpredictable recurrences, with increasing histological grade and distant metastasis. Malignant forms exist, which may develop distant metastases usually to the lung, pleura, bone, and liver. CNS metastasis of phyllodes tumor is rare and associated with a poor prognosis, with resistance to chemotherapy and radiation. We present a rare case of cerebellar metastasis in recurrent phyllodes tumor breast with subsequent rapid downhill course.
Keywords: Breast, CNS, cerebellum, metastasis, phyllodes tumor
|How to cite this article:|
Singh J, Majumdar K, Gupta R, Batra VV. Cerebellar metastases of recurrent phyllodes tumor breast; a rare phenomenon reflecting the unpredictable outcome. J Can Res Ther 2015;11:1035
|How to cite this URL:|
Singh J, Majumdar K, Gupta R, Batra VV. Cerebellar metastases of recurrent phyllodes tumor breast; a rare phenomenon reflecting the unpredictable outcome. J Can Res Ther [serial online] 2015 [cited 2020 Jul 3];11:1035. Available from: http://www.cancerjournal.net/text.asp?2015/11/4/1035/154031
| > Introduction|| |
Carcinomas of lung, breast, colon, kidney, and malignant melanomas are the most common malignancies that metastasize to the central nervous system (CNS). Phyllodes tumor is a rare fibroepithelial tumor of the breast that accounts for less than 1% of all breast neoplasms. Malignant forms comprise nearly 25% of the cases. Around 13-20% of patients with malignant phyllodes tumors develop distant metastases, usually to the lung, pleura, bone, and liver. CNS metastasis of phyllodes tumor is rare and associated with a poor prognosis. ,
| > Case report|| |
A 41-year-old female patient presented with progressively increasing headache, vomiting, and giddiness for 7 days. She had a history of a small nodule in the left breast enucleated 7 years back and reported as phyllodes tumor. One year back, she developed a large recurrent lump in the same breast involving all quadrants, with associated nipple deformity. The lump was not adhered to the pectoralis muscles and fascia, and there was no lymphadenopathy. Mammography showed areas of necrosis and calcification [Figure 1]a and b]. A simple mastectomy was performed, and histology confirmed a recurrent benign phyllodes tumor. However, the tumor showed mild nuclear atypia and increased mitotic activity (less than 5 per 10 high power field (HPF)).
|Figure 1: (a and b) Mammography breast lump showing areas of necrosis and calcification. (c) Postoperative CT showing the resected cerebellar mass lesion. (d) Intraoperative squash smear showing oval to spindle markedly atypical cells in fascicles (toluidine blue, X200). CT = Computed tomography|
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After 8 months, a second recurrence was observed in the form of two fleshy nodules measuring 2 × 2 cm in the left anterior chest wall, with similar histopathology. The patient subsequently developed neurological symptoms for which she was referred to this hospital for further workup.
Magnetic resonance imaging (MRI) brain showed an ill-defined, right cerebellar mass hypointense on T1-weighted imaging, with heterogeneous enhancement on contrast. The tumor was excised through right suboccipital paramedian craniotomy [Figure 1]c]. It was well-encapsulated, lobulated, greyish white, and firm in consistency. Squash smear cytology with histological correlation revealed a highly cellular tumor composed of sheets of markedly atypical spindle cells in fascicular arrangement, representing a fibrosarcoma-like appearance [Figure 1]d and [Figure 2]a]. The individual cells showed moderate nuclear pleomorphism, brisk mitosis (around 8-10 per 10 HPF) [Figure 2]b] and areas of necrosis. Epithelial elements were not seen. The tumor was seen to infiltrate into the adjacent cerebellar tissue.
|Figure 2: (a) Photomicrograph showing a cellular tumor comprising of atypical spindle cells arranged in fascicles (H and E, X200). (b) Cells showing moderate nuclear pleomorphism and brisk mitosis (arrow; H and E, X400). (c) Tumor cells negative for GFAP (X200) and (d) positive for SMA (X200). H and E = Hematoxylin and eosin, GFAP = glial fibrillary acidic protein, SMA = smooth muscle actin|
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The tumor cells were positive for smooth muscle actin (SMA) [Figure 2]d]; focally positive for epithelial membrane antigen (EMA); and negative for CD34, glial fibrillary acidic protein (GFAP) [Figure 2]c], vimentin, and S-100. Immunohistochemistry (IHC) for estrogen and progesterone receptors (ER and PR) and Her2neu were negative. A diagnosis of recurrent phyllodes tumor breast with progressively increasing malignant potential and cerebellar metastasis was considered. The patient survived only for 1 month after surgery.
| > Discussion|| |
The stromal component of the phyllodes tumor breast determines the histological grade as benign or malignant. Although usually benign, these tumors may have an unpredictable clinical course with multiple recurrences and dissemination, irrespective of the initial histological grade.  Patients presenting with headache, weakness, hemiparesis, and history of previous breast surgeries provide a clue for CNS metastasis. 
Phyllodes tumors metastasizing to the CNS have been described in a single small series of 11 cases (of which seven cases involved the brain) and two isolated reports. ,, The lesions involve the cerebral parenchyma, and rarely the spinal cord and brainstem.  Only one very recent case to the best of our knowledge has mentioned cerebellar metastasis.  Distant metastasis may be detected many years after initial diagnosis and management (range 3-5 months to 14 years). ,, In this case, cerebellar metastasis was detected 7 years after the initial detection of the breast lesion. Usually, CNS involvement implies high tumor burden, already with multiple recurrences and metastases, and hence poor survival. , Cerebellar metastases have different presenting symptoms with a possibility of poorer survival. 
Microscopic appearance of phyllodes tumors may vary within the same tumor. Characteristic leaf-like projections of stroma bearing uniform spindle cells, with interspersed benign ductal epithelium are usually identified. Features suggestive of malignancy include atypia of the stromal cells, increased mitosis (>5 per 10 HPF), infiltrating margins, and necrosis. A mitotic rate of 10 per 10 HPF is considered highly significant.
Histology of recurrent or metastatic lesions shows gradual reduction in epithelial component; metastatic lesions often consist purely of stromal component of higher histological grade. , In this case, the primary tumor was benign; while the recurrent lesions showed mild atypia with increased mitosis. However, the cerebellar metastasis showed transformation into a high-grade fibrosarcoma, comprising of markedly hypercellular fascicles of spindle cells with nuclear atypia and high mitosis (8-10 per 10 HPF). Epithelial component was not appreciated.
Occasionally, specific lines of differentiation resembling liposarcoma, osteosarcoma, or rarely chondrosarcoma may be observed. The presence of malignant heterologous elements is a sign of poor prognosis.  A tiny focus of malignant change or heterologous element may be missed due to inadequate sampling. A wide local excision with adequate tumor-free margin is recommended to prevent recurrence and metastasis.
Metastatic phyllodes tumor needs to be differentiated from primary spindle cell neoplasms of the CNS, including fibrous meningioma, solitary fibrous tumor/hemangiopericytoma, gliosarcoma, lieomyosarcoma, and melanocytoma. This case did not show any whorling pattern, nuclear inclusions, or appreciable immunoreactivity for EMA and S100 as in meningioma. There were no stag horn vascular channels and the tumor cells were negative for CD34 and S100 excluding hemangiopericytoma/solitary fibrous tumor. Morphologically, the tumor did not show any astrocytic component and was completely negative for GFAP, thus excluding a gliosarcoma. There was no pigment in the cytoplasm and no macronucleoli as in melanocytoma. The tumor was positive for SMA, and only focally positive for EMA. IHC for ER, PR, and Her2neu were negative.
Metastatic phyllodes tumor is not responsive to most currently available chemotherapy or radiation. Rare patients showed remission with ifosfamide and palliation with combination chemoradiotherapy.  Occasional case reports mention cerebellar metastatic phyllodes responding to chemoradiation. 
To conclude, we present a rare case of cerebellar metastasis in recurrent phyllodes tumor breast, with increasing histological grade. Cerebellar symptoms with previous breast surgeries may provide the initial diagnostic clue. Phyllodes tumor follows an unpredictable clinical course irrespective of the initial histology. CNS metastasis is rare and indicates advanced disease and unfavorable outcome, usually with resistance to chemotherapy and radiation.
| > References|| |
Hlavin ML, Kaminski HJ, Cohen M, Abdul-Karim FW, Ganz E. Central nervous system complications of cystosarcoma phyllodes. Cancer 1993;72:126-30.
Büchler T, Vorzilková E, Koukolík F, Melínova H, Abrahámová J. Malignant subtype of cystosarcoma phyllodes with brain metastases. Klin Onkol 2010;23:446-8.
Rowe JJ, Prayson RA. Metastatic malignant phyllodes tumor involving the cerebellum. J Clin Neurosci 2015;22:226-7.
Udelnow A, Leinung S, Dannenberg C, Trantakis Ch, Schober R, Schönfelder M, et al
. A giant malignant tumour of the skull-Case report and differential diagnosis. Zentralbl Chir 2002;127:243-5.
Chaichana KL, Rao K, Gadkaree S, Dangelmajer S, Bettegowda C, Rigamonti D, et al
. Factors associated with survival and recurrence for patients undergoing surgery of cerebellar metastases. Neurol Res 2014;36:13-25.
Grimes MM, Lattes R, Jaretzki A 3 rd
. Cystosarcoma phyllodes. Report of an unusual case, with death due to intraneural extension to the central nervous system. Cancer 1985;56:1691-5.
Rosen PP. Fibroepithelial neoplasms. In: Rosen PP editor. Rosen's Breast Pathology. 3 rd
ed. Philadelphia, US: Lippincott Williams and Wilkins; 2009. p. 202-26.
[Figure 1], [Figure 2]