Bone metastasis from malignant phyllodes breast tumor: report of two cases
© El Ochi et al. 2016
Received: 30 December 2015
Accepted: 23 February 2016
Published: 29 February 2016
Phyllodes tumors are rare fibroepithelial tumors accounting for less than 1 % of all breast neoplasms. They are malignant in 20 % of cases. Only a few cases of malignant phyllodes tumors metastatic to bone have been reported.
Case 1: A 40 year-old white woman presented with three-week history of pain and functional impairment of the left lower limb. Her clinical past was remarkable for previous left mastectomy and radiotherapy for malignant phyllodes tumor performed one year ago. Computed tomography revealed a moth-eaten appearance of the left femoral head. The patient underwent computed guided femoral head biopsy. Pathological findings were consistent with metastatic malignant phyllodes tumor. The patient received ifosfamide and adriamycin chemotherapy. She is doing well without any evidence of progression on her imaging follow- up after 8 months.
Case 2: A 48 year-old white woman, with history of bilateral mastectomy and radiotherapy for malignant phyllodes tumor performed one and two year ago, presented with four-week left lower quadrant abdominal pain. Computed tomography and magnetic resonance imaging revealed a solid aggressive osteolytic mass of the left iliac bone with extensive soft tissue invasion. Biopsy of the tumor was performed and showed a sarcomatous proliferation consistent with metastatic malignant phyllodes tumor. The patient received the same chemotherapy regimen as in the first case but without any response on her imaging follow up after 6 months.
Malignant phyllodes tumor is a rare and aggressive fibroepithelial neoplasm. An accurate diagnosis of metastases should be based on clinicopathological correlation allowing exclusion of differential diagnoses. The goal of successful managing this tumor is early detection and complete resection prior to dissemination.
KeywordsBone Metastatic Phyllodes Tumor Breast
Only a few cases of PT metastatic to bone have been reported . To our knowledge, only 2 cases involving the iliac bone [6, 7] and 1 case involving the femur  are described in the literature. These papers have mainly focused on their radiological aspects. We report 2 cases of metastatic malignant PT of the breast involving the femoral head and the iliac bone and discuss the histopathological differential diagnoses.
Case 1: Clinical history
Radiologic and histopathologic findings
malignant PT was made. The patient received ifosfamide and adriamycin chemotherapy. She is doing well without any evidence of progression on her imaging follow-up after 8 months.
Case 2: Clinical history
Radiologic and histopathologic findings
PT is a rare fibroepithelial tumor accounting for less than 1 % of all breast neoplasms [1, 2]. They usually arise in women between ages 35 and 55 years and are classified as benign, borderline and malignant [2, 3]. Malignant types present approximately 20 % of all cases . Actually, malignant PTs should be treated by conservative surgery with adequate negative surgical margins; the use of radiotherapy may be limited to patients with positive surgical margins [9, 10]. Distant metastases are seen in 10–20 % of cases . They can occur even after technically adequate initial breast surgery . The most reliable predictive factors for development of distant metastases are stromal overgrowth, nuclear pleomorphism and high mitotic activity [9, 11], whereas the role of tumor size and local recurrence is controversial [1, 11, 12]. Tan et al. found, by multivariate analysis, that stromal atypia, overgrowth, surgical margins and mitoses are independently predictive of clinical behaviour . He developed a nomogram based on these criteria to predict recurrence-free survival, but the amalgamation of local with distant recurrences and the low rate of metastasis in this series could limit its ability in predicting dissemination. The recurrence free survival was 0,8 and 0,47 at 1 and 3 years for the first case, 0,76 and 0,4 at 1 and 3 years for the second case. Al-Masry et al. have shown that the expression of CD10 can be used to predict the occurrence of distant metastasis .
Metastatic PTs mainly develop from 3 to 10 years after the inital therapy, but they can be delayed or occur as soon as synchronous presentation . The lung is the most common site of metastatic spread [2, 3, 15]. Only a few cases of PT metastatic to bone have been reported  with 2 cases involving the iliac bone [6, 7] and 1 case involving the femur .
Clinical features are not specific and vary among location of bone metastasis. Radiographs and computed tomography may show a solid mass adjacent to the involved bone and infiltrating the cortex and medulla in a permeative pattern . The magnetic resonance imaging may better delineate the metastatic extent .
Positivity of estrogen and progesterone receptors had never been reported. These morphological and immunohistochemical findings play an important role in excluding sarcomas, myoepithelioma, metastatic sarcomatoid carcinoma, melanoma and gastrointestinal stromal tumor. Generally, it’s difficult to make a specific diagnosis only by microscopic examination, but the final diagnosis should be based on clinicopathological correlation. There is no consensus regarding adjuvant therapy. Both radiotherapy and chemotherapy are recommended in metastatic PTs [2, 6, 16]. Ifosfamide is the most active agent ; antiestrogen therapy is not indicated [3, 16]. Some studies revealed several potentially targetable pathway including epidermal growth factor receptor, angiogenesis (vascular endothelial growth factor A, angiopoietin-2, vascular cell adhesion molecule 1, platelet- derived growth factor receptor A, pituitary tumor-transforming1) and immunotherapy (programmed cell death protein 1, programmed death-ligand 1) for patients with locally advanced or metastatic tumors [4, 10]. Park et al. reported a major response to sunitinib and paclitaxel in a case of lung metastatic malignant PT of breast .
Little is known about the prognosis of bone metastasis from malignant PT. Nguyen  report one case involving the left iliac bone with good response after radiotherapy. The prognosis of malignant PT metastatic to the lung seems to be worse .
In summary, malignant PT is a rare and aggressive fibroepithelial neoplasm. An accurate diagnosis of metastases should be based on clinicopathological correlation allowing exclusion of differential diagnoses. The goal of successful managing this tumor is early detection and complete resection prior to dissemination.
Written informed consents were obtained from the patients for publication of these Cases Report and any accompanying images. Copies of the written consents are available for review by the Editor-in-Chief of this journal.
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- Parker S, Harries SA. Phyllodes tumours. Postgrad Med J. 2001;77:428–35.PubMed CentralView ArticlePubMedGoogle Scholar
- Chen WH, Cheng SP, Tzen CY, Yang TL, Jeng KS, Liu CL, et al. Surgical treatment of phyllodes tumors of the breast: retrospective review of 172 cases. J Surg Oncol. 2005;91:185–94.View ArticlePubMedGoogle Scholar
- Lightner AL, Shurell E, Dawson N, Omidvar Y, Foster N. A single-center experience and review of the literature: 64 cases of phyllodes tumors to better understand risk factors and disease management. Am Surg. 2015;81:309–15.PubMedGoogle Scholar
- Gatalica Z, Vranic S, Ghazalpour A, Xiu J, Ocal IT, McGill J. et al. Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast. Oncotarget. 2015; doi:10.18632/oncotarget.6421.
- Rowe JJ, Prayson RA. Metastatic malignant phyllodes tumor involving the cerebellum. J Clin Neurosci. 2015;22:226–7.View ArticlePubMedGoogle Scholar
- Nguyen BD. Imaging of pelvic bone metastasis from malignant phyllodes breast tumor. Radiology Case Report. 2006;1:15.View ArticleGoogle Scholar
- Goldschmidt RA, Resnik CS, Mills AS, Walsh JW. Case report 266. Diagnosis: metastasis to right ilium from cystosarcoma phylloides of breast. Skeletal Radiol. 1984;11:213–5.View ArticlePubMedGoogle Scholar
- Singer A, Tresley J, Velazquez-Vega J, Yepes M. Unusual aggressive breast cancer: metastatic malignant phyllodes tumor. Journal of Radiology Case report. 2013;7:24–37.Google Scholar
- Carter BA, Page DL. Phyllodes tumor of the breast: local recurrence versus metastatic capacity. Hum Pathol. 2004;35:1051–2.View ArticlePubMedGoogle Scholar
- Spitaleri G, Toesca A, Botteri E, Bottiglieri L, Rotmensz N, Boselli S, et al. Breast phyllodes tumor: a review of literature and a single center retrospective series analysis. Crit Rev Oncol Hematol. 2013;88:427–36.View ArticlePubMedGoogle Scholar
- Kapiris I, Nasiri N, A’Hern R, Healy V, Gui GP. Outcome and predictive factors of local recurrence and distant metastases following primary surgical treatment of high-grade malignant phyllodes tumours of the breast. Eur J Surg Oncol. 2001;27:723–30.View ArticlePubMedGoogle Scholar
- Asoglu O, Ugurlu MM, Blanchard K, Grant CS, Reynolds C, Cha SS, et al. Risk factors for recurrence and death after primary surgical treatment of malignant phyllodes tumors. Ann Surg Oncol. 2004;11:1011–7.View ArticlePubMedGoogle Scholar
- Tan PH, Thike AA, Tan WJ, Thu MM, Busmanis I, Li H, et al. Predicting clinical behaviour of breast phyllodes tumours: a nomogram based on histological criteria and surgical margins. J Clin Pathol. 2012;65:69–76.View ArticlePubMedGoogle Scholar
- Al-Masri M, Darwazeh G, Sawalhi S, Mughrabi A, Sughayer M, Al-Shatti M. Phyllodes tumor of the breast: role of CD10 in predicting metastasis. Ann Surg Oncol. 2012;19:1181–4.View ArticlePubMedGoogle Scholar
- Al-Rabiy FN, Ali RH. Malignant phyllodes tumor with osteosarcomatous differentiation metastasizing to small bowel and causing intestinal obstruction. Diagn Histopathol. 2015;46:165–68.View ArticleGoogle Scholar
- Asoglu O, Karanlik H, Barbaros U, Yanar H, Kapran Y, Kecer M, et al. Malignant phyllodes tumor metastatic to the duodenum. World J Gastroenterol. 2006;12:1649–51.PubMed CentralPubMedGoogle Scholar
- Park IH, Kwon Y, Kim EA, Lee KS, Ro J. Major response to sunitinib (Sutene) in metastatic malignant phyllodes tumor of breast. Invest New Drugs. 2009;27:387–8.View ArticlePubMedGoogle Scholar