Phyllodes tumors of the breast
- Ana M Grau, MD, FACS
Ana M Grau, MD, FACS
- Associate Professor
- Vanderbilt University
- A Bapsi Chakravarthy, MD, FASTRO
A Bapsi Chakravarthy, MD, FASTRO
- Vanderbilt University
- Rashmi Chugh, MD
Rashmi Chugh, MD
- Associate Professor of Medical Oncology
- University of Michigan Medical School
- Section Editors
- Lori J Pierce, MD
Lori J Pierce, MD
- Section Editor — Radiation Therapy
- Professor of Radiation Oncology
- University of Michigan School of Medicine
- Daniel F Hayes, MD
Daniel F Hayes, MD
- Section Editor — Breast Cancer
- Professor of Medicine
- University of Michigan School of Medicine
- Anees B Chagpar, MD, MSc, MA, MPH, MBA, FACS, FRCS(C)
Anees B Chagpar, MD, MSc, MA, MPH, MBA, FACS, FRCS(C)
- Section Editor — Breast Surgery
- Associate Professor, Department of Surgery
- Yale University School of Medicine
Phyllodes tumors are uncommon fibroepithelial breast tumors that are capable of a diverse range of biologic behaviors. In their least aggressive form, phyllodes tumors behave like benign fibroadenomas, although with a propensity to recur locally following excision without wide margins. At the other end of the spectrum, other phyllodes tumors can metastasize distantly, sometimes degenerating histologically into sarcomatous lesions that lack an epithelial component [1,2].
The term "phyllodes," which means leaf-like, describes the typical papillary projections that are seen on pathologic examination. Although they were originally called "cystosarcoma phyllodes" by Johannes Müller in 1838 , phyllodes tumors only occasionally have cystic components and are not true sarcomas by either cellular origin or biologic behavior. The terminology has since evolved, with over 60 synonyms having been applied to this entity before the term "phyllodes tumors" was adopted by the World Health Organization [3,4].
The clinical presentation, diagnosis, treatment, and prognosis of breast phyllodes tumors are discussed in this topic. Other benign (eg, fibroadenoma) or malignant lesions of the breast are discussed elsewhere. (See "Overview of benign breast disease" and "Clinical features, diagnosis, and staging of newly diagnosed breast cancer" and "Overview of the treatment of newly diagnosed, non-metastatic breast cancer".)
EPIDEMIOLOGY AND RISK FACTORS
Phyllodes tumors account for less than 0.5 percent of all breast malignancies [4,5]. Given their rarity, epidemiologic data are scant. In a study from Los Angeles county over a 17-year period, the average annual incidence rate was 2.1 per million women, and the incidence was higher in Latina whites than in non-Latina whites, Asians, and African Americans .
The vast majority of phyllodes tumors occur in women, with a median age of presentation of 42 to 45 years (range 10 to 82 years) [3,6-8]. Higher-grade tumors are more common in older patients . In men, phyllodes tumors usually occur in association with gynecomastia .
- Chaney AW, Pollack A, McNeese MD, et al. Primary treatment of cystosarcoma phyllodes of the breast. Cancer 2000; 89:1502.
- Calhoun K, Allison KH, Kim JN, et al.. Phyllodes tumors. In: Diseases of the breast, Harris J, Lippman ME, Morrow M, Osborne KC. (Eds), Lippincott Williams and Wilkins, 2014.
- Tavassoli FA, Devilee P. and genetics of tumours of the breast and female genital organs. In: World Health Organization Classification of Tumours, IARC Press, Lyons 2003. p.99.
- Reinfuss M, Mituś J, Duda K, et al. The treatment and prognosis of patients with phyllodes tumor of the breast: an analysis of 170 cases. Cancer 1996; 77:910.
- Geisler DP, Boyle MJ, Malnar KF, et al. Phyllodes tumors of the breast: a review of 32 cases. Am Surg 2000; 66:360.
- Bernstein L, Deapen D, Ross RK. The descriptive epidemiology of malignant cystosarcoma phyllodes tumors of the breast. Cancer 1993; 71:3020.
- Norris HJ, Taylor HB. Relationship of histologic features to behavior of cystosarcoma phyllodes. Analysis of ninety-four cases. Cancer 1967; 20:2090.
- Barrio AV, Clark BD, Goldberg JI, et al. Clinicopathologic features and long-term outcomes of 293 phyllodes tumors of the breast. Ann Surg Oncol 2007; 14:2961.
- Karim RZ, Gerega SK, Yang YH, et al. Phyllodes tumours of the breast: a clinicopathological analysis of 65 cases from a single institution. Breast 2009; 18:165.
- Birch JM, Alston RD, McNally RJ, et al. Relative frequency and morphology of cancers in carriers of germline TP53 mutations. Oncogene 2001; 20:4621.
- Telli ML, Horst KC, Guardino AE, et al. Phyllodes tumors of the breast: natural history, diagnosis, and treatment. J Natl Compr Canc Netw 2007; 5:324.
- Macdonald OK, Lee CM, Tward JD, et al. 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.
- Mangi AA, Smith BL, Gadd MA, et al. Surgical management of phyllodes tumors. Arch Surg 1999; 134:487.
- Yabuuchi H, Soeda H, Matsuo Y, et al. Phyllodes tumor of the breast: correlation between MR findings and histologic grade. Radiology 2006; 241:702.
- Farria DM, Gorczyca DP, Barsky SH, et al. Benign phyllodes tumor of the breast: MR imaging features. AJR Am J Roentgenol 1996; 167:187.
- Tan H, Zhang S, Liu H, et al. Imaging findings in phyllodes tumors of the breast. Eur J Radiol 2012; 81:e62.
- Jacklin RK, Ridgway PF, Ziprin P, et al. Optimising preoperative diagnosis in phyllodes tumour of the breast. J Clin Pathol 2006; 59:454.
- El Hag IA, Aodah A, Kollur SM, et al. Cytological clues in the distinction between phyllodes tumor and fibroadenoma. Cancer Cytopathol 2010; 118:33.
- Dillon MF, Quinn CM, McDermott EW, et al. Needle core biopsy in the diagnosis of phyllodes neoplasm. Surgery 2006; 140:779.
- Lee AH. Recent developments in the histological diagnosis of spindle cell carcinoma, fibromatosis and phyllodes tumour of the breast. Histopathology 2008; 52:45.
- Lee AH, Hodi Z, Ellis IO, Elston CW. Histological features useful in the distinction of phyllodes tumour and fibroadenoma on needle core biopsy of the breast. Histopathology 2007; 51:336.
- Tan BY, Acs G, Apple SK, et al. Phyllodes tumours of the breast: a consensus review. Histopathology 2016; 68:5.
- de Roos WK, Kaye P, Dent DM. Factors leading to local recurrence or death after surgical resection of phyllodes tumours of the breast. Br J Surg 1999; 86:396.
- Lakhani SR, Ellis IO, Schnitt SJ, et al. WHO Classification of Tumours of the Breast, 4th ed, World Health Organization, 2012.
- Hawkins RE, Schofield JB, Fisher C, et al. The clinical and histologic criteria that predict metastases from cystosarcoma phyllodes. Cancer 1992; 69:141.
- Fajdić J, Gotovac N, Hrgović Z, et al. Phyllodes tumors of the breast diagnostic and therapeutic dilemmas. Onkologie 2007; 30:113.
- Pietruszka M, Barnes L. Cystosarcoma phyllodes: a clinicopathologic analysis of 42 cases. Cancer 1978; 41:1974.
- Powell CM, Rosen PP. Adipose differentiation in cystosarcoma phyllodes. A study of 14 cases. Am J Surg Pathol 1994; 18:720.
- 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.
- Fletcher CDM, Chibon F, Mertens F. Undifferentiated/unclassified sarcomas. In: WHO classifiction of tumours of soft tissue and bone, 4th, Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F. (Eds), IARC, Lyon 2013. p.236.
- Carter BA, Page DL. Phyllodes tumor of the breast: local recurrence versus metastatic capacity. Hum Pathol 2004; 35:1051.
- Mituś JW, Blecharz P, Reinfuss M, et al. Changes in the clinical characteristics, treatment options, and therapy outcomes in patients with phyllodes tumor of the breast during 55 years of experience. Med Sci Monit 2013; 19:1183.
- Parker SJ, Harries SA. Phyllodes tumours. Postgrad Med J 2001; 77:428.
- Belkacémi Y, Bousquet G, Marsiglia H, et al. Phyllodes tumor of the breast. Int J Radiat Oncol Biol Phys 2008; 70:492.
- Barth RJ Jr. Histologic features predict local recurrence after breast conserving therapy of phyllodes tumors. Breast Cancer Res Treat 1999; 57:291.
- Tan PH, Thike AA, Tan WJ, et al. Predicting clinical behaviour of breast phyllodes tumours: a nomogram based on histological criteria and surgical margins. J Clin Pathol 2012; 65:69.
- Karim RZ, O'Toole SA, Scolyer RA, et al. Recent insights into the molecular pathogenesis of mammary phyllodes tumours. J Clin Pathol 2013; 66:496.
- Kuijper A, Buerger H, Simon R, et al. Analysis of the progression of fibroepithelial tumours of the breast by PCR-based clonality assay. J Pathol 2002; 197:575.
- Tan J, Ong CK, Lim WK, et al. Genomic landscapes of breast fibroepithelial tumors. Nat Genet 2015; 47:1341.
- Ng CC, Tan J, Ong CK, et al. MED12 is frequently mutated in breast phyllodes tumours: a study of 112 cases. J Clin Pathol 2015; 68:685.
- Cani AK, Hovelson DH, McDaniel AS, et al. Next-Gen Sequencing Exposes Frequent MED12 Mutations and Actionable Therapeutic Targets in Phyllodes Tumors. Mol Cancer Res 2015; 13:613.
- Jang JH, Choi MY, Lee SK, et al. Clinicopathologic risk factors for the local recurrence of phyllodes tumors of the breast. Ann Surg Oncol 2012; 19:2612.
- Spitaleri G, Toesca A, Botteri E, et al. Breast phyllodes tumor: a review of literature and a single center retrospective series analysis. Crit Rev Oncol Hematol 2013; 88:427.
- Kapiris I, Nasiri N, A'Hern R, et al. 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.
- Yom CK, Han W, Kim SW, et al. Reappraisal of conventional risk stratification for local recurrence based on clinical outcomes in 285 resected phyllodes tumors of the breast. Ann Surg Oncol 2015; 22:2912.
- Confavreux C, Lurkin A, Mitton N, et al. Sarcomas and malignant phyllodes tumours of the breast--a retrospective study. Eur J Cancer 2006; 42:2715.
- Barth RJ Jr, Wells WA, Mitchell SE, Cole BF. A prospective, multi-institutional study of adjuvant radiotherapy after resection of malignant phyllodes tumors. Ann Surg Oncol 2009; 16:2288.
- Chen WH, Cheng SP, Tzen CY, et al. Surgical treatment of phyllodes tumors of the breast: retrospective review of 172 cases. J Surg Oncol 2005; 91:185.
- Bhargav PR, Mishra A, Agarwal G, et al. Phyllodes tumour of the breast: clinicopathological analysis of recurrent vs. non-recurrent cases. Asian J Surg 2009; 32:224.
- Moutte A, Chopin N, Faure C, et al. Surgical Management of Benign and Borderline Phyllodes Tumors of the Breast. Breast J 2016; 22:547.
- Onkendi EO, Jimenez RE, Spears GM, et al. Surgical treatment of borderline and malignant phyllodes tumors: the effect of the extent of resection and tumor characteristics on patient outcome. Ann Surg Oncol 2014; 21:3304.
- Borhani-Khomani K, Talman ML, Kroman N, Tvedskov TF. Risk of Local Recurrence of Benign and Borderline Phyllodes Tumors: A Danish Population-Based Retrospective Study. Ann Surg Oncol 2016; 23:1543.
- Soumarová R, Seneklová Z, Horová H, et al. Retrospective analysis of 25 women with malignant cystosarcoma phyllodes--treatment results. Arch Gynecol Obstet 2004; 269:278.
- Pezner RD, Schultheiss TE, Paz IB. Malignant phyllodes tumor of the breast: local control rates with surgery alone. Int J Radiat Oncol Biol Phys 2008; 71:710.
- Zeng S, Zhang X, Yang D, et al. Effects of adjuvant radiotherapy on borderline and malignant phyllodes tumors: A systematic review and meta-analysis. Mol Clin Oncol 2015; 3:663.
- Gnerlich JL, Williams RT, Yao K, et al. Utilization of radiotherapy for malignant phyllodes tumors: analysis of the National Cancer Data Base, 1998-2009. Ann Surg Oncol 2014; 21:1222.
- Morales-Vásquez F, Gonzalez-Angulo AM, Broglio K, et al. Adjuvant chemotherapy with doxorubicin and dacarbazine has no effect in recurrence-free survival of malignant phyllodes tumors of the breast. Breast J 2007; 13:551.
- Burton GV, Hart LL, Leight GS Jr, et al. Cystosarcoma phyllodes. Effective therapy with cisplatin and etoposide chemotherapy. Cancer 1989; 63:2088.
- Sapino A, Bosco M, Cassoni P, et al. Estrogen receptor-beta is expressed in stromal cells of fibroadenoma and phyllodes tumors of the breast. Mod Pathol 2006; 19:599.
- Tse GM, Lee CS, Kung FY, et al. Hormonal receptors expression in epithelial cells of mammary phyllodes tumors correlates with pathologic grade of the tumor: a multicenter study of 143 cases. Am J Clin Pathol 2002; 118:522.
- Patel SR, Zagars GK, Pisters PW. The follow-up of adult soft-tissue sarcomas. Semin Oncol 2003; 30:413.
- Grabowski J, Salzstein SL, Sadler GR, Blair SL. Malignant phyllodes tumors: a review of 752 cases. Am Surg 2007; 73:967.
- National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology (NCCN Guidelines). Soft Tissue Sarcoma. Version 2.2016. www.nccn.org (Accessed on February 22, 2016).
- Allen R, Nixon D, York M, Coleman J. Successful chemotherapy for cystosarcoma phyllodes in a young woman. Arch Intern Med 1985; 145:1127.
- National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (Accessed on February 27, 2016).
- Kessinger A, Foley JF, Lemon HM, Miller DM. Metastatic cystosarcoma phyllodes: a case report and review of the literature. J Surg Oncol 1972; 4:131.
- Hawkins RE, Schofield JB, Wiltshaw E, et al. Ifosfamide is an active drug for chemotherapy of metastatic cystosarcoma phyllodes. Cancer 1992; 69:2271.
- EPIDEMIOLOGY AND RISK FACTORS
- CLINICAL PRESENTATION
- DIAGNOSTIC EVALUATION
- - Mammography
- - Ultrasonography
- - MRI
- - Fine needle aspiration
- - Core needle biopsy
- - Excisional biopsy
- - Gross
- - Microscopic
- - Histologic
- - Molecular
- Surgical resection
- - Breast surgery
- - Axillary surgery
- Radiation therapy
- Hormone therapy
- POST-TREATMENT SURVEILLANCE
- RECURRENT AND MESTASTATIC DISEASES
- Local recurrence
- Metastatic disease
- SUMMARY AND RECOMMENDATIONS