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 behavior. In their least aggressive form, they behave similarly to benign fibroadenomas, although with a propensity to recur locally following excision without wide margins. At the other end of the spectrum are tumors that metastasize distantly, sometimes degenerating histologically into sarcomatous lesions that lack an epithelial component [1,2].
The terminology of phyllodes tumors has evolved. All such tumors were originally called "cystosarcoma phyllodes" by Johannes Muller in 1838 . However, they only occasionally have cystic components, and they are not true sarcomas by either cellular origin or biologic behavior. The term "phyllodes", which means leaf-like, describes the typical papillary projections that are seen on pathologic examination. Since the original description, over 60 synonyms have been applied to this entity until the adoption of the term phyllodes tumors by the World Health Organization [3,4].
EPIDEMIOLOGY AND RISK FACTORS
Phyllodes tumors account for fewer 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 there was a higher incidence in Latina whites, as compared to non-Latina whites, Asians, and African American women .
The vast majority occur in women, in whom the median age at presentation is 42 to 45 (range 10 to 82 years) [3,6-8]. Data indicate that the tumor grade increases with mean age at diagnosis . Some case reports describe these tumors in men, usually in association with gynecomastia .
No etiologic or predisposing factors have been associated with phyllodes tumors, with the exception of Li-Fraumeni syndrome, a rare autosomal dominant condition that is characterized by the development of multiple tumors . (See "Overview of hereditary breast and ovarian cancer syndromes" and "Li-Fraumeni syndrome".)
- Calhoun K, Lawton TJ, Kim JM, et al. Phyllodes tumors. In: Diseases of the breast, Harris J, Lippman ME, Osborne CK, Morrow M (Eds), Lippincott Williams and Wilkins, 2010 2010. p.781.
- Chaney AW, Pollack A, McNeese MD, et al. Primary treatment of cystosarcoma phyllodes of the breast. Cancer 2000; 89:1502.
- 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.
- 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.
- 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.
- Wurdinger S, Herzog AB, Fischer DR, et al. Differentiation of phyllodes breast tumors from fibroadenomas on MRI. AJR Am J Roentgenol 2005; 185:1317.
- 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.
- 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.
- 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).
- 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.
- Carter BA, Page DL. Phyllodes tumor of the breast: local recurrence versus metastatic capacity. Hum Pathol 2004; 35:1051.
- 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.
- 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.
- 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.
- Barth RJ Jr. Histologic features predict local recurrence after breast conserving therapy of phyllodes tumors. Breast Cancer Res Treat 1999; 57:291.
- Belkacémi Y, Bousquet G, Marsiglia H, et al. Phyllodes tumor of the breast. Int J Radiat Oncol Biol Phys 2008; 70:492.
- Pietruszka M, Barnes L. Cystosarcoma phyllodes: a clinicopathologic analysis of 42 cases. Cancer 1978; 41:1974.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Allen R, Nixon D, York M, Coleman J. Successful chemotherapy for cystosarcoma phyllodes in a young woman. Arch Intern Med 1985; 145:1127.
- 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.
- 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 1.2013. www.nccn.org (Accessed on February 24, 2014).
- EPIDEMIOLOGY AND RISK FACTORS
- CLINICAL PRESENTATION AND DIAGNOSIS
- Physical examination
- Surgical resection
- Radiation therapy
- Hormone therapy
- ADVANCED AND RECURRENT DISEASE
- Local recurrence
- Metastatic disease
- SURVEILLANCE AFTER THERAPY
- SUMMARY AND RECOMMENDATIONS