Phyllodes Tumor (Cystosarcoma Phyllodes)

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Phyllodes tumor—once more commonly referred to as cystosarcoma phyllodes (from Greek kystis [“sac, bladder”], sarkoma [“fleshy tumor”], and phyllon [“leaf”])—is a rare, predominantly benign tumor that occurs almost exclusively in the female breast. ^{[1, 2]} Grossly, the tumor displays characteristics of a large, malignant sarcoma, takes on a leaflike appearance when sectioned, and displays epithelial, cystlike spaces when viewed histologically.

Because most of these tumors are benign, the term cystosarcoma is potentially misleading. Accordingly, the term currently favored is phyllodes tumor.

Phyllodes tumor is the most commonly occurring nonepithelial neoplasm of the breast, though it represents only about 1% of tumors in the breast. ^[3]  It has a smooth, sharply demarcated texture and typically is freely movable. It is a relatively large tumor, with an average size of 5 cm (though lesions larger than 30 cm have been reported). The etiology of phyllodes tumors is unknown.

Because of limited data, the relative percentages of benign and malignant phyllodes tumors are not well defined. Reports have suggested, however, that about 85-90% of phyllodes tumors are benign and that approximately 10-15% are malignant. ^[4]

Although benign phyllodes tumors do not metastasize, they have a tendency to grow aggressively and can recur locally. ^[3]  Like other sarcomas, malignant phyllodes tumors metastasize hematogenously. Unfortunately, the pathologic appearance of a phyllodes tumor does not always predict the neoplasm’s clinical behavior; in some cases, therefore, there is a degree of uncertainty about the lesion’s classification.

The characteristics of a malignant phyllodes tumor include the following ^[5] :

Although most phyllodes tumors are benign, it is nonetheless important not to underestimate the potential of these lesions for malignancy. Moreover, some juvenile fibroadenomas in teenagers can look like phyllodes tumors on histologic examination; however, they behave in a benign fashion similar to that of other fibroadenomas. The difficulty of distinguishing among fibroadenomas, benign phyllodes tumors, and malignant phyllodes tumors may be vexing for even the most experienced pathologist. ^[7]

Phyllodes tumors occur almost exclusively in females, though rare cases have been reported in males. The tumors can develop in people of any age; however, the median age is the fifth decade of life.

If a phyllodes tumor is benign, the long-term prognosis is excellent after adequate local excision. However, the possibility for local recurrence after excision always exists, particularly with lesions that display malignant histology. ^{[8, 9, 10]} If the tumor recurs locally after excision, further local excision or total mastectomy is typically curative. Metastatic disease is typically observed in the lung, mediastinum, and skeleton. ^[5]

A study from the British Columbia Cancer Agency analyzed local recurrence, overall survival, and disease-free survival (DFS) in 183 patients with newly diagnosed benign (n = 83), borderline (n = 50), or malignant (n = 49) phyllodes tumors who were followed for a median of 65 months (range, 0.5-197 months). ^[11]  Overall, 8.7% experienced local recurrence, 4.4% distant metastasis, and 3.8% cause-specific death. With respect to individual subgroups, 5-year outcomes for women with benign, borderline, and malignant phyllodes tumors were as follows:

The 5-year local recurrence rates were 8% for women with negative margins, 6% for those with close margins, and 37% for those with positive margins. ^[11] The corresponding rates for intermediate, pushing, and infiltrative borders were 6%, 6%, and 33%, respectively. Positive margins and infiltrative tumor borders were significantly associated with increased local recurrence.

As for all breast neoplasms, self-examination remains the most important initial detection mechanism for phyllodes tumors. Appropriate teaching of this procedure is vital for early detection of all breast neoplasms.

For patient education information, see the Women’s Health Center and the Cancer Center, as well as Breast Cancer and Breast Self-Exam.

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Parker SJ, Harries SA. Phyllodes tumours. Postgrad Med J. 2001 Jul. 77 (909):428-35. [Medline]. [Full Text].

Jones AM, Mitter R, Poulsom R, Gillett C, Hanby AM, Tomlinson IP, et al. mRNA expression profiling of phyllodes tumours of the breast: identification of genes important in the development of borderline and malignant phyllodes tumours. J Pathol. 2008 Dec. 216 (4):408-17. [Medline].

Abe M, Miyata S, Nishimura S, Iijima K, Makita M, Akiyama F, et al. Malignant transformation of breast fibroadenoma to malignant phyllodes tumor: long-term outcome of 36 malignant phyllodes tumors. Breast Cancer. 2011 Oct. 18 (4):268-72. [Medline].

Brooks HL, Priolo S, Waxman. Cystosarcoma phylloides: a case report of an 11-year survival and review of surgical experience. Contemp Surg. 1998. 53:169-72.

Yohe S, Yeh IT. “Missed” diagnoses of phyllodes tumor on breast biopsy: pathologic clues to its recognition. Int J Surg Pathol. 2008 Apr. 16 (2):137-42. [Medline].

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 Jul 1. 71 (3):710-3. [Medline].

Jones AM, Mitter R, Springall R, Graham T, Winter E, Gillett C, et al. A comprehensive genetic profile of phyllodes tumours of the breast detects important mutations, intra-tumoral genetic heterogeneity and new genetic changes on recurrence. J Pathol. 2008 Apr. 214 (5):533-44. [Medline].

Wei J, Tan YT, Cai YC, Yuan ZY, Yang D, Wang SS, et al. Predictive factors for the local recurrence and distant metastasis of phyllodes tumors of the breast: a retrospective analysis of 192 cases at a single center. Chin J Cancer. 2014 Oct. 33 (10):492-500. [Medline].

Rodrigues MF, Truong PT, McKevitt EC, Weir LM, Knowling MA, Wai ES. Phyllodes tumors of the breast: The British Columbia Cancer Agency experience. Cancer Radiother. 2018 Apr. 22 (2):112-119. [Medline].

Nabi J, Akhter SM, Authoy FN. A case of large phyllodes tumor causing “rupture” of the breast: a unique presentation. Case Rep Oncol Med. 2013. 2013:871292. [Medline]. [Full Text].

Jung YY, Lee YK, Koo JS. Expression of lipid metabolism-related proteins in breast phyllodes tumors. Neoplasma. 2016. 63 (2):254-62. [Medline].

Bellezza G, Prosperi E, Del Sordo R, Colella R, Rulli A, Sidoni A. IMP3 Is Strongly Expressed in Malignant Phyllodes Tumors of the Breast: An Immunohistochemical Study. Int J Surg Pathol. 2016 Feb. 24 (1):37-42. [Medline].

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 Apr. 19 (4):1181-4. [Medline].

Jardim DL, Conley A, Subbiah V. Comprehensive characterization of malignant phyllodes tumor by whole genomic and proteomic analysis: biological implications for targeted therapy opportunities. Orphanet J Rare Dis. 2013 Jul 30. 8:112. [Medline]. [Full Text].

Cole-Beuglet C, Soriano R, Kurtz AB, Meyer JE, Kopans DB, Goldberg BB. Ultrasound, x-ray mammography, and histopathology of cystosarcoma phylloides. Radiology. 1983 Feb. 146 (2):481-6. [Medline]. [Full Text].

Kawashima H, Miyati T, Ohno N, Ohno M, Inokuchi M, Ikeda H, et al. Differentiation between phyllodes tumours and fibroadenomas using intravoxel incoherent motion magnetic resonance imaging: comparison with conventional diffusion-weighted imaging. Br J Radiol. 2018 Apr. 91 (1084):20170687. [Medline].

Yasir S, Gamez R, Jenkins S, Visscher DW, Nassar A. Significant histologic features differentiating cellular fibroadenoma from phyllodes tumor on core needle biopsy specimens. Am J Clin Pathol. 2014 Sep. 142 (3):362-9. [Medline].

Efared B, Ebang GA, Tahiri L, Sidibé IS, Erregad F, Hammas N, et al. Phyllodes tumors of the breast: clinicopathological analysis of 106 cases from a single institution. Breast Dis. 2018. 37 (3):139-145. [Medline].

[Guideline] Bendifallah S, Canlorbe G. [Common benign breast tumors including fibroadenoma, phyllodes tumors, and papillary lesions: Guidelines]. J Gynecol Obstet Biol Reprod (Paris). 2015 Dec. 44 (10):1017-29. [Medline].

Adam MJ, Bendifallah S, Kalhorpour N, Cohen-Steiner C, Ropars L, Mahmood A, et al. Time to revise classification of phyllodes tumors of breast? Results of a French multicentric study. Eur J Surg Oncol. 2018 Aug 18. [Medline].

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 Sep 1. 91 (3):185-94. [Medline].

Contarini O, Urdaneta LF, Hagan W, Stephenson SE Jr. Cystosarcoma phylloides of the breast: a new therapeutic proposal. Am Surg. 1982 Apr. 48 (4):157-66. [Medline].

Onkendi EO, Jimenez RE, Spears GM, Harmsen WS, Ballman KV, Hieken TJ. 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 Oct. 21 (10):3304-9. [Medline].

[Guideline] Lavoué V, Fritel X, Antoine M, Beltjens F, Bendifallah S, Boisserie-Lacroix M, et al. Clinical practice guidelines from the French College of Gynecologists and Obstetricians (CNGOF): benign breast tumors – short text. Eur J Obstet Gynecol Reprod Biol. 2016 May. 200:16-23. [Medline].

Gullett NP, Rizzo M, Johnstone PA. National surgical patterns of care for primary surgery and axillary staging of phyllodes tumors. Breast J. 2009 Jan-Feb. 15 (1):41-4. [Medline].

Donald R Lannin, MD Professor, Department of Surgery, Section of Oncology, Director Emeritus, Yale-New Haven Breast Center

Donald R Lannin, MD is a member of the following medical societies: Alpha Omega Alpha, American Cancer Society, American College of Surgeons

Disclosure: Nothing to disclose.

Anastasios K Konstantakos, MD Clinical Associate Surgeon, Department of Cardiovascular Surgery, Billings Clinic

Disclosure: Nothing to disclose.

John H Raaf, MD, PhD (Retired) Professor, Department of Surgery, Case Western Reserve University School of Medicine

John H Raaf, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American College of Surgeons, Central Surgical Association, Society of Surgical Oncology, American Association of Endocrine Surgeons, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

John Geibel, MD, DSc, MSc, AGAF Vice Chair and Professor, Department of Surgery, Section of Gastrointestinal Medicine, Professor, Department of Cellular and Molecular Physiology, Yale University School of Medicine; Director of Surgical Research, Department of Surgery, Yale-New Haven Hospital; American Gastroenterological Association Fellow

John Geibel, MD, DSc, MSc, AGAF is a member of the following medical societies: American Gastroenterological Association, American Physiological Society, American Society of Nephrology, Association for Academic Surgery, International Society of Nephrology, New York Academy of Sciences, Society for Surgery of the Alimentary Tract

Disclosure: Nothing to disclose.

Brian James Daley, MD, MBA, FACS Associate Program Director, Professor, Department of Surgery, Division of Trauma and Critical Care, University of Tennessee School of Medicine

Brian James Daley, MD, MBA, FACS is a member of the following medical societies: American Association for the Surgery of Trauma, American College of Chest Physicians, American College of Surgeons, American Medical Association, Association for Academic Surgery, Association for Surgical Education, Eastern Association for the Surgery of Trauma, Shock Society, Society of Critical Care Medicine, Southeastern Surgical Congress, andTennessee Medical Association

Disclosure: Nothing to disclose.

Michael A Grosso, MD Consulting Staff, Department of Cardiothoracic Surgery, St Francis Hospital

Michael A Grosso, MD is a member of the following medical societies: American College of Surgeons, Society of Thoracic Surgeons, and Society of University Surgeons

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

Phyllodes Tumor (Cystosarcoma Phyllodes)

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