The phyllodes tumor of the breast
A phyllodes tumor, which derives from the Greek word ‘phullon‘ or leaf, is a rare breast tumor usually effecting pre-menopausal women in their 40s. The behavior of phyllodes breast tumors cannot easily be generalized. Phyllodes tumors can either be benign, suspicious of malignancy, or overtly malignant; it will depend upon the specific histological findings in each case. Breast phyllodes tumors account for about 0.5% of all breast neoplasms, and they are formed from a combination of stromal and epithelial cellular elements. Phyllodes breast tumors are thought to represent about 2%-3% of all fibroepithelial breast tumors.
I just want to let you know that we have created a newer version of this page with more up-to-date information on Phyllode tumors. Nevertheless, this page is still quite useful!
A phyllodes tumor of the breast is often referred to as a ‘sarcoma‘, because it develops in the connective tissue of the breast (the ‘stroma’) and not in the epithelial tissues that line the breast ducts and lobules. Phillodes tumors (PT) are also sometimes called (or spelled) phylloides tumor, cystosarcoma phyllodes, cystosarcoma phylloides, and sometimes informally as “giant fibroadenomas“. They tend to be large, very fast-growing breast tumors that evolve in a ‘leaf-shaped‘ growth pattern. Not all phyllodes breast tumors are considered to be breast cancer, but they are treated more seriously than other benign tumors, because some can become malignant.
Most phyllodes breast tumors are either low grade or benign
The majority of the breast phyllodes tumors, however, are low-grade/benign tumors. Still, estimates for malignant presentations range between 20%-50% of all cases. Phyllodes breast tumors tend to develop in premenopausal adult women. Though phyllodes tumors of the breast can be confused with a benign breast fibroadenoma, fibroadenomas tend to develop in women in their 20s, not their 40s and 50s.
Clinical diagnosis of phyllodes tumor of the breast
Phyllodes breast tumors are quite often discovered as a firm, bumpy, and smooth-sided mass. Breast skin covering the tumor might be warm to the touch, and reddish in color. Patients will frequently report that a lump has appeared and grown quickly, even within a few short weeks.
Microcalcifications are generally not found in breast phyllodes tumors
On a mammogram, a phyllodes breast tumor will tend to be a lobulated, round, or oval mass, with a well-defined border. Phyllodes tumors tend not to be associated with microcalcifications.
Ultrasound cannot distinguish between phyllodes tumor and fibroadenoma
On breast ultrasound, a phyllodes tumour will usually appear as a well-defined ‘macro-lobulated‘ mass with heterogeneous internal echoes. Some phyllodes breast tumors show posterior acoustic enhancement, but not all. If sonography suggests a fluid filling clefts or ‘elongated spaces‘ in the mass, this would also point to a diagnosis of phyllodes tumor. However, neither mammogram nor breast ultrasound will be able to distinguish convincingly between a phyllodes breast tumor, or a breast fibroadenoma, so a biopsy will have to be taken.
Histological features typical of phyllodes breast tumors
The ‘hallmark‘ microscopic feature common to all phyllodes breast tumors is stromal hypercellularity and overgrowth. Phyllodes tumors tend to be characterized by a combination of hypercellular stroma and ‘cleft-like‘ or cystic spaces lined by epithelium. Into these spaces typically grow projectsion of breast stromas tissues in a characteristic ‘leaf-like‘ pattern. Not all phyllodes breast tumors show the classic ‘leaf-like‘ pattern, however. Some are simply solid and only vaguely lobulated. The glandular elements of phyllodes tumors are typically widely spaced, dilated, and irregular with prominent side branches. Epithelial elements are quite often hyperplastic, and atypical columnar cell breast hyperplasia is not an uncommon co-finding. Expression of epithelial ER and PR proteins is also common in phyllodes breast tumors, occurring at rates of about 43% to 84% respectively.
Diagnositc features of a phyllodes breast tumors more suggests of malignant behavior
Some of the histological features of a breast phyllodes tumor that would be more suggestive of malignancy include mitotic activity, stromal overgrowth, stromal cellularity, and infiltration at the tumor’s edge. Probably the two most important histological determiners for the ‘grade‘ of phyllodes breast tumors are the speed at which the cells are dividing (mitosis) and the number of irregularly shaped cells. In terms of cell mitosis and potential malignancy, counts of 10 mitoses per 10 high power fields suggest a malignant tumor. Malignancy in phyllodes breast tumors also tends to be associated with increased patient age and tumor size. There is also some indication that ‘microvessel density‘ and also the presence of the p53 protein, are also suggestive of malignancy in phyllodes tumors.
Infiltrating margins are also stong indicators for malignancy, as well as the presence of necrosis and hemorrhage. There is also some indication that increased expression of c-kit (c-kit is a proto-oncogene that encodes a tyrosine kinase receptor, CD115), might also be more suggestive of a malignant tumor. Up to 46% of malignant breast phyllodes tumors are positive for c-kit expression, with a significantly lower rate in benign phyllodes tumors. Ki-67 antigen expression has also been identified as a marker for a more malignant phyllodes breast tumor course.
Excisional biopsies are preferred when phyllodes tumor is suspected
Generally speaking, physicians have greater confidence in the results of an excisional biopsy than just fine needle aspiration when it comes to cytological evaluation of suspected phyllodes breast tumors.
Treatment and prognosis for phyllodes breast tumors
Phyllodes breast tumors tend to be treated by wide local excision. Historically, radiation and chemotherapy have not tended to be effective treaments for phyllodes breast tumors. The risk of local recurrence or distant metastasis cannot really be generalized for phyllode’s tumors, but will tend to be related to the cancer’s histological grade. Benign phyllodes tumors which are very large might even require a mastectomy, but generally, mastecomy is held off until there is evidence of a recurring tumor.
The outlook for benign phyllodes tumors is extremely positive
The outlook for women with benign phyllodes breast tumors is very good, with a very low chance of recurrence after treatment for women over 45. In some cases of phyllodes tumor, the breast stroma may undergo metaplasia with underlying cartilage, bone, fat, and skeletal muscle. Where these additional metaplastic elements are also cytologically malignant, the prognosis is much poorer.
Local recurrence of a breast phyllodes tumor is very low
Following surgical excision, the recurrence rate of a phyllodes tumor of the breast is estimated at just under 13%, though other estimates place it has high as 20%. (The higher number is associated with margins which were not completely clear). However, local recurrence per se is not necessarily an indicator of malignancy with phyllodes breast tumors. The main indicators of breast tumor recurrence include grade classification, evidence of stromal atypica, stromal hypercellularity, and infiltrative borders. Other indicators for a less likely recurrence of breast phyllodes tumors include the presence of pseudoangiomatous stromal hyperplasia (PASH) and negative surgical margins.
Malignant phyllodes tumors metastize less than 20% of the time
Metastases to distant areas is estimated to occur at around 19% for malignant phyllodes breast tumors, but it should be added that even some benign phyllodes tumors have been known to metastize. The metastatic spread of phyllodes breast tumors seems actually to be associated with ‘haematogenous‘ elements (blood oxygenization), and tends to occur in the bone, pleura, and the lungs. Interestingly, less than 1% of phyllodes breast tumors metastize to the axillary lymph nodes. For this reason, routine axillary node dissection is generally not indicated in treating aggressive phyllodes tumors.
Let’s do a little Q&A quiz…
- What causes a phyllodes tumor? Some inherited genetic disorders are known to increase the risk of developing a phyllodes tumor, but in most cases, the causes are unknown.
- Are phyllodes tumors cancerous? Although most phyllodes tumors are benign (not cancerous), some are malignant (cancerous) and some are also borderline (in between cancerous and non-cancerous), depending on histologic features including stromal cellularity, infiltration at the tumors edge, and mitotic activity.
- How fast do phyllodes tumors grow? They tend to grow very quickly in just a few weeks, to the size of 2-3 cm or sometimes larger.
- How do you treat a phyllodes tumor? The common treatment is a wide local excision. Other than surgery, there is no other possible cure. Chemotherapy and radiation therapy are not effective what-so-ever.
- What are the symptoms? The most common symptom is a breast lump, that you and your doctor can feel while examining the breasts.
- Is a phyllodes tumor painful? Not usually.
- What happens if a phyllodes tumor is not checked out? If left unchecked, the lump can create a visible bulge as it pushes against the skin. It can also cause an ulcer or an open wound to form on the breast skin.
- How are phyllodes tumors diagnosed? A physical examination, a mammogram, an ultrasound, MRI, or biopsy (core needle, or excisional).
- How to prevent a phyllodes tumor? Local therapy is aimed at preventing the tumor from coming back in the breast. Local therapy will include wide excision or mastectomy.
- Belkacmi Y, Bousquet G, Marsiglia H, et al. Phyllodes Tumor of the Breast. Int J Radiat Oncol Biol Phys (2007). 70 (2): 492.
- Kuijper, A., Progressive Deregulation of the Cell Cycle With Higher Tumor Grade in the Stroma of Breast Phyllodes Tumors. Am J Clin Pathol 2005;123:690-698.
- Tse GM, Lui PC, Scolyer RA, Putti TC, Kung FY, Law BK, Lau TS, Lee CS. Tumour angiogenesis and p53 protein expression in mammary phyllodes tumors. Mod Pathol. 2003 Oct;16(10):1007-13.
- Tse GM, Putti TC, Lui PC, Lo AW, Scolyer RA, Law BK, Karim R, Lee CS. Increased c-kit (CD117) expression in malignant mammary phyllodes tumors. Mod Pathol. 2004 Jul;17(7):827-31.
- Tan, PH., et al. Phyllodes Tumors of the Breast The Role of Pathologic Parameters. Am J Clin Pathol 2005;123:529-540.
- Kleer,CG, etal. Pathologic, Immunohistochemical, and Molecular Features of Benign and Malignant Phyllodes Tumors of the Breast. Mod Pathol 2001;14:185-190
- Tse GM, Lee CS, Kung FY, Scolyer RA, Law BK, Lau TS, Putti TC.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 Oct;118(4):522-6
- Uriev, L., Maslovsky, I., Vainshtien, P., Yoffe, B., Ben-Dor, D., Malignant phyllodes tumor with heterologous liposarcomatous differentiation and tubular adenoma-like epithelial component. Int. J. Med. Sci. 2006, 3
- Moffat CJC, Pinder SE, Dixon AR, Elston CW, Blarney RW, Ellis IO. Phyllodes tumors of the breast: a clinicopathological review of thirty-two cases. Histopathology. 1995; 27: 205-218.3.
- Lerwill MF. Biphasic lesions of the breast. Semin Diagn Pathol. 2004; 21: 48-56.
- Nishimura R, Hasebe T, Imoto S, Mukai K. Malignant phylloides tumour with a non-invasive ductal carcinoma component. Virchows Arch. 1998; 432: 89-93.
- Muttarak, M., Lerttumnongtum, P., Somwangjaroen, A., Chaiwun., B., Phyllodes tumour of the breast. Biomed Imaging Interv J 2006; 2(2):e33
- Muller J. Uber den feinern bau und die formen der krankhaften geschwulste. Vol. 1. Berlin, Germany: Reimer, 1838:54-60.
- Liberman L, Bonaccio E, Hamele-Bena D, et al. Benign and malignant phyllodes tumors: mammographic and sonographic findings. Radiology 1996;198(1):121-4.
- Rosen PP ed. Rosens breast pathology. 2 edition. Philadelphia, PA: Lippncott Williams & Wilkins, 2001:163-200.
- Lifshitz OH, Whitman GJ, Sahin AA, et al. Radiologic-pathologic conferences of the University of Texas M.D. Anderson Cancer Center. Phyllodes tumor of the breast. AJR Am J Roentgenol 2003;180(2):332.
- Rosen PP, Oberman HA. Cystosarcoma phyllodes. Rosai J, Sobin LH, eds. Atlas of tumor pathology: tumors of the mammary glands. Vol. 7. Wasghington, DC: Armed Forces Institute of Pathology, 1993:107-14.
- Salvadori B, Cusumano F, Del Bo R, et al. Surgical treatment of phyllodes tumors of the breast. Cancer 1989;63:2532 -2536