- Email: [email protected]
Phyllodes tumour of the breast: a retrospective analysis of 30 cases
The Breast (1999) 8, 278–281 © 1999 Harcourt Publishers Ltd
ORIGINAL ARTICLE
Phyllodes tumour of the breast: a retrospective analysis of 30 cases K. Mokbel, R. K. Price, A. Mostafa, C. A. Wells and R. Carpenter The Breast Unit, St Bartholomew’s Hospital, London EC1A 7BE, UK S U M M A R Y. Phyllodes tumour (PT) is a rare neoplasm of the female breast that resembles fibroadenoma but occurs in an older age group. We retrospectively reviewed the medical records of 30 women who were treated for phyllodes tumour in our centre. Histological examination was performed by an experienced breast pathologist in all cases and tumours were classified as benign, border line malignant or malignant according to standard hisotological criteria. The mean age at diagnosis was 49 years (range: 19–80 years). Twenty-one (70%) of 30 tumours were benign and 9 (30%) were malignant (n=7) or borderline malignant (n=2). The mean tumour size was 46 mm (range : 20–100 mm). The final microscopic margins contained tumour in 13 (43%) of 30 cases and were free of tumour in 17 (57%) of 30 patients. After a median follow-up period of 6 years (range : 6 months – 20 years), the tumour recurred locally in 5 (17%) patients. One patient had six local recurrences over an 18-year period. Local recurrences were more frequently observed in patients with malignant tumours compared with those with benign lesions (33% versus 10%). However, this association failed to reach statistical significance. There was no association between local recurrence, patient age, tumour size or positive microscopic margins. There was one death (3%) associated with a completely excised malignant tumour. The present study suggests that histological type and margins do not accurately predict the clinical course of PT and that there is a need to identify novel biological markers that more accurately predict the behaviour of this rare neoplasm. © 1999 Harcourt Publishers Ltd
INTRODUCTION
This retrospective study examines the histopathological findings and clinical outcome in 30 phyllodes tumours treated in our centre.
Phyllodes tumour is a rare neoplasm of the breast that accounts for 0.4% of breast tumours in women.1,2 The tumour is usually seen in women aged 35–55 years and its peak incidence occurs 10 years later than that of fibroadenoma. In men a few cases have been reported.3 On the basis of the criteria proposed by Azzopardi1 and Salvadori4 phyllodes tumours can be classified into benign, borderline malignant and malignant. The histological features used in this classification include the following: the number of mitoses per 10 high power fields (HPF); stromal cellularity (slight or severe); cellular atypia (absent, slight or severe); tumour margin (pushing or infiltrating); tumour necrosis (absent or present); and stromal overgrowth. Nevertheless, lack of standard interpretation of the histological features is an important reason for the different relative distribution between benign, borderline and malignant histiotypes reported in the various series.4–6
PATIENTS AND METHODS We retrospectively reviewed the medical records of 30 patients who had histologically confirmed phyllodes tumours. The tumours were classified into benign, borderline malignant and malignant according to standard criteria.1,4 The patients age at diagnosis, the tumours size, type and margins status, treatment and clinical outcome were known in all cases. In our centre, specimen margins are assessed by histological examination of shavings (< 10 µm thick) obtained from the circumferential margins of the specimens. All patients were initially treated by local excision and subsequently 8 patients had a further local excision and 2 patients had a total mastectomy for positive margins or local recurrence. One patient received adjuvant radiotherapy following local excision of a 7 cm malignant phyllodes tumour. The association between local recurrence, tumour size,
Address correspondence to: Mr K. Mokbel FRCS (Gen), The Breast Unit, St Bartholomew’s Hospital, London, UK. Tel.: 0171 601 7032; Fax: 0171 601 7034
278
Phyllodes tumour of the breast: a retrospective analysis of 30 cases 279 histological type and margin status were examined using the χ2 test with Yate’s correction. The Student t test was used to compare the mean age at diagnosis between the two groups (local recurrence group versus no local recurrence). A P value of <0.05 was considered to be statistically significant.
RESULTS A total of 30 patients with a histological diagnosis of PT were reviewed. The mean age at diagnosis was 49 years (range : 19–82 years). The mean tumour size was 46 mm (range 20–100 mm). All patients were initially treated by local excision of the tumour. Subsequently 8 patients had re-excision for positive margins and 2 patients underwent mastectomy for locally recurrent malignant tumours. One patient had postoperative radiotherapy following a wide local excision of a 7 cm malignant PT. Of the 30 tumours examined, 21 (70%) were classified as benign and 9 (30%) as malignant (n=7) or borderline malignant (n=2). The final histological margins were free of microscopic disease in 17 (57%) of 30 patients. After a median follow-up period of 6 years (range 6 months – 20 years), 5 patients developed local recurrence (Table 1). The initial PT was malignant in 3 patients and benign in 2. Therefore the local recurrence rate was 33% for malignant PT and 10% for benign PT. One patient died of metastatic disease within one year of complete excision of a 30 mm malignant PT. This patient received radiotherapy for skeletal metastases involving T6 and T7 vertebrae and the left shoulder. The association between local recurrence and malignant hisotological type was not statistically significant. There was no statistically significant association between local recurrence tumour size and the presence of microscopic disease at the margins. In fact 3 (60%) of the cases with local recurrence were observed in patients with histologically completely excised PT compared with 2 (40%) recurrences in patients with positive tumour margins. There was no statistically significant difference in the mean age at diagnosis between patients with local recurrence and those without (57 versus 46 years respectively).
DISCUSSION In the present study, malignant and borderline malignant tumours accounted for 30% of phyllodes tumours examined (Figs 1 and 2). This relative incidence is similar to that found by Zurrida et al7 who reported the largest series in the literature. The authors examined 216 phyllodes tumours, and detected malignancy or borderline malignancy in 35%
Fig. 1 Benign phyllodes tumour. The stromal cells show no atypia or increased mitotic activity. (Magnification ×40)
Fig. 2 Malignant phyllodes tumour with stroma composed of spindle cells showing atypia and increased mitotic activity. (Magnification ×40).
Table 1 Characteristics of patients with recurrent phyllodes tumours (n=5) Parameter
Age at diagnosis
Initial tumour type
Initial tumour size (mm)
Margin status
Period to recurrence (year)
Case 1 Case 2 Case 3 Case 4
53 82 34 57
Malignant Benign Benign Malignant
25 35 50 40
(+) ve (+) ve (–) ve (–) ve
19 2 6 18
Case 5
61
Malignant
30
(–) ve
1
Comments
Had a total of 6 local recurrences. Systemic recurrence.
280
The Breast
of cases. The incidence of malignant or borderline malignant tumours reported in other series ranged from 8.5% to 62.7%.8,9 The lack of standard interpretation of the histological features is an important cause for this variation in the relative incidence of benign and malignant tumours. Phyllodes tumour is currently treated by local excision with an adequate resection margin (1–2 cm), and simple enucleation should be avoided.2,4,7 Obtaining an adequate resection margin of normal breast tissue is particularly important in the case of malignant or borderline malignant lesions. Mastectomy is no longer considered the treatment of choice for malignant phyllodes tumour provided adequate excision is feasible, since local recurrence does not seem to be associated with systemic metastases and can be treated by further local excision or mastectomy.2,4 In the present study, adequate local excision was achieved in 57% of cases and this is due to the fact that our current policy of ensuring complete surgical excision with negative margins was not strictly adhered to in the earlier part of the documented study period. The presence of positive microscopic margins, however, did not influence the incidence of local recurrence in our limited study. In fact several authors have recommended a surveillance policy for benign phyllodes tumours with positive microscopic margins.7,10 The present study demonstrated a clinically significant association between local recurrence and histological type (33% for malignant Phyllodes tumours and 10% for benign Phyllodes tumour, odds ratio = 3.3) and this is similar to that reported in previously published series.4,9 The failure to reach statistical significance is almost certainly caused by the small sample size. Several authors have reported a significant association between local recurrence, type of surgery and surgical margins.11,12 More recently in a retrospective study of 38 patients, de Roos et al.13 observed that local recurrence was significantly associated with involved margins but not with tumour size, histological grade, type of surgery or patient’s age. However, the authors reported a significant association between mortality and tumour size and grade. One of our patients died of metastatic disease from a malignant phyllodes tumour (30 mm) treated by adequate local excision. Although local and systemic recurrence occur mainly in malignant and borderline malignant tumours, benign phyllodes tumours treated by complete surgical excision are also associated with a significant incidence of local and systemic recurrence.2,5,7 Reinfuss et al.5 reported 3 cases of pulmonary metastases associated with ‘benign’ phyllodes tumours treated by wide local excision and found no correlation between clinical outcome and histological type or local therapy in their study. The role of adjuvant radiotherapy after surgery is unclear but it has been used.5
A limited response of metastatic disease to chemotherapy has been reported with the use of certain agents such as ifosfamide, doxorubicin, cisplatin and etoposide.14 The present study and other studies reported in the literature suggest that the histological type and the extent of local resection are not good predictors of clinical outcome in PT.5,7 Some authors, have investigated the role of other factors such as the degree of stromal growth,15 the presence of tumour necrosis16 and mitotic activity6,15 and reported a correlation between these variables and malignant behaviour. Flow cytometry as a prognostic predictor has also been investigated with conflicting results.3,6,18 We have recently examined telomerase activity in two locally recurrent tumours.19 Both tumours (one benign and one malignant) expressed telomerase activity and the role of this enzyme as a prognostic predictor should be investigated.
References 1. Azzopardi J G. Sarcoma of the breast. In: Bennington J, ed. Problems in breast pathology. Vol. II Major problems in pathology. Philadelphia: WB Saunders Co., 1979: 355–359. 2. Rowell M D, Perry R R, Hsiu J G, Barranco S C. Phyllodes tumours. Am J Surg 1993; 165: 376–379. 3. Keelan P A, Myers J L, Wold L E, Katzmann J A, Gibney D J. Phyllodes tumour: clinicopathologic review of 60 patients and flow cytometric analysis in 30 patients. Hum Pathol 1992; 23:1048–1054. 4. Salvadori B, Cusumano F, Bo R D et al. Surgical treatment of phyllodes tumours of the breast. Cancer 1989; 63: 2532–2536. 5. Reinfuss M, Mitus J, Duda K. The treatment and prognosis of patients with phyllodes tumour of the breast. Cancer 1996; 77: 910–916. 6. Grimes M M. Cystosarcoma phyllodes of the breast: histological features, flow cytometric analysis, and clinical correlations. Mod Pathol 1992; 5: 232–9. 7. Zurrida S, Bartoli C, Galimberti V et al. Which therapy for unexpected phyllodes tumour of the breast? Eur J Cancer 1992; 28: 654–657. 8. Chua C L, Thomas A. Cystosarcoma phyllodes tumours. SGO 1988; 166: 302–6. 9. Ciatto S, Bonardi R, Cataliotti L, Cardona G and members of the Coordinating Centre and Writing Committee of FONCAM. Phyllodes tumour of the breast: a multicentre series of 59 cases. Eur J Surg Oncol 1992; 18: 545–9. 10. Bartoli C, Zurridia S M, Clemente C. Phyllodes tumour in male patients with bilateral gynaecomastia induced by oestrogen therapy for prostate cancer. Eur J Surg Oncol 1991; 17: 215–217. 11. Cohn-Cedermark G, Rutqvist L E. Rosendahl I, Silfverswar C. Prognostic factors in cystosarcoma phyllodes. A clinicopathologic study of 77 patients. Cancer 1991; 68: 2017–22. 12. Bennett I C, Khan A, De Freitas R, Chaudary M A, Millis R Phyllodes tumours: A clinicopathological review of 30 cases. Aust N Z J Surg 1992; 62: 628–33. 13. de Roos W K, Kaye P, Dent D M Factors leading to local recurrence or death after surgical resection of phllodes tumours of the breast. Br J Surg 1999; 89: 396–399. 14. Burton G V, Hart L L, Leigh G S, Iglehart J D, McCarty K S, Cox E B. Cystosarcoma phyllodes. Effective therapy with cisplatin and etoposide chemotherapy. Cancer 1989; 63: 2088–2092. 15. Hawkins R E, Schofield J B, Fisher C, Wiltshaw E, McKinna J A.
Phyllodes tumour of the breast: a retrospective analysis of 30 cases 281 The clinical and histological criteria that predict metastases from cystosarcoma phyllodes. Cancer 1992; 69: 141–7. 16. Murad T M, Hines J R, Beal J, Bauer K. Histopathological and clinical correlations of cystosarcoma phyllodes. Arch Pathol Lab Med 1988; 112: 752–6. 17. Palko M J, Wang S E, Shakney S E, Cottington E M, Levitt S B, Hartsock R J. Flow cytometric S fraction as a predictor of clinical
outcome in cystosarcoma phyllodes. Arch Pathol Lab Med 1990; 114: 949–52. 18. Layfield L J, Hart J, Neuwirth H, Bohman R, Trumbull W E, Giuliano A E. Relation between DNA ploidy and the clinical behavior of phyllodes tumours. Cancer 1989; 64: 1486–1489. 19. Mokbel K M, Ghilchik M, Parris C N et al. Telomerase activity in phyllodes tumours. Eur J Surg Oncol 1999; 25: 269–272.
ORIGINAL ARTICLE
Phyllodes tumour of the breast: a retrospective analysis of 30 cases K. Mokbel, R. K. Price, A. Mostafa, C. A. Wells and R. Carpenter The Breast Unit, St Bartholomew’s Hospital, London EC1A 7BE, UK S U M M A R Y. Phyllodes tumour (PT) is a rare neoplasm of the female breast that resembles fibroadenoma but occurs in an older age group. We retrospectively reviewed the medical records of 30 women who were treated for phyllodes tumour in our centre. Histological examination was performed by an experienced breast pathologist in all cases and tumours were classified as benign, border line malignant or malignant according to standard hisotological criteria. The mean age at diagnosis was 49 years (range: 19–80 years). Twenty-one (70%) of 30 tumours were benign and 9 (30%) were malignant (n=7) or borderline malignant (n=2). The mean tumour size was 46 mm (range : 20–100 mm). The final microscopic margins contained tumour in 13 (43%) of 30 cases and were free of tumour in 17 (57%) of 30 patients. After a median follow-up period of 6 years (range : 6 months – 20 years), the tumour recurred locally in 5 (17%) patients. One patient had six local recurrences over an 18-year period. Local recurrences were more frequently observed in patients with malignant tumours compared with those with benign lesions (33% versus 10%). However, this association failed to reach statistical significance. There was no association between local recurrence, patient age, tumour size or positive microscopic margins. There was one death (3%) associated with a completely excised malignant tumour. The present study suggests that histological type and margins do not accurately predict the clinical course of PT and that there is a need to identify novel biological markers that more accurately predict the behaviour of this rare neoplasm. © 1999 Harcourt Publishers Ltd
INTRODUCTION
This retrospective study examines the histopathological findings and clinical outcome in 30 phyllodes tumours treated in our centre.
Phyllodes tumour is a rare neoplasm of the breast that accounts for 0.4% of breast tumours in women.1,2 The tumour is usually seen in women aged 35–55 years and its peak incidence occurs 10 years later than that of fibroadenoma. In men a few cases have been reported.3 On the basis of the criteria proposed by Azzopardi1 and Salvadori4 phyllodes tumours can be classified into benign, borderline malignant and malignant. The histological features used in this classification include the following: the number of mitoses per 10 high power fields (HPF); stromal cellularity (slight or severe); cellular atypia (absent, slight or severe); tumour margin (pushing or infiltrating); tumour necrosis (absent or present); and stromal overgrowth. Nevertheless, lack of standard interpretation of the histological features is an important reason for the different relative distribution between benign, borderline and malignant histiotypes reported in the various series.4–6
PATIENTS AND METHODS We retrospectively reviewed the medical records of 30 patients who had histologically confirmed phyllodes tumours. The tumours were classified into benign, borderline malignant and malignant according to standard criteria.1,4 The patients age at diagnosis, the tumours size, type and margins status, treatment and clinical outcome were known in all cases. In our centre, specimen margins are assessed by histological examination of shavings (< 10 µm thick) obtained from the circumferential margins of the specimens. All patients were initially treated by local excision and subsequently 8 patients had a further local excision and 2 patients had a total mastectomy for positive margins or local recurrence. One patient received adjuvant radiotherapy following local excision of a 7 cm malignant phyllodes tumour. The association between local recurrence, tumour size,
Address correspondence to: Mr K. Mokbel FRCS (Gen), The Breast Unit, St Bartholomew’s Hospital, London, UK. Tel.: 0171 601 7032; Fax: 0171 601 7034
278
Phyllodes tumour of the breast: a retrospective analysis of 30 cases 279 histological type and margin status were examined using the χ2 test with Yate’s correction. The Student t test was used to compare the mean age at diagnosis between the two groups (local recurrence group versus no local recurrence). A P value of <0.05 was considered to be statistically significant.
RESULTS A total of 30 patients with a histological diagnosis of PT were reviewed. The mean age at diagnosis was 49 years (range : 19–82 years). The mean tumour size was 46 mm (range 20–100 mm). All patients were initially treated by local excision of the tumour. Subsequently 8 patients had re-excision for positive margins and 2 patients underwent mastectomy for locally recurrent malignant tumours. One patient had postoperative radiotherapy following a wide local excision of a 7 cm malignant PT. Of the 30 tumours examined, 21 (70%) were classified as benign and 9 (30%) as malignant (n=7) or borderline malignant (n=2). The final histological margins were free of microscopic disease in 17 (57%) of 30 patients. After a median follow-up period of 6 years (range 6 months – 20 years), 5 patients developed local recurrence (Table 1). The initial PT was malignant in 3 patients and benign in 2. Therefore the local recurrence rate was 33% for malignant PT and 10% for benign PT. One patient died of metastatic disease within one year of complete excision of a 30 mm malignant PT. This patient received radiotherapy for skeletal metastases involving T6 and T7 vertebrae and the left shoulder. The association between local recurrence and malignant hisotological type was not statistically significant. There was no statistically significant association between local recurrence tumour size and the presence of microscopic disease at the margins. In fact 3 (60%) of the cases with local recurrence were observed in patients with histologically completely excised PT compared with 2 (40%) recurrences in patients with positive tumour margins. There was no statistically significant difference in the mean age at diagnosis between patients with local recurrence and those without (57 versus 46 years respectively).
DISCUSSION In the present study, malignant and borderline malignant tumours accounted for 30% of phyllodes tumours examined (Figs 1 and 2). This relative incidence is similar to that found by Zurrida et al7 who reported the largest series in the literature. The authors examined 216 phyllodes tumours, and detected malignancy or borderline malignancy in 35%
Fig. 1 Benign phyllodes tumour. The stromal cells show no atypia or increased mitotic activity. (Magnification ×40)
Fig. 2 Malignant phyllodes tumour with stroma composed of spindle cells showing atypia and increased mitotic activity. (Magnification ×40).
Table 1 Characteristics of patients with recurrent phyllodes tumours (n=5) Parameter
Age at diagnosis
Initial tumour type
Initial tumour size (mm)
Margin status
Period to recurrence (year)
Case 1 Case 2 Case 3 Case 4
53 82 34 57
Malignant Benign Benign Malignant
25 35 50 40
(+) ve (+) ve (–) ve (–) ve
19 2 6 18
Case 5
61
Malignant
30
(–) ve
1
Comments
Had a total of 6 local recurrences. Systemic recurrence.
280
The Breast
of cases. The incidence of malignant or borderline malignant tumours reported in other series ranged from 8.5% to 62.7%.8,9 The lack of standard interpretation of the histological features is an important cause for this variation in the relative incidence of benign and malignant tumours. Phyllodes tumour is currently treated by local excision with an adequate resection margin (1–2 cm), and simple enucleation should be avoided.2,4,7 Obtaining an adequate resection margin of normal breast tissue is particularly important in the case of malignant or borderline malignant lesions. Mastectomy is no longer considered the treatment of choice for malignant phyllodes tumour provided adequate excision is feasible, since local recurrence does not seem to be associated with systemic metastases and can be treated by further local excision or mastectomy.2,4 In the present study, adequate local excision was achieved in 57% of cases and this is due to the fact that our current policy of ensuring complete surgical excision with negative margins was not strictly adhered to in the earlier part of the documented study period. The presence of positive microscopic margins, however, did not influence the incidence of local recurrence in our limited study. In fact several authors have recommended a surveillance policy for benign phyllodes tumours with positive microscopic margins.7,10 The present study demonstrated a clinically significant association between local recurrence and histological type (33% for malignant Phyllodes tumours and 10% for benign Phyllodes tumour, odds ratio = 3.3) and this is similar to that reported in previously published series.4,9 The failure to reach statistical significance is almost certainly caused by the small sample size. Several authors have reported a significant association between local recurrence, type of surgery and surgical margins.11,12 More recently in a retrospective study of 38 patients, de Roos et al.13 observed that local recurrence was significantly associated with involved margins but not with tumour size, histological grade, type of surgery or patient’s age. However, the authors reported a significant association between mortality and tumour size and grade. One of our patients died of metastatic disease from a malignant phyllodes tumour (30 mm) treated by adequate local excision. Although local and systemic recurrence occur mainly in malignant and borderline malignant tumours, benign phyllodes tumours treated by complete surgical excision are also associated with a significant incidence of local and systemic recurrence.2,5,7 Reinfuss et al.5 reported 3 cases of pulmonary metastases associated with ‘benign’ phyllodes tumours treated by wide local excision and found no correlation between clinical outcome and histological type or local therapy in their study. The role of adjuvant radiotherapy after surgery is unclear but it has been used.5
A limited response of metastatic disease to chemotherapy has been reported with the use of certain agents such as ifosfamide, doxorubicin, cisplatin and etoposide.14 The present study and other studies reported in the literature suggest that the histological type and the extent of local resection are not good predictors of clinical outcome in PT.5,7 Some authors, have investigated the role of other factors such as the degree of stromal growth,15 the presence of tumour necrosis16 and mitotic activity6,15 and reported a correlation between these variables and malignant behaviour. Flow cytometry as a prognostic predictor has also been investigated with conflicting results.3,6,18 We have recently examined telomerase activity in two locally recurrent tumours.19 Both tumours (one benign and one malignant) expressed telomerase activity and the role of this enzyme as a prognostic predictor should be investigated.
References 1. Azzopardi J G. Sarcoma of the breast. In: Bennington J, ed. Problems in breast pathology. Vol. II Major problems in pathology. Philadelphia: WB Saunders Co., 1979: 355–359. 2. Rowell M D, Perry R R, Hsiu J G, Barranco S C. Phyllodes tumours. Am J Surg 1993; 165: 376–379. 3. Keelan P A, Myers J L, Wold L E, Katzmann J A, Gibney D J. Phyllodes tumour: clinicopathologic review of 60 patients and flow cytometric analysis in 30 patients. Hum Pathol 1992; 23:1048–1054. 4. Salvadori B, Cusumano F, Bo R D et al. Surgical treatment of phyllodes tumours of the breast. Cancer 1989; 63: 2532–2536. 5. Reinfuss M, Mitus J, Duda K. The treatment and prognosis of patients with phyllodes tumour of the breast. Cancer 1996; 77: 910–916. 6. Grimes M M. Cystosarcoma phyllodes of the breast: histological features, flow cytometric analysis, and clinical correlations. Mod Pathol 1992; 5: 232–9. 7. Zurrida S, Bartoli C, Galimberti V et al. Which therapy for unexpected phyllodes tumour of the breast? Eur J Cancer 1992; 28: 654–657. 8. Chua C L, Thomas A. Cystosarcoma phyllodes tumours. SGO 1988; 166: 302–6. 9. Ciatto S, Bonardi R, Cataliotti L, Cardona G and members of the Coordinating Centre and Writing Committee of FONCAM. Phyllodes tumour of the breast: a multicentre series of 59 cases. Eur J Surg Oncol 1992; 18: 545–9. 10. Bartoli C, Zurridia S M, Clemente C. Phyllodes tumour in male patients with bilateral gynaecomastia induced by oestrogen therapy for prostate cancer. Eur J Surg Oncol 1991; 17: 215–217. 11. Cohn-Cedermark G, Rutqvist L E. Rosendahl I, Silfverswar C. Prognostic factors in cystosarcoma phyllodes. A clinicopathologic study of 77 patients. Cancer 1991; 68: 2017–22. 12. Bennett I C, Khan A, De Freitas R, Chaudary M A, Millis R Phyllodes tumours: A clinicopathological review of 30 cases. Aust N Z J Surg 1992; 62: 628–33. 13. de Roos W K, Kaye P, Dent D M Factors leading to local recurrence or death after surgical resection of phllodes tumours of the breast. Br J Surg 1999; 89: 396–399. 14. Burton G V, Hart L L, Leigh G S, Iglehart J D, McCarty K S, Cox E B. Cystosarcoma phyllodes. Effective therapy with cisplatin and etoposide chemotherapy. Cancer 1989; 63: 2088–2092. 15. Hawkins R E, Schofield J B, Fisher C, Wiltshaw E, McKinna J A.
Phyllodes tumour of the breast: a retrospective analysis of 30 cases 281 The clinical and histological criteria that predict metastases from cystosarcoma phyllodes. Cancer 1992; 69: 141–7. 16. Murad T M, Hines J R, Beal J, Bauer K. Histopathological and clinical correlations of cystosarcoma phyllodes. Arch Pathol Lab Med 1988; 112: 752–6. 17. Palko M J, Wang S E, Shakney S E, Cottington E M, Levitt S B, Hartsock R J. Flow cytometric S fraction as a predictor of clinical
outcome in cystosarcoma phyllodes. Arch Pathol Lab Med 1990; 114: 949–52. 18. Layfield L J, Hart J, Neuwirth H, Bohman R, Trumbull W E, Giuliano A E. Relation between DNA ploidy and the clinical behavior of phyllodes tumours. Cancer 1989; 64: 1486–1489. 19. Mokbel K M, Ghilchik M, Parris C N et al. Telomerase activity in phyllodes tumours. Eur J Surg Oncol 1999; 25: 269–272.