1. Phyllodes breast tumor
Joint Hospital Surgical Grand Round
26 April 2014
Ng Yuen Shan, Sandy
(Tuen Mun Hospital)

2. Phyllodes tumor
Rare fibroepithelial breast tumor (1% of all breast tumors, 2.5% of all fibroepithelial tumors)
A spectrum of disease
Epithelial and cellular stromal component
Histological classification:
Benign (60%)
Borderline (20%)
Malignant (20%)  distant metastasis

3. Median age of presentation at 40-50 years
Palpable mass with rapid growth, large size (>2cm)
Poor pre-operative diagnostic accuracy
Triple assessment, in patients with phyllodes tumors, all three methods individually have low sensitivity and, even in combination, the diagnostic accuracy is often poor because mammary phyllodes tumors rarely develop and their clinical, imaging and cytology and histology findings are similar to those of fibroadenomatous breast tumor, which has a high incidence.

4. Case scenario Margin POSITIVE F/40
2.5cm L12H breast mass, interval growth.
MMG/US: well-circumscribed lobulated mass
FNAC: benign.
Excisional pathology:
Benign phyllodes tumor
Margin POSITIVE

5. Pok Oi Hospital
A review of 28 consecutive patients with phyllodes tumour excision in in Pok Oi Hospital
11 operations performed for recurrent phyllodes tumour (6 patients) have been excluded.
Recurrence 1-5 (mean = 2.5)
Recurrence = 5: benign PT with close margin; 1st recurrence at 5mths; total 5 recurrences in 2.5 yrs

6. Operation type Indication Total no. Margin +ve
Simple enucleation
Benign breast mass 5
3 (60%)
Wide local excision
Clinical/ pathological diagnosis of phyllodes tumour 20
2 (10%)
Mastectomy
Large tumor-breast ratio,
or suspicious malignant 4
1 (25%)
Preoperative histology favour phyllodes tumor = 65.5% (19/29)
60% of the patients treated with simple enucleation had margin involvement, including the patient who suffered from recurrence. On the other hand, 10% (2/20) of wide local excisions and 25% (1/4) of mastectomies resulted in positive margin.

7. Margin status and histological grade
Involved
Touch/ close
<1 cm
>/= 1 cm
Malignant 2 4
Borderline 1 3
Benign
Margin was involved in 6 specimens. 6 were described as touch or close, and 10 were measured to be less than 1 cm. 3 were measured to be more than or equal to 1 cm. 4 were described as clear.
Close follow-up

8. Margin-involved outcomes
Age
Grade
Tumour size (cm)
Primary Operation
FU duration (months)
Lost to FU
Reoperation
Patient A 63
Malignant
3.2
WLE 48 No
Patient B 11
Mastectomy 18
Patient C 42
Borderline 6 14
Mastectomy for co-existing DCIS
Patient D 50
Benign
7.5
Enucleation 57
Wide local excision for recurrent phyllodes
Patient E 21
3.5 35
Yes
Patient F 40
2.2 47
1 recurrence case: normal P/E; detected by MMG/US for FU other breast imaging abnormalities (3 years post-op)
6 cases, heterogeneous, difficult conclusion
Malignant margin +ve: reoperation not done as the margin is not marked
Mean FU period: 36 months

9. POH case series Results:
Local recurrence rate in margin-involved = 16.7%
No recurrence was detected in close or clear margin.
Conclusion:
Margin status of the primary resection is probably the most important factor in determining risk of recurrence.
Limitation:
Experience of surgeon not stratified
Patients Tx in private sector not included; 7 lost to FU

10. Margin-involved phyllodes tumor
Why does it matter?
What to do next?
How to “prevent”?

11. Local recurrence Meta-analysis (83 articles, 5530 patients)
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 Nov;88(2):

12. Local recurrence Associated factors: - + Asoglu, 2004 Chen, 2005
Study
Stromal atypia
Positive margin
Necrosis
Fibroproliferation
Asoglu, 2004 - +
Chen, 2005
Barrio, 2007
Lenhard, 2007
Telli, 2007
Belkacemi, 2008
Stromal atypia: marked in borderline/ malignant
Sample size: 50/ 172/ 293/ 33/ 443
Calhoun KE, Lawton TJ, Kim JN, Lehman CD, Anderson BO. Phyllodes tumors. In: Harris JR, Lippman ME, Morrow M, Osborne CK, eds. Diseases of the Breast. 4th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2010:

13. Disease-free survival curves of 42 patients treated with breast-conservative surgery for phyllodes tumor.
Taira’s series of 45 patients (15 positive surgical margin, with 6 recurrences). In univariate analysis, a positive surgical margin, stromal overgrowth and histological classification were predictive factors for local recurrence after breast-conservation surgery. A positive surgical stump was the only independent predictor of local recurrence in multivariate analysis (P=0.012). Stromal overgrowth was a predictive factor for local recurrence in cases with a positive surgical margin (P=0.0139).
Taira N, Takabatake D, Aogi K, et al. Phyllodes Tumor of the Breast: Stromal Overgrowth and Histological Classification are Useful Prognosis-predictive Factors for Local Recurrence in Patients with a Positive Surgical Margin. Jpn J Clin Oncol 2007;37(10)730–736

14. Factors involved in local recurrence were investigated in the 15 stump-positive cases, and stromal overgrowth was found to be a significant prognosis-predictive factor. Histological malignancy was excluded as an investigative factor in this analysis because it was found in stromal overgrowth-positive cases.
Taira N, Takabatake D, Aogi K, et al. Phyllodes Tumor of the Breast: Stromal Overgrowth and Histological Classification are Useful Prognosis-predictive Factors for Local Recurrence in Patients with a Positive Surgical Margin. Jpn J Clin Oncol 2007;37(10)730–736

15. Margin-involved phyllodes tumor
Why does it matter?
Predictor of local recurrence
What to do next?
How to “prevent”?

16. If margin positive…
Stromal growth as a predictive factor of local recurrence in positive margin cases
One of the malignant features
POH: benign, subcut Mx, margin clear, stromal overgrowth  total 5 recurrences in 3 yrs (1st recurrence at 5mths)
Histological malignancy was excluded as an investigative factor in this analysis because it was found in stromal overgrowth-positive cases.
Taira N, Takabatake D, Aogi K, et al. Phyllodes Tumor of the Breast: Stromal Overgrowth and Histological Classification are Useful Prognosis-predictive Factors for Local Recurrence in Patients with a Positive Surgical Margin. Jpn J Clin Oncol 2007;37(10)730–736

17. If margin positive…
Some authors had suggested “wait-and-see” policy for benign phyllodes tumor
Chua, 1989 (106 patients)
Zurrida, 1992 (216 patients): recurrence 8%
In a review of 106 benign phyllodes tumor patients (15-year period), in whom 71.7% were mistakenly operated on for fibroadenoma. Since only 15.8% of this group developed local recurrence, Chua et al. concluded that because only 16% of patients presumptively operated on fibroadenoma developed a local recurrence, a policy of close follow-up may be acceptable.
Zurrida et al. from Milan based on their series of 216 patients, with a mean period of follow-up of 118 months, they found that only 8% of benign lesions recurred (vs 20% to 23% for borderline or malignant phyllodes tumors), and that these recurrences occurred significantly later following initial diagnosis (32 months vs. 18 to 22 months on average).
On this basis, these authors suggest that a “wait-and-watch” policy for benign phyllodes tumors may be considered as an alterative to mandatory surgical reexcision.
Chua CL, Thomas A, Ng BK. Cystosarcoma phyllodes: a review of surgical options. Surgery 1989;105(2 Pt 1):
Zurrida S, Bartoli C, Galimberti V, et al. Which therapy for unexpected phyllodes tumour of the breast? Eur J Cancer 1992;28(2-3):

18. Management strategy of Margin-involved phyllodes tumor
Benign “wait-and-see”
Malignant  Re-excision
Follow-up every 6 months for initial 2-3 years (highest chance of recurrence)
Then yearly
Self breast examination
Clinical suspicion on follow-up: triple assessment
In margin-involved cases, POH recurrence rate: 16.7% (meta-analysis LR: benign 15%, borderline 17%, malignant 28%; overall 19%)
POH: one case malignant margin +ve, no recurrence in 43 mths

19. Margin-involved phyllodes tumor
Why does it matter?
What to do next?
How to “prevent”?

20. Phyllodes tumor
Difficult preoperative diagnosis…..

21. Phyllodes tumor – Initial workup
Patient presentation
Triple assessment
Clinical suspicious of phyllodes tumor
- Palpable mass
- Rapid growth
- USG suggestive of fibroadenoma except for size (>2cm) / rapid growth
- History and P/E
- USG
- MMG for >30yo
Core needle biopsy
Fibroadenoma
Fibroadenoma or indeterminate
Phyllodes tumor (benign, borderline, malignant)
PT>FA: Round/lobulated shape, well-defined margins, heterogenous internal structure, non-enhancing internal septations
Imaging (MMG/USG): unreliable in differentiating benign/malignant vs fibroadenomas
FNAC will not, and core biopsy may not, distinguish FA from PT (some PT arise in a background of FA)
Malignant PT: LN met <1%, therefore AD only when histologically positive malignant cells
Core biopsy
-> benign or borderline: observe
-> malignant: as soft tissue sarcoma (e.g. RT to chest wall if margin close, chest wall involvement, >5cm with stromal overgrowth; or only partial Mx performed)
XRT: if mastectomy was performed and margins were concerning/close, tumor involved the fascia or chest wall, or tumor was very large (greater than 5 centimeters), then recommend XRT to chest wall.
Observe
Excisional biopsy
Wide excision (>=1cm) without axillary staging
M D Anderson Cancer Center 2012

22. Margin-involved phyllodes tumor
Why does it matter
What to do next
How to “prevent” ?

23. Thank you

24. WHO classification

25. Phyllodes tumors are usually differentiated histologically from FA by its increased stromal cellularity and mitotic activity. However, benign phyllodes tumor by definition lacks marked atypia and excess mitotic activity in its stromal component.

26. To improve preoperative diagnosis
Paddington Clinicopathological Suspicion Score
Clinical findings
Sudden increase in size in a longstanding breast lesion
Apparent fibroadenoma >3cm diameter or in patient >35 years
Imaging findings
MMG: Rounded borders/ lobulated appearance
USG: Attenuation or cystic areas within a solid mass
FNAC findings
Presence of hypercellular stromal fragments
Indeterminate features
ANY 2 features mandate core biopsy
criteria to assist in the selection of patients for core biopsy, for use in conjunction with existing local protocols.
R K Jacklin, P F Ridgway, P Ziprin, et al. Optimising preoperative diagnosis in phyllodes tumour of
the breast. J Clin Pathol 2006;59:454–459.

27. Phyllodes tumor - Recurrence
Patient presentation
Workup
Local recurrent breast mass after excision of phyllodes tumor
- History and P/E
- MMG, USG
- Core needle biopsy
- Consider chest imaging
No metastatic disease
Metastatic disease
Distant met (Hemat): 10%; usually w/o evidence of local recurrence; lungs (66%), bones (28%), brain (9%)
Determined by tumor biology, not extend of initial surgery
LN met <1% (LN enlargement in 10%); AD if histo malig +ve
There is no prospective randomized data supporting the use of radiation treatment with phyllodes tumor. However, in the setting where additional recurrence would create significant morbidity e.g. chest wall recurrence following salvage mastectomy, radiation therapy may be considered, following the same principles that are applied to the treatment of soft tissue sarcoma.
Re-excision with wide margins without axillary staging
As soft tissue sarcoma
Consider post-op RT
M D Anderson Cancer Center 2012