Histopathology and Management of Phyllodes Tumors
Histopathologic Features
Phyllodes tumors are classified into benign, borderline, and malignant subtypes based on four key stromal features: tumor margin characteristics (pushing versus infiltrative), stromal cellularity and overgrowth, mitotic activity, and degree of cellular atypia. 1, 2
Key Microscopic Characteristics:
- Leaf-like architecture with stromal fronds protruding into cystic spaces (the defining feature) 1
- Both epithelial and stromal components present, with the stromal component determining malignancy grade 1, 2
- Benign tumors: well-defined margins, mild stromal cellularity, <5 mitoses per 10 high-power fields, minimal atypia 3, 2
- Borderline tumors: intermediate features between benign and malignant 3, 2
- Malignant tumors: infiltrative margins, marked stromal overgrowth, ≥10 mitoses per 10 high-power fields, severe cellular atypia 3, 2
- Tumor necrosis is a significant negative prognostic factor associated with increased recurrence risk in malignant disease 4
Diagnostic Pitfalls:
- Core needle biopsy frequently cannot distinguish phyllodes from fibroadenoma because the characteristic leaf-like architecture may not be sampled 1, 5
- Spindle cell-predominant variants may be misdiagnosed as sarcomatoid carcinoma or smooth muscle tumors 1
- For any rapidly enlarging or large (>2 cm) "fibroadenoma," perform excisional biopsy to pathologically exclude phyllodes tumor 1
Management of Benign Phyllodes Tumors
All benign phyllodes tumors require surgical excision with tumor-free margins of ≥1 cm, with breast-conserving surgery as the preferred approach. 1, 6
Surgical Management:
- Lumpectomy or partial mastectomy is the preferred initial therapy 1, 6, 3
- Target margins of ≥1 cm to minimize local recurrence 1, 7, 8
- Mastectomy is indicated ONLY if negative margins cannot be achieved with breast conservation 1, 6
- Do NOT perform axillary staging or lymph node dissection—phyllodes tumors metastasize to lymph nodes in <1% of cases 1, 6
- Re-excision is necessary only for positive margins; negative margins (even close margins) are acceptable 8
Adjuvant Therapy:
- No radiotherapy, chemotherapy, or endocrine therapy is indicated for benign phyllodes tumors 1, 6, 7
- Despite 58% containing ER and 75% containing PR, endocrine therapy does not reduce recurrence or death 1, 6
Outcomes:
- 5-year disease-free survival of 95.7% 3
- Local recurrence rate of approximately 4% after adequate excision 3
Management of Borderline Phyllodes Tumors
Borderline phyllodes tumors require wide excision with ≥1 cm margins, with selective use of adjuvant radiotherapy only for high-risk features. 7
Surgical Management:
- Same surgical principles as benign tumors: breast-conserving surgery with ≥1 cm margins 7
- Mastectomy only when adequate margins cannot be achieved 7
- No axillary staging required 7
Adjuvant Radiotherapy Indications:
Consider radiotherapy ONLY for borderline tumors with the following high-risk features: 7
- Tumor size >5 cm 7
- Infiltrative margins 7
- Inability to achieve clear margins despite re-excision attempts 7
- Radiotherapy improves local control (from 34-42% to 90-100% at 5 years) but does not improve overall survival 7
Reconstruction Timing:
- Avoid immediate reconstruction in borderline tumors with high-risk features 7
- Delayed reconstruction is preferred after completing primary oncological management and when local recurrence risk has diminished 7
Multidisciplinary Management:
- Refer all borderline phyllodes tumors to specialist sarcoma centers for pathology review and multidisciplinary team discussion 1, 7
Outcomes:
- 5-year disease-free survival of 73.7% 3
Management of Malignant Phyllodes Tumors
Malignant phyllodes tumors require surgical excision with ≥1 cm margins, with consideration of adjuvant radiotherapy for high-risk features, but no role for chemotherapy or endocrine therapy in the adjuvant setting. 6
Surgical Management:
- Breast-conserving surgery with ≥1 cm margins is preferred 6
- Mastectomy if negative margins cannot be achieved 6
- Do NOT perform axillary staging—nodal metastases occur in <1% 6
Adjuvant Radiotherapy Indications:
Consider radiotherapy for malignant tumors with: 6, 7
- Tumor size >5 cm 6
- Infiltrative margins 6
- Inability to achieve clear margins despite re-excision 6
- Local recurrence where additional recurrence would create significant morbidity 6, 7
Adjuvant Systemic Therapy:
- Neither chemotherapy nor endocrine therapy has any proven role in adjuvant treatment 1, 6
- Do not use breast cancer chemotherapy regimens for phyllodes tumors 6
- Do not prescribe tamoxifen or aromatase inhibitors despite hormone receptor positivity 6
Outcomes:
Management of Metastatic Phyllodes Tumors
For metastatic disease, surgical resection or local ablative therapy of metastatic lesions is the primary treatment approach given the relatively indolent nature of these tumors. 6
Treatment Algorithm:
- First-line: Surgical resection or local ablative therapy of metastatic lesions (most commonly lung metastases) 1, 6
- Second-line (when surgery not possible or after progression): Sarcoma-directed chemotherapy regimens such as Doxorubicin-Ifosfamide (AI), NOT breast cancer protocols 6
- Follow NCCN Guidelines for Soft Tissue Sarcoma for systemic therapy decisions 1
Critical Points:
- Do NOT use breast cancer chemotherapy regimens—phyllodes tumors are sarcomas, not epithelial breast cancers 6
- Metastatic disease should be managed according to sarcoma protocols 1, 6
Management of Local Recurrence
Re-excision with wide tumor-free margins without axillary staging is the treatment for local recurrence. 1, 7
Treatment Approach:
- Re-excision with ≥1 cm margins 1, 7
- Consider postoperative radiation therapy if additional recurrence would create significant morbidity 1, 7
- Do NOT perform axillary staging for recurrent disease 7
Critical Clinical Pitfalls to Avoid
- Do NOT rely on core needle biopsy to exclude phyllodes tumor in rapidly growing or large breast masses 1, 5
- Do NOT perform routine axillary staging—this adds unnecessary morbidity without benefit 1, 6, 7
- Do NOT use adjuvant chemotherapy or endocrine therapy—these have no proven efficacy 1, 6, 7
- Do NOT routinely recommend radiotherapy for all phyllodes tumors—reserve for high-risk cases only 1, 7
- Do NOT accept inadequate surgical margins—margin status is more important than histologic subtype for predicting local recurrence 1
- Do NOT use breast cancer treatment protocols for metastatic disease—use sarcoma-directed therapy 6