Phyllodes tumour

Section: Breast Curriculum: Curriculum, page 9

Definition

• Phyo = Leaf in Greek
• Stromal fibro-epithelial neoplasms that are known to recur locally
• 80% are benign, 15% border-line, 5% malignant
• Li-Fraumeni syndrome

Incidence

• Affects pre-menopausal women (40-70yrs); most present in 50-60s
• Account for 0.3-0.5% of all breast tumours
• Accounts for 2.5% of fibroepithelial tumours
• Associated with Li-Fraumeni syndrome

Aetiology

• Unknown

Clinical

• Rapid growth
  • May present as enlargement of the whole breast
  • Often present like a Fibroadenoma but larger – average = 5cm
• Palpable axillary lymphadenopathy in 20% of pts – most are reactive, metastatic involvement of lymph nodes rare
• 20% present as non-palpable mass on screening mammogram
• Ultrasound features:
  • Well-defined mass
  • Heterogeneous echogenicity
  • Oval or lobulated
  • Cystic spaces
• Mammogram features:
  • Well-defined mass
  • No calcifications
• MRI features:
  • Benign phyllodes: Irregular shape, ill-defined margins, echogenic heterogeneity
  • Malignant phyllodes: Irregular shape, contrast medium wash-out phenomenon

Pathology

• Arise from intralobular stroma (like a Fibroadenoma)
  • Epithelial (benign) & stromal (benign or malignant) components
• Microscopic
  • Like fibroadenoma, intracanalicular pattern (but hypercellular stroma)
  • Fleshy & lobulated, clefting in lobules containing papillary projections of epithelial-lined stroma (leaf-like)
  • May have cystic components with a cut surface resembling a fern leaf (“phyllodes”)
• Radial growth creating pseudo-capsule through which tongues of stroma protrude and grow into adjacent breast tissue
• Frequently large with small surface protrusions which if left → recurrence
• Abnormality of the stromal component determines malignant potential and risk of local recurrence
• Has sarcoma-like behaviour
  • Metastasizes to lungs, not LN
  • However < 25% malignant phyllodes metastasise

Histological Classification

• Classified as benign, borderline or malignant based on 5 features
  1. Degree of stromal cellular atypia
  2. Mitotic activity
  3. Infiltrative or circumscribed tumour margins
  4. Presence or absence of stromal overgrowth (i.e. presence of pure stroma devoid of epithelium)
  5. Stromal cellularity
• Stromal overgrowth most consistently associated with aggressive (metastatic) behaviour
• 50%: benign, 25%: malignant
• Benign – better local control and disease-free survival vs. borderline/malignant tumours
  • Benign and borderline rarely recur following wide excision

Classification	Stromal Cellularity	Cellular Atypia	Tumour Margins	Mitotic Rate	Stromal Overgrowth
Benign Tumours	Increased	Mild-moderate	Circumscribed	Low (< 4 mitoses per 10 high-power fields)	Absent
Borderline Tumours	Greater degree	Greater degree	Microscopic infiltrative	4-9 mitoses per 10 high-power fields	Absent
Malignant Tumours	Marked	Marked	Infiltrative	High (>10 mitoses per 10 high-power fields)	Presence

Investigations

• Phyllodes and fibroadenoma usually indistinguishable on imaging & FNA
• Core Bx (correct diagnosis 50%) or excision (with a margin) required
• If result is “cellular fibroadenoma”, “cellular fibroepithelial lesion”, or “fibroepithelial lesion with cellular stroma” – excisional biopsy required
• 25-30% false negative rate

Management

• Should be treated with Wide Local Excision (≥ 1 cm margin)
• Large / malignant tumours may need mastectomy (± with muscle) ± reconstruction
• LN dissection not required
• Mets: Poorly responsive to chemo/radiation
• Positive margins require re-excision
• Breast-conserving surgery equivalent to mastectomy for cause-specific survival regardless of tumour size
• Mastectomy not indicated for benign phyllodes unless negative margins unable to be achieved or tumour too large to allow breast conservation therapy

Adjuvant Treatment

Adjuvant Radiotherapy

• Indications:
  • Borderline or Malignant but not benign tumours
  • Recurrent disease
• Reduces local recurrences of borderline/malignant phyllodes after breast conserving surgery but no effect on overall or disease-free survival

Chemotherapy

• Limited data
  • Consider in
    • Large (> 10cm)
    • High risk
    • Recurrent Malignant Phyllodes Tumours
• Use protocols designed for soft tissue sarcomas instead of breast cancers

Hormonal Therapy

• Not used
• Hormone receptors on epithelial component but stromal component is main neoplastic cell population responsible for metastasis

Post-Treatment Follow-up

• Most recurrences happen in first 2 years after treatment
• Hx and exam every 6 months for 2 years, and then reduced to annually
• Annual mammograms
• Pts with large (≥ 5cm) or Malignant Phyllodes at higher risk of mets thus:
  • More frequent hx and exam follow up
  • CXR or CT-scan added for surveillance

Natural Hx

• Most behave in a benign fashion but 25% 10-year recurrence rate
• Recurrence related to surgery
  • Enucleation: 2-60%
  • WLE: 0-40%
  • Mastectomy:0-14%
• Rarely high-grade lesions behave aggressively: local recurrence & distant (haematogenous) mets in 1/3 of cases
• Spread to lung & bone (rarely nodes), can be locally invasive
  • Mets → Poor prognosis (most pts die within 3 years)
  • ≈ 1/3 of pts with malignant phyllodes die of their disease