🧝♀️Phyllodes Tumor & Fibroadenoma Flashcards
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Differences between Phyllodes tumor and Fibroadenoma
What is Phyllodes Tumour ?
Phyllodes = leaf like, typical papillary projections on pathologic examination.
Benign Fibroepithelial breast tumor with malignant potential and diverse biologic behavior from similar to benign fibroadenoma to sarcomatous lesions.
- a.k.a - Serocystic disease of Brodie or Cystosarcoma phylloides
Classification of Breast Tumour
Classification of Phyllodes Tumour
Base on mitotic activity, infiltration (stomal margin), Stromal overgrowth
- Only the stromal cells have the potential to metastasize.
- All phyllodes tumours should be regarded with malignant potential.
Epidemiology of Phyllodes Tumour
- Incidence 1: 2,100,000, uncommon
- < 0.5% of all breast cancer.
- Median age 45, 25-30 years in Asians.
Risk factor of Phyllodes Tumour
- Li Fraumeni syndrome. ( usually associated with abnormalities in the tumor suppressor protein P53 gene (TP53) located on chromosome 17p13)
- No other known risk factor
Presentation of Phyllodes Tumour
Presentation very similar to Fibroadenoma. Difficult to differentiate.
- 2 key features are large size & rapid growth.
Clinically palpable lump.
- Smooth, multinodular, firm, well defined mass usually 4 – 7 cm.
- Skin stretched, shiny with dilated veins.
- More aggressive tumor will have skin and nipple ulcerations, fixation to the skin or pectoralis muscles has been reported, nipple retraction is rare.
- Palpable axillary lymphadenopathy can be identified in up to 20% of patients but nodal metastases are uncommon.
Investigation for Phyllodes Tumour
Triple Assessment
MMG
- Nonspecific large round, lobulated mass with radiolucent halo around the lesion, due to compression of the surrounding breast stroma.
- Coarse microcalcification has been reported within both fibroadenomas and phyllodes tumours but “malignant” microcalcification is rare.
- No mammographic indicators have been identified that allow differentiation between benign and malignant tumours.
USG
- Non-specific and can mimic that of a fibroadenoma.
- Heterogenous, solid mass with single/multiple cleft like cystic spaces showing posterior acoustic enhancement.
MRI- oval, round, or lobulated masses with circumscribed margins. Signal characteristics can vary with histological gradebut in general
FNA
- Has high false negative
- 3 Cytology features: Fibro myxoid stromal fragments with spindle nuclei, fibroblastic pavements & spindle cells.
CNB preferred.
- Cellularity, mitosis, stromal overgrowth, fragmentation.
- If any doubt regarding biopsy result, WLE is recommended. - Tumor marker (Ki67, p53) & estrogen receptor has no role. Stromal cells: Vimentin, desmin, CD34, bcl2, ER-beta, S100 (variable).
Management of Phyllodes Tumour
Management principle according to sarcoma.
Surgery - Mainstay of treatment.
Breast
- BCS with minimum 1cm histological margin. Inadequate margin warrants re-excision
- Mastectomy – generally for tumor > 5 cm.
- Mastectomy not required, even for malignant phyllodes tumours, provided adequate resection margins can be achieved.
- LR for margin < 1cm - 60%, margin > 1cm - 28%.
Axilla
- ALND only if axillary LN involvement.
- Malignant phyllodes tumours undergo hematogenous spread, lymph node metastases approximately 10% and routine axillary clearance is not recommended.
RT
- Borderline or malignant phyllodes tumors
- Benefit of RT in margin > 1cm - less clear.
Chemotherapy
- Tumor > 5cm
- High risk or recurrent malignant tumors
- Decision is individualized.
- Regime: docetaxel and gemcitabine or doxorubicin with ifosfamide.
Hormonal therapy
- Up to 40% of phyllodes tumours are ER +ve and as with fibroadenomas, almost all are PR +ve.
- Despite these features, the use of endocrine therapy in either the adjuvant or palliative setting has not been extensively studied.
Local Recurrence of Phyllodes tumour
- Usually within 2 years. Shorter for malignant phyllodes
- Resectable : Re-excision with WLE or mastectomy followed by RT.
- Non Resectable : Palliative RT
Metastatic
- Overall, 10% of patients with phyllodes tumours and 20% of patients with malignant tumours develop distant metastases.
- Most common to lungs, bone, and abdominal viscera. Mean OS is 30 months
- Resectable : BCS
- Non Resectable : Chemotherapy.
Surveillance for Phyllodes tumour patient
- History, PE & CXR : 6 mthly for 2 years then annually
- Breast : Annual MMG ± USG in malignant patient.
Prognosis of Phyllodes Tumour
- Benign & borderline : Majority cured after treatment
- Malignant : 60 – 80% 5-year survival.
- Prognosis correlates with histologic grade
- Positive margin status associated with local recurrence
- Tumor size is an independent risk factor for local recurrence
Pathology of Phyllodes Tumour
- Connective tissue and epithelium
- Macro : Round to oval multinodular mass, grey white resemble cauliflower. Pseudo capsule indicate stromal growth into breast tissue. Necrosis & hemorrhage
- Whorled, bosselated cut surface in a leaf-like pattern
- Skin ulceration, hemorrhage and cystic changes in large lesions
- Ulceration and hemorrhage do not indicate malignant behavior per se
- Infarcted or very large benign phyllodes tumor can also show necrosis
- Micro: Leaf-like architecture with cleft like space containing papillary projections. Predominantly stromal elements to differentiate phyllodes from FA. Only the stromal cells have the potential to metastasize.
Aberrations of normal breast development and involution (ANDI)
- The breast passes through phases related to breast development, cyclical change and involution.
- Defining what represents breast disease and what is normal is not a new problem.
- The ANDI classification was developed to provide a framework to help understanding of the pathogenesis and subsequent management of conditions that develop during the specific phases of breast development, cyclical change and involution.
- Some conditions are so common that they should not be considered as disease but rather as aberrations
Fibroadenoma
Painless, unilateral, firm, solitary, mobile benign breast mass (breast mice - due to high mobility) < 3 cm.
> 3 cm suspect Phyllodes.
Estrogen dependent, slow growing, occurs in women between ages of 14 to 35 years (reproductive years), can increase in size during pregnancy or with estrogen therapy. Usually, regress after menopause.
- Malignant transformation 0.002%.
- 50% were LCIS
- 20% were ILC
- 20% were DCIS
- 10% were IDC
- Multiple in 20%
Presentation of Fibroadenoma
Presentation
- Non-tender or painless, Mobile, Solitary, Rapidlygrowing solid lump with rubbery consistency and regular borders.
Investigation for Fibroadenoma
MMG - spectrum of features
- Well-circumscribed discrete oval mass,
- Hypo- or isodense to the breast glandular tissue,
- Mass with macro lobulation or partially obscured margin
- Elderly, typically postmenopausal may become involuted and contain calcifications often producing classic, coarse popcorn, fish bone calcification appearance.
- may also present as crushed stone-like micro-calcification which makes differentiation from malignancy difficult.
USG
- well-circumscribed, round to ovoid, or macro-lobulated mass with generally uniform hypo-echogenicity.
- Intralesional calcification may be seen in ~10%
- ± thin echogenic rim (pseudocapsule) may be seen.
Types of Fibroadenoma
Juvenile fibroadenoma:variant seen in young and adolescent women, with history of rapid growth. There is epithelial and stromal hyperplasia.
Complex fibroadenoma:Fibroadenoma with fibrocystic changes, with the presence of apocrine change, sclerosing adenosisand cyst formation
Giant fibroadenoma :Tumor reaches massive size, i.e. > 5 - 10 cm.
- Rapidly growing masses that cause asymmetry of the breast, distortion of the overlying skin, and stretching of the nipple.
- HPE : more cellular and have less lobular components than do simple fibroadenomas. do not undergo transformation into malignancy.
Pathology of Fibroadenoma
Cytology
- Abundant stromal cell & sheets of epithelial cells in honeycomb pattern.
HPE
- Macro : Cut surface is homogenous, firm, grey white, lobulated, cauliflower like, with a whorl-like pattern and irregularly slit-like spaces.
- Micro : Mixed epithelial (being polyclonal – non neoplastic) proliferation in a single terminal ductal unit surrounded by stromal (fibroblastic – being monoclonal neoplastic) components with intact capsule. The basement membrane is intact. Ratio between stroma to glands is relatively constant throughout the entire lesion.
- 2 Histological types
- Intra-canalicular – stromal proliferation predominates & compress ducts
- Peri-canalicular - Fibrous stroma proliferates around ductal spaces, no compression
- Despite the patterns and histological variants of fibroadenomas, this does not change the benign nature of the lesion
Management of Fibroadenoma
- If increasing size excision mandated TRO malignancy. If > 3cm HPE to rule out phyllodes.
Surgery:
- Excision
- Observation
- Cryoablation - core needle biopsy must be performed before cryoablation to confirm the fibroadenoma
- Percutaneous vacuum-assisted ultrasound-guided excision.
Dietary:
- Insufficient evidence for any benefit in evening primrose oil, Vitamin E, Pyridoxine
- No solid evidence for preventing fibrocystic disease by dietary alterations such as low-fat, high-fiber, and soy isoflavone
Hormonal treatment
- Danazol is an anti-gonadotrophin that acts as an impeded androgen; however, side effects include nausea, depression, menstrual irregularity and headaches
- Bromocriptine is a prolactin inhibitor
- Tamoxifen is a partial anti-estrogen
- With these three agents, pain can be relieved in 75-90% of cases
- Usually hormone treatment is avoided unless the patient has pain to the extent that it interferes with her daily activities
Differences between Fibroadenoma and BENIGN Phyllodes
Differences between Fibroadenoma and MALIGNANT Phyllodes
Staining for Fibroadenoma, Benign Phyllodes and Malignant Phyllodes
