Intraductal Papilloma
Etiology & Epidemiology:
Common sites:
- Central (solitary) (most)
- Peripheral (multiple)
Gross features:
- Central:
- Well-circumscribed round tumour
with papillary fronds
- Attached by one or more pedicles ot the wall of a dilated duct
- Up to 5 cm
- Focal necrosis or hemorrhage maybe in larger
lesions
- Peripheral:
- Usually not palpable (presents with nipple
discharge)
- Mammogram:
- Circumscribed retro-areolar mass of benign
appearance
- Solitary retro-areolar dilated duct
- Microcalcifications (rare)
- Ultrasound:
- Well-defined
- Smooth walled
- Solid
- Hypoechoic nodule
- Lobulated maybe
- Cystic /solid maybe
- Intraluminal filling defect or duct dilation on galactopgraphy
- Larger lesions can have irregular margins on MRI
Histologic features:
- Cohesive but arborescent structure
- Fibrovascular
cores covered by a layer of myoepithelial cells with overlying
epithelial cells
- Epithelial component may be one layer (cuboidal
to columnar) or may show foci of usual ductal hyperplasia (UDH)
- Heterogenous population of luminal cells, myoepithelial cells, UDH, +/-
apocrine metaplasia and hyperplasia
- Apocrine change frequently
- Squamous metaplasia maybe (associated with
infarction)
- Mucinous, clear cell, and sebaceous metaplasia
(rarely)
- Collagenous spherulosis
maybe
- Mitoses extremely rare or absent in epithelial
component
- no cellular atypia
- dilated duct containing branching/arborizing fibrovascular cores
- myoepithelial layer investing the cores
(always)
- smooth-muscle myosin heavy chain, calponin, or p63 can be very useful in confirming
their presence
- myoepithelial hyperplasia occasionally
- also surrounds the periphery of the involved
duct
- IHC findings:
- P63 present in papillary fronds and periphery
of the lesion
- HMWK (CK5/6, CK14) positive in myoepithelial
cells and heterogeneously in UDH areas, negative in apocrine metaplasia
- ER/PR patchy positivity in luminal cells and
in UDH, and negative in apocrine metaplasia
- central (solitary): usually not involving the
terminal-duct lobular unit (TDLU)
- peripheral (multiple): usually have their roots
in the TDLU and may extend into ducts
- stromal fibrosis common (esp. after needling or
torsion)
- sclerosing
papilloma, ductal adenoma
- epithelial cells may become entrapped and mimic
invasive carcinoma (myoepithelial layer intact)
- duct ectasia nearby frequently
- Papilloma with ADH and DCIS:
- Focal population of monotonous cells with cytologic and architectural features of low-grade
ductal neoplasia
- Myoepithelial cells scant or absent in areas of
ADH/DCIS
- (Myoepithelial cells characteristically
present throughout and at periphery for intraductal
papilloma without ADH/DCIS)
- P63 may be scant in the ADH/DCIS component, and
present at the periphery of the lesion
- HMWK (CK5/6, CK14) negative in atypical
epithelial cells usually
- ER uniform positive strong, diffuse in ADH/DCIS
areas
- ADH:
- DCIS:
- >= 3 mm (not required if intermediate or
high-grade nuclei)
- (proportion criteria previously proposed is
not favoured by WHO)
- (Papillary DCIS is a different entity with no
identifiable benign papilloma associated)
Immunophenotype:
Marker:
|
Sensitivity:
|
Specificity:
|
p63
|
|
|
HMWK
(CK 5/6, CK14)
|
|
|
ER/PR
|
|
|
- Papilloma:
- P63 present in papillary fronds and periphery
of the lesion
- HMWK (CK5/6, CK14) positive in myoepithelial
cells and heterogeneously in UDH areas, negative in apocrine metaplasia
- ER/PR patchy positivity in luminal cells and in
UDH, and negative in apocrine metaplasia
- Papilloma with ADH and DCIS:
- P63 may be scant in the ADH/DCIS component, and
present at the periphery of the lesion
- HMWK (CK5/6, CK14) negative in atypical
epithelial cells usually
- ER uniform positive strong, diffuse in ADH/DCIS
areas
Molecular features:
- Monoclonal
- PIK3CA activating point mutations (higher
frequency than in papillary carcinomas)
- AKT1 activating point mutations (higher
frequency than in papillary carcinomas)
- RAS family activating point mutations (higher
frequency than in papillary carcinomas)
- LOH:
- TSC2/PKD1 gene region (16p13) (also found in
papillary carcinomas)
- NOT at D16S476 marker (16q23) (was only found
in malignant papillary lesions)
Other features:
- Associated risk of subsequent invasive breast
carcinoma
- 2X for central, 3X for peripheral
- 7.5X for atypical papillomas
(ipsilateral) (another study showed 5X in central, 7X in peripheral,
bilateral risk)
- Note that this risk is obscured by concurrent
ADH or DCIS in the surrounding breast
- Risk may be more closely related to ADH/DCIS
outside of the papilloma than within it
- Benign
- most common cause of bloody nipple discharge
- small-duct papillomas
are usually multiple and increase the risk of subsequent carcinoma
- usually clinically and mammographically
occult
References:
- Lakhani SR, et al (eds.) WHO Classification of Tumours of the Breast (2012)