Papillary lesions of the breast

Cecily Quinn Irish National Breast Screening Programme & St. Vincent’s University Hospital, Dublin

Papillary lesions of the breast

Central, solitary Classical

Sclerosing

Complications

Variants

Central, solitary, Classical (intracystic) ? In situ ? Invasive

Solid

Invasive

Peripheral, multiple Peripheral, multiple

Benign intraduct papilloma

• Large ducts

• Solitary

• Female • 30 – 50 years • Symptomatic

– Nipple discharge – Lump

• Mammographic lesion

Intraduct papilloma

Intraduct papilloma

Microscopy

• Intraductal lesion

• FV cores covered by epithelial & myoep. cells

p63, calponin, actin, sm. myosin

• Apocrine metaplasia 20%

• Epithelial hyperplasia Cytokeratin 5/6 (HMW) useful

• Myoepithelial hyperplasia

p63

Papillomatosis (Peripheral papillomas)

Microscopy

• Papillary fronds supported by fibrovascular stalks in multiple TDLUs

• Epithelial & myoep. cell layer present

Complications of papilloma

Sclerosis •Entrapment of tubules in duct wall •Overdiagnosis of malignancy

Infarction •Spontaneous •Post core biopsy •Squamous metaplasia •Cytologic atypia •Difficulty in diagnosis

Sclerosing papilloma

• Papilloma that has become sclerotic

• TDLUs affected by sclerosing adenosis surround & invaginate duct

taking a covering of epithelial and myoepithelial cells into the lumen - broad papillae containing glandular structures

Sclerosing papilloma

Variants of papilloma

Ductal adenoma Adenomyoepithelioma Pleomorphic adenoma

Papilloma with atypical intraduct epithelial proliferation (AIDEP)

Papilloma with AIDEP

• Papilloma with ADH or non HG DCIS < 1/3 of lesion

= Atypical papilloma

• Papilloma with non high grade DCIS >1/3 and <90% or Papilloma with high grade DCIS

= Papilloma with DCIS

• Papilloma with DCIS > 90% of lesion

= Papillary carcinoma (in situ)

Papilloma with AIDEP

• Papilloma with ADH = Papilloma with ADH!

• Papilloma with DCIS = Papilloma with DCIS!

• Biological course most likely determined by

pathology in the surrounding breast tissue

Classical papillary carcinoma Epidemiology

• Large ducts

• Central

• Female • 50-70 years • Symptomatic

– Nipple discharge – Subareolar lump

• Mammographic lesion

Classical papillary carcinoma

• Friable bosselated mass within a cystic space • ? Dilated duct / ? Thick capsule

• Intracystic papillary carcinoma (descriptive term)

Classical papillary carcinoma Microscopy

• Circumscribed

• Thick capsule

• Complex papillary architecture

• ‘Falling apart’

• Haemorrhage

Classical papillary carcinoma Microscopy

• Papillae slender cores

• May be fibrotic

• Covered by atypical epithelial cells

• May be multilayered

• Cytokeratin 5/6 negative

• No myoepithelial cells within the lesion

p63

Classical papillary carcinoma Dimorphic variant

• No me cells on fv cores

• Epithelial cells in direct contact with cores morphologically different ‘globoid’

• May mimic ME cells – ME marker negative

– Cam 5.2 positive

Myoepithelial cells were completely absent in 33/40 (82%) IPCs and only focal in the remaining 7/40 (18%).

IPC constitutes a spectrum of in situ and invasive carcinoma with a predominance of the latter. IPC carries a very good prognosis.

Classical papillary carcinoma ? True nature

• Traditionally regarded as in situ lesion

• Recent studies - no peripheral ME cell layer

• Case reports of ipsilateral LN metastases

• Indolent biological course

p63

Solid papillary carcinoma Epidemiology

• Female • 60-80 years • Symptomatic

– Nipple discharge – Subareolar lump

• Mammographic lesion

Solid papillary carcinoma Microscopy

• Nodular

(one or more)

• Well circumscribed

• May be fibrous

capsule

Solid papillary carcinoma Microscopy

• Uniform population of epithelial cells

• Mild to moderate atypia

• Solid growth pattern

• Interrupted by narrow FV cores – scaffolding

• No classical papillae

• No ME cells within lesion

Solid papillary carcinoma Microscopy

• Cells have granular eosinophilic cytoplasm

• Cytokeratin 5/6 neg.

• Focal chromogranin & synaptophysin pos.

• Endocrine DCIS Azzopardi JG and colleagues.

Histopathology 1985

Chromogranin

Grimelius

Invasive papillary carcinoma Microscopy

• Papillary architecture

• Infiltrative outline

• Rare

• Conventional IDC adjacent to ‘papillary carcinoma’ more common

Papillary carcinomas low histological grade, IHC markers consistent with luminal type,

lower rate of lymph node metastases & less genomic aberrations than grade and ER matched IDCs

Papillary carcinomas are part of the spectrum of ER positive breast cancers.

Papillary DCIS Microscopy

• Malignant equivalent of papillomatosis

• Variant of usual type ductal carcinoma in situ

• Multiple small to medium sized ducts involved

Papillary lesions Diagnosis on needle

core biopsy

Papillary lesion on NCB

B3a B3b

Guidelines for non operative diagnosis and reporting in breast cancer screening. NHSBSP UK June 2001

It is anticipated that the majority of papillary lesions will be designated B3

Papillary lesion on NCB

• Assess H& E Are there ME cells on papillae? Associated epithelial proliferation Benign or atypical? • Immunohistochemistry ME cell markers – p63, calponin Epithelial proliferation - Cytokeratin 5/6

• Check radiology Size of lesion Any unusual features

Papillary lesions Non-operative diagnosis

B2 B3 B4 B5

Histopathology only one part of the diagnostic process Talk to our multidisciplinary colleagues

And LISTEN!!

Relationship of papilloma to carcinoma?

Concurrent risk Pathology heterogeneous

Subsequent risk Increased

Accompanying changes (atypia or DCIS) within the lesion or surrounding tissue main risk determinant

Predictive value of NCB diagnoses of lesions of uncertain malignant potential in abnormalities

detected by mammographic screening

• 124 patients NCB diagnosis of papilloma

• Malignancy in 13 patients (10%)

El-Sayed ME, Rakha EA, Reed J, et al. Histopathology 2008;53:650-657

Atypia on NCB in 9/25 patients (36%)

No atypia on NCB in 4/99 patients (4%)

Can we reduce surgical excision

rate for B3 papillary lesions ?

Mammotome biopsy

Papillary lesion

No atypia Atypia

No further action Excise or observe