 Terminology

o Papilloma with atypical ductal hyperplasia (ADH) or < 3 mm of monomorphic

proliferation resembling DCIS
 Imaging
o No specific imaging findings distinguish malignant from atypical or benign
papillary lesion
 Tend to be larger, irregular, include Ca⁺⁺, peripherally located (> 3 cm
from nipple), multiple
o Mammography: Frequently occult; may see mass(es) ± Ca⁺⁺, isolated Ca⁺⁺ or
dilated duct(s)
o Ductography: May show filling defect(s) or abrupt termination of dilated duct
(cutoff sign)
o US: Hypoechoic solid mass, intraductal mass, complex cystic and solid mass ±
debris/fluid-debris level; often vascular
o MR: High duct signal on T1 and T2: Hyperintense duct; enhancing mass with
washout; linear, clumped NME
 Top Differential Diagnoses
o Benign papilloma, encapsulated papillary carcinoma (EPC)
o Fibroadenoma, sclerosing/nodular adenosis
 Pathology
o CK5/6 staining absent in ADH, DCIS; retained in UDH
o DCIS if ≥ 3 mm of monomorphic proliferation
o p63 (myoepithelial cell marker) absent in EPC capsule
 Clinical Issues
o Spontaneous bloody/clear nipple discharge; occasionally palpable
o Atypical papilloma at CNB or VAB should be excised
o Average 37% rate of upgrade to malignancy at excision (DCIS > invasive
carcinoma) after CNB or VAB
o 4-5x risk of developing breast cancer; 7x if multiple
 Risk equal in both breasts

 Synonyms
o Papilloma with atypia; atypical papillary lesion
 Definitions
o Papilloma or papillary lesion with
 Associated atypical ductal hyperplasia (ADH) within or adjacent
 Or associated monomorphic proliferation which would otherwise meet
criteria for low-grade DCIS but < 3 mm in size
 Cellular atypia in a papilloma can be seen but no longer = atypical
papilloma

 General Features
o Best diagnostic clue
 No specific imaging findings to distinguish malignant papillary lesion
from atypical or benign
  Masses more likely to be larger, irregular, and contain Ca⁺⁺ than
benign papillomas
o Location
 Papillomas located > 3 cm from nipple more likely to contain ADH
than those within 2 cm
 Mammographic Findings
o Frequently not visible; may see mass(es) (segmental distribution, ± Ca⁺⁺),
isolated Ca⁺⁺ or dilated duct(s)
o Ductography: May show filling defect(s) or dilated duct which terminates
abruptly (cutoff sign)
 Ultrasonographic Findings
o Intraductal mass, complex cystic and solid mass ± fluid-debris level (blood)
o Hypoechoic mass, variable shape/margins, posterior enhancement, ±
echogenic foci (Ca⁺⁺), ± cystic change
o Doppler: Internal flow, fibrovascular stalk
o Elastography: Intermediate to hard
 MR Findings
o T1WI
 Precontrast T1-hyperintense duct (blood)
o STIR
 May see T2-hyperintense duct with hypo-/isointense intraductal mass
= noncontrast "MR ductography"
o T1WI C+ FS
 Enhancing mass, linear or clumped NME, rapid initial enhancement
with frequent washout
 Image-Guided Biopsy
o Preferred: Vacuum-assisted biopsy (VAB) > core needle biopsy (CNB); FNA
not reliable
o Including margin of mass may help
 Loss of myoepithelial cells (p63 staining) in fibrous capsule of
encapsulated papillary carcinoma (EPC)
 Imaging Recommendations
o Best imaging tool
 US, US-guided core or vacuum biopsy

 Papillary Neoplasia
o Spectrum from benign papilloma → EPC → invasive papillary carcinoma
o Sclerosing papilloma: Pseudoinvasive growth pattern, ± spiculated, frequently
mistaken for atypia/carcinoma
 Intraductal Epithelial Proliferations
o Papillomatosis lacks fibrovascular core; not true papillary lesion ± usual ductal
hyperplasia (UDH); ADH; DCIS
 Fibroadenoma
o Circumscribed, oval mass ± Ca⁺⁺, not intraductal
 Sclerosing/Nodular Adenosis
 o May form oval mass ± punctate or amorphous Ca⁺⁺

 Microscopic Features
o Papillary neoplasm: Proliferation of epithelial cells overlying fibrovascular
stalk
o ADH within papilloma; < 3 mm area resembling low-grade DCIS; often
concurrent ADH in surrounding breast parenchyma
o CK5/6 staining absent in ADH, retained in UDH

 Presentation
o Most common signs/symptoms
 Spontaneous bloody or clear nipple discharge; palpable if large or
within hugely dilated duct
 Often asymptomatic, screen-detected
 Natural History & Prognosis
o 4-5x risk of future breast CA; multiple: 7x risk, both breasts
 Treatment
o Surgical excision recommended when diagnosed on CNB or VAB; no role for
imaging follow-up
o Meta-analysis of 26 studies: 37% (95%CI 29 to 44) upgrade rate to carcinoma
at excision (Wen): DCIS > invasive ductal carcinoma

 Consider
o Peripheral, multiple papillomas more often atypical than solitary, central; ↑
upgrade to malignancy
o Factors that ↑ upgrade to malignancy: Multiplicity, ↑ vascularity, palpability
(some series)
o Atypical papilloma at CNB or VAB should be excised
o Frequent upgrade of benign papilloma on CNB to atypical papilloma at
excision