Update on Papillary Lesions of

the Breast

Victor P. Carlo, MD, FCAP

Laboratory Director

Anatomic Pathology

Hospital Auxilio Mutuo

Integrated Pathology, PSC

Importance of papillary lesions

• Often challenging histologic

diagnoses

– Benign vs. malignant

– In situ vs invasive

• Management issues

– Papilloma without atypia on core needle

biopsy

– Sentinel node biopsy for papillary

carcinoma

– Staging of encapsulated papillary

carcinoma

Papillary neoplasm:

Definition

• Neoplasms

characterized by

fibrovascular

cores with

surrounding cells

in an arborizing

or wart-like

growth pattern

Main patterns of papillary

neoplasms

• Ovoid well circumscribed mass

• Multiple smaller ducts

• Infiltrative

Ovoid well-

circumscribed

mass

• Papilloma

• Atypical papilloma

• Solid papillary

carcinoma

• Encapsulated

papillary

carcinoma

Multiple smaller ducts

• Papillomatosis

• DCIS, papillary

pattern

Isolated or associated with other

forms of carcinoma

Papillary

neoplasm

DCISINFILTRATING

CARCINOMA

WHO 5th edition

Papillary Tumors of the breast• Intraductal papilloma

– Without atypia

– Atypical papilloma / ADH in papilloma

– Papilloma with ductal carcinoma in situ (within papilloma)

• Ductal carcinoma in situ, papillary pattern

• Encapsulated papillary carcinoma

• Solid papillary carcinoma

– In situ

– With invasion

• Invasive Papillary Carcinoma

Intraductal papilloma (IDP)

• Central and solitary

– Unilateral clear, sometimes bloody

nipple discharge

– Palpable mass

– Any age

– Size: mm to more than 5 cm

• Peripheral papillomas

– Rare, usually incidental

Intraductal papilloma (IDP)

WHO Classification of Breast

Tumors, 5th edition, 2019

• Benign neoplasm within a duct

composed of papillary projections

with fibrovascular cores covered by

an epithelial and myoepithelial layer

Papillomas have variable

morphologic spectrum• Usual ductal hyperplasia

• Apocrine metaplasia

• Sclerosis

• Infarction

• Epithelial cell displacement post core bx

– Stroma

– Vessels

• ADH or DCIS within a papilloma (atypical

papilloma)

• ADH or DCIS in ducts adjacent to

papilloma

Displaced cells

Atypical papilloma has been

variably defined

• Page: Papilloma with a focus of DCIS

measuring less than 3 mm

• Tavasolli:

– Histology consistent with DCIS

involving less than 30% of a papilloma

• Schnitt: qualitative rather than

determined by extent

– Papilloma with DCIS

– Papilloma with ADH

Atypical papilloma vs DCIS in

papilloma

WHO 5th classification

• Atypical papilloma

• ADH in papilloma

• Papilloma with

ADH

– ADH is less than 3

mm in size

– Within the

papilloma

• DCIS in papilloma

– Low nuclear grade

and more than 3

mm

– Intermediate or

high nuclear grade,

any size

Atypical papilloma

Diagnostic criteria

Kraus and Neubecker

Cancer, 1962;15:444-455.

• PAPILOMA

– Epithelial +

myoepithelial

– Normochromatic nuclei

– Complex glandular

pattern

– Often prominent

fibrosis with epithelial

entrapment

– Hyperplasia in adjacent

ducts

– Sclerosing adenosis

sometimes present

• PAPILLARY CA.

– Epithelial only

– Hyperchromatic nuclei

– Cribriform pattern

– Delicate or absent

fibrosis

– ADH, DCIS often

present in adjacent

ducts

– Sclerosing adenosis

usually absent

PAPILLOMA PAPILLARY CARCINOMA

Sources of error

• Heterogenous morphology of

papillomas

• Papillary carcinoma is rare (<1% of

all carcinoma)

• Sampling on core biopsy

• Dimorphic papillary carcinoma

• Misinterpretation of IHC or lack of

correlation with H&E stains

Problems with papillary lesions

on core needle biopsy

• US features of benign and malignant

papillary neoplasms overlap

• Reliability of diagnoses

• Reliability of sampling

– Atypia is unevenly distributed in

papillomas

– Surrounding breast stroma

Dimorphic encapsulated papillary

carcinoma (EPC)

Prospective Excision of Papilloma

without atypia multi-institutional

study (TBCRC 034)

116 papillomas w/o atypia (LOCAL)

31 (27%) NOT confirmed

2 (6%) Atypical papilloma

8 (26%) ADH near IDP

21 (68%) benign mimics of IDP

85 (73%) confirmed

Nakhlis, Ann Surg Oncol. 2021 May;28(5):2573-2578

CENTRAL REVIEW

Should all papillary neoplasms

be excised?

… including benign papillomas

diagnosed on core biopsy?

Reference Sample

size

Papilloma

(%)

Atypia

(%)

Malignant

(%)

Upgrade (%) Recommendatio

n

Rozentsvayg 67 81 12 7 19 Excision

Sakr 48 79 6 15 21 Excision

Rizzo 86 75 14 10 25 Excision

Skandarajah 80 68 14 19 33 Excision

Ashkenazi 20 65 20 35 35 Excision

Valdes 36 84 0 14 14 Excision

Liberman 25 80 0 20 20 Excision

Mercado 36 39 22 6 28 Excision

Gendler 13 69 16 16 31 Excision

Puglisi 31 94 0 6 6 Excision

Rosen 14 78 14 7 21 No excision

Ahmadiyeh 29 97 0 3 3 No excision

Renshaw 8 8 0 0 0 No excision

Agoff 11 10 0 0 0 No excision

Plantade 37 86 0 14 14 No excision

Ivan 6 100 0 0 0 No excision

Sydnor 38 97 0 3 3 No excision

Ipsilateral carcinomas and ADH on excision after core biopsy dx of papilloma w/o atypia

Brogi,E, USCAP 2021

Rad path concordant CNB of

papillary lesion without atypia

• American Society of Breast Surgeons-

Guidelines for management of high-risk

lesions

• Decision to excise based on risk,

including such criteria as size,

symptomatology, including palpability and

presence of nipple discharge; and breast

cancer risk factors

• Follow closely with imaging those that are

not excised

Management of atypical papillomas

Atypical papilloma

• Complete excision with

close follow up

Atypical papilloma + DCIS

in surrounding tissue

• Manage according to

findings in adjacent

tissue

Diagnostic criteria

Kraus and Neubecker

Cancer, 1962;15:444-455.

• PAPILOMA

– Epithelial +

myoepithelial

– Normochromatic nuclei

– Complex glandular

pattern

– Often prominent

fibrosis with epithelial

entrapment

– Hyperplasia in adjacent

ducts

– Sclerosing adenosis

sometimes present

• PAPILLARY CA.

– Epithelial only

– Hyperchromatic nuclei

– Cribriform pattern

– Delicate or absent

fibrosis

– ADH, DCIS often

present in adjacent

ducts

– Sclerosing adenosis

usually absent

Myoepithelial cell markers

• SMA

• SMMHC

• Calponin

• P63

• Ck 5/6

• 34BE12

• CD10

Collins LC, Carlo VP, et al. Am J Surg Pathol 2006:30 (8):1002-1007

Immunohistochemistry in papillary

breast lesions

• Myoepithelial cell markers (MEC)

• Lack of MEC at the periphery of

encapsulated papillary carcinoma (EPC)

and solid papillary carcinoma (SPC)

suggests these may represent

circumscribed forms of invasive tumors

Encapsulated Papillary Carcinoma

(EPC) with invasion (NOS)

Solid Papillary Carcinoma with

extracellular mucin secretion

Prognosis of encapsulated

papillary carcinoma

• Data is limited, mostly retrospective

studies

– Reports of lymph node metastasis in

older reports of “intracystic”papillary

carcinoma

– Recent data report excellent prognosis

when EPC occurs as an isolated lesion

• Carter D, et al. Cancer. 1983;52:14–19.

• Lefkowitz M. Hum Pathol. 1994;25:802–809.

Staging of encapsulated papillary

carcinoma (EPC)

WHO

• EPC only: stage as pTis

• EPC + other infiltrating carcinoma

(NOS): stage as per infiltrating

component

Lymph node mets in pure EPC

• Mulligan AM, O’Malley F., Int J Surg Pathol. 2007 • 15(2): 143-147

Rakha EA, Ellis IO, et al.Am J Surg Pathol 2011; 35(8): 1093-1103

IPC (n=207) SPC (n=30)

Age, median 69 76

Size, median (range) cm 1.7 (0.3-9.0) 1.5 (0.3- 3.2 cm)

Grade 1 63 (47%) 12 (40%)

Grade 2 67 (50%) 15 (50%)

Grade 3 3 (3%) 3 (10%)

No DCIS 43 (30%) 9 (33%)

DCIS present 102 (70%) 18 (67%)

LVI absent 165 (98%) 19 (95%)

LVI present 4 (2%) 1 (5%)

Lymph node negative 61 (97%) 15 (88%)

Lymph node metastasis 2 (3%) 2 (12%)

No recurrence 78 (86%) 24 (96%)

Diagnosed as recurrent 6 (6%) 1 (4%)

Recurred during follow up 7 (8%) 0 (0%)

Sentinel node biopsy

in encapsulated papillary

carcinoma and solid papillary

carcinoma

• Limited data available

• Wang, Clin Breast Cancer 2017

Apr;17(2):127

• Risk tolerance?

• Age

• Infiltrating component on core

biopsy?

• Imaging findings

Summary

• Papillary lesions show considerable

morphologic overlap

• MEC markers are very useful in the

differential dx of papillary

neoplasms

• For papilloma without atypia,

pathologic-radiologic

correlation and other clinical

features are crucial for management

– Low risk of DCIS or invasive on excision

Pure EPC:

Diagnostic and Management

Recommendations

• Perform MEC markers on all EPC

• Some may represent true DCIS, manage

accordingly

• Some (about 85%) represent invasive carcinoma,

special type

– Staging with sentinel node may be reasonable

– Exclude associated infiltrative carcinoma,

stage accordingly

– Manage similar to DCIS if node(s) are negative

Summary Cont.

EPC + invasive carcinoma NOS

• Report only the size of the NOS

invasive carcinoma

• Manage accordingly to stage of NOS

component

Summary Cont.