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Breast-nonmalignant

Benign tumors / changes

Papilloma of breast

 

Reviewer: Hind Nassar, M.D. in January 2009 (see Authors page)

Revised: 16 April 2010, last major update April 2010

Copyright: (c) 2002-2010, PathologyOutlines.com, Inc.

 

Definition

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● Intraductal proliferation of epithelial and myoepithelial cells overlying fibrovascular stalks

 

Terminology

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● “Papillomatosis” is a confusing term because it may refer to hyperplasia or multiple papillomas

 

Epidemiology

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● Common; mean age 48 years

 

Sites

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Etiology

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● Arises from large or small ducts (arising from terminal duct lobular unit)

● May be related to ductal adenoma

 

Clinical features

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● Central or peripheral

Central (large duct): close to nipple within principal lactiferous ducts, 90% solitary, 70% associated with nipple discharge; usually ages 30-49 years but any age

Peripheral: often clinically occult, discovered by mammographic calcifications

Single papillomas: no increased risk of subsequent malignancy with or without associated ADH/ALH (Am J Surg Pathol 2006;30:665), although in one study, 16% contained carcinoma (Eur J Surg Oncol 2010;36:384)

Multiple papillomas: increased risk of subsequent malignancy, particularly if ADH/ALH is present (Am J Surg Pathol 2006;30:665)

- 5 or more papillomas are associated with coexisting atypical (ALH/LCIS, ADH) or malignant breast lesions, also recurrence and contralateral disease (Hum Pathol 2003;34:234)

Atypical papillomas: distinction from papillary DCIS is based on size of atypical area or % of papilloma

- 4x increased risk of invasive carcinoma compared to papillomas without atypia, usually near site of original papilloma (Cancer 1996;78:258

 

Prognostic factors

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Case reports

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● 47 year old woman with coexisting breast and sentinel node papillomas (Am J Surg Pathol 2008;32:784)

57 year old man on long-term phenothiazines (Breast Cancer 2006;13:84) 

Associated with Costella syndrome (Cir Esp 2007;81:345)

 

Treatment

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● Local excision or microdochectomy (removal of breast duct)

● Core biopsy diagnosis of papilloma even without ADH probably requires excision (Ann Surg Oncol 2008;15:2272, Am J Surg Pathol 2002;26:1095, Eur J Surg Oncol 2008;34:1304, AJR Am J Roentgenol 2006;186:1328, Cancer 2009;115:2837), but see Am J Clin Path 2004;122:440, Am J Clin Path 2004;122:217 (no need for excision if no atypia)

 

Clinical images

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Gross description (Macroscopy)

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● Well circumscribed, polypoid intraductal mass, usually < 3 cm, soft, hemorrhagic

● Often infarcted 

 

Gross images

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Polypoid intraductal mass


Other: hemorrhagic cyst with tan tumor

 

Micro description (Histopathology)

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● Multiple papillae in complex arborizing pattern with well-developed vascular connective tissue core surrounded by epithelial and myoepithelial cells

● Benign nuclei, frequent apocrine metaplasia, inflammation

● May arise within a large cystic duct, have comedo-type necrosis without DCIS (Ann Diagn Pathol 2004;8:276), rarely sebaceous metaplasia (Virchows Arch 2001;438:505)

Infracted cases may have squamous metaplasia or appear pseudoinfiltrative due to fibrosis (Hum Pathol 1984;15:764

● Fibrosis at edge of papillomas may entraps glands and resemble invasion (Semin Diagn Pathol 2010;27:13)

● Glandular proliferation within stalks may resemble cribriform DCIS

● Needle biopsies can deposit clusters of benign cells in a distribution that resembles invasive carcinoma

 

Micro images

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Various images

 

 

            

 

      

 

Dilated ducts containing connective tissue cores with multiple fingerlike projections

 

 

               

Multiple nodules and stromal fibrosis

 

 

      

Epithelial and myoepithelial cells                                                  

 

 

  

Stromal fibrosis resembles invasion

 

 

         

Central papilloma                                     Papilloma with florid ductal hyperplasia

 

 

                                               

Encysted papilloma           Peripheral papilloma         Within lymph node

with hyperplasia

 

 

               

Apocrine intraductal papilloma with large nuclei and prominent nucleoli 

 

 

      

Solid type

 

 

               

Fusion of adjacent papillae

creates gland-like spaces

 

 

                                  

Resembles sclerosing                      Infarcted papilloma

adenosis

 

 

`                                              

With fibroblasts, fibrosis                  Small ducts surrounded by

and chronic inflammatory                hyalinized fibrous tissue

infiltrate

 

 

         

Squamous metaplasia

 

 

      

With spindle cells                                     Vessels but not spindle

      cells are actin+

 

 

                               

Atypia/malignancy              Papilloma with atypia        Papilloma with separate focus of ADH

 

 

         

Papilloma with severe atypia                                                   With micropapillary DCIS

 

 

      

With LCIS spreading in a pagetoid manner beneath ductal epithelium (plaque-like pattern)

 

 

         

Various images     p63                            Smooth muscle     CD10 and smooth

                                                                      actin                         muscle actin

 

Other images: #1#2;  #3 

 

Virtual Slides

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Intraductal papilloma

 

Peripheral papillomas and usual ductal hyperplasia

 

Videos

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Intraductal papilloma

 

Cytology description

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● High positive predictive value (Diagn Cytopathol 2006;34:818)

Infarcted papillomas - early stages show numerous degenerated cells with smudged nuclei, ghost cells and necrotic debris; late stages show clusters of fibroblasts, ductal cells and necrotic debris (Diagn Cytopathol 2006;34:373)

 

Cytology images

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Other images: #1#2#3

 

Positive stains

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Epithelium:  CK 5/6, CK14, 34betaE12 (Virchows Arch 2007;450:539); also CD44s (J Clin Pathol 1999;52:862)

Myoepithelium: actin, S100, p63 (Am J Surg Pathol 2001;25:1054), calponin, smooth muscle myosin heavy chain (Am J Clin Path 2005;123:36), CD10 (Mod Pathol 2002;15:397)

 

Negative stains

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Electron microscopy descriptions

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Electron microscopy images

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Molecular / cytogenetics description

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● Clonal

 

Molecular / cytogenetics images

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Differential Diagnosis

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Papillary DCIS: delicate or absent fibrovascular core, often atypical nuclei or atypical mitotic figures, pseudostratification, usually no apocrine metaplasia; other DCIS may be present, 71% have no/incomplete myoepithelal layer, 76% are 34betaE12 negative, 67% are positive for neuroendocrine markers (Virchows Arch 2007;450:539)

Micropapillary DCIS

Invasive papillary carcinoma: invasion into stroma, no myoepithelial layer

 

Additional references

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End of Breast-nonmalignant > Benign tumors / changes > Papilloma

 

 

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