Breast-nonmalignant - Papilloma of breast

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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

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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