Breast-nonmalignant - Columnar cell lesions of breast

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Breast-nonmalignant

Fibrocystic changes

Columnar cell lesions of breast

Reviewer: Hind Nassar, M.D. in January 2010 (see Authors page)

Revised: 6 October 2012, last major update May 2010

Definition

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● Enlarged terminal duct lobular units (TDLU) with dilated acini lined by tightly packed columnar epithelial cells with prominent apical cytoplasmic snouts and intraluminal secretions

Terminology

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● Also called blunt duct adenosis, columnar alteration with prominent apical snouts and secretions (CAPPS), columnar metaplasia, enlarged lobular units with columnar alteration (Am J Surg Pathol 2005;29:105)

● Lesions without atypia are called columnar cell change (CCC) or columnar cell hyperplasia (CCH) (Semin Breast Dis 2004; 21:18)

● Lesions with atypia are called flat epithelial atypia

Classification

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● Classification below is by Schnitt (Adv Anat Path 2003;10:113) modified by Simpson (Am J Surg Pathol 2005;29:734)

● Note: all have variable dilated acini, cytoplasmic snouts and intraluminal secretions

● Several types may coexist in same breast

● Note: classifications with atypia (types 3-6) have lowest diagnostic reproducibility (J Clin Pathol 2005;58:705)

● Type 1 (columnar cell change, CCC): 1-2 cell layers

● Columnar cells have uniform ovoid/elongated nuclei perpendicular to basement membrane; no/inconspicuous nucleoli; may have apical snouts but usually not prominent

● Type 2 (columnar cell hyperplasia, CCH): >2 stratified cell layers with variable nuclear crowding and cellular micropapillations, but no complex architectural patterns (i.e. no rigid bars, bridges or well-formed micropapillary structures); cytology similar to type 1 but may have hobnail cells

● Associated with intraluminal calcification

● Type 3 (columnar cell hyperplasia with architectural atypia): >2 stratified cell layers with complex architectural patterns (micropapillary, tufts, fronds, arcades, rigid bridges or punched out spaces); type 2 cytology

● Type 4 (columnar cell hyperplasia with cytologic atypia): type 2 architecture; mild to moderate cytologic atypia, may resemble tubular carcinoma

● Type 5 (columnar cell hyperplasia with cytologic and architectural atypia): type 3 architecture; type 4 cytology

● Type 6 (columnar cell change with cytologic atypia): 1-2 cell layers; type 4 cytology

● Note: can also be classified as (a) no nuclear atypia and less pronounced hyperplasia; or (b) generally more atypical (Pathology 2010;42:28)

● WHO recognizes flat epithelial atypia (FEA) as a category defined by the presence of “a neoplastic intraductal proliferation characterized by replacement of the native epithelial cells by a single or 3-5 layers of mildly atypical cells” (synonyms: Simpson’s Type 4 and Type 6 and Schnitt’s CCC and CCH with cytologic atypia) (WHO Pathology and Genetics of Tumours of the Breast and Female Genital Organs, 2003, pages 65-66)

Epidemiology

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● Mean age younger than ADH or DCIS

● Frequent finding in breast biopsies for mammographic calcifications (Am J Surg Pathol 1998;22:1521); may be associated with lobular neoplasia in these patients (Am J Clin Pathol 2008;130:254)

Sites

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● Affect both breasts

● Can affect breast inclusions in lymph nodes (Am J Clin Pathol 2008;130:21) (J Surg Oncol 2007;95:593)

Etiology

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● Unknown

Radiology

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● Calcifications can be round, with indistinct shape, or pleomorphic (Pathology 2009;41:18)

● In most cases, indeterminate or suspicious microcalcifications or BI-RADS category 4

● Ossifying-type calcifications: a peculiar, infrequent type of calcification found in mammary duct lumina, with a central core of calcification and a rim of ossifying-type matrix reminiscent of osseous tissue but not lined by osteoblasts or osteocytes (Archives 2002;126:995)

Clinical features

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● Non-specific, similar to fibrocystic change in general, usually a mammographic finding

Prognostic factors

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● May be associated with atypical hyperplasia, but otherwise no significantly increased risk of breast carcinoma (Cancer 2008;113:2415)

Case reports

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● 43 year old woman with columnar cell hyperplasia and mucocele-like lesion (J Med Case Reports 2008 Apr 30;2:138)

Treatment

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● Excision is recommended if atypia is found at core biopsy (Am Surg 2007;73:984); excision is not done in cases without atypia.

● Recommended to merely identify ADH, DCIS or invasion on excision; in these cases the treatment is similar to that of ADH, DCIS or invasive carcinoma

● If flat epithelial atypia (FEA) is the “highest grade” lesion found on excision, submit additional tissue / obtain additional levels to rule out ADH/DCIS (Am J Surg Pathol 2002;26:1095); if ADH/DCIS is not present, no further treatment is required (Mod Pathol 2009;22:762)

Gross description (Macroscopy)

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● No specific gross features

Micro description (Histopathology)

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● Enlarged terminal duct lobular units (TDLUs) lined by tightly packed columnar epithelial cells with prominent apical cytoplasmic snouts and intraluminal secretions

● Cells may have clear or granular cytoplasm

● Variable cytologic atypia and architectural complexity (see classification)

● May have pseudoangiomatous hyperplasia-like stroma (Int J Clin Exp Pathol 2009;3:87)

● By hierarchical cluster analysis, features are very heterogeneous (Pathology 2010;42:28)

Micro images

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Columnar cell change - various images

PASH-like stroma (H&E) ER-beta+ CD34+

Ossifying-type calcifications (dense basophilic, smooth, round calcifications surrounded by ossifying matrix

”Blunt duct adenosis”

Adenosis with columnar cell change with DCIS

Columnar cell hyperplasia In mucocele-like tumor

Columnar cell hyperplasia with atypia Columnar cell change with flat epithelial atypia

Virtual Slides

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Columnar cell change with atypia

Cytology description

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● Flat sheets of cells with distinct cell borders, finely granular cytoplasm, enlarged nuclei

● Usually few myoepithelial cells

● Resembles papillary neoplasms and well differentiated adenocarcinoma (Diagn Cytopathol 2007;35:73)

● Atypical features: cohesive 3D clusters of enlarged polygonal epithelial cells mixed with myoepithelial cells centrally and palisading columnar cells peripherally; often bipolar nuclei and apical snouts (Diagn Cytopathol 2004;31:370)

Positive stains

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● ER (strong, Breast J 2005;11:326), PR

● Also bcl2, Ki-67 increased but less than carcinoma (Hum Path 2007;38:284)

● Low molecular weight keratin (CK 8, 18, 19)

Negative stains

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● High molecular weight keratin (CK 5/6, CK14, 34betaE12) HER2, p53

Electron microscopy descriptions

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● Epithelial cells and myoepithelial cells plus associated basement membrane-like material (Breast J 2000;6:199)

Molecular / cytogenetics description

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● Appears to be a clonal (neoplastic), non-obligate, intermediate step in development of some forms of low grade DCIS and invasive carcinoma (Am J Surg Pathol 2005;29:734); present in 95%+ cases of tubular carcinoma (Am J Surg Pathol 2007;31:417, Adv Anat Pathol 2008;15:140, Am J Surg Pathol 2009;33:1646)

● No mutational changes in simple columnar change; progressive accumulation of allelic damage with atypia, DCIS or invasive carcinoma, involving 9q, 10q, 17p and 17q (Mod Path 2006;19:344)

Differential Diagnosis

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● Atypical ductal hyperplasia, DCIS

● Apocrine metaplasia

● Cystic hypersecretory hyperplasia: secretions, but no apical snouts, no apocrine metaplasia

● Cysts

Additional references

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● Stanford University

End of Breast-nonmalignant > Fibrocystic changes > Columnar cell lesions

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