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Breast-nonmalignant

Atypical hyperplasia

Atypical lobular hyperplasia (ALH) of breast

 

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

Revised: 5 October 2012, last major update March 2010

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

 

Definition

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● Part of spectrum of lobular neoplasia, which also includes LCIS (see Breast-malignant chapter)

 

Terminology

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● Also called lobular intraepithelial neoplasia 1 (LIN1) and occasionally flat epithelial atypia (although this is a separate topic, click here)

 

Epidemiology

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Sites

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Etiology

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Clinical features

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Usually not associated with specific mammographic findings

Does not form a palpable mass

19% develop invasive cancer at mean 15 years after diagnosis (4-5x usual risk), 42% are special subtypes with good prognosis (Cancer 2006;107:1227)

 

Prognostic factors

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● 4-5x usual risk of carcinoma, higher in ipsilateral breast, higher if age < 50 years (Am J Surg Pathol 2002;26:421, Cancer 2007;109:180); risk increased further if ductal involvement (Hum Path 1988;19:201)

 

If present at core biopsy, is surgical excision appropriate?

Many studies support excision due to risk of subsequent in situ or invasive carcinoma

Yes: DCIS/invasive carcinoma occurs in 6-8% (Archives 2008;132:979, Am J Surg Pathol 2007;31:717), invasive ductal/lobular carcinoma occurs in 25% (Am J Surg Pathol 2005;29:534, AJR Am J Roentgenol 2008;190:637)

No, unless: radiologic-pathologic discordance suggests that the targeted lesion was not excised, other high risk lesions such as ADH are present that would warrant further surgery, ALH has features resembling DCIS (Am J Surg Pathol 2002;26:1095), ALH has pleomorphic features (Mod Pathol 2008;21:1208, Cancer 2008;112:2152), or there is diffuse lobular neoplasia at core biopsy (Breast J 2007;13:55)

No: because there is no significantly increased risk and any subsequent cancer is diffuse, bilateral and not at location of biopsy (Am J Surg 2009;198:792)

 

Case reports

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Treatment

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● Life long follow up is recommended

 

Clinical images

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Gross description (Macroscopy)

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● Usually an incidental finding, not a palpable mass

 

Gross images

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Micro description (Histopathology)

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● Resembles LCIS but does not fill or distend 50% or more acini within a lobule (i.e. some features of LCIS but not uniformly present throughout entire lobule)

● May be no/minimal inflammatory response

 

Micro images

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Atypical cells with focal preservation of luminal spaces

 

 

           

Pagetoid ductal involvement and clover leaf pattern

 

 

Involving sclerosing adenosis 

 

 

AFIP Images (Figure number is in URL)

                                                                       

Focal preservation of luminal spaces               Neoplastic cells occupy <50% of acini

 

 

                                                                      

Loss of cell cohesion, disorderly spread and             Haphazardly dispersed atypical cells

pagetoid involvement into normal acini                        (arrows) have partially replaced normal

(but <50% of acini involved)                                             lobular cells

 

 

                                                                       

Expansion of acini on left side                                        Tumor cells with loss of cohesion have

almost entirely filled lumina

 

 

                                                                       

Clover-leaf pattern of proliferation around                  Ill defined glandular proliferation

terminal duct with preservation of normal                  around terminal duct

epithelium centrally

 

 

         

 

         

 

          

ALH - various images

 

 

ALH in fibroadenoma

 

 

               

ALH and LCIS


                                                               

Microglandular adenosis with adjacent ALH              Tubular adenoma with ALH

 

 

E-cadherin is focally negative

 

Virtual Slides

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ALH and ADH involving a fibroadenoma                       ALH and focal LCIS

 

 

ALH involving sclerosing adenosis

 

Videos

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Cytology description

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● Loosely cohesive cell clusters composed of uniform cells with occasional intracytoplasmic lumina, minimal nuclear atypia but frequent eccentric nuclei

 

Cytology images

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Positive stains

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● ER (ER alpha stronger than ER beta, Virchows Arch 2007;451:893)

CK 34betaE12 (polarized)

● p120catenin (cytoplasmic, not membranous staining, Am J Surg Pathol 2007;31:427)

Also ER, PR

 

Negative stains

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● E-cadherin (Mod Path 2005;18:741), HER2

 

Electron microscopy descriptions

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● Intracytoplasmic lumina, microvilli with secretory droplets; basement membrane and myoepithelial cells are present

 

Electron microscopy images

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Molecular / cytogenetics description

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● Diploid

 

Molecular / cytogenetics images

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Differential Diagnosis

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● Solid ductal intraepithelial neoplasias: usually cohesive cells with multiple secondary lumina, rosette-like nuclei, E-cadherin+

 

Additional references

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Stanford University

 

End of Breast-nonmalignant > Atypical hyperplasia > Atypical lobular hyperplasia (ALH) of breast

 

 

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