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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: 25 March 2010, last major update March 2010

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

Involving sclerosing adenosis

AFIP Images (Figure number is in URL)

AFIP - 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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