Atypical Lobular Hyperplasia

Atypical Lobular Hyperplasia

ALH is composed of a monomorphic proliferation of discohesive polygonal or cuboidal cells that are small and round. In lobules, these cells begin to fill acinar spaces, but few are widely distended image.

The cytologic features of ALH, LCIS, and invasive lobular carcinoma are identical. Differentiating ALH from LCIS is based on the extent of the lesion and the degree of distension image of acini.



  • Atypical lobular hyperplasia (ALH)


  • Lobular intraepithelial neoplasia 1 (LIN1)


  • ALH is cytologically identical to lobular carcinoma in situ (LCIS) but is more limited in extent

  • Term “lobular neoplasia” (LN) includes both ALH and LCIS


Molecular Pathology

  • The hallmark feature of ALH, LCIS, and invasive lobular carcinoma is loss of expression of the E-cadherin gene (CDH1)

    • E-cadherin plays a major role in intercellular adhesion and cell polarity

    • Loss of E-cadherin membrane expression can be shown by immunohistochemistry

    • Loss of expression is accompanied by E-cadherin DNA alterations in LCIS but not in ALH

      • Suggests that E-cadherin may be inactivated by means other than mutation in ALH

  • ALH and LCIS share similar losses and gains of DNA

    • Loss at 16q21-q23.1 (location of E-cadherin gene)

    • Gain at 14q32.33 (site of AKT1 gene) (involved in luminal morphogenesis)

  • Genetic changes in invasive lobular carcinomas can also be found in adjacent LN

    • Evidence that LN may be a precursor lesion for invasive carcinoma

    • However, LN is a nonobligate precursor as the majority of women with ALH do not develop invasive carcinoma



  • Incidence

    • ALH and LCIS without invasive carcinoma are found in only 0.5-4% of breast biopsies

    • Incidental findings in biopsies performed for other indications

    • True incidence of ALH in the general population is unknown

  • Age

    • ALH is more common in premenopausal women (peak incidence in mid 40s)


  • ALH can be multicentric and is frequently bilateral


  • Asymptomatic


  • In order to reduce risk, both breasts require treatment

    • Chemoprevention with tamoxifen reduces risk of ER-positive invasive carcinoma

    • Bilateral mastectomy reduces risk

  • However, the majority of women will not develop invasive carcinoma, and most choose surveillance


Jul 6, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Atypical Lobular Hyperplasia

Full access? Get Clinical Tree

Get Clinical Tree app for offline access
%d bloggers like this: