Noninvasive lobular neoplasia

Atypical lobular hyperplasia

Editor-in-Chief: Debra L. Zynger, M.D.
Eric Statz, M.D.
Julie M. Jorns, M.D.

Last author update: 16 March 2020
Last staff update: 29 December 2021

Copyright: 2002-2023,, Inc.

PubMed Search: Atypical lobular hyperplasia [title]

Eric Statz, M.D.
Julie M. Jorns, M.D.
Page views in 2022: 11,121
Page views in 2023 to date: 13,712
Cite this page: Statz E, Jorns JM. Atypical lobular hyperplasia. website. Accessed November 29th, 2023.
Definition / general
  • A clonal proliferation of discohesive epithelial cells arising in terminal duct lobular units
  • Similar histologic features to lobular carcinoma in situ (LCIS) but of insufficient quantity
Essential features
  • Clonal proliferation of discohesive cells identical to lobular carcinoma in situ but in smaller quantity
  • Typical dysfunction / loss of E-cadherin
  • Generally considered incidental finding (clinically / radiologically occult)
  • 4 - 5 times increased risk of (bilateral risk but higher risk ipsilateral) invasive breast carcinoma compared with general population
  • Does not necessarily require excision if isolated finding
  • Lobular intraepithelial neoplasia 1 (LIN1)
ICD coding
  • ICD-10: N60.8 - other benign mammary dysplasias
  • ICD-10: N60.9 - unspecified benign mammary dysplasia
  • Bilateral breasts with no specific location
Pathophysiology and etiology
Clinical features
  • Frequently associated with columnar cell lesions and flat epithelial atypia; less commonly associated with low grade invasive carcinomas which may have mammographically detectable calcifications, density or mass targeted on biopsy (Am J Surg Pathol 1998;22:1521Am J Surg Pathol 2007;31:417)
  • Does not form a palpable mass
  • 19% develop invasive cancer at mean 15 years after diagnosis (4 - 5 times usual risk), 42% are special subtypes with good prognosis (Cancer 2006;107:1227)
  • Core biopsy
  • Incidental after mammography, ultrasound or MRI
Radiology description
  • Classically considered to be an incidental finding with no radiologic correlates
  • Calcifications, if associated with atypical lobular hyperplasia in biopsy or non-mass enhancement on MRI, may be considered concordant after biopsy is read (Breast Dis 2016;36:5)
Prognostic factors
Case reports
  • Controversial; some surgeons excise, others get lifelong screening / follow up screening intervals
  • Growing evidence to avoid excision for well sampled lesions (Ann Surg Oncol 2017;24:2848)
  • Selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs) can lower risk of subsequent invasive carcinoma in patients with atypical hyperplasias (atypical lobular hyperplasia or atypical ductal hyperplasia not separated) (J Natl Compr Canc Netw 2018;16:1391)
Gross description
  • No specific gross findings
  • May be associated with calcifications but typically due to other coexisting lesions
Microscopic (histologic) description
  • Solid, discohesive proliferation of cells that are monomorphic, small, have pale pink cytoplasm, uniform oval nuclei and indistinct nuclei
  • Some cells have plasmacytoid or signet ring appearance (intracytoplasmic vacuoles)
  • Do not form arcades, lumens or papillary projections
  • Criteria of Page et al. (Schnitt: Biopsy Interpretation of the Breast, 3rd Edition, 2017):
    • Distends 50% or more acini within a lobule (so resembles lobular carcinoma in situ) but not uniformly present throughout entire lobule OR
    • Involves all acini in a terminal duct lobular unit (TDLU) and so resembles lobular carcinoma in situ but does not distend the acini (i.e. caliber of the involved acini is similar to that of uninvolved acini)
  • Can involve ducts; alteration occurs around the duct as outpouchings producing a cloverleaf pattern
  • Lacks intracytoplasmic mucin
  • May be no / minimal inflammatory response
Microscopic (histologic) images

Contributed by Eric Statz, M.D. and Julie M. Jorns, M.D.

ALH in fibroadenoma

ALH in fat

Plasmacytoid ALH

Duct with ALH

Lobule expanded by ALH

ALH full lobule

Loss of E-cadherin

Loss of E-cadherin

Cytology description
  • Loosely cohesive cell clusters composed of uniform cells with occasional intracytoplasmic lumina, minimal nuclear atypia but frequent eccentric nuclei
Positive stains
Negative stains
Electron microscopy description
  • Intracytoplasmic lumina, microvilli with secretory droplets; basement membrane and myoepithelial cells are present
Molecular / cytogenetics description
Sample pathology report
  • Left breast, 12 o'clock, core biopsy:
    • Atypical lobular neoplasia (ALH) (see comment)
    • Comment: An immunohistochemical stain for E-cadherin is negative in the atypical focus, supporting the diagnosis of ALH. Controls are appropriate.
Differential diagnosis
Board review style question #1

    A lesion was biopsied with immunohistochemistry pictured above. It is best diagnosed as

  1. Atypical apocrine adenosis (AAA)
  2. Atypical ductal hyperplasia (ADH)
  3. Atypical lobular hyperplasia (ALH)
  4. Flat epithelial atypia (FEA)
Board review style answer #1
C. Atypical lobular hyperplasia (ALH)

Explanation: The above images show an in situ proliferation of small to moderate sized, monotonous epithelial cells with mild expansion of involved glands. There are a few cells with intracytoplasmic vacuoles as well as variably prominent cell borders. Thus, the differential diagnosis includes atypical ductal hyperplasia (ADH) with a solid growth pattern and atypical lobular hyperplasia (ALH). Atypical apocrine adenosis (AAA) has larger cells with apocrine cytology including large, round nuclei with prominent nucleoli and abundant eosinophilic cytoplasmic. Flat epithelial atypia (FEA) has dilated glands with atypical low columnar to cuboidal epithelium with high nuclear cytoplasmic ratio and lack of orientation toward lumina. Characteristic features of AAA and FEA are lacking in the pictured lesion. In the differential of ALH and solid ADH immunohistochemistry can be very helpful, with ALH showing lack or attenuation of E-cadherin and cytoplasmic staining via p120 as shown above. ADH in contrast has strong, diffuse E-cadherin staining and membranous staining via p120.

Comment Here

Reference: Atypical lobular hyperplasia (ALH)
Board review style question #2
    Atypical lobular hyperplasia (ALH) seen on core biopsy most frequently correlates to the following feature via breast imaging

  1. Asymmetry
  2. Calcifications
  3. Mass
  4. No specific finding
Board review style answer #2
D. No specific finding

Explanation: Atypical lobular hyperplasia (ALH) is typically not identified via standard imaging modalities. Occasionally ALH has calcifications, although if a core biopsy that has ALH has an indication of calcifications, these are more frequently identified in other lesions in the biopsy such as fibrocystic change or other atypias (e.g. flat epithelial atypia or atypical ductal hyperplasia). ALH is not typically identified as a mass or asymmetry on breast imaging.

Comment Here

Reference: Atypical lobular hyperplasia (ALH)
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