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Preinvasive

Atypical adenomatous hyperplasia

Authors: Sherman Lin, Matthew J. Cecchini, M.D., Ph.D.

Editorial Board Member: Jefree J. Schulte, M.D.

Last author update: 22 August 2022

Last staff update: 20 January 2023

Copyright: 2003-2024 PathologyOutlines.com, Inc.

PubMed Search: Bronchioloalveolar atypical adenomatous hyperplasia

Table of Contents

Cite this page: Lin S, Cecchini MJ. Atypical adenomatous hyperplasia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lungtumorbronchAAH.html. Accessed December 19th, 2024.

Definition / general

Atypical adenomatous hyperplasia (AAH) is a small, localized proliferation of atypical pneumocytes (usually ≤ 5 mm) that line intact alveolar spaces
AAH is recognized as a precursor lesion to invasive adenocarcinoma (Cancer Metastasis Rev 2010;29:15)

Essential features

Small, localized lesion (usually ≤ 5 mm)
Discrete from alveolar parenchyma with proliferation of atypical pneumocytes
Forms a discontinuous monolayer of cells
Surrounding parenchyma should be devoid of substantial inflammation or fibrosis

Terminology

Obsolete terms (not recommended): atypical alveolar epithelial hyperplasia, atypical bronchoalveolar cell hyperplasia, atypical alveolar cell hyperplasia, bronchoalveolar cell adenoma, bronchial adenoma

ICD coding

ICD-O: 8250/0 - atypical adenomatous hyperplasia
ICD-11: 2F0Z & XH5QL3 - benign neoplasms of unspecified respiratory and intrathoracic organs & atypical adenomatous hyperplasia

Epidemiology

Commonly seen in lung resections as an incidental finding
In some series, AAH has been reported in ≤ 30.2% of female patients undergoing a resection for adenocarcinoma (Br J Cancer 2000;83:632)
In autopsy series, AAH has been reported in 2 - 4% of cases without cancer (Mod Pathol 1997;10:469, Lung Cancer 2000;29:125)
F > M (Br J Cancer 2000;83:632)
Associated CYP19A1 polymorphisms have been reported (Carcinogenesis 2010;31:1794)

Sites

More common in the upper lobes (Thorax 2001;56:302)

Pathophysiology

Conceptualized as the earliest morphologically recognizable lesion in the proposed stepwise progression of lung adenocarcinoma (Int J Mol Sci 2018;19:1259)

Etiology

Unknown; some series suggest that AAH is not correlated with smoking (Thorax 2001;56:302)

Clinical features

AAH is usually undetectable by imaging techniques and is typically found incidentally in surgical pathology specimens
Larger lesions may be present on high resolution CT imaging (Eur Radiol 2001;11:811)

Diagnosis

Typically diagnosed in lung resection specimens (often incidentally)
Usually not diagnosed on small core needle or transbronchial biopsies since the lesion should be examined in its entirety

Laboratory

Not typically assessed in AAH

Radiology description

Present as faint, not solid, nodules on CT scans (J Thorac Dis 2018;10:S790)

Radiology images

Images hosted on other servers:

Conventional TSCT

Prognostic factors

Patients are cured upon resection

Case reports

12 year old girl presenting with incidental AAH upon bulla surgical resection (Korean J Thorac Cardiovasc Surg 2016;49:141)
50 year old woman with 3 ground glass nodules showing coexistence of atypical adenomatous hyperplasia, minimally invasive adenocarcinoma and invasive adenocarcinoma (Thorac Cancer 2021;12:693)
73 year old woman with AAH nodule progressing to semisolid lesion (Cureus 2019;11:e6079)

Treatment

CT surveillance; frequency and duration dependent on size of nodule (JAMA 2022;327:264)
Patients are cured with resection

Gross description

Gray, tan-yellow, ill defined area
Can be multifocal
Localization: peripheral lung parenchyma, near pleura
Size: measures ≤ 5 mm

Frozen section description

Diagnosis is not typically made on frozen section, given the subtle changes associated with this lesion
Some cases with subtle atypia on frozen section, may turn out to be classified as AAH based on permanent sections

Microscopic (histologic) description

Proliferation of atypical pneumocytes
- Mild to moderate atypia with increased cell size and nuclear to cytoplasmic ratio; nuclei are hyperchromatic and can have intranuclear eosinophilic inclusions
- Cells are present along intact alveolar spaces
- Atypical cells form a discontinuous monolayer of cells
- Mitotic activity is typically minimal
Lesion is composed of a mixture of club cells and type II pneumocytes
- Club cells can be recognized as columnar cells with eosinophilic and cytoplasmic snouts
- Type II pneumocytes are cuboidal with finely vacuolated to clear cytoplasm
Absence of significant parenchymal inflammation or fibrosis

Microscopic (histologic) images

Contributed by Sherman Lin and Matthew J. Cecchini, M.D., Ph.D.

Small proliferation
of larger
hyperchromatic
cells

Proliferation of atypical pneumocytes

Discontinuous monolayer of atypical cells

Positive stains

Positive for TTF1 but is not commonly required or recommended (Virchows Arch 1997;431:415)

Molecular / cytogenetics description

Lesional cells have been shown to be clonal in nature
Degree of copy number change and mutations has been shown in some studies to be less than in adenocarcinoma in situ (Nat Commun 2019;10:2978)
AAH has been found to have driver mutations such as KRAS, EGFR and BRAF (J Thorac Oncol 2018;13:1776)
Given that these lesions are cured with resection, molecular testing is not typically indicated in most clinical settings

Sample pathology report

Right lung, middle lobe, wedge resection:
- Atypical adenomatous hyperplasia (AAH) (see comment)
- 3 mm in greatest dimension
- Comment: Atypical adenomatous hyperplasia (AAH) is a preinvasive lesion in the adenocarcinoma spectrum and is regarded as a precursor to adenocarcinoma in situ. No invasive or in situ malignancy is present.

Differential diagnosis

Nonmucinous (adenocarcinoma in situ):
- Adenocarcinoma in situ (AIS) is typically > 5 mm
- More cellular cuboidal / columnar cells forming a continuous monolayer
- AIS typically has a sharper (abrupt) cutoff with the background lung parenchyma
- Distinguishing between AIS and AAH can be challenging in some cases since there is overlap in morphology; however, this is of limited clinical relevance in most cases as both lesions are cured by resection
Reactive pneumocyte hyperplasia:
- In reactive hyperplasia, the atypical pneumocytes tend to be more diffuse and do not form well defined nodular areas
- There is often a background of inflammation, fibrosis or features of acute lung injury seen admixed with the atypical cells

Board review style question #1

Which of the following histologic features seen in the image above, best supports the classification of this sample as atypical adenomatous hyperplasia (AAH) over adenocarcinoma in situ (AIS)?

Absence of significant inflammation
Architectural changes
Discontinuous nature of the atypical cells
Loss of polarity
Mild to moderate atypia

Board review style answer #1

C. Discontinuous nature of the atypical cells. Discontinuous atypical cells are most often seen in small atypical pneumocyte proliferations that are best classified as AAH. Architectural changes are not typically seen in AAH or AIS. Absence of significant inflammation can be seen in AAH and AIS. Mild to moderate atypia and loss of polarity can be seen in both AAH and AIS.

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Reference: Atypical adenomatous hyperplasia

Board review style question #2

How is atypical adenomatous hyperplasia typically identified / detected?

After workup for hemoptysis
As an incidental solid lesion on CT scan
Based on PET scan
Incidental finding in resected lung tissue

Board review style answer #2

D. Incidental finding in resected lung tissue. Atypical adenomatous hyperplasia is typically identified as an incidental finding in resected lung tissue. It is not easily appreciated based on imaging studies and patients are normally asymptomatic.

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