The association between atypical adenomatous hyperplasia and primary lung cancer

Chapman, Andrea D.; Kerr, Keith M.

doi:10.1054/bjoc.2000.1317

Cited by 120 publications

(71 citation statements)

References 28 publications

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“…Weng et al also reported that there is no definite correlation between smoking history and the occurrence of AAH. In contrast, Chapman and Kerr (36) have recently demonstrated that a greater percentage of women with adenocarcinoma had AAH (30.2%) than did men with adenocarcinoma (18.8%).…”

Section: Epidemiologymentioning

confidence: 86%

“…Miller (26) examined 247 cases of surgically resected lung carcinomas by sectioning all areas of the lung transversely at 1.0-to 1.5-cm intervals and found 23 (9.3%) of lesions to be what she called bronchioloalveolar cell adenomas. Other investigators have reported a frequency of AAH of 5 to 20% in surgically resected lungs for pulmonary carcinoma (20,(32)(33)(34)(35)(36). Weng et al (32) reviewed the literature that examined the incidence of AAH and found that it was notably higher in specimens obtained from patients with primary lung carcinoma (20.0%) than in those with nonprimary lung carcinoma (4.8%).…”

Section: Epidemiologymentioning

confidence: 99%

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Atypical Adenomatous Hyperplasia of the Lung: A Probable Forerunner in the Development of Adenocarcinoma of the Lung

et al. 2001

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An increasingly large body of work suggests that atypical adenomatous hyperplasia (AAH) of the lung may be a forerunner of pulmonary adenocarcinoma. Recognizing this fact, the World Health Organization now acknowledges the existence of AAH while noting difficulties that may be encountered in distinguishing AAH from the nonmucinous variant of bronchioloalveolar carcinoma. Regrettably, a universally acceptable definition of morphologic criteria for the diagnosis of AAH has not been achieved. This review of the literature examines the epidemiology, gross appearance, light microscopic findings, morphometry, immunohistochemistry, and molecular features of AAH and suggests a set of histopathologic features that may help the practicing pathologist identify this intriguing lesion. These features include the following: irregularly bordered focal proliferations of atypical cells spreading along the preexisting alveolar framework; prominent cuboidal to low columnar alveolar epithelial cells with variable degree of atypia but less than that seen in adenocarcinoma; increased cell size and nuclearcytoplasmic ratio with hyperchromasia and prominent nucleoli, generally intact intercellular attachment of atypical cells with occasional empty-looking spaces between them without high cellularity and without tufting or papillary structures; and slight thickening of the alveolar walls on which the AAH cells have spread, with some fibrosis but without scar formation or significant chronic inflammation of the surrounding lung tissue. Several lines of evidence indicate that AAH is a lesion closely associated with adenocarcinoma of the lung, suggesting AAH may be involved in the early stage of a complex multistep carcinogenesis of pulmonary adenocarcinoma.

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Section: Epidemiologymentioning

confidence: 86%

Section: Epidemiologymentioning

confidence: 99%

Atypical Adenomatous Hyperplasia of the Lung: A Probable Forerunner in the Development of Adenocarcinoma of the Lung

et al. 2001

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“…These lesions resemble human atypical adenomatous hyperplasia, which is considered a precursor lesion to lung adenocarcinoma. 19 In mouse gene-targeting models where lung tumorigenesis is caused by somatic K-ras2 activation (mutation), massive alveolar hyperplasia/dysplasia precedes tumor development, 20,21 indicating that these early morphologic alterations are caused by K-ras2 mutations. Accordingly, K-ras2 mutations have been reported in both human and carcinogen-induced mouse lung hyperplasia.…”

Section: Discussionmentioning

confidence: 99%

Cancer modifier alleles inhibiting lung tumorigenesis are common in inbred mouse strains

Manenti

Acevedo

Galbiati

et al. 2002

Intl Journal of Cancer

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A few inbred mouse strains characterized thus far are highly susceptible to lung tumorigenesis; e.g., A/J and SWR/J mice develop 15-30 tumors/mouse after urethane treatment. 1 Among the remaining strains, about half are intermediate-susceptible (i.e., 1-4 tumors/mouse) and half are resistant (i.e., 0 -1 tumors/ mouse). 1 Lung tumorigenesis in the mouse is under polygenic control. The pulmonary adenoma susceptibility 1 (Pas1) locus represents the major determinant of inherited susceptibility to lung cancer, as confirmed in independent studies from different laboratories and using different chemical carcinogens. [2][3][4] We previously showed that all of the highly and intermediately susceptible strains carry the same haplotype in the Pas1 region, 5 with the same Pas1 susceptibility allele (Pas1 s ) probably deriving from an ancestral progenitor mouse. Thus, Pas1 s occurs frequently in inbred mouse strains. However, in a survey of mouse strains, 9/14 strains carrying the Pas1 s allele developed 3-to 10-fold fewer lung tumors per mouse compared to the highly susceptible strains. 1,5,6 Resistance to lung tumorigenesis is provided in some strains by resistance alleles carried at pulmonary adenoma resistance (Par) loci. Par loci have not been formally defined, though their designation pulmonary adenoma resistance implies this biologic activity. We suggest that Par loci comprise a null allele, with no effects on lung tumor susceptibility, and a resistance allele, which inhibits lung tumor multiplicity in a dominant or codominant way. Indeed, on a Pas1-susceptible genetic background, a single Par resistance allele may reduce carcinogen-induced lung tumor multiplicity up to 10-fold. 7,8 BALB/c is an example of an intermediate-susceptible mouse strain carrying Par loci that inhibit the high susceptibility conferred by the Pas1 s allele also carried by this strain. 9 Indeed, F 1 mice of the BALB/c strain crossed with either A/J or SWR/J mice show reduced lung tumor multiplicity to an intermediate level; genetic linkage studies mapped the Par2 and Par4 loci, whose BALB/c-derived cancer resistance alleles reduce lung tumor multiplicity. 9 -13 To determine whether intermediate susceptibility or complete resistance to lung tumorigenesis of strains carrying the Pas1 s allele results from resistance alleles at Par loci carried by these strains, we examined lung tumor multiplicity in F 1 crosses between intermediate or resistant strains and the highly susceptible strain A/J compared to the A/J parent and F 1 hybrids between A/J mice and strains not carrying Par loci, e.g., C57BL/6J. 4 In 7 strains, multiplicity of lung tumors induced by urethane was significantly decreased compared to A/J mice or (A/J ϫ C57BL/6J)F 1 mice. MATERIAL AND METHODS Mouse treatment and phenotypeMale 129/SvJ, CBA/J, C57BL/6J, DBA/2J, ST/J, LP/J, C57L/J, SJL/J, PL/J and RF/J mice were purchased from the Jackson Laboratory (Bar Harbor, ME); SPW inbred mice, derived from wild Mus spretus, were bred in the University of La Laguna Laboratory (Tenerife, Spai...

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“…2 Adenocarcinoma is considered to develop by a pathway of atypical adenomatous hyperplasia and bronchioloalveolar carcinoma. [2][3][4] However, whether atypical adenomatous hyperplasia-bronchioloalveolar carcinoma pathway is really the only pathway for pulmonary adenocarcinoma has been questioned on the basis of a number of observations. 5 First, atypical adenomatous hyperplasias are not as common as adenocarcinomas with features of bronchioloalveolar carcinoma or premalignant lesions in other organs.…”

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confidence: 99%

Ciliated adenocarcinomas of the lung: a tumor of non-terminal respiratory unit origin

et al. 2012

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Whereas most carcinomas occur through a sequential step, atypical adenomatous hyperplasia and bronchioloalveolar carcinoma pathway is known for pulmonary adenocarcinoma. This type is known as terminal respiratory unit adenocarcinoma. Based on our observation of transitions from normal ciliated columnar cells to adenocarcinoma via dysplastic mucous columnar cells, we reviewed our archive of pulmonary adenocarcinoma. Terminal respiratory unit type adenocarcinoma was defined as adenocarcinoma with type II pneumocyte, Clara cell, or bronchiolar cell morphology according to previous reports. Among 157 cases, 121 cases have been identified as terminal respiratory unit type adenocarcinoma and 36 cases as non-terminal respiratory unit type adenocarcinoma. Among non-terminal respiratory unit type adenocarcinoma, 24 cases revealed mucous columnar cell changes that were continuous with bronchial ciliated columnar cells. The mucous columnar cells became dysplastic showing loss of cilia, disorientation, and enlarged nuclei. Adenocarcinoma arose from these dysplastic mucous columnar cells and, characteristically, this type of adenocarcinoma showed acute inflammation, and honeycombing changes in the background. TTF1 immunostaining was consistently negative. In a case study with 14 males and 10 females, including 12 smokers or ex-smokers, EGFR and KRAS mutations were detected in 3 and 6 patients, respectively. We think that this kind of adenocarcinoma arising through mucous columnar cell change belongs to non-terminal respiratory unit type adenocarcinoma, and mucous columnar cell change is a precursor lesion of pulmonary adenocarcinoma. Keywords: adenocarcinoma; lung; mucous columnar cell change Most carcinomas, including squamous cell carcinoma in the head and neck, uterine cervix, and skin, and adenocarcinomas in sites including the gastrointestinal tract, biliary tract, breast, and prostate occur through a sequence of steps from normal epithelium to hyperplasia, dysplasia, carcinoma in situ, and invasive carcinoma. 1 In the lung, squamous carcinoma arises by a similar pathway, beginning from squamous metaplasia in bronchus or bronchiole that is caused by various irritants. 2 Adenocarcinoma is considered to develop by a pathway of atypical adenomatous hyperplasia and bronchioloalveolar carcinoma. 2-4 However, whether atypical adenomatous hyperplasia-bronchioloalveolar carcinoma pathway is really the only pathway for pulmonary adenocarcinoma has been questioned on the basis of a number of observations. 5 First, atypical adenomatous hyperplasias are not as common as adenocarcinomas with features of bronchioloalveolar carcinoma or premalignant lesions in other organs. 3,5 Second, atypical adenomatous hyperplasia is morphologically different from pre-adenocarcinoma lesions in other organs such as adenoma, prostatic intraepithelial neoplasia, or biliary intraepithelial neoplasia showing nuclear stratification, elongation, and overlap. Third, peripheral pulmonary parenchyma in which atypical adenomatous hyperplasia or bronchioloalv...

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The association between atypical adenomatous hyperplasia and primary lung cancer

Cited by 120 publications

References 28 publications

Atypical Adenomatous Hyperplasia of the Lung: A Probable Forerunner in the Development of Adenocarcinoma of the Lung

Atypical Adenomatous Hyperplasia of the Lung: A Probable Forerunner in the Development of Adenocarcinoma of the Lung

Cancer modifier alleles inhibiting lung tumorigenesis are common in inbred mouse strains

Ciliated adenocarcinomas of the lung: a tumor of non-terminal respiratory unit origin

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