Abstract
Atypical adenomatous hyperplasia (AAH) has been suggested as the adenoma in an adenoma–carcinoma sequence in the lung periphery. From 1989–1998, we undertook a systematic, prospective search for AAH in lungs resected for cancer. AAH was found in 67 of 554 patients (12.1%) with primary lung carcinoma (9.2% in male patients and 19.0% in females). AAH was found in lungs bearing adenocarcinoma (23.2%) more frequently than with large cell undifferentiated carcinoma (12.5%) or squamous carcinoma (3.3%). A greater percentage of females with adenocarcinoma had AAH (30.2%) than did males with adenocarcinoma (18.8%). Numbers of AAH ranged from 1–42 per patient and more patients had small numbers of AAH, although 12 patients had 6 or more AAH foci. Larger numbers of AAH tended to be found in adenocarcinoma-bearing lungs. Ten of the 67 patients with AAH and primary lung carcinoma (15%) had multiple primary cancers (range 2–6), all of which were adenocarcinoma. Synchronous cancers were rare in lung tumour-bearing resections without AAH. Patients with AAH show no difference in post-operative survival to those without, for all stages of carcinoma and for Stage I disease alone. This study provides evidence for a strong association between atypical adenomatous hyperplasia and primary lung adenocarcinoma and lends weight to the AAH/adenoma-carcinoma hypothesis. © 2000 Cancer Research Campaign
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Anami Y, Matsuno Y, Yamada T, Takeuchi T, Nakayama H, Hirohashi S & Noguchi M (1998) A case of double primary adenocarcinoma of the lung with multiple atypical adenomatous hyperplasia. Pathol Int 48: 634–640
Barsky SH, Grossman DA, Ho J & Holmes EC (1994) The multifocality of bronchioloalveolar lung carcinoma: Evidence and implications of a multiclonal origin. Mod Pathol 7: 633–640
Carey FA, Wallace WAH, Fergusson RJ, Kerr KM & Lamb D (1992) Alveolar atypical hyperplasia in association with primary pulmonary adenocarcinoma: a clinicopathological study of 10 cases. Thorax 47: 1041–1043
Carey FA, Donnelly SC, Walker WS, Cameron EW & Lamb D (1993) Synchronous primary lung cancers: prevalence in surgical material and clinical implications. Thorax 48: 344–346
Connolly CK, Crawford SM, Rider PL, Smith AD, Johnston CF & Muers MF (1997) Carcinoma of the bronchus in the Yorkshire region of England 1976–1990: trends since 1984. Eur Resp J 10: 397–403
Cooper CA, Carey FA, Bubb VJ, Lamb D, Kerr KM & Wyllie AH (1997) The pattern of K-ras mutation in pulmonary adenocarcinoma defines a new pathway of tumour development in the human lung. J Pathol 181: 401–404
Hammar SP (1993) Common neoplasms. Pulmonary Pathology, Dail DH, Hammar SP (eds) pp 1123–1278, Springer-Verlag: New York
Hayashi H, Miyamoto H, Ito T, Kameda Y, Nakamura N, Kubota Y Y & Kitamura H (1997) Analysis of p21Waf1/Cip1 expression in normal, premalignant, and malignant cells during the development of human lung adenocarcinoma. Am J Pathol 151: 461–470
Holst VA, Finkelstein S & Yousem SA (1998) Bronchioloalveolar adenocarcinoma of lung. Monoclonal origin for multifocal disease. Am J Surg Pathol 22: 1343–1350
Kerr KM (2000) Pulmonary preinvasive neoplasia. J Clin Pathol, (in press)
Kerr KM, Carey FA, King G & Lamb D (1994) Atypical alveolar hyperplasia: relationship with pulmonary adenocarcinoma, p53, and c-erbB-2 expression. J Pathol 174: 249–256
Kerr KM, Johnson SK, Kennedy MM & Jeffrey RR (1996) Rising incidence of primary lung adenocarcinoma in North East Scotland. Thorax 51: A56
Kitamura H, Kameda Y, Ito T & Hayashi H (1999) Atypical adenomatous hyperplasia of the lung. Implications for the pathogenesis of peripheral lung adenocarcinoma. Am J Clin Pathol 111: 610–622
Kodama T, Biyajima S, Watanabe S & Shimosato Y (1986) Morphometric study of adenocarcinoma and hyperplastic epithelial lesions in the peripheral lung. Am J Clin Pathol 85: 146–151
Kodama T, Nishiyama H, Nishiwaki Y, Takanashi K, Kuroki M, Hayashibe A, Nukariya N, Kitaya T & Matusuyama T (1988) Histopathological study of adenocarcinoma and hyperplastic epithelial lesions of the Lung. Lung Cancer (Haigan) 8: 325–333
Kurasono Y, Ito T, Kameda Y, Nakamura N & Kitamura H (1998) Expression of cyclin D1, retinoblastoma gene protein, and p16 MTS1 protein in atypical adenomatous hyperplasia and adenocarcinoma of the lung. An immunohistochemical analysis. Virchows Arch 432: 207–215
Miller RR (1990) Bronchioloalveolar cell adenomas. Am J Surg Pathol 14: 904–912
Miller RR, Nelems B, Evans KG, Müller NL & Ostrow DN (1988) Glandular neoplasia of the lung. A proposed analogy to colonic tumours. Cancer 61: 1009–1014
Mori M, Chiba R & Takahashi T (1993) Atypical adenomatous hyperplasia of the lung and its differentiation from adenocarcinoma. Cancer 72: 2331–2340
Morinaga S & Shimosato Y (1987) Pathology of the microadenocarcinoma in the periphery of the lung. Pathol Clin Med Jpn 5: 74–80
Nadav Y, Pastorino U & Nicholson AG (1998) Multiple synchronous lung cancers and atypical adenomatous hyperplasia in Li-Fraumeni syndrome. Histopathol 33: 52–54
Nakanishi K (1990) Alveolar epithelial hyperplasia and adenocarcinoma of the lung. Arch Pathol Lab Med 114: 363–368
Nakayama H, Noguchi M, Tsuchiya R, Kodama T & Shimosato Y (1990) Clonal growth of atypical adenomatous hyperplasia of the lung: cytofluorometric analysis of nuclear DNA content. Mod Pathol 3: 314–320
Niho S, Yokose T, Suzuki K, Kodama T, Nishiwaki Y & Mukai K (1999) Monoclonality of atypical adenomatous hyperplasia of the lung. Am J Pathol 154: 249–254
Noguchi M & Shimosato Y (1995) The development and progression of adenocarcinoma of the lung. Cancer Treat Res 72: 131–142
Sharp L & Brewster D (1999) The epidemiology of lung cancer in Scotland: a review of trends in incidence, survival and mortality and prospects for prevention. Health Bull 57: 318–331
Shimosato Y, Kodama T & Kameya T (1982) Morphogenesis of peripheral type adenocarcinoma of the lung. In: Morphogenesis of lung cancer Volume 1, Shimosato Y, Melamed MR, Nettesheim P (eds) pp 65–90, CRC Press: Boca Raton, FI
Sterner DJ, Mori M, Roggli VL & Fraire AE (1997) Prevalence of pulmonary atypical alveolar cell hyperplasia in an autopsy population: a study of 100 cases. Mod Pathol 10: 469–473
Suzuki K, Nagai K, Yoshida J, Yokose T, Kodama T, Takahashi K, Nishimura M, Kawasaki H, Yokozaki M & Nishiwaki Y (1997) The prognosis of resected lung carcinoma associated with atypical adenomatous hyperplasia: a comparison of the prognosis of well-differentiated adenocarcinoma associated with atypical adenomatous hyperplasia and intrapulmonary metastasis. Cancer 79: 1521–1526
Suzuki K, Takahashi K, Yoshida J, Nishimura M, Yokose T, Nishiwaki Y & Nagai K (1998a) Synchronous double primary lung carcinomas associated with multiple atypical adenomatous hyperplasia. Lung Cancer 19: 131–139
Suzuki K, Ogura T, Yokose T, Nagai K, Mukai K, Kodama T, Nishiwaki Y & Esumi H (1998b) Loss of heterozygosity in the tuberous sclerosis gene associated regions in adenocarcinoma of the lung accompanied by multiple atypical adenomatous hyperplasia. Int J Cancer (Pred Oncol) 79: 384–389
Takigawa N, Segawa Y, Nakata M, Saeki H, Mandai K, Kishino D, Shimono M, Ida M & Eguchi K (1999) Clinical investigation of atypical adenomatous hyperplasia of the lung. Lung Cancer 25: 115–121
Travis WD, Travis LB & Devesa SS (1995) Lung Cancer. Cancer 75(Suppl): 191–202
Travis WD, Colby TV, Corrin B, Shimosato Y & Brambilla E (1999) Histological typing of lung and pleural tumours. WHO International histological classification of tumours, 3rd edition, Springer: Berlin
Weng S, Tsuchiya E, Satoh Y, Kitagawa T, Nakagawa K & Sugano H (1990) Multiple atypical adenomatous hyperplasia of type II pneumocytes and bronchiolo-alveolar carcinoma. Histopathol 16: 101–103
Weng SY, Tsuchiya E, Kasuga T & Sugano H (1992) Incidence of atypical bronchioloalveolar cell hyperplasia of the lung: relation to histological subtypes of lung cancer. Virchows Arch 420: 463–471
Westra WH, Baas IO, Hruban RH, Askin FB, Wilson K, Offerhaus GJ & Slebos RJ (1996) K-ras oncogene activation in atypical alveolar hyperplasias of the human lung. Cancer Res 56: 2224–2228
Wistuba II, Behrens C, Milchgrub S, Bryant D, Hung J, Minna JD & Gazdar AF (1999) Sequential molecular abnormalities are involved in the multistage development of squamous cell lung carcinoma. Oncogene 18: 643–650
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Chapman, A., Kerr, K. The association between atypical adenomatous hyperplasia and primary lung cancer. Br J Cancer 83, 632–636 (2000). https://doi.org/10.1054/bjoc.2000.1317
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1054/bjoc.2000.1317
Keywords
This article is cited by
-
Updates in grading and invasion assessment in lung adenocarcinoma
Modern Pathology (2022)
-
Targeted sequencing reveals clonal genetic changes in the progression of early lung neoplasms and paired circulating DNA
Nature Communications (2015)
-
Prognostic significance of promoter CpG island hypermethylation and repetitive DNA hypomethylation in stage I lung adenocarcinoma
Virchows Archiv (2015)
-
Fibroblast phenotypes in different lung diseases
Journal of Cardiothoracic Surgery (2014)
-
Ciliated adenocarcinomas of the lung: a tumor of non-terminal respiratory unit origin
Modern Pathology (2012)
