Skip to main content
SpringerLink
Log in

The Classification of Pre-invasive Lesions

  • Chapter
  • First Online:
Molecular Pathology of Lung Cancer

Part of the book series: Molecular Pathology Library ((MPLB,volume 6))

Abstract

This chapter discusses the three pre-invasive lesions recognised in the WHO classification of lung tumours. Squamous dysplasia and carcinoma in situ is a group of lesions recognised in the epithelium of bronchi. These lesions probably originate from hyperplasia of basal cells of the bronchial epithelium and ultimately may progress to invasive squamous cell carcinoma and possibly other bronchogenic tumours. Squamous dysplasia is classified in three grades; mild, moderate and severe dysplasia, with carcinoma in situ a separate, more advanced lesion. Distinct from central bronchial squamous carcinogenesis, atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS) are the pre-invasive lesions which define peripheral lung adenocarcinogenesis. These lesions arise from peripheral airway bronchiolo-alveolar epithelium, sometimes referred to as the terminal respiratory unit. AAH may be regarded as “dysplasia” arising in this epithelium and is a precursor of AIS, which then gives rise to peripheral type pulmonary adenocarcinoma. The least common, by far, of the pulmonary pre-invasive lesions is diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. A rare condition with an associated asthma-like syndrome, this condition is associated, in most examples, with the development of peripheral, spindle cell-type carcinoid tumours, hence its inclusion in the WHO classification.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Travis WD, Brambilla E, Muller-Hermelink HK, et al., editors. World Health Organisation Classification of Tumours. Pathology and genetics of tumours of the lung, pleura, thymus and heart. Lyon: IARC Press; 2004.

    Google Scholar 

  2. Franklin WA, Wistuba II, Geisinger KR, et al. Squamous dysplasia and carcinoma in situ. In: Travis WD, Brambilla E, Muller-Hermelink HK, et al., editors. World Health Organisation Classification of Tumours. Pathology and genetics of tumours of the lung, pleura, thymus and heart. Lyon: IARC Press; 2004. p. 68–72.

    Google Scholar 

  3. Kerr KM, Fraire AE, Pugatch B, et al. Atypical adenomatous hyperplasia. In: Travis WD, Brambilla E, Muller-Hermelink HK, et al., editors. World Health Organisation Classification of Tumours. Pathology and genetics of tumours of the lung, pleura, thymus and heart. Lyon: IARC Press; 2004. p. 73–5.

    Google Scholar 

  4. Travis WD, Brambilla E, Noguchi M, et al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma. J Thorac Oncol. 2011;6:244–85.

    Article  PubMed  Google Scholar 

  5. Travis WD, Gosney JG. Diffuse pulmonary neuroendocrine cell hyperplasia. In: Travis WD, Brambilla E, Muller-Hermelink HK, et al., editors. World Health Organisation Classification of Tumours. Pathology and genetics of tumours of the lung, pleura, thymus and heart. Lyon: IARC Press; 2004. p. 76–8.

    Google Scholar 

  6. Ullman R, Bongiovanni M, Halbwedl I, et al. Bronchiolar columnar cell dysplasia—genetic analysis of a novel preneoplastic lesion of peripheral lung. Virchows Arch. 2003;442:429–36.

    Google Scholar 

  7. Pankiewicz W, Sulewska A, Niklinska W, et al. Immunoexpression of P16INK4a, Rb and TP53 proteins in bronchiolar columnar cell dysplasia (BCCD) in lungs resected due to primary non-small cell lung cancer. Folia Histochem Cytobiol. 2008;46:89–96.

    Article  PubMed  Google Scholar 

  8. Kerr KM, Fraire AE. Pre-invasive diseases. In: Tomashefski J, Cagle P, Farver C, editors. Dail & Hammar’s pulmonary pathology. 3rd ed. New York: Springer; 2008. p. 158–215.

    Chapter  Google Scholar 

  9. Kerr KM. Pre-existing lung disease and lung cancer. In: Cagle PT, Allen TC, Dacic S, et al., editors. Advances in surgical pathology. Lung cancer, Ch 29. Philadelphia: Lippincott Williams & Wilkins; 2010. p. 275–87.

    Google Scholar 

  10. Travis WD. Lung. In: Henson DE, Albores-Saavedra J, editors. Pathology of incipient neoplasia. New York: Oxford University Press; 2001. p. 295–316.

    Google Scholar 

  11. Woolner LB, Fontana RS, Cortese DA, et al. Roentgenographically occult lung cancer: pathologic findings and frequency of multicentricity during a 10-year period. Mayo Clin Proc. 1984;59:453–66.

    PubMed  CAS  Google Scholar 

  12. Carter D, Marsh BR, Baker RR, et al. Relationship of morphology to clinical presentation in ten cases of early squamous cell carcinoma of the lung. Cancer. 1976;37:1389–96.

    Article  PubMed  CAS  Google Scholar 

  13. Nagamoto N, Saito Y, Sato M, et al. Clinicopathological analysis of 19 cases of isolated carcinoma in situ of the bronchus. Am J Surg Pathol. 1993;17:1234–43.

    Article  PubMed  CAS  Google Scholar 

  14. Lam S, MacAulay C, LeRiche JC, et al. Detection and localization of early lung cancer by fluorescence bronchoscopy. Cancer. 2000;89:2468–73.

    Article  PubMed  CAS  Google Scholar 

  15. Banerjee AK, Rabbitts PH, George J. Lung cancer 3: fluorescence bronchoscopy: clinical dilemmas and research opportunities. Thorax. 2003;58:266–71.

    Article  PubMed  CAS  Google Scholar 

  16. Lam S, Kennedy T, Unger M, et al. Localization of bronchial intraepithelial lesions by fluorescence bronchoscopy. Chest. 1998;113:696–702.

    Article  PubMed  CAS  Google Scholar 

  17. George JP, Banerjee AK, Read CA, et al. Surveillance for the detection of early lung cancer in patients with bronchial dysplasia. Thorax. 2007;62:43–50.

    Article  Google Scholar 

  18. Banerjee AK. Preinvasive lesions of the bronchus. J Thorac Oncol. 2009;4:545–51.

    Article  PubMed  Google Scholar 

  19. Nicholson AG, Perry LJ, Cury PM, et al. Reproducibility of the WHO/IASLC grading system for pre-invasive squamous lesions of the bronchus: a study of inter-observer and intra-observer variation. Histopathology. 2001;38:202–8.

    Article  PubMed  CAS  Google Scholar 

  20. Venmans BJ, Van der Linden JC, Elbers JRJ, et al. Observer variability in histopathological reporting of bronchial biopsy specimens: influence on the results of autofluorescence bronchoscopy in detection of bronchial neoplasia. J Bronchol. 2000;7:210–4.

    Article  Google Scholar 

  21. Meert A-P, Feoli F, Martin B, et al. Angiogenesis in preinvasive, early invasive bronchial lesions and micropapillomatosis and correlation with EGFR expression. Histopathology. 2007;50:311–7.

    Article  PubMed  Google Scholar 

  22. Muller KM, Muller G. The ultrastructure of preneoplastic changes in the bronchial mucosa. Curr Top Pathol. 1983;73:233–63.

    Article  PubMed  CAS  Google Scholar 

  23. Keith RL, Miller YE, Gemmill RM, et al. Angiogenic squamous dysplasia in bronchi of individuals at high risk for lung cancer. Clin Cancer Res. 2000;6:1616–25.

    PubMed  CAS  Google Scholar 

  24. Kerr KM, Popper HH. The differential diagnosis of pulmonary pre-invasive lesions. Eur Respir Mon. 2007;39:37–62.

    Article  Google Scholar 

  25. Yatabe Y, Mitsudomi T, Takahashi T. TTF-1 expression in pulmonary adenocarcinomas. Am J Surg Pathol. 2002;26:767–73.

    Article  PubMed  Google Scholar 

  26. Noguchi M. Stepwise progression of pulmonary adenocarcinoma—clinical and molecular implications. Cancer Metastasis Rev. 2010;29:15–21.

    Article  PubMed  Google Scholar 

  27. Kerr KM. Atypical adenomatous hyperplasia. In: Cagle PT, Allen TC, Dacic S, et al., editors. Advances in surgical pathology. Lung cancer, Ch 29. Philadelphia: Lippincott Williams & Wilkins; 2010. p. 245–262.

    Google Scholar 

  28. Miller RR, Nelems B, Evans KG, et al. Glandular neoplasia of the lung. A proposed analogy to colonic tumours. Cancer. 1988;61:1009–14.

    Article  PubMed  CAS  Google Scholar 

  29. Sterner DJ, Masuko M, Roggli VL, et al. Prevalence of pulmonary atypical alveolar cell hyperplasia in an autopsy population: a study of 100 cases. Mod Pathol. 1997;10:469–73.

    PubMed  CAS  Google Scholar 

  30. Yokose T, Ito Y, Ochiai A. High prevalence of atypical adenomatous hyperplasia of the lung in autopsy specimens from elderly patients with malignant neoplasms. Lung Cancer. 2000;29:125–30.

    Article  PubMed  CAS  Google Scholar 

  31. Yokose T, Doi M, Tanno K, et al. Atypical adenomatous hyperplasia of the lung in autopsy cases. Lung Cancer. 2001;33:155–61.

    Article  PubMed  CAS  Google Scholar 

  32. Weng S-Y, Tsuchiya E, Kasuga T, et al. Incidence of atypical bronchioloalveolar cell hyperplasia of the lung: relation to histological subtypes of lung cancer. Virchows Arch A Pathol Anat Histopathol. 1992;420:463–71.

    Article  PubMed  CAS  Google Scholar 

  33. Miller RR. Bronchioloalveolar cell adenomas. Am J Surg Pathol. 1990;14:904–12.

    Article  PubMed  CAS  Google Scholar 

  34. Chapman AD, Kerr KM. The association between atypical adenomatous hyperplasia and primary lung cancer. Br J Cancer. 2000;83:632–6.

    Article  PubMed  CAS  Google Scholar 

  35. Nakahara R, Yokose T, Nagai K, et al. Atypical adenomatous hyperplasia of the lung: a clinicopathological study of 118 cases including cases with multiple atypical adenomatous hyperplasia. Thorax. 2001;56:302–5.

    Article  PubMed  CAS  Google Scholar 

  36. Koga T, Hashimoto S, Sugio K, et al. Lung adenocarcinoma with bronchioloalveolar carcinoma component is frequently associated with foci of high-grade atypical adenomatous hyperplasia. Am J Clin Pathol. 2002;117:464–70.

    Article  PubMed  Google Scholar 

  37. Anami Y, Matsuno Y, Yamada T, et al. A case of double primary adenocarcinoma of the lung with multiple atypical adenomatous hyperplasia. Pathol Int. 1998;48:634–40.

    Article  PubMed  CAS  Google Scholar 

  38. Dohmoto K, Fujita J, Ohtsuki Y, et al. Synchronous four primary lung adenocarcinoma associated with multiple atypical adenomatous hyperplasia. Lung Cancer. 2000;27:125–30.

    Article  PubMed  CAS  Google Scholar 

  39. Suzuki K, Takahashi K, Yoshida J, et al. Synchronous double primary lung carcinomas associated with multiple atypical adenomatous hyperplasia. Lung Cancer. 1998;19:131–9.

    Article  PubMed  CAS  Google Scholar 

  40. Kishi K, Homma S, Kurosaki A, et al. Multiple atypical adenomatous hyperplasia with synchronous multiple primary bronchioloalveolar carcinomas. Intern Med. 2002;41:474–7.

    Article  PubMed  Google Scholar 

  41. Seki M, Akasaka Y. Multiple lung adenocarcinomas and AAH treated by surgical resection. Lung Cancer. 2007;55:237–40.

    Article  PubMed  Google Scholar 

  42. Takigawa N, Segawa Y, Nakata M, et al. Clinical investigation of atypical adenomatous hyperplasia of the lung. Lung Cancer. 1999;25:115–21.

    Article  PubMed  CAS  Google Scholar 

  43. Kerr KM, Devereux G, Chapman AD, et al. Is survival after surgical resection of lung cancer influenced by the presence of atypical adenomatous hyperplasia (AAH)? J Thorac Oncol. 2007;2 Suppl 4:S401–2.

    Article  Google Scholar 

  44. Noguchi M, Morokawa A, Kawasaki M, et al. Small adenocarcinoma of the lung. Histologic characteristics and prognosis. Cancer. 1995;75:2844–52.

    Article  PubMed  CAS  Google Scholar 

  45. Minami Y, Matsuno Y, Iijima T, et al. Prognostication of small-sized primary pulmonary adenocarcinomas by histopathological and karyometric analysis. Lung Cancer. 2005;48:339–48.

    Article  PubMed  Google Scholar 

  46. Nakata M, Sawada S, Saeki H, et al. Prospective study of thoracoscopic limited resection for ground-glass opacity selected by computed tomography. Ann Thorac Surg. 2003;75:1601–5.

    Article  PubMed  Google Scholar 

  47. Kodama K, Higashiyama M, Yokouchi H, et al. Prognostic value of ground-glass opacity found in small lung adenocarcinoma on high-resolution CT scanning. Lung Cancer. 2001;33:17–25.

    Article  PubMed  CAS  Google Scholar 

  48. Travis WD, Garg K, Franklin WA, et al. Evolving concepts in the pathology and ct imaging of lung adenocarcinoma and bronchioloalveolar carcinoma. J Clin Oncol. 2005;23:3279–87.

    Article  PubMed  Google Scholar 

  49. Kerr KM. Pulmonary adenocarcinomas: classification and reporting. Histopathology. 2009;54:12–27.

    Article  PubMed  Google Scholar 

  50. Aguayo SM, Miller YE, Waldron JA, et al. Idiopathic diffuse hyperplasia of pulmonary neuroendocrine cells and airway disease. N Engl J Med. 1992;327:1285–8.

    Article  PubMed  CAS  Google Scholar 

  51. Davies SJ, Gosney JR, Hansell DM, et al. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: an under-recognised spectrum of disease. Thorax. 2007;62:248–52.

    Article  PubMed  Google Scholar 

  52. Brown MJ, English J, Muller NL. Bronchiolitis ­obliterans due to neuroendocrine hyperplasia: high-resolution CT-pathologic correlation. Am J Roent­genol. 1997;168:1561–2.

    CAS  Google Scholar 

  53. Miller RR, Muller NL. Neuroendocrine cell hyperplasia and obliterative bronchiolitis in patients with peripheral carcinoid tumours. Am J Surg Pathol. 1995;19:653–8.

    Article  PubMed  CAS  Google Scholar 

  54. Churg A, Warnock ML. Pulmonary tumourlet. A form of peripheral carcinoid. Cancer. 1976;37:1469–77.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Aberdeen Royal Infirmary, Aberdeen University Medical School, Foresterhill, Aberdeen, AB25 2ZD, Scotland, UK

    Keith M. Kerr MD, FRCPath

Authors
  1. Keith M. Kerr MD, FRCPath
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Keith M. Kerr MD, FRCPath .

Editor information

Editors and Affiliations

  1. , Department of Pathology, The Methodist Hospital, 6565 Fannin Street, Houston, 77030, Texas, USA

    Philip T. Cagle

  2. Health Science Center at Tyler, Department of Pathology, The University of Texas, 11937 US Highway 271, Tyler, 75708, Texas, USA

    Timothy Craig Allen

  3. , Department of Pathology, Mount Sinai Medical Center, 1 Gustave L. Levy Place, New York, 10029, New York, USA

    Mary Beth Beasley

  4. , Department of Pathology, Brigham and Women's Hospital, 75 Francis St., Boston, 02115, Massachusetts, USA

    Lucian R. Chirieac

  5. Medical Center, Department of Pathology, University of Pittsburgh, 200 Lothrop St. - PUH C608, Pittsburgh, 15213, Pennsylvania, USA

    Sanja Dacic

  6. Medical Center, Department of Pathology &, Columbia University, 630 W. 168th Street VC-14-215, New York, 10032, New York, USA

    Alain C. Borczuk

  7. Medical School, Department of Pathology, Aberdeen University, Foresterhill, Aberdeen, Scotland, AB25 2ZD, United Kingdom

    Keith M. Kerr

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media New York

About this chapter

Cite this chapter

Kerr, K.M. (2012). The Classification of Pre-invasive Lesions. In: Cagle, P., et al. Molecular Pathology of Lung Cancer. Molecular Pathology Library, vol 6. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3197-8_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-3197-8_5

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-3196-1

  • Online ISBN: 978-1-4614-3197-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation