Facts and fiction: premalignant lesions of lung tissues

Our plain-English summary of Facts and fiction: premalignant lesions of lung tissues, by S. Klebe, D.W. Henderson (Pathology, 2013).

The study

• Authors: S. Klebe, D.W. Henderson
• Journal: Pathology
• Published: 2013;45(3):305-15
• Type of article: Review
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Lung cancer is now the leading cause of death from cancer in Australia. Most patients are diagnosed with late-stage disease. Although diagnosis at pre-invasive stages could theoretically improve outcomes, mooted precursor lesions are often asymptomatic and often undetectable by non-invasive investigations. Nonetheless, they merit study to identify early and essential molecular steps involved in lung carcinoma pathogenesis, with the aim of developing therapies targeted against one or more such steps. Some lung cancers appear to develop via a series of progressive morphological changes with correlating molecular alterations, but others seem to arise in histologically normal epithelium, and these differences may reflect anatomically and functionally distinct epithelial compartments of the respiratory tract. Pre-invasive precursor lesions recognised by the World Health Organization (WHO) include squamous metaplasia with dysplasia and carcinoma in situ, atypical adenomatous hyperplasia, and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. Other lesions that likely represent pre-invasive lesions, but which are not currently WHO-listed, include human papillomavirus (HPV)-related respiratory papillomatosis and mesothelioma in situ. No single cancer stem cell marker has been identified. Field cancerisation plays an important role in lung cancer development, and includes the spread of pre-invasive clones along the respiratory epithelium or the occurrence of multiple separate foci of pre-invasive abnormalities such as squamous dysplasia and carcinoma in situ.In addition to well-characterised step-wise progression in squamous cell carcinomas and some adenocarcinomas, alternative pathways exist, and are currently being investigated. In addition, molecular techniques, including miRNA screening on blood samples or cytology samples--such as sputum samples--may become clinically relevant and more accurate in predicting lung cancer progression.

In plain English

This article was a narrative review of lesions that may come before lung cancer and mesothelioma. It did not report a new study of patients, and it did not discuss asbestos exposure. The authors reviewed the lesions the World Health Organization lists as precursors: squamous dysplasia and carcinoma in situ, atypical adenomatous hyperplasia, and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). They also reviewed two lesions that are not listed: HPV-related respiratory papillomatosis and mesothelioma in situ. They judged the evidence for DIPNECH as a precursor to be extremely weak. On mesothelioma in situ, they wrote that there is consensus it cannot currently be diagnosed reliably on tissue examination unless invasive tumour is present nearby. They added that no stains or molecular tests reliably tell it apart from reactive mesothelial proliferations, and that they follow the recommendation to report such cases as "atypical mesothelial proliferation". An illustrative biopsy from a 73-year-old man with extensive pleural plaques showed atypical cells but no invasion. The authors concluded that HPV-related papillomatosis and mesothelioma in situ may represent pre-invasive lesions. They also concluded that even well-characterised precursor lesions are of extremely limited clinical usefulness.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: narrative review of the literature, with illustrative cases from the authors' own material
• Who was studied: No study population; published research on precursor lesions of lung and pleural tumours, illustrated with individual cases, including a 73-year-old man with extensive pleural plaques and a pleural effusion
• Exposure: Not an exposure study; asbestos is not mentioned. The review discusses cigarette smoking (and HPV infection) in relation to some precursor lesions.
• Main results:
  • The authors judged the evidence for some WHO-listed lesions as precursors, especially DIPNECH, to be extremely weak.
  • According to the authors, there is consensus that mesothelioma in situ cannot currently be diagnosed reliably by tissue examination without adjacent invasive tumour.
  • The authors stated that no immunohistochemical stains or molecular techniques currently reliably distinguish in situ mesothelioma from reactive mesothelial proliferations. They follow the recommendation to report such cases as 'atypical mesothelial proliferation'.
  • In the illustrative pleural biopsy from the 73-year-old man with extensive pleural plaques, prominent cellular atypia was seen but no invasion was found.
  • The authors stated there is good evidence for adding HPV-related respiratory papillomatosis to the WHO list of pre-invasive lesions, citing a case of a young woman infected with HPV at birth who had metastatic pulmonary squamous cell carcinoma by age 21.
  • The authors stated there is good molecular evidence that not all lung cancers develop in a step-wise manner, especially small cell lung carcinoma and some adenocarcinoma.
• The authors' conclusion: The authors concluded that HPV-related squamous papillomatosis and in situ mesothelioma are not WHO-listed but may represent pre-invasive lesions. They also concluded that the clinical usefulness of even relatively well-characterised precursor lesions is extremely limited.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Carcinoma, Epithelium, Idiopathic, Mesothelioma in Situ, STEM, Squamous Cell Carcinoma, Adenocarcinoma.

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• Cellular ingestion, toxic effects, and lesions observed in human bronchial epithelial tissue and cells cultured with asbestos and glass fibers — A. Haugen, P.W. Schafer, et al. (1982)
• Asbestos dust as a nucleation center in the calcification of old fibrous tissue lesions, and the possible association of this process to the formation of asbestos bodies — J.M. Davis (1970)

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