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PubMed Search: Lung tumor Preinvasive[title]

Roseann I. Wu, M.D., M.P.H.
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Cite this page: Wu R. Preinvasive-general. website. Accessed November 29th, 2023.
Definition / general
    Pulmonary preneoplastic changes include (Respir Res 2002;3:20):
  • Bronchial squamous dysplasia and in situ carcinoma preceding invasive squamous cell carcinoma and basaloid carcinoma
  • Atypical adenomatous hyperplasia preceding bronchioloalveolar carcinoma
  • Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, a proposed precursor for carcinoid tumor
Essential features
  • Squamous dysplasia / CIS is a multifocal and clonal condition strongly associated with cigarette smoking i.e. “field cancerization”
  • High grade squamous dysplasia / CIS is associated with an increased risk of invasive squamous cell carcinoma
  • Squamous dysplasia / CIS tends to arise in large central airways
  • “Dysplasia” usually used for squamous bronchial lesions
  • Angiogenic squamous dysplasia = capillary blood vessels closely juxtaposed to and projecting into metaplastic or dysplastic squamous bronchial epithelium (Clin Cancer Res 2000;6:1616)
ICD coding
  • D02.20: Carcinoma in situ of unspecified bronchus and lung
  • D02.21: Carcinoma in situ of right bronchus and lung
  • D02.22: Carcinoma in situ of left bronchus and lung
  • Squamous dysplasia / CIS with propensity for large central airways, usually around bifurcations, less commonly in trachea
  • May precede mass by many years
  • Pre invasive lesions and subsequent cancers are clonally related (J Pathol 2011;224:153)
  • Evidence for stepwise progression relatively weak, but concept of field carcinogenesis is strongly supported (Cancer Metastasis Rev 2010;29:5)
  • Associated with smoking
  • Possible progression from basal cells or metaplastic goblet cells to squamous metaplasia, dysplasia, CIS
Clinical features
  • Usually not symptomatic on its own
  • Image enhanced endoscopy i.e. autofluorescence bronchoscopy (AFB), high magnification bronchovideoscopy (HMS), narrow band imaging (NBI), endobronchial ultrasonography (EBUS), optical coherence tomography (OCT) (Clin Chest Med 2013;34:373)
  • Frequently encountered in resection specimens, but not often on endoscopic biopsy specimens
Prognostic factors
  • Some preneoplastic lesions regress, while others progress
  • No difference in progression rate and time to progression based on initial histologic grading; cannot differentiate the potentially more malignant lesions (Clin Cancer Res 2005;11:537)
  • Persistence of dysplasia associated with development of invasive carcinoma (Cancer Prev Res 2016;9:96)
  • Squamous dysplasia with high telomerase activity, increased Ki67 and p53 positivity tend to persist and might progress to carcinoma (Lung Cancer 2004;46:187)
  • CIS is strong predictor of progression to invasive squamous cell carcinoma (Cancer Metastasis Rev 2010;29:5)
Case reports
  • Three men ages 63, 65 and 71 years old with dysplastic lesions in bronchi which progressed to squamous cell carcinoma (Br J Cancer 1997;75:678)
  • Bronchoscopic followup of severe dysplasia and CIS, endobronchial or surgical techniques (Chest 2007;132:221S)
Gross description
  • Either unremarkable mucosa or papillary and granular with loss of folds
Microscopic (histologic) description
  • Histological patterns of bronchial epithelial dysplasia: basal cell dysplasia, columnar cell dysplasia, bronchial epithelial dysplasia with transitional differentiation and squamous dysplasia (Mod Pathol 2006;19:429)
  • Squamous dysplasia: focal to full thickness replacement of epithelium by squamous cells with increased nuclear to cytoplasmic ratio, nuclear pleomorphism, mitotic activity but intact basement membrane
    • No invasive growth although may extend into ducts of submucosal glands
    • Graded with a 4 tier (mild / moderate / severe / CIS) or 2 tier system (low grade / high grade) (J Clin Pathol 2001;54:257)
    • Mild dysplasia: minimal abnormalities with basal expansion, increased cellularity, vertically oriented nuclei, limited to bottom third of epithelium, mitoses absent or rare, maturation present
    • Moderate dysplasia: more abnormalities, partial maturation, extending to lower two thirds of epithelium, mitoses limited to lower two thirds
    • Severe dysplasia: cellular pleomorphism, coarse chromatin, frequent nucleoli, basal zone to upper third, mitoses confined to lower two thirds, superficial cell flattening
    • CIS: lack of maturation, significant cytologic abnormalities, coarse chromatin, inconsistent nuclear orientation, mitoses present in full thickness
  • Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH): preinvasive proliferation of pulmonary neuroendocrine cells
    • Proposed criteria for diagnosis on lung resection is multifocal neuroendocrine cell hyperplasia as defined by 5 or more pulmonary neuroendocrine cells in at least 3 separate small airways combined with 3 or more carcinoid tumorlets (Semin Diagn Pathol 2015;32:438, Lung 2015;193:659)
Microscopic (histologic) images

Contributed by Roseann Wu, M.D., M.P.H.
Moderate to severe dysplasia

Moderate to severe dysplasia

Images hosted on other servers:
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Various images

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Normal bronchial mucosa

Positive stains
Molecular / cytogenetics description
Differential diagnosis
  • Squamous metaplasia and reactive / reparative atypia
  • Basal cell hyperplasia
  • Squamous papilloma
Additional references
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