Lung tumor
Dysplasia / carcinoma in situ
Dysplasia - general

Author: Roseann Wu, M.D., M.P.H. (see Authors page)

Revised: 14 November 2016, last major update November 2016

Copyright: (c) 2003-2016, PathologyOutlines.com, Inc.

PubMed Search: Lung tumor Dysplasia[title]
Cite this page: Dysplasia - general. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lungtumordysplasiagen.html. Accessed December 8th, 2016.
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
Terminology
  • “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-10 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
Epidemiology
Sites
  • Squamous dysplasia / CIS with propensity for large central airways, usually around bifurcations, less commonly in trachea
Pathophysiology
  • 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)
Etiology
  • 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
Diagnosis
  • 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)
Treatment
  • Bronchoscopic followup of severe dysplasia and CIS, endobronchial or surgical techniques (Chest 2007;132:221S)
Clinical Images
Gross Description
  • Either unremarkable mucosa or papillary and granular with loss of folds
Micro 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)
Micro Images

Images hosted on Pathout server:

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



Images hosted on other servers:
Missing Image

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