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Imaging, Diagnosis, Prognosis

The Natural Course of Preneoplastic Lesions in Bronchial Epithelium

Roderick H. Breuer, Arifa Pasic, Egbert F. Smit, Esther van Vliet, Anton Vonk Noordegraaf, Elle J. Risse, Pieter E. Postmus and Thomas G. Sutedja
Roderick H. Breuer
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Arifa Pasic
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Egbert F. Smit
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Esther van Vliet
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Anton Vonk Noordegraaf
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Elle J. Risse
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Pieter E. Postmus
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Thomas G. Sutedja
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DOI:  Published January 2005
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  • Fig. 1
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    Fig. 1

    A representative example of histology of each preneoplastic lesions (HE 400×). A, squamous metaplasia; B, mild dysplasia; C, moderate dysplasia; D, severe dysplasia; E, CIS.

  • Fig. 2
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    Fig. 2

    Distribution of preneoplastic lesions and outcome of a longitudinal study in 52 individuals at risk harboring squamous metaplasia, mild, moderate, and severe dysplasia at baseline examination. Preneoplastic lesions progressing to CIS or SCC and its corresponding time to progression. Note that in comparison with Fig. 3, individuals at risk may initially harbor and/or develop multiple progressive lesions during follow-up. Outcome is determined by the highest grade of each preneoplastic lesion at the last analysis closest to the March 1, 2003 time point, (R, regression; S, stable; P, progression).

  • Fig. 3
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    Fig. 3

    Outcome of preneoplastic lesions per individual at risk. HGD cohort consists of 18 individuals with ≥1 severe dysplasia at baseline whether or not accompanied by ≥1 LGD. LGD group consists of 34 individuals with ≥1 squamous metaplasia, mild dysplasia, or moderate dysplasia preneoplastic lesion at baseline (thus without severe dysplasia). Outcome is determined by the highest grade of any preneoplastic lesion at the last analysis closest to the March 1, 2003 time point in each individual of any preneoplastic lesion during follow up (R, regression; S, stable preneoplastic lesion; P, progression).

  • Fig. 4
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    Fig. 4

    Examples of the nonstepwise changes of preneoplastic lesions in four patients (A-D) according to the WHO morphological classification. 1, Normal; 2, hyperplasia; 3, squamous metaplasia; 4, mild dysplasia; 5, moderate dysplasia; 6, severe dysplasia; 7, CIS/microinvasive SCC. RB3, segmental carina anterior right upper lobe; RB6, segmental carina superior right lower lobe; LB6, segmental carina superior left lower lobe.

Tables

  • Figures
  • Table 1

    Characterisitics of 52 individuals at risk harboring preneoplastic lesions (preneoplastic lesions: squamous metaplasia, mild, moderate, and severe dysplasia) in the central airways at baseline bronchoscopic examinations

    Total number of individuals52
    Gender:
        Male44
        Female8
    Median age (y), (range)64 (42-78)
    COPD31
    Non-COPD21
    Smoking history
        Current smokers12
        Ex-smokers38
        Never-smokers2
    Median no. (range) of pack-years smoked39.5 (0-120)
    Age (range) at smoking initiation19 (8-27)
    Median no. years (range) after smoking cessation3.5 (1-39)
    Medical history
        Group 1: at risk for lung cancer primary21
        Group 2: at risk for subsequent primary
        Past ENT cancer8
        Past lung cancer treated surgically11
        Past lung cancer treated bronchoscopically5
        ≥2 primaries: ENT-Lung; Lung-Lung7
    Total no. of bronchoscopies237
    Median no. (range) of bronchoscopies per subject4 (2-19)
    Total no. of lesions (preneoplastic lesions) sampled longitudinally483
    Median no. lesions (preneoplastic lesions) sampled per subject5 (2-61)
  • Table 2

    The distribution of preneoplastic lesions at baseline bronchosocpic examinations in 52 individuals, tabulated according to factors such as gender, COPD, etc

    No. patientsTotal no. lesionsAverage no. lesionsPLGDPHGDPProgression to CIS/SCCP
    Gender521340.51.00.23
        Male44 (85%)115 (85%)2.629 (66%)15 (34%)1.012/44 (27%)
        Female8 (15%)19 (15%)2.45 (62%)3 (38%)4/8 (50%)
    COPD31 (60%)85 (63%)2.70.420 (65%)1.011 (35%)1.011/31 (35%)0.54
    Non-COPD21 (40%)49 (37%)2.314 (67%)7 (33%)5/21 (24%)
    Medical history
    At risk21 (40%)56 (42%)2.70.9012 (57%)0.219 (43%)0.387/21 (33%)0.77
    Previous primaries31 (60%)78 (58%)2.522 (71%)9 (29%)9/31 (29%)
    Current smokers (average pack years 47)12 (23%)36 (27%)3.00.378 (67%)1.04 (33%)1.00.30
    Ex-smokers+ (average pack-years = 42 )40* (77%)98 (73%)2.526 (65%)14 (35%)14/40 (35%)
    Ex-smokers38960.850.740.18
        Stop <5 y20 (53%)57 (59%)2.812 (60%)8 (40%)0.749/20 (45%)
        Stop ;≥5 y18 (47%)39 (41%)2.212 (67%)6 (33%)4/18 (22%)
    Pack-years520.160.21160.51
        0-2515* (29%)32 (24%)2.112 (80%)3 (20%)0.216/15 (40%)
        >2637 (71%)102 (76%)2.722 (59%)15 (41%)10/37 (27%)
    • NOTE. LGD cohort of individuals (harboring ≥1 squamous metaplasia, mild, or moderate dysplasia) is compared with HGD cohort of individuals (harboring ≥1 severe dysplasia whether or not accompanied by ≥1 LGD lesion). Progression rate to CIS or SCC and Ps are also shown.

    • ↵* Including two never smokers.

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Clinical Cancer Research: 11 (2)
January 2005
Volume 11, Issue 2
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The Natural Course of Preneoplastic Lesions in Bronchial Epithelium
Roderick H. Breuer, Arifa Pasic, Egbert F. Smit, Esther van Vliet, Anton Vonk Noordegraaf, Elle J. Risse, Pieter E. Postmus and Thomas G. Sutedja
Clin Cancer Res January 15 2005 (11) (2) 537-543;

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The Natural Course of Preneoplastic Lesions in Bronchial Epithelium
Roderick H. Breuer, Arifa Pasic, Egbert F. Smit, Esther van Vliet, Anton Vonk Noordegraaf, Elle J. Risse, Pieter E. Postmus and Thomas G. Sutedja
Clin Cancer Res January 15 2005 (11) (2) 537-543;
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