TY - JOUR
T1 - Diagnosis of urothelial carcinoma in situ using blue light cystoscopy and the utility of immunohistochemistry in blue light-positive lesions diagnosed as atypical
AU - Pederzoli, Filippo
AU - Amador, Belkiss Murati
AU - Samarska, Iryna
AU - Lombardo, Kara A.
AU - Kates, Max
AU - Bivalacqua, Trinity J.
AU - Matoso, Andres
N1 - Funding Information:
Funding/Support: This work was supported by the Department of Pathology at Johns Hopkins University and by a National Institutes of Health Institutional Research Training Grant (T32 CA193145 to B. M. A.).
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/8
Y1 - 2019/8
N2 - Carcinoma in situ (CIS) is difficult to visualize with white light cystoscopy (WLC), whereas blue light cystoscopy (BLC) using photosensitizing agents improves detection rates. We retrospectively reviewed transurethral biopsies of bladder tumors in which both WLC and BLC evaluations were performed (n = 135 samples from 79 patients). Biopsies were classified based on the presence/absence of fluorescence under BLC and the final pathological report (CIS/benign/atypical). Forty-one (30%) cases were diagnosed as CIS; of those, 38 (93%) were BLC(+), including 23 that were WLC(-). Conversely, 51 (38%) lesions were BLC(+) but classified as non-CIS. Eleven BLC(+) cases were diagnosed as "atypical." These cases were anonymized and reviewed by 7 pathologists for concordance and then immunostained for CK20, p53, and Ki-67. Immunohistochemistry results were interpreted as consistent with CIS if there was full thickness staining of CK20, more than 50% p53-positive cells, and more than 50% Ki-67 positive cells. Review of BLC(+)/atypical cases showed a mean agreement of 79%, and none of the cases showed staining pattern consistent with CIS. Therefore, all 11 cases of BLC(+)/atypical were considered non-CIS for the final analysis. All patients with BLC(+)/atypical lesions had a history of intravesical Bacillus Calmette-Guerin and/or mitomycin. Using final pathology as the reference, sensitivity, specificity, and negative predictive value of BLC were 93% (confidence interval [CI], 80.1%-98.5%), 46% (CI, 35.4%-56.3%), and 94% (CI, 82.5%-97.8%), respectively. The low specificity of BLC leads to BLC(+) lesions with atypical diagnosis. Morphological classification of these lesions is fairly consistent among different pathologists. Immunohistochemistry for p53/CK20/Ki-67 in this setting is only helpful to potentially avoid overcalling CIS. (C) 2019 Elsevier Inc. All rights reserved.
AB - Carcinoma in situ (CIS) is difficult to visualize with white light cystoscopy (WLC), whereas blue light cystoscopy (BLC) using photosensitizing agents improves detection rates. We retrospectively reviewed transurethral biopsies of bladder tumors in which both WLC and BLC evaluations were performed (n = 135 samples from 79 patients). Biopsies were classified based on the presence/absence of fluorescence under BLC and the final pathological report (CIS/benign/atypical). Forty-one (30%) cases were diagnosed as CIS; of those, 38 (93%) were BLC(+), including 23 that were WLC(-). Conversely, 51 (38%) lesions were BLC(+) but classified as non-CIS. Eleven BLC(+) cases were diagnosed as "atypical." These cases were anonymized and reviewed by 7 pathologists for concordance and then immunostained for CK20, p53, and Ki-67. Immunohistochemistry results were interpreted as consistent with CIS if there was full thickness staining of CK20, more than 50% p53-positive cells, and more than 50% Ki-67 positive cells. Review of BLC(+)/atypical cases showed a mean agreement of 79%, and none of the cases showed staining pattern consistent with CIS. Therefore, all 11 cases of BLC(+)/atypical were considered non-CIS for the final analysis. All patients with BLC(+)/atypical lesions had a history of intravesical Bacillus Calmette-Guerin and/or mitomycin. Using final pathology as the reference, sensitivity, specificity, and negative predictive value of BLC were 93% (confidence interval [CI], 80.1%-98.5%), 46% (CI, 35.4%-56.3%), and 94% (CI, 82.5%-97.8%), respectively. The low specificity of BLC leads to BLC(+) lesions with atypical diagnosis. Morphological classification of these lesions is fairly consistent among different pathologists. Immunohistochemistry for p53/CK20/Ki-67 in this setting is only helpful to potentially avoid overcalling CIS. (C) 2019 Elsevier Inc. All rights reserved.
KW - Urothelial carcinoma in situ
KW - Blue light cystoscopy
KW - Photosensitizing agents
KW - HEXAMINOLEVULINATE FLUORESCENCE CYSTOSCOPY
KW - BLADDER-CANCER
KW - PHASE-III
KW - PHOTODYNAMIC DIAGNOSIS
KW - P53
KW - KI-67
KW - CYTOKERATIN-20
KW - RECURRENCE
KW - CK20
U2 - 10.1016/j.humpath.2019.04.018
DO - 10.1016/j.humpath.2019.04.018
M3 - Article
C2 - 31071342
SN - 0046-8177
VL - 90
SP - 1
EP - 7
JO - Human Pathology
JF - Human Pathology
ER -