RESUMEN
OBJECTIVES: The microscopic features of urine cytology specimens are subjective and may not reliably distinguish between benign urothelial cells and low-grade urothelial carcinoma (UC). Prior studies demonstrated that keratin 17 (K17) detection in biopsies is highly sensitive for UC. The current study aimed to define K17 diagnostic test performance for initial screening and detect recurrent UC in urine specimens. METHODS: K17 was detected by immunocytochemistry (ICC) in consecutively collected urine specimens (2018-2019). A qualitative score for the K17 test was determined in 81 samples (discovery cohort) and validated in 98 samples (validation cohort). K17 sensitivity and specificity were analyzed in both cohorts across all grades of UC. RESULTS: Based on the discovery cohort, the presence of 5 or more K17 immunoreactive urothelial cells (area under the curve = 0.90; P < .001) was the optimal threshold to define a K17-positive test. The sensitivity of the K17 ICC test for biopsy-confirmed UC was 35 of 36 (97%) and 18 of 21 (86%) in the discovery and validation cohorts, respectively. K17 was positive in 16 of 19 (84%) specimens with biopsy-confirmed low-grade UC and in 34 of 34 (100%) of specimens with high-grade UC. CONCLUSIONS: K17 ICC is a highly sensitive diagnostic test for initial screening and detection of recurrence across all grades of UC.
Asunto(s)
Biomarcadores de Tumor/orina , Carcinoma de Células Transicionales/diagnóstico , Citodiagnóstico/métodos , Queratina-17/orina , Neoplasias de la Vejiga Urinaria/diagnóstico , Adulto , Anciano , Carcinoma de Células Transicionales/orina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Neoplasias de la Vejiga Urinaria/orinaRESUMEN
INTRODUCTION: Only 15%-20% of newly diagnosed pancreatic ductal adenocarcinoma (PDAC) cases are surgically operable. Cytology samples may be the only source for guiding clinical management. Current research indicates that mismatch repair (MMR) status could be valuable for implementing novel treatment modalities. In this study, immunohistochemical (IHC) MMR protein expression on cytology cell blocks was compared with that of the correlating surgical resection specimens. MATERIALS AND METHODS: A retrospective review of 120 pancreatic solid tumor needle biopsies from 2016 to 2019 was performed, and 15 experimental cases were selected comprising of cellular (>100 tumor cells and >100 benign positive control cells that include benign ductal cells and/or lymphocytes) alcohol-prefixed formalin-fixed cytology cell blocks (CB), and corresponding subsequent surgical resections (Surg). The cases include 13 PDACs (87%), 1 (6.5%) low grade neuroendocrine tumor (PNET), and 1 (6.5%) acinar cell carcinoma (ACC). A routine four-panel (MLH1, MSH2, MSH6, and PMS2) MMR IHC testing was performed. The percentage of protein expression was evaluated and compared between individual CB-Surg pairs. RESULTS: About 8 of the 15 (53.3%) cytology cases showed matching protein expressivity with the surgical specimens for all four MMR markers (Table 1). The remaining 7 pairs (46.7%) appeared to have a partial concordance, including 6 values for which a surgical marker showed less expression, and 13 values for which a cytological marker showed less expression. [Table: see text] CONCLUSION: Cytology CB MMR protein panel testing could be a useful consideration for inoperable patients who would benefit from medical therapy such as immune checkpoint inhibition. However, the cellularity and overall quality of the CB is expected to be paramount in obtaining satisfactory IHC MMR results. The MMR results could be more confidently trusted when the staining is intact, but when not retained, they should be interpreted with caution in a low cellularity sample to avoid mistakenly identifying MMR-deficient tumors.