Bile cytology diagnosis in challenging cases: Validation of diagnostic bile cytology criteria and extensive study for immunocytochemical markers

Abstract

Background Bile cytology is useful in diagnosing biliary tract lesions, albeit often challenging due to equivocal findings. To achieve better diagnoses for clinical decisions, we conducted cytomorphological and immunocytochemical studies of bile cytology cases. Materials and methods We re‐evaluated 40 bile cytology cases with initial equivocal diagnoses, taken from the cytology records of Jichi Medical University Hospital, including 1778 bile cytology specimens. First, we assessed the cases by the diagnostic bile cytology criteria of the Japanese Society of Clinical Cytology. Second, we searched for useful immunocytochemical markers by extensive immunohistochemical analyses using tissue microarray for 10 antibodies: S100P, IMP3, GLUT1, p53, S100A4, Mapsin, MUC17, CD10, MDM2, and SMAD4. Microarrays were from 257 extrahepatic bile duct carcinoma cases. To elucidate the utility of immunocytochemistry, we applied selected markers to immunocytochemical evaluation of the equivocal cases after cell transfer. Results The criteria indicated a sensitivity 60%, specificity 87%, and accuracy 70%. Irregularly overlapping (88%), arranged (96%), and shaped (76%) nuclei were more common in malignant cases, while enlarged nuclei were more frequent in benign cases (67% vs. 28%). We applied S100P and IMP3, which showed higher accuracy (88% and 77%) in tissue microarray, to immunocytochemistry. The sensitivity of S100P and IMP3 were 69% and 70%, respectively. The specificity of S100P and IMP3 were 50% and 100%, respectively. Conclusion The criteria showed a certain effectiveness even in challenging cases, and some pitfalls associated with reactive changes of benign cells. Although comprehensive diagnosis including cytomorphology seems preferable, S100P and IMP3 are promising immunocytochemical markers.

Verifying a novel bile cytology scoring system

“…Therefore, we also believe that it is necessary to construct a scoring system that focuses on differentiating between WDAC and benign cells in the future. Moreover, Sano et al 9 also reported that combined immunocytochemistry and morphological evaluation might facilitate a more accurate diagnosis. Therefore, further improvements in accuracy can be achieved by combining the scoring system with immunostaining or fluorescent in situ hybridization (FISH).…”

“…Regarding WDAC determination, a factor contributing to the compromised diagnostic accuracy of bile cytology, differentiation of malignant cells is difficult owing to weak atypia, which often resembles benign cells. 9,16 Our SSBC was designed to improve the accuracy of differentiating between malignant and benign cells, including WDAC cells, while also reducing the number of indeterminate cases.…”

“…Therefore, we also believe that it is necessary to construct a scoring system that focuses on differentiating between WDAC and benign cells in the future. Moreover, Sano et al 9 also reported that combined immunocytochemistry and morphological evaluation might facilitate a more accurate diagnosis.…”

“…As described above, distinguishing between malignant and benign cells is often difficult, and cytological diagnostic accuracy is not always satisfactory. For that reason, several studies have reported the distinction between benign and malignant cells in bile cytology 1–11 . In Japan, the storage bile cytology criteria, 6 proposed by Hirooka et al, serve as a helpful tool for beginners and are widely used by cytotechnologists to identify adenocarcinoma.…”

“…For that reason, several studies have reported the distinction between benign and malignant cells in bile cytology. [1][2][3][4][5][6][7][8][9][10][11] In Japan, the storage bile cytology criteria, 6 proposed by Hirooka et al, serve as a helpful tool for beginners and are widely used by cytotechnologists to identify adenocarcinoma. However, in some cases, applying bile cytology criteria is challenging.…”