Editors: Rouzan Karabakhtsian, MD, PhD, professor of pathology and director of the Women’s Health Pathology Fellowship, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY; Shaomin Hu, MD, PhD, staff pathologist, Cleveland Clinic; S. Emily Bachert, MD, associate pathologist, Brigham and Women’s Hospital, Boston; and Amarpreet Bhalla, MD, assistant professor of pathology, Albert Einstein College of Medicine, Montefiore Medical Center.
AKR1B10 as a marker for fumarate hydratase-deficient renal cell carcinoma
April 2024—Fumarate hydratase-deficient renal cell carcinoma is a rare and distinct subtype of renal cancer caused by FH gene mutations. FH negativity and s-2-succinocysteine (2SC) positivity on IHC can be used to screen for FH-deficient renal cell carcinoma (RCC), but their sensitivity and specificity are imperfect. The expression of AKR1B10, an aldo-keto reductase that catalyzes cofactor-dependent oxidation-reduction reactions, in RCC is unclear. The authors compared AKR1B10, 2SC, and FH as diagnostic biomarkers for FH-deficient RCC. They included genetically confirmed FH-deficient RCCs (n=58), genetically confirmed TFE3 translocation RCCs (TFE3-tRCC; n=83), clear cell RCCs (n=188), chromophobe RCCs (n=128), and papillary RCCs (pRCC; n=97). AKR1B10, 2SC, and FH were informative diagnostic markers. AKR1B10 exhibited 100 percent sensitivity and 91.4 percent specificity for FH-deficient RCC. The nonspecificity of AKR1B10 was shown in 26.5 percent of TFE3-tRCCs and 21.6 percent of pRCCs. 2SC exhibited 100 percent sensitivity and 88.9 percent specificity. However, nonspecificity for 2SC was evident in multiple RCCs, including pRCC, TFE3-tRCC, clear cell RCC, and chromophobe RCC. FH was 100 percent specific but 84.5 percent sensitive. AKR1B10 served as a highly sensitive and specific diagnostic biomarker. The findings suggest the value of combining AKR1B10 and 2SC to screen for FH-deficient RCC. AKR1B10+/2SC+/FH− cases can be diagnosed as FH-deficient RCC. Patients with AKR1B10+/2SC+/FH+ are highly suspicious for FH-deficient RCC and should be referred for FH genetic testing after excluding TFE3-tRCC.
Zheng L, Zhang X, Pan X, et al. AKR1B10 is a new sensitive and specific marker for fumarate hydratase-deficient renal cell carcinoma. Mod Pathol. 2023;36(11). doi:10.1016/j.modpat.2023.100303
Correspondence: Dr. Ni Chen at chenni1@163.com or Dr. Hao Zeng at kucaizeng@163.com
Intraoperative communication between pathologists and surgeons
Clear communication between pathologists and surgeons during intraoperative consultation contributes to optimal patient care. The authors conducted pre- and postintervention studies to examine the concordance between intraoperative diagnoses recorded in pathology reports and surgeon-dictated operative notes and to assess how interventions impact discrepancy rates. Discrepancies between pathologists’ intended communication and surgeons’ interpretation were characterized as minor with no crucial clinical impact or major with the potential of altering patient management. The authors examined 223 surgical cases with 578 intraoperative consultations in the preintervention study. In 23 percent (51) of the cases, the intraoperative diagnosis was not recorded in the operative reports. The authors found minor discrepancies in 34 percent (59) and major discrepancies in two percent (three) of the remaining cases. Deferrals accounted for 24 percent (14 of 59) of the minor and 33 percent (one of three) of the major discrepancies. Among the discrepant cases, 56 percent (35 of 62) were multipart cases, including all major discrepancies. After implementing corrective intervention that included education, information sharing, and a change in protocol, the authors conducted the postintervention study, which involved 101 cases with 186 intraoperative interpretations. No documentation of intraoperative consultation was found in operative reports in 16 percent of cases. Minor discrepancies were found in 11 percent of the postintervention cases, indicating significant improvement (P<.001). The authors concluded that intraoperative diagnoses can be miscommunicated or misinterpreted, or both, potentially impacting intraoperative management, particularly in multipart cases and those involving deferrals. This study highlights the importance of auditing intraoperative communications and addressing the findings through local intervention.
Wiggett A, Fischer G. Intraoperative communications between pathologists and surgeons: Do we understand each other? Arch Pathol Lab Med. 2023;147(8):933–939.
Correspondence: Dr. Gabor Fischer at gabor.fischer@umanitoba.ca
Ability of high mesothelin expression by IHC to predict survival with pleural mesothelioma
Mesothelin is a cancer-associated antigen that is overexpressed in malignancies such as mesothelioma and pancreatic and ovarian cancer. It is also a target for novel personalized therapies, including antibodies, antibody-drug conjugates, and chimeric antigen receptor T cells. Immunohistochemistry may predict those who would respond best to anti-mesothelin therapies and guide decisions in therapeutic strategy. The authors conducted a study to assess the intensity and distribution of mesothelin immunostaining in mesothelioma and ascertain the prognostic value of mesothelin expression for determining which patients are suitable for anti-mesothelin-targeted therapies, which could help in designing future clinical trials. The MN1 anti-mesothelin antibody was used to stain formalin-fixed, paraffin-embedded tissue microarrays of histologically confirmed mesothelioma from 75 consecutive patients who had undergone pleurectomy with or without decortication. Mesothelin positivity, staining intensity, distribution of staining, and histochemical score (H-score) were evaluated. The correlation of H-score with prognosis was investigated. Sixty-six percent of epithelioid tumors were mesothelin positive, with expression in more than five percent of tumor cells. Of the mesothelin-expressing epithelioid tumors, 70.4 percent had moderate (2+) or strong (3+) intensity mesothelin immunostaining, although only 37 percent of samples had staining in 50 percent or more of tumor cells. In multivariate analysis, mesothelin H-score as a continuous variable and an H-score of 33 or more were independent predictors of improved survival (P= .04 and P<.001, respectively). The authors concluded that mesothelin expression was more heterogenous in epithelioid mesothelioma than reported previously. Therefore, it is appropriate to use IHC as a diagnostic assay to stratify and select patients suitable for receiving mesothelin-targeted personalized therapies in future clinical trials.
Chu GJ, Linton A, Kao S, et al. High mesothelin expression by immunohistochemistry predicts improved survival in pleural mesothelioma. Histopathology. 2023;83(2):202–210.
Correspondence: Dr. John E. J. Rasko at j.rasko@centenary.org.au or Dr. Wendy A. Cooper at wendy.cooper@health.nsw.gov.au