Pathologic Misclassification of Renal Cell Carcinoma in Adolescents and Young Adults

Background and Objective: Diagnosis of TFE3-rearranged RCC (tRCC) requires a pathologist’s expertise and a high index of suspicion. The objectives of this study were to determine the rate of misclassification of RCC in the adolescent and young adult (AYA) patient population, identify any clinically significant impact associated with misclassification, and compare oncologic outcomes between patients with tRCC vs. other RCC subtypes. Methods: All patients < 50 years who underwent renal surgery and were diagnosed with renal cell carcinoma at a single institution from 2004 to 2019 were identified retrospectively. Pathology specimens were reviewed by a genitourinary pathologist. Changes in a pathologic diagnosis were denoted as “misclassified.” Clinical and oncologic data were analyzed comparing misclassified and non-misclassified groups as well as tRCC and other RCC diagnoses. A survival analysis was used to compare oncologic outcomes. Results: In total, 169 patients were identified, and 20/169 (11.8%) patients were misclassified after pathologic review, with 50% (n = 84) of this cohort < 40 years of age at diagnosis. There were significant differences between misclassified and non-misclassified groups with respect to race (p = 0.002), Appalachian county status (p = 0.035), and initial RCC subtype (p = 0.004). There were no significant differences in clinical or oncologic outcomes between tRCC and other RCC groups. There were no significant differences in time to death or recurrence in misclassified vs. non-misclassified patients (p = 0.83 and 0.68, respectively) or between patients with tRCC and other RCC subtypes (p = 0.45 and 0.062, respectively). Conclusions: >10% of patients with RCC were misclassified on the original pathologic diagnosis; however, there was no significant impact on oncologic outcomes. This identifies diagnostic blind spots for tRCC diagnosis in a young cohort. Perhaps reflex IHC or molecular testing could be of importance upfront for the AYA population with renal masses.