Abstract 1518: Benign oncocytic tumors in the setting of HLRCC syndrome
Authors: Akbulut Dilara , Ball Mark , Raffeld Mark , Linehan Marston , Merino Maria J. 
Published: April 2023

Abstract
Background: Renal cell carcinomas developing in patients with HLRCC syndrome are known to be aggressive single tumors of variable sizes, with a well-established morphology. Other morphological tumor types occurring in association with classic HLRCC tumors as independent neoplasias in this syndrome, have not been clearly recognized and described. We describe four patients with known HLRCC syndrome with confirmed germ line mutation who developed benign oncocytic renal tumors. Since HLRCC can also be oncocytic in many instances, it is important to be aware of the possible benign oncocytic tumors in this patient group.
Design: Four patients with known positive germ line FH mutation and known HLRCC syndrome developed associated or new oncocytic tumors. All tumors were morphologically evaluated, IHC staining was done for FH, 2SC, CKIT, CK7, PAX8 and molecular studies were performed with TSO-500 for the evaluation of other genes. Clinicopathological correlation was done in all cases.
Results: The tumors had been identified radiologically and were suspicious for malignancy. Age range was 37-73 years, and all the patients were female. Two patients had coexistent HLRCC cancers while two only had the oncocytomas. Localization was left kidney for all the masses, which were brown in color and well circumscribed and varied in size from 0.7 to 4 cm. In one patient, four separate masses were identified with different locations and sizes, but with the same morphology. This specific patient presented with two additional masses in the opposite kidney later. Tumors were composed of large oncocytic cells with prominent granular eosinophilic cytoplasm and dark pyknotic nuclei. No evidence of atypia, mitosis or necrosis was found. FH was positive, 2SC and CK7 were negative on IHC stains, whereas CKIT showed diffuse membranous positivity. Tumors were diagnosed as oncocytomas. All patients were positive for FH germ line mutation and the mutation was also identified in the tissues. Other molecular studies on the patient with multiple tumors showed additional pathogenic ERCC2 inactivating mutation, suggesting germline, which is rarely encountered in kidney tumors. All the patients are alive and free of disease up to 10 years after diagnosis.
Conclusion: HLRCC cancers can have a variety of morphologic patterns and frequently have oncocytic features. Clinical information, genetic testing and special techniques are helpful in the diagnosis of these high-grade tumors. Recognizing that other benign indolent tumors with oncocytic features can occur in this syndrome is important to avoid errors in diagnosis and treatment.
Citation Format: Dilara Akbulut, Mark Ball, Mark Raffeld, Marston Linehan, Maria J. Merino. Benign oncocytic tumors in the setting of HLRCC syndrome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1518.