843 Expanding Horizons: A Deeper Dive into the Morphologic and Genomic Landscape of ALK-Rearranged Renal Cell Carcinomas
Recommended Citation
Lobo A, Sangoi A, Al-Obaidy K, Akgul M, Acosta A, Kandukuri S, Jha S, Kaushal S, Satturwar S, Osunkoya A, Parwani A, Dhillon J, Williamson S, Shah R, Cheng L, Mohanty S. 843 Expanding Horizons: A Deeper Dive into the Morphologic and Genomic Landscape of ALK-Rearranged Renal Cell Carcinomas. Lab Invest 2025; 105(3).
Document Type
Conference Proceeding
Publication Date
3-24-2025
Publication Title
Lab Invest
Keywords
Caucasian, clinical article, conference abstract, diagnosis, diagnostic error, epithelioid histiocyte, female, fluorescence in situ hybridization, follow up, gene rearrangement, high throughput sequencing, histopathology, human, human cell, human tissue, immunofluorescence, immunohistochemistry, immunoreactivity, male, metastasis, microsatellite instability, middle aged, oncogene, renal cell carcinoma, RNA sequencing, spindle cell, tubulocystic renal cell carcinoma, tumor mutational burden, tumor volume
Abstract
Disclosures: Anandi Lobo: None; Ankur Sangoi: None; Khaleel Al-Obaidy: None; Mahmut Akgul: None; Andres Acosta: None; Shivani Kandukuri: None; Shilpy Jha: None; Seema Kaushal: None; Swati Satturwar: None; Adeboye Osunkoya: None; Anil Parwani: None; Jasreman Dhillon: None; Sean Williamson: None; Rajal Shah: None; Liang Cheng: None; Sambit Mohanty: None Background: Heterogeneous morphology and rarity of ALK-rearranged renal cell carcinoma (ALK-RCC) hinders their diagnosis solely based on histopathology leading to classifying these tumors into the RCC,NOS category. ALK oncogene rearrangement as seen in this neoplasm is a therapeutic target and the patients potentially benefit from ALK-inhibitors. Therefore, we attempt to elucidate the clinicopathologic characteristics of a cohort of ALK-RCC through an international collaboration. Design: Sixteen cases were collated to comprehend the overarching clinical, gross, microscopic, immunohistochemical (IHC), molecular features (DNA and RNA sequencing, FISH, microsatellite instability and tumor mutational burden) and follow-up data. Results: Clinical presentation: There were 9 males and 7 females, tumor size ranging from 2 to 12.2cm (mean=7.1cm). (Table 1) Histopathologic features: All tumors were solid, tan-white with focal cystic changes and gelatinous appearance. Necrosis was seen in 6 tumors. Heterogeneous pattern was observed; mucinous tubular spindle (7),papillary (5), tubulocystic (2), pleomorphic epithelioid cells (6), sarcomatoid (2), rhabdoid (4) and intranuclear pseudoinclusions (6). (Figures 1 and 2) Detailed histopathologic features, IHC, molecular profile, treatment and follow-up are given in Table 1 and Figures 1 and 2. [Formula presented] [Formula presented] [Formula presented] Conclusions: 1. Our study further expands the clinicopathologic, morphologic and molecular genetic spectrum of ALK-RCC. 2. This is the largest series till date, enrolling 16 tumors through a multi-institutional collaboration. 3. This series adds to the growing body of literature on this distinct entity, supporting and expanding upon the observations by previous studies. 4. ALK-RCC can be morphologically heterogeneous and mimic other well established entities (mucinous tubular and spindle cell RCC, tubulocystic RCC, papillary RCC, clear cell papillary tumor, BAP1 deficient RCC, TFE3-rearranged RCC, and others) posing a misdiagnosis if appropriate IHC and/or molecular studies are not performed. 5. Accurate diagnosis is of clinical significance as patients with this neoplasm may potentially benefit from ALK-inhibitors, particularly in a metastatic setting. 6. As TFE3 immunoreactivity is not uncommon in ALK-RCC, a molecular assay of ALK gene rearrangements either by FISH or NGS is mandatory for a definite diagnosis.
Volume
105
Issue
3
