L1 cell adhesion molecule (L1CAM) expression and molecular alterations distinguish low-grade oncocytic tumor from eosinophilic chromophobe renal cell carcinoma Journal Article
| Authors: | Alghamdi, M.; Chen, J. F.; Jungbluth, A.; Koutzaki, S.; Palmer, M. B.; Al-Ahmadie, H. A.; Fine, S. W.; Gopalan, A.; Sarungbam, J.; Sirintrapun, S. J.; Tickoo, S. K.; Reuter, V. E.; Chen, Y. B. |
| Article Title: | L1 cell adhesion molecule (L1CAM) expression and molecular alterations distinguish low-grade oncocytic tumor from eosinophilic chromophobe renal cell carcinoma |
| Abstract: | Renal low-grade oncocytic tumor (LOT) is a recently recognized renal cell neoplasm designated within the “other oncocytic tumors” category in the 2022 World Health Organization classification system. Although the clinicopathologic, immunohistochemical, and molecular features reported for LOT have been largely consistent, the data are relatively limited. The morphologic overlap between LOT and other low-grade oncocytic neoplasms, particularly eosinophilic chromophobe renal cell carcinoma (E-chRCC), remains a controversial area in renal tumor classification. To address this uncertainty, we characterized and compared large cohorts of LOT (n = 67) and E-chRCC (n = 69) and revealed notable differences between the 2 entities. Clinically, LOT predominantly affected women, whereas E-chRCC showed a male predilection. Histologically, although almost all LOTs were dominated by a small-nested pattern, E-chRCC mainly showed solid and tubular architectures. Molecular analysis revealed that 87% of LOT cases harbored mutations in the tuberous sclerosis complex (TSC)-mTOR complex 1 (mTORC1) pathway, most frequently in MTOR and RHEB genes; a subset of LOT cases had chromosomal 7 and 19q gains. In contrast, E-chRCC lacked mTORC1 mutations, and 60% of cases displayed chromosomal losses characteristic of chRCC. We also explored the cell of origin for LOT and identified L1 cell adhesion molecule (L1CAM), a collecting duct and connecting tubule principal cell marker, as a highly sensitive and specific ancillary test for differentiating LOT from E-chRCC. This distinctive L1CAM immunohistochemical labeling suggests the principal cells as the cell of origin for LOT, unlike the intercalated cell origin of E-chRCC and oncocytoma. The ultrastructural analysis of LOT showed normal-appearing mitochondria and intracytoplasmic lumina with microvilli, different from what has been described for chRCC. Our study further supports LOT as a unique entity with a benign clinical course. Based on the likely cell of origin and its clinicopathologic characteristics, we propose that changing the nomenclature of LOT to “Oncocytic Principal Cell Adenoma of the Kidney” may be a better way to define and describe this entity. © 2024 United States & Canadian Academy of Pathology |
| Keywords: | immunohistochemistry; adult; human tissue; protein expression; aged; unclassified drug; gene mutation; human cell; major clinical study; disease course; histopathology; cancer grading; differential diagnosis; protein; cohort analysis; oncocytoma; cytoplasm; mtor signaling; mitochondrion; cell adhesion molecule; chromosome 7; chromosome 19q; mammalian target of rapamycin complex 1; cell ultrastructure; chromophobe renal cell carcinoma; rheb protein; microvillus; human; male; female; article; l1 cell adhesion molecule; l1cam; low-grade oncocytic tumor; principal cells; renal oncocytic neoplasm; tsc/mtor; tuberous sclerosis complex protein; eosinophilic chromophobe renal cell carcinoma |
| Journal Title: | Modern Pathology |
| Volume: | 37 |
| Issue: | 5 |
| ISSN: | 0893-3952 |
| Publisher: | Nature Research |
| Date Published: | 2024-05-01 |
| Start Page: | 100467 |
| Language: | English |
| DOI: | 10.1016/j.modpat.2024.100467 |
| PUBMED: | 38460672 |
| PROVIDER: | scopus |
| PMCID: | PMC11102321 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF. Corresponding MSK author is Ying-Bei Chen -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work