Hybrid Oncocytic Tumors (HOTs) in Birt-Hogg-Dubé Syndrome Patients—A Tale of Two Cities: Sequencing Analysis Reveals Dual Lineage Markers Capturing the 2 Cellular Populations of HOT
\nWang, Xiao-Ming; Mannan, Rahul; Zhang, Yuping; More
\nThe American Journal of Surgical Pathology. 48(2):163-173, February 2024.
\nFREE LINK (expires 4\/22\/24)
\n<a
\nhttps:\/\/journals.lww.com\/ajsp\/fulltext\/2024\/02000\/hybrid_oncocytic_tumors__hots__in_birt_hogg_dub_.5.aspx <\/p>\n
Précis<\/em><\/p>\n The authors evaluated the expression of the principal cell marker L1CAM and intercalated cell marker LINC01187 in a series of Birt-Hogg-Dubé (BHD) and non-BHD associated renal tumors. The first cohort comprised 13 hybrid oncocytic tumor (HOT), 3 chromophobe renal cell carcinoma (ChrRCC), and 2 unclassified oncocytic RCC, whereas the non-BHD renal tumors included ChrRCC, 6 eosinophilic pattern ChrRCC, 18 renal oncocytoma (RO), 5 low-grade oncocytic tumor (LOT), 6 oncocytic unclassified RCC, 8 clear cell RCC (ccRCC), 11 papillary RCC (PRCC), 5 clear cell papillary renal cell tumor (CCPRCT), MiTF aberration-associated RCC (MiTF-RCC) including 4 TFE3-rearranged RCC, 1 TFEB-rearranged RCC and 2 TFEB amplified RCC, 7 eosinophilic solid and cystic renal cell carcinoma (ESC-RCC), 5 acquired cystic disease-associated RCC (ACD-RCC), 1 mucinous tubular and spindle cell carcinoma (MTSCC), and 1 succinated dehydrogenase B (SHDB) deficient RCC. Using immunohistochemistry and RNA in situ hybridization, the researchers found that the membranous L1CAM and nuclear LINC01187 expressions were observed in HOT tumor cells with clear and eosinophilic cytoplasm, respectively, resulting in a unique checkered pattern that allowed to distinguish HOT from BHD-associated unclassified RCC, the latter being L1CAM+\/LINC01187-. In the sporadic tumor cohort, classic ChrRCC, RO, and unclassified tumors, were L1CAM-\/LINC01187+; conversely, LOT, SDHB deficient RCC, and CCPRCT were L1CAM+\/LINC01187-. Most other tumors showed lack of LINC01187 expression, along with variable L1CAM staining.<\/p>\n Comment<\/em><\/p>\n A hybrid tumor featuring an admixture of chromophobe and eosinophilic cells is the most common tumor type seen in BHD patients, with a corresponding checkered expression of CD117 and CK7 in the two morphologically distinct areas. In this study, the authors elegantly demonstrate the presence of 2 different specific markers, L1CAM and LINC01187 for each cellular population within the tumor. The same expression profile is demonstrated in a patient with multiple nodules showing morphologies of HOT and unclassified RCC, arguing for intertumoral heterogeneity in BHD-associated tumors. The authors provide evidence for double pathogenesis of HOT, whose different cell populations are thought to arise from different cell types within the distal tubule, namely both IC cells and PC cells. These results allow for further speculation. ChrRCC and RO are both CD117+, and are believed to derive from IC, as demonstrated by their shared L1CAM-\/LIN01187+ pattern. Conversely, 5 LOT in this cohort, besides being CD117-, uniformly exhibited L1CAM+\/LINC01187-, further demonstrating that this histotype, despite showing oncocytic morphology, has a different pathogenesis and biological characteristics as compared to tumors in the chromophobe\/oncocytic spectrum. Interestingly, unclassified oncocytic RCC showed an opposite staining profile in sporadic (L1CAM-\/LINC01187+, likewise ChrRCC and RO) and syndromic (L1CAM+\/LIN01187-) settings, the latter overlapping with oncocytic nodules. Such studies underline the usefulness of immunohistochemical and in situ hybridization methods to precisely characterize distinct cellular populations and tumors; this is particularly important for implementing new markers in clinical practice, especially in diagnostically challenging settings.<\/p>\n Reviewed by: Francesca Sanguedolce MD PhD<\/p>\n The author responds (Dr. Rohit Mehra):<\/em><\/p>\n We agree with the summary.<\/p>\n<\/body><\/html>\n","protected":false},"excerpt":{"rendered":" Hybrid Oncocytic Tumors (HOTs) in Birt-Hogg-Dubé Syndrome Patients—A Tale of Two Cities: Sequencing Analysis Reveals Dual Lineage Markers Capturing the 2 Cellular Populations of HOT Wang, Xiao-Ming; Mannan, Rahul; Zhang, Yuping; More The American Journal of Surgical Pathology. 48(2):163-173, February 2024. FREE LINK (expires 4\/22\/24) <a https:\/\/journals.lww.com\/ajsp\/fulltext\/2024\/02000\/hybrid_oncocytic_tumors__hots__in_birt_hogg_dub_.5.aspx Précis The authors evaluated the expression of the … Continue reading FIRST QUARTER of 2024<\/span>