Succinate dehydrogenase deficient renal cell carcinoma frequently expresses GATA3 and L1CAM

Ankur R Sangoi¹, Sean R Williamson², Murat Oktay³, Anthony J Gill^{4

5}, Kiril Trpkov⁶, Farshid Siadat⁶, Fiona MacLean⁷, Laurence A Galea⁸, Dilek Ertoy Baydar⁹, Caglar Cakir¹⁰, Yasemin Yuyucu Karabulut¹¹, Deniz Baycelebi¹², Ganime Coban¹³, Banu Sarsik¹⁴, Busra Yaprak Bayrak¹⁵, Levente Kuthi^{16

17}, Boglarka Posfai¹⁸, Aysha Mobeen¹⁹, Sambit K Mohanty²⁰, Xulang Zhang²¹, Mohammed A Alghamdi²¹, Liang Cheng²², Michelle S Hirsch²³, Mahmut Akgul²⁴

Affiliations

¹ Department of Pathology, Stanford University, Stanford, CA, USA.
² Department of Pathology and Laboratory Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA.
³ Department of Pathology, Memorial Hospital, Istanbul, Türkiye.
⁴ Sydney Medical School, University of Sydney, Sydney, Australia.
⁵ Department of Anatomical Pathology, NSW Health Pathology, Royal North Shore Hospital, St Leonards, Australia.
⁶ Department of Pathology and Laboratory Medicine, Alberta Precision Laboratories and University of Calgary, Calgary, AB, Canada.
⁷ Douglass Hanly Moir Pathology, Macquarie Park, Australia.
⁸ Department of Pathology, Melbourne Hospital/Sonic Healthcare, Melbourne, VIC, Australia.
⁹ Department of Pathology, Koc University, Istanbul, Türkiye.
¹⁰ Department of Pathology, Cemil Tascioglu Hospital, Istanbul, Türkiye.
¹¹ Department of Pathology, Mersin University School of Medicine, Mersin, Türkiye.
¹² Department of Pathology, Ondokuz Mayis University, Samsun, Türkiye.
¹³ Department of Pathology, Department of Pathology, Bezmialem University, Istanbul, Türkiye.
¹⁴ Department of Pathology, Ege University School of Medicine, Izmir, Türkiye.
¹⁵ Department of Pathology, Kocaeli University School of Medicine, Kocaeli, Türkiye.
¹⁶ Department of Surgical and Molecular Pathology Center, National Institute of Oncology, Budapest, Hungary.
¹⁷ Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
¹⁸ Department of Pathology, Szeged University School of Medicine, Szeged, Hungary.
¹⁹ Department of Pathology and Laboratory Medicine, University of New Mexico, Albuquerque, NM, USA.
²⁰ Core Diagnostics, Gurgaon, India.
²¹ Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA.
²² Department of Pathology and Laboratory Medicine, Department of Surgery (Urology), Brown University Warren Alpert Medical School, the Legorreta Cancer Center at Brown University, and Brown University Health, Providence, RI, USA.
²³ Department of Pathology and Laboratory Medicine, Brigham and Women's Hospital, 75 Francis St, Room AL.360E, Boston, MA, 02115, USA.
²⁴ Department of Pathology and Laboratory Medicine, Brigham and Women's Hospital, 75 Francis St, Room AL.360E, Boston, MA, 02115, USA. makgul@bwh.harvard.edu.

PMID: 40100385
DOI: 10.1007/s00428-025-04078-6

Multicenter Study

Succinate dehydrogenase deficient renal cell carcinoma frequently expresses GATA3 and L1CAM

Ankur R Sangoi et al. Virchows Arch. 2025 Jun.

. 2025 Jun;486(6):1247-1256.

doi: 10.1007/s00428-025-04078-6. Epub 2025 Mar 18.

Authors

Affiliations

¹ Department of Pathology, Stanford University, Stanford, CA, USA.
² Department of Pathology and Laboratory Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA.
³ Department of Pathology, Memorial Hospital, Istanbul, Türkiye.
⁴ Sydney Medical School, University of Sydney, Sydney, Australia.
⁵ Department of Anatomical Pathology, NSW Health Pathology, Royal North Shore Hospital, St Leonards, Australia.
⁶ Department of Pathology and Laboratory Medicine, Alberta Precision Laboratories and University of Calgary, Calgary, AB, Canada.
⁷ Douglass Hanly Moir Pathology, Macquarie Park, Australia.
⁸ Department of Pathology, Melbourne Hospital/Sonic Healthcare, Melbourne, VIC, Australia.
⁹ Department of Pathology, Koc University, Istanbul, Türkiye.
¹⁰ Department of Pathology, Cemil Tascioglu Hospital, Istanbul, Türkiye.
¹¹ Department of Pathology, Mersin University School of Medicine, Mersin, Türkiye.
¹² Department of Pathology, Ondokuz Mayis University, Samsun, Türkiye.
¹³ Department of Pathology, Department of Pathology, Bezmialem University, Istanbul, Türkiye.
¹⁴ Department of Pathology, Ege University School of Medicine, Izmir, Türkiye.
¹⁵ Department of Pathology, Kocaeli University School of Medicine, Kocaeli, Türkiye.
¹⁶ Department of Surgical and Molecular Pathology Center, National Institute of Oncology, Budapest, Hungary.
¹⁷ Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
¹⁸ Department of Pathology, Szeged University School of Medicine, Szeged, Hungary.
¹⁹ Department of Pathology and Laboratory Medicine, University of New Mexico, Albuquerque, NM, USA.
²⁰ Core Diagnostics, Gurgaon, India.
²¹ Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA.
²² Department of Pathology and Laboratory Medicine, Department of Surgery (Urology), Brown University Warren Alpert Medical School, the Legorreta Cancer Center at Brown University, and Brown University Health, Providence, RI, USA.
²³ Department of Pathology and Laboratory Medicine, Brigham and Women's Hospital, 75 Francis St, Room AL.360E, Boston, MA, 02115, USA.
²⁴ Department of Pathology and Laboratory Medicine, Brigham and Women's Hospital, 75 Francis St, Room AL.360E, Boston, MA, 02115, USA. makgul@bwh.harvard.edu.

PMID: 40100385
DOI: 10.1007/s00428-025-04078-6

Erratum in

Correction to: Succinate dehydrogenase defcient renal cell carcinoma frequently expresses GATA3 and L1CAM.
Sangoi AR, Williamson SR, Oktay M, Gill AJ, Trpkov K, Siadat F, MacLean F, Galea LA, Baydar DE, Cakir C, Karabulut YY, Baycelebi D, Coban G, Sarsik B, Bayrak BY, Kuthi L, Posfai B, Mobeen A, Mohanty SK, Zhang X, Alghamdi MA, Cheng L, Hirsch MS, Akgul M. Sangoi AR, et al. Virchows Arch. 2025 Sep;487(3):723-724. doi: 10.1007/s00428-025-04194-3. Virchows Arch. 2025. PMID: 40711546 No abstract available.

Abstract

Succinate dehydrogenase deficient renal cell carcinoma (SDH RCC) is an uncommon, familial RCC that has overlapping morphologic features with other low grade eosinophilic tumors of the kidney. Although the diagnosis of SDH RCC relies on loss of SDHB by immunohistochemistry (IHC), not all laboratories have access to this antibody. GATA3 and L1CAM are increasingly utilized in the diagnosis of eosinophilic renal tumors; however, their expression profile has not been studied in SDH RCC. We evaluated clinical parameters and GATA3 and L1CAM reactivity in a large nephrectomy cohort (n = 40) of patients with SDH RCC. The male-to-female ratio was 3:1 and the median age was 48 years (range: 17 to 79 years). Specimens included 20 radical resections, 19 partial resections, and 1 unknown procedure. Tumor laterality was nearly equal (right:left = 18:20; one case was bilateral). Tumors in 4 (10%) patients were multifocal. Median tumor size was 2.0 cm (range 1 - 14.8 cm). Tumor stage distribution was: pT1a (n = 16, 40%), pT1b (n = 7, 18%), pT2a (n = 5, 13%), pT2b (n = 4, 10%), pT3a (n = 6, 15%), and pT4 (n = 1, 3%). Most cases (n = 33, 83%) exhibited classical morphologic features, whereas 2/40 (5%) had sarcomatoid differentiation. GATA3 was positive in 37/39 (95%) tumors, with more than 50% of cells positive in 35/37 (95%), and with moderate-high intensity (2/3 +) in 33/37 (89%). L1CAM was expressed in 13/18 (72%) tumors, with moderate-high intensity (2/3 +) in 10/13 (77%). When both markers were performed, dual GATA3/L1CAM expression was present in 12/17 (71%) tumors. As L1CAM has been postulated to represent a marker of principal cell of the distal nephron, frequent L1CAM expression in SDH RCC suggests that they may originate from the principal cells of the distal nephron.

Keywords: GATA3; L1CAM; Succinate dehydrogenase deficient renal cell carcinoma.

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Conflict of interest statement

Declarations. In this retrospective study, all participating institutions contributed archival material under the approval of each institution’s review board, and the completely de-identified information does not interfere with the patients’ treatment. Conflict of interest: The authors did not receive support from any organization for the submitted work. The authors have no competing interests to declare that are relevant to the content of this article.

References

1. Gill AJ et al (2014) Succinate dehydrogenase (SDH)-deficient renal carcinoma: a morphologically distinct entity: a clinicopathologic series of 36 tumors from 27 patients. Am J Surg Pathol 38(12):1588–1602 - PubMed - PMC
1. Gill AJ (2018) Succinate dehydrogenase (SDH)-deficient neoplasia. Histopathology 72(1):106–116 - PubMed
1. Fuchs TL et al (2022) Expanding the clinicopathological spectrum of succinate dehydrogenase-deficient renal cell carcinoma with a focus on variant morphologies: a study of 62 new tumors in 59 patients. Mod Pathol 35(6):836–849 - PubMed
1. Williamson SR et al (2015) Succinate dehydrogenase-deficient renal cell carcinoma: detailed characterization of 11 tumors defining a unique subtype of renal cell carcinoma. Mod Pathol 28(1):80–94 - PubMed
1. Ding CC et al (2022) An exploration in pitfalls in interpreting SDHB immunohistochemistry. Histopathology 81(2):264–269 - PubMed

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Succinate dehydrogenase deficient renal cell carcinoma frequently expresses GATA3 and L1CAM

Affiliations

Succinate dehydrogenase deficient renal cell carcinoma frequently expresses GATA3 and L1CAM

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

References

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LinkOut - more resources

Full Text Sources

Research Materials