Renal neuroendocrine tumors: clinical and molecular pathology with an emphasis on frequent association with ectopic Cushing syndrome.

Kasajima, Atsuko; Pfarr, Nicole; von Werder, Alexander; Schwamborn, Kristina; Gschwend, Jürgen; Din, Nasir Ud; Esposito, Irene; Weichert, Wilko; Pavel, Marianne; Agaimy, Abbas; Klöppel, Günter

doi:10.1007/s00428-023-03596-5

journal article

Title:: Renal neuroendocrine tumors: clinical and molecular pathology with an emphasis on frequent association with ectopic Cushing syndrome.
Document type:: Article; Journal Article
Author(s):: Kasajima, Atsuko; Pfarr, Nicole; von Werder, Alexander; Schwamborn, Kristina; Gschwend, Jürgen; Din, Nasir Ud; Esposito, Irene; Weichert, Wilko; Pavel, Marianne; Agaimy, Abbas; Klöppel, Günter
Abstract:: Renal neuroendocrine tumors (RenNETs) are rare malignancies with largely unknown biology, hormone expression, and genetic abnormalities. This study aims to improve our understanding of the RenNETs with emphasis of functional, hormonal, and genetic features. Surgically resected RenNETs (N = 13) were retrieved, and immunohistochemistry and next-generation sequencing (NGS) were performed in all cases. In addition, all published RenNETs were systematically reviewed. Our cohort (4 men and 9 women, mean age 42, mean tumor size 7.6 cm) included 2 patients with Cushing syndrome (CS). WHO grade (23% G1, 54% G2, and 23% G3) and tumor progression did not correlate. CS-associated RenNETs (CS-RenNETs) showed a solid and eosinophilic histology and stained for ACTH, while the remaining non-functioning tumors had a trabecular pattern and expressed variably hormones somatostatin (91%), pancreatic polypeptide (63%), glucagon (54%), and serotonin (18%). The transcription factors ISL1 and SATB2 were expressed in all non-functioning, but not in CS-RenNETs. NGS revealed no pathogenic alterations or gene fusions. In the literature review (N = 194), 15 (8%) of the patients had hormonal syndromes, in which CS being the most frequent (7/15). Large tumor size and presence of metastasis were associated with shorter patients' survival (p < 0.01). RenNETs present as large tumors with metastases. CS-RenNETs differ through ACTH production and solid-eosinophilic histology from the non-functioning trabecular RenNETs that produce pancreas-related hormones and express ISL1 and SATB2. MEN1 or DAXX/ARTX abnormalities and fusion genes are not detected in RenNETs, indicating a distinct yet unknown molecular pathogenesis.
Journal title abbreviation:: Virchows Arch
Year:: 2023
Journal volume:: 483
Journal issue:: 4
Pages contribution:: 465-476
Fulltext / DOI:: doi:10.1007/s00428-023-03596-5
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/37405461
Print-ISSN:: 0945-6317
TUM Institution:: Institut für Allgemeine Pathologie und Pathologische Anatomie (Dr. Mogler komm.); Klinik und Poliklinik für Innere Medizin II, Gastroenterologie (Prof. Schmid); Klinik und Poliklinik für Urologie (Prof. Gschwend)
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