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

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

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)465-476
Number of pages12
JournalVirchows Archiv
Volume483
Issue number4
DOIs
Publication statusPublished - Oct 2023

Keywords

  • Hormone
  • ISL1
  • Kidney
  • Neuroendocrine neoplasms
  • SATB2

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