Müllerian-Type Clear Cell Carcinoma of Donor Origin in a Male Patient with a Kidney Transplant: Ascertained by Molecular Testing

Authors

J Bryan Iorgulescu
Leah K Shaw
Asif Rashid
Priya Rao
Sreedhar Mandayam
Keyur P Patel
Kathleen M Schmeler
Richard K Yang
Pavlos Msaouel

Publication Date

10-5-2023

Journal

Current Oncology

Abstract

Clear cell carcinomas of Müllerian origin have a strong female predominance and only extremely rarely will arise within the kidney, presumably due to ectopic Müllerian embryogenesis. Herein, we report a unique case of metastatic Müllerian type clear cell carcinoma in a 37-year-old patient who had previously received a transplanted kidney from his father at age 11 (due to severe bilateral vesicoureteral reflux) and remained on chronic immunosuppression. The tumor was highly aggressive and demonstrated somatic mutations in NF2 and SETD2. Imaging of the transplanted kidney did not reveal any clear evidence of malignancy. However, targeted multigene sequencing and short tandem repeat testing revealed that the cancer was of donor origin, presumably from ectopic Müllerian tissue transplanted to the patient along with the kidney graft. The tumor was resistant to first-line therapy with a triple combination of carboplatin plus paclitaxel plus bevacizumab, as well as to second-line immunotherapy with nivolumab plus ipilimumab after tapering down the patient's immunosuppression. Despite the tumor being genetically distinct from the host, the use of immune checkpoint therapy with nivolumab plus ipilimumab did not yield a response. This unique case showcases the value of molecular testing in determining the tumor origin in patients with solid organ transplants who present with cancers of unknown primary. This can prompt the potential investigation of other recipients from the same donor.

Keywords

Humans, Male, Female, Child, Adult, Kidney Transplantation, Nivolumab, Ipilimumab, Molecular Diagnostic Techniques, Carcinoma, clear cell carcinoma, Müllerian type, transplant kidney, short tandem repeat testing, next-generation sequencing

Comments

Data Availability Statement

PMID: 37887551