Background
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare and underreported hereditary syndrome resulting from a fumarate hydratase (FH) pathogenic variant. It is characterized by cutaneous leiomyomata, uterine fibroids and/or renal cell carcinoma. Management of HLRCC lacks robust evidence, although promising results in case series have been reported with the use of bevacizumab and erlotinib for advanced disease.
Case presentation
A 35-year-old male presented to his general practitioner with back pain. His background included childhood asthma and prior appendectomy. He was married with two daughters. His family history was significant for kidney cancer in his father.
Investigations
Ultrasound and computed tomography revealed a large left renal mass and lesions in the left 7th and right 11th ribs. Biopsy demonstrated metastatic renal carcinoma with histopathology composed of oncocytic cells arranged in a tubulocystic pattern with heterogeneous FH staining and positive IHC making this highly suspicious for HLRCC. Germline testing demonstrated heterozygous variant of uncertain significance (VUS) in FH gene (c.1016C>A in exon 7).
Treatment
Radiotherapy to the left 7th rib, scapula and right 10th rib was performed followed by systemic therapy with intravenous bevacizumab 10mg/kg two-weekly and oral erlotinib 150mg daily. Despite four cycles of therapy, restaging demonstrated rapid widespread progression of bony disease. The patient proceeded to further radiation therapy and second line treatment with cabozantinib.
Discussion
As is typical for HLRCC, this patient presented with advanced disease which rapidly progressed and was refractory to anti-tumour effects of bevacizumab and erlotinib. Additionally, the patient yielded a FH variant which has been associated with HLRCC but for which there is insufficient evidence to determine its impact on management. With increasing use of genetic testing, there has been rapid expansion of VUS identification. Further research to understand the pathogenicity of variants would enhance clinical decision-making for management and surveillance.