22. Hereditary leiomyomatosis and renal cell carcinoma syndrome: a case report

Abstract

Background Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an autosomal dominant familial syndrome characterised by cutaneous and uterine leiomyoma and renal cell carcinoma. The kidney tumours are typically described as having features of type 2 papillary carcinoma; however, other types of renal cell cancers have also been reported. The tumours tend to be aggressive, with frequent and early nodal and distant metastases despite the often small size of the primary tumour. Case report We present an unusual case of HLRCC in a 53-year-old male who was referred to a Family Cancer Service with a strong personal and family history of renal cancer. He was diagnosed at age 31 with a ‘Grawitz tumour’. The histology of his renal cell carcinoma was reviewed following recognition of HLRCC in the family. The patient’s tumour had solid and cystic areas with tubulopapillary architecture. The tumour cells had a moderate amount of eosinophilic cytoplasm, with Fuhrman nuclear grade 3. Many of the nuclei showed prominent eosinophilic nucleoli, with a clear halo surrounding the nucleolus. No invasion of the renal capsule or vessels was seen. Initially no underlying genetic cause for renal cancer in the family was found. The family history then evolved with a female relative developing both cutaneous and uterine leiomyoma and her dermatologist suspected HLRCC as the cause. A New Zealand Family Cancer Clinic arranged genetic testing of an affected relative and a causative germline mutation was identified in the fumarate hydratase (FH) gene [p.Gly354Arg (G354R)]. Genetic testing for our patient was then arranged and this confirmed he had inherited the family mutation in the FH gene. He remains disease free. His offspring are being tested. Conclusion This case report reviews the molecular genetics of HLRCC and the pathological features of renal cell carcinoma, with discussion on possible characteristic histological features that may help to alert the pathologist to the possibility of a familial cancer syndrome.