#3697 FAMILIAL PAPILLARY RENAL CELL CARCINOMA: A CASE REPORT

Abstract

Abstract Background and Aims The incidence of Renal Cell Carcinoma (RCC) is the 9th commonest cancer worldwide. It originates from the renal tubular epithelium and to date has been subclassified into five different categories. Of which, papillary carcinoma is one subclassification and it includes two variants: sporadic and hereditary. This case report aims to outline a rare case of hereditary papillary RCC and the implications for the family involved. Method We performed a retrospective assessment of clinical and radiological characteristics of the index patient and affected relatives. Genetic diagnosis and management have been summarised. Results A 62-year-old male (II.1) was diagnosed with RCC after presenting with right-sided flank pain and multiple complex cystic lesions within both kidneys. A kidney biopsy revealed a papillary structure with foamy histocytes and clear cell-type epithelium clusters. Immunostaining of tumour cells demonstrated CK7 and P504S positivity consistent with RCC. Subsequently, he underwent bilateral nephrectomies and being rendered anephric, was commenced on haemodialysis. He underwent deceased donor renal transplantation four years later at the age of 66 (HLA 1:2:1, CMV -/-, cRF 35%) and remains dialysis independent six years on. After the diagnosis of the index patient, his son (III.1) was found to have multifocal papillary RCC, having also presented with flank pain, but this time in his 30s (Fig. 1). Patient III.1 underwent genetic testing which revealed a missense variant in the MET gene (NM_000245.4 c.3308G>A; p.Gly1103Glu). The variant affects a highly conserved residue in the Tyrosine Kinase domain of the MET protein. Pathogenic activating variants are associated with RCC. Identification of the same variant in the affected father with bilateral disease allowed classification of the variant as likely pathogenic according to the ACMG criteria [1]. The father has seven children, all of whom have now been tested. 5/7 of them have been found to carry the likely pathogenic MET missense variant. Of the 4 asymptomatic carriers, all are under surveillance by regular renal imaging and (one has had radiofrequency ablation). Conclusion The case outlines a rare form of hereditary RCC and the implications that detection of the genetic variant has meant in terms of early diagnosis of disease. Incidence of RCC is increasing worldwide. Hereditary papillary RCC is rare, it is typically inherited in an autosomal dominant pattern. Germline mutations in the MET proto-oncogene are located at 7q31, which encodes for the tyrosine kinase signaling pathway. Variants lead to uncontrolled activation of MET protein and aberrant cell growth [2]. Discussion Hereditary papillary RCC has an estimated incidence of < 1:1500000, its rarity highlighted by the fact that only ∼35 families have been reported worldwide in literature. In these cases it exhibits 100% penetrance, with patients developing renal cell carcinoma typically between their fifth and sixth decade [3]. We would like to acknowledge the family involved in this case report. As with many cancers, early diagnosis is helped by detection of a genetic variant, leading to improved long-term disease-free survival. In the case of metastatic papillary RCC 2-year survival is still estimated at 18% (3).