Isolated Pancreatic Metastases of Renal Cell Cancer: Genetics and Epigenetics of an Unusual Tumour Entity

SIMPLE SUMMARY: The entity of isolated pancreatic metastases is very rare in metastatic renal cell carcinoma and is characterized by unusual features: 1. The isolated occurrence of pancreatic metastases itself; 2. the long interval between treatment of renal cell carcinoma and the occurrence of pancreatic metastases (9.6 years); 3. the frequent multiple occurrence of isolated pancreatic metastases (36%); and 4. the favourable prognosis after surgical therapy (5-year survival rate 75%). Some of the causes of this protracted course can already be traced back to specific genetic/epigenetic changes. ABSTRACT: Isolated pancreatic metastases of renal cell carcinoma (isPMRCC) are a rare manifestation of metastatic renal cell carcinoma (mRCC) characterized by two peculiarities: (1). The definite or at least long-term exclusive occurrence of metastases in the pancreas and (2). an unusual low tumour aggressiveness with slow tumour progression and consecutive, good treatment results. According to current knowledge, the exclusive occurrence of pancreatic metastases is due to a highly specific and highly selective seed and soil mechanism, which does not allow metastases settlement outside the pancreas, and whose detailed genetic/epigenetic causes are not yet elucidated. Recent studies have shed light on some of the pathways involved for the protracted course of the disease and highlighted a special genetic profile (lack of loss of 9p, lower weight genome instability index, low frequency of BAP1 alterations, and a high frequency of PBRM1 loss), which deviates from the conventional mRCC profile. Finally, the question of the reasons for the long-term relative genetic stability of the involved cell clones, which is an essential prerequisite for a favourable prognosis, remains unanswered.