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

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.

Metastasis from Renal Cell Carcinoma to Ectopic Pancreas Diagnosed after Resection

“…However, biological studies have not yet conclusively demonstrated the proclivity of renal cell carcinoma to metastasize to the pancreas exclusively. It was recently reported that isolated pancreatic metastasis of renal cell carcinoma exhibit genetic changes (lack of 9p loss, reduced-weight genome instability index, low frequency of BAP1 alterations, and a high frequency of PBRM1 loss) that are associated with low tumor aggression ( 19 ). In the present case, the blood supply to the pancreatic lesion was from the celiac artery, and that to the ectopic pancreas in the duodenum was from the superior mesenteric artery.…”

Case Report: Pancreatic metastasis of renal cell carcinoma 16 years after nephrectomy

“…In terminal systemic disease tumors, pancreatic metastasis rarely occurs, in approximately 2% of surgical cases, with a corresponding poor prognosis ( 8 , 9 ). However, among patients with multi-organ site mRCC, concomitant PM presents a better prognosis compared to the cases without PM (median OS: 42 months vs. 23 months) ( 10 ). Furthermore, isPMRCC is characterized by an unusually favorable prognosis after surgical therapy.…”

“…Pancreatectomy for metastasis is not common, although RCC is the most common primary source ( 33 ). A survival benefit is associated with this subset of patients when they undergo surgery (complete oncological resection is associated with a 5-year survival rate of 75%) ( 10 ), particularly if RCC is the primary source ( 34 ). However, it has been reported that after the treatment of isPMRCC, 41.5% of patients present recurrence (125 patients among 301 patients relapsed after a 30-month interval) ( 10 ).…”

Isolated Pancreatic Metastases of Renal Cell Carcinoma—Clinical Particularities and Seed and Soil Hypothesis

“…The definite or at least for a very long time exclusive occurrence of PM in RCC cannot, as initially assumed, be due to the topographic proximity of the kidney and pancreas via pre-existing lymphatic [22,66,79,84,138,154,161,177] or venous renal-portal vascular connections between the kidney and the nearby pancreas [84,295,296] or by acquired pathological tumour vessels of hyper-vascularised tumours [10,22,66,79,84,115,138,153,161,173,205]. As our working group pointed out already in 2018, the local metastasis pathway is not compatible with the following characteristics of the isPMRCC [297]: (1) The independence of the distribution of metastases in the pancreas from the side of the primary RCC [106,143,160,183,184,188,211,233,259,297,298], (2) the even distribution of isolated PM within the pancreas [299], (3) the rare occurrence (6.2% [300]) of regional LNN metastases [99,102,111,116,121,143,…”