Due to their expansive growth pattern, isolated RCC pancreatic metastases produce specific symptoms only when the size of the tumor is quite large. In these patients, the clinical presentation may include gastrointestinal bleeding and anemia due to the hypervascularity of the lesions and, consequently, erosion of the duodenal wall, jaundice, or duodenal obstruction. Rarer symptoms of pancreatic insufficiency, palpable tumor, and pancreatitis have been described. Other, generic symptoms are fatigue, weight loss, and abdominal pain. Serum tumor markers are generally within the limits, as is the case with other metastatic diseases in the pancreas [15–19].

However, almost half of the patients are asymptomatic at diagnosis and the pancreatic lesions are discovered by ultrasound (US) during a routine program of follow-up after RCC resection, or for other non-specific abdominal complaints following surgery for RCC even if it occurred many years earlier [19]. This is consistent with the typically long interval between RCC primary resection and pancreatic metastases, which according to reports is 10 years on average but as long as 32.7 years [13, 17, 20–23]. Consequently a yearly abdominal US examination is strongly recommended for all patients with a history of resected RCC, and a pancreatic metastasis should be considered as the first diagnostic likelihood whenever a hypervascularized tumor in the pancreas is detected.

Typically, hypervascular, pancreatic metastases from RCC can be characterized by dynamic imaging, which easily rules out a differential diagnosis of pancreatic ductal adenocarcinoma [24, 25]. However, the imaging features of pancreatic metastases from RCC cannot be differentiated from those of neuroendocrine tumors (NETs). The differential diagnosis is therefore based on the clinical history and symptoms, including a correlation with a specific hypersecretory syndrome. Non-functioning NETs are indistinguishable from RCC metastases; thus, in such patients only a history of nephrectomy can lead to the correct diagnosis. Also helpful is that metastatic lesions are typically multi-focal (Fig. 15.4) at the time of diagnosis. Consequently, to obtain a final diagnosis, biopsy must be accompanied by panoramic imaging studies for tumor staging.

The imaging methods most often used in clinical practice, including for the detection of metastatic RCC, is multi-detector computed tomography (MDCT) due to its high spatial and temporal resolution, which allows the identification of small lesions. As noted above, pancreatic metastasis of RCC are usually hypervascular, which makes them readily detectable in the arterial phase of a contrast-enhanced MDCT examination (Fig. 15.4a). Sometimes, in larger lesions, hypodense central areas of necrosis are present. In later phases of the contrast-enhanced MDCT study, the lesions may be more difficult to detect because the difference in the density of the mass vs. that of the normal pancreatic gland decreases (Fig. 15.4b). Other rare and non-specific features of these lesions are calcifications, ductal and biliary obstruction, vascular extension, and cystic degeneration.

Surgical Treatment for Resectable Disease

The first report of a pancreatic resection for metastatic RCC was published 60 years ago [26]. Since then, results have been published as case reports, small single-institution series, and, more recently, as in-depth reviews of the entire literature [12, 13, 19, 27].

Since RCC metastases to the pancreas are rare, prospective randomized trials to evaluate the role of surgical resection in the multi-modal treatment of these patients have not been possible. In fact, there have been no more than 500 reported pancreatic resections over these last 60 years, and the conclusions are not sufficiently definitive to comprise an adequate level of evidence. Furthermore, only a few authors have tried to compare outcomes in patients with resected and non-resected disease [13, 19, 28], with debatable results due to the difficulty of the comparisons. For example, among the latter group, single pancreatic metastases are rare and diffuse extrapancreatic disease at the time of the diagnosis is frequently observed [28].

Despite these intrinsic limitations, some evidence is available to guide therapeutic decision-making in patients with RCC pancreatic metastasis. Firstly, accurate staging, including a total-body CT scan, is necessary to discover asymptomatic distant metastases to the brain and lung, while bone scintigraphy should be performed to exclude skeletal metastases. Another tool useful in the risk stratification of these patients, developed to ensure that only those who will truly benefit from surgical resection will be offered this form of treatment, was recently developed at the Memorial Sloan Kettering Cancer Center (MSKCC) [29]. This prognostic model divides patients into one of three classes based upon five parameters: time to recurrence (< or > 12 months), tumor burden (LDH), hematopoietic suppression or skeletal involvement (serum hemoglobin and calcium), and performance status. A final score of 0 points identifies a group considered to be at favorable risk: metachronous metastasis arising > 1 year after nephrectomy, serum hemoglobin > 13 and 11.5 gm/dl in males and females, respectively, serum calcium < 10 mg/dl, serum LDH < 300 U/l, and Karnofsky performance status ≥ 80%. Intermediate risk patients have a score of 1–2 points and those at high risk a score of 3–5 points. If extrapancreatic disease has been ruled out, most authors agree that a surgical approach to the lesion should be recommended whenever a R0 resection is likely to be achieved in a favorable risk patient.

The surgical technique should be based on a well-defined protocol, similar to that developed for pancreatic NETs in MEN1 patients. In fact, RCC metastases in the pancreas are multiple in up to 45% of surgical specimens, as widely reported in the recent literature [13, 19, 28, 30], but multiple nodules are well documented in the preoperative diagnostic work-up only in half of the pathological cases [28, 30]. Following accurate palpation of the entire gland after its wide exposure along its posterior surface, intraoperative US (IOUS) should be performed for lesion detection and to allow a surgical resection with a minimally invasive approach. IOUS provides details on the contiguity between the lesions and the main pancreatic duct, enabling the surgeon to choose the most appropriate approach to the nodule. Whenever possible, any single nodule is preferably resected while sparing healthy parenchyma, thus avoiding a total pancreatectomy. However, the latter is mandatory if the multiple nodules are large and involve the main pancreatic duct. In case of body and tail lesions and a small nodule in the uncinate process that does not involve the Wirsung duct, a distal pancreatectomy associated with an enucleation of the main nodule is warranted. Frozen sections of the resected margins are mandatory. An initial report of a high local recurrence rate after parenchyma-sparing surgery [30] was not confirmed in subsequent reports. Nonetheless, the entire gland should be carefully inspected in order to detect any single lesion [28, 31], avoiding removal of the pancreas due to a fear of local relapse. Indeed, despite the adoption of a policy of atypical resection [28, 31], the incidence of pancreatic recurrences was negligible. An adequate follow-up with US or magnetic resonance imaging (MRI) is strongly encouraged given the possibility of a new localization in the remnant pancreas, which occurs in 4% of cases according to a recent complete literature review [19], but also because of the high rate (17%) of extrapancreatic recurrences after pancreatic resection. However, new localizations of RCC are still amenable to surgical resection, as the disease can eventually be eradicated in around 45% of patients [19]. Standard peri-pancreatic lymph node dissection is largely sufficient because the rate of nodal involvement is negligible in most series, with an incidence of 10% reported by the Johns Hopkins Surgical Department [32] and 20% by the Heidelberg Surgical Department [31]; the latter is the highest ever reported.