The mean age of patients with disease is about 65 years with a slight male gender predominance. As in our patient, approximately 55% of patients with metastatic renal cell carcinoma to the pancreas are asymptomatic1. These cases may be an incidental discovery during non-related imaging or during long-term interval surveillance after diagnosis of the primary renal carcinoma. In some instances, the pancreatic metastasis may be the primary indication of an underlying primary renal neoplasm. In symptomatic patients, the most common symptoms may include weight loss, abdominal pain, jaundice and gastrointestinal bleeding1.
Secondary neoplasms of the pancreas have a variable frequency ranging from 2-5%1 (up to 11%2; 43%3 ) of all malignancies involving the pancreas. The most common primaries are renal cell carcinoma, melanoma, colorectal carcinoma, lung carcinomas, breast carcinoma, ovary and sarcomas1, 3. Interestingly, multifocal disease may range from 20%-45%1, and is relatively common with metastases of non-renal primary. While multifocal metastasis indicates systemic disease from another organ, renal carcinomas may present as an isolated metastasis. In this setting, metastatic renal cell carcinoma to the pancreas has the possibility of treatment by surgical resection1.
According to Cheng et al., the tumor foci are usually hypervascular, circumscribed with tumor size ranging from 1.5-12 cm. Metastatic renal cell carcinomas most commonly involve the pancreatic head, and if multifocal, will eventually reach an even distribution throughout the organ.
As in primary renal cell carcinoma, the cytologic findings are similar in metastatic foci. Due to the inherent tumor vascularity, it is common to encounter excess blood. The excess blood can obscure or entrap the diagnostic cells in clot, which may limit cytologic visualization. Likewise the excess blood may be a subtle clue to an underlying vascularized metastatic renal cell carcinoma. The tumor cells may be single, clumped or in sheets. The cytoplasm of the clear cell variant is finely vacuolated and envelopes round nuclei with usually prominent nucleoli (higher nucleolar grade in metastases).
The differential diagnosis for clear cell neoplasms in the pancreas should be broad. In cases when there is no prior history, other considerations should include a pancreatic primary. The most common is a clear cell pancreatic ductal carcinoma; however these usually have a component of classic pancreatic ductal carcinoma or at least some of the diagnostic nuclear atypia. Solid pseudopapillary tumors have a mixture of discohesive cells and cell groups with nuclear grooves and less conspicuous nucleoli. Solid serous cystadenomas are cytologically bland; but immunohistochemically are CK7+ and PAX8 (-).
While the clear cell subtype of renal carcinoma is the most common, there are cases of metastatic chromophobe renal cell carcinoma (PAX8+ CK7+ CD117+). This must be distinguished from a pancreatic endocrine tumor, which may also display a discohesive population. A pancreatic endocrine tumor will show round nuclei, fine salt and pepper chromatin (without prominent nucleoli) and will have positive neuroendocrine immunohistochemical stains. Interestingly, octreotide scans may also be positive in renal cell carcinomas and another study showed somatostatic receptors in renal cell carcinoma. 2 Given the wide differential, a cell block preparation is most helpful for accurate diagnosis.
Differential Diagnoses of Clear Cell Neoplasms of the Pancreas
Clear cell renal cell carcinoma
CD10+, PAX8+, RCC, CK7 (-)
Pancreatic ductal carcinoma with clear cell features
PAS+ intracytoplasmic glycogen; lost with PAS/D
Pancreatic endocrine tumor, clear cell type
Chromogranin +, synaptophysin +
Serous cystadenoma of pancreas
CK7+, PAX8 (-), CD10 (-)
Solid pseudopapillary tumor of pancreas, clear cell variant
Synaptophysin +, B-catenin +
Perivascular epithelioid cell tumor (PEComa)
HMB-45 +, SMA +
Intraductal tubulopapillary neoplasm
Carbonic anhydrase IX +, CD10+, mucin +
In summary, although metastases to the pancreas are infrequent, renal cell carcinoma represents one of most frequent primaries. Unlike other organs, an isolated metastasis may be the initial finding of metastatic renal cell carcinoma; therefore careful pathologic consideration of morphology, past medical history, radiologic-correlation and cell block for immunohistochemical stains is essential for assessment of a clear cell neoplasm of the pancreas.