Pancreatic Metastasis from Renal Cell Carcinoma Several Years after Nephrectomy: Two Case Reports and Literature Review

Abstract

Metastases of renal cell carcinoma (RCC) to the pancreas are infrequent, comprising only 1 to 4% of pancreatic malignancies. These cases are distinguished by a prolonged period of being free from the disease following the initial surgery. We present here two rare cases of isolated pancreatic metastases from RCC, occurring 7 to 8 years after nephrectomy. The patients were asymptomatic; the masses were discovered incidentally during their routine annual health checkup. Surgical resection of these oligometastases was the appealing choice for managing these cases, potentially complemented by systemic treatment. The late onset of metastasis from RCC in solid organs should always be considered when dealing with patients with a history of RCC. Additionally, the follow-up following nephrectomy for RCC should be extended over 10 years.

Keywords

renal cell carcinoma - pancreatic metastasis - pancreatectomy - metastasectomy - late onset

Renal cell carcinoma (RCC) is a malignant tumor originating from the renal epithelial cells. It accounts for 80 to 90% of all kidney malignancies.[1] Around 25% of patients have metastatic disease at presentation and more than one-third will develop metastases after nephrectomy.[2] Distant metastasis from RCC occurs most commonly to the lungs (45.2%), bone (29.5), liver (20.3%), adrenals gland (8.9%), and brain (8.1%).[2] RCC metastases to the pancreas are rare and account for 1 to 4% of all pancreatic malignancies.[3] They are characterized by a long-term disease-free period after the initial surgery.[3]

Most patients with pancreatic metastases are asymptomatic.[1] Long-term follow-up succeeding nephrectomy for RCC and high clinical suspicion based on patient's history are the keys for early diagnosis.[2] Surgical treatment for isolated metachronous pancreatic metastases from RCC has been reported to improve prognosis.[2]

We hereby present two cases of RCC interval metastasis to the pancreas that were treated surgically.

Case 1

A 70-year-old female patient, known to have diabetes mellitus type 2, hypertension, and dyslipidemia, presents to her physician for her annual checkup, after undergoing right total nephrectomy for RCC, 7 years ago. The patient required no adjuvant treatment, and her follow-ups were uneventful over the last 7 years.

On the seventh year of follow-up, her yearly magnetic resonance imaging (MRI) showed a new 1.7 × 1.5 cm lesion at the pancreatic head–neck junction showing intermediated signal on T2-weighted images and low signal on T1-weighted images. This lesion showed diffusion restriction and hypoenhancement. There was secondary ductal dilatation reaching 6 mm as well as pancreatic atrophy distal to the tumor with the pancreatic parenchyma showing low signal on T1-weighted images. The lesion was abutting the proximal aspect of the superior mesenteric vein (SMV) and no contact with other intra-abdominal vessels.

Her lab workup and physical exam were unremarkable. An ultrasound-guided fine-needle aspiration biopsy of the lesion was performed and the pathological report revealed pancreatic tissue with few atypical cells that had clear bubbly cytoplasm. These features suggested renal clear cell carcinoma, but a definitive diagnosis could not be made on the sampled tissue. Immunohistochemistry PAX-8 stain was positive in several cells.

The decision was made to undergo enucleation of the pancreatic head mass ([Figs. 1], [2]). Intraoperative frozen sections confirmed the presence of RCC metastasis. A Roux-en-Y, side-to-side, pancreatojejunostomy at the site of the resected mass was performed, and the jejunojejunal anastomosis was created around, 70-cm distal to the ligament of Treitz. The final pathology result specimen revealed a portion of pancreatic tissue weighing 6.2 g and measuring 3 × 3 × 2 cm consistent with metastatic clear cell renal carcinoma and negative surgical margins.

Fig. 1 Excised pancreatic mass.

Fig. 2 Pancreatic bed after mass enucleation (yellow circle).

The postoperative period was uneventful and the patient was discharged home after 5 days.

Case 2

A 51-year-old female patient who had undergone left nephrectomy 8 years ago for RCC came in for routine checkup. Her medical history was otherwise negative. The operated tumor was classified as Grade 1 clear RCC according to the Fuhrman grading system. No adjuvant treatment was required, and the 7-year follow-up period was uneventful.

At her eighth-year annual abdomen pelvis computed tomography (CT) scan, a 2-cm hypodense lesion anterior to the isthmus of the pancreas was identified ([Fig. 3]). All laboratory studies and the physical examination were unremarkable.

Fig. 3 A 2-cm hypodense lesion anterior to the pancreatic isthmus (yellow arrow).

An abdomen MRI was performed for better assessment of the lesion and showed a well-defined 2-cm hyperenhancing lesion along the anteroinferior aspect of the body of the pancreas and a similar lesion in the tail of the pancreas measuring 9 mm. The pancreatic duct was not dilated ([Fig. 4]). Whole-body positron emission tomography (PET) scan showed no significant abnormal activity associated with the pancreatic nodules. Endoscopic ultrasound showed a 21 × 22 mm isoechoic lesion in the body of the pancreas and a similar 10-mm lesion in the tail of the pancreas. No vascular invasion was noted. Fine-needle biopsy of the larger mass was consistent with metastatic RCC, grade 1.

Fig. 4 Magnetic resonance imaging showing an anterior inferior (22 × 21 mm) lesion in the body of the pancreas and a similar lesion in the tail of the pancreas (9 mm) pancreatic lesions (yellow arrow).

Distal pancreatectomy with spleen preservation was performed, involving both lesions and negative margins on frozen sections. The final pathology result showed a 1-cm well-demarcated, golden-yellow soft nodule, and another similar 2-cm nodule, 6 cm away from the first one. Microscopic examination of the pancreatic nodules showed a neoplastic proliferation made up essentially of acinar structures. Cytologically, the neoplastic cells are columnar with a round to oval slightly irregular nucleus, with tiny nucleoli and an abundant clear acidophilic cytoplasm. The immunostaining was negative for the anti-cytokeratin 7 antibody. The pathological findings indicated that the lesions were metastases from clear cell RCC and surgical margins negative for tumors.

The postoperative period was uneventful and the patient was discharged home after 5 days.

Discussion

RCC accounts for around 2% of all adults' malignancies and has a high overall survival rate, up to 95%, in cases of limited kidney disease.[4] It is considered to have a high metastatic potential.[4] Metastasis of RCC to the pancreas is a rare entity accounting for only 1 to 4% of all pancreatic tumors.[3] It has several distinguishing characteristics, which include its presentation as an isolated metastasis, a long disease-free period after the initial surgery, and a favorable prognosis.[3]

Approximately 20 to 30% of patients with RCC, present with synchronous metastases, with a 5-year survival rate of less than 10%, whereas another 30% will develop metachronous metastases along the course of their disease.[4] Pancreatic metastases from RCC are characterized by a slow-growing behavior, and a long disease-free interval (>10 years). Hence, a long postnephrectomy follow-up (over 10 years) should be considered even in asymptomatic patients.[2] This was the case for both our patients, presenting with RCC recurrence, 7 and 8 years after initial diagnosis.

The relation between the metastatic location and the pancreas and the primary RCC has not been well elucidated.[5] It can either be via hematogenous spread or via lymphatics. Hematogenous spread may occur along the draining collateral vein of a hypervascular renal tumor, and the spread through lymphatics may occur by retrograde lymph flow secondary to tumor infiltration of the retroperitoneal lymph nodes.[6] Moreover, the patient may have been chronically harboring RCC micrometastases, and his immune-surveillance served to maintain a relative balance that lasted many years.[1]

The preoperative diagnosis of pancreatic metastases begins with a suspicion based on the patient's history. The patients with pancreatic metastasis from RCC can present with a variety of nonspecific gastrointestinal symptoms ranging from abdominal pain, gastrointestinal bleeding, obstructive jaundice, pancreatitis, or diabetes.[4] Therefore, RCC pancreatic metastases are often detected incidentally.[2] The presented cases were asymptomatic, and the diagnosis resulted from their annual imaging follow-up.

Follow-up after nephrectomy, including abdominal imaging, is rarely performed after 5 years.[2] Imaging modalities such as CT, MRI, PET, and endoscopic ultrasound (EUS) help support the diagnosis.[6] When the tumor metastasizes to a single organ or site, the preoperative misdiagnosis reaches 70%. The imaging characteristics of most metastatic tumors are similar to those of tumors originating from the metastatic site.[1] Pancreatic metastases from RCC are identified as hypervascular tumors on CT and consequently display homogeneous contrast medium enhancement in the arterial phase; however, their features are similar to those of primary neuroendocrine neoplasms, intrapancreatic accessory spleens, and vascular lesions.[5] Histology is the gold standard for diagnosing metastasis. Light microscopy alone cannot help in differentiating metastatic RCC from other clear cell tumors and immunohistochemistry is required for accurate diagnosis.[7] In both of our cases, there was a strong clinical suspicion of RCC metastasis, given the prior medical history. Both patients underwent EUS with biopsy, which helped in establishing the suspected pathology. This diagnosis was subsequently confirmed by the final pathology and immunohistochemistry as RCC metastasis.

There are currently two treatment options for RCC metastasis, including local and systemic therapies.[1] Local therapies are surgical resection or radiotherapy. Systemic therapies include molecular-targeted therapy and chemotherapy; these are immune checkpoint inhibitors.[1] It is believed that metastasectomy should be used in combination with systemic therapies. Local excision of the metastases reduces the tumor growth factors inflammatory cytokines and immunosuppressive factors secreted by cancer cells, thereby improving the effects of systemic treatment.[2] Unlike other malignancies affecting the pancreas, RCC may spread to the pancreas as the only secondary site, which makes surgical resection of isolated RCC metastasis to the pancreas an attractive option.[8] The choice between pancreatoduodenectomy, middle segment excision, or distal pancreatectomy depends on the location of the tumor within the pancreas.[4] Radical surgery for multifocal metastases from RCC to the pancreas appears to be as justified as that for a solitary metastasis.[6] In the first case presented, the location of the tumor was at the head of the pancreas, so we opted for an enucleation of the lesion at this site. A pancreaticojejunostomy was performed as a precautionary method against any potential leak. Whereas, in the second case, the two metastatic lesions were located in the body and tail of the pancreas. Therefore, a decision for distal pancreatectomy was the best course of action in order to address both lesions effectively.

Regarding lymphatic spread, peripancreatic lymph node involvement is very rare or even absent. Therefore, lymph node dissection should be performed only in cases of suspected lymph node involvement detected pre- or intraoperatively. As for splenectomy, it could be performed only for a pancreatic tail lesion close to the hilum, or in certain cases involvement of lymph nodes close to the hilum is suspected.[2] In our second case where the lesion was located in the tail of the pancreas, we had the possibility to spare the spleen, provided that the lesion was not in close proximity to the hilum.

RCC metastases to the pancreas have now a better prognosis with a 5-year survival rate that improved from 11 to 44% when the tumor is resected compared with cases when the tumor is not removed.[9]

Conclusion

While it is uncommon for RCC to metastasize to the pancreas after a radical nephrectomy, both health care providers and patients should remain mindful of this potential occurrence. These instances of RCC metastasis to the pancreas are marked by a period of over 10 years without disease. Therefore, the late onset of metastasis from RCC in solid organs should always be considered when dealing with patients with a history of RCC, as well as follow-up after nephrectomy for RCC should be extended over 10 years. Extra surveillance could prove beneficial, given the potential curative context provided for the patient, whenever resection is feasible. An individual-tailored follow-up can be devised, depending on patients' history, tumor aggressiveness, initial presentation, and concomitant clinical conditions. This would require a broader analysis of the reported cases and merits further consideration in future studies.

Conflict of Interest

None declared.

Acknowledgments

We would like to acknowledge the efforts of the General Surgery Department at Saint George Hospital University Medical Center and the encouragement of the faculty of Balamand for the completion of this work.

Ethical Approval

Case report approved for publishing by Ethical Committee at the Saint George Hospital University Medical Center, and Head of General Surgery Division.

Data Availability Statement

All data were obtained from the patient for publication of this case report and accompanying images. All data are available for review by the Editor-in-Chief of this journal on request.

• References

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Publication History

Received: 04 December 2024

Accepted: 17 April 2025

Article published online:
20 May 2025