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A healthy 46-year-old woman presents to the hospital in Dammam, Saudi Arabia for investigation of an incidental localized right renal mass, discovered in the course of an examination for gallstones. The mass is clinical stage I. Clinicians note that the patient has good performance status, and she reports no active concerns.

Findings from their initial assessment are unremarkable -- a systemic review is normal and the patient reports having no family history of kidney problems or renal cancers. Clinicians' physical examination reveals nothing unusual, and results of lab tests are normal.

Clinicians perform a right radical nephrectomy, and pathologic analysis of the mass identifies clear cell renal cell carcinoma (ccRCC).

Six years later, the patient comes to the hospital's emergency department with vomiting and generalized pain in her abdomen. Clinicians order imaging, which reveals a pancreatic mass localized in the head of the pancreas. Blood tests show normal amylase and lipase levels. Clinicians perform a Whipple procedure, and send a sample to pathology, which indicates metastatic ccRCC.

Two years later, the patient presents to the hospital due to having trouble swallowing; she tells clinicians she is not experiencing any breathing difficulties or shortness of breath. Clinicians perform a physical examination, which shows an obvious mass in both lobes of her thyroid.

Ultrasound imaging reveals four hypervascular nodules on the thyroid, the largest in the left lobe. Clinicians obtain a sample of the nodules using fine-needle aspiration; analysis shows evidence of inflammatory changes, but findings are inconclusive.

Pathological diagnosis proves to be difficult, but clinicians determine that the nodules are metastatic ccRCC after total thyroidectomy.

One year later, the woman presents with a suspicious soft lump on her forearm -- it has clearly defined boundaries and a smooth surface, and no skin discoloration, scales, or ulcers. Clinicians excise the mass with negative margins. A biopsy identifies the sample as metastatic ccRCC.

When the patient returns for follow-up almost 5 years after the Whipple procedure, examination reveals another suspicious mass, which clinicians excise from the remaining pancreatic tissue. As a result, she undergoes complete removal of both her pancreas and spleen, which the pathology report classifies as ccRCC metastasis.

Twelve years after her right radical nephrectomy and 6 years after the cancer's initial metastasis, routine follow-up imaging reveals a mass in her left kidney, which clinicians consider a candidate for a partial nephrectomy. Following that surgery, tissue sent to pathology is also identified as metastatic ccRCC. Pathology sections of primary kidney cancer, as well as pancreas, thyroid, and soft tissue masses, are illustrated in Figure 1.

The patient develops perirenal hematoma and swelling of the kidney due to incomplete drainage; clinicians decide to address these complications conservatively and insert a DJ stent (classified as Clavien IIIb).

Subsequent follow-up finds that her perirenal hematoma is resolved, and her hydronephrosis is alleviated. The patient's kidney function is maintained and her creatinine level remains stable.

One year after partial nephrectomy, a number of stable pulmonary nodules are detected, which clinicians determine are not candidates for surgical removal. They start the patient on treatment with the tyrosine kinase inhibitor sunitinib. Imaging on follow-up reveals numerous stable pulmonary nodules with no clinical problems. Bone and PET/CT scans show no signs that the cancer has metastasized to the woman's bones. Her Eastern Cooperative Oncology Group (ECOG) score and findings from laboratory investigations are unremarkable. The hospital does not have facilities to perform genetic testing.

The woman's survival over 10 years of cancer metastasis to multiple sequential organs, which, except for the lung lesions, are successfully managed with complete surgical removal, highlights the survival that this approach can achieve in selected patients. Clinicians obtain the patient's permission to report the case.

Discussion

Clinicians presenting this of a patient with asynchronous consecutive metastatic ccRCC to various unusual organs noted that surgical resection of such ccRCC metastases is rarely reported.

Most existing data are from retrospective studies and case reports, with no higher levels of evidence, authors observed. Thus, treatment approaches -- which now include novel immunotherapies -- continue to be debated.

Where possible, and patient's clinical status allows, surgical resection of metastases is preferred, regardless of the organs involved. However, authors noted that a positive surgical margin might dissuade patients from further surgical resection of metachronous metastases, in favor of immunotherapy alone.

While ccRCC generally metastasizes after treatment of the primary tumor, about one-third of newly diagnosed patients do present with metastasis, authors observed. Possible factors independently linked with a poor prognosis include the number of metastatic organs, performance status, male sex, and disease-free interval <1 year, as well as tumor size, age, race, and family history.

A found that patients with metastases to the pancreas and thyroid had the highest rates of favorable-risk disease (34% and 37%, respectively) and lowest rates of poor-risk disease (12% and 17%, respectively). Conversely, bone, liver, pleura, and bowel showed a tendency toward higher-risk disease (favorable risk <20% and poor risk >30%).

Published reports of metastatic ccRCC are inconsistent regarding sites involved, case authors noted; the lung is a common site of metastases, although the reasons for this are not clear. may be relatively favorable, particularly cases that collectively involve solitary lesions, small lesion sizes, and absence of lymph node involvement, which have a 5-year patient survival rate of about 45%.

The second most frequent site of RCC metastasis are the bones, seen in about 20% of patients, while metastasis to the pancreas affects only 1% to 2% of patients. The pathophysiological process for metastasis from kidney to pancreas has not been described, authors noted. However, it may involve the lymphatic system; some have suggested the may have a role in pancreatic metastasis.

Suspicion of potential metastasis to the pancreas may be increased based on patient history and normal pancreatic enzymes, along with imaging evidence of a hypervascular lesion, authors wrote; they cited data suggesting increased survival associated with the Whipple procedure or complete pancreatectomy, with or without adjunct immunotherapy.

to the thyroid is rare, occurring in about 1% of cases, authors said, adding that RCC is a culprit when thyroid metastasis is discovered. Diagnosis of these metastases can be complicated, especially when initial presentation -- which generally occurs 5 to 10 years after initial RCC diagnosis -- is a solitary thyroid mass. These metastases may be associated with an abnormal thyroid gland, although some research has failed to find differences in the incidence of thyroid metastases among normal and abnormal thyroids, authors noted.

Skin metastasis of RCC -- often to the scalp and face -- affects less than 1% of patients. Differential diagnostic considerations include hemangioma, pyogenic granuloma, or even primary skin cancer, case authors wrote; bilateral synchronous and metachronous nonfamilial renal masses are often ccRCC and account for more than 85% of such cases.

A large analysis of risk factors in 80,000 patients with RCC in the Surveillance, Epidemiology, and End Results (SEER) database found that of the 1% who developed a , more than 70% were diagnosed 10 years after the initial RCC, and the risk remained permanent even at a follow-up time ≥10 years. Those authors demonstrated a cumulative incidence of 1.5%, 3.1%, and 4.7% at 10, 20, and 30 years, respectively. Younger age, male gender, Black race, and papillary histology were demonstrated to predispose to contralateral metachronous RCC.

The case authors noted that in this patient, consecutive surgical resections of metastasis increased her survival by more than 10 years from the first metastasis. "The clinical presentation and laboratory investigations of the metastasis were nonspecific; proper imaging has an essential role, and careful pathology reporting is critical for not missing such rare metastatic presentations," they wrote, citing a of 6 months for patients with no metastasis treatment.

Evidence suggests that surgery has a beneficial role in prolonging patient survival, they concluded. Supporting enrollment of such patients in clinical trials of metastasectomy for advanced RCC will help demonstrate its clinical utility.

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