Mediastinal Metastasis 10 Years after Primary Renal Cell Carcinoma —a Report of a Case and a Review

Late recurrence of renal cell carcinoma (RCC), arbitrarily defined, as >10 years post-nephrectomy, is rare. Here we review 43 reports comprising 467 cases. Metastasis occurred between few months and 45 years. We report a new case with a 10-year interval to metastasis.


Introduction
The incidence of late recurrence of metastatic RCC is 11% in patients surviving for 10 years after the initial diagnosis [1].T-stage, grade and sarcomatoid differentiation independently dictate the risk of tumor recurrence.Recurrences (distant and/or local) could represent more than half of the cases [2].The mean and median time to recurrence varies from series to series (Table 1) [1]- [43].It ranges from few months to decades [24].
Late recurrence of renal cell carcinoma (RCC), arbitrarily defined, as >10 years post-nephrectomy, is rare [24].Here we review previous cases and report one new case.
We describe one new case.

Report of Case
The patient is a seventy-four-year old female from Iraq.There is a history of long-standing hypertension and atrial fibrillation and was put on warfarin since 2005.She had cholecystectomy then right radical nephrectomy for renal cell carcinoma in 2006.She had CVA in 2009 without residuals.She presented recently with cough and shortness of breath for one-month duration.Her cough was severe and more at night.It was productive of small brownish sputum, which became yellowish later.There was orthopnea too.There is bilateral lower limbs swelling and shortness of breath, which was not related to exertion.There was no weight loss or night sweats.
Serum creatinine was normal.CT-scan with contrast enhancement (Figures 2-4) showed a large heterogeneously enhancing solid lesion with irregular central necrosis measuring about 6.7 cm seen in the right side of mediastinum located posterior to the superior vena cava and the aortic arch.It was superior to the right pulmonary artery and i lateral to the trachea.There is no evidence of hilar or mediastinal lymph node enlargement.There is collapse consolidation of the lower lung lobes seen with air bronchogram and right-sided pleural effusion.A small left-sided pleural effusion with atelectasis of the basal lung tissue is also noted.The rest of lung fields are clear.A small cystic nodule measuring about 1 cm is seen in the right lobe of thyroid gland.Chest wall and rib cage are unremarkable.
Bone Scan showed multiple abnormal areas of increased radiotracer uptake involving skull, both shoulder joints, right 5th rib anteriorly, several ribs anteriorly at costo-chondral junction, lower lumbar spine, proximal end of right humerus, sternum, bilateral sterno-clavicular joints, and both knee joints.Right kidney is not visualized    (Rt.Nephrectomy).There is high target to soft tissue uptake ratio throughout the skeleton, with increased uptake along both lower limbs.Appearances are consistent with metabolic bone disease, pulmonary hypertrophic osteoarthpathy secondary to intra thoracic mass, renal osteodystrophy and osteoporosis.There was no scintigraphic evidence of bone metastasis.
US abdomen and pelvis findings: The liver showed normal echogenieity and echotcxture, no visible focal lesions or megaly.Right nephrectomy and cholecystectomy were obvious.
The right renal bed shows no masses.The left kidney shows increased parenchymal echogenicity with lobulated contour, it measures 9.6 cm-length, no stones, masses, or hydronephrosis.Small right-sided plural effusion is noted.The visualized portions of the pancreas and retroperitoneal area appeared normal.The spleen has normal sonographic appearances.The urinary bladder has no luminal defects.The uterus shows no masses and the pelvis shows no cysts or masses.
ECG showed atrial fibrillation.ECHO showed left and right atrium enlargement.Ejection fraction was 65%.Under ultrasound guidance aspiration of about 300 cc of bloody right pleural effusion was performed.There was segmental collapse of right lower lobe.The cytology was negative for malignant cells.
CT-guided Truecut needle biopsy from that mass was taken and the specimen sent for histopathology.No pneumothorax occurred and there was only lung contusion.
Figure 8 shows Vimetin immunohistochemical stain showing positive cytoplasmic staining of tumor cells (Ventana Benchmark)-high power view (magnification × 400).She was put on Sutant (Sunitinib) 50 mg orally 1 × 1 for 4 weeks then another cycle for 4 weeks with 2 weeks interval in between.

Discussion
Renal cell carcinoma (RCC) is the most common renal malignancy (approximately 90% of cases) with high metastatic potential.Most of these tumors are incidentally discovered at abdominal imaging and usually carry a better prognosis owing to early-stage disease.Approximately 20% of patients will go on to develop metastatic disease within the first 3 to 5 years after treatment of the primary tumor.Sites of metastases include the lungs, liver, bone, and brain, contra lateral kidney renal fossa, rectum and stomach [6] [27] [31] [35] [37] [39].
Brain metastasis occurs in 3.9% -24% of patients with renal cell carcinoma (RCC), with an average interval from nephrectomy to brain metastasis of 1 to 3 years.A few cases have been reported where brain metastasis occurred following a delay of 15 to 20 years after a nephrectomy for RCC [4]    Thyroid and salivary glands metastasis was reported at 10 and 19 years after nephrectomy for renal cell carcinoma [5] [13]- [15] [20] [28].Also falx metastasis was described 20 years afterward right nephrectomy for renal cell carcinoma.Dural metastases after renal cell carcinoma are very rare [7].
Metastatic non-colorectal cancer of the anal canal is a rare entity.To date, only four cases have been described in the literature.It can present as a hemorrhoid [8].
A rare case of RCC metastasis in the parotid gland was described eleven years after the initial diagnosis [11].Metastasis of renal cell carcinoma to the buccal mucosa occurred 19 years after radical nephrectomy [17].
Walter and Gellespie reported the longest known clinical disease-free interval of 36 years in 1960 [24].However, Helene Tapper et al. [24] reported the 45-year interval between nephrectomy and clinical recurrence of RCC.It appears to be the longest on record [24].McNichols et al. reported a recurrence rate of 11% in a series of 506 patients.This estimate is based on 18 late recurrences in 158 patients who were followed over a period of 24 to 37 years.Since most of the patients (348) in this series died from other causes, the actual recurrence rate may be less than 11% [24].
This report presents a mediastinal mass consistent with metastatic RCC 10 years after successful treatment of the primary RCC.Clearly, this is rare, but the case serves to remind the need for vigilance in dealing with cases having a history of previous malignancy.The case presented confirms the possibility that this rare event may present even 10 or more years after nephrectomy has been performed.
Renal cell carcinoma contains glycogen, making it PAS-positive and diastase-negative.Additionally, RCC shows immunohistochemically positive staining with keratin and vimentin and CEA negativity, supporting the diagnosis of metastatic RCC.
It is well known that solitary metastasis and a greater interval between the primary treatments to the appearance of the metastasis are favorable prognostic factors in RCC [14].
We offered adjuvant treatment (Sunitinib), because of patient's poor general condition.Treatment was well tolerated.Sunitinib is an oral inhibitor of tyrosine kinases, including vascular endothelial growth factor receptor and platelet-derived growth factor receptor, and has been associated with higher response rates and longer progression-free survival in patients with metastatic RCC as compared to interferon and might also show activity in the adjuvant and neoadjuvant setting [3].
RCC patients require long-term follow-up, to assist in early detection of metastasis and early treatment.

Figure 2 .
Figure 2. CT-scan with contrast enhancement showed a large heterogeneously enhancing solid lesion with irregular central necrosis measuring about 6.7 cm seen in the right side of mediastinum located posterior to the superior vena cava and the aortic arch.It was superior to the right pulmonary artery and i lateral to the trachea.There is no evidence of hilar or mediastinal lymph node enlargement.There is collapse consolidation of the lower lung lobes seen with air bronchogram and rightsided pleural effusion.A small left-sided pleural effusion with atelectasis of the basal lung tissue is also noted.The rest of lung fields are clear.

Figure 3 .
Figure 3. CT-scan with contrast enhancement showed a large heterogeneously enhancing solid lesion with irregular central necrosis measuring about 6.7 cm seen in the right side of mediastinum located posterior to the superior vena cava and the aortic arch.It was superior to the right pulmonary artery and i lateral to the trachea.There is no evidence of hilar or mediastinal lymph node enlargement.There is collapse consolidation of the lower lung lobes seen with air bronchogram and rightsided pleural effusion.A small left-sided pleural effusion with atelectasis of the basal lung tissue is also noted.The rest of lung fields are clear.

Figure 4 .
Figure 4. CT-scan with contrast enhancement showed a large heterogeneously enhancing solid lesion with irregular central necrosis measuring about 6.7 cm seen in the right side of mediastinum located posterior to the superior vena cava and the aortic arch.It was superior to the right pulmonary artery and i lateral to the trachea.There is no evidence of hilar or mediastinal lymph node enlargement.There is collapse consolidation of the lower lung lobes seen with air bronchogram and right-sided pleural effusion.A small left-sided pleural effusion with atelectasis of the basal lung tissue is also noted.The rest of lung fields are clear.

Figure 5 (
a) and Figure 5(b) show renal cell carcinoma-low and high power view (magnification × 40 and × 400 respectively) showing optically clear cytoplasm and sharp cell membranes.

Figure 5 .
Figure 5. Shows renal cell carcinoma-low and high power view (magnification × 40 and × 400 respectively) showing optically clear cytoplasm and sharp cell membranes.