While renal cell carcinoma is the most commonly diagnosed neoplasm of the kidney, its simultaneous diagnosis with a gastrointestinal malignancy is a rare, but well reported phenomenon. This discussion focuses on three independent cases in which each patient was diagnosed with renal cell carcinoma and a unique synchronous gastrointestinal malignancy. Case
Renal cell carcinoma (RCC) is the most common neoplasm of the kidney, affecting 15.5 people per 100,000 men and women each year and accounting for only 3.8% of new cancer cases diagnosed annually in the United States [
This discussion utilizes the Warren and Gates definition to identify synchronous tumors: each tumor must present with a definite picture of malignancy, each must be distinct, and the possibility that one is a metastasis of the other must be excluded [
It has been well reported that RCC is associated with other primary malignancies, including prostate, bladder, and rectal cancers, as well as non-Hodgkin’s lymphoma [
A 66-year-old man presented to the clinic with a history of acute onset right lower quadrant abdominal pain, hematuria, and flank pain. General physical examination revealed no significant findings. The patient’s family history revealed his mother had both thyroid and colon cancer, though the details of each were unknown.
Initial laboratory findings included mild iron deficiency anemia with elevated white blood cell count, increased BUN and creatinine, and a urine analysis positive for blood and protein. Abdominal CT scan revealed a hypervascular multilocular solid renal mass that had compromised Gerota’s fascia and was occupying the right renal vein. Also noted on CT scan was an enhancing partially necrotic solid nodule within the left mesentery, as well as multiple diminutive ill-defined hepatic lesions.
The patient then underwent a right radical nephrectomy with tumor thrombectomy and retroperitoneal lymph node dissection. During intraoperative inspection of the mesenteric region, an ileal mass was encountered, and an
Evaluation of the nephrectomy specimen revealed a 7 cm Fuhrman grade 2 clear cell RCC invading the renal vein with lymphovascular invasion and clear surgical margins without invasion of Gerota’s fascia or the renal sinus (T3aN0M0) (Figure
The surgically resected specimen consisted of clear cell renal carcinoma with tumor thrombus (arrow).
Histological examination (hematoxylin-eosin staining; magnification 4x) of the resected small bowel specimen showing a neuroendocrine carcinoma composed of islands of uniform cells embedded within fibrous tissue.
A 61-year-old man presented with constant dull right lower quadrant pain associated with fatigue and malaise. Initial CT scan showed an enlarged appendix and a partially exophytic, enhancing mass located in the upper pole of the left kidney with an enlarged para-aortic lymph node (Figure
CT scans reveal a partially enhancing mass ((a) arrow) located on the upper pole of the left kidney. The presence of para-aortic lymphadenopathy ((b) arrowhead) as well as a prominent appendiceal mass ((c) arrow) was also noted.
Initial examination of the patient revealed an asymptomatic well-developed man. Besides a past medical history of hypertension, the patient was otherwise healthy. Upon physical examination, findings included bilaterally descended testes, left grade II varicocele, and lack of lymphadenopathy or hernia. The patient’s family history was insignificant. The patient’s CBC and serum chemistry panel were normal. Urinary analysis found 3 RBCs per high-power field but was otherwise normal.
The patient then underwent left-sided robotic-assisted partial nephrectomy with para-aortic lymphadenectomy. Histological findings of the renal mass confirmed a 3 cm Fuhrman grade 3, clear cell RCC limited to the renal parenchyma with negative margins. Resection of lymph nodes revealed 0/6 perihilar and 1/14 para-aortic nodes with metastasis. He was, therefore, staged as a T1aN1M0. Following removal of tumors, the patient recovered without complication. A follow-up CT scan was performed four months postoperatively and showed no evidence of metastasis. The patient is currently in good health and has no evidence of disease at four-month follow-up.
A 36-year-old female initially presented for evaluation of a left supraclavicular neck mass. The patient underwent fine needle aspiration of the mass, which revealed adenocarcinoma favoring renal cell. CT scan of the chest, abdomen, and pelvis revealed a large left renal mass 9 cm in diameter. The scan incidentally also detected a possible filling defect in the transverse colon. The patient underwent colonoscopy, and a mass was visualized and biopsied. Histological examination found the mass to be positive for invasive adenocarcinoma.
Physical examination of the patient revealed an overweight woman with a past medical history of hypertension. The patient denied any changes in bowel habits or urinary complaints other than intermittent left flank pain. The patient reported that her family history was negative for cancer or polyps. General physical examination revealed a small nodule palpable in the left supraclavicular region of the patient’s neck. Laboratory findings were normal except for presence of iron deficiency anemia.
The patient then underwent left radical nephrectomy with periaortic lymphadenectomy and extended right hemicolectomy. Histological examination of the left kidney confirmed a 7.5 cm Fuhrman grade 4, clear cell RCC limited within Gerota’s fascia with no lymphovascular invasion. The tumor was present in 5/5 periaortic lymph nodes that were resected (T2aN1Mx). The resected large bowel specimens demonstrated tubular adenoma present in the cecum and hepatic flexure; also noted was moderately differentiated invasive adenocarcinoma extending into the submucosa of the transverse colon (T1N0M0) (Figure
Histological examination (hematoxylin-eosin staining; magnification 3x) of the resected large bowel specimen showing a moderately differentiated adenocarcinoma invading into the submucosa.
She was started on sunitinib postoperatively but failed therapy after developing bilateral malignant pleural effusion and malignant disease progression and was subsequently given temsirolimus.
After one month, postoperative CT scan revealed local recurrence in the kidney bed, suggesting highly aggressive cancer. Imaging also found enhancing enlarged supraclavicular lymph nodes extending cranially along the jugular chain and caudally into the mediastinum. This finding was strongly suggestive of metastatic disease. PET scan was performed and confirmed diffuse nodal metastasis throughout the thorax and neck. She then underwent chest wall biopsy and pleurodesis using video-assisted thoracoscopic surgery, the results of which confirmed malignant RCC. The patient died approximately one year following initial resection.
The occurrence of synchronous malignancies has been well established in the literature. In the case of RCC, multiple primary malignancies associated with this neoplasm have been the focus of many studies within the past decade. Beisland et al. [
The etiology and pathogenesis of multiple primary malignancies have yet to be explained. It has been thought that interplay of genetic and environmental risk factors common to both cancers could cause multiple malignancies to arise. Common risk factors include tobacco, pollution, ultraviolet light, therapeutic chemotherapy and radiotherapy, and endocrine factors. It is thought that these factors may act individually or in combination [
Considering the three cases presented, each patient did not smoke and had no prior medical illness that could point to a common risk factor. The patient presented in Case 1 reported a family history of thyroid and colon cancer. A possible underlying genetic variation may have been present, although no genetic testing was performed on either the first or the second patient presented. The third case discussed demonstrates a well-established genetic predisposing factor. Individuals with HNPCC are known to have various mismatch repair genes that are functionally affected, with patients having 80% lifetime risk of developing colon cancer [
A common finding among the three clinical cases presented was that, in each case, the renal malignancy was aggressive clear cell RCC. This may be a coincidental finding, as clear cell is the most common form of RCC [
Current guidelines by the American Urological Association regarding the management of clinical stage 1 renal masses lack an explicit recommendation for clinicians to be aware of the possibility of a secondary primary malignancy [
The authors have no conflict of interests.
The funding source had no involvement in this paper.