Introduction
============

Renal cell carcinoma (RCC) as the most common malignant tumor of the kidney has an unpredictable and bizarre natural history, i.e. on the one hand it has an indolent growth rate and showed metastasis at the time of presentation and on the other hand it can remain stable years after nephrectomy.^[@B1]^

The most common sites of metastasis in RCC are the lung and bone; other less common metastatic locations are lymph nodes, adrenal, liver, opposite kidney and brain.^[@B2]^

Gastrointestinal metastasis of RCC is rare and reported in 4% of the cases, however, in the GI tract, the least common site of metastasis is small intestine and it is extremely rare for metastatic RCC to be presented as duodenal ulcer and melena.^[@B3]^

To the best of our knowledge, less than 30 cases of duodenal metastasis of RCC have been reported in the English literature and the longest duration after nephrectomy has been 13 years. 

Herein we report our experience with a 61-year-old man presented with melena 16 years after nephrectomy that was diagnosed to be metastatic RCC.  The patient underwent Whipple's operation with excellent postoperative course. 

Case Report
===========

A 61-year-old man was presented with melena.  He was in a good health condition.  His past medical history showed right kidney nephrectomy (16 years ago) with the diagnosis of clear cell RCC without any further treatment.  He had been completely normal during the last 16 years. 

Laboratory findings were:

-   Liver function tests were normal: ALT=19 U/L (normal\<40), AST=25 U/L (normal\<40), Alkaline phosphatase=193 U/L (normal 80-306)

-   Complete Blood Count was normal: WBC: 6000/µl, RBC: 5×10^6^/µl, and Platelet: 263000/µl

Physical examination showed normal heart and lung examination.  There was no lymphadenopathy.  Blood pressure, pulse rate, heart rate, and temperature were all unremarkable. 

Stool occult blood test was positive in several occasions, so the patient underwent upper and lower gastrointestinal endoscopy.  An ulcer was found in the second part of duodenum with fine oozing of blood ([figure 1a, 1b](#F1){ref-type="fig"} as indicated by arrows).  A biopsy was taken and sections from duodenum showed surface ulceration beneath of which there was subepithelial collection of cells with clear cytoplasm ([figure 2a, 2b](#F2){ref-type="fig"}).  Immunohistochemistry was positive for cytokeratin, CD10, vimentin, and RCC antibody ([figure 3a, 3b](#F3){ref-type="fig"}). 

![( A and B) Endoscopy of the duodenum shows ulcers (Arrows).](ijms-40-175-g001){#F1}

![ High and low power view of duodenal ulcer biopsy show collections of clear cells. ( A: H&E ×100, B: H&E ×250).](ijms-40-175-g002){#F2}

![ Immunohistochemistry was positive for cytokeratin (A) and vimentin (B).](ijms-40-175-g003){#F3}

With the pathologic diagnosis of metastatic RCC, abdominal CT scan was performed that showed a mass in the distal pancreas measuring 7 cm in greatest diameter with central necrosis, most probably arisen from duodenum extending to the pancreas ([figure 4](#F4){ref-type="fig"}).  Whipple's operation was performed and the pancreatoduodenal mass was resected.  The specimen showed a mass measuring 7×5.5 cm in the duodenum extending to the head of the pancreas ([figure 5](#F5){ref-type="fig"}).  Pathology of the specimen showed metastatic RCC involving the duodenum and distal pancreas ([figure 6](#F6){ref-type="fig"}).  The patient was discharged in good condition to be followed for further evaluation. 

![ Abdominal CT scan shows pancreaticoduodenal mass and absence of right kidney.](ijms-40-175-g004){#F4}

![ Gross specimen of the duodenal mass shows relatively well defined mass beneath the small intestinal wall (arrows show mucosa of duodenum).](ijms-40-175-g005){#F5}

![ Sections from ampulla of vater show subepithelial tumoral tissue with clear cell morphology. ( H&E ×100)](ijms-40-175-g006){#F6}

This case is being reported by the informed consent of the patient. 

Discussion
==========

The behavior of RCC is completely unpredictable.  Metastatic masses can be the first presentation of RCC or can be diagnosed years after the initial diagnosis and nephrectomy.^[@B4]^ Most common sites of metastatic RCC are the liver and lung.^[@B2]^ Metastases to the pancreas and small intestine are rare, but can present as gastrointestinal bleeding*.*^[@B5]^ About 4% of RCCs metastasize to the small intestine, of these; the duodenum is the least frequent site and can be involved by direct invasion of the tumor, or through lymphatic, transcoelomic or haematogenous spread and also direct invasion of pancreatic metastasis.^[@B5]^ In our patient, at the time of surgery, the main bulk of tumor was in the duodenum with extension to the head of pancreas. 

According to the previous reports, duodenal involvement of RCC can be presented with jaundice, anemia and gastrointestinal bleeding, malabsorption and obstruction.^[@B6]^ Primary presentation of metastatic RCC as gastrointestinal bleeding has been rarely reported.^[@B7]^

The longest duration between nephrectomy and duodenal metastasis was 13 years in previous reports.^[@B8]^

Diagnosis of duodenal metastasis in RCC most commonly has been made by endoscopy.  On endoscopy, the lesion can be seen as an ulcer, submucosal mass with ulceration or multiple nodules or small polyps of varying sizes.^[@B9]^

Some patients present with concomitant metastasis in more body locations or other segments of the intestine such as the colon and duodenum.^[@B10]^

Our case presented with melena and duodenal ulcer 16 years after right nephrectomy for RCC.  In previous studies, most of the duodenal metastasis of RCC was after right kidney nephrectomy.^[@B8]^

Most of the metastatic RCCs in the duodenum were primarily in the second portion with and without pancreatic involvement.^[@B9]^

The treatment of choice for localized metastatic RCC is surgery.^[@B2]^ In previous reports, most of the patients with duodenal metastasis of RCC were treated with Whipple's operation; however, there were successful surgeries of duodenal saving segmental or wedge resection.^[@B3],[@B11]^ Any type of metastasectomies can increase the survival of the patient.^[@B5]^

To the best of our knowledge, less than 30 cases of RCC with duodenal metastasis have been reported in the English literature ([table 1](#T1){ref-type="table"}).  The longest duration after nephrectomy has been 13 years.  Our case presented with melena 16 years after right nephrectomy for RCC, which to the best of our knowledge is the longest duration after nephrectomy. 

###### 

Clinical characteristic of the previous cases of duodenal metastasis of RCC

  **Author/Year**                  **Sex/Age**   **Presenting symptom**      **Concomitant other organ involvement**   **Years after initial nephrectomy**   **Treatment**
  -------------------------------- ------------- --------------------------- ----------------------------------------- ------------------------------------- -------------------------
  Lawson et al./1966^[@B12]^       69/F          Anemia , GI bleeding        \-                                        0                                     Whipple's operation
  Heyman et al./1978^[@B13]^       64/M          GI bleeding                 Colon                                     8 years                               Complex resection
  McNicholas/1981^[@B14]^          52/M          Malabsorption               \-                                        10 years                              No surgery
  Lynch et al./1987^[@B15]^        67/M          GI bleeding                 Pancreas                                  2 years                               No surgery
  Lynch et al./1987^[@B15]^        61/M          Jaundice                    \-                                        6 years                               No surgery
  Lynch et al./1987^[@B15]^        16/M          GI bleeding                 \-                                        1 year                                No surgery
  Robertson et al./1990^[@B16]^    70/M          GI bleeding                 Pancreas                                  13 years                              Whipple's operation
  Toh et al./1996^[@B2]^           59/F          Anemia, Bowel obstruction   \-                                        10 years                              Segmental resection
  Ohmura et al./2000^[@B17]^       62/M          Obstruction                 \-                                        5 years                               \-
  Hashimoto et al./2000^[@B18]^    57/M          GI bleeding                 Pancreas                                  11 years                              Pancreaticoduodenectomy
  Nabi et al et al./2001^[@B19]^   40/M          Obstruction                 \-                                        4 years                               Segmental resection
  Lee et al./2002^[@B10]^          76/F          Abdominal pain              Colon                                     4 years                               No surgery
  Loualidi et al./2004^[@B6]^      76/M          Anemia, GI bleeding         \-                                        5 years                               No surgery
  Chang et al./2004^[@B20]^        63/F          GI bleeding                 \-                                        9 years                               Segmental resection
  Bhatia et al./2006^[@B9]^        50/M          Jaundice                    Liver                                     1 year                                No surgery
  Sadler et al./2007^[@B5]^        67/M          GI bleeding                 \-                                        0                                     No surgery
  Sadler et al./2007^[@B5]^        75/M          Anemia                      \-                                        9                                     No surgery
  Adamo et al./2008^[@B21]^        86/F          Anemia, Obstruction         \-                                        9 years                               Pancreaticoduodenectomy
  Eo et al./2009^[@B22]^           47/M          Intussception               Lung                                      2 years                               Segmental resection
  Teo MY/2010^[@B8]^               50/F          Jaundice                    Lung                                      1 year                                No surgery
  Rustagi et al./2011^[@B23]^      66/M          GI bleeding                 \-                                        13 years                              Whipple's operation
  Cherian et al./2011^[@B24]^      80/M          GI bleeding                 Lung and Bone                             11 months                             No surgery
  Vashi et al./2011^[@B25]^        53/M          GI bleeding                 \-                                        2 weeks                               Segmental resection
  Chua et al./2011^[@B26]^         56/M          GI bleeding, Anemia         Lung                                      0                                     Segmental resection
  Zhao et al./ 2012^[@B3]^         56/M          GI bleeding                 \-                                                                              Whipple's operation
  Yang et al./2012^[@B4]^          72/M          GI bleeding                 \-                                        10 years                              Whipple's operation
  Ashraf Teli et al./2012^[@B7]^   52/M          GI bleeding                 Liver                                     8 years                               Segmental resection
  Current Case                     61/M          GI bleeding                 \-                                        16 years                              Whipple's operation

As a conclusion, distant metastasis of RCC can be presented very late with unusual and unpredictable symptoms.  In all patients with a history of RCC, GI bleeding should be considered as a possible cause of metastasis. 

**Conflict of Interest:** None declared.