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Solitary Duodenal Metastasis from Renal Cell Carcinoma with Metachronous Pancreatic Neuroendocrine Tumor: Review of Literature with a Case Discussion

CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2019; 40(S 01): S185-S190

DOI: DOI: 10.4103/ijmpo.ijmpo_214_17

Author : Baghmar, Saphalta, Shasthry, S M; Singla, Rajesh, Patidar, Yashwant, Bihari, Chhagan B, Sarin, S K

Abstract

Renal cell cancinoma (RCC) is a unique malignancy with features of late recurrences, metastasis to any organ, and frequent association with second malignancy. It most commonly metastasizes to the lungs, bones, liver, renal fossa, and brain although metastases can occur anywhere. RCC metastatic to the duodenum is especially rare, with only few cases reported in the literature. Herein, we review literature of all the reported cases of solitary duodenal metastasis from RCC and cases of neuroendocrine tumor (NET) as synchronous/metachronous malignancy with RCC. Along with this, we have described a unique case of an 84-year-old man who had recurrence of RCC as solitary duodenal metastasis after 37 years of radical nephrectomy and metachronous pancreatic NET.

Keywords

Late recurrence - pancreatic neuroendocrine tumor - renal cell carcinoma - second malignancy - solitary duodenal metastasis


Publication History

Article published online:
24 May 2021

© 2019. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

Abstract

Renal cell cancinoma (RCC) is a unique malignancy with features of late recurrences, metastasis to any organ, and frequent association with second malignancy. It most commonly metastasizes to the lungs, bones, liver, renal fossa, and brain although metastases can occur anywhere. RCC metastatic to the duodenum is especially rare, with only few cases reported in the literature. Herein, we review literature of all the reported cases of solitary duodenal metastasis from RCC and cases of neuroendocrine tumor (NET) as synchronous/metachronous malignancy with RCC. Along with this, we have described a unique case of an 84-year-old man who had recurrence of RCC as solitary duodenal metastasis after 37 years of radical nephrectomy and metachronous pancreatic NET.


Keywords

Late recurrence - pancreatic neuroendocrine tumor - renal cell carcinoma - second malignancy - solitary duodenal metastasis

Introduction

Renal cell carcinoma (RCC) is unique to have many unusual features such as metastasis to almost every organ in the body, late recurrences, and frequent association with second malignancy. The most common sites of metastasis are the lung, lymph nodes, liver, bone, adrenal glands, kidney, brain, heart, spleen, and skin. Solitary duodenal metastasis from RCC is one of the unusual sites of metastasis. Late recurrences can be as long as 32.7 years.[1] Second malignancies associated with RCC have been reported with an incidence that varies from 5% to 27%.[2] [3] Here, we have reviewed all the reported cases of RCC with solitary duodenal metastasis and cases of synchronous/metachronous neuroendocrine tumor (NET). Here, we present a unique case of a patient with duodenal metastasis who presented with anemia and gastrointestinal (GI) bleeding, 37 years after nephrectomy. Duodenal biopsy performed revealed metastasis from RCC. He also had a history of recurrent diarrhea and abdominal pain, and on evaluation, he found to have cytology-proven metachronous pancreatic NET.


Case Presentation

An 84-year-old man with a medical history notable for hypertension and RCC, 37 years postright radical nephrectomy status, presented to his primary care physician with fatigue. When found to be anemic, he was treated with iron supplementation and blood transfusions. His stool was heme-positive. There was no history of jaundice, abdominal distension, bleeding tendency, melena, or altered sensorium. Laboratory investigations on admission were significant for microcytic hypochromic anemia with hemoglobin 6.8 g/dl and hematocrit 16.8%. Liver enzymes and serum levels of the tumor markers CA 19-9 and carcinoembryonic antigen were within normal range. Serum chromogranin levels were more than 650 ng/ml.

His history also included his presentation with repeated increased frequency of stool 3–4/day, semisolid without blood or mucus in December 2006. 68Ga-labelled [1,4,7,10-tetraazacyclododecane-1,4,7,10tetraacetic acid]-1-Nal3-octreotide (68Ga-DOTA-NOC) positron-emission tomography (PET) suggested enhancing pancreatic head (HOP) mass with central necrosis which was non-fluoro deoxycolic glucose (FDG) avid on PET-computed tomography. With the suspicion NET, the patient was advised surgery, but he denied any intervention.

For the current presentation, the patient underwent upper GI endoscopy which was suggestive of a large hiatus hernia with a large polypoidal lesion in D1–D2 junction, with ulcerations, without any active bleed [Figure 1a]. Endoscopic ultrasound was done which showed an ill-defined mass lesion measuring 7.8 cm × 7.8 cm in the HOP, not infiltrating into adjacent duodenum. The superior mesenteric vein was splayed by the mass. Gastroduodenal artery was piercing the mass, but the flow was intact. Duodenal polypoidal mass was arising from the second layer with intact third and fourth layer [Figure 1b].


| Figure. 1  (a) Endoscopic image of polypoidal lesion (white arrow) in D1–D2 junction; (b) endoscopic ultrasound image showing pancreatic head mass


The HOP mass (8.3 cm × 6.2 cm × 6.2 cm) was more 68Ga-DOTA-NOC avid while the D1–D2 mass (2.4 cm × 2.9 cm) was more FDG avid [Figure 2].



| Figure. 2 Axial fluoro deoxycolic glucose positron-emission tomography and (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-1-Nal3-octreotide positron-emission tomography image of the upper abdomen reveal large soft tissue intensely (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-1-Nal3-octreotide avid and fluoro deoxycolic glucose positron-emission tomography nonavid mass in the head and uncinate process of pancreas (white arrows in image a, b, and c) and another polypoidal intraluminal fluoro deoxycolic glucose positron-emission tomography avid and (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-1-Nal3-octreotide nonavid mass in D2 part of duodenum (dashed white arrows in image a, b, and c)


Tissue was obtained from both the pancreatic as well as the duodenal lesions. HOP mass turned out to be NET [Figure 3a], grade could not be ascertained as tissue was inadequate for Ki-67 index] while the duodenal lesion was recurrence of RCC [Figure 3b], showing surface epithelial denudation and lamina propria are infiltrated by tumor glands which are positive for CD10 [Figure 3c], Paired box (PAX) 8, and vimentin and negative for cytokeratin, CD20, synaptophysin, chromogranin, indicating metastatic RCC].



| Figure. 3  (a) Fine-needle aspiration cytology smear showing loosely cohesive sheet of monomorphic tumor cells with nuclear streaking. Nuclei have even distribution of stippled chromatin: indicating neuroendocrine tumor; (b) duodenal biopsy showing surface epithelial denudation and lamina propria is infiltrated by tumor glands; (c) the glands are positive CD10, indicating metastatic RCC


He was advised tablet sunitinib which is effective in both as the lesion was unresectable. He opted for only symptomatic management.


Discussion

Late recurrences

RCC has a potential to metastasize to any organ in an unpredictable manner, and late recurrence is a known feature. Eleven percent of these metastases have been described in the literature as occurring more than 10 years after the initial radical surgical procedure.[4] Ours has very exceptional late recurrence after 37 years. This suggests that very long follow-up and surveillance are necessary in RCC. It is important to remain vigilant in postnephrectomy patients on presentation of new clinical symptoms.


Sites of metastasis

The routes for metastasis can be hematogenous, lymphatic, or peritoneal dissemination as well as direct spread from an intra-abdominal malignancy.[5] The most common sites of metastasis in the descending order of frequency are the lung, lymph nodes, liver, bone, adrenal glands, kidney, brain, heart, spleen, and skin.[5] It is also known to have metastasis to unusual sites.[6] Duodenal metastasis generally occurs when there is widespread nodal and visceral involvement and evidence of metastatic disease elsewhere in the body.[7] Our case had solitary duodenal metastasis from RCC which is rare and only few cases have been described in the English literature [Table 1]. The patients commonly present with GI bleeding and sequelae may include anemia, melena, fatigue, and early satiety as in our case or intestinal obstruction.[19] Such metastatic lesions to the upper GI tract are sometimes diagnosed on endoscopy.[28] Endoscopically, they are seen as submucosal tumors and polypoid masses, with erosion, plaque, or ulceration being the usual morphological findings.[19] In the present case, the metastatic lesion was seen as ill-defined polypoidal mass lesion measuring 2.9 cm × 2.2 cm with ulceration in the second part of duodenum.


Table 1

Summary of case reports on solitary duodenal metastasis from renal cell cancer in English literature

Treatment

Treatment options in a case of RCC metastasis depend on the extent and location of the lesion, so the therapy must be individualized. Procedures ranging from Classic Whipple to transarterial embolization have been reported.[14] For disseminated malignancy, mainly supportive care and therapeutic methods including palliative surgery, radiotherapy, chemotherapy, target therapy (sunitinib), or immune-stimulating agents (interleukin-2) have been used.[6] [29] [30] In our case, the duodenal metastasis was large and unresectable, he was advised sunitinib, but he opted for best supportive care.


Survival

In a large series of unusual sites of metastasis from RCC reported that the patients who present with an initial solitary metastatic lesion to an unusual site had a better survival compared to patients who primarily presented with multiple metastases, 17.0 versus 3.0 months. Resection of the unusual metastasis improved survival.[6] Kavolius et al.[31] reported in their series of 278 patients with recurrent RCC after a disease-free interval longer than 1 year had better prognosis while Villarreal-Garza et al. found none.[6]


Second primary malignancy

Incidence of synchronous or metachronous RCC with other malignancy has been reported in 3.7% of cases.[32] Such malignancies include intrahepatic cholangiocarcinoma,[33] hepatocellular carcinoma,[34] nasopharyngeal carcinoma,[35] urological cancers,[36] stomach cancer, esophageal carcinomas, duodenal carcinoma,[37] colorectal carcinomas, lung cancer, breast cancer, gynecological cancer, sarcoma and non-Hodgkin’s lymphoma,[38] and melanoma.[39] We could find only six cases of synchronous/metachronous NET with RCC in the English literature [Table 2]. Our patient developed pancreatic NET during follow-up of RCC, postnephrectomy.

Ref

Year

Age/sex

Years postnephrectomy

Presentation

Treatment

Survival (months)

GI – Gastrointestinal; NA – Not available

Baghmar et al.

This article

84/male

31

Easy fatigue, anemia

Supportive care

12

Geramizadeh et al. [8]

2015

61/male

16

GI bleeding

Classic Whipple

NA

Hu[9]

2014

51/male

12

Fatigue, dyspepsia, black tarry stools, generalized weakness

Pancreaticoduodenectomy

6

Zhao et al. [10]

2012

56/male

5

GI bleeding

Classic Whipple

NA

Yang et al. [11]

2012

12/male

10

GI bleeding

Classic Whipple

NA

Rustagi et al. [12]

2011

66/male

13

Easy fatigue, anemia, GI bleeding

Pylorus-preserving pancreaticoduodenectomy

NA

Vashi et al.[13]

2011

53/male

2 weeks

GI bleeding

Segmental resection

3

Adamo et al.[14]

2008

86/female

13

Easy fatigue, anemia

Classic Whipple

1

Sadler et al. [15]

2001

15/male

9

Anemia

Supportive care

NA

Pavlakis et al.[16]

2004

65/male

2

Obstruction

Intestinal resection

9

Chang et al.[17]

2004

63/female

9

GI bleeding

Radical subtotal gastrectomy

10

Loualidi et al.[18]

2004

16/male

5

GI bleeding

Palliative radiotherapy

NA

Nabi et al.[19]

2001

40/male

4

Epigastric pain, obstruction with bilious vomiting

Proximal gastrojejunal bypass

Died 1 days post-op of sepsis

Le Borgne et al.[20]

2000

12/female

1

GI bleeding

Classical Whipple

18

Le Borgne et al.[20]

2000

48/male

13

GI bleeding

Classical Whipple

53

Ohmura et al.[21]

2000

62/male

5

Obstruction

Embolization+local resection

-

Toh and Hale[22]

1996

59/female

10

Abdominal pain, anorexia

Duodenotomy, excision of mass

NA

Freedman et al.[23]

1992

65/male

12

GI bleeding, fatigue

Classical Whipple

66

Lynch-Nyhan et al.[24]

1981

16/male

1

GI bleeding

Embolization

6

Lynch-Nyhan et al.[24]

1981

61/male

6

Jaundice

Embolization

NA

McNichols et al.[4]

1981

52/male

10

Malabsorption

Diagnostic only

NA

Heymann and Vieta[25]

1918

64/male

8

GI bleeding

Complex procedure

3 weeks

Tolia and Whitmore[26]

1915

-/male

16

NA

NA

5

Lawson et al. [11]

1966

69/female

0

GI bleeding

Classical Whipple

NA
Table 2

Summary of cases of neuroendocrine tumor with renal cell cancer


At present, he has duodenal metastasis from RCC measuring 2.9 cm × 2.4 cm and pancreatic NET measuring 8.4 cm × 6.2 cm × 6.2 cm.


Conclusion

To highlight, solitary metastatic RCC to the duodenum is extremely rare. Awareness of this entity and aggressive workup of GI symptoms in patients postnephrectomy for RCC are very important. In these patients with symptoms of GI bleeding, fatigue, anemia, and early satiety or obstruction, all should undergo complete endoscopic evaluation and biopsy, as well as radiologic investigation to evaluate for the presence and the extent of metastatic disease. Any patient with solitary metastatic RCC to the duodenum should be considered a candidate for complete surgical excision if medically and technically feasible, both for palliation of symptoms, and because it gives the opportunity for better survival.

Based on this case report and the literature, we believe that the practicing physicians should be aware of the unique feature of RCC for risk of a simultaneous separate primary malignancy and approach patients’ new symptoms with diligence. The presence of any clinical or radiological conflicting lesion should be further evaluated.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.


Conflict of Interest

There are no conflicts of interest.

  • References

Author

Year

Age/sex

Site of NET origin

Treatment

Survival/follow up in months

NA – Not available; NET – Neuroendocrine tumor

Baghmar et al.

Present article

84/male

Pancreas

Supportive care

12

Edwards et al.[40]

2017

71/female

Ileocecal valve

Right hemicolectomy, radical nephrectomy

NA

Athiyappan et al. [41]

2015

56/male

Rectum

Radical nephrectomy and chemotherapy

3

Sun et al.[42]

2013

37/male

Horseshoe kidney

Surgical resection

9

Morelli et al.[43]

2007

27/male

Gallbladder

Cholecystectomy with partial hepatectomy and a polar renal resection

NA

Dafashy et al.[2]

2016

66/male

Ileum

Radical nephrectomy, ileal resection

20

Addeo et al.[44]

2013

27/female

Pancreas

Whipple procedure and wedge resections of the right renal neoplasm

6
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  3. Müller SA, Pahernik S, Hinz U, Martin DJ, Wente MN, Hackert T. et al. Renal tumors and second primary pancreatic tumors: a relationship with clinical impact?. Patient Saf Surg 2012; 6: 18
  4. McNichols DW, Segura JW, DeWeerd JH. Renal cell carcinoma: long-term survival and late recurrence. J Urol 1981; 126: 17-23
  5. Ritchie AW, Chisholm GD. The natural history of renal carcinoma. Semin Oncol 1983; 10: 390-400
  6. Villarreal-Garza C, Perez-Alvarez SI, Gonzalez-Espinoza IR, Leon-Rodriguez E. Unusual Metastases in Renal Cell Carcinoma: A Single Institution Experience and Review of Literature. World J Oncol 2010; 1: 149-57
  7. Dodge OG. The Spread of Tumours in the Human Body. Br J Cancer 1974; 29: 343-4
  8. Geramizadeh B, Mostaghni A, Ranjbar Z, Moradian F, Heidari M, Khosravi MB. et al. An Unusual Case of Metastatatic Renal Cell Carcinoma Presenting as Melena and Duodenal Ulcer, 16 Years After Nephrectomy; a Case Report and Review of the Literature. Iran J Med Sci 2015; 40: 175-80
  9. Jeming Hu, Sheng-Tang Wu, Yu-Chieh Lin. Metachronous Duodenal Metastasis from Renal Cell Carcinoma. J Med Sci 2014; 34: 186-9
  10. Zhao H, Han K, Li J, Liang P, Zuo G, Zhang Y. et al. A case of wedge resection of duodenum for massive gastrointestinal bleeding due to duodenal metastasis by renal cell carcinoma. World J Surg Oncol 2012; 10: 199
  11. Yang J, Zhang YB, Liu ZJ, Zhu YF, Shen LG. Surgical treatment of renal cell carcinoma metastasized to the duodenum. Chin Med J (Engl) 2012; 125: 3198-200
  12. Rustagi T, Rangasamy P, Versland M. Duodenal Bleeding from Metastatic Renal Cell Carcinoma. Case Rep Gastroenterol 2011; 5: 249-57
  13. Vashi PG, Abboud E, Gupta D. Renal Cell Carcinoma with Unusual Metastasis to the Small Intestine Manifesting as Extensive Polyposis: Successful Management with Intraoperative Therapeutic Endoscopy. Case Rep Gastroenterol 2011; 5: 471-8
  14. Adamo R, Greaney PJ, Witkiewicz A, Kennedy EP, Yeo CJ. Renal Cell Carcinoma Metastatic to the Duodenum: Treatment by Classic Pancreaticoduodenectomy and Review of the Literature. J Gastrointest Surg 2008; 12: 1465-8
  15. Sadler GJ, Anderson MR, Moss MS, Wilson PG. Metastases from renal cell carcinoma presenting as gastrointestinal bleeding: two case reports and a review of the literature. BMC Gastroenterol 2007; 7: 4
  16. Pavlakis GM, Sakorafas GH, Anagnostopoulos GK. Intestinal metastases from renal cell carcinoma: a rare cause of intestinal obstruction and bleeding. Mt Sinai J Med N Y 2004; 71: 127-30
  17. Chang WT, Chai CY, Lee KT. Unusual upper gastrointestinal bleeding due to late metastasis from renal cell carcinoma: a case report. Kaohsiung J Med Sci 2004; 20: 137-41
  18. Loualidi A, Spooren PF, Grubben MJ, Blomjous CE, Goey SH. Duodenal metastasis: An uncommon cause of occult small intestinal bleeding. Neth J Med 2004; 62: 201-5
  19. Nabi G, Gandhi G, Dogra PN. Diagnosis and management of duodenal obstruction due to renal cell carcinoma. Trop Gastroenterol Off J Dig Dis Found 2001; 22: 47-9
  20. Le Borgne J, Partensky C, Glemain P, Dupas B, de Kerviller B. Pancreaticoduodenectomy for metastatic ampullary and pancreatic tumors. Hepatogastroenterology 2000; 47: 540-4
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  22. Toh SK, Hale JE. Late presentation of a solitary metastasis of renal cell carcinoma as an obstructive duodenal mass. Postgrad Med J 1996; 72: 178-9
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Address for correspondence

Dr. Saphalta Baghmar
Department of Medical Oncology, Institute of Liver and Biliary Sciences
Vasant Kunj, New Delhi - 110 070
India   

Publication History

Article published online:
24 May 2021

© 2019. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

  • References

  1. Thompson LD, Heffess CS. Renal cell carcinoma to the pancreas in surgical pathology material. Cancer 2000; 89: 1076-88
  2. Dafashy TJ, Ghaffary CK, Keyes KT, Sonstein J. Synchronous Renal Cell Carcinoma and Gastrointestinal Malignancies. Case Rep Urol 2016; 2016: e7329463
  3. Müller SA, Pahernik S, Hinz U, Martin DJ, Wente MN, Hackert T. et al. Renal tumors and second primary pancreatic tumors: a relationship with clinical impact?. Patient Saf Surg 2012; 6: 18
  4. McNichols DW, Segura JW, DeWeerd JH. Renal cell carcinoma: long-term survival and late recurrence. J Urol 1981; 126: 17-23
  5. Ritchie AW, Chisholm GD. The natural history of renal carcinoma. Semin Oncol 1983; 10: 390-400
  6. Villarreal-Garza C, Perez-Alvarez SI, Gonzalez-Espinoza IR, Leon-Rodriguez E. Unusual Metastases in Renal Cell Carcinoma: A Single Institution Experience and Review of Literature. World J Oncol 2010; 1: 149-57
  7. Dodge OG. The Spread of Tumours in the Human Body. Br J Cancer 1974; 29: 343-4
  8. Geramizadeh B, Mostaghni A, Ranjbar Z, Moradian F, Heidari M, Khosravi MB. et al. An Unusual Case of Metastatatic Renal Cell Carcinoma Presenting as Melena and Duodenal Ulcer, 16 Years After Nephrectomy; a Case Report and Review of the Literature. Iran J Med Sci 2015; 40: 175-80
  9. Jeming Hu, Sheng-Tang Wu, Yu-Chieh Lin. Metachronous Duodenal Metastasis from Renal Cell Carcinoma. J Med Sci 2014; 34: 186-9
  10. Zhao H, Han K, Li J, Liang P, Zuo G, Zhang Y. et al. A case of wedge resection of duodenum for massive gastrointestinal bleeding due to duodenal metastasis by renal cell carcinoma. World J Surg Oncol 2012; 10: 199
  11. Yang J, Zhang YB, Liu ZJ, Zhu YF, Shen LG. Surgical treatment of renal cell carcinoma metastasized to the duodenum. Chin Med J (Engl) 2012; 125: 3198-200
  12. Rustagi T, Rangasamy P, Versland M. Duodenal Bleeding from Metastatic Renal Cell Carcinoma. Case Rep Gastroenterol 2011; 5: 249-57
  13. Vashi PG, Abboud E, Gupta D. Renal Cell Carcinoma with Unusual Metastasis to the Small Intestine Manifesting as Extensive Polyposis: Successful Management with Intraoperative Therapeutic Endoscopy. Case Rep Gastroenterol 2011; 5: 471-8
  14. Adamo R, Greaney PJ, Witkiewicz A, Kennedy EP, Yeo CJ. Renal Cell Carcinoma Metastatic to the Duodenum: Treatment by Classic Pancreaticoduodenectomy and Review of the Literature. J Gastrointest Surg 2008; 12: 1465-8
  15. Sadler GJ, Anderson MR, Moss MS, Wilson PG. Metastases from renal cell carcinoma presenting as gastrointestinal bleeding: two case reports and a review of the literature. BMC Gastroenterol 2007; 7: 4
  16. Pavlakis GM, Sakorafas GH, Anagnostopoulos GK. Intestinal metastases from renal cell carcinoma: a rare cause of intestinal obstruction and bleeding. Mt Sinai J Med N Y 2004; 71: 127-30
  17. Chang WT, Chai CY, Lee KT. Unusual upper gastrointestinal bleeding due to late metastasis from renal cell carcinoma: a case report. Kaohsiung J Med Sci 2004; 20: 137-41
  18. Loualidi A, Spooren PF, Grubben MJ, Blomjous CE, Goey SH. Duodenal metastasis: An uncommon cause of occult small intestinal bleeding. Neth J Med 2004; 62: 201-5
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