SURGERY Renal Cell Carcinoma Metastasis to the Pancreas: the Aggressive Nature of Synchronous Presentation—Case Report and Comprehensive Review of the Literature Joshua Schammel 1 & Christine Schammel 2 & David Schammel 2 & Steven D. Trocha 3 Accepted: 25 June 2020 # Springer Nature Switzerland AG 2020 Abstract Typically presenting as local disease, renal cell carcinoma (RCC) is metastatic in 16% of cases, typically spreading to the lungs, brain, bones, or liver. Less common are pancreatic metastases from RCC with isolated metastasis comprising 60% of cases. We report RCC with a synchronous solitary pancreatic lesion resected leaving the patient disease free. At 3.5 years, the patient presented with recurrent multiple pancreatic lesions, suggesting an aggressive biology and an altered treatment paradigm. Keywords Renal cell carcinoma . Synchronous metastasis to pancreas . Solitary lesion . Aggressive biology Introduction Renal cell carcinoma (RCC) is the sixth most common malig- nancy in the USA and is expected to contribute to over 15,000 deaths (2019) [1]. Typically presenting as local disease, RCC has been shown to be metastatic to the lungs, brain, bones, or liver in < 16% of cases [2, 3]. Less commonly (2–5%), RCC can metastasize to the pancreas [2] most often as solitary le- sions [3–5]; however, multiple lesions have been reported (39%) [6]. Overall, RCC metastases account for only 2% of all malignant pancreatic tumors [1] and are considered the principal source of pancreatic metastasis overall [2]. Case Presentation We report a case of a solitary pancreatic RCC metastasis in a 58-year-old male. On initial presentation at an outside institution, the patient reported flank pain and hematuria. An MRI revealed a 1.8-cm mass in his right kidney (Fig. 1). A right nephrectomy was completed with a Furhman/ISUP nu- clear grade 2 RCC extending into the inferior vena cava (stage T3a; Fig. 2). As RCC typically follows an indolent clinical course [6], observation by quarterly CT imaging of the abdo- men and pelvis was indicated. The 1-month follow-up CT did not identify any recurrent local disease; however, a 1.7-cm splenic aneurysm and a 1.8- cm enhancing mass of the pancreatic tail with mild ductal dilation were identified (Figs. 3 and 4). The patient was re- ferred. Postoperative imaging indicated an enhancement pat- tern of the pancreatic lesion consistent with a neuroendocrine tumor or RCC metastasis. Review of preoperative films noted the presence of the aneurysm and pancreatic lesion on MRI; however, both were deemed inconspicuous due to respiratory motion. Since metastatic RCC typically presents in the lungs, brain, bones, or liver, the differential for the pancreatic lesion was a neuroendocrine tumor; resection was scheduled. A ro- botic distal pancreatectomy and splenectomy was completed without complications. The pancreatic lesion was identified as a 2.3-cm RCC metastasis with negative margins; there was a benign thrombus within the splenic artery aneurysm. The pa- tient’s postoperative course included a pancreatic leak identi- fied on postoperative day three. His drain was removed on postoperative day five. The 3-month follow-up CT indicated no evidence of new or recurrent disease. Observation by quar- terly imaging was warranted and the patient was deemed clin- ically disease free. However, the 3.5-year CT revealed This article is part of the Topical Collection on Surgery * Steven D. Trocha [email protected]1 University of South Carolina School of Medicine Greenville, Greenville, SC, USA 2 Pathology Associates, Greenville, SC, USA 3 Department of Surgery, Prisma Health Upstate, 890 W Faris Rd Suite 320, Greenville, SC 29605, USA https://doi.org/10.1007/s42399-020-00386-x / Published online: 11 July 2020 SN Comprehensive Clinical Medicine (2020) 2:1272–1281
Transcript
SURGERY
Renal Cell Carcinoma Metastasis to the Pancreas: the AggressiveNature of Synchronous Presentation—Case Reportand Comprehensive Review of the Literature
Joshua Schammel1 & Christine Schammel2 & David Schammel2 & Steven D. Trocha3
Accepted: 25 June 2020# Springer Nature Switzerland AG 2020
AbstractTypically presenting as local disease, renal cell carcinoma (RCC) is metastatic in 16% of cases, typically spreading to the lungs,brain, bones, or liver. Less common are pancreatic metastases from RCC with isolated metastasis comprising 60% of cases. Wereport RCC with a synchronous solitary pancreatic lesion resected leaving the patient disease free. At 3.5 years, the patientpresented with recurrent multiple pancreatic lesions, suggesting an aggressive biology and an altered treatment paradigm.
Renal cell carcinoma (RCC) is the sixth most common malig-nancy in the USA and is expected to contribute to over 15,000deaths (2019) [1]. Typically presenting as local disease, RCChas been shown to be metastatic to the lungs, brain, bones, orliver in < 16% of cases [2, 3]. Less commonly (2–5%), RCCcan metastasize to the pancreas [2] most often as solitary le-sions [3–5]; however, multiple lesions have been reported(39%) [6]. Overall, RCC metastases account for only 2% ofall malignant pancreatic tumors [1] and are considered theprincipal source of pancreatic metastasis overall [2].
Case Presentation
We report a case of a solitary pancreatic RCC metastasis in a58-year-old male. On initial presentation at an outside
institution, the patient reported flank pain and hematuria. AnMRI revealed a 1.8-cm mass in his right kidney (Fig. 1). Aright nephrectomy was completed with a Furhman/ISUP nu-clear grade 2 RCC extending into the inferior vena cava (stageT3a; Fig. 2). As RCC typically follows an indolent clinicalcourse [6], observation by quarterly CT imaging of the abdo-men and pelvis was indicated.
The 1-month follow-up CT did not identify any recurrentlocal disease; however, a 1.7-cm splenic aneurysm and a 1.8-cm enhancing mass of the pancreatic tail with mild ductaldilation were identified (Figs. 3 and 4). The patient was re-ferred. Postoperative imaging indicated an enhancement pat-tern of the pancreatic lesion consistent with a neuroendocrinetumor or RCC metastasis. Review of preoperative films notedthe presence of the aneurysm and pancreatic lesion on MRI;however, both were deemed inconspicuous due to respiratorymotion. Since metastatic RCC typically presents in the lungs,brain, bones, or liver, the differential for the pancreatic lesionwas a neuroendocrine tumor; resection was scheduled. A ro-botic distal pancreatectomy and splenectomy was completedwithout complications. The pancreatic lesion was identified asa 2.3-cm RCC metastasis with negative margins; there was abenign thrombus within the splenic artery aneurysm. The pa-tient’s postoperative course included a pancreatic leak identi-fied on postoperative day three. His drain was removed onpostoperative day five. The 3-month follow-up CT indicatedno evidence of new or recurrent disease. Observation by quar-terly imaging was warranted and the patient was deemed clin-ically disease free. However, the 3.5-year CT revealed
This article is part of the Topical Collection on Surgery
additional pancreatic lesions (4; 3 in the head and 1 in thebody). Further imaging revealed recurrence limited to the pan-creas and the patient was referred for adjuvant/palliative sys-temic therapy and possible future total pancreatectomy.
Conclusions
An isolated metastasis of RCC to the pancreas remains a rare,well-documented event, and, as such, a comprehensive reviewof the literature was completed using “renal cell carcinomametastases to the pancreas” as the primary search term andutilizing the skill set of institutional librarians. Overall, 137cases of isolated RCC metastases to the pancreas have beenreported in the literature (Table 1). In addition to the solitarylesions, 113 cases of multiple RCC metastases to the pancreas
have also been documented (Table 2). A summary of bothsolitary and multiple RCC metastases to the pancreas de-scribed in the literature with a comparison to two recent re-views evaluating surgical management of these lesions [97,98] is outlined in Table 3.
While it has been noted that solitary lesions are the mostfrequent manifestation of RCC metastases to the pancreas[3–5], the review of the cases reported in the literature re-vealed that 55% were solitary and 45% multiple at presenta-tion. A comparison of solitary and multiple lesions revealedthat pancreatic metastases are slightly more frequent in men(56% for solitary and 51% for multiple) in the 6th decade of
Fig. 3 Abdominal CT. The image is highlighting the incidental splenicartery aneurysm
Fig. 4 Abdominal MRI. The image is highlighting the solitary pancreaticmetastasis
Fig. 2 Abdominal MRI. The image is highlighting the inferior vena cavathrombus. Thrombus in the presence of cancer is indicative of advanceddisease
Fig. 1 Abdominal MRI. Image is highlighting the right-sided renal cellcarcinoma primary
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Table 1 Case reports of solitary RCC metastases to the pancreas
Author Year Cases Age Gender Location Procedure Presentation (yrs)*Jenssen 1952 1 64 M Head Whipple 14
Lawson 1966 1 69 F Ampulla Whipple 0
Marpauand 1971 1 50 M Head Whipple 0
Guttman 1972 1 66 M Head Total Pancreatectomy 13
Hermanutz 1977 1 60 M Head Whipple 14
Saxon 1980 1 43 F Head Whipple 0.5
Yazaki 1981 1 76 M Body Whipple 0
Whittington 1982 1 62 M Tail Radiation 17
Kishimoto 1985 1 72 M Tail Total Pancreatectomy 0
Audisio 1985 1 66 F Head Whipple 20
Carini 1988 1 66 F Head Whipple 12
Sharma 1988 1 60 F Tail Distal Pancreatectomy/Splenectomy 0
Gohji 1989 1 59 M Tail Distal Pancreatectomy 9
Robertson 1990 1 70 M Head Whipple 12
Derias 1993 1 82 M Head Radiotherapy 22
Nakeeb 1995 1 52 M Whipple 7.7
Carson 1995 1 75 F Head
Dousset 1995 1 61 F Head Whipple 6
Hirota 1996 1 81 F Body Distal Pancreatectomy 8
Barras 1996 1 53 M TailDistal Pancreatectomy/Splenectomy/Partial
Gastrectomy/Left hemicolectomy10
Leslie 1996 1 78 F Head Pylorus Preserving Whipple 10
Kanemura 1997 1 57 M Head Whipple 0
Hashimoto 1998 1 58 M Head Partial Resection 4
Jingu 1998 1 47 M Head Pylorus Preserving Whipple 3
Gupta 1998 1 63 M Head Radiotherapy 6
Sahin 1998 1 61 F Head Whipple 18
Tuech 1999 5
53
6564
49
59
F
MM
F
F
Head (5) Whipple (5)
7.1
104.3
4.1
7
Eriguchi 1999 1 71 M Body Distal Pancreatectomy/Splenectomy 8
Kassabian 2000 1 45 M Head Pylorus Preserving Whipple 12
Le Borgne 2000 3
48
7252
M
FF
Duoden.
Duoden.Head
Whipple
WhipplePylorus Preserving Whipple
13
713
Faure 2001 5
65
59
5364
67
M
F
FM
F
Whipple (5)
10
7
7.14.3
10
Sohn† 2001 6
Distal PancreatectomyWhipple
Whipple
Distal PancreatectomyPylorus Preserving Whipple
Pylorus Preserving Whipple
06
7
78
11
Yachida 2002 266
81
M
F
Body
Head
Distal Pancreatectomy
Pylorus Preserving Whipple
17
24
Giulini 2003 1 73 F Isthmus Whipple 24
Pecchi 2003 1 67 M Head Whipple 11
Hernandez 2003 1 64 M Tail Distal Pancreatectomy
Nakaghori 2003 1 71 M Head Partial Resection
Zacharoulis 2003 257
66
M
MHead (2)
Whipple
Pylorus preserving Whipple
3
0
Uemura 2003 1 70 M Body Pancreatectomy 17
Law 2003 7
44
67
5869
74
7159
F
M
FF
F
FF
Distal Pancreatectomy
Whipple
Distal PancreatectomyWhipple
Distal Pancreatectomy
WhippleDistal Pancreatectomy
0
9
59
8
30.7
Kijvikai 2004 1 66 F Tail Distal Pancreatectomy 12
Norton 2004 1 62 M Body/Tail Distal Pancreatectomy/Splenectomy 22
Shola 2005 1 63 M Head Whipple 0
Wente 2005 8
60
64
66
M
F
F
Whipple
Partial Resection
Partial Resection
18.4
5.3
6.3
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Table 1 (continued)
66
7652
60
58
F
FM
F
M
Partial Resection and enucleation
Pylorus preserving WhippleWhipple/R hemicolectomy
Segment Resection
Segment Resection with Nephrectomy
19.8
106.8
12.8
0
DeWitt 2005 8
6073
62
7970
62
6670
MF
M
FM
F
MM
HeadBody
Body
TailHead
Head
TailBody
Surgical ResectionCytomorphology (8)
2323
1.3
812
10
1020
Ninan 2005 1 63 M Head Whipple 0
Sotiropoulos 2005 1 54 F Tail Distal Pancreatectomy/Nephrectomy 2
David 2006 1 51 M Head Whipple 16
Sellner 2006 1 55 M Body Distal Pancreatectomy 1
Shrikhande 2006 1 62 M Body/Tail Distal Pancreatectomy/Splenectomy 1
Karimi 2007 27056
FF
Tail (2) Distal Pancreatectomy/Splenectomy (2)5
15
Kato 2007 1 59 F Body Distal Pancreatectomy/Splenectomy 13
Akatsu 2007 35252
80
MM
F
Body (3) Distal Pancreatectomy/Splenectomy (3)5.30
Thadani 2011 1 67 F Tail Distal Pancreatectomy/Splenectomy 13
Bhalla 2012 1 70 M Head Whipple 6
Hata# 2013 1 50 F Tail Whipple; repeated pancreatectomy 10
Ingle 2017 1 58 M Head Sunitinib Maleate 10
Cheong# 2018 1 62 M Ampulla Whipple
Ayari 2019 1 65 F Head Sunitinib 2
Schammel 2019 1 58 M Tail Distal Pancreatectomy/Splenectomy 0
*Time of presentation of the pancreatic metastasis after the initial diagnosis of RCC. Zero indicates that the metastasis was identified synchronously with the RCCdiagnosis; gray boxes indicate that the report did not have the information recorded;
NR indicates that the location for one of the metastases in the case series was not reported; cases correspond to references 3–5, 7–71, respectively; †these studiesreported both single and multiple metastases to the pancreas, and thus, the studies are noted in both tables but the citation is with the references corresponding toTable 1 only
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Table 2 Case reports and series of multiple RCC metastases to the pancreas
Author Year Case Age Gender Location #Foci Procedure Presentation (yrs)*Weerdenburg 1984 1 58 F Diffuse Mult. Total Pancreatectomy 13
Skaarup 1984 1 55 M Head/Tail 2 Total Pancreatectomy 15
Rumancik 1984 1 63 F Diffuse Mult. 17
Gohki 1990 1 52 M Tail 2 Distal Pancreatectomy6.8
2.5
Stankard 1992 1 56 F Head/Tail 2 Total Pancreatectomy 4
Fabre 1995 26969
FF
HeadBody/Tail
33
Pancreatectomy (2)0
3.3
Nakeeb 1995 1 52 M 7.5
Robbins 1996 1 57 F Head/Tail 2 Distal Pancreatectomy/Whipple 7
Z’graggen 1998 2Diffuse
Diffuse
Mult.
Mult.Total Pancreatectomy (2)
10
22
Augustin 1999 1 60 M Body/Tail 2 Distal Pancreatectomy/Splenectomy 8
Sugiyama 1999 1 53 F Diffuse Mult. Whipple 3
Kassabian 2000 1 52 M Diffuse Mult. Total Pancreatectomy 4
Le Borgne 2000 267
69
M
F
Head/Tail
Diffuse
4
3
Total Pancreatectomy
Pylorus Preserving Whipple
2
0
Ghavamian 2000 6
53
46
7870
51
73
M
M
MM
F
F
Distal Pancreatectomy
Distal Pancreatectomy
Total Pancreatectomy/SplenectomyMegesterol Acetate
ERCP
Distal Pancreatectomy
13.5
2.8
189.7
18.6
24.6
Faure 2001 34950
55
FF
F
25
3
Total PancreatectomyTotal Pancreatectomy
Total Pancreatectomy
4.26.8
1
Hashimoto 2001 1 57 MDuodenal Bulb
Body2 Pylorus-Preserving Whipple 11
Sohn† 2001 2Diffuse
Diffuse
Mult.
Mult.
Total Pancreatectomy
Pylorus Preserving Total Pancreatectomy
9
13
Yachida 2002 3
60
58
47
M
M
F
Diffuse
Head/Tail
Diffuse
3
2
7
Total Pancreatectomy (3)
3
12
5
Chou 2002 1 73 M Diffuse 4 Whipple 9
Bechade 2002 282
71
M
M
Head/Isthmus
Head/Body
2
6
Whipple
No Treatment
16
14
Hiotis 2002 10
Whipple (3)
Total Pancreatectomy (1)
Distal Pancreatectomy (6)
Eloubeidi 2002 1 69 M Diffuse 3 Immunotherapy 13
Zacharoulis 2003 1 55 F Head/Body Mult. Declined treatment 2
Sperti 2003 270
53
M
F
Mult.
2
Total Pancreatectomy
Middle Pancreatectomy/Enucleation
1
19
Elias 2003 260
60
M
M
Head
Body/Tail
2
2
Duodenopancreatectomy
Enucleation
2
0
Law 2003 4
6169
44
59
MF
F
M
42
2
4
Total PancreatectomyWhipple
Whipple
Total Pancreatectomy
512
0.5
14
Moussa 2004 6
5764
61
6563
67
MM
M
FF
F
WhippleTotal Pancreatectomy
Whipple
ImmunotherapyIsthmectomy w immunotherapy
Whipple w enucleation
12.34.3
6.2
6.27.9
9.8
Ascenti 2004 1 71 M Body 2 0
Kobayashi 2004 1 53 F Diffuse 5 Total Pancreatectomy 9
Wente 2005 4
55
59
6160
F
M
MF
Mult.
Mult.
3Mult.
Total Pancreatectomy/Splenectomy
Total Pancreatectomy/Splenectomy
Partial Resection/SplenectomyTotal Pancreatectomy
21.5
6
4.312.9
DeWitt 2005 262
67
M
M
Head/Body/Tail
Head
5
2
Cytomorphology
Surgical Resection
0.4
9.8
Sellner 2006 261
60
F
F
Head/Body
Diffuse
2
Mult.
Distal Pancreatectomy
Total Pancreatectomy
14
8
Karimi 2007 1 63 F Tail 2 Distal Pancreatectomy/Splenectomy 15
Akatsu 2007 1 62 M Head 2 Pylorus Preserving Whipple 8.7
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life (mean 63.5 solitary; mean 62.2 multiple), matching theprofile of our patient (male 58 years old).
The indolent nature of RCC is demonstrated in the factthat pancreatic metastases present 5–15 years post-primarydiagnosis in 72% of solitary and 80% of multiple lesions(average 9 years; Lee 9 years, Di Franco 7 years; Table 3).More rarely, RCC metastases to the pancreas were diag-nosed synchronously or within a year of the primary diag-nosis (14% for solitary; 7% for multiple), suggesting adifferent biology. While the solitary 1.8-cm RCC lesionreported here was diagnosed within a month of the initialdiagnosis, it was present on preoperative imaging for theprimary renal malignancy. Considering the typically local-ized nature of RCC with the low probability of a pancreaticmetastasis, upon discovery, a neuroendocrine primary wasconsidered and resection completed. However, the location
of the primary RCC was not considered in assessing thelesion. When the primary tumor involves the inferior venacava, venous access of the tumor would suggest hematog-enous spread; [99] however, risk stratification does notconsider location. Thus, when other, more common, sitesof RCC metastasis are absent, management of solitary pan-creatic metastases is unclear [99].
As surgical resection is preferred for solitary lesions, adistal pancreatectomy was completed [3–5]. As the lesion inthe case presented here was small, 2.3 cm (solitary lesionmean 2 cm) [6], postoperative observation by imaging waswarranted [100, 101]. No signs of recurrent disease were de-tected by CT imaging until the 3.5-year scan revealed addi-tional pancreatic lesions, suggesting that observation [100]through CTmay be insufficient for a synchronously identifiedprimary RCC/solitary pancreatic metastasis. In fact, it has
Macrí 2014 1 Body/Tail 2 Distal Pancreatectomy and Splenectomy 5
*Time of presentation of the pancreatic metastasis after the initial diagnosis of RCC; patients with multiple lesions may have more than one date of presentation.Zero indicates that the metastasis was identified synchronously with the RCC diagnosis; gray boxes indicate that the report did not have the information recorded;†these studies reported both single and multiple metastases to the pancreas, and thus, the studies are noted in both tables but the citation is with the referencescorresponding to Table 1 only; “Unc Proc” refers to the uncinate process; studies represented in this table correlate to references 3–5, 22, 35–37, 39, 44, 49, 50, 54,56, 61, 65, 72–96, respectively
1277SN Compr. Clin. Med. (2020) 2:1272–1281
been recommended that, for RCC metastases to the pancreas,surgical resection is the most favorable treatment [97, 98].
While outcomes for patients diagnosed with synchronousRCC/pancreatic metastases are scant, the simultaneous natureof these lesions may suggest aggressive biology [100], neces-sitating an alternate treatment paradigm. CT may not be suf-ficient to identify smaller metastases [99, 101];MRI should beconsidered the optimal modality for vigilant monitoring inpatients with synchronous lesions. Identification of smallerlesions (< 3 cm) coupled with the advent of tyrosine kinaseinhibitor-targeted therapy for RCC has been noted to portenda more favorable outcome [2, 102], particularly in patientswith multiple pancreatic lesions. Thus, identification of earlypancreatic RCC lesions and initiation of systemic therapy hasthe potential to optimally control disease, avoid total pancre-atectomy, and preserve pancreatic exocrine and endocrinefunction for a better quality of life for these patients.
Overall, primary location and synchronous RCC/pancreatic lesion identification may warrant an amended treat-ment regimen, including MRI to identify additional/subsequent lesions earlier. While small lesions may be surgi-cally resected and/or targeted systemic therapies may be uti-lized to preserve pancreatic function and possibly avoid totalpancreatectomy, resection of RCC metastases to the pancreasshould remain the primary consideration to optimize patientquality of life outcomes.
Authors’ Contributions All authors have read and approved this manu-script. Joshua Schammel completed the primary data collection/literaturereview and wrote the initial manuscript. Christine Schammel was theprimary editor. David Schammel was the pathology collaborator andprovided pictures; he also served as an editor. Steven Trocha was theprimary care giver to the patient and provided all the clinical details,follow-up, and edited the manuscript.
Compliance with Ethical Standards
Conflict of Interest All authors report no conflict of interest. IRB ap-proval was obtained prior to the writing of the manuscript. The IRBdeemed this project “non-human research” as it was a case report andthe patient signed a universal consent.
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