- Email: [email protected]
Metachronous colonic metastasis from pancreatic cancer presenting as mechanical obstruction: a case report
Metachronous colonic metastasis from pancreatic cancer presenting as mechanical obstruction: A case report Woogyeong Kim, Yedaun Lee PII: DOI: Reference:
S0899-7071(15)00012-1 doi: 10.1016/j.clinimag.2015.01.010 JCT 7768
To appear in:
Journal of Clinical Imaging
Received date: Revised date: Accepted date:
27 October 2014 30 December 2014 13 January 2015
Please cite this article as: Kim Woogyeong, Lee Yedaun, Metachronous colonic metastasis from pancreatic cancer presenting as mechanical obstruction: A case report, Journal of Clinical Imaging (2015), doi: 10.1016/j.clinimag.2015.01.010
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Metachronous colonic metastasis from pancreatic cancer presenting as mechanical
T
obstruction: A case report
RI P
Woogyeong Kim, MD1, Yedaun Lee, MD² 1
1435, Jwa-dong, Haeundae-gu, Busan 612-896, Korea 2
SC
Department of Pathology, Haeundae Paik Hospital, Inje University College of Medicine,
MA NU
Department of Radiology, Haeundae Paik Hospital, Inje University College of Medicine,
1435, Jwa-dong, Haeundae-gu, Busan 612-896, Korea Corresponding Author:
ED
Yedaun Lee, MD.
Department of Radiology, Haeundae Paik Hospital, Inje University College of Medicine, 875
PT
(Jwa-dong) Haeundae-ro, Haeundae-gu, Busan 612-030, Korea
CE
Tel. : (82-51) 797-0356, Fax. : (82-51) 797-0379
AC
E-mail: [email protected]
Type of Manuscript: Case report
ACCEPTED MANUSCRIPT Abstract Colonic metastasis from pancreatic cancer is extremely rare. We present the case of a 64-year-old
RI P
T
man who developed colonic metastasis of pancreatic cancer 2 years after distal pancreatectomy. CT scan showed cecal mass with small bowel dilatation. The level of carbohydrate antigen 19-9 (CA19-9) was elevated to 5133.0 U/mL. Under the diagnosis of colon cancer, right hemicolectomy was
SC
performed. Pathologic diagnosis was a metastasis from the primary pancreatic cancer. Based on the
MA NU
present case, colonic metastasis should be included in the differential diagnosis of colonic mass with
AC
CE
PT
ED
elevated CA 19-9 and history of curative resection of primary pancreatic cancer.
ACCEPTED MANUSCRIPT Introduction Pancreatic cancer is the fourth most common cause of cancer-related deaths in United States (1). The
RI P
T
high mortality rate of pancreatic cancer is associated with the delayed diagnosis at advanced stage and no effective treatment. Common sites of metastasis include liver, lymph nodes, lung and peritoneum (2). Metastasis to colon is very rare. To the best of our knowledge, only three cases of
SC
colonic metastasis from the pancreatic cancer have been reported in the English literatures (3-5).
MA NU
Here we report a case of a 64 year-old man with metachronous colonic metastasis from pancreatic cancer presenting as colonic obstruction.
Case Report
A 64-year old man underwent distal pancreatectomy with splenectomy in February 2012 for
ED
pancreatic tail cancer. The pathologic diagnosis was a moderately differentiated adenocarcinoma with
PT
only perineural invasions without lymphovascular tumor invasion or metastatic lymph nodes. The stage of pancreatic cancer was IIA, pT3N0M0 according to American Joint Committee on Cancer
CE
staging system 7th edition (6). The carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) levels were elevated to 3341 U/mL (upper limit of normal range < 37 U/mL) and 74.3 ng/mL
AC
(upper limit of normal range < 5 ng/mL) before the pancreatectomy. After the operation, the CA19-9 and CEA level were decreased to 6.9 U/mL and 4.8 ng/mL. He had regular follow-ups every 6 months with a protocol including computed tomography (CT) and a biological tumor marker CA19-9 and there was no evidence of recurrence during the first fifteen months. However, from May 2013, serum CA 19-9 and CEA level began to increase (334.8 U/mL and 18.2 ng/mL) and thorough CT evaluation was carried out to reveal any recurrent mass but none was found. In January 2014, he was admitted due to clinical symptoms of diffuse abdominal pain for two weeks. On physical examination, the abdomen was distended and bowel sound was tympanic. The level of CA19-9 was elevated to 5133.0 U/mL and CEA level was 54.5 ng/mL. Abdominal CT scan showed enhancing cecal mass which caused narrowing of ileocecal valve and it was infiltrating into the pericolic fat (Fig 1). And also, diffuse distension of small bowel loops was
ACCEPTED MANUSCRIPT observed. There was no abnormal lesion in the liver and remnant pancreas. The patient underwent a right-hemicolectomy with lymph node dissection under the clinical impression of colon cancer.
T
Intraoperative findings revealed a solid mass in the cecum with small bowel obstruction. The mass
RI P
invaded adjacent right psoas muscle.
Intraoperative frozen section was performed to evaluate the nature of the obstruction and it was
SC
confirmed as adenocarcinoma. Subsequent right hemicolectomy with lymphadenectomy was done. Macroscopically, the specimen revealed a 5.0cm length of wall thickening with mucosal ulceration in
MA NU
cecum but without definite mucosal adenomatous change. Histopathological examination showed glandular cancer nests with stromal desmoplasia diffusely infiltrating pericecal adipose tissue, muscularis propria and extending into the mucosal layer. Multifocal areas of remaining superficial normal colonic mucosa were observed. The neoplastic cancer nests consist of small to medium sized
ED
tubular glands lined by epithelial cells with moderate pleomorphism (Fig 2A). Multiple lymphatic invasions were present and 2 out of 39 dissected regional lymph nodes had metastatic
PT
adenocarcinomas.
CE
Immunohistochemical stains revealed diffuse strong expression of cytokeratin 7 and weak expression of cytokeratin 19 in adenocarcinoma (Fig 2B-C). Cytokeratin 20 was negative in cancer
AC
nests and was only expressed in the remnant normal colonic mucosa (Fig 2D). Focal positivity of carcinoembryonic antigen (CEA) of the tumor component was also present. Histopathological patterns of the previous pancreatic ductal adenocarcinoma specimen were reviewed and compared. The two tumors had almost identical features. Therefore, based on the clinicopathologic findings and the results of immunohistochemical stains, the final diagnosis of the right hemicolectomy specimen was moderately differentiated metastatic adenocarcinoma primarily originating in pancreas. Postoperative course of recovery was uneventful and the patient was discharged on the 15 th postsurgical day. The CA19-9 and CEA levels decreased to 1404.0 U/mL and 28.3 ng/mL, respectively. He was treated with gemcitabine following right hemicolectomy and is still alive 6 months after the diagnosis of colonic metastasis.
ACCEPTED MANUSCRIPT Discussion More than 50 % of the patients with pancreatic cancer have advanced disease at the time of diagnosis.
RI P
T
Despite improvement in management, the prognosis of pancreatic cancer is poor. The overall 5-year survival rate is less than 5 % (7). The majority of metastasis occurs in the liver, lung, abdomen, regional lymph nodes and peritoneum. Even though colonic metastasis from primary pancreatic
SC
cancer is very rare, it can occur years after the curative resection of the primary cancer. Until now,
MA NU
three cases of colonic metastasis from pancreatic cancer have been reported (3-5). Among them, two cases were metachronous metastasis from pancreatic cancer (3,5) and one case was synchronous colonic metastasis as initial presentation of pancreas cancer (4). To our knowledge, our case is the third reported case of metachronous colonic metastasis from pancreatic cancer. Because of its rarity, all cases of colonic metastasis from pancreatic cancer including our case were
ED
not diagnosed preoperatively. All the cases were presumed as having primary colon cancer before the
PT
operation. It is difficult to differentiate colonic metastasis from primary colon cancer because it has similar radiologic features and clinical presentations with primary colon cancer (8). In previous
CE
reports (3-5), the CT scan showed thickened colonic wall or an enhancing mass. Our case had similar findings with previous cases as showing heterogeneous enhancing mass in the cecum. Therefore,
AC
diagnostic imaging alone might not reach the correct preoperative diagnosis. However, prompt diagnosis is very important because misdiagnosing a resectable primary colon cancer as metastasis or treating colonic metastasis as a primary colon cancer could result in inappropriate management (9). In order to make an accurate diagnosis, histological examination including immunohistochemistry stains are mandatory. The defining feature of primary colorectal adenocarcinoma is neoplastic change of mucosal glands and invasion through the muscularis mucosae into the submucosa (10) with presence of an adjacent precursor lesion (adenoma or serrated polyp) (11). Absence of mucosal involvement or the presence of extensive mucosal-submucosal lymphatic involvement is strong evidence in favor of a metastasis (11). In cases where metastases are favored, immunohistochemistry is helpful to determine the primary origin of the tumor.
ACCEPTED MANUSCRIPT Cytokeratins are proteins of keratin-containing intermediate filaments found in epithelial tissues. The expressions of subtypes of cytokeratins (CK) in epithelial cells depend on the type of specific
T
epithelium which helps in determining the origin of epithelia based upon their CK expression profile
RI P
(12). CK7 is commonly expressed in simple glandular epitheliums of lung, breast, stomach, ducts of hepatobiliary system and pancreas (13). CK19 is normally expressed in the lining of the
SC
gastroenteropancreatic and hepatobiliary tracts (14). In contrast, CK20 is a major cellular protein found in mature enterocytes and goblet cells, and is identified in all cases of adenocarcinomas of
MA NU
lower gastrointestinal tract and transitional cell carcinoma (13,15,16). Therefore, combination of CK7 and CK20 are used as a panel to determine the primary origin when metachronous or synchronous colon cancers occur in conjunction with carcinomas of other sites, such as ovary and breast. In colon cancers, strong and diffuse expression of CK7 and loss of CK20 strongly suggests metastases (13).
ED
It is not uncommon to encounter a metastatic adenocarcinoma in an extrapancreatic location for
PT
which the pancreas appears to be a possible primary (10), with the most common sites being lymph nodes, liver, lung, abdominal cavity and adrenal glands (2). However, metastasis of pancreatic cancer
CE
to colon is extremely rare and therefore, no clear mechanism has been stated. This present case had a metastatic tumor in cecum which is located anatomically not so distantly from the pancreas. The
AC
metastatic colon cancer included multiple lymphatic tumor invasions and metastasis in 2 out of 39 dissected lymph nodes but original pancreatic cancer otherwise had no lymphovascular tumor involvement or metastatic lymph nodes. Inada et al. reported a cognate case in which the primary pancreas cancer with lymph node metastasis had metastasized to ascending colon after 7 years of follow up and the author assumed peritoneal metastasis more likely than lymphatic spread (3). Likewise, based on clinicopathological findings, peritoneal drop down metastasis instead of lymphatic spread is more suggested as the pathway in this present case. In our patient, the level of CA19-9 was elevated to 5133.0 U/mL at the time of admission. And CA19-9 level was also elevated to 1886.6 U/mL in the case of Inada et al (3). In both cases, there was no evidence of local recurrence at the previous pancreatectomy site. The elevated CA19-9 level and
ACCEPTED MANUSCRIPT no evidence of local tumor recurrence may raise suspicion of a metastatic disease. However, both patients were not preoperatively suspected of having colonic metastasis because of its extremely low
T
incidence of metastasis from primary pancreatic cancer. Considering these reported cases, although it
RI P
is very rare, colonic metastasis should be included when searching for a metastatic site when CA19-9 is elevated. And the preoperative suspicion of metastasis is important because it is helpful to make an
MA NU
SC
accurate diagnosis and treatment.
Conclusion
In conclusion, we present a rare case of metachronous colonic metastasis from pancreatic cancer. Combination of CK7 and CK20 on immunohistochemical stain were useful to distinguish metastasis
ED
from primary colon cancer. Although it is rare, colonic metastasis should be included in the differential diagnosis of colonic mass when CA 19-9 is elevated in the patient have the history of
AC
CE
PT
primary pancreatic cancer.
ACCEPTED MANUSCRIPT References Hidalgo M. Pancreatic cancer. N Engl J Med 2010;362:1605-1617.
2.
Hess KR, Varadhachary GR, Taylor SH, et al. Metastatic patterns in adenocarcinoma. Cancer
T
1.
3.
RI P
2006;106:1624-1633.
Inada K, Shida D, Noda K, Inoue S, Warabi M, Umekita N. Metachronous colonic metastasis from pancreatic cancer seven years post-pancreatoduodenectomy. World J Gastroenterol 2013;19:1665-1668.
Bellows C, Gage T, Stark M, McCarty C, Haque S. Metastatic pancreatic carcinoma
SC
4.
presenting as colon carcinoma. South Med J 2009;102:748-750. Ogu US, Bloch R, Park G. A rare case of metachronous skip metastasis of pancreatic cancer
MA NU
5.
to the colon. Am Surg 2012;78:E342-343. 6.
Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 2010;17:1471-1474.
7.
Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010;60:277-300.
8.
Yokota T, Kunii Y, Kagami M, et al. Metastatic breast carcinoma masquerading as primary
9.
ED
colon cancer. Am J Gastroenterol 2000;95:3014-3016. Voravud N, el-Naggar AK, Balch CM, Theriault RL. Metastatic lobular breast carcinoma simulating primary colon cancer. Am J Clin Oncol 1992;15:365-369. Bosman FT, Carneiro F, Hruban RH, Theise ND. WHO Classification of Tumours of the
PT
10.
Digestive system: International Agency for Research on Cancer, 2010. Robert DO, John RG. Surgical Pathology of the GI Tract, Liver, Biliary Tract, and Pancreas:
CE
11.
Saunders Elsevier, 2009. 12.
Schweizer J, Bowden PE, Coulombe PA, et al. New consensus nomenclature for mammalian
13.
AC
keratins. J Cell Biol 2006;174:169-174. Chu P, Wu E, Weiss LM. Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases. Mod Pathol 2000;13:962-972. 14.
Jain
R,
Fischer
S,
Serra
S,
Chetty
R.
The
Use
of
Cytokeratin
19
(CK19)
Immunohistochemistry in Lesion of the Pancreas, Gastsrointestinal Tract, and Liver. Appl Immunohistochem Mol Morphol 2010;18:9-15. 15.
Moll R, Zimbelmann R, Goldschmidt MD, et al. The human gene encoding cytokeratin 20 and its expression during fetal development and in gastrointestinal carcinomas. Differentiation 1993;53:75-93.
16.
Wildi S, Kleeff J, Maruyama H, et al. Characterization of cytokeratin 20 expression in pancreatic and colorectal cancer. Clin Cancer Res 1999;5:2840-2847.
ACCEPTED MANUSCRIPT Figure legend
T
Figure 1. Contrast enhanced axial (A) and coronal (B) CT scan shows enhancing cecal mass (arrow)
RI P
invading ileocecal valve with distension of small bowel loop. The mass also shows pericolic fat infiltration and invasion into adjacent right psoas muscle (arrowhead).
SC
Figure 2. Microscopic findings of the right hemicolectomy specimen showed adenocarcinoma,
MA NU
composed of small to medium sized glandular structures with pleomorphic nuclei, growing in haphazard pattern with desmoplastic stroma (A: HEx200). Immunohistochemical stains of the adenocarcinoma showing strong positivity in cytokeratin 7 (B) and diffuse weak positivity in cytokeratin 19 (C). Cytokeratin 20 stain was negative in the neoplastic glandular components but was
AC
CE
PT
ED
strongly expressed in the remaining normal colonic glands in the surface (D).
MA NU
SC
RI P
T
ACCEPTED MANUSCRIPT
AC
CE
PT
ED
Figure 1a
MA NU
SC
RI P
T
ACCEPTED MANUSCRIPT
AC
CE
PT
ED
Figure 1b
SC
RI P
T
ACCEPTED MANUSCRIPT
AC
CE
PT
ED
MA NU
Figure 2a
SC
RI P
T
ACCEPTED MANUSCRIPT
AC
CE
PT
ED
MA NU
Figure 2b
SC
RI P
T
ACCEPTED MANUSCRIPT
AC
CE
PT
ED
MA NU
Figure 2c
SC
RI P
T
ACCEPTED MANUSCRIPT
AC
CE
PT
ED
MA NU
Figure 2d
S0899-7071(15)00012-1 doi: 10.1016/j.clinimag.2015.01.010 JCT 7768
To appear in:
Journal of Clinical Imaging
Received date: Revised date: Accepted date:
27 October 2014 30 December 2014 13 January 2015
Please cite this article as: Kim Woogyeong, Lee Yedaun, Metachronous colonic metastasis from pancreatic cancer presenting as mechanical obstruction: A case report, Journal of Clinical Imaging (2015), doi: 10.1016/j.clinimag.2015.01.010
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Metachronous colonic metastasis from pancreatic cancer presenting as mechanical
T
obstruction: A case report
RI P
Woogyeong Kim, MD1, Yedaun Lee, MD² 1
1435, Jwa-dong, Haeundae-gu, Busan 612-896, Korea 2
SC
Department of Pathology, Haeundae Paik Hospital, Inje University College of Medicine,
MA NU
Department of Radiology, Haeundae Paik Hospital, Inje University College of Medicine,
1435, Jwa-dong, Haeundae-gu, Busan 612-896, Korea Corresponding Author:
ED
Yedaun Lee, MD.
Department of Radiology, Haeundae Paik Hospital, Inje University College of Medicine, 875
PT
(Jwa-dong) Haeundae-ro, Haeundae-gu, Busan 612-030, Korea
CE
Tel. : (82-51) 797-0356, Fax. : (82-51) 797-0379
AC
E-mail: [email protected]
Type of Manuscript: Case report
ACCEPTED MANUSCRIPT Abstract Colonic metastasis from pancreatic cancer is extremely rare. We present the case of a 64-year-old
RI P
T
man who developed colonic metastasis of pancreatic cancer 2 years after distal pancreatectomy. CT scan showed cecal mass with small bowel dilatation. The level of carbohydrate antigen 19-9 (CA19-9) was elevated to 5133.0 U/mL. Under the diagnosis of colon cancer, right hemicolectomy was
SC
performed. Pathologic diagnosis was a metastasis from the primary pancreatic cancer. Based on the
MA NU
present case, colonic metastasis should be included in the differential diagnosis of colonic mass with
AC
CE
PT
ED
elevated CA 19-9 and history of curative resection of primary pancreatic cancer.
ACCEPTED MANUSCRIPT Introduction Pancreatic cancer is the fourth most common cause of cancer-related deaths in United States (1). The
RI P
T
high mortality rate of pancreatic cancer is associated with the delayed diagnosis at advanced stage and no effective treatment. Common sites of metastasis include liver, lymph nodes, lung and peritoneum (2). Metastasis to colon is very rare. To the best of our knowledge, only three cases of
SC
colonic metastasis from the pancreatic cancer have been reported in the English literatures (3-5).
MA NU
Here we report a case of a 64 year-old man with metachronous colonic metastasis from pancreatic cancer presenting as colonic obstruction.
Case Report
A 64-year old man underwent distal pancreatectomy with splenectomy in February 2012 for
ED
pancreatic tail cancer. The pathologic diagnosis was a moderately differentiated adenocarcinoma with
PT
only perineural invasions without lymphovascular tumor invasion or metastatic lymph nodes. The stage of pancreatic cancer was IIA, pT3N0M0 according to American Joint Committee on Cancer
CE
staging system 7th edition (6). The carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) levels were elevated to 3341 U/mL (upper limit of normal range < 37 U/mL) and 74.3 ng/mL
AC
(upper limit of normal range < 5 ng/mL) before the pancreatectomy. After the operation, the CA19-9 and CEA level were decreased to 6.9 U/mL and 4.8 ng/mL. He had regular follow-ups every 6 months with a protocol including computed tomography (CT) and a biological tumor marker CA19-9 and there was no evidence of recurrence during the first fifteen months. However, from May 2013, serum CA 19-9 and CEA level began to increase (334.8 U/mL and 18.2 ng/mL) and thorough CT evaluation was carried out to reveal any recurrent mass but none was found. In January 2014, he was admitted due to clinical symptoms of diffuse abdominal pain for two weeks. On physical examination, the abdomen was distended and bowel sound was tympanic. The level of CA19-9 was elevated to 5133.0 U/mL and CEA level was 54.5 ng/mL. Abdominal CT scan showed enhancing cecal mass which caused narrowing of ileocecal valve and it was infiltrating into the pericolic fat (Fig 1). And also, diffuse distension of small bowel loops was
ACCEPTED MANUSCRIPT observed. There was no abnormal lesion in the liver and remnant pancreas. The patient underwent a right-hemicolectomy with lymph node dissection under the clinical impression of colon cancer.
T
Intraoperative findings revealed a solid mass in the cecum with small bowel obstruction. The mass
RI P
invaded adjacent right psoas muscle.
Intraoperative frozen section was performed to evaluate the nature of the obstruction and it was
SC
confirmed as adenocarcinoma. Subsequent right hemicolectomy with lymphadenectomy was done. Macroscopically, the specimen revealed a 5.0cm length of wall thickening with mucosal ulceration in
MA NU
cecum but without definite mucosal adenomatous change. Histopathological examination showed glandular cancer nests with stromal desmoplasia diffusely infiltrating pericecal adipose tissue, muscularis propria and extending into the mucosal layer. Multifocal areas of remaining superficial normal colonic mucosa were observed. The neoplastic cancer nests consist of small to medium sized
ED
tubular glands lined by epithelial cells with moderate pleomorphism (Fig 2A). Multiple lymphatic invasions were present and 2 out of 39 dissected regional lymph nodes had metastatic
PT
adenocarcinomas.
CE
Immunohistochemical stains revealed diffuse strong expression of cytokeratin 7 and weak expression of cytokeratin 19 in adenocarcinoma (Fig 2B-C). Cytokeratin 20 was negative in cancer
AC
nests and was only expressed in the remnant normal colonic mucosa (Fig 2D). Focal positivity of carcinoembryonic antigen (CEA) of the tumor component was also present. Histopathological patterns of the previous pancreatic ductal adenocarcinoma specimen were reviewed and compared. The two tumors had almost identical features. Therefore, based on the clinicopathologic findings and the results of immunohistochemical stains, the final diagnosis of the right hemicolectomy specimen was moderately differentiated metastatic adenocarcinoma primarily originating in pancreas. Postoperative course of recovery was uneventful and the patient was discharged on the 15 th postsurgical day. The CA19-9 and CEA levels decreased to 1404.0 U/mL and 28.3 ng/mL, respectively. He was treated with gemcitabine following right hemicolectomy and is still alive 6 months after the diagnosis of colonic metastasis.
ACCEPTED MANUSCRIPT Discussion More than 50 % of the patients with pancreatic cancer have advanced disease at the time of diagnosis.
RI P
T
Despite improvement in management, the prognosis of pancreatic cancer is poor. The overall 5-year survival rate is less than 5 % (7). The majority of metastasis occurs in the liver, lung, abdomen, regional lymph nodes and peritoneum. Even though colonic metastasis from primary pancreatic
SC
cancer is very rare, it can occur years after the curative resection of the primary cancer. Until now,
MA NU
three cases of colonic metastasis from pancreatic cancer have been reported (3-5). Among them, two cases were metachronous metastasis from pancreatic cancer (3,5) and one case was synchronous colonic metastasis as initial presentation of pancreas cancer (4). To our knowledge, our case is the third reported case of metachronous colonic metastasis from pancreatic cancer. Because of its rarity, all cases of colonic metastasis from pancreatic cancer including our case were
ED
not diagnosed preoperatively. All the cases were presumed as having primary colon cancer before the
PT
operation. It is difficult to differentiate colonic metastasis from primary colon cancer because it has similar radiologic features and clinical presentations with primary colon cancer (8). In previous
CE
reports (3-5), the CT scan showed thickened colonic wall or an enhancing mass. Our case had similar findings with previous cases as showing heterogeneous enhancing mass in the cecum. Therefore,
AC
diagnostic imaging alone might not reach the correct preoperative diagnosis. However, prompt diagnosis is very important because misdiagnosing a resectable primary colon cancer as metastasis or treating colonic metastasis as a primary colon cancer could result in inappropriate management (9). In order to make an accurate diagnosis, histological examination including immunohistochemistry stains are mandatory. The defining feature of primary colorectal adenocarcinoma is neoplastic change of mucosal glands and invasion through the muscularis mucosae into the submucosa (10) with presence of an adjacent precursor lesion (adenoma or serrated polyp) (11). Absence of mucosal involvement or the presence of extensive mucosal-submucosal lymphatic involvement is strong evidence in favor of a metastasis (11). In cases where metastases are favored, immunohistochemistry is helpful to determine the primary origin of the tumor.
ACCEPTED MANUSCRIPT Cytokeratins are proteins of keratin-containing intermediate filaments found in epithelial tissues. The expressions of subtypes of cytokeratins (CK) in epithelial cells depend on the type of specific
T
epithelium which helps in determining the origin of epithelia based upon their CK expression profile
RI P
(12). CK7 is commonly expressed in simple glandular epitheliums of lung, breast, stomach, ducts of hepatobiliary system and pancreas (13). CK19 is normally expressed in the lining of the
SC
gastroenteropancreatic and hepatobiliary tracts (14). In contrast, CK20 is a major cellular protein found in mature enterocytes and goblet cells, and is identified in all cases of adenocarcinomas of
MA NU
lower gastrointestinal tract and transitional cell carcinoma (13,15,16). Therefore, combination of CK7 and CK20 are used as a panel to determine the primary origin when metachronous or synchronous colon cancers occur in conjunction with carcinomas of other sites, such as ovary and breast. In colon cancers, strong and diffuse expression of CK7 and loss of CK20 strongly suggests metastases (13).
ED
It is not uncommon to encounter a metastatic adenocarcinoma in an extrapancreatic location for
PT
which the pancreas appears to be a possible primary (10), with the most common sites being lymph nodes, liver, lung, abdominal cavity and adrenal glands (2). However, metastasis of pancreatic cancer
CE
to colon is extremely rare and therefore, no clear mechanism has been stated. This present case had a metastatic tumor in cecum which is located anatomically not so distantly from the pancreas. The
AC
metastatic colon cancer included multiple lymphatic tumor invasions and metastasis in 2 out of 39 dissected lymph nodes but original pancreatic cancer otherwise had no lymphovascular tumor involvement or metastatic lymph nodes. Inada et al. reported a cognate case in which the primary pancreas cancer with lymph node metastasis had metastasized to ascending colon after 7 years of follow up and the author assumed peritoneal metastasis more likely than lymphatic spread (3). Likewise, based on clinicopathological findings, peritoneal drop down metastasis instead of lymphatic spread is more suggested as the pathway in this present case. In our patient, the level of CA19-9 was elevated to 5133.0 U/mL at the time of admission. And CA19-9 level was also elevated to 1886.6 U/mL in the case of Inada et al (3). In both cases, there was no evidence of local recurrence at the previous pancreatectomy site. The elevated CA19-9 level and
ACCEPTED MANUSCRIPT no evidence of local tumor recurrence may raise suspicion of a metastatic disease. However, both patients were not preoperatively suspected of having colonic metastasis because of its extremely low
T
incidence of metastasis from primary pancreatic cancer. Considering these reported cases, although it
RI P
is very rare, colonic metastasis should be included when searching for a metastatic site when CA19-9 is elevated. And the preoperative suspicion of metastasis is important because it is helpful to make an
MA NU
SC
accurate diagnosis and treatment.
Conclusion
In conclusion, we present a rare case of metachronous colonic metastasis from pancreatic cancer. Combination of CK7 and CK20 on immunohistochemical stain were useful to distinguish metastasis
ED
from primary colon cancer. Although it is rare, colonic metastasis should be included in the differential diagnosis of colonic mass when CA 19-9 is elevated in the patient have the history of
AC
CE
PT
primary pancreatic cancer.
ACCEPTED MANUSCRIPT References Hidalgo M. Pancreatic cancer. N Engl J Med 2010;362:1605-1617.
2.
Hess KR, Varadhachary GR, Taylor SH, et al. Metastatic patterns in adenocarcinoma. Cancer
T
1.
3.
RI P
2006;106:1624-1633.
Inada K, Shida D, Noda K, Inoue S, Warabi M, Umekita N. Metachronous colonic metastasis from pancreatic cancer seven years post-pancreatoduodenectomy. World J Gastroenterol 2013;19:1665-1668.
Bellows C, Gage T, Stark M, McCarty C, Haque S. Metastatic pancreatic carcinoma
SC
4.
presenting as colon carcinoma. South Med J 2009;102:748-750. Ogu US, Bloch R, Park G. A rare case of metachronous skip metastasis of pancreatic cancer
MA NU
5.
to the colon. Am Surg 2012;78:E342-343. 6.
Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 2010;17:1471-1474.
7.
Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010;60:277-300.
8.
Yokota T, Kunii Y, Kagami M, et al. Metastatic breast carcinoma masquerading as primary
9.
ED
colon cancer. Am J Gastroenterol 2000;95:3014-3016. Voravud N, el-Naggar AK, Balch CM, Theriault RL. Metastatic lobular breast carcinoma simulating primary colon cancer. Am J Clin Oncol 1992;15:365-369. Bosman FT, Carneiro F, Hruban RH, Theise ND. WHO Classification of Tumours of the
PT
10.
Digestive system: International Agency for Research on Cancer, 2010. Robert DO, John RG. Surgical Pathology of the GI Tract, Liver, Biliary Tract, and Pancreas:
CE
11.
Saunders Elsevier, 2009. 12.
Schweizer J, Bowden PE, Coulombe PA, et al. New consensus nomenclature for mammalian
13.
AC
keratins. J Cell Biol 2006;174:169-174. Chu P, Wu E, Weiss LM. Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases. Mod Pathol 2000;13:962-972. 14.
Jain
R,
Fischer
S,
Serra
S,
Chetty
R.
The
Use
of
Cytokeratin
19
(CK19)
Immunohistochemistry in Lesion of the Pancreas, Gastsrointestinal Tract, and Liver. Appl Immunohistochem Mol Morphol 2010;18:9-15. 15.
Moll R, Zimbelmann R, Goldschmidt MD, et al. The human gene encoding cytokeratin 20 and its expression during fetal development and in gastrointestinal carcinomas. Differentiation 1993;53:75-93.
16.
Wildi S, Kleeff J, Maruyama H, et al. Characterization of cytokeratin 20 expression in pancreatic and colorectal cancer. Clin Cancer Res 1999;5:2840-2847.
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Figure 1. Contrast enhanced axial (A) and coronal (B) CT scan shows enhancing cecal mass (arrow)
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invading ileocecal valve with distension of small bowel loop. The mass also shows pericolic fat infiltration and invasion into adjacent right psoas muscle (arrowhead).
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Figure 2. Microscopic findings of the right hemicolectomy specimen showed adenocarcinoma,
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composed of small to medium sized glandular structures with pleomorphic nuclei, growing in haphazard pattern with desmoplastic stroma (A: HEx200). Immunohistochemical stains of the adenocarcinoma showing strong positivity in cytokeratin 7 (B) and diffuse weak positivity in cytokeratin 19 (C). Cytokeratin 20 stain was negative in the neoplastic glandular components but was
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strongly expressed in the remaining normal colonic glands in the surface (D).
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Figure 2a
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Figure 2b
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Figure 2c
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Figure 2d