Background: Intraductal papillary-mucinous neoplasms (IPMNs) are potentially malignant intraductal epithelial neoplasms that sometimes penetrate into other organs. To the best of our knowledge, no report has yet described a case with penetration into the spleen. We recently encountered a case of IPMN with penetration of the stomach and spleen that was successfully treated by total pancreatectomy. Case presentation: A 70-year-old female visited our hospital with a complaint of fever and abdominal pain. Contrast-enhanced computed tomography (CT) revealed dilatation of the main pancreatic duct in the entire pancreas and penetration into the stomach and spleen. Upper gastrointestinal endoscopy revealed mucin extruding from four openings of the fistula in the stomach. No malignancy was detected based on cytology of the mucin. Inflammation markers and tumor markers (CEA, CA19–9) were elevated in the blood. The pre- operative diagnosis was IPMN of main pancreatic duct type penetrating into the stomach and spleen. A total pancreatectomy and splenectomy were performed, combined with distal gastrectomy including resection of the fistulas between the pancreas and stomach. No postoperative complications were noted. Histopathological examination of the resected specimen revealed atrophy of the pancreatic parenchyma, and the main duct of the pancreas was filled with mucin. Mucin-producing malignant tumor cells were detected in the epithelium of the main pancreatic duct with no signs of invasion. No malignancy was found at the fistulas between the pancreas and stomach or spleen. The patient was finally diagnosed with non-invasive intraductal papillary- mucinous carcinoma (IPMC) of main pancreatic duct type. Mechanical penetration was suspected as a mechanism of the penetration. The patient remained disease-free without evidence of recurrence more than 15 months after the operation. Conclusion: Though IPMNs sometimes penetrate into other adjacent organs, penetration into two organs, including the spleen, is rare. The rare case of IPMC penetrating into the stomach and spleen presented here was treated successfully by total pancreatectomy. Keywords: Intraductal papillary-mucinous neoplasm, Pancreas, Penetration, Fistula * Correspondence: email@example.com Department of Surgery, Toyonaka Municipal Hospital, 4-14-1 Shibahara, Toyonaka, Osaka 560-8565, Japan Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Harino et al. Surgical Case Reports (2018) 4:117 Page 2 of 5 Background (carcinoembryonic antigen = 9.4 U/mL, cancer antigen In 1982, intraductal papillary-mucinous neoplasm (IPMN) 19-9 = 550 U/mL). Pancreatic tumor markers were not el- was reported by Ohashi et al. as a mucus-producing pan- evated (s-pancreas-1 antigen = 20.0 U/mL, duke pancreatic creatic carcinoma characterized by a favorable prognosis monoclonal antigen type 2 ≤ 25 U/mL). Contrast-en- . IPMNs are potentially malignant, grossly visible intra- hanced computed tomography (CT) revealed a markedly ductal epithelial neoplasms composed of mucin-producing dilated main pancreatic duct (MPD) 55 mm in length in columnar cells. The lesions exhibit papillary proliferation, the whole pancreas, and the whole pancreatic parenchyma cyst formation, and varying degrees of cellular atypia. was thinning with atrophy (Fig. 1a). In addition, gastropan- IPMNs can be classified into three types based on imaging creatic fistula and splenopancreatic fistula were detected, studies and/or histopathology: main duct, branch duct, suggesting penetration of the pancreatic tumor (Fig. 2a, c, and mixed type. d). As seen on the CT examination, dilatation of the MPD Kimura et al. initially reported nine cases of IPMN was detected on magnetic resonance imaging, and its con- penetrating into other organs, such as the common bile tent was visualized using low signal intensity on duct, or developed fistula formation . Kobayashi et al. T1-weighted images and high signal intensity at T2- reported that the incidence of fistula formation is 6.6% weighted images (Fig. 1b). The wall of the MPD and fistula (18 of 274 cases) ; the organs penetrated were the had high signal intensity on diffusion-weighted images. duodenum (67%), stomach (44%), common bile duct Upon examination by upper gastrointestinal endoscopy, (33%), colon (6%), and small intestine (6%). Notably, four gastropancreatic fistulas were identified on the poster- 39% of the cases with fistula formation developed into ior wall of the gastric body and mucus discharged from multiple organ fistula formation. To the best of our the gastropancreatic fistulas (Fig. 2b). Cytological examin- knowledge, there have been no reports of penetration ation of the mucus did not reveal any signs of malignancy. into the spleen. In this context, penetration into multiple On the basis of the findings, the patient was organs including the spleen is very rare. Here, we report pre-operatively diagnosed with IPMN of main ductal type a case of IPMN with penetration not only into the stom- penetrating into the stomach and spleen and surgery ach, but also the spleen, that was successfully treated by planned for her treatment. A total pancreatectomy, splen- total pancreatectomy. ectomy, and distal gastrectomy combined with resection of the fistulas were performed. Considering the malignant Case presentation potential based on the main ductal type with > 10 mm A 70-year-old woman was admitted to our hospital be- MPD dilatation, we also performed lymphadenectomy. cause of upper abdominal pain. Her medical history The total operation time was 426 min, and the total intra- included appendicitis at 20 years old. Upon physical exam- operative blood loss was 575 mL. Macroscopic examin- ination, left hypochondriac pain and tenderness in the ation of the resected specimen indicated swelling of the upper abdomen were noted. The laboratory examinations whole pancreas. When the resected specimen was divided, revealed elevated inflammatory markers (white blood cell mucus swelled out, and then most of the cut surface of the count = 13400/μL, C-reactive protein = 11.58 mg/dL) and whole pancreas was occupied by the dilated MPD and the biliary enzymes (lactate dehydrogenase = 250 U/L, alkaline mucus accompanied by atrophy of the pancreatic paren- phosphatase = 535 U/L, γ-glutamyltranspeptidase = 76 U/ chyma (Fig. 3a). The gastropancreatic fistula (Fig. 3b)and L). The levels of tumor markers were also elevated splenopancreatic fistula (Fig. 3c) were macroscopically Fig. 1 Dilatation of the main pancreatic duct in the entire pancreas. a Contrast-enhanced computed tomography revealed a markedly dilated main pancreatic duct (55 mm) and thinning pancreatic tissue (white arrow). b Magnetic resonance cholangiography revealed main pancreatic duct dilatation (white arrow) Harino et al. Surgical Case Reports (2018) 4:117 Page 3 of 5 Fig. 2 Gastropancreatic fistula and splenopancreatic fistula. a Contrast-enhanced computed tomography (CT) revealed fistulas (white arrow) between the pancreas and stomach. b Upper gastrointestinal endoscopy revealed four gastropancreatic fistulas on the posterior wall of the gastric body (four white arrows) and mucus discharge from the gastropancreatic fistulas. c, d Contrast-enhanced CT revealed fistulas (white arrows) between the pancreas and spleen Fig. 3 Macroscopic findings for the resected specimen. a Most of the cut surface of the whole pancreas was occupied by the dilated main pancreatic duct and the mucus accompanied by atrophy of the pancreatic parenchyma. b A gastropancreatic fistula was identified between the main pancreatic duct and the posterior wall of the gastric body. c A splenopancreatic fistula was identified (white arrow), and bleeding and infarction were detected in the spleen with mucus penetration Harino et al. Surgical Case Reports (2018) 4:117 Page 4 of 5 identified. In the spleen, bleeding and infarction were de- or developed fistula formation . Kobayashi et al. also tected in addition to the mucus penetration. Microscopic investigated that the incidence of the fistula formation examination of the resected specimen revealed cancer was 6.6% (18 out of 274 cases) . The organs pene- cells in the epithelium of the MPD in part of the tumor trated were also reported in their investigation: duode- (Fig. 4a). There was no sign of infiltration on the cancer num (67%), stomach (44%), common bile duct (33%), cells, and the remaining part of the MPD epithelium was colon (6%), and small intestine (6%). Notably, 39% of adenoma (Fig. 4b). At the gastropancreatic fistula (Fig. 4c) the cases with fistula formation developed into multiple and splenopancreatic fistula (Fig. 4d), no cancer cells were organs fistula formation. In the report, the spleen is not detected, only mucus and inflammatory cells. Finally, we reported as the organ penetrated into by IPMN, and fur- diagnosed the tumor as non-invasive intraductal thermore, to the best of our knowledge, there have been papillary-mucinous cancer (IPMC) of the pancreas. No no reports describing IPMN cases penetrating into the postoperative complications were noted. The patient has spleen. In this context, our IPMN case, which exhibited remained disease-free without evidence of recurrence for penetration into multiple organs including the spleen, is 15 months. very rare, suggesting significance of reporting the case. The pathogenesis of fistula formation in IPMN is generally Discussion considered to be divided into two main types based on the During the last three decades, an increasing number of underlying mechanism: invasive penetration of cancer reports of IPMN of the pancreas have been published cells and mechanical penetration. Though invasive pene- [2, 4, 5]. Though IPMNs originate from the pancreatic tration is derived from direct invasion of organs by cancer duct cells similar to invasive ductal adenocarcinoma of cells, mechanical penetration is due to the high inner the pancreas, IPMN exhibits a unique clinical feature pressure of a mucus-filled pancreatic duct [3, 6]. Kobaya- different from invasive ductal adenocarcinoma, such as shi et al. reported that three out of nine cases (33%) had secretion of a large quantity of mucin by the neoplasm, invasive penetration, and mechanical penetration was and slow and expansive growth associated with low ma- shown in the remaining six cases (67%) . In the current lignant potentials for metastasis and invasion compared case, cancer cells did not exist in the area of the fistulas, to invasive ductal adenocarcinoma. Fistula formation suggesting mechanical penetration as the underlying into other organs is also one of the characteristic fea- mechanism in the development of the fistula. Our finding tures of IPMNs. With regard to its incidence, Kimura that the mucus in the MPD swelled out when the resected et al. initially reported nine cases with IPMN which specimen was divided may be associated with the high penetrated into other organs such as common bile duct inner pressures, which may support mechanical Fig. 4 Microscopic findings of the resected specimen. a Cancer cells were detected in the epithelium of the main pancreatic duct, though there were no signs of invasion. b Adenoma was identified on the remaining part of the epithelial cells of the pancreatic duct. c A gastropancreatic fistula was microscopically detected, and no cancer cells were detected on the area. d Microscopic examination identified a splenopancreatic fistula where no cancer cells were detected Harino et al. Surgical Case Reports (2018) 4:117 Page 5 of 5 penetration as the pathogenesis of fistula formation in this Received: 9 July 2018 Accepted: 7 September 2018 case. Several previous studies have reported that inflam- mation is also involved in mechanical penetration [7–10]. References Based on our finding of inflammatory cells at the fistulas 1. Ohashi K, Murakami Y, Maruyama M, Takekoshi T, Ohta H, Ohashi I, et al. Four cases of mucus-secreting pancreatic cancer (in Japanese). Prog Digest in this case, inflammation may exist at the fistula, resulting Endosc. 1982;20:348–51. in mechanical penetration. Furthermore, when consider- 2. Kimura W, Sasahira N, Yoshikawa T, Muto T, Makuuchi M. Duct-ectatic type ing mechanical penetration apart from invasive penetra- of mucin producing tumor of the pancreas - new concept of pancreatic neoplasia. Hepatogastroenterology. 1996;43:692–709. tion, a pressure gradient seems to be necessary for fistula 3. Kobayashi G, Fujita N, Noda Y, Ito K, Horaguchi J, et al. Intraductal papillary development. Lumen organs, including the duodenum, mucinous neoplasms of the pancreas showing fistula formation into other stomach, and bile duct, may easily be under lower pres- organs. J Gastroenterol. 2010;45:1080–9. 4. Tanaka M, Chari S, Adsay V, Fernandez-del Castillo C, Falconi M, et al. sure than solid organs, such as the spleen, which could be International consensus guidelines for management of intraductal papillary one reason why fistula formation into the spleen is rare mucinous neoplasms and mucinous cystic neoplasms of the pancreas. compared to the lumen organs. Kawarada et al. reported a Pancreatology. 2006;6:17–32. 5. Tanaka M, Fernández-del Castillo C, Adsay V, Chari S, Falconi M, et al. 5-year survival rate of IPMC with penetration of 46.5% in International consensus guidelines 2012 for the management of IPMN and Japan . Kimura et al. reported a 5-year survival rate of MCN of the pancreas. Pancreatology. 2012;12:183–97. IPMC with penetration or invasion of neighboring organs 6. Kurihara K, Nagai H, Kasahara K, Kanazawa K, Kanai N. Biliopancreatic fistula associated with intraductal papillary-mucinous pancreatic cancer: institutional of 28% . In our case, the follow-up period was just experience and review of the literature. Hepato-Gastroenterology. 2000;47:1164–7. 15 months. Although the previously reported prognosis 7. Baek Y, Midorikawa T, Nagasaki H, Kikuchi H, Kitamura N, et al. A case report might not be applied to our case since the abovemen- of pancreatic mucinous cystadenocarcinoma with penetration to the stomach. J Jpn Gastroenterol (In Japanese). 1999;96:685–90. tioned prognosis was concerning about cases with invasive 8. Watanabe N, Hasegawa H, Tsuneya Y, Kumazawa M, Baba M, et al. A case of carcinoma, not about non-invasive carcinoma, further ob- mucinous cystadenocarcinoma with a fistula between cyst and stomach. J servation would be necessary in our case. Jpn Gastroenterol (In Japanese). 2003;100:349–53. 9. Goto N, Yoshioka M, Hayashi M, Itani T, Mimura J, et al. Intraductal papillary- mucinous neoplasm of the pancreas penetrating to the stomach and the Conclusions common bile duct. J Pancreas. 2012;13:61–5. 10. Umemura S, Naitoh I, Nakazawa T, Katoh A, Hori Y, et al. A case of pancreatic We experienced a case of IPMN of the pancreas penetrat- mucinous carcinoma derived from branch duct intraductal papillary mucinous ing into the stomach and spleen that was successfully neoplasm penetrating into the stomach and colon. Therapeutic Res Hepato- treated by total pancreatectomy. This case could contribute Biliary-Pancreatic Dis. 2014;12:65–72. 11. Kawarada Y, Iwata M, Yokoi H. Prognosis of invasive intraductal papillary to improving our understanding of this type of neoplasm. carcinoma of the pancreas - cases with invasion of other organs. J Biliary Tract & Pancreas (In Japanese). 1999;20:51–6. Authorship declaration All authors are in agreement with the content of the manuscript. Authors’ contributions TH and YT conceived of the case presentation and drafted the manuscript. HT and SA wrote the histopathological details of the manuscript. KN, HN, TO, MH, KO, TT, SN, HI, TI, and KA organized the manuscript. MY and TN prepared the endoscopic details of the manuscript. KD supervised the writing of the manuscript. All authors read and approved the final manuscript. Ethics approval and consent to participate Written informed consent was obtained from the patient for the participation. The Human Ethics Review Committee of Toyonaka Municipal Hospital approved this study. Consent for publication Written informed consent was obtained from the patient for the publication of this case report and any accompanying images. Competing interests The authors declare that they have no competing interests. Publisher’sNote Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Author details Department of Surgery, Toyonaka Municipal Hospital, 4-14-1 Shibahara, Toyonaka, Osaka 560-8565, Japan. Department of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Japan. Department of Pathology, Toyonaka Municipal Hospital, Toyonaka, Japan.
Surgical Case Reports – Springer Journals
Published: Sep 15, 2018
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