case report Available from: URL: http://www.jgld.ro/2015/2/21.html DOI: http://dx.doi.org/10.15403/jgld.2014.1121.242.hdk

A Case of Primary Pancreatic non-Hodgkin B-cell Mimicking Autoimmune

Andrea Anderloni1, Chiara Genco2, Marco Ballarè3, Stefania Carmagnola4, Serena Battista5, Alessandro Repici1

1) Department of Abstract , Endoscopy Unit, IRCCS Istituto Clinico Non Hodgkin lymphoma frequently involves the gastrointestinal tract, in particular the stomach and the Humanitas, Milan; small bowel. Rarely, it can also be a cause of pancreatic masses. Clinical presentation is often non-specific and 2) Division of Endoscopy, may overlap with other pancreatic conditions such as carcinoma, neuroendocrine tumours and autoimmune Istituto Europeo Oncologico, pancreatitis. We report a case of primary pancreatic lymphoma in a young woman with , fever and Milan; abdominal pain mimicking autoimmune pancreatitis. Clinical evaluation included the abdominal Computed 3) Gastrointestinal and Tomography scan, Magnetic Resonance Imaging and an upper gastrointestinal endoscopy that revealed a large Digestive Endoscopy Unit, duodenal mass. Endoscopic biopsies were performed and eventually histological examination was coherent AOU Maggiore della Carità, with a diagnosis of primary pancreatic lymphoma. Novara; 4) Gastrointestinal and Key words: primary pancreatic lymphoma – autoimmune pancreatitis – non-Hodgkin lymphoma. Digestive Endoscopy Unit, AOU Luigi Sacco, Milan; Abbreviations: AIP: autoimmune pancreatitis; CT: computed tomography; LDH: lactate dehydrogenase; 5) Department of Pathology, MRI: magnetic resonance; NHL: non Hodgkin lymphoma; PPL: primary pancreatic lymphoma; UGIE: upper IRCCS Istituto Clinico gastrointestinal endoscopy Humanitas, Milan, Italy

Introduction marrow biopsy [2]. Clinical presentation is often non-specific and includes abdominal pain, weight loss, vomiting and more Address for correspondence: Non-Hodgkin lymphoma rarely jaundice, night sweats and fever (2% of cases) [3-5]. Andrea Anderloni (NHL) frequently involves Lactate dehydrogenase (LDH) is not necessarily elevated in Department of the gastrointestinal tract, in PPL [2], while levels of CA 19.9 are usually normal unless Gastroenterology, particular the stomach and the biliary obstruction is present [5]. Clinical and imaging features IRCCS Istituto Clinico small bowel. Rarely, it can also of PPL may often overlap with other pancreatic conditions Humanitas present as pancreatic masses. such as carcinoma, neuroendocrine tumors and autoimmune Via Alessandro Manzoni 56, Primary pancreatic lymphoma pancreatitis (AIP), therefore histological diagnosis is advisable 20089 Rozzano, (PPL) accounts for less than due to the different prognosis and therapeutic approaches of Milan, Italy 1% of all primary pancreatic such conditions. We report a case of PPL in a young woman [email protected] tumors, while 1.25% to 2.2% with jaundice, fever and abdominal pain mimicking an AIP. of all patients with NHL have a secondary involvement of the Case report at presentation [1, 2]. Primary pancreatic A 33-year-old woman was admitted to the emergency unit Received: 23.02.2015 are usually of for jaundice, fever and a two week history of abdominal pain Accepted: 10.03.2015 B-cell lineage and show the radiating to the back. Past medical history was unremarkable following features: 1) pancreatic except for gestational diabetes 8 months previously. At mass with peripancreatic presentation, the laboratory tests showed total bilirubin lymphadenopathies; 2) absence 7.5 mg/dL (0.3-1.2 mg/dL), conjugated bilirubin 5 mg/dL, of thoracic or superficial alanine aminotransferase 578 IU/L (0-40 IU/L), aspartate adenopathies and hepatosplenic aminotransferase 110 IU/L (0-40 IU/L), alkaline phosphatase involvement; 3) normal white 1135 IU/L (70-290 IU/L), gamma-glutamyl transpeptidase blood cell count and bone 376 IU/L (0-50 IU/L), CA 19-9 33.3 U/mL (0.0-37 IU/mL)

J Gastrointestin Liver Dis, June 2015 Vol. 24 No 2: 245-248 246 Anderloni et al with normal blood count. Abdominal ultrasound revealed two pancreatic hypoechoic lesions in the head (3 x 3.5 cm) and in the isthmus (2 cm), with one peripancreatic lymph node of 10 mm. Abdominal Computed Tomography (CT) scan with iodinate contrast medium showed a dilation of the common bile duct (diameter 10 mm) with a pancreatic hypodense mass (4.5 x 4 x 5 cm) involving the head of the pancreas with diffuse enlarged “sausage-shaped” pancreatic gland and irregular narrow pancreatic duct suggestive for autoimmune pancreatitis (Fig. 1). Furthermore, abdominal Magnetic Resonance (MRI) showed a hypovascular enlargement of the whole pancreas with homogeneous enhancement in the tardive phases and multiple bilateral hypovascular renal lesions (Fig. 2). Since serum IgG4 levels were elevated (183 mg/dL, normal values 8-140 mg/ dL), a diagnosis of AIP was made and steroid treatment was started (prednisone 1 mg/Kg), followed by progressive jaundice resolution (bilirubin at discharge: 2.4 mg/dL).

Fig. 1. CT scan (arterial phase) showing diffuse hypodense enlargement of pancreatic head and body.

Fig. 3 A, B. Upper gastrointestinal endoscopy showing the presence of a large sessile and ulcerated lesion of descending duodenum proximal to the papilla which is normal.

After three weeks of therapy the patient was readmitted for jaundice with serum bilirubin 6.5 mg/dL (conjugated bilirubin 5 mg/dL). The laboratory tests revealed a mild leucocytosis (white blood cells count 15,740/mmc). Radiological findings were similar to the previous ones. During hospitalization the patient developed nausea and severe epigastric pain; therefore, an upper gastrointestinal endoscopy (UGIE) was performed, which revealed a duodenal ulcerated sessile lesion proximal to the papilla (diameter 3 cm) (Fig. 3). The histological examination of the prelevated biopsies concluded for a non- Hodgkin B cell lymphoma (Figs 4, 5). The patient was then referred to oncologists and started chemotherapy. One year after the initial diagnosis her clinical condition is stable, with complete resolution of the duodenal and pancreatic lesions.

Discussion

Fig. 2. MRI scans showing enlargement of the Primary pancreatic lymphoma accounts for less than 1% pancreas, biliary dilation and multiple hypovascular of all malignant lymphomas and for 0.2% of all pancreatic areas in both kidneys malignancies [1, 6]. It frequently represents a diagnostic

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Fig. 4 A, B. Lymphoid infiltrate (cells of large size) with prevalent expression of anti CD20 antibody supporting a diagnosis of B cell non-Hodgkin lymphoma (x40).

Fig. 5 A, B. Intense lymphoid infiltrate characterized by large pleomorphic elements with irregular nuclei and scant cytoplasm, surrounding pancreatic glandular structures, without cohesion and organization. Pancreatic glands are entrapped by cells that do not show atypias (H&E x40). challenge as it shares clinical and radiological findings with gastrointestinal hemorrhage due to erosion of the duodenal other pancreatic disorders such as other neoplasms and wall by a pancreatic lymphoma [8]. AIP, an inflammatory disease of the pancreas that usually After diagnosis, our patient was successfully treated with presents with painless obstructive jaundice, pancreatic chemotherapy. Common protocols consider the use of anti mass/enlargement and response to steroids administration. CD20 antibodies or anthracyclines with satisfactory results Diagnostic criteria for AIP include: typical imaging findings and the 5 years mortality refers to 45% of the cases [5, 9-11]. on CT/MRI dynamic scans, elevated levels of serum IgG4, other organs involvement (renal masses, tubulointerstitial CONCLUSION nephritis, sclerosing cholangitis, retroperitoneal fibrosis, submandibular masses), steroid responsiveness and, when The present case underlines the fact that conventional available, histology with immunostaining. In cases with typical diagnostic criteria for AIP are not always adequately sensitive CT/MRI features for AIP and serum elevation of IgG4 or other and specific to achieve a clear differential diagnosis with other organs involvement, a diagnosis of type 1 AIP can be made pancreatic diseases, especially in the presence of overlapping without tissue confirmation, reserving histological / cytological clinical and radiological presentation. The therapeutic examination to patients with non-conclusive results on other approach and prognosis of these two diseases are dramatically examinations [7]. different, and given the risk of possible misdiagnosis or delay We describe the case of a young woman with a PPL in diagnosis, further assessment is advisable when doubts are mimicking an AIP. Clinical presentation of the disease and present and novel diagnostic methods should be investigated. radiological appearance including renal involvement were coherent with a diagnosis of AIP, eventually confirmed by the Conflicts of interest: None to declare. presence of elevated levels of IgG4; the initial clinical response to administration of steroids gave further strength to the initial Authors’ contribution: A.A. and C.G. wrote the manuscript. M.B. and hypothesis. When typical clinical, radiological and serological S.C. performed endoscopic examination and established the diagnosis. findings are present, diagnosis of AIP does not include S.B. evaluated histologic data. A.R. reviewed the manuscript for its histology [7]. In this particular case, the relapse of jaundice intellectual content after steroids, administration required further evaluations and tissue sampling became mandatory. References guided needle aspiration or CT guided core biopsies were not conducted since UGIE revealed the presence of a duodenal 1 Freeman C, Berg JW, Cutler SJ. Occurrence and prognosis of extranodal mass that was easily biopsied allowing the diagnosis of a PPL. lymphomas. Cancer 1972; 29: 252-260. Gastrointestinal involvement by pancreatic lymphoma 2. Fukita Y, Asaki T, Adachi S, Yasuda I, Toyomizu M, Katakura Y. is reported in the literature as a possible but infrequent Non-Hodgkin lymphoma mimicking pancreatic adenocarcinoma presentation of the disease [6]. To our knowledge, the only and peritoneal carcinomatosis. J Clin Oncol 2013; 31: e373-e376. doi: recent case was reported by Dupre et al. in 2011 as a fatal upper 10.1200/JCO.2012.45.2904

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3. Dawson IM, Cornes JS, Morson BC. Primary malignant lymphoid type 1 and type 2. Gut 2013; 62: 1373-1380. doi: 10.1136/ tumours of the intestinal tract. Report of 37 cases with a study of gutjnl-2012-304224 factors influencing prognosis. Br J Surg 1961; 49: 80-89. doi:10.1002/ 8. Dupre MP, Dixon E, Heitman SJ. Primary pancreatic lymphoma: bjs.18004921319 a rare cause of massive upper gastrointestinal hemorrhage. Can J 4. Behrns KE, Sarr MG, Strickler JG. Pancreatic lymphoma: is it a surgical Gastroenterol 2011; 25: 532-533. disease? Pancreas 1994; 9: 662-667. 9. Freedman A. Follicular lymphoma: 2012 update on diagnosis 5. Sandrasegaran K, Tomasian A, Elsayes KM, et al. Hematologic and management. Am J Hematol 2012; 87: 988-995. doi: 10.1002/ malignancies of the pancreas. Abdom Imaging 2015; 40: 411-423. doi: ajh.23313 10.1007/s00261-014-0217-7 10. Seiler TM, Hiddemann W. Advances in the management of follicular 6. Sadot E, Yahalom J, Do RK, et al. Clinical features and outcome of lymphoma. Curr Opin Oncol 2012; 24: 742-747. doi: 10.1097/ primary pancreatic lymphoma. Ann Surg Oncol 2015; 22: 1176-1184. CCO.0b013e328358f602 doi: 10.1245/s10434-014-4176-6 11. Ujjani C, Cheson BD. The current status and future impact of targeted 7. Kamisawa T, Chari ST, Lerch MM, Kim MH, Gress TM, therapies in non-Hodgkin lymphoma. Expert Rev Hematol 2013; 6: Shimosegawa T. Recent advances in autoimmune pancreatitis: 191-202. doi: 10.1586/ehm.13.6

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