mantle cell lymphoma presented as enteric intussusception and involved gallbladder a case report and review of the literature

Accepted Manuscript Mantle cell lymphoma presented as enteric intussusception and involved gallbladder: A case report and review of the literature Chih-Ching Chin, Junping Shiau, Wei-Ciao Wu PII: S2311-3006(16)30163-X DOI: 10.1016/j.jcrpr.2016.11.006 Reference: JCRPR 47 To appear in: Journal of Cancer Research and Practice Received Date: 27 September 2016 Revised Date: November 2016 Accepted Date: 29 November 2016 Please cite this article as: Chin CC, Shiau J, Wu WC, Mantle cell lymphoma presented as enteric intussusception and involved gallbladder: A case report and review of the literature, Journal of Cancer Research and Practice (2017), doi: 10.1016/j.jcrpr.2016.11.006 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 Title: Mantle cell lymphoma presented as enteric intussusception and involved gallbladder: a case report and review of the literature Authors: Chih-Ching Chin, M.D.1,3,4, Junping Shiau, M.D.2,3,4,Wei-Ciao Wu, M.D.2,3,4 RI PT Affiliations: Department of pathology1, Department of surgery2, E-DA hospital and E-DA Cancer Hospital3, I-Shou University4 SC Abstract Background: Intussusception caused by a lymphomatous mass is extremely rare in adults To date, only four cases of mantle cell lymphoma have intussusception as a M AN U treatment sequelae or complication Case presentation: A 72-year-old previously healthy male presented to the emergency department with an ileocolic intussusception related small bowel obstruction Laparoscopic examination showed two solid masses with the terminal ileum as the lead point, and a whitish mass was incidentally found at the gallbladder fundus Laparoscopic right hemicolectomy and cholecystectomy was performed and the pathological report declared mantle cell lymphoma of ileum and TE D gallbladder Conclusion: This is the first reported case of incidental mantle cell lymphoma initially presented as intussusception with a skip lesion at the gallbladder Keywords: mantle cell lymphoma, intussusception, ileum, colon, gallbladder Running title: Mantle cell lymphoma with intussusception EP Acknowledgments and credits: Nil AC C Corresponding author: Name: Junping Shiau, M.D Address: No.21, Yida Rd., Yanchao Dist., Kaohsiung City 824, Taiwan Phone: 886-7-6150011-2983 E-mail: gp5066@gmail.com Author information: Name: Chih-Ching Chin, M.D Address: No.21, Yida Rd., Yanchao Dist., Kaohsiung City 824, Taiwan Phone: 886-7-6150011-2983 E-mail: chinchihching@gmail.com ACCEPTED MANUSCRIPT Name: Wei-Ciao Wu, M.D Address: No.21, Yida Rd., Yanchao Dist., Kaohsiung City 824, Taiwan AC C EP TE D M AN U SC RI PT Phone: 886-7-6150011-2983 E-mail: i5491142@gmail.com ACCEPTED MANUSCRIPT Title: Mantle cell lymphoma presented as enteric intussusception and involved gallbladder: a case report and review of the literature Abstract Background: Intussusception caused by a lymphomatous mass is extremely rare in adults To date, only four cases of mantle cell lymphoma have intussusception as a RI PT treatment sequelae or complication Case presentation: A 72-year-old previously healthy male presented to the emergency department with an ileocolic intussusception related small bowel obstruction Laparoscopic examination showed two solid masses with the terminal ileum as the lead point, and a whitish mass was SC incidentally found at the gallbladder fundus Laparoscopic right hemicolectomy and cholecystectomy was performed and the pathological report declared mantle cell lesion at the gallbladder M AN U lymphoma of ileum and gallbladder Conclusion: This is the first reported case of incidental mantle cell lymphoma initially presented as intussusception with a skip Keywords: Mantle cell lymphoma; intussusception; ileocolic; gallbladder AC C EP TE D Running title: Mantle cell lymphoma with intussusception ACCEPTED MANUSCRIPT Introduction Mantle cell lymphoma (MCL) is a distinct type of B-cell lymphoma that RI PT comprises only 4% of non- Hodgkin’s lymphomas in the US and 8% in Europe.1 It affects middle-aged to older individuals with a median age of about 60, with marked male predominance Most patients present with stage III or IV disease, initially SC respond to rituximab-CHOP therapy but the remission period is short, which leads to M AN U a poor overall survival of 3-4 years The diagnosis of MCL is usually through immunophenotype over expression, and cyclin-D1 (also known as CCND1, BCL-1, B-cell lymphoma 1) is the most specific marker for confirmation Gastrointestinal involvement is common in most MCL patients, usually at a microscopic level under TE D negative endoscopic results Inflammation, ulceration, multiple lymphomatous polyposis (MLP) and mucosal thickening may also present endoscopically in MCL EP patients.2-3 To date, there were only four cases of intussusception reported related to AC C MCL, and most of them were related to complications from chemotherapy.4-6 We herein report a previously healthy patient who initially presented to emergency department due to ileocecal intussusception related to a small bowel obstruction, and for whom the final diagnosis, following laparoscopic right hemicolectomy and cholecystectomy, was mantle cell lymphoma involving the ileum, large intestine, appendix and gallbladder ACCEPTED MANUSCRIPT Case report A previously healthy 74-year-old male presented to the emergency department RI PT with nausea, vomiting and abdominal pain for two days He had suffered no weight loss or other constitutional symptoms recently Upon physical examination, the patient had slight distension around epigastric area, increased bowel sound and SC tenderness at the right lower quadrant However, there was no palpable M AN U lymphadenopathy at bilateral neck, axilla, or inguinal area Laboratory tests revealed normal neutrophil and hemoglobin levels, liver and renal function were within the normal range Laboratory examination disclosed white blood cell count of 12790/mm3 with 38% neutrophils, 9% monocytes, 50% lymphocytes, 2% TE D eosinophils and 0% basophils, platelet count of 336000/mm3, and hemoglobin concentration of 14.4 g/dL Lactate dehydrogenase was 289 U/L The levels of EP aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, AC C glucose, and electrolytes were within normal limits Computed tomography scan of the chest, abdomen, and pelvis showed intussusceptions at the ileocecal area, small bowel dilatation, and multiple hyperplastic mesentery lymph nodes in the intussuscepted area (Fig.1) An immediate colonscopy was conducted but failed to pass through the obstructed level at the ascending colon, and showed normal mucosal findings at the distal colon and ACCEPTED MANUSCRIPT rectum Laparoscopic examination was performed soon after, and a retrograde intussusception was noted at the terminal ileum and two-thirds of the ascending RI PT colon (Fig 2C) After reduction, the leading point was two adjacent solid masses at the ileum about 15 cm proximal to ileocecal valve Another 1.5 cm whitish mass was also noted at the fundus of gallbladder (Fig 2D) Finally, the patient underwent SC laparoscopic right hemicolectomy and cholecystectomy The recovery period was M AN U smooth without further events, and the patient discharged six days after the operation On gross examination, there were two gray-white, solid and fleshy masses protruding into the lumen from the terminal ileum wall: one ulcerative, fungating TE D mass measured 3.5 x 3.0 x 1.0 cm, and another flat-topped mass measured 4.0 x 3.5 x 0.5 cm Both tumors involved mucosa, submucosa, muscularis propria and EP subserosal layer, but left the serosa intact An additional 18 polyps in the cecum and AC C ascending colon were also present The mucosa of the appendix was thickened and occluded the lumen One enlarged lymph node measuring 1.6 x 1.0 x 1.0 cm was seen in the subserosal layer of the gallbladder fundus; considered as a neoplasm during the operation Microscopic sections of the ileal tumors showed mucosal ulceration and ill-demarcated aggregation lymphoma cells: small to medium-sized lymphoid cells ACCEPTED MANUSCRIPT with irregular nuclear contours, reminiscent of centrocytes Lamina propria is also expanded by the lymphoma cells On immunohistochemical study, the tumor cells RI PT were CD20(+), CD5(+), cyclinD1(+), bcl-2(+), CD3(-), CD10(-), CD23(-), and bcl-6(-)(Fig 3) Proliferation marker MIB1 is presented in approximately 15% to 18% of cells SC In this case, the patient and family refused chemotherapy due to old age, and M AN U multiple lymphadenopathy occurred just months after surgery Discussion Mantle cell lymphoma is a distinct type of mature B-cell neoplasm that accounts for approximately 3-10% of non-Hodgkin’s lymphoma.7 It is referred to TE D several aliases, such as lymphocytic lymphoma of intermediate differentiation, mantle zone lymphoma, centrocytic lymphoma Diffusion of nodular intermediate EP lymphocytic lymphoma tends to occur in middle-aged to older individuals with a AC C higher incidence in males.4, Patients usually present with stage III or IV disease, and more than third-quarter of them have extranodal involvement, such as spleen, bone marrow, and gastrointestinal (GI) tract.3 Multiple lymphoid polyposis (MLP) was first described by Cornes et al as a distinctive pattern of GI tract involvement as several long intestinal segments are infiltrated by white nodular or polypoid tumors Most patients with MLP will have MCL, but this presentation may also occur in ACCEPTED MANUSCRIPT follicular lymphoma, marginal zone lymphoma, adult T-cell leukemia/lymphoma, and angioimmunoblastic T-cell lymphoma.10-11 The immunophenotype of the MCL RI PT cells is typically CD20 (+), CD5 (+), CD10 (-), CD23 (-), and cyclin-D1 (+) (also known as CCND1, BCL-1, B-cell lymphoma 1) Cyclin-D1 was due to a translocation of the cyclin-D1 gene on 11q13 to the promoter of the immunoglobulin SC heavy chain on 14q32.7 Overexpression of cyclin-D1 can be detected in the tumor M AN U cells by fluorescence in situ hybridization (FISH) and had been suggested as the highly specific marker of MCL In various series, GI tract involvement may be seen in 10% - 30% MCL cases,3 however, two recent prospective reports showed a much higher rate The frequency of upper GI microscopic involvement was 43 % and 77%, TE D while lower GI microscopic involvement was 77 % and 88%.2-3 Antonio et al reported 92% of MCL patients had upper or lower GI tract infiltration in biopsy EP specimen while 63% had unremarkable gastroscopic examination and 71% had AC C normal colonscopic appearance with microscopic evidence of MCL under biopsy The ileocecal region is most commonly involved area, whereas the esophagus and anus are rarely affected.7-8 Multiple lymphomatous polyposis was commonly seen in MCL patients during endoscopic examination of the gastrointestinal tract,4 however, it may also present endoscopically as inflammation, ulceration, mucosal thickening, and tumoral masses ACCEPTED MANUSCRIPT 2-3 Chung et al reported MCL patients involving gastrointestinal tract presented bowel wall thickening or mass formation during computed tomography scan.4 RI PT Intussusception is rare in adults, and neoplasm usually presents as a lead point in most cases Malignant adenocarcinoma, metastatic tumor, and benign neoplasms as lipoma or Peutz-Jegher adenoma were the most common causes of SC intussusception.12 Malignant lymphoma is an uncommon cause of intussusception M AN U and accounts for less than % of cases.12 To date, only four cases of intussusception have been reported as disease sequelae in previously diagnosed MCL patients, and three of these four patients were reported as a complication after chemotherapy One patient had an intestinal lipoma as a lead point, which is irrelevant to the underlying TE D disease.4-6 In this case, the unique point is that intussusception related abdominal pain was the initial presentation of MCL without other detectable lymphadenopathy EP during thorough examination The whole segment of ileum, ileocecal valve, cecum, AC C ascending colon, appendix and even gallbladder, have at least a microscopic level of disease It also involved the regional lymph nodes The evidence supported our hypothesis that the origin site was the intestinal mucosa Gallbladder lymphoma or extrahepatic bile duct lymphoma presenting with symptoms of cholecystitis, cholelithiasis or jaundice are exceedingly rare Only one case regarding metastatic MCL in the gallbladder was found in the literature.13 ACCEPTED MANUSCRIPT Haresh et al reported 14 cases of gallbladder and extrahepatic bile duct lymphoma and reviewed an additional 52 cases in the literature Extranodal marginal zone RI PT lymphoma was the most common lymphoma type Other miscellaneous types include diffuse large B cell lymphoma, B-lymphoblastic lymphoma and follicular lymphoma, classical Hodgkin lymphoma, etc.14 In our case, the lesion at the tip of SC the gallbladder fundus was an accidental finding, and microscopically, the M AN U lymphoma cells involved both subserosal lymph node and the gallbladder submucosal layer The findings were compatible with previous reports as a microscopic invasion in macroscopical normal gallbladder mucosa.2, 14 MCL has a poor long-term response to current treatment strategies, for the most TE D commonly used R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone), the remission rate is good (75-96%) but brief in duration Despite the study of several other chemotherapy regimens, the median overall EP 15 AC C survival of MCL is only two to five years Conclusion Though mantle cell lymphoma is a hematological disease, it has a high propensity of gastrointestinal involvement Intussusception can be the initial presentation of this disease and surgeons should be aware of this and conduct a thorough investigation during surgery ACCEPTED MANUSCRIPT References: Vose JM Mantle cell lymphoma: 2012 update on diagnosis, risk-stratification, and clinical management American journal of hematology 2012; 87:604-609 Romaguera JE, Medeiros LJ, Hagemeister FB, et al Frequency of RI PT gastrointestinal involvement and its clinical significance in mantle cell SC lymphoma Cancer 2003; 97: 586-591 Salar A, Juanpere N, Bellosillo B, et al Gastrointestinal involvement in mantle M AN U cell lymphoma: a prospective clinic, endoscopic, and pathologic study The American journal of surgical pathology 2006; 30: 1274-1280 Chung HH, Kim YH, Kim JH, et al Imaging findings of mantle cell lymphoma TE D involving gastrointestinal tract Yonsei medical journal 2003; 44: 49-57 Grin A, Chetty R, Bailey D Mantle cell lymphoma as a rare cause of AC C 398-401 EP intussusception: a report of cases Annals of diagnostic pathology 2009; 13: Sucker C, Klima KM, Doelken G, et al Unusual sites of involvement in non-Hodgkin's lymphoma: Case Intussusception as a rare complication of mantle-cell lymphoma J Clin Onco 2002; 20: 4397-4398 Witzig, T E., Current treatment approaches for mantle-cell lymphoma J Clin Onco 2005; 23: 6409-6414 Argatoff LH, Connors JM, Klasa RJ, et al Mantle cell lymphoma: a ACCEPTED MANUSCRIPT clinicopathologic study of 80 cases Blood 1997;89 : 2067-2078 Cornes JS Multiple lymphomatous polyposis of the gastrointestinal tract RI PT Cancer 1961; 14: 249-257 10 Hashimoto Y, Nakamura N, Kuze T, et al Multiple lymphomatous polyposis of the gastrointestinal tract is a heterogenous group that includes mantle cell SC lymphoma and follicular lymphoma: analysis of somatic mutation of M AN U immunoglobulin heavy chain gene variable region Human pathology 1999; 30: 581-587 11 Kodama T, Ohshima K, Nomura K, et al Lymphomatous polyposis of the TE D gastrointestinal tract, including mantle cell lymphoma, follicular lymphoma and mucosa-associated lymphoid tissue lymphoma Histopathology 2005; 47: 467-478 EP 12 Chiang JM, Lin YS Tumor spectrum of adult intussusception Journal of AC C surgical oncology 2008; 98: 444-447 13 Pherson M, Yon JR, Wilhelm S, et al Mantle cell lymphoma metastasis to the gallbladder The American surgeon 2014; 80: e198-199 14 Mani H, Climent F, Colomo L, et al Gall bladder and extrahepatic bile duct lymphomas: clinicopathological observations and biological implications The American journal of surgical pathology 2010; 34: 1277-1286 ACCEPTED MANUSCRIPT 15 Romaguera JE, Fayad LE, McLaughlin P, et al Phase I trial of bortezomib in combination with rituximab-HyperCVAD alternating with rituximab, AC C EP TE D M AN U SC British journal of haematology 2010; 151: 47-53 RI PT methotrexate and cytarabine for untreated aggressive mantle cell lymphoma ACCEPTED MANUSCRIPT Figure Legends: Fig.1 Computed Tomography shows ileocecal intussusception related to small bowel obstruction without obvious regional lymphadenopathy RI PT (Fig A&B) Multilayers of bowel wall were noticed at right lower quadrant of abdomen in the horizontal plane (B) AC C EP (A) TE D M AN U colon in the sagittal plane SC (Fig C&D) The distal ileum was intussuscepted into two-third of the ascending (C) (D) ACCEPTED MANUSCRIPT Fig Laparoscopic findings: (A) Grossly clean peritoneum and liver surface with minimal clear ascites RI PT (B) Proximal small bowel dilatation due to obstruction (C) The mass-forming intussusception was located at right lower quadrant of abdomen (Arrow) (B) AC C EP (A) TE D M AN U SC (D) One 1.5 cm whitish mass noted at the fundus of gallbladder (Arrow) (C) (D) ACCEPTED MANUSCRIPT Fig.3 Microscopic findings: (A) Ileal mass with mantle cell lymphoma (12.5x) which lead to luminal occlusion (12.5x) RI PT (B) The lymphoma cells distended the mucosa and submucosa of the appendix, (C) Gallbladder mucosa is involved by lymphoma cells (40x) SC (D) Cyclin-D1 over-expression was seen in abundant lymphoid infiltration of the (B) AC C EP (A) TE D M AN U gallbladder wall (200x) (C) (D) ... MANUSCRIPT Haresh et al reported 14 cases of gallbladder and extrahepatic bile duct lymphoma and reviewed an additional 52 cases in the literature Extranodal marginal zone RI PT lymphoma was the. .. lymphoma presented as enteric intussusception and involved gallbladder: a case report and review of the literature Abstract Background: Intussusception caused by a lymphomatous mass is extremely rare... count of 336000/mm3, and hemoglobin concentration of 14.4 g/dL Lactate dehydrogenase was 289 U/L The levels of EP aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, AC