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

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: S2311-30061

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: 7 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.

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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

Affiliations: Department of pathology1, Department of surgery2, E-DA hospital and E-DA Cancer Hospital3, I-Shou University4

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

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

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

Acknowledgments and credits: Nil

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

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Address: No.21, Yida Rd., Yanchao Dist., Kaohsiung City 824, Taiwan

Phone: 886-7-6150011-2983

E-mail: i5491142@gmail.com

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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

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 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; ileocolic; gallbladder

Running title: Mantle cell lymphoma with intussusception

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1 Introduction

Mantle cell lymphoma (MCL) is a distinct type of B-cell lymphoma that

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

respond to rituximab-CHOP therapy but the remission period is short, which leads to

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

negative endoscopic results Inflammation, ulceration, multiple lymphomatous

polyposis (MLP) and mucosal thickening may also present endoscopically in MCL

patients.2-3 To date, there were only four cases of intussusception reported related to

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

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2 Case report

A previously healthy 74-year-old male presented to the emergency department

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

tenderness at the right lower quadrant However, there was no palpable

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%

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

aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine,

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

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rectum Laparoscopic examination was performed soon after, and a retrograde

intussusception was noted at the terminal ileum and two-thirds of the ascending

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

laparoscopic right hemicolectomy and cholecystectomy The recovery period was

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

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

subserosal layer, but left the serosa intact An additional 18 polyps in the cecum and

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

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with irregular nuclear contours, reminiscent of centrocytes Lamina propria is also

expanded by the lymphoma cells On immunohistochemical study, the tumor cells

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

In this case, the patient and family refused chemotherapy due to old age, and

multiple lymphadenopathy occurred just 3 months after surgery

3 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

several aliases, such as lymphocytic lymphoma of intermediate differentiation,

mantle zone lymphoma, centrocytic lymphoma Diffusion of nodular intermediate

lymphocytic lymphoma tends to occur in middle-aged to older individuals with a

higher incidence in males.4, 8 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 9

Most patients with MLP will have MCL, but this presentation may also occur in

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follicular lymphoma, marginal zone lymphoma, adult T-cell leukemia/lymphoma,

and angioimmunoblastic T-cell lymphoma.10-11 The immunophenotype of the MCL

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

heavy chain on 14q32.7 Overexpression of cyclin-D1 can be detected in the tumor

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%,

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

specimen while 63% had unremarkable gastroscopic examination and 71% had

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

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2-3

Chung et al reported MCL patients involving gastrointestinal tract presented

bowel wall thickening or mass formation during computed tomography scan.4

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

intussusception.12 Malignant lymphoma is an uncommon cause of intussusception

and accounts for less than 1 % 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

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

during thorough examination The whole segment of ileum, ileocecal valve, cecum,

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

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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

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

the gallbladder fundus was an accidental finding, and microscopically, the

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

commonly used R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin,

vincristine, prednisolone), the remission rate is good (75-96%) but brief in duration

15

Despite the study of several other chemotherapy regimens, the median overall

survival of MCL is only two to five years

5 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

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References:

1 Vose JM Mantle cell lymphoma: 2012 update on diagnosis, risk-stratification,

and clinical management American journal of hematology 2012; 87:604-609

2 Romaguera JE, Medeiros LJ, Hagemeister FB, et al Frequency of

gastrointestinal involvement and its clinical significance in mantle cell

lymphoma Cancer 2003; 97: 586-591

3 Salar A, Juanpere N, Bellosillo B, et al Gastrointestinal involvement in mantle

cell lymphoma: a prospective clinic, endoscopic, and pathologic study The

American journal of surgical pathology 2006; 30: 1274-1280

4 Chung HH, Kim YH, Kim JH, et al Imaging findings of mantle cell lymphoma

involving gastrointestinal tract Yonsei medical journal 2003; 44: 49-57

5 Grin A, Chetty R, Bailey D Mantle cell lymphoma as a rare cause of

intussusception: a report of 2 cases Annals of diagnostic pathology 2009; 13:

398-401

6 Sucker C, Klima KM, Doelken G, et al Unusual sites of involvement in

non-Hodgkin's lymphoma: Case 3 Intussusception as a rare complication of

mantle-cell lymphoma J Clin Onco 2002; 20: 4397-4398

7 Witzig, T E., Current treatment approaches for mantle-cell lymphoma J Clin

Onco 2005; 23: 6409-6414

8 Argatoff LH, Connors JM, Klasa RJ, et al Mantle cell lymphoma: a