Solitary primary gastric mantle cell lymphoma.

Abstract

Mantle cell lymphoma (MCL) is a relatively rare subgroup of non-Hodgkin's lymphoma that is characterized by an aggressive and severe disease course with frequent involvement of regional lymph nodes and/or early metastasis. Because most cases of MCL are diagnosed in the advanced stages, clinical data on extranodal or early stage MCL is lacking, and MCL that is both extranodal and diagnosed during the early stages is even more rare. There have been several case reports on primary gastric MCL, which comprise a type of extranodal MCLs. However, to our knowledge, there have been no reports on solitary primary gastric MCL without regional lymph node involvement or distant metastasis. Recently, the authors experienced an uncommon case of MCL with the aforementioned characteristics that was managed with chemotherapy followed by allogenic stem cell transplantation.

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case report
Gut and Liver, Vol. 5, No. 4, December 2011, pp. 527-531
Solitary Primary Gastric Mantle Cell Lymphoma
Chang Ha Kim*, Hoon Jai Chun*, Tae Hyung Kim*, Wonho Jung*, Sunwon Kim*, Jong Jin Hyun*, Bora Keum*, Yeon
Seok Seo*, Yong Sik Kim*, Yoon Tae Jeen*, Hong Sik Lee*, Soon Ho Um*, Chang Duck Kim*, Ho Sang Ryu*, and Insun
Kim†
*Division of Gastroenterology and Hepatology, Department of Internal Medicine, and †Department of Pathology, Korea University College of
Medicine, Seoul, Korea
Mantle cell lymphoma (MCL) is a relatively rare subgroup of
non-Hodgkin’s lymphoma that is characterized by an aggres-
sive and severe disease course with frequent involvement
of regional lymph nodes and/or early metastasis. Because
most cases of MCL are diagnosed in the advanced stages,
clinical data on extranodal or early stage MCL is lacking, and
MCL that is both extranodal and diagnosed during the early
stages is even more rare. There have been several case
reports on primary gastric MCL, which comprise a type of ex-
tranodal MCLs. However, to our knowledge, there have been
no reports on solitary primary gastric MCL without regional
lymph node involvement or distant metastasis. Recently, the
authors experienced an uncommon case of MCL with the
aforementioned characteristics that was managed with che-
motherapy followed by allogenic stem cell transplantation.
(Gut Liver 2011;5:527-531)
Key Words: Mantle cell lymphoma; Stomach; Primary; Soli-
tary, Cyclin D1 positive
INTRODUCTION
Mantle cell lymphoma (MCL) is a unique subgroup of non-
Hodgkin’s lymphoma, which accounts for approximately 6%
of non-Hodgkin’s lymphoma. MCL is characterized by t(11;14)
(q13;q32) and cyclin D1 overexpression in a vast majority of
cases. It is also characterized by aggressive disease course with
many cases being diagnosed in the advanced stages, and fre-
quent involvement of regional lymph nodes and/or early metas-
tasis.1 In addition to the regional lymph nodes, extranodal sites
such as gastrointestinal tract are frequently involved. According
to previous studies, the frequency of extranodal involvement
Correspondence to: Hoon Jai Chun
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, 126-1 Anamdong 5-ga,
Seongbuk-gu, Seoul 136-705, Korea
Tel: +82-2-920-5699, Fax: +82-2-953-1943, E-mail: drchunhj@chol.com
Received on June 5, 2010. Accepted on July 19, 2010.
pISSN 1976-2283 eISSN 2005-1212 http://dx.doi.org/10.5009/gnl.2011.5.4.527
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0)
which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
was reported up to 80%, and 15% to 30% of MCL had gastro-
intestinal tract involvement.2,3 However, solitary and primary
involvement of extranodal sites is rare, and solitary primary ex-
tranodal MCL diagnosed in the early stage is even rarer. To the
best of our knowledge, a few cases on primary gastric MCL were
reported,4-6 but there had been no documented reports dealing
with solitary primary gastric MCL without regional lymph node
involvement or distant metastasis.
Herein, we report the first case of primary gastric MCL which
was found as solitary lesion in the stomach without any region-
al lymph nodes involvement or distant metastasis.
CASE REPORT
A 48-year-old man presented to the department of gastro-
enterology with epigastric soreness of 8 months’ duration. On
arrival, his vital signs were stable: blood pressure was 110/70
mm Hg, pulse rate was 70 beats/min, and body temperature was
36.8oC. On physical examination, no mass could be palpated, no
organ enlargement such as hepatosplenomegaly or lymph node
enlargement was noted, and neither tenderness nor rebound
tenderness was present. Initial laboratory findings were as fol-
lows: hemoglobin, 13.0 g/dL; white blood cell count, 5,750/μL
(45.6%: neutrophils); platelet count, 215,000/μL; blood urea ni-
trogen, 13 mg/dL; creatinine, 1.1 mg/dL; total protein, 6.4 g/dL;
albumin, 3.4 g/dL; total bilirubin, 0.62 mg/dL; alkaline phos-
phatase, 70 IU/L; alanine aminotransferase, 24 IU/L; aspartate
aminotransferase, 23 IU/L; gamma glutamyl transferase, 13 IU/
L; lactate dehydrogenase, 388 IU/L; prothrombin time, 13.1 sec
(INR, 0.98); amylase, 83 IU/L; ESR, 17 mm/hr; CRP, 2.570 mg/L;
alpha-fetoprotein, 7.1 ng/mL. Hepatitis B surface antigen (HB-
sAg) was positive, and hepatitis B envelope antigen/antibody

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528 Gut and Liver, Vol. 5, No. 4, December 2011
(HBeAg/Ab) was positive/negative. Antibody against hepatitis
B surface antigen (anti-HBs Ab) and antibody against hepati-
tis C (anti-HCV Ab) were all negative. Initial gastrofiberscopic
examination showed two masses: a 3×3×1.5 cm sized smaller
crater-like ulcerating mass with central ulceration (1×1 cm) on
the high-body anterior wall and a 6.5×4.5×2.5 cm sized larger
swimming goggle shaped ulcerofungating mass with central
ulceration (2.5×2 cm) on the low-body along the greater curva-
ture (Fig. 1).
The biopsy specimen obtained from the low-body showed
Fig. 1. Initial gastrofiberscopy shows
a goggle-shaped ulcerofungating
mass on the low body along the
greater curvature (A) and a crater-
like ulcerative mass with bleeding
on the high-body anterior wall (B).
Fig. 2. Gastric mucosal biopsy from the low body shows diffuse infiltration of medium-sized lymphoid cells with a dispersed chromatin pattern (A,
H&E stain, ×40; B, ×400).
Fig. 3. Immunohistochemistry with the same specimen from Fig. 2 shows that these cells were diffusely and strongly positive for CD20 (A, ×40)
and cyclin D1 (B, ×400).

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Kim CH, et al: Solitary Primary Gastric Mantle Cell Lymphoma 529
diffuse infiltration of relatively monotonous, medium-sized
lymphoid cells with dispersed chromatin pattern (Fig. 2). These
cells were diffusely and strongly positive for CD20 (Fig. 3A),
CD5, CD43, and cyclin D1 (Fig. 3B), but negative for CD3, CD21,
CD10, and TdT. Some bcl 6-positive cells were also seen. Most
cells were positive for Ki-67 (Fig. 4A). Therefore, it could be di-
agnosed as mantle cell lymphoma, blastoid variant. The biopsy
specimen obtained from the high-body showed focal lymphoid
infiltration in lamina propria (Fig. 4B). These infiltrates were
mixture of CD20-positive B cells and CD3-positve T cells. How-
ever, immunostain for cyclin D1 was negative and Ki-67 label-
ing was low. Because the mucosa was intact and the lymphoid
infiltrates were localized, the biopsy might be obtained from the
periphery of the ulcerating lesion, representing chonic follicular
gastritis. Therefore, the possibility of concomitant MCL could
not be completely ruled out, which might have been due to in-
adequate amount of biopsy specimen.
On endoscopic ultrasonography, the larger swimming goggle
shaped ulcerofungating mass on the low-body seemed to have
advanced to the muscularis propria without involvement of
the serosa (Fig. 5). Abdominal computed tomography (CT) scan
showed 6.5×2.5 cm sized lobulated enhancing mass with ulcer-
ation in the center, which was located on the low-body. How-
ever, neither definite metastatic lesion nor regional lymph node
involvement was seen. Colonoscopy, chest CT, bone scan, PET-
CT scan, and bone marrow biopsy were performed for further
staging work-up but no regional lymph node involvement or
distant metastasis was found. Conventional cytogenetic analysis
was also performed with the specimen obtained from the bone
marrow biopsy; the karyotype was 46,XY and no abnormal
clone was detected.
Therefore, the patient was diagnosed as stage 1E MCL, and
was treated with hyperCVAD/MA (cyclophosphamide 300 mg/
m2, vincristine 2 mg, doxorubicin 50 mg/m2, dexamethasone 40
mg; alternated with methotrexate 1 g/m2 and cytarabine 1 g/m2
every 4 weeks or earlier). Follow-up gastrofiberscopy performed
26 days after third cycle showed that the mass on the high-body
had been completely resolved leaving behind only a scar, and
the lesion on the low-body had markedly decreased in size (Fig.
6A).
Because of prolonged febrile neutropenia after third cycle,
the dose was reduced by 25% on fourth cycle. The patient
was scheduled to undergo stem cell transplantation after the
completion of fifth cycle, but since not enough stem cell could
be collected for autologous stem cell transplantation, the patient
underwent allogenic stem cell transplantation instead 69 days
after fifth cycle. Follow-up gastrofiberscopy performed 40 days
after allogenic stem cell transplantation showed that the mass
on the low-body had completely resolved (Fig. 6B). He has com-
pletely recovered afterwards and is currently being followed-
Fig. 4. Immunohistochemistry with the specimen from the low body shows high Ki-67 labeling (A, ×400), but the specimen from the high body,
which showed lymphoid infiltrates, was negative for cyclin D1 (B, ×40).
Fig. 5. On endoscopic ultrasonography, the mass on the low body
along the greater curvature shows involvement of the muscularis
propria (arrows) with an intact serosa.

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530 Gut and Liver, Vol. 5, No. 4, December 2011
up at the outpatient department without any complaints and
further complications.
DISCUSSION
MCL is a relatively uncommon and aggressive disorder, being
incurable in many cases, with median survival of three to four
years in affected patients.7
Current World Health Organization guideline suggests that
morphological examination and immunophenoty ping, with
demonstration of cyclin D1 protein overexpression and/or
t(11;14)(q13;q32), are needed for confirmative diagnosis of
MCL.8 Morphologically, MCL is generally classifyed into several
subgroups: classic, small cell, blastoid, marginal zone-like, and
pleomorphic with some interplay between them. Among these
subgroups, the blastoid subgroup has the worst prognosis and it
is composed of variable cell population in size and shape, with
frequent mitotic figures, oval to irregular nuclear contours, pale
cytoplasm, and prominent nucleoli.7,9,10 Immunophenotypically,
MCL resembles that of a mature B-lymphocyte (CD10-, CD19+,
CD20+, CD22+, CD43+, CD79a+) with coexpression of the T-cell
antigen CD5; in contrast to CLL, cells are usually CD23 nega-
tive.11 In addition, cyclin D1 is almost always overexpressed,
making it the most important and useful finding for diagnosing
MCL.7,9,10 Furthermore, t(11;14)(q13;32) is also seen in most of
the MCL patients, although some cases of t(11;14)(q13;32) nega-
tive MCL have been reported.12-15 However, chromosomal study
with the lymphoma mass was not performed in this patient.
In general, early stage MCL is rare since MCL is diagnosed in
the advanced stages commonly accompanied by regional lymph
node involvement, hepatosplenomegaly, bone-marrow involve-
ment, and leukemic spread.7,9 Primary focus of MCL being other
than the lymph nodes, i.e., extranodal, is also rare. There have
been some case reports on primary gastric MCL, but systemic
involvement4,5 or regional lymph node involve ment6 was al-
ways present. There was one case report on solitary primary
gastric MCL, but gastric MCL was accompanied by synchronous
early gastric cancer in this case.16 Primary extranodal MCL
without regional involvement and/or distant metastasis is even
rarer, which has been reported by Estrozi et al.;17 it was primary
cutaneous blastoid subgroup of MCL in right temporal region
without regional lymph node involvement and distant metas-
tasis (stage 1E). As far as we know there have been no reports
on isolated primary gastric MCL in which solitary mass in the
stomach was the only tumor focus without regional lymph node
involvement and/or distant metastasis.
Unfortunately there is no established standard treatment
guideline in patients with MCL. However, the consensus for
the treatment of MCL is either with myeloablative regimens
followed by autologous stem cell transplantation after ini-
tial CHOP- (cyclophosphamide, vincristine, doxorubicin, and
prednisone) or DHAP- (dexamethaso ne, high-dose Ara-C, and
cisplatin) like induction therapy, or with upfront dose intensifi-
cation (HyperCVAD/MA plus rituximab, a monoclonal antibody
against the protein CD20).1 But, since MCL has very aggressive
disease course and is often diagnosed in the advanced stages,
the treatment is often unsuccessful. Despite of the initial re-
sponse to chemotherapy, the disease may relapse in many pa-
tients. Therefore, in order to improve the treatment outcomes,
various intensive chemotherapy combinations, radiotherapy,
stem cell transplantation, and molecular targeted approaches
have been tried. Among aforementioned three cases of primary
gastric MCL, one case reported a 60-year-old man with systemic
lymph node involvement who was treated with HyperCVAD/
MA plus rituximab followed by stem cell transplantation. He
had no recurrence for 50 months thereafter.4 Another case re-
ported a 65-year-old man with synchronous colonic MCL who
was treated with COP (cyclophosphamide, vincristine, predni-
sone). He also had a complete resolution after six cycles. In the
last case report, a 74-year-old man with regional lymph node
involvement suffering from long-standing crohn’s disease was
treated with rituximab-CHOP. The patient had maintained com-
plete remission state for 18 months after completion of 2 cycles.
In our case, the patient was very responsive to HyperCVAD/
MA, showing dramatic size reduction of the gastric MCL on
follow-up gastrofiberscopy resulting in complete remission. But
unfortunately, he could not undergo autologous stem cell trans-
plantation because not enough stem cells could be collected
Fig. 6. After the third cycle of che-
motherapy, the huge ulcerofungat-
ing mass on the low-body along
the greater curvature is markedly
reduced in size (A). After allogenic
stem cell transplantation, the lesion
has completely resolved, leaving be-
hind only a scar (B).

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Kim CH, et al: Solitary Primary Gastric Mantle Cell Lymphoma 531
for autologous stem cell transplantation. This might have been
due to bone marrow suppression after intensive chemotherapy.
Due to the fact that no established standard treatment guideline
exist, not to mention that for each stages of MCL, many doc-
tors follow similar treatment protocol regardless of the stage at
diagnosis and thus managing toxicity is another problem MCL
patents have to face.
CONFLICTS OF INTEREST
No potential conflict of interest relevant to this article was
reported.
REFERENCES
1. Dreyling M, Hiddemann W; European MCL Network. Current
treatment standards and emerging strategies in mantle cell lym-
phoma. Hematology Am Soc Hematol Educ Program 2009:542-
551.
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 involve-
ment in mantle cell lymphoma: a prospective clinic, endoscopic,
and pathologic study. Am J Surg Pathol 2006;30:1274-1280.
4. Kikuchi T, Asano N, Noguchi T, et al. A case of primary gas-
tric mantle cell lymphoma. Nihon Shokakibyo Gakkai Zasshi
2009;106:1168-1176.
5. Pitigoi D, Stoica V, Stoia R, Dobrea C, Becheanu G, Diculescu M.
Gastric and colonic mantle cell lymphoma - incidental discovery.
J Gastrointestin Liver Dis 2009;18:85-88.
6. Raderer M, PM, Pe A, Birkner T, Streubel B, Chott A. Primary gas-
tric mantle cell lymphoma in a patient with long standing history
of Crohn’s disease. Leuk Lymphoma 2004;45:1459-1462.
7. Jares P, Campo E. Advances in the understanding of mantle cell
lymphoma. Br J Haematol 2008;142:149-165.
8. Jaffe ES, Harris NL, Diebold J, Muller-Hermelink HK. World Health
Organization classification of neoplastic diseases of the hemato-
poietic and lymphoid tissues. A progress report. Am J Clin Pathol
1999;111(1 Suppl 1):S8-S12.
9. Swerdlow SH, Campo E, Harris NL, et al. WHO classification of
tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon:
IARC, 2008.
10. Pileri SA, Ascani S, Sabattini E, et al. The pathologist’s view point.
Part I--indolent lymphomas. Haematologica 2000;85:1291-1307.
11. Weigert O, Unterhalt M, Hiddemann W, Dreyling M. Mantle cell
lymphoma: state-of-the-art management and future perspective.
Leuk Lymphoma 2009;50:1937-1950.
12. Rosenwald A, Wright G, Wiestner A, et al. The proliferation gene
expression signature is a quantitative integrator of oncogenic
events that predicts survival in mantle cell lymphoma. Cancer Cell
2003;3:185-197.
13. Hunt KE, Reichard KK, Wilson CS. Mantle cell lymphoma lacking
the t(11;14) translocation: a case report and brief review of the
literature. J Clin Pathol 2008;61:869-870.
14. Fu K, Weisenburger DD, Greiner TC, et al. Cyclin D1-negative
mantle cell lymphoma: a clinicopathologic study based on gene
expression profiling. Blood 2005;106:4315-4321.
15. Yatabe Y, Suzuki R, Tobinai K, et al. Significance of cyclin D1
overexpression for the diagnosis of mantle cell lymphoma: a clini-
copathologic comparison of cyclin D1-positive MCL and cyclin
D1-negative MCL-like B-cell lymphoma. Blood 2000;95:2253-
2261.
16. Chong Y, Shin JJ, Cho MY, Cui Y, Kim HY, Park KH. Synchronous
primary gastric mantle cell lymphoma and early gastric carci-
noma: a case report. Pathol Res Pract 2008;204:407-411.
17. Estrozi B, Sanches JA Jr, Varela PC, Bacchi CE. Primary cutaneous
blastoid mantle cell lymphoma-case report. Am J Dermatopathol
2009;31:398-400.