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Primary Gastric T-Cell Lymphoma Not Associated with
Human T-Lymphotropic Virus Type 1
Tomoaki Ito
1
, Koichi Sato
1
, Hiroshi Maekawa
1
, Mutsumi Sakurada
1
, Hajime Orita
1
and Ryo Wada
2
Affiliations:
1
Department of Surgery and
2
Department of Pathology, Juntendo Shizuoka Hospital, Juntendo University School of Medicine, Shizuoka, Japan
ABSTRACT
Most primary gastric lymphomas are of B-cell origin, whereas a gastric T-cell lymphoma is extremely rare. We report a 73-year-old Japanese
man with primary gastric T-cell lymphoma not associated with human T-lymphotropic virus type 1 (HTLV-1). In March 2009, the patient was
admitted to our hospital with the chief complaint of weight loss of 6 kg over 6 months. HTLV-1 was negative by the particle agglutination (PA)
method. An upper gastrointestinal endoscopy revealed a large ulcerated tumor with a partially cleaved bank at the greater curvature of the
cardia. A computed tomography scanning demonstrated thickening of the gastric wall and tumor invasion into the liver and spleen; no
apparent lymph node swelling was noted in the chest or abdomen. Total gastrectomy with splenectomy and partial resection of the
diaphragm and liver were performed in May 2009. Hematoxylin and eosin staining of the surgical specimens showed diffuse infiltration with
medium atypical lymphocytes. Immunohistochemically, the cells were positive for CD3, CD8, CD45RO, and CD30, but negative for CD4 and
CD79a. Based on these histological findings, the tumor was diagnosed as a diffuse, medium type according to the Lymphoma Study Group
classification and peripheral T-cell lymphoma, unspecified as per the WHO histological classification. Currently, at 17 months since
diagnosis, the patient is still alive.
Keywords: T-cell lymphoma, gastric lymphoma, HTLV-1
Correspondence: Tomoaki Ito, Department of Surgery, Juntendo Shizuoka Hospital, Juntendo University School of Medicine, 1129 Nagaoka,
Izunokuni-shi, Shizuoka 410-2295, Japan. Tel: (81)-55-948-3111; Fax: (81)-55-946-0514; e-mail: tomo-ito@k4.dion.ne.jp
INTRODUCTION
Most primary gastric lymphomas are of B-cell origin,
whereas a gastric T-cell lymphoma is extremely rare.
1
The
majority of primary gastric T-cell lymphoma cases are
secondary to adult T-cell leukemia/lymphoma (ATL).
2
Human
T-lymphotropic virus type 1 (HTLV-1) is a retrovirus and is
prevalent in southern Japan, the Caribbean Basin, and Africa.
HTLV-1 infection is widely accepted as a cause of ATL.
3
The
clinicopathological features of primary gastric T-cell lym-
phoma remain to be clarified. Here, we report a case of
primary gastric T-cell lymphoma not associated with HTLV-1,
and compare the findings from our case with those from
other cases reported in Japan.
CASE REPORT
In March 2009, a 73-year-old Japanese man was admitted to
our hospital with the chief complaint of weight loss of 6 kg over
6 months. Physical examination on admission revealed a body
height of 160 cm, weight of 49.0 kg, blood pressure of 159/81
mmHg, and a regular pulse of 61 beats/min. History disclosed
that he was not born in a nonendemic area for HTLV-1. His
lymph nodes, tumor, liver, or spleen were not palpable.
Laboratory examination showed mild anemia (RBC, 394
10
4
/mL; Hb, 12.1 g/dL; Hct, 36.3%) and a slightly increased
leukocyte count (10 200/mL); the serum level of soluble IL-2
receptor was 428 U/mL. The level of carcinoembryonic antigen,
a tumor marker, was normal and HTLV-1 was negative by the
particle agglutination (PA) method.
An upper gastrointestinal series demonstrated a large tumor
at the gastric cardia occupying the posterior wall (Figure 1).
Upper gastrointestinal endoscopy showed a large ulcerated
tumor with a partially cleaved bank at the greater curvature of
the cardia (Figure 2). Hematoxylin and eosin (H & E) staining
of the biopsy specimens revealed medium atypical lympho-
cytes, suggesting a malignant gastric lymphoma. However, it
was difficult to establish a definitive diagnosis because of the
presence of necrosis and crushed cells.
A computed tomography scan showed thickening of the
gastric wall and tumor invasion of the liver and spleen, but
there was no apparent swelling of the lymph nodes in either
the chest or abdomen (Figure 3).
On laparotomy we noted that the tumor had directly invaded
both the diaphragm and liver. Total gastrectomy, splenect-
omy, and partial resection of the diaphragm and liver were
then performed in May 2009.
In the resected specimen, a type 2 tumor measuring
10.0 cm9.0 cm was identified at the greater curvature of
the upper body of the stomach (Figure 4). H & E staining
of the surgical specimen showed diffuse infiltration with
medium atypical lymphocytes (Figure 5) and infiltration of
lymphoma cells into the liver and the regional lymph nodes.
Immunohistochemically, the cells were positive for CD3,
ANNALS OF GASTROENTEROLOGY & HEPATOLOGY CASE REPORT
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CD8, CD45RO (Figure 6A), and CD30, but negative for CD4
and CD79a(Figure 6B). Based on these histological findings,
the tumor was diagnosed as a diffuse, medium type according
to the Lymphoma Study Group (LSG) classification
4
and
peripheral T-cell lymphoma, unspecified as per the WHO
histological classification. According to the Lugano Interna-
tional Conference classification,
5
this case was designated as
Stage IIE.
Postoperatively, the patient was treated by adjuvant che-
motherapy with cyclophosphamide, doxorubicin, vincristine,
and prednisolone. After chemotherapy, the patient was
treated with radiotherapy. Currently, at 17 months since
diagnosis, the patient is still alive.
DISCUSSION
Primary gastrointestinal lymphoma is the most frequent
type of extranodal malignant lymphoma, accounting for 30
45% of all extranodal lymphomas.
69
Dawson et al.
10
proposed the following five criteria for diagnosing primary
gastrointestinal malignant lymphoma: (1) superficial lymph
nodes not palpable, (2) no swelling of the mediastinal lymph
nodes as identified on a radiograph, (3) normal leukocyte
counts and fractions on a peripheral-blood profile, (4) the
main lesion is in the gastrointestinal tract, and (5) no tumors
identified in the liver or spleen.
Most cases of primary gastric malignant lymphoma are
B-cell lymphoma, whereas gastric T-cell lymphoma is rare.
1
The incidence of gastric T-cell lymphoma among patients
with primary gastric lymphoma ranges from 6% to 10%.
1113
Figure 1. Upper gastrointestinal series demonstrating a large tumor
occupying the posterior wall at the gastric cardia.
Figure 2. Upper gastrointestinal endoscopy showing a large ulcerated
tumor with a partially cleaved bank at the greater curvature of the cardia.
The elevated area near the ulceration was covered with normal mucosa
overlying a submucosal tumor.
Figure 3. Computed tomography scan demonstrating the thickening of the
gastric wall and tumor invasion into the liver and spleen, no swelling of
lymph nodes is apparent in either the chest or abdomen.
Figure 4. Macroscopic examination of the resected specimen shows a
tumor measuring 10.0 cm9.0 cm at the greater curvature of the upper
body of the stomach. A protruding area with a swollen fold was found by the
ulceration showing as scirrhous gastric cancer.
Annals of Gastroenterology & Hepatology
AGH 2012; 3:(1). March 2012 142 www.slm-gastroenterology.com
Most cases of primary gastric T-cell lymphoma are secondary
to ATL.
2
HTLV-1 is a retrovirus, and is prevalent in southern
Japan, the Caribbean Basin, and Africa. HTLV-1 infection is
widely accepted as a cause of ATL, HTLV-1 associated
myelopathy, and immunosuppressive disorders.
3
The inci-
dence of HTLV-1 associated primary gastric T-cell lymphoma
among patients with primary gastric T-cell lymphoma ranges
from 40% to 75%.
1416
We reviewed the literature describing 50 cases
2,1640
of
primary gastric T-cell lymphoma not associated with HTLV-1
in Japan, including our patient (Table 1). The median patient
age was 58 years (range, 3383; data for 18 cases were not
available) and the ratio of males to females was 33:17.
Regarding the location, nine lesions (18%) were located in the
cardia, 21 (42%) in the body, six (12%) in the cardia to body,
two (4%) in the antrum to body, two (4%) in the antrum, and
in nine patients the location was not stated. With regard to
the appearance of the lymphoma, the superficial type was
found in seven cases (14%), a protruding tumor in 16 (32%),
an ulcerated tumor in 26 (52%), and no description was
stated for one case. According to the LSG classification,
4
these tumors consisted of two (4%) diffuse small cell types,
27 (54%) diffuse large cell types, 12 (24%) diffuse medium
cell types, three (6%) diffuse mixed cell types, and six (12%)
diffuse pleomorphic cell types.
According to the Lugano International Conference classifi-
cation for tumors,
5
8 (16%) were classified as Stage I, 10
(20%) were classified as Stage II1, 3 (6%) were classified as
Stage II2, 10 (20%) were classified as Stage IIE, 7 (14%) were
classified as Stage IV, and in 12 cases the classification was
not established.
Treatment data were available for 30 of the 50 reported
patients. A combination of surgical resection and chemother-
apy was performed in 15 (30%) patients. Surgery alone was
performed in nine patients (18%), chemotherapy alone in
four patients (8%), and chemotherapy and radiotherapy were
conducted in one patient (2%). Most cases of the 50 reported
patients performed surgery.
However, recently published studies have suggested that
using primary chemotherapy and radiation without surgery
can produce outcomes similar to that obtained with surgery
and adjuvant treatment.
41
The treatment for primary gastric T-cell lymphoma has yet
to be established. However, Yachida et al.
39
reported that a
case in which surgery was performed followed by chemother-
apy remained free of recurrence for 86 months. They
concluded that primary gastric T-cell lymphoma without
HTLV-1 should be managed in the same way as the more
common diffuse large B-cell type gastric lymphomas.
In our case, we performed surgery before chemotherapy
because it was difficult to establish a definitive diagnosis
based on the biopsy specimen obtained by upper gastro-
intestinal endoscopy and there was a risk for perforation
and hemorrhage. We conclude that the primary resection is
available to precise histologic classification and staging in
cases that it was difficult to establish a definitive diagnosis,
Figure 5. Hematoxylin and eosin staining of the surgical specimen showing
diffuse infiltration with medium atypical lymphocytes. Magnification 100 .
Figure 6. A) Immunohistochemical analysis showing cells positive for
CD45RO, B) but negative for CD79a. Magnification 100.
Primary gastric T-cell lymphoma
www.slm-gastroenterology.com 143 AGH 2012; 3:(1). March 2012
and avoidance of complications such as perforation or
hemorrhage. And chemotherapy is able to be done
smoothly.
Nakamura et al.
11
reported 455 primary gastrointestinal
lymphoma cases wherein patients with T-cell lymphoma had
poorer overall survival and event-free survival rates than
patients with high-grade B-cell lymphoma. A review of
previously reported primary gastric T-cell lymphoma cases
also indicated that the prognosis was better in cases without
HTLV-1 infection.
32,39
Kawamoto et al.
40
reported 20 primary gastric T-cell lym-
phoma cases without HTLV-1. They stated that the 5-year
survival rate was 54% and that the cases in an early clinical
stage (I/II) showed a better prognosis than cases in Stages
IIE/IV. Therefore, they concluded that a medium-sized cell
lymphoma was a significantly better prognostic factor.
Since our case was a medium-sized cell lymphoma but was
classified as Stage IIE, it was necessary that we closely
observe this patient in the future. Moreover, additional
reports of primary gastric T-cell lymphoma need to be
accumulated to clarify the clinicopathological features of
this rare lymphoma.
Disclosure: Dr Tomaki Ito is the principal investigator of this
report.
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No. of cases 50
Age 3383 (median age 58) (NA 18 cases)
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Location
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body 21 (42%)
cardia to body 6 (12%)
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antrum 2 (4%)
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NA 9
Appearance
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ulcerated 26 (52%)
NA 1
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Diffuse,medium 12 (24%)
Diffuse,mixed 3 (6%)
Diffuse,pleomorphic 6 (12%)
Lugano International Conference
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IIE 10 (20%)
IV 7 (14%)
NA 12
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Op, Cx 15 (30%)
Op, Cx, Ra 1 (2%)
Cx 4 (8%)
Cx, Ra 1 (2%)
NA 20
NA, not available; Op, operation; Cx, chemotherapy; Ra, radiation therapy
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