4. DISCUSSION
The GI tract is the most common site of extra-nodal lymphoma
involvement. Primary GIL accounts for 30-40% of extranodal lymphomas
and 15-20% of all non-Hodgkin’s lymphomas [1,19,20]. In majority of
studies, stomach is the commonly affected site followed by small
intestine. Stomach (50–60%) is the commonest site followed by small
intestine while colon, rectum and esophagus (<1%) account for
a minority of cases [4,7]. The GILs are active aggressively and
require early diagnosis and management [1,2,21]. Unusual synchronous
cases of lymphoma and non-lymphoid malignancies and another cancers are
well described [2,4,6,20]. The coexistence of double primary
malignancies especially malignant lymphomas of the jejunum is extremely
rare [4,8]. Multiple lymphomatous polyposis (MLP) is a primary GIL
with a distinctive entity and rare solid lymphoma intestinal segment
involvement. The Dawson criteria are identified the classic tests for
diagnosis of GIL include followings as absence of palpable
lymphadenopathy in clinical examination; absence of mediastinal
lymphadenopathy in a chest x-ray; normal range of total WBC and
differential count; disease confined to the intestine and adjacent nodes
involvement; no evidence of liver or spleen involvement [11].
Intussusception in adults is usually related to the underlying
pathology. In previous well-documented adult intestinal intussusception
caused by benign (63%), idiopathic (23%) and malignant (14%) lesions
[4.22] The most common site of small bowel lymphoma is the ileum,
ileocecal region followed by the jejunum and duodenum
[2,4,14,19,23]. The GI tract NHL/DLBCL is unusual pathological lead
point that can cause to intussusception in older children and in adults
[1,8,18,24]. Although intussusception is very common in children, a
leading cause of childhood intestinal obstruction [1.3], but it
accounts for 5% of all intussusception, intestinal obstruction in
adults accounting for 1-5% [3]. Clinically, adult intussusception
is rarely considered in the differential diagnosis of patients with
abdominal discomfort. However, adult intussusception preoperative
diagnosis is difficult because the typical symptoms. The incidence of
average age was 55 years (range 21-79 years old), male to female ratio
was 2.6: 1 [25]. A study reviewed 36 published cases of
intussusception caused by lymphoma from 2000 to 2011 [1.5]. These
ages of the patients ranged from 16 to 86 years old. Among 36 patients
in the 16 to 24 age group, only 7 patients developed secondary NHL with
intussusception [5]. The clinical features of small intestinal
lymphoma are non-specific. Common clinical manifestations of adult
intussusception include symptoms such as colicky abdominal cramps,
nausea, vomiting, weight loss, and rarely have acute obstruction
symptoms, ulceration, intussusception, intestinal perforation or
diarrhea [1,4].
The simultaneous occurrence of DLBCL is even rarer in the jejunum.
Synchronous primary DLBCL of the jejunum is extremely uncommon and only
three cases have been reported because of JJ intussusception caused by
NHL in adult [1,8,16,26]. This additional case is synchronous DLBCs
and the clinical manifestations presented as JJ intussusception with
intestinal perforation with multiple lymph nodes and pleural metastasis.
In literatures review that have been described a first rare case of
DLBCL presenting with 2 areas of JJ intussusception only once previously
[8], and a similar case with one area of JJ intussusception caused
by DLBCL has been reported [1,8,16,19]. The previous rare case
report has been described multiple recurrent JJ and ileo-ilea
intussusceptions due to multiple lymphomatous polyposis associated with
high-grade DLBCL of small intestinal in a child [1]. Obstruction and
perforation is uncommon and life-threatening complications of NHL, which
can occur at the time of diagnosis or during treatment. Previously,
reported one case of concurrent malignant B-cell lymphoma of the jejunum
and multiple synchronous colon cancers [7], and one case with
synchronous perforation of primary non-Hodgkin’s T-cell lymphoma (NHTL)
of the jejunum and descending colon presented with perforation and
peritonitis.6
Clinically, the pathophysiology of primary pleural effusion or secondary
malignant (metastatic) pleural effusion must to do differential
diagnosis. Primary GI-DLBCL initially presented as unexplained pleural
effusion is extremely rare. Recently, this an unusual case of unilateral
pleural effusion associated with primary rectal DLBCL reported
[2,9]. It is indeed extremely rare that synchronous DLBCLs with
multiple lymph node and bilateral pleural metastasis in the same tissue
and clinically characterized by JJ intussusception is indeed extremely
rare. This present case concerns considering an extremely rare
manifestation of synchronous primary DLBCLs of the jejunum with
disseminating multiple lymph nodal and pleural involvement presenting as
intestinal obstruction with perforation associating with two areas of JJ
intussusception in an elderly male in clinically. To be best our
knowledge and review, there is still no same case report in the
published English literature.
The non-specific clinical manifestations make preoperative diagnosis
difficult. The staging of primary GI-DLBCL is completed by considering
imaging examination and bone marrow aspiration and biopsy evaluation. To
establish an accurate diagnosis and staging of this heterogeneous group
of lymphomas, applications of different procedures have been used,
including endoscopic ultrasound (EUS), endoscopic biopsies, computed
tomography (CT), magnetic resonance imaging (MRI), diagnostic
laparoscopy, scintigraphy, angiography, positron emission tomography
(FDG-PET), and/or molecular cancer markers [1,2,4,11]. Typical
imaging features of intussusception include cross-sectional target sign
or donut sign, longitudinal cross-sectional false kidney sign, sandwich
sign, or pitchfork sign [1,2].
For the pathological diagnosis of surgical resection specimens, in terms
of pathological diagnosis, histology and morphology, high-grade DLBCL
must be differentiated from epithelial carcinomas, lymphoid or
hematological neoplasms and/or leukemia. Currently widely used IHC
staining could to do differential diagnosis. Histopathologic and IHC
examinations, the specificity and sensitivity of CD19, CD20, CD79a and
PAX5 markers to detect B-cell lineage lymphoma/leukemia-derived are
analyzed on the tissue microarray by IHC [2,4,18,20]. In present
case, IHC detection demonstrated CD20 marker shows strong and diffuse
membranous staining, transcriptional factor (MUM1/IRF4) expressed in
final step of intra-germinal center B cell differentiation and in
post-germinal center (late centrocytes) B cells. CD10, BCL6, and MUM1
expression in DLBCL [1,4,6,27].
Primary GIL should always be retained in the differential diagnosis of
intussusception cases, especially in older age and children groups. The
therapeutic strategy for gastrointestinal lymphoma depends on the
patient’s age, clinical condition, histological subtype, extent and
burden of the disease, and comorbidities. The effective treatment
strategy generally includes surgery, radiotherapy and further
chemotherapy (Rituximab with cyclophosphamide, doxorubicin, vincristine,
and prednisolone R-CHOP) in such our case. Surgical resection combined
with chemotherapy that has been shown to improve overall survival
independent intestine large B-cell lymphoma [2,26-29]. The outcomes
are directly related to the stage of at the diagnosis, with long term
survival rate reported is close to 75 % overall [12]. The
evaluation of prognosis of synchronous primary lymphoma in the intestine
correlates better with the depth of invasion, tumor size, and
lymphadenopathy. It was previously reported that the prognosis of GIL is
very poor. This present case was late stage of disease with complicated
critical conditions with microcytic anemia, hypoalbuminemia, and
hyponatremia, pleural effusion, and poor survival could be predicted.
Prognostic factors include the evaluation of stage at diagnosis, the
presence of perforations, tumor resectability, histological subtype and
multimodal treatment [9,12,21,29]. Lymphoma perforations with
involving pleural and nodes generally have higher tumor stage and poorer
prognosis in such our case. DLBCL of the small intestine has
significantly improved stage I and stage II survival. Previous study
data showed that early stage (stage I and II) patients have a longer
cumulative survival compared to stage III or IV patients [12]. Early
diagnosis and further management are important to improve the prognosis
of intestinal intussusception in patients with NHL-DLBCL.