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.