Discussion
Gastrointestinal lymphoma accounts for 5–10% of all non-Hodgkin’s lymphoma with intestinal lymphoma contributing 15–20% of all gastrointestinal lymphoma [
1]. Majority of these arise in the stomach (up to 65% of all GI lymphoma) followed by the small bowel (20–30%) with rest arising in the colon and rectum [
1‐
3,
5]. B cell lymphoma of the colon is the third commonest malignancy of the colon after carcinoma and carcinoid though its incidence is less than 0.5%. Primary gastrointestinal malignancies are very rare in children with non-Hodgkin’s lymphoma being the most common [
7]. Within the colon, the involvement of caecum is the commonest, and Gonzalez et al. [
5] found caecum (60%) to be the commonest site, followed by the right (27%) and the sigmoid colon (13%). Bairey et al. [
3] in their case series of 17 patients also found ileocaecal region to be the most common site of colonic lymphoma accounting for 76% of cases. In our case reports, the site of involvement was also caecum and ascending colon in one and rectosigmoid junction in the second.
According to the World Health Organization (WHO) classification, B cell lymphomas are classified into diffuse large B cell lymphoma, extranodal marginal zone lymphoma (mucosa-associated lymphoid tissue [MALT]-associated lymphoma), mantle cell lymphoma (MCL), Burkitt’s lymphoma, and follicular lymphoma [
8]. Diffuse large cell B lymphoma (DLBCL) is the most frequent histological subtype affecting the gastrointestinal tract and colon [
9]. DLBCL are composed of rapidly proliferating cells and are more aggressive than other B cell lymphomas.
Primary colorectal lymphoma mainly affects older age group in the fifth to seventh decade of life with male:female ratio being 1.5:1 [
10]. Wong and Eu [
11] in their study of 14 cases found mean age of presentation to be 61 years, whereas Bairey et al. [
3] found it to be 72 years. In contrast to the above studies, our patient presented with lymphoma at 13 and 20 years of age probably the youngest reported case in the literature.
The presentation of B cell lymphoma is varied, and symptoms depend on the site of lesion. Most commonly, abdominal pain, weight loss, abdominal mass, and hematochezia, besides the features of obstruction like nausea, vomiting, change in bowel habits [
1,
3], obstruction [
1,
5], intussusceptions [
12,
13], and acute peritonitis due to intestinal perforation [
1,
3], are present. Fan et al. [
10] in their series of 37 patients reported abdominal pain and weight loss in 62% and 43% of cases respectively, whereas Bairey et al. [
3] reported abdominal pain and weight loss respectively in 56% and 29% of cases. Intestinal obstruction is a very rare presentation due to more pliable nature of colorectal lymphoma and the absence of desmoplastic response; however, symptoms of partial obstruction are more frequent. More than half of the patients present with bulky disease usually more than 5 cm [
3,
10,
14]. Surprisingly, in most cases of colonic B cell lymphoma reported in the literature, the B symptoms are often absent and fever is very rarely a presenting symptom. This is probably due to anatomical location wherein bowel-related symptoms appear first.
The most common imaging modalities used to image colonic lymphoma are contrast-enhanced computed tomography (CECT) of the abdomen or double contrast barium enema (DCBE), both of which complement each other. CECT abdomen provides extraluminal information like tumour size, depth of invasion, and regional nodal involvement, whereas DCBE provides more information about mucosal changes and gross tumour morphology. It is to be noted that both these modalities are not able to differentiate colonic carcinoma from lymphoma and diagnosis has to be confirmed by colonoscopy and biopsy. Immunohistochemistry are required for sub-classification. Full haematology including a peripheral smear, biochemistry, chest X-ray, CT scans, and bone marrow biopsy are required to rule out systemic involvement and for staging the disease. Though there is no consensus on what is ideal investigation for staging, evidence is slowly emerging to suggest usefulness of PET-CT for extranodal lymphoma as well.
The most widely used staging system in clinical practice is the Lugano classification which is based on Ann Arbor system modified by Carbone et al. [
15]. Stage I is involvement of a single nodal group or single extranodal site (IE). Stage II comprises of involvement of more than one nodal group on the same side of the diaphragm or single extranodal site and adjacent lymph nodes (IIE). In stage III, there is involvement of multiple nodal sites on both sides of the diaphragm, including extranodal sites (IIIE) or spleen (IIIS). Stage IV is involvement of bone marrow, central nervous system, or diffuse visceral involvement.
The principal modality of treatment is combined modality treatment that includes surgery and chemotherapy [
16]. Early stage tumours are treated with surgery followed by polychemotherapy, and advanced stage tumours are treated with multidrug chemotherapy [
1,
3,
17]. However, since the availability of rituximab, the CD20-positive B cell lymphomas can be treated with polychemotherapy combined with immunotherapy with complete and lasting response making the surgery redundant in these cases, as can be seen from the present case reports wherein surgery was avoided due to preoperative diagnosis and polychemoimmuno therapy.
Stage IE or IIE, disease confined to the colon or rectum with (IIE) or without (IE) regional lymph node involvement, had been treated with surgery followed by adjuvant chemotherapy [
18]. In most series of published literature, surgery was followed by adjuvant multiagent chemotherapy (CHOP) which has led to improved outcomes [
2,
18,
19]. Adjuvant chemotherapy has been shown to improve median survival from 36 to 53 months in a series of 15 patients (out of which 8 received adjuvant therapy) [
20]. Similarly, Fan et al. [
10] reported an improvement in median survival from 24 to 36 months. Aviles et al. [
19] reported 83% 10-year overall survival in patients with stage IE treated with surgery followed by adjuvant chemotherapy. However, other studies found surgical resection of localised, primary colonic lymphoma to provide excellent local disease control [
2,
5]. One of the reasons for avoiding primary chemotherapy is the fear of perforation of the bowel.
Surgery is the prime mode of therapy for palliation of pain and emergent conditions like obstruction, perforation, and bleeding. In a series of 43 patients reported by Cai et al. [
21], 56% of the patients required emergency operation. Similarly, in a case series of 46 patients by Zhai et al. [
22], 13 patients required emergency surgery.
Rapidly proliferating and aggressive advanced lymphoma is best treated with chemotherapy. The CHOP chemotherapeutic regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone) is a mainstay of treatment for all moderate and high grade B cell lymphomas. Addition of rituximab to standard CHOP regimen has led to improvement of progression-free, event-free, disease-free, and overall survival [
23]. With the advent of new monoclonal antibodies like rituximab, there is a shifting trend towards use of chemotherapy in all cases with surgery reserved mainly for palliation of emergent condition [
24].
However, due to rarity of disease, no prospective randomised clinical trials have been designed yet to define the optimal therapy of primary colonic lymphoma. Treatment decisions mainly depend upon expert opinion and consensus made on the basis of level II/III and IV evidence that is in abundance (Table
1).
Table 1
Published studies on colorectal lymphoma
| 17 | Diffuse large B cell lymphoma | Multimodality, 9 Chemotherapy, 6 Surgery, 2 | Median, 44 months |
Musallam et al. 2010 [ 26] | 9 | Diffuse large B cell lymphoma, 6 Burkitt lymphoma, 3 | Multimodality, 5 Chemotherapy, 3 Surgery, 1 | Median, 25 months |
| 14 | Diffuse large B cell lymphoma | Multimodality, 11 Surgery, 3 | 5-year overall survival, 57% |
| 95 | B cell, 82.1% T cell, 17.9% | Multimodality, 57 Chemotherapy, 23 Surgery, 15 | 5-year overall survival, 55.2% |
| 8 | Large cell, 3 Small cell, 1 Mix large and small, 3 Lymphoblastic, 1 | Surgery with adjuvant therapy in all | 66% 4 years |
| 22 | Diffuse histiocytic lymphoma | Multimodality, 14 Surgery, 8 | N/A |
Zighelboim and Larson 1994 [ 30] | 15 | | Multimodality, 3 Chemotherapy, 12 | 5-year survival, 27% |
| 15 | | Multimodality, 12 Surgery, 3 | Median survival, 60 months |
| 7 | Small non-cleaved, 5 Large cell, 2 | Multimodality, 6 Surgery, 1 | N/A |
| 23 | | Multimodality, 14 Chemotherapy, 4 Surgery, 3 | 10-year survival, 61% |
| 37 | High grade, 29 Intermediate and low grade, 8 | Multimodality, 22 Chemotherapy, 2 Surgery, 13 | Median survival, 24 months |
Stanojevic et al. 2008 [ 14] | 24 | | Multimodality, 20 Surgery, 4 | Median survival, 41.9% |
| 19 | | Multimodality, 14 Chemotherapy, 4 Surgery, 1 | Median survival, 45 months |
| 32 | High grade, 26 Low grade, 6 | Multimodality, 22 Chemotherapy, 10 | 5-year overall survival, 59% |
| 32 | B cell, 22 (DLBCL most common) T cell, 10 | B cell, multimodality (22) T cell, surgery (8) | B cell DFS at 55 months, 88.2% T cell, 3 alive after 23 months |
| 10 | B cell, 8 Burkitt, 1 Mantle cell, 1 | Surgery, 7 Chemotherapy, 3 | Median survival Surgery, 17 months Chemotherapy, 13 months |
| 46 | B cell origin, 35 T cell, 11 | | 5-year survival, 64.2% Progression-free survival, 49.3% |
| 7 | Diffuse large B cell lymphoma, 6 Follicular lymphoma, 1 | Multimodality, 2 Chemotherapy, 2 Surgery, 3 | N/A |
| 52 | Diffuse large B cell lymphoma, 64.4% | Multimodality, 43 Chemotherapy, 9 | 5-year survival, 71% |
| 11 | Diffuse large B cell lymphoma | Multimodality, 9 Chemotherapy, 1 Radiotherapy alone, 1 | Median event-free survival, 10 months |
Prognosis is often mixed with median survival of above 5 years reported in various series. Fan et al. [
10] found stage to be the most important prognostic factors for survival. Others found histological grade to be the most important prognostic factor [
3,
14,
21]. Urgency of surgical operation has also been reported as an important factor affecting survival [
3,
14] along with histological subtype wherein B cell lymphomas have better prognosis than T cell phenotype [
22,
25].