The gastrointestinal (GI) tract is the most common site of primary extranodal lymphoma, with the majority being non-Hodgkin lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) of the colon is the most common subtype of extranodal NHL, usually affecting the cecum.1 The etiology of colorectal lymphoma is unknown. It has been linked to states of immunosuppression, including inflammatory bowel disease, HIV, or after organ transplantation.2 Primary lymphoma of the colon is rare and comprises 0.2%–1% of colon malignancies. Advanced-stage tumors have been treated with multidrug chemotherapy, showing a complete and lasting response.3
A 71-year-old man with a history of Stage IV Burkitt lymphoma presented with right lower quadrant abdominal pain for 6 weeks. Additional symptoms included fever, fatigue, weight loss of 30 pounds, night sweats, hematochezia, melena, light-headedness, and pruritus. Family history was significant for chronic myelogenous leukemia in the father. Digital rectal examination revealed dark black stool. Laboratory results revealed hemoglobin 7 g/dL and platelet 43 × 109/L, from a baseline of 15 g/dL and 165 × 109/L, respectively. Potassium, phosphate, and calcium levels were 4.8 mEq/L, 5.5 mg/dL, and 6.6 mg/dL, respectively. The uric acid level was 11.0 mg/dL (reference 3.5–8.5 mg/dL). Creatinine was 3.22 mg/dL compared with the baseline of 1.06 mg/dL. The fibrinogen level was 489 mg/dL (reference 200–393 mg/dL). Prothrombin time, partial thromboplastin time, and D-dimer were within normal limits, and disseminated intravascular coagulation was not suspected. Abdominal computed tomography of the showed a large cecal mass (10 × 11 × 12) and lymphadenopathy in the right lower quadrant, pelvis, and retroperitoneum. A positron emission tomography (PET) scan revealed an intense hypermetabolic cecal mass and abdominopelvic nodal masses. Colonoscopy confirmed a friable, centrally ulcerated cecal mass (Figure 1), which revealed DLBCL, positive CD20, CD 79a, BCL6, CD 10, and Ki-67 (80%–90%). B-cell clonality assay was inconclusive, although pathology showed DLBCL as a new diagnosis and did not find any evidence of transformation from Burkitt lymphoma.
The oncological history included a diagnosis of Burkitt lymphoma in 2015. At that time, he was found to have cervical and axillary adenopathy with extensive disease throughout, along with skeletal involvement seen on a baseline PET scan. He achieved remission with 6 cycles of hyper-CVAD (cyclophosphamide, vincristine sulfate, doxorubicin, adriamycin, and dexamethasone) and 2 cycles of maintenance therapy with POMP (6-mercaptopurine + vincristine + methotrexate + prednisone). Given his findings and suspected tumor lysis syndrome, he was transfused with packed red blood cells, platelets, and rasburicase. Bone marrow biopsy was negative for lymphoma involvement. The thrombocytopenia was attributed to immune thrombocytopenic purpura given active lymphoma and appropriate response to intravenous immunoglobulin infusions but not platelet transfusions. He was given 4 cycles of R-ICE (rituximab, ifosfamide, carboplatin, and etoposide) therapy in subsequent visits. A repeat PET scan showed a complete metabolic response. The Deauville scores before and after were 5 and 2, respectively. He continued to follow-up at the lymphoma clinic every 3 months for post-treatment surveillance.
Diagnostic criteria for primary colorectal lymphoma were initially established in 1961.4 It required histological confirmation and the following: no superficial enlarged lymph nodes on examination, no mediastinal lymph node enlargement on chest x-ray, normal white blood cell counts, laparotomy showing only regional node involvement, and tumor-free liver and spleen. If an infiltrative process and enlarged lymph nodes are seen on the computed tomography scan, lymphoma must be excluded by endoscopic biopsy.5 There is now a more liberal definition of primary extranodal NHL based on a study by Krol et al.6 In disseminated disease, if NHL originated from an extranodal site and is clinically dominant, it can be classified as primary extranodal NHL. Colonoscopy, followed by biopsy, plays a valuable role, although it is not feasible in urgent settings often because of inadequate samples needing multiple biopsies and time required for immunohistochemical staining. Typical colonoscopy findings are large polyps and mucosal ulceration, the latter of which was seen here.7 Ultimately, diagnosis is based on histologic, flow cytometric, and molecular evaluation of an adequate tissue specimen.8
Tumor cells in this index case were positive for B-cell markers CD20 and CD79a, typical in DLBCL. BCL-6 and CD10 expressions are also common findings in DLBCL seen in our patient. BCL-6 expression leads to an uncontrolled cell cycle while CD10 expression indicates a follicular-derived DLBCL. There are studies on the prognostic role of CD10 in DLBCL, although they are contradictory with no clear consensus.9 Staging is performed by the Ann Arbor system, and although it is useful for nodal NHL, it is not optimal for extranodal lymphoma. A modified TNM staging system proposed by the European Gastrointestinal Lymphoma Study Group is used to characterize extranodal lymphoma because it adjusts to the GI origin of lymphoma and considers histopathological characteristics of both extranodal B-cell and T-cell lymphomas.10
For unresectable DLBCL of the colon that has metastasized, rituximab added to a CHOP-like regimen has proven to be effective.11 CHOP is a combination of cyclophosphamide, doxorubicin, vincristine, and prednisone that was the first-line therapy for DLBCL for many years. Although it achieved an appropriate initial response, only 50% of the responses were durable.12 Rituximab, a monoclonal antibody against B-cell antigen CD20, was approved in 1997 based on the trial by McLaughlin et al, in which it showed significant response rates in indolent lymphoma.13 Hyper-CVAD was first described in 1997 by Koller et al14 and represents a more intensive regimen than CHOP. R-ICE shows efficacy in patients with relapsed DLBCL, with a complete response rate of 53% compared with 27% in patients receiving ICE alone.15
The optimal regimen for relapsed DLBCL has yet to be established. Because <10% of patients obtain long-term disease-free survival, it is accepted that response to chemotherapy should be consolidated with hematopoietic stem cell transplantation.16 Given our patient's history of Burkitt lymphoma and a prior chemotherapy regimen, R-ICE was given, with ongoing evaluations for future hematopoietic stem cell transplantation. We present a rare case of primary lymphoma of the colon in an atypical location, which is the cecum. Although our patient did achieve complete remission, he will need regular surveillance to monitor for recurrence.
Author contributions: All authors contributed equally to this manuscript. F. Azad is the article guarantor.
Financial disclosure: None to report.
Informed consent was obtained for this case report.
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