Bollen, Patrick; Bourgain, Claire*; Van Berlaer, Gerlant; Duville, Lieve†; Vandenplas, Yvan
Departments of Pediatrics, *Pathology, and †Gastroenterology, Academic Children's Hospital, Free University of Brussels, Brussels, Belgium
Received October 11, 1999;
revised April 3, 2000; accepted April 3, 2000.
Address correspondence and reprint requests to Dr. Y. Vandenplas, Academic Children's Hospital, Free University of Brussels, Laarbeeklaan 101, 1090 Brussels, Belgium.
Non-Hodgkin lymphoma originates mostly from the lymphoid tissue of the small intestine (1). Most solitary rectal polyps in children are histologically classified as juvenile, although inflammatory, adenomatous, and Peutz–Jeghers types also occur (2). Very rare cases of benign lymphoid colorectal polyps have also been reported (3,4). Malignant polyps are usually adenocarcinomas (5). We report a patient with a solitary rectal polyp, which on pathologic examination was diagnosed as non-Hodgkin diffuse large B-cell lymphoma.
A 9-year-old boy was referred with a 3-week history of intermittent, red, painless rectal bleeding. Medical history was unremarkable. There was no familial history of intestinal polyps or of any gastrointestinal or immunologic disease. His general condition was good, and a physical examination disclosed no abnormality. A proctosigmoidoscopy revealed a solitary pedunculated polyp of 2 cm in length at 4 cm above the anal margin. The polyp was completely resected by electrocautery snare. Grossly, the polyp had a nodular, irregular appearance with a granular surface and bled easily.
Pathologic examination revealed diffuse large B-cell lymphoma. The tissue was almost totally replaced by a population of large lymphoid cells. No lymphoepithelial lesions were observed. This was confirmed by immunohistochemical markers for cytokeratin. The lymphoid cells were irregular in shape, noncleaved, with a slightly basophilic cytoplasm. The nuclei displayed one or two large nucleoli. There was a very high mitotic rate and multiple apoptotic bodies. In this lymphoid population, the presence of a few stainable body macrophages was established (Fig. 1, A and B).
Immunohistochemical phenotyping of the lymphoma cells was performed with the following antibodies: CD3, CD4, CD5, CD8, CD10, CD15, CD19, CD20, CD22, CD30, CD45, and CD45RO and light and heavy immunoglobulin chain. This revealed a B-cell phenotype (the cell surface was positive for CD45, CD19, CD20, and CD22) (6). All cells expressed exclusively κ light chains on their surfaces. A monoclonal rearrangement of IgG heavy-chain genes was found. In situ hybridization for Epstein–Barr virus was negative. The tumor cells were positive for p53 protein and negative for B-cell lymphoma type 2 (BCL2).
Subsequently, a total colonoscopy was performed to disclose multiple lymphomatous lesions. Biopsy specimens obtained at random from several levels of macroscopically normal-appearing mucosa displayed diffuse large B-cell lymphoma cells infiltrating the mucosa. Further investigations including a gastroduodenoscopy, with specimens from the esophagus, stomach, and duodenum revealing no pathologic findings. There was no Helicobacter pylori infection. The duodenal biopsy showed no sign of celiac disease. Ultrasound, computed tomographic (CT) scan of the abdomen, and X-ray transit were normal. Bilateral bone marrow aspirates showed no evidence of bone marrow invasion. Serologies for human immunodeficiency virus and Epstein–Barr virus were negative. Serum levels of immunoglobulin (Ig)G, IgA, and IgM were within normal limits. The absolute numbers of blood lymphocytes, CD4 and CD8 lymphocytes, and natural killer cells were normal.
The patient was treated with four cycles of chemotherapy: two cycles of prednisolone, methotrexate, cyclophosphamide, doxorubicin, vincristine and intrathecal methotrexate and hydrocortisone (COPADEM) and two cycles of methotrexate and cytosine-arabinoside and intrathecal methotrexate, hydrocortisone, and cytosine-arabinoside (CYM). Twenty-three days after the end of the chemotherapy, colonoscopy was performed, and tissue obtained by biopsy in different areas showed normal morphology. A control endoscopy was performed every 6 months, and biopsies were performed at different levels of the colon during each colonoscopy. At 36 months after the completion of chemotherapy, the lymphoma remained in remission.
Rectal blood loss is a frequent symptom in young children. Colonoscopy most often reveals a solitary juvenile or inflamed polyp. Benign lymphoid hyperplasia and lymphoid polyps are much less frequent (3,4).
Colonic B-cell lymphoma is considered to be very rare in children. Bethel et al. (7) reviewed a large series of malignancies occurring throughout the entire gastrointestinal tract diagnosed in children during a period of 44 years. They reported that the incidence of colonic lymphoma was 28 (0.6%) of 4547 pediatric tumor cases (colonic lymphoma comprised 21 cases of Burkitt's lymphoma and only 3 cases of large B-cell type) (7). In adults, 10% to 20% of the primary gastrointestinal tract lymphomas occur in the colon (1,5). Of these large-bowel lymphomas, 60% are located in the cecum, 20% in the rectum, and the remainder throughout the colon. In this patient, the presence of malignant cells within the mucosa at a distance from the polypous lesion was unexpected, but it is rather frequently seen in small intestine and colonic lymphoma in adults. For those reasons, pathologic examination of every colonic polyp in a child is mandatory. We recommend performing a total colonoscopy and also obtaining biopsy specimens from different levels of normal-appearing mucosa.
In the present case, the polyp had the endoscopic appearance of a juvenile polyp, but the histologic examination revealed a malignant non-Hodgkin diffuse large B-cell lymphoma. The malignant nature of the lymphoid proliferation was ascertained on the basis of the histologic features and of the monoclonality (6,8,9). No predisposing condition for development of intestinal lymphoma was found, such as human immunodeficiency virus infection, Epstein–Barr virus infection, ataxia telangiectasia, celiac disease (10), agammaglobulinemia (11), or ulcerative colitis (12,13).
In conclusion, this is a rare case of abdominal lymphoma in a child. We emphasize performing total colonoscopy in every child with a polyp. A pathologic examination of every resected polyp is mandatory, because macroscopic examination cannot exclude malignancy. In this case, with multiple foci of diffuse large B-cell lymphoma, simple resection would not have cured the patient.
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