**6.1 Intestinal and extra-intestinal lymphoma**

Lymphoma may present at a variety of sites amongst IBD patient but these can broadly be classified as intestinal and extra-intestinal.

Up to 15% of extra-nodal lymphoma involves the GI tract (Newton et al., 1997). In a series of 15 cases of intestinal lymphoma, 60% were colorectal, 27% involved the small bowel and there were individual cases in the stomach, duodenum and ileal pouch, each constituting 6.25% of this series (Holubar et al., 2010). In 80% of these cases, the location of the lymphoma was congruous to the site of IBD. In another series of 14 colorectal lymphomas, the commonest sites were the caecum and rectosigmoid but these were not IBD patients (Wong and Eu, 2006). Gastric mantle cell lymphoma has also been reported by Raderer et al in a patient with a 14 year history of Crohn's disease (Raderer et al., 2004). Ileal pouch lymphoma has also been reported in a number of other publications (Sengul et al., 2008,

Evaluating Lymphoma Risk in Inflammatory Bowel Disease 325

expected events in a study population. This is a useful comparator to analyse the risk of

A cohort study identified 3,585 patients attending a single IBD centre in Indianapolis, USA. Data was collected retrospectively between 1990 and 2005. Since 2005, the registry was updated prospectively. An electronic database was interrogated for diagnoses of Hodgkin's and non-Hodgkin's lymphoma and compared to expected age-standardised incident rates from the SEER registry. This study also used a case matched control group with a ratio of 1:10 to determine risk factors for lymphoma development. The population consisted of 2,277 Crohn's patients and 1,308 UC patients with no significant demographic differences between groups. 8 patients were identified with a diagnosis of lymphoma (6 NHL and 2 HL). Only 3 patients had thiopurine exposure but 2 of these patients had also received TNF antagonists and were EBV positive. The study did not find any statistically significant relationship between diagnosis of lymphoma with demographics, drug therapy, duration of treatment and length of diagnosis. Based on SEER statistics, the overall SIR for lymphoma

**Incidence and Risk Factors for Lymphoma in a Single-Center Inflammatory Bowel** 

lymphoma in IBD patients and has been used in much of the literature.

was 1.6 (95% CI 0.6 to 3.0) but this was not significant. (Chiorean et al., 2010)

**Population-Based Case-Control Study (Armstrong et al 2010)** 

background population in this study. (Armstrong et al., 2010)

was not calculated by the authors. (Van Domselaar et al., 2010)

**et al 2010)** 

**Nationwide Study (Vos et al)** 

**Risk of Cancer in Inflammatory Bowel Disease Treated with Azathioprine: A UK** 

This was a nested case-control study using the General Practice Research Database (GPRD) in the UK which was interrogated for patients with a diagnosis of IBD, any previous prescriptions for azathioprine or mercaptopurine and a subsequent diagnosis of any cancer. The GPRD is the largest longitudinal primary care database in the world containing approximately 50 million patient years of data. The control group consisted of all IBD patients who had not been diagnosed with a cancer. The total number of patients included in the study was 15,471 and 15 patients had diagnoses of lymphoma (2 HL, 6 NHL and 7 unspecified). The group found the risk of lymphoma for patients who had ever received thiopurines versus those that had never received such drugs was increased by an OR of 3.22 (95% CI 1.01 to 10.18). An SIR was not calculated for the risk of lymphoma compared to the

**Lymphoproliferative Disorders in an Inflammatory Bowel Disease Unit (Van Domselaar** 

This was a retrospective study of 911 patients attending a tertiary IBD clinic in Madrid followed up for a mean of 32.3 months. There were 7 cases of lymphoma identified in the cohort (6 NHL and 1 HL). The mean age at diagnosis was 53 years and the mean time from IBD to lymphoma diagnosis was 4.82 years (range 0 to 20 years). Three cases were associated with EBV. An SIR of 3.72 can be calculated from the figures presented though this

**Risk of Malignant Lymphoma in Patients with Inflammatory Bowel Diseases: A Dutch** 

The authors identified all IBD patients diagnosed with lymphoma between 1997 and 2004 from a Dutch nationwide histo- and cyto-pathology database known as PALGA. Age adjusted incidence of lymphoma was obtained from the Netherlands Central Bureau for

**Disease Population (Chiorean et al 2010)** 

Frizzi et al., 2000, Nyam et al., 1997) and one publication suggests EBV may be involved in the aetiology (Schwartz et al., 2006). Lymphoma at an ileostomy site has also been reported (Pranesh, 2002). Metachronous colonic lymphoma (Hill et al., 1993) as well as synchronous colonic adenocarcinoma and lymphoma (Hope-Ross et al., 1985, Nishigami et al., 2010) have been described in IBD patients.

In addition, a number of extra-intestinal sites of lymphoma amongst IBD patients have been reported. Hepatosplenic T-cell lymphoma (HSTCL) has become a concern amongst IBD physicians and this will be discussed in further detail. Owen et al reports a patient with UC treated with azathioprine who develops a B-cell lymphoproliferative disorder on her eyelid following a recent illness diagnosed as infectious mononucleosis (Owen et al., 2010). Deneau et al recently described the case of a child with an EBV-driven NK-cell lymphoma involving the skin and GI tract causing hepatosplenomegaly (Deneau et al., 2010). Other cutaneous lymphomas are described in the literature (Adams et al., 2004, Martinez Tirado et al., 2001). Vulval and peri-anal lymphoma has also been identified (Winnicki et al., 2009, Sivarajasingham et al., 2003). Kastner et al present a young lady with ulcerative colitis, previously treated with azathioprine, who presents with seizures and is found to have cerebral lesions of high grade B cell lymphoma (Kastner et al., 2007). Plamacytoma (a mature B-cell lymphoma) can present as a paravertebral mass (Redmond et al., 2007).
