**6. Presentation of lymphoma in IBD**

The presentation of lymphoma amongst IBD patients is very heterogenous and occurs in both Crohn's disease and ulcerative colitis.

There are abundant reports of lymphoma of the gastro-intestinal tract mimicking presentations of Crohn's disease (Kashi et al., 2010, Kang et al., 2007, Hurlstone, 2002, Jouini et al., 2001, Vincenzi et al., 2001, Camera et al., 1997, Maaravi et al., 1993, Scully et al., 1993,

reporting schemes, such as the FDA's Adverse Events Recording System (AERS) in the United States (FDA, 2011) or the MHRA's Yellow Card System in the United Kingdom (MHRA, 2011). Important information may come from drug specific data such as the TREAT registry (Lichtenstein et al., 2006), which is an on-going large-scale observational registry that was designed to examine the safety of Crohn's Disease therapies including infliximab. This type of data provides a *real world* experience with a heterogeneous group of patients suffering a variety of co-morbidities and taking concomitant medication. However, such schemes are generally voluntary systems which are prone to under-reporting and hence an

The low incidence of lymphoma, even in higher risk populations, poses a challenge to evaluating this risk. The incidence of all types of lymphoma diagnosed in the United Kingdom in 2007 was about 17 cases per 100,000 population (Cancer-Research-UK, 2011). A study of almost 3 million individuals would be necessary to detect an adverse event of this frequency with a confidence interval of 95%. No studies of this magnitude are available nor

The literature pertaining to the risk of lymphoma amongst IBD patients is dominated by case reports and case series. However, a number of large population studies have also been published over the last three decades which have been extremely valuable because they allow approximation of the risk of lymphoma (Loftus et al., 2000, Lewis et al., 2001, Beaugerie et al., 2009a, Greenstein et al., 1985). This information must be considered within the limitations of this type of study. A small number of meta-analyses have attempted to combine information from these population-based studies (Kandiel et al., 2005, Siegel et al., 2009). Post-marketing surveillance for drugs such as azathioprine, mercaptopurine and methotrexate are not available but some data regarding the newer anti-TNF therapies in IBD

Interest in the risk of developing lymphoma in the context of IBD and its treatment has grown exponentially (see Figure 3). This coincides with increasing use of immunomodulators in the management of IBD and concerns over their safety. Prior to the 1990s, only sporadic case reports and case series were available. More recently, a number of population based studies, review articles and meta-analyses have been published which are

Additionally, changes in the classification of lymphoid neoplasia makes evaluation of the literature difficult in certain circumstances where there are overlapping features between

The presentation of lymphoma amongst IBD patients is very heterogenous and occurs in

There are abundant reports of lymphoma of the gastro-intestinal tract mimicking presentations of Crohn's disease (Kashi et al., 2010, Kang et al., 2007, Hurlstone, 2002, Jouini et al., 2001, Vincenzi et al., 2001, Camera et al., 1997, Maaravi et al., 1993, Scully et al., 1993,

under estimation of true incidence.

are likely to be available in the future.

now exists (Lichtenstein et al., 2006).

discussed in this report.

diagnoses (Swerdlow et al., 2008).

**6. Presentation of lymphoma in IBD** 

both Crohn's disease and ulcerative colitis.

**5.2 Available data** 

Fig. 3. Medline cited publications regarding lymphoma risk in IBD patients since 1950.

McCullough et al., 1992, Pohl et al., 1991, Bartram and Chrispin, 1973) and ulcerative colitis (Isomoto et al., 2003, Luo et al., 1997, Wagonfeld et al., 1976, Myerson et al., 1974, Parnes et al., 1974, Friedman et al., 1968, Federman et al., 1963). Clearly, lymphoma of the GI tract frequently occurs in the absence of inflammatory bowel disease. In a series from the Mayo Clinic spanning 40 years in the pre-biologic era, of the 2,332 cases of primary intestinal lymphoma identified, only 15 patients had concomitant inflammatory bowel disease (Holubar et al., 2010). These cases are not discussed further here.
