physicians have shown great concern on the relationship between lymphoma and inflammatory bowel disease ( ibd ) over the years . in 1928 , bargen described initial report of lymphosarcoma in a patient with ulcerative colitis . since then , numerous case reports and meta - analyses have been presented , but composite lymphoma in ibd patients had not previously been reported .
composite lymphoma is a rare malignancy and defined as the presence of two or more distinct cytological and histological variant of lymphoma in the same tissue .
this combination consists of hodgkin lymphoma ( hl ) with non - hodgkin lymphoma ( nhl ) or b - cell nhl with t -cell nhl , or two distinct subtype of b - cell or t - cell nhl . in this study , we present a case of a composite diffuse large b - cell lymphoma and nodular sclerosing hl in para - aortic lymph node and spleen in a 45-year- old female patient diagnosed with ulcerative colitis .
the patient was a 45-year - old female with a 2-year history of left - sided ulcerative colitis .
only mesalamine was responsible for keeping the disease under control and no other immunosuppressive agents such as azathioprine and anti tnf were administered .
the patient was referred to hematologic ward with a one - month history of malaise , weakness and fatigue . upon physical examination ,
hematologic findings consisted of pancytopenia , elevated erythrocyte sedimentation rate ( esr ) and lactate dehydrogenase ( ldh )
. results of renal and liver function tests , electrolytes , urine analysis and hiv test were within the normal range .
contrast - enhanced computed tomography scan of the chest and abdominopelvic regions showed lymphadenopathy of middle and posterior mediastinum , para - aortic lymphadenopathy and splenomegaly with heterogeneous density ( fig.1 ) . to achieve a definite diagnosis , splenectomy , excisional biopsy of para - aortic lymph node , aspiration and biopsy of marrow
histomorphological evaluation of the spleen and para aortic lymph node ( fig : 2 ) show focal involvement by classical hodgkin s lymphoma and nodular sclerosis variant , wherein typical nodules are seen in which the lacunar cells and classic red - sternberg ( r - s ) cells are surrounded by small mature lymphocytes with a few eosinophils and plasma cells .
however , in other areas , diffuse sheets of centroblastic and ( less ) immunoblastic cells are also evident , which is in keeping with diffuse large b - cell lymphoma ( dlbcl ) .
3 ) , the lacunar cells and r - s cells in the hl component show negative leukocyte common antigen ( lca ) , cd20 and positive ki - a10 ( one of the hl associated markers ) although cd30 and cd15 are negative . accordingly , there is strong positivity of lca and cd20 in the dlbcl component .
treatment of composite lymphoma depends on histological grading of components and is towards the high grade histology .
the patient was treated with r - chop- based chemotherapy ( rituximab , cyclophosphamide , adriamycin , vincristine and prednisolone ) . after eight courses of chemotherapy with r - chop and one course of high - dose methotrexate , complete remission was achieved .
the patient was a 45-year - old female with a 2-year history of left - sided ulcerative colitis .
only mesalamine was responsible for keeping the disease under control and no other immunosuppressive agents such as azathioprine and anti tnf were administered .
the patient was referred to hematologic ward with a one - month history of malaise , weakness and fatigue . upon physical examination ,
hematologic findings consisted of pancytopenia , elevated erythrocyte sedimentation rate ( esr ) and lactate dehydrogenase ( ldh )
. results of renal and liver function tests , electrolytes , urine analysis and hiv test were within the normal range .
contrast - enhanced computed tomography scan of the chest and abdominopelvic regions showed lymphadenopathy of middle and posterior mediastinum , para - aortic lymphadenopathy and splenomegaly with heterogeneous density ( fig.1 ) . to achieve a definite diagnosis , splenectomy , excisional biopsy of para - aortic lymph node , aspiration and biopsy of marrow
histomorphological evaluation of the spleen and para aortic lymph node ( fig : 2 ) show focal involvement by classical hodgkin s lymphoma and nodular sclerosis variant , wherein typical nodules are seen in which the lacunar cells and classic red - sternberg ( r - s ) cells are surrounded by small mature lymphocytes with a few eosinophils and plasma cells .
however , in other areas , diffuse sheets of centroblastic and ( less ) immunoblastic cells are also evident , which is in keeping with diffuse large b - cell lymphoma ( dlbcl ) .
3 ) , the lacunar cells and r - s cells in the hl component show negative leukocyte common antigen ( lca ) , cd20 and positive ki - a10 ( one of the hl associated markers ) although cd30 and cd15 are negative . accordingly , there is strong positivity of lca and cd20 in the dlbcl component .
treatment of composite lymphoma depends on histological grading of components and is towards the high grade histology .
the patient was treated with r - chop- based chemotherapy ( rituximab , cyclophosphamide , adriamycin , vincristine and prednisolone ) .
after eight courses of chemotherapy with r - chop and one course of high - dose methotrexate , complete remission was achieved .
inflammatory bowel disease is a chronic disorder of gastrointestinal tract including two main diseases : ulcerative colitis and crohn s disease .
the etiology of these diseases is unknown , but evidence suggests that genetically susceptible patients immune dysfunction triggered by environmental factors is responsible for disease . the risk of lymphoma in ibd patients has been a great concern in the medicine for many years .
environmental , genetic , infectious and iatrogenic factors in the patients with inflammatory bowel disease can predispose them to increase the risk of lymphoma .
overall risk of lymphoma in ibd patients is not higher than general population , but the basic question is whether treatment with immunomedulatory agents can lead to an increased risk of lymphoma .
the use of azathioprine /6-mercaptopurine increases the incidence of lymphoma in patients with inflammatory bowel disease although usefulness of azathioprine therapy outweigh the risk of lymphoma has been suggested in decision analysis model .
ebv in the patients with ibd who received azathioprine/6-mercaptopurine associated with increased risk of lymphoma .
methotrexate is another immunomedulatory drug which is used as alternative treatment in moderate to severe crohn s disease .
unlike azathioprine , there is no repeated and reliable data for the risk of lymphoma in ibd patients treated with methotrexate . in the cesame study conducted by beaugerie et al . , ( 2009 )
some studies like those conducted on rheumatoid arthritis provide some information on the effect of methotrexate . in these studies
, there was no increase in the risk of lymphoma among patients treated with methotrexate .
at that time , anti - tnf agents such as infliximab were approved for the treatment of crohn s disease .
there is a great concern over safety of drugs ; moreover , the assessment of specific risk of these agents on lymphoma development is difficult because most patients had a previous exposure to methotrexate and azathioprine .
a comprehensive meta - analysis that was conducted by siegel et al . , ( 2009 ) showed that the rate of nhl in patients with crohn s disease who treated with anti - tnf agents in combination with immunomedulators was not increased .
non - hodgkin s lymphoma , particularly diffuse large b - cell lymphoma , appears to be more common than other types of lymphoma in the patients with inflammatory bowel disease .
she had no exposure to azathioprine , methotrexate or anti tnf agents . despite the large number of ibd patients with lymphoma ,
the incidence rate of composite lymphoma , known as rare malignancy , is estimated to be 1 to 4.7% of all other types of lymphoma .
in contrast , the combination of non - hodgkin s lymphoma and hodgkin s disease rarely occurs .
nodular lymphocyte - predominant hodgkin s lymphoma and diffuse b - cell lymphoma are more frequently found among these combinations .
 a 45-year - old female patient with a diagnosis of ulcerative colitis complicated with composite lymphoma in the spleen and para - aortic lymph node presented with a one - month history of malaise , weakness and fatigue . 
 only mesalamine kept ulcerative colitis under control . in physical examination , 
 splenomegaly was revealed and pancytopenia was obtained from laboratory data . computed tomography scan revealed para - aortic mediastinal lymphadenopathy with splenomegaly . 
 splenectomy and excisional biopsy of abdominal lymph node were performed and disease was diagnosed as composite lymphoma , consisting of diffuse large b - cell lymphoma and nodular sclerosing hodgkin lymphoma . 
INTRODUCTION
Case presentation
DISCUSSION