Could celiac disease be a premalignant condition?

Manuscript type : Case Report | Article Date : 2016/12/23

  • Autors

    1. Asadollahi Hamid
    2. Moghimi Mansour
    3. Amirbeigy Mohammad Kazem
  • Abstract

    Celiac disease (CD) is an immune-mediate enteropathy with variable presentations which is triggered by exposure to dietary gluten in genetically predisposed people. Here, we describe a 57 year-old woman, with no past history of CD-related features presenting with abdominal pain, iron deficiency anemia and elevated liver enzymes, as well as T cell lymphoma and portal vein thrombosis (PVT). To date, there are few reports of CD concomitant with PVT but to the best of our knowledge, none of them described the concurrent T cell lymphoma. Chronic inflammation due to the underlying CD is likely the most plausible explanation for developing both T cell lymphoma and hypercoagulability state leading to PVT.
  • Description


    Celiac disease (CD) is a chronic immune-mediated enteropathy of the small intestine triggered by exposure to gluten in genetically predisposed people1 affecting about 1% of the general population across various ethnic groups.2 Symptomatic CD is characterized by intestinal and/or extraintestinal symptoms. Patients with intestinal manifestations may present with classical symptoms such as diarrhea or non-classical symptoms including constipation and abdominal pain. Extra intestinal manifestations such as iron deficiency anemia and elevated liver enzymes might be the only features or be detected together with intestinal symptoms. Importantly, a proportion of CD patients also remain silent presenting with chronic complications such as malignancies.1 The overall risk of developing cancer in CD patients is approximately twice of the general population, which mainly include enteropathy associated T-cell lymphoma (EATL) and carcinomas of the small intestine, esophagus and oropharynx.3 Here, we report a patient with very rare concomitant presentations of T cell lymphoma and portal vein thrombosis (PVT) in the background of CD.

    Case Report

    A 57-year-old female w as admitted to our gastroenterology ward with chief complaints of abdominal swelling and loss of appetite since the past 2 months. Her chief complaints were concomitant with constipation, mild insidious pain in epigastrium exacerbated by eating and a significant weight loss within the last 2 months. She denied any previous history of such symptoms. She was hospitalized in the gynecology ward 1 month earlier and reproductive organ malignancies were ruled out. On arrival to us, she had tachycardia with low-grade fever and blood pressure of 90/60 with normal respiration. She looked cachectic and pale but there was no sign of icterus. Abdomen was distended with mild tenderness in the epigastrium but no organomegaly or ascites and physical examination was otherwise unremarkable. Her laboratory work-up frequently revealed normal platelet count but leukocytopenia and a hypochromic microcytic anemia, as well as hyponatermia, and increased liver enzymes and LDH (Table 1). Also on her arrival PTT, PT and INR were above the normal range (Table 1). HBs Ag, HBcAb, HCV Ab were negative. Abdominal ultrasound showed normal liver but mild ascites and enlargement of multiple lymph nodes in paraaortic and mesenteric areas and hilum of the liver. Following an abdominal CT scan with contrast, partial thrombosis of portal vein and total thrombosis in one branch of inferior mesenteric vein were also detected. Anticardiolipin (IgG and IgM) and lupus anticoagulant antibodies were negative. Positive result of the serum IgA tissue transglutaminase (tTG) antibody (>100 u/ml) was suggestive of CD. Furthermore, we conducted a diagnostic endoscopy which did not show any macroscopic abnormality of the upper GI but pathologic evaluation of the duodenal biopsy showed partial villous flattening with intraepithelial lymphocyte infiltration indicative of CD but no features of malignancy (Fig. 1). Histopathologic examination of biopsy of peritoneum and liver were normal, however, biopsy of the omentum showed some diffuse moderate-large atypical CD3+ and CD20­– lymphocytes (Fig. 2). Accordingly, the overall features were suggestive of a concomitant T-cell lymphoma in the background of CD. The patient underwent anticoagulant therapy as well as gluten free diet and was referred to an oncologist for further management. Although we tried to call the patient after her discharge from our ward, we could not reach her. Therefore, there is no further information available about the follow up of her disease.


    Our patient was admitted with features suggestive of a malignancy including loss of appetite, significant weight loss in a short period of time and ascites, as well as abdominal lymphadenopathy and PVT shown in her abdominal ultrasound and CT scan. These findings together with pathologic data eventually led to the finding of malignant T cells in her omentum in favor of T cell lymphoma. CD was also confirmed by positive tTG antibody and duodenal biopsy. The pathogenesis of CD depends on the interaction of genetic susceptibility and exposure to gluten. Numerous genetic predisposing factors including human leukocyte antigen (HLA) class II (HLA-DQ2 and HLA-DQ8) and non-HLA genes have been associated to CD.4, 5 Contrary to the physiologic state, in genetically predisposed individuals, paracellular permeability is enhanced and therefore gluten peptides pass through epithelial barrier where HLA-DQ2 and HLA-DQ8 present them to CD4+ T cells leading to the production of proinflammatory cytokines. These cytokines further induce villus atrophy through the activation of immune system.6 Consequent flattening of villi decreases intestinal absorbing surface and patients may present with malabsorption features. Chronic inflammation in CD also increases the risk of non-Hodgkin lymphomas such as EATL even outside of the intestine.7 Notably, neoplastic cells in EATL are medium-large sized with round or indented nuclei and commonly positive for CD3, CD30 and CD103 and negative for CD4, CD8 and CD20.8 Due to the limitation of our resources, we could not evaluate all required CD markers. However, morphology of malignant cells and their CD3+ and CD20- status were compatible with EATL. Mild to moderate elevation of liver enzymes with normal bilirubin level and non-specific findings in liver biopsy has been reported in about 40% of adults with classical CD at the time of diagnosis.9 Likewise, in our patient despite the elevation of liver enzymes, there was no sign of cholestasis and abdominal CT scan as well as liver biopsy did not show any abnormality suggesting the presence of isolated hypertransaminasemia. Importantly in her abdominal CT scan we detected PVT extending to mesenteric vein. To the best of our knowledge, this is the first report of concomitant T cell lymphoma and PVT in the background of CD. The leading cause of thrombosis in non-Hodgkin lymphomas is vessel compression by lymph nodes or masses10 but in our case CT scan did not show any compression on vessels and due to the overall findings in our patient, significant thrombophilia due to the chronic inflammation of CD seems to be the most plausible cause of PVT. Inflammatory mediators induce hypercoagulability status through the stimulation of coagulation factors and suppression of anticoagulants and fibrinolysis.11 However, inherited risk factors such as mild forms of protein C and S deficiencies and factor V Leiden could also be the concomitant predisposing factors for developing PVT.12 Here, we would also like to remind the fact that CD may have a late onset presentation with only nonspecific features and/or malignancies. Early diagnosis of CD by measurement of tTG Ab is the way to prevent its serious complications through early prescription of gluten free diet.13, 14 Although some studies have suggested the HLA genetic testing as an appropriate way for selecting high risk individuals for tTG Ab evaluation,5, 15 only 1% of HLA-DQ2/DQ8 positive population develop the disease. Therefore, further genes linked to CD are needed to be identified for optimizing the genetic tests. This can lead to the early detection and prevention of complications such as those seen in our patient.


    We describe a CD patient with T cell lymphoma and PVT. There are few reports of CD concomitant with PVT but to the best of our knowledge, none of them described the concurrent T cell lymphoma. Chronic inflammation due to the underlying CD is likely the most plausible explanation for developing both T cell lymphoma and hypercoagulability state leading to PVT.


    We sincerely thank the affected individual for her permission to publish the results. We would also like to thank Dr. Reza Asadollahi, Medical Geneticist at University of Zurich, and Professor Mohammad Bagher Owlia, Rheumatologist at Shahid Sadoughi University of Medical Sciences, for their helpful comments on the manuscript.

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