Malignancy In Coeliac Disease Research Articles

Esophagus adenocarcinoma in a young patient with celiac disease; Is celiac disease a predisposing factor for esophagus adenocarcinoma as well as squamous cell carcinoma?

We report a 36-year-old female with longstanding oily diarrhea and new-onset dysphagia that was diagnosed as celiac disease and esophagus adenocarcinoma. Celiac is a multisystemic autoimmune disease associated with a longstanding inflammatory process, especially in the gastrointestinal tract. This chronic inflammation may lead to a modest increase in neoplasia risk. There is a modest increased risk of malignancy in celiac disease, particularly adenocarcinoma and T-cell lymphoma of the small intestine and squamous cell carcinoma (SCC) of the esophagus, mouth, and pharynx. Although there is an association between SCC of the esophagus and celiac disease, there are no reports in the English literature about a relationship between celiac disease and esophageal adenocarcinoma. This case shows that as well as SCC, adenocarcinoma of the esophagus may also occur in patients with longstanding celiac disease.

Mucosal Healing and Risk for Lymphoproliferative Malignancy in Celiac Disease

Celiac disease (CD) is associated with an increased risk for lymphoproliferative malignancy (LPM). Whether this risk is affected by the results of follow-up intestinal biopsy, performed to document mucosal healing, is unknown. To examine the association between mucosal healing in CD and subsequent LPM. Population-based cohort study. 28 pathology departments in Sweden. 7625 patients with CD who had follow-up biopsy after initial diagnosis. The risk for LPM was compared with that of the general population by using expected rates. The rate of LPM in patients with persistent villous atrophy was compared with that of those with mucosal healing by using Cox regression. Among 7625 patients with CD and follow-up biopsy, 3308 (43%) had persistent villous atrophy. The overall risk for LPM was higher than that in the general population (standardized incidence ratio [SIR], 2.81 [95% CI, 2.10 to 3.67]) and was greater among patients with persistent villous atrophy (SIR, 3.78 [CI, 2.71 to 5.12]) than among those with mucosal healing (SIR, 1.50 [CI, 0.77 to 2.62]). Persistent villous atrophy compared with mucosal healing was associated with an increased risk for LPM (hazard ratio [HR], 2.26 [CI, 1.18 to 4.34]). The risk for T-cell lymphoma was increased (HR, 3.51 [CI, 0.75 to 16.34]) but not for B-cell lymphoma (HR, 0.97 [CI, 0.21 to 4.49]). No data on dietary adherence. Increased risk for LPM in CD is associated with the follow-up biopsy results, with a higher risk among patients with persistent villous atrophy. Follow-up biopsy may effectively stratify patients with CD by risk for subsequent LPM.

Su1019 Mucosal Healing and Risk of Lymphoproliferative Malignancy in Celiac Disease

Background: Celiac disease (CD) is associated with an increased risk of lymphoproliferative malignancy (LPM). It is unknown whether this risk is affected by the results of the followup intestinal biopsy, performed to document mucosal healing. We aimed to quantify the risk of LPM in those patients with CD who had persistent villous atrophy and those patients who had mucosal healing on follow-up biopsy. Methods: Using a population-based database that included all pathology departments in Sweden (n=28), we identified all patients with CD (equal to villous atrophy, Marsh histopathology stage 3) who had a follow-up biopsy between six months and five years after initial diagnosis, and compared the risk of LPM to that of the general population using expected rates based on age, gender, and calendar year. We used Cox regression to compare the rate of LPM in those with persistent villous atrophy to those with mucosal healing. Results: Among 7,625 patients with CD and a follow-up biopsy, persistent villous atrophy was present in 3,308 (43%). LPM developed in 53 (0.7%) patients, with a median time to LPM of 4.9 years after follow-up biopsy. The overall risk of LPM was increased compared to the general population (Standardized incidence ratio, SIR 2.81; 95% CI 2.10-3.67), but this increase was limited to those with persistent villous atrophy (SIR 3.78; 95% CI 2.71-5.12) with no significant increased risk among those with mucosal healing (SIR 1.50; 95% CI 0.77-2.62). Persistent villous atrophy compared to mucosal healing was associated with an increased risk of LPM (Hazard ratio, HR 2.26; 95% CI 1.18-4.34). This risk was primarily observed for T cell lymphoma (HR 3.51; 95% CI 0.75-16.34), with no association for B cell lymphoma (HR 0.97; 95% CI 0.21-4.49). Patients with subtotal or total villous atrophy on follow-up biopsy had a greater increase in LPM risk (HR 3.96; 95% 1.65-9.50) compared to those with partial villous atrophy (HR 1.90; 95% CI 0.70-5.19). Conclusions: The increased risk of LPM in CD is markedly influenced by the results of the follow-up biopsy; those with mucosal healing have an LPM risk similar to that of the general population. The increased risk of LPM among those with persistent villous atrophy is mainly for T cell lymphoma. Follow-up biopsy can effectively stratify CD patients regarding subsequent LPM risk.

Letter: Adnab‐9 as a potential non‐invasive biomarker for prediction of malignancy in coeliac disease

Letter: Adnab‐9 as a potential non‐invasive biomarker for prediction of malignancy in coeliac disease

Risk of Lymphoproliferative Malignancy in Relation to Small Intestinal Histopathology Among Patients With Celiac Disease

Celiac disease is associated with an increased risk of malignant lymphomas. The risk of lymphoproliferative malignancies in patients with small intestinal inflammation without villous atrophy and in patients with latent celiac disease is unknown. We performed a cohort study using duodenal and jejunal biopsy data that were collected from all 28 Swedish pathology departments (July 1969 to February 2008). We identified two population-based cohorts composed of 28,989 individuals with biopsy-verified celiac disease (villous atrophy, Marsh stage 3) and 13,140 individuals with small intestinal inflammation without villous atrophy (Marsh 1 + 2) and a regional cohort of 3711 individuals with latent celiac disease (positive celiac disease serology and normal mucosa). Cancer data were obtained by linkage to the National Cancer Registry. We used Cox regression to estimate hazard ratios (HRs) for lymphoproliferative malignancy and any solid cancer among the three cohorts compared with a total of 227,911 age- and sex-matched reference individuals. Although biopsy-verified celiac disease and intestinal inflammation were associated with lymphoproliferative malignancy (for celiac disease, HR = 2.82; 95% confidence interval [CI] = 2.36 to 3.37, n = 193; for inflammation, HR = 1.81; 95% CI = 1.42 to 2.31, n = 89), latent celiac disease was not associated with lymphoproliferative malignancy (HR = 0.97; 95% CI = 0.44 to 2.14, n = 7). The absolute rates of lymphoproliferative malignancies among persons with celiac disease, small intestinal inflammation, and latent celiac disease were 70.3 per 100,000 person-years, 83.4 per 100,000 person-years, and 28.0 per 100,000 person-years, respectively. Compared with individuals with celiac disease, individuals with small intestinal inflammation or latent celiac disease were at a statistically significantly lower risk of lymphoproliferative malignancy. Risk of any solid cancer was not increased beyond the first year of follow-up in any cohort. Celiac disease was associated with Hodgkin lymphoma and both T-cell and B-cell non-Hodgkin lymphomas. The risk of lymphoproliferative malignancy in celiac disease is dependent on small intestinal histopathology, with no increased risk in latent celiac disease.

Association of celiac disease and intestinal lymphomas and other cancers

Celiac disease (CD) is associated with intestinal lymphoma and other forms of cancer, especially adenocarcinoma of the small intestine, of the pharynx, and of the esophagus. Enteropathy-associated T-cell lymphoma (EATL) is a rare form of high-grade, T-cell non-Hodgkin lymphoma (NHL) of the upper small intestine that is specifically associated with CD. This NHL subtype arises in patients with either previously or concomitantly diagnosed CD. In a subgroup of patients, there is progressive deterioration of a refractory form of CD. EATL derives from a clonal proliferation of intraepithelial lymphocytes and is often disseminated at diagnosis. Extraintestinal presentations are not uncommon in the liver/spleen, thyroid, skin, nasal sinus, and brain. The outlook of EATL is poor. Recent studies indicated that (1) CD is associated with a significantly increased risk for NHL, especially of the T-cell type and primarily localized in the gut (EATL); (2) the CD-lymphoma association is less common than previously thought, with a relative risk close to 3; (3) CD screening is not required in patients with NHL of any primary site at the onset, unless suggested by specific findings (T-cell origin and/or primary gut localization). The risk of NHL associated with clinically milder (or silent) forms could be lower than in typical cases of CD. Several follow-up studies suggest that the GFD protects from cancer development, especially if started during the first years of life. Strict adherence to the GFD seems to be the only possibility of preventing a subset of rare but very aggressive forms of cancer.

Synchronous and metachronous small bowel adenocarcinomas in a patient with celiac disease

Synchronous and metachronous small bowel adenocarcinomas in a patient with celiac disease

Antiendomysium antibodies in Brazilian patients with celiac disease and their first-degree relatives.

Literature data have shown high specificity of antiendomysial antibodies (EmA IgA) in celiac disease. The scarcity of Brazilian reports concerning this subject motivated the present study. To determine the sensitivity and specificity of antiendomysial IgA antibodies in Brazilian celiac patients at diagnosis and after treatment, to confirm patient adherence to a gluten-free diet and to screen first-degree relatives. An extensive clinical and serological study was performed by investigating the presence of these antibodies in 392 individuals from Southern Brazil. Indirect immunofluorescence using human umbilical cord as substrate was employed and the total levels of IgA were determined by turbidimetry in all groups. The study was conducted on 57 celiac patients (18 at diagnosis, 24 who adhered to a gluten-free diet and 15 with marked or slight transgression of the diet), 115 relatives of celiac patients (39 families), 94 patients with other gastrointestinal diseases, and 126 healthy individuals from the general population. The results demonstrated 100% positivity for the recently diagnosed patients and for those consuming gluten, in contrast to the patients who complied with the diet (0%). In the control group one individual was positive, but refused to undergo a biopsy. In the group of other gastrointestinal diseases, one positive patient presented ulcerative colitis, Down's syndrome and epilepsy, and the intestinal biopsy was diagnostic for celiac disease. These data showed 99.3% specificity for the test. Eighteen relatives were positive for antiendomysial antibodies IgA (15.65%), and comparison with the healthy population revealed a significant difference. An intestinal biopsy was obtained from seven subjects (one with total villous atrophy and six without alterations in the mucosal architecture, but all with a high number of intra-epithelial lymphocytes). The method revealed 100% sensitivity and 99.3% specificity. Because it is not an invasive method it can be used for the screening of atypical and latent forms of celiac disease to avoid serial biopsies and to control adherence to a gluten-free diet with implications in the prevention of malignancy in celiac disease.

Malignancy in coeliac disease--effect of a gluten free diet.

Two hundred and ten patients with coeliac disease previously reported from this unit were reviewed at the end of 1985 after a further 11 years of follow up. The initial review at the end of 1974 could not demonstrate that a gluten free diet (GFD) prevented these complications, probably because the time on diet was relatively short. The same series has therefore been kept under surveillance with the particular aim of assessing the effects of diet on malignancy after a further prolonged follow up period. Twelve new cancers have occurred: of which one was a carcinoma of the oesophagus and two lymphomas. Thirty nine cancers developed in 38 patients and of 69 deaths, 33 were the result of malignancy. A two-fold relative risk (RR) of cancer was found and was because of an increased risk of cancer of the mouth and pharynx (RR = 9.7, p less than 0.01, 95% confidence interval (CI) = 2.0-28.3), oesophagus (RR = 12.3, p less than 0.01, CI = 2.5-36.5), and of non-Hodgkin's lymphoma (RR = 42.7, p less than 0.001, CI = 19.6-81.4). The results indicate that for coeliac patients who have taken a GFD for five years or more the risk of developing cancer over all sites is not increased when compared with the general population. The risk is increased, however, in those taking a reduced gluten, or a normal diet, with an excess of cancers of the mouth, pharynx and oesophagus (RR = 22.7, p < 0.001), and also of lymphoma (RR = 77.8, p < 0.001). A significant decreasing trend in the excess morbidity rate over increasing use of a GFD was found. The results are suggestive of a protective role for a GFD against malignancy in coeliac disease and give further support for advising all patients to adhere to a strict GFD for life.

Body content of selenium in coeliac disease.

Concentrations of selenium in whole blood, plasma, and leucocytes were determined in 16 patients with coeliac disease confirmed by biopsy and 32 controls. All the patients were clinically well and receiving gluten free diets. The concentrations of selenium were significantly lower in the leucocytes, blood, and plasma of patients compared with controls, probably indicating a decrease in the body content of selenium. A high incidence of malignancy in coeliac disease has been reported. As a protective role for selenium against cancer has been postulated, the importance of this unexpected observation of lowered tissue concentrations of selenium requires further investigation.

HLA antigens in coeliac disease associated with malignancy.

Coeliac patients are at greater risk than the general population of developing malignant neoplasms, particularly lymphomas. The establishment at the Clinical Research Centre of a national collaborative study of coeliac patients with malignancy provided the opportunity to carry out HLA typing for 55 HLA-A, B and C and the 10 recognised DR antigens on a group of coeliac patients with malignancy. Study of a sample of 44 patients with biopsy proven coeliac disease and histologically confirmed malignancy, including 12 with malignant histiocytosis, and 57 coeliac patients without malignancy, failed to show any significant differences in antigen frequencies between patients with and without malignancy. These results indicate that there are no HLA genetic markers associated specifically with the development of malignancy in coeliac disease.

Coeliac disease, splenic function, and malignancy.

Blood films from 41 cases of coeliac disease complicated by malignancy were examined and evidence of hyposplenism found in 12 cases (29%). This is similar to the proportion of adult coeliacs without malignancy who have hypoplenism and it is concluded that impaired splenic function is not associated with the development of malignancy in coeliac disease.

Depressed cell-mediated immunity in coeliac disease.

Fourteen coeliac patients on a gluten free diet (GFD) and 10 on a normal diet were studied by lymphocyte transformation in response to PHA to assess the integrity of cell-mediated immunity (CMI). Transformation was depressed in the majority taking a normal diet, with improvement after a GFD. In some patients the depression may have been due to a serum factor, as transformation was more nearly normal when the lymphocytes were cultured in pooled AB serum than in their own serum. There was no correlation between transformation and nutritional deficiencies. Mantoux tests were performed in some of these and other coeliac patients and there was a very significant reduction in the incidence of positive tests compared with controls. These findings provide evidence of depressed CMI in coeliac patients taking a normal diet with improvement on a GFD and may be of relevance to the high risk of malignancy in coeliac disease, further strengthening the case for a strict GFD.

Home Graduates Only

Two hundred and ten patients with coeliac disease previously reported from this unit were reviewed at the end of 1985 after a further 11 years of follow up. The initial review at the end of 1974 could not demonstrate that a gluten free diet (GFD) prevented these complications, probably because the time on diet was relatively short. The same series has therefore been kept under surveillance with the particular aim of assessing the effects of diet on malignancy after a further prolonged follow up period. Twelve new cancers have occurred: of which one was a carcinoma of the oesophagus and two lymphomas. Thirty nine cancers developed in 38 patients and of 69 deaths, 33 were the result of malignancy. A two-fold relative risk (RR) of cancer was found and was because of an increased risk of cancer of the mouth and pharynx (RR = 9.7, p less than 0.01, 95% confidence interval (CI) = 2.0-28.3), oesophagus (RR = 12.3, p less than 0.01, CI = 2.5-36.5), and of non-Hodgkin9s lymphoma (RR = 42.7, p less than 0.001, CI = 19.6-81.4). The results indicate that for coeliac patients who have taken a GFD for five years or more the risk of developing cancer over all sites is not increased when compared with the general population. The risk is increased, however, in those taking a reduced gluten, or a normal diet, with an excess of cancers of the mouth, pharynx and oesophagus (RR = 22.7, p &lt; 0.001), and also of lymphoma (RR = 77.8, p &lt; 0.001). A significant decreasing trend in the excess morbidity rate over increasing use of a GFD was found. The results are suggestive of a protective role for a GFD against malignancy in coeliac disease and give further support for advising all patients to adhere to a strict GFD for life.