Are Complicated Forms of Celiac Disease Cryptic T-Cell Lymphomas?

Blood ◽  
1998 ◽  
Vol 92 (10) ◽  
pp. 3879-3886 ◽  
Author(s):  
Franck Carbonnel ◽  
Laurence Grollet-Bioul ◽  
Jean Claude Brouet ◽  
Marie Françoise Teilhac ◽  
Jacques Cosnes ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Celiac Disease ◽  
T Cell ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Cell Receptor ◽  
T Cell Lymphoma ◽  
Gluten Free Diet ◽  
Gluten Free ◽  
Duodenal Biopsies

Abstract We assessed the clonality of duodenal mucosal T cells in patients with celiac disease and controls. Fifteen adult patients were studied. Four patients had a complicated celiac disease, 3 did not respond to a gluten-free diet, and 2 had an ulcerative jejunitis (including 1 patient with nonresponsive celiac disease). Seven patients had an untreated celiac disease responsive to a gluten-free diet. Histological examination of duodenal biopsies of these 11 patients showed benign-appearing celiac disease without evidence of lymphoma. Four patients with nonulcer dyspepsia and normal duodenal biopsies served as controls. TCRγ gene rearrangements were analyzed by multiplex polymerase chain reaction on DNA extracted from duodenal biopsies. Major clonal rearrangements of the T-cell receptor were found in 4 cases, all with complicated celiac disease. Monoclonality was confirmed by DNA sequencing of the junctional region in 3 cases and by hybridization with clone-specific oligoprobes. Patients with celiac disease responsive to gluten-free diet had mainly a polyclonal pattern, with 1 of them having an oligoclonal rearrangement. An oligoclonal pattern was also observed in 2 control patients. Three patients with complicated celiac disease evolved to T-cell lymphoma with liver (n = 2) or bone marrow (n = 1) invasion. Identical clones were found in the enteropathic duodenojejunum and peripheral blood in the patient with large-cell lymphoma with bone marrow invasion. This study suggests that complicated celiac disease is a cryptic T-cell lymphoma.

Are Complicated Forms of Celiac Disease Cryptic T-Cell Lymphomas?

Blood ◽  
1998 ◽  
Vol 92 (10) ◽  
pp. 3879-3886
Author(s):  
Franck Carbonnel ◽  
Laurence Grollet-Bioul ◽  
Jean Claude Brouet ◽  
Marie Françoise Teilhac ◽  
Jacques Cosnes ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Celiac Disease ◽  
T Cell ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Cell Receptor ◽  
T Cell Lymphoma ◽  
Gluten Free Diet ◽  
Gluten Free ◽  
Duodenal Biopsies

We assessed the clonality of duodenal mucosal T cells in patients with celiac disease and controls. Fifteen adult patients were studied. Four patients had a complicated celiac disease, 3 did not respond to a gluten-free diet, and 2 had an ulcerative jejunitis (including 1 patient with nonresponsive celiac disease). Seven patients had an untreated celiac disease responsive to a gluten-free diet. Histological examination of duodenal biopsies of these 11 patients showed benign-appearing celiac disease without evidence of lymphoma. Four patients with nonulcer dyspepsia and normal duodenal biopsies served as controls. TCRγ gene rearrangements were analyzed by multiplex polymerase chain reaction on DNA extracted from duodenal biopsies. Major clonal rearrangements of the T-cell receptor were found in 4 cases, all with complicated celiac disease. Monoclonality was confirmed by DNA sequencing of the junctional region in 3 cases and by hybridization with clone-specific oligoprobes. Patients with celiac disease responsive to gluten-free diet had mainly a polyclonal pattern, with 1 of them having an oligoclonal rearrangement. An oligoclonal pattern was also observed in 2 control patients. Three patients with complicated celiac disease evolved to T-cell lymphoma with liver (n = 2) or bone marrow (n = 1) invasion. Identical clones were found in the enteropathic duodenojejunum and peripheral blood in the patient with large-cell lymphoma with bone marrow invasion. This study suggests that complicated celiac disease is a cryptic T-cell lymphoma.

Effect of a Gluten-free Diet on the Risk of Enteropathy-associated T-cell Lymphoma in Celiac Disease

2007 ◽  
Vol 53 (4) ◽  
pp. 972-976 ◽  
Author(s):  
Marco Silano ◽  
Umberto Volta ◽  
Alessandro De Vincenzi ◽  
Mariarita Dessì ◽  
Massimo De Vincenzi ◽  
...  
Keyword(s):  
Celiac Disease ◽  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Gluten Free Diet ◽  
Gluten Free

scholarly journals An unexpected deterrent in diagnosing refractory celiac disease and enteropathy-associated T-cell lymphoma: a gluten-free diet

2018 ◽  
Vol 8 (4) ◽  
pp. 233-236
Author(s):  
Nooreen Hussain ◽  
Faiz Hussain ◽  
Tulika Chatterjee ◽  
Jan N. Upalakalin ◽  
Teresa Lynch
Keyword(s):  
Celiac Disease ◽  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Gluten Free Diet ◽  
Gluten Free ◽  
Refractory Celiac Disease

Increased IgA Glycoprotein-2 Specic Antibody Titres in Refractory Celiac Disease

2014 ◽  
Vol 23 (2) ◽  
pp. 127-133 ◽  
Author(s):  
Sascha Gross ◽  
Sjoerd F. Bakker ◽  
Adriaan A. Van Bodegraven ◽  
Ingrid M.W. Van Hoogstraten ◽  
Kyra A. Gelderman ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Celiac Disease ◽  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Gluten Free Diet ◽  
Gluten Free ◽  
Refractory Celiac Disease

Background & Aims: In most cases celiac disease (CD) is successfully treated with a gluten-free diet (GFD). However, some patients become refractory to the GFD. Refractory CD (RCD) patients have an increased risk for developing enteropathy associated T-cell lymphoma and early diagnosis is therefore of importance. Currently, RCD diagnosis relies on endoscopy and adequate serological markers are lacking. Antibodies against glycoprotein-2 (GP2A) were described in Crohn's disease (CrD) and active CD but not in ulcerative colitis (UC), suggesting this is a specific marker for small intestinal lesions.Methods: Sera obtained from patients visiting our outpatient clinic for routine serological tests for diagnosis and/or follow-up of inflammatory bowel disease (n=78), active CD (n=45), GFD (n=34) and RCD (n=15) were analysed for GP2A titres.Results: Increased GP2A-IgA levels in CrD and active CD as compared to controls (p<0.001) and lack thereof in UC was confirmed. However, we could not confirm the association with small bowel localization within the CrD patient group. Within CD patients, we demonstrated a significant decrease of GP2A-IgA titres upon a GFD and increased levels in RCD patients as compared to patients on a GFD. Although GP2A-IgA was not associated with the degree of villous atrophy, GP2A-IgA levels were able to distinguish RCD patients from GFD patients (ROC AUC=0.79, p=0.002).Conclusion: Follow-up of GP2A-IgA titres in CD patients on a GFD may help to identify patients at risk for developing RCD.Abbreviations: ABSA: anti-bovine serum albumine; ASCA: anti- Saccharomyces cerevisiae antigen; AU:artificial units; AUC: area under the curve; CD: celiac disease; CrD: Crohn's disease; EATL: enteropathyassociated T-cell lymphoma; EmA: anti-endomysium antibodies; GFD: gluten free diet; GP2A: glycoprotein 2 antibodies; IEL: intraepithelial lymphocytes; RCD: refractory celiac disease; ROC: receiver operator curve; TG2A: transglutaminase-2 antibodies; UC: ulcerative colitis.

scholarly journals Molecular diagnosis angioimmunoblastic T-cell lymphoma

2019 ◽  
Vol 91 (7) ◽  
pp. 63-69
Author(s):  
N G Chernova ◽  
Y V Sidorova ◽  
S Y Smirnova ◽  
N V Ryzhikova ◽  
E E Nikulina ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
T Cell ◽  
Peripheral Blood ◽  
Cell Lymphoma ◽  
Cell Receptor ◽  
T Cell Lymphoma ◽  
Tissue Samples ◽  
Angioimmunoblastic T Cell Lymphoma ◽  
Allele Specific

Aim: to determine molecular diagnostics routine for different tissue samples in angioimmunoblastic T-cell lymphoma. Materials and methods. Molecular studies were performed for 84 primary AITL patients. The median age was 61 year (29-81); the male to female ratio was 48/36. T-cell and B-cell clonality was assessed by GeneScan analysis of rearranged T-cell receptor (TCRG, TCRB) and immunoglobulin heavy chain genes. For the quantitative determination of cells with RHOA G17V mutation real - time polymerase chain reaction (PCR) with allele - specific LNA modified primers was used. Results. In lymph nodes rearrangements of T-cell receptor genes were determined in 76 (90.5%) of 84 patients and were absent in 8 (9.5%) cases. Identification of the same clonal products of the TCRG and TCRB genes in the lymph node and in peripheral blood and/or bone marrow indicated the prevalence of the tumor process and was observed in 64.7% of patients. Clonal products in peripheral blood and/or bone marrow different from those in the lymph node indicated reactive cytotoxic lymphocyte population and were noted in 58.8% of AITL cases. Simultaneous detection of T- and B-cell clonality in the lymph node was observed in 20 (24.7%) of 81 patients. Cells with RHOA G17V mutation were detected in lymph node in 45 (54.9%) of 82 patients. The use of allele - specific PCR with LNA modified primers revealed presence of the tumor cells in peripheral blood in 100% and in bone marrow in 93.9% of patients with G17V RHOA mutation in the lymph nodes. Conclusion. The validity of different molecular assays performed on certain tissue samples for the diagnosis of angioimmunoblastic T-cell lymphoma has been evaluated. Quantitative allele - specific PCR assay for RHOA G17V mutation based on LNA modified primers possesses sufficient sensitivity for tumor process prevalence evaluation and minimal residual disease monitoring.

Ehrlichiosis Mimicking T-Cell Lymphoma/Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4343-4343
Author(s):  
Ashok Malani ◽  
Robert Weigand ◽  
Vicram Gupta ◽  
Lawrence Hertzberg ◽  
Gautam Rangineni
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
T Cell ◽  
T Cell Receptor ◽  
Gene Rearrangement ◽  
Bone Marrow Cells ◽  
Cell Lymphoma ◽  
Cell Receptor ◽  
T Cell Lymphoma ◽  
Pcr Analysis

Abstract Immunophenotyping by flow cytometry has revolutinized the diagnosis of blood cell disorders such as leukemias and lymphomas and is now commonly used in diagnosis and prognosis of such patients. We describe a case of human ehrlichiosis mimicking T-cell lymphoma/leukemia based on flow cytometry of bone marrow cells and confirmed by T-cell receptor gene rearrangement (TCR) by polymerase chain reaction (PCR). Treatment with doxycycline reversed these findings. A 20-year-old, Amish female presented with fatigue, fever, chills, sweating, low back pain, and lower abdominal pain for 2 days. She admitted to multiple bites from ticks 2 weeks prior to presentation and also reported having numerous animals such as cats, dogs, cows, goats, horses at her farm where she lived. Clinical exam was significant for fever of 101.4 F, heart rate of 118/min, BP of 80/60 mm Hg and a distended urinary bladder which was treated by catheter drainage. Relevant laboratory tests are shown in table 1. Table 1 Hemoglobin 9.7 12–16 gm/dl WBC 0.8 4–10.8 k/mm3 Platelets 16 150–400 k/mm3 Segments 62% 50–75% Lymphocytes 15% 20–40% Sodium 140 125–135 mmol/L AST 126 0–37 IU/L ALT 71 0–65 IU/L Alk. Phos. 49 50–136 IU/L LDH 691 91–190 IU/L Chest radiograph, Ultrasound and Computed tomography scan of the abdomen were within normal limits. With a provisional diagnosis of septic shock and suspicion for Ehrlichiosis, therapy with intravenous(IV) fluids, vasopressors and doxycycline was initiated. Blood was cultured and a sample was forwarded to CDC for analysis of tick borne infections. In order to evaluate and exclude blood disorders like leukemia and lymphoma in a patient with fever and pancytopenia, a bone marrow aspiration and biopsy was performed. It showed cytologically abnormal-appearing, large sized lymphocyte population with irregular nuclear membranes. Flow cytometry of the bone marrow cells revealed 8–10% of phenotypically abnormal T-cells with abnormally weak intensity of membrane surface CD3, CD5, and CD7 expression and negativeCD4 and CD8 expression. These cells also expressed HLA-DR and CD38 at uncommonly bright intensity and there were no CD34 benign immature B-cells. Cytogenetics however was normal. Interestingly, PCR analysis was positive for clonal TCR gamma gene rearrangement. These results were reported as consistent with involvement of marrow by a peripheral T-cell lymphoma/leukemia T-Cell receptor PCR analysis T-Cell receptor PCR analysis Since the patient was steadily improving with IV Doxycycline, we decided to wait and repeated the bone marrow aspiration a week later. This time the bone marrow exam was found to be normal morphologically, on flow cytometry and TCR gamma gene rearrangement by PCR. Patient was discharged on oral doxycycline after a stay of 13 days in the hospital. The blood test for ehrlichiosis from CDC was reported 3 weeks later as positive for Ehrlichia chaffeensis by PCR. Patient is doing well 6 months after the illness. This case illustrates that Ehrlichiosis can transiently cause T cell abnormalities resulting in false positive analysis on flow cytometry and TCR gamma gene rearrangement, thereby leading to false positive diagnosis of Ehrlichiosis. Reconfirmation with repeat studies need to be done before considering active treatment for lymphoma/leukemia.

Defective synthesis or association of T-cell receptor chains underlies loss of surface T-cell receptor–CD3 expression in enteropathy-associated T-cell lymphoma

Blood ◽  
2008 ◽  
Vol 112 (13) ◽  
pp. 5103-5110 ◽  
Author(s):  
Jennifer M. L. Tjon ◽  
Wieke H. M. Verbeek ◽  
Yvonne M. C. Kooy-Winkelaar ◽  
Binh H. Nguyen ◽  
Arno R. van der Slik ◽  
...  
Keyword(s):  
Celiac Disease ◽  
T Cell ◽  
Cell Surface ◽  
Cell Line ◽  
T Cell Receptor ◽  
Cell Lymphoma ◽  
Cell Receptor ◽  
Intraepithelial Lymphocytes ◽  
T Cell Lymphoma ◽  
Cell Surface Expression

Abstract Enteropathy-associated T-cell lymphoma, an often fatal complication of celiac disease, can result from expansion of aberrant intraepithelial lymphocytes in refractory celiac disease type II (RCD II). Aberrant intraepithelial lymphocytes and lymphoma cells are intracellularly CD3ϵ+ but lack expression of the T-cell receptor (TCR)–CD3 complex on the cell surface. It is unknown what causes the loss of TCR-CD3 expression. We report the isolation of a cell line from an RCD II patient with the characteristic phenotype of enteropathy-associated T-cell lymphoma. We demonstrate that in this cell line the TCR-α and -β chains as well as the CD3γ, CD3δ, CD3ϵ, and ζ-chains are present intracellularly and that assembly of the CD3γϵ, CD3δϵ, and ζζ-dimers is normal. However, dimerization of the TCR chains and proper assembly of the TCR-CD3 complex are defective. On introduction of exogenous TCR-β chains, but not of TCR-α chains, assembly and functional cell surface expression of the TCR-CD3 complex were restored. Defective synthesis of both TCR chains was found to underlie loss of TCR expression in similar cell lines isolated from 2 additional patients. (Pre)malignant transformation in RCD II thus correlates with defective synthesis or defective association of the TCR chains, resulting in loss of surface TCR-CD3 expression.

Long Term Results of Autologous Hematopoietic Cell Transplantation (AHCT) for Peripheral T Cell Lymphoma: The Stanford Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1906-1906 ◽  
Author(s):  
Andy I. Chen ◽  
Alex McMillan ◽  
Robert S. Negrin ◽  
Sandra J. Horning ◽  
Ginna G. Laport
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Cell Lymphoma ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
Long Term Results ◽  
High Dose ◽  
Refractory Disease ◽  
Anaplastic Lymphoma ◽  
First Remission

Abstract The peripheral T cell lymphomas (PTCL) are uncommon malignancies that typically carry a worse prognosis than the B cell non-Hodgkins lymphomas. There is no uniform standard therapy for PTCL, and AHCT is often offered at relapse or as consolidation in first remission due to the inherently poor prognoses. We conducted a retrospective review of patients who underwent AHCT for PTCL from 1989 to 2006 at Stanford, excluding mycosis fungoides and lymphoblastic lymphoma. Fifty-eight cases were identified: systemic anaplastic large cell (ALCL, n=18), PTCL unspecified (NOS, n=17), angioimmunoblastic (AITL, n=9), nasal type extranodal NK/T (nNK/T, n=7), primary cutaneous anaplastic large cell (n=5), hepatosplenic (n=2), and adult T cell lymphoma/leukemia (n=1). The median age at AHCT was 45 years (range 18–73), and 57% were male. The graft source was mobilized peripheral blood HC in 86% and bone marrow in 14%. The graft was T cell purged in 86% of cases. The conditioning regimen was high dose cyclophosphamide, carmustine, and etoposide in 83% of cases with the rest receiving total body irradiation, carmustine, and etoposide. Fifteen patients were transplanted in first complete or partial response (CR/PR1); 32 in second or beyond CR or PR (CR/PR2+); and 11 with primary refractory disease (REF). The PTCL subtypes transplanted in CR1 (n=12) and PR1 (n=3) included nNK/T (5), AITL (4), NOS (2), hepatosplenic (2), and ALCL (2). Multiple regimens were required to achieve first response in 5 patients. Only one ALK+ (anaplastic lymphoma kinase) ALCL pt was transplanted in CR/PR1 and required 3 induction regimens. The median follow up was 5 years (yr) (range 1–12). For all subjects, five yr overall survival (OS) was 49% and 5 yr progression free survival (PFS) was 24%. Disease status at AHCT had a strong impact on PFS (p=.004) and OS (p=0.06). Five yr PFS was 51%, 17%, and 0%, respectively, and the PFS curve appeared to plateau at 5 yrs. Corresponding OS at 5 yrs for the CR/PR1, CR/PR2+, and REF patients were 76%, 41%, and 36%, respectively. The number of prior regimens and achievement of CR at day +90 post AHCT were also significant factors for PFS by univariate analysis. Age, bone marrow involvement, B symptoms, stage, and histology were not significant for PFS or OS. By multivariate analysis, CR at day +90 remained a highly significant factor for both PFS and OS (p&lt;0.0001 and p=0.0025, respectively). Only 1 patient died from treatment related mortality (&lt;2%). Of interest, 8 patients who progressed after AHCT had a stable CR to subsequent salvage therapy or allogeneic transplant. In summary, about half of PTCL transplanted in CR/PR1 are progression free at 5 yrs, but CR/PR2+ and REF patients fared poorly. CR status at day +90 after AHCT was also a robust predictor for PFS and OS. Based on these results, AHCT may benefit PTCL patients who are consolidated in first remission and deserves further study. In contrast, those with relapsed or refractory disease experienced minimal benefit, and thus novel strategies are especially needed for this group of patients.

scholarly journals Synchronous Collagenous Sprue and Enteropathy-Type T Cell Lymphoma: Variants of the Same Disease

2004 ◽  
Vol 18 (5) ◽  
pp. 329-332 ◽  
Author(s):  
SAC Medlicott ◽  
PL Beck ◽  
S Loken ◽  
T Crabtree
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Receptor Gene ◽  
Cell Receptor ◽  
T Cell Lymphoma ◽  
Gluten Free ◽  
Chain Reaction ◽  
Free Air ◽  
Polymerase Chain ◽  
T Cell Receptor Gene

A 64-year-old man with treated hypothyroidism had 10 months of diarrhea, abdominal pain, anorexia and recent involuntary 13.6 kg weight loss. He presented to hospital with an acute abdomen that had a radiological correlate of free air under the diaphragm. He was diagnosed with a perforated mid-jejunum due to an ulcerated enteropathy-type T cell lymphoma (ETL), complicating collagenous sprue and cryptic celiac disease. Polymerase chain reaction verified monoclonal g- and b-T cell receptor gene rearrangements in the neoplasm. He had a complete resolution of symptoms when treated with a gluten-free diet in the postoperative period. This is apparently the first report describing collagenous sprue and ETL as synchronous lesions. Because atypical CD8+ lymphocytes are in both the collagenous sprue epithelium and ETL, the implication is that collagenous sprue is a noninvasive component of the ETL.

CD30+ Anaplastic Enteropathy-Associated T-cell Lymphoma Mimicking Crohn’s Disease

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S95-S96
Author(s):  
J L Harbert ◽  
F Da Silva Lameira ◽  
W Beversdorf ◽  
R Bhalla ◽  
E Rinker
Keyword(s):  
Crohn’S Disease ◽  
Celiac Disease ◽  
T Cell ◽  
Crohn's Disease ◽  
Cell Lymphoma ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
Fistula Formation ◽  
Peripheral T Cell Lymphoma ◽  
Eosinophilic Infiltrate

Abstract Introduction/Objective Enteropathy-associated T-cell lymphoma (EATL) is an aggressive peripheral T-cell lymphoma with a very poor prognosis. It is not uncommon for patients with EATL to present with intestinal obstruction or perforation, with the diagnosis made following surgical resection or autopsy. Although EATL is associated with celiac disease, this diagnosis may be made concomitant with EATL. The symptomology is often non-specific, particularly without a known history of celiac disease, and progression may be rapid. Methods/Case Report We describe the case of a 57 year old male who presented with several months of diarrhea, fatigue, night sweats, severe weight loss, and failure to thrive. Initial workup indicated positivity for Clostridium difficile and cryptosporidium, leading to antibiotic treatment. His symptoms persisted without significant improvement and a presumptive diagnosis of Crohn’s disease was made based on colonoscopy with biopsy and imaging that showed inflammatory changes with entero-enteric fistula formation. Further clinical decline necessitated exploratory laparotomy which revealed multiple enteric strictures, intra-loop abscesses, and necrotic ulceration necessitating segmental ileal resections. There was no associated lymphadenopathy. Microscopically, there was a dense, polymorphic lymphoid population within the bowel wall with associated mucosal ulceration and abundant necrosis. Striking anaplastic cytomorphology was present, with a heavy intratumoral eosinophilic infiltrate. Neoplastic lymphocytes were CD3+, CD30+ T cells with a CD7+, CD5-, CD4-, CD8-, CD56-, ALK- immunophenotype. The adjacent intestinal mucosa showed features of celiac disease (villous atrophy, intraepithelial lymphocytosis). Results (if a Case Study enter NA) NA Conclusion The prominent anaplastic morphology in combination with strong, diffuse CD30 expression prompted consideration of other T cell lymphomas, including anaplastic large cell lymphoma and peripheral T cell lymphoma, NOS, within the differential. The presence of coexisting histologic changes of celiac disease, dense eosinophilic infiltrate, and absence of lymphadenopathy were clues to the correct diagnosis. Notably, the frequency of CD30 expression in EATL is variable but common among cases manifesting large cell morphology.

Sign in / Sign up

Export Citation Format

Share Document