Human leukocyte antigen-DQ2 homozygosity and the development of refractory celiac disease and enteropathy-associated T-cell lymphoma.

BACKGROUND & AIMS: Celiac disease (CD) is a common gluten-sensitive enteropathy associated with human leukocyte antigen (HLA)-DQ2 and HLA-DQ8. The aim of this study was to determine if a particular HLA-DQ subtype predisposes to complications such as refractory CD with (RCD II) or without aberrant T cells (RCD I), and enteropathy-associated T-cell lymphomas (EATL). METHODS: Molecular HLA-DQ typing was performed on 43 RCD I, 43 RCD II, and 30 EATL patients, and compared with age-matched groups of 121 patients with histologically defined uncomplicated CD and 183 healthy controls. All individuals were Dutch Caucasians and were at least 21 years of age. RESULTS: HLA-DQ2 was present in 79% of RCD I, 97.7% of RCD II, and 96.6% of EATL patients. The differences were significant when compared with 28.9% in controls but not with 91.7% in uncomplicated CD. Homozygosity for HLA-DQ2 was observed in 25.5% of RCD I, 44.1% of RCD II, and 53.3% of EATL patients vs 20.7% of uncomplicated CD patients and 2.1% of controls. HLA-DQ8 was present in 10.7% of CD, 16.2% of RCD I, 9.3% of RCD II, and 6.6% of EATL patients vs 20.2% of controls. CONCLUSIONS: Homozygosity for HLA-DQ2 is associated with RCD II and EATL. Early identification of HLA-DQ2 homozygous CD patients may help to recognize CD patients at risk for developing these severe complications.     

An unusual enteropathy-associated T-cell lymphoma with MYC translocation arising in a Japanese patient: a case report

Enteropathy-associated T-cell lymphoma (EATL) is a rare peripheral T-cell lymphoma classified into 2 types, with or without celiac disease, based on histology. Type 2 EATL is less commonly associated with celiac disease, in which cells are characterized by being monomorphic and small- to medium-sized. Cells are characterized by CD8 and CD56 expression and c-MYC oncogene locus gain. We present an atypical case of type 2 EATL in the jejunum, with human T-lymphotropic virus-1 that was CD4- CD8+ CD56- CD30- CD25- TIA-1+ and granzyme B+ on immunohistological staining. It also displayed translocation of chromosome 8p24 (c-MYC), as determined by fluorescent in situ hybridization. Mucosal spreading and intraepithelial invasion by lymphoma with villous atrophy were detected adjacent to the mucosal layer. The lymphoma may be derived from intraepithelial CD8+ T cells, similar to celiac disease.     

Refractory sprue syndrome with clonal intraepithelial lymphocytes evolving into overt enteropathy-type intestinal T-cell lymphoma

INTRODUCTION: Recently, patients with refractory sprue have been shown to contain a clonal proliferation of phenotypically abnormal intraepithelial lymphocytes in their intestine. Whether this signifies early enteropathy-type intestinal T-cell lymphoma (EITCL) or a reactive condition is not clear. We report on a patient presenting with the findings of refractory sprue who subsequently developed overt EITCL. MATERIAL AND METHODS: Duodenal biopsies from 1997 (refractory sprue) and duodenal and jejunal biopsies from 1998 (intestinal T-cell lymphoma) were compared by immunohistochemistry and PCR for the detection of T-cell receptor (TCR)-gamma gene rearrangements. Clonal PCR products were sequenced. RESULTS: The duodenal biopsies from both 1997 and 1998 and the jejunal tumor biopsy showed villus atrophy and an increase of intraepithelial lymphocytes with an abnormal immunophenotype (CD3+, CD4-, CD8- and TCR-beta-). In all duodenal specimens including the one from 1997, and the jenunal tumor biopsy, an identical clonal amplificate was detected by enzymatic amplification of the TCR-gamma gene. CONCLUSION: These data suggest that refractory sprue containing a clonal proliferation of phenotypically abnormal intraepithelial lymphocytes may represent an early manifestation of EITCL. The detection of immunohistochemical negativity for several antigens normally found on intraepithelial lymphocytes such as CD8 or the TCR-beta chain in combination with clonal T-cell populations by PCR may be helpful in identifying refractory sprue with a malignant transformation.     

Characterization of novel natural killer (NK)-cell and gammadelta T-cell lines established from primary lesions of nasal T/NK-cell lymphomas associated with the Epstein-Barr virus

Studies on nasal T/natural killer (NK)-cell lymphoma have been hampered by its tendency to cause necrosis. Thus, the establishment of cell lines of this neoplasm would seem to be valuable. This study attempted to establish cell lines from primary lesions of this tumor, and successfully obtained 2 novel Epstein-Barr virus (EBV)-positive cell lines, SNK-6 and SNT-8, by means of high-dose recombinant interleukin 2. Flow cytometry showed that SNK-6 had an NK-cell phenotype, CD3- CD4- CD8- CD19- CD56+ T-cell receptor (TCR) alpha/beta- TCR gamma/delta-, whereas SNT-8 was CD3+ CD4- CD8- CD19- CD56+ TCR alpha/beta- TCR gamma/delta+. These were consistent with immunophenotypes of their original tumors, and the cell lines had monoclonal EBV clones identical to ones in their original tumors. Thus, the cell lines developed from cells forming the primary lesions. Genotypic analysis showed that SNK-6 had unrearranged TCR and immunoglobulin heavy-chain genes, supporting the conclusion that SNK-6 was of NK-cell lineage. On the other hand, SNT-8 had rearranged TCR beta-, gamma-, and delta-chain genes, and together with its phenotype, SNT-8 proved to be a gammadelta T-cell line. This is the first report of the establishment of cell lines from primary lesions of nasal T/NK cell lymphomas, and the results demonstrated that there are at least 2 lineages, NK- and gammadelta T-cell, in this neoplasm. Moreover, it has been suggested that nasal T/NK cell lymphomas of these lineages may belong to the same clinicopathologic entity because both types of cases shared common clinical and histopathologic features.     

Coeliac disease and (extra)intestinal T-cell lymphomas: definition, diagnosis and treatment

Intestinal lymphomas encompass those lymphomas with a dominant or only localized occurrence in the intestinal tract. Coeliac disease is highly associated with enteropathy-associated T-cell lymphomas (EATLs). Coeliac disease-related lymphomas can appear at nodal or extranodal sites. EATL is often multifocal with ulcerative lesions, which explains the high perforation rate at presentation or during chemotherapy. Staging includes ear-nose-throat examination and CT scan of the chest and abdomen. Positron emission tomography (PET) scanning may be valuable. Accurate diagnosis based on endoscopic biopsies is preferable; if necessary, full thickness laparoscopic small-bowel biopsies are mandatory. Refractory coeliac disease (RCD) with aberrant T cells carries a high risk of development of EATLs. There is no satisfactory treatment for EATL, the only possibility of preventing EATL development in RCD being autologous bone marrow transplantation. EATLs can present in 20% of patients as extra-small-bowel T-cell lymphomas; such as subcutaneous panniculitis-like lymphoma, hepatosplenic gamma/delta lymphoma, nodal as well as sinus, gastric or colon disease and extraintestinal T-cell lymphomas. The majority of EATLs present as large cell lymphoma CD3+, CD8-, CD30+; however, they also present as small cell lymphoma CD3+, CD8+, CD30-. Sometimes gamma/delta lymphomas in CD are recognized. Work-up of EATL must include immunohistology, T-cell flow cytometry, T-cell rearrangement and adequate imaging with CT and PET scanning.     

T-cell lymphoma associated with natural killer-like T-cell reaction

We report a case of T-cell lymphoma showing in the peripheral blood (PB) exclusively T-lymphocytes with suppresser T-cell preponderance and a high percentage of natural killer (NK) marker positive cells by flow cytometry. A T-cell receptor (TCR) gene analysis of the PB leukocytes demonstrated rearrangements of TCRα, TCRβ, and TCRγ genes. Therefore, the phenotype and genotype appeared to be consistent with an NK-like T-cell leukemia/lymphoma. However, when the PB lymphocytes were separated by size, it was found that 80% of NK marker positive cells were in the smaller cell population, while the neoplastic cells were in the large cell gate. A diagnosis of T-cell lymphoma with reactive NK-like T-cells was finally confirmed by demonstrating the presence of both large atypical lymphoid cells and large granular lymphocytes (LGL) on PB smears. Although immunoperoxidase stain of bone marrow and colon showed positive T-cell markers in the tumor cell population, cytoplasmic granules could not be identified in tissue sections and, thus, a distinction between T-cell lymphoma and NK-like T-cell lymphoma could not be made by light microscopy until NK markers were studied. CD57 was demonstrated immunohistochemically in small lymphocytes but not in the large tumor cells in the colon. Electron microscopy, however, demonstrated LGL reaction to the lymphoma cells in the colonic biopsy. NK-like T-cell lymphoma usually carries a poorer prognosis than peripheral T-cell lymphoma, thus the distinction of these neoplasms is important. This study emphasizes that T-cell lymphoma may cause an LGL reaction or proliferation. If the lymphoma cells were of the same size as LGL, flow cytometric studies may have misled the diagnosis to NK-like T-cell-lymphoma. Am. J. Hematol. 57:331–337, 1998. © 1998 Wiley-Liss, Inc.     

Multiple cerebral lesions in a patient with refractory celiac disease: A case report

BACKGROUNDEnteropathy-associated T cell lymphoma (EATL) is an aggressive intestinal T cell lymphoma derived from intraepithelial lymphocytes, which occurs in individuals with celiac disease (CD). Cerebral involvement is an extremely rare condition and as described so far, lymphoma lesions may present as parenchymal predo-minantly supratentorial or leptomeningeal involvement. We describe a case of EATL with multifocal supra- and infratentorial brain involvement in a patient with refractory celiac disease (RCD).CASE SUMMARYA 58-years old man with known CD developed ulcerative jejunitis and was diagnosed with RCD type II. Six months later he presented with subacute cerebellar symptoms (gait ataxia, double vision, dizziness). Cranial magnetic resonance imaging (MRI) revealed multifocal T2 hyperintense supra- and infratentorial lesions. Laboratory studies of blood and cerebrospinal fluid were inconspicuous for infectious, inflammatory or autoimmune diseases. ¹⁸F-fluorodeoxyglucose-positron emission tomography/computed tomography (¹⁸FDG-PET/CT) scan showed a suspect hypermetabolic lesion in the left upper abdomen and consequent surgical jejunal resection revealed the diagnosis of EATL. During the diagnostic work-up, neurological symptoms aggravated and evolved refractory to high-dosage cortisone. Recurrent MRI scans showed progressive cerebral lesions, highly suspicious for lymphoma and methotrexate chemotherapy was initiated. Unfortunately, clinically the patient responded only transiently. Finally, cerebral biopsy confirmed the diagnosis of cerebral involvement of EATL. Considering the poor prognosis and deterioration of the performance status, best supportive care was started. The patient passed away three weeks after diagnosis.CONCLUSIONEATL with cerebral involvement must be considered as a possible differential diagnosis in patients with known RCD presenting with neurological symptoms.     

How I treat enteropathy-associated T-cell lymphoma

Enteropathy-associated T-cell lymphoma (EATL) is a complication of celiac disease (CD). This tumor derives from the neoplastic transformation of aberrant intraepithelial T lymphocytes emerging in celiac patients unresponsive to a gluten-free diet. Poor adherence to a gluten-free diet, HLA-DQ2 homozygosity, and late diagnosis of CD are recognized as risk factors for malignant evolution of CD. Recurrence of diarrhea, unexplained weight loss, abdominal pain, fever, and night sweating should alert physicians to this complication. The suspicion of EATL should lead to an extensive diagnostic workup in which magnetic resonance enteroclysis, positron emission tomography scan, and histologic identification of lesions represent the best options. Treatment includes high-dose chemotherapy preceded by surgical resection and followed by autologous stem cell transplantation, although biologic therapies seem to be promising. Strict adherence to a gluten-free diet remains the only way to prevent EATL.     

CD56- and CD4-positive non-Hodgkin's lymphoma of probable T-cell origin]

A 65-year-old man was admitted with swelling of the right neck and bilateral inguinal lymph nodes. Endoscopic examination revealed no nasal infiltration. Pathological examination of a neck lymph node biopsy specimen revealed peripheral T-cell lymphoma according to the Revised European-American Classification of Lymphoid Neoplasms (REAL). The phenotype of the lymphoma cells was CD56+, CD16-, CD2+, surface CD3-, cytoplasmic CD3+, CD4+, CD8-, CD5+, CD7- and CD45RO+. May-Giemsa staining demonstrated no azurophilic granules in the lymphoma cells. Immunohistopathologic examination showed negativity for TIA-1 and granzyme B, and rearrangement of the TCR C beta 1 gene was also noted. These findings strongly suggested that this was a T-cell lymphoma. The patient received 8 courses of CHOP chemotherapy plus sobuzoxane. This led to a marked decrease of lymph node swelling, and currently the patient is still in remission. According to the REAL classification, T/NK-cell lymphomas are included among the peripheral T cell tumours, and seem to constitute a heterogeneous group of neoplasms. Although some cases of CD4+ CD56+ lymphoma have been reported, the present case appears to be the first example to show TCR gene rearrangement and negativity for TIA-1 and granzyme B. Since the classification of T/NK-cell lymphoma is still controversial, accumulation of such cases may help to better define T/NK-cell neoplasms.     

Aggressive natural killer cell leukaemia/lymphoma in two patients with lethal midline granuloma

Summary. We report two patients with leukaemic proliferations of large granular lymphocytes. The immunophenotype study showed that the leukaemic cells were positive for CD2, CD38, CD56 and anti-HLA-DR monoclonal antibodies and negative for other T-cell (CD3, CD4, CD8) and B-cell markers (CD19, CD20 and surface immunoglobulins). The clinical course was acute and a diagnosis of aggressive natural killer cell leukaemia/lymphoma was made. No clonal rearrangements of either Cβ T-cell receptor or J_H immunoglobulin genes were found. Functional studies done in one patient demonstrated non-restricted cytotoxic activity after activation with IL-2. Lethal midline granuloma had been previously diagnosed in both patients. A possible relationship between this entity and the natural killer cell leukaemia is discussed.     

Ulcerative colon T-cell lymphoma: an unusual entity mimicking Crohn's disease and may be associated with fulminant hemophagocytosis

Primary gastrointestinal T-cell lymphoma is uncommon. Most arise from the small intestine and are usually associated with chronic celiac disease; the so-called enteropathy associated T-cell lymphoma. Primary colon T-cell lymphoma is much more rare. We present two patients with primary colon T-cell lymphoma. Both patients had chronic diarrhea and significant weight loss. Endoscopically, the lymphoma was characterized by the presence of multiple skipped ulcers distributed from the terminal ileum to the descending colon. It was differentiated from Crohn's disease by the absence of fistula or thickening of the intestinal walls. Histologically, the lymphoma was composed of medium to large atypical cells located in the ulcer base with extension to the muscular layer and the adjacent atrophic mucosa. Occasional increased intraepithelial lymphocytes were also seen. Immunohistochemically, the lymphoma cells and intraepithelial lymphocytes were CD3+, CD4-, CD56- and CD8-. It was difficult to diagnosis this unusual lymphoma by biopsy. Because most biopsy specimens showed mixed inflammation within which the lymphoma cell was sometimes hard to identify. Both patients died of fulminant hemophagocytic syndrome and Epstein-Barr virus genome was detected in the lymphoma cells using in situ hybridization on the final surgical specimens. Our study indicates that it is important to recognize this ulcerative colon T-cell lymphoma and to differentiate it from inflammatory bowel disease because of its much more aggressive clinical behavior.     

Survival in refractory coeliac disease and enteropathy-associated T-cell lymphoma: retrospective evaluation of single-centre experience

BACKGROUND: Coeliac disease may be regarded as refractory disease (RCD) when symptoms persist or recur despite strict adherence to a gluten-free diet. RCD may be subdivided into types I and II with a phenotypically normal and aberrant intraepithelial T-cell population, respectively. RCD I seems to respond well to azathioprine/prednisone therapy. RCD II is usually resistant to any known therapy and transition into enteropathy-associated T-cell lymphoma (EATL) is common. AIM: To provide further insight into RCD and the development of EATL, by reporting on long-term survival and risk of transition of RCD into EATL in a large cohort of patients with complicated coeliac disease. Design and METHODS: Retrospective comparison of responses to therapy in four groups of patients with complicated coeliac disease: 43, RCD I; 50, RCD II (total), of whom 26 with RCD II developed EATL after a period of refractoriness to a gluten-free diet (secondary EATL) and 13 were EATL patients without preceding history of complicated coeliac disease (de novo EATL). RESULTS: No coeliac-disease-related mortality was recognised in the RCD I group. The overall 5-year survival in the RCD I group it was 96%; in the RCD II (total) group was 58%; and in the RCD II group after developing EATL it was only 8%. The 2-year survival in the de novo EATL group was 20% versus 15% in secondary EATL group (p = 0.63). Twenty-eight (56%) of the 50 patients with RCD II died, 23 (46%) due to EATL, 4 due to a progressive refractory state with emaciation and 1 from neurocoeliac disease. CONCLUSION: Remarkably, no patient with RCD I developed RCD II or EATL within the mean follow-up period of 5 years (range 2-15 years). A total of 52% of the RCD II patients developed EATL within 4-6 years after the diagnosis of RCD II. More aggressive and targeted therapies seem necessary in RCD II and EATL.     

The serine protease granzyme M is preferentially expressed in NK-cell,gamma delta T-cell,and intestinal T-cell lymphomas: evidence of origin from lymphocytes involved in innate immunity

Granzyme M (GM) is a novel serine protease whose expression is highly restricted to natural killer (NK) cells, CD3(+)CD56(+) T cells, and gamma delta T cells. Using a GM-specific monoclonal antibody, we analyzed the expression of GM in 214 mature T-cell and NK-cell lymphomas. GM was preferentially expressed in nasal NK/T-cell lymphomas (100%), gamma delta T-cell lymphomas (100%), and intestinal T-cell lymphomas (85%). In contrast, GM expression was present at low prevalence in mycosis fungoides/Sézary syndrome (3%), anaplastic large-cell lymphoma (6%), panniculitis-like T-cell lymphoma (11%), and angioimmunoblastic T-cell lymphoma (0%) cases. Peripheral T-cell lymphomas of unspecified subtype showed an intermediate frequency (37%) of GM expression, consistent with their heterogeneous origin. We conclude that GM expression is a distinctive feature of the nasal NK/T-cell, gamma delta T-cell, and intestinal T-cell lymphomas, and suggest that these tumors develop from lymphocytes involved in innate immunity.     

Mucosal intra-epithelial lymphocytes in enteropathy-associated T-cell lymphoma, ulcerative jejunitis, and refractory celiac disease constitute a neoplastic population.

Loss of response to a gluten-free diet (refractory sprue) and ulcerative jejunitis are complications of celiac disease that may progress to enteropathy-associated T-cell lymphoma (EATL). Both conditions are characterized by the presence of a nonlymphomatous monoclonal T-cell population in the enteropathic mucosa. In EATL, a similar monoclonal population that shows clonal identity with the lymphoma itself is also present in the enteropathic mucosa. In this study we show that in all three circumstances the monoclonal T-cell population is constituted by cytologically normal, noninvasive intraepithelial T lymphocytes that share an identical aberrant immunophenotype with EATL. Patients with refractory sprue and/or ulcerative jejunitis are, therefore, suffering from a neoplastic T-cell disorder for which hematological treatment strategies need to be devised.     

Hepatosplenic γδ T-cell lymphoma

AIM: To investigate the clinicopathologic characteristics, immunophenotype and TCR gene rearrangements of hepatosplenic T-cell lymphoma in eight Chinese patients.METHODS: Eight Chinese patients with hepatosplenic γδ T-cell lymphomas were studied. Hematoxylin-eosin-stained slides and clinical histories were reviewed. We also carried out immunohistochemical staining for CD3, CD4,CD8, CD20, CD43, CD56, CD79a, UCHL-1, and TCR γδ. Rearrangements of TCR gamma and delta chain genes were also studied.RESULTS: The spleens were enlarged and the cut surfaces were homogeneous and red-purple in color without identifiable gross lesions or enlarged hilar lymph nodes. Histologically, lymphoma cells infiltrated the cords of Billroth and often packed the sinuses. Liver biopsy showed lymphoma cell infiltrations in the sinusoids, and three cases showed involvements of the portal tracts. Immunohistochemically lymphoma cells were positive for CD3, CD43, and CD56 in all cases. Four of eight cases were positive for CD8, and all cases were negative for CD4 (6/6). Monoclonal rearrangements of TCR γ gene were demonstrated by PCR analysis in five out of the eight cases. TCR δ gene rearrangements were detected in six out of the eight cases, which demonstrated single bands on PAGE gel, and the amplification products in two cases were confirmed by sequencing.CONCLUSION: The clinicopathology of hepatosplenic γδ T-cell lymphoma in Chinese patients is similar to what was previously reported except that the splenomegaly is not so massive, and CD8 is positive.     

Hepatosplenic γδ T-cell lymphoma

AIM: To investigate the clinicopathologic characteristics, immunophenotype and TCR gene rearrangements of hepatosplenic T-cell lymphoma in eight Chinese patients. METHODS: Eight Chinese patients with hepatosplenic γδ T-cell lymphomas were studied. Hematoxylin-eosin-stained slides and clinical histories were reviewed. We also carried out immunohistochemical staining for CD3, CD4, CD8, CD20, CD43, CD56, CD79a, UCHL-1, and TCR γδ. Rearrangements of TCR gamma and delta chain genes were also studied. RESULTS: The spleens were enlarged and the cut surfaces were homogeneous and red-purple in color without identifiable gross lesions or enlarged hilar lymph nodes. Histologically, Iymphoma cells infiltrated the cords of Billroth and often packed the sinuses. Liver biopsy showed Iymphoma cell infiltrations in the sinusoids, and three cases showed involvements of the portal tracts. Immunohistochemically Iymphoma cells were positive for CD3, CD43, and CD56 in all cases. Four of eight cases were positive for CD8, and all cases were negative for CD4 (6/6). Monoclonal rearrangements of TCR γ gene were demonstrated by PCR analysis in five out of the eight cases. TCR δ gene rearrangements were detected in six out of the eight cases, which demonstrated single bands on PAGE gel, and the amplification products in two cases were confirmed by sequencing. CONCLUSION: The clinicopathology of hepatosplenic γδ T-cell lymphoma in Chinese patients is similar to what was previously reported except that the splenomegaly is not so massive, and CD8 is positive.     

Nonhepatosplenic gamma delta T-cell lymphoma with initial testicular compromise

We report here a case of nonhepatosplenic gammadelta T-cell lymphoma with undescribed initial localization in testis, without hepatosplenomegaly or adenopathies, and subsequent development in the maxillary sinus. The maxillar mass biopsy revealed a T-cell infiltration, and its immunologic characterization by flow cytometry showed a gammadelta T-cell phenotype (CD45+, CD3+, CD2+, TCR gammadelta+), without expression of CD7, CD5, CD1a, TdT, CD4, CD8, TCR alphabeta, or NK antigens (CD16, CD56, and CD57). Clonal gamma-chain gene rearrangement by polymerase chain reaction (PCR) was detected in testicular and maxillar biopsies. Epstein-Barr virus type 1 (EBV) sequences were detected by molecular biology in the biopsy material, suggesting that this oncogenic virus may play a role in the genesis of the clonal expansion of gammadelta T-cells. The patient was initially treated with standard chemotherapeutic protocols, with poor response and aggressive course.     

CD5-CD56+ T-cell receptor silent peripheral T-cell lymphomas are natural killer cell lymphomas [see comments]

Non-Hodgkin's lymphomas are divided into B- and T-cell neoplasms. The existence and the clinical relevance of lymphomas derived from the third lymphocyte lineage, ie, natural killer (NK) cells are still controversial. NK cells are lymphocytes that mediate cytotoxicity without prior sensitization. NK cells also have phenotypic and genotypic characteristics: they express the NK-related antigen CD56, T- cell markers such as CD2 and CD7, but do not express CD5 and T-cell receptor (TCR) proteins, and their TCR locus is not rearranged. Therefore, if NK cell lymphomas exist, they should express some T-cell markers, but not alpha beta or gamma delta TCR proteins. Such lymphomas are actually called TCR silent peripheral T cell lymphomas (PTCL). To detect and characterize NK cell lymphomas, we investigated the immunophenotype and immunogenotype of 35 patients with TCR silent PTCL. The first group included 16 patients with a lymphoma of CD5-CD56+ phenotype, which is identical to normal NK cells. These patients had either a nasal/nasopharyngeal lymphoma (11 cases) or a lymphoma with predominant non-nasal/non-nodal initial involvement (five cases). Eight of the nine cases for which immunogenotypic data were available lacked clonal rearrangement of the TCR gamma genes. Thus, these tumors are likely to be NK cell lymphomas. The second group of 15 cases had a CD5+ phenotype (14 were CD56-, and 1 was CD56+) and clonal rearrangement of TCR gamma genes, indicating that they were true PTCL with unproductive TCR rearrangement. The four remaining cases were CD5- CD56- lymphomas and disclosed either a clonal (two cases) or no clonal (two cases) rearrangements of the TCR gamma genes. Altogether these findings show that CD5-CD56+ so-called "TCR silent PTCL" bear the immunophenotype and immunogenotype of normal NK cells and display peculiar clinical features distinct from true PTCL.     

Enteropathy-associated T-cell lymphoma complicating an autoimmune enteropathy

Enteropathy-associated T-cell lymphoma (EATL) is a rare non-Hodgkin lymphoma frequently associated with celiac disease. We report a case of EATL complicating adult autoimmune enteropathy (AIE). Analysis of phenotype, rearrangements in T-cell receptor genes, and chromosome alterations by high-resolution comparative genomic hybridization identified features distinct from those described for types I and II EATL. Furthermore, EATL arose from a single T-cell clone that had been present for several years in AIE-associated, oligoclonal, intestinal T-cell infiltrate. Emerging T-cell clones should be monitored in patients with AIE who receive long-term immunosuppressive therapy.