Resolution of Small Bowel Follicular Lymphoma With Treatment of Concomitant Hepatitis B.

We report a case of small bowel follicular lymphoma regression with hepatitis B virus treatment. Our patient underwent surveillance colonoscopy that showed profound nodularity in the terminal ileum that was consistent with non-Hodgkin's lymphoma (NHL) on biopsy. Upon further testing the patient was found to be infected with hepatitis B virus. We decided to treat hepatitis B first to prevent its reactivation if the patient underwent therapy for NHL and with the thought that NHL can be stimulated by immunological response to antigens. Our patient was started on Entecavir, and fortunately the NHL regressed with no recurrence on follow-up endoscopies and biopsies.

[Anticipated efficacy of HPV vaccination in prophylaxis against nongenital cancers]. / Predpokládaná úcinnost HPV vakcinace v profylaxi nongenitálních karcinomu

BACKGROUND: There is a considerable number of studies on the efficacy HPV (human papillomavirus) vaccination against different cancers but relevant information is scattered in diverse journals. This paper is a review summarizing current knowledge of the potential of HPV vaccination against all HPV related cancers. AIM: HPV infection is probably the most frequent sexually transmitted disease. At least 13 HPV genotypes are classified as carcinogenic or probably carcinogenic in respect to cervical cancer. Almost 100% of cervical cancers are linked to HPV infection. HPV 16 and HPV 18 are the most frequently involved genotypes and account together for approximately 70% of cervical cancer in the world. Persistent high risk HPV infection is responsible for a significant proportion of vulvar, vaginal, anal and penile carcinomas. The virus has also been implicated in oncogenesis of head and neck cancers, including oropharyngeal cancers. HPV infection can play an important role in cancerogenesis of lung, esophagus, breast, and colon and rectum. On the contrary, published results indicate that HPV infection is not associated with prostate oncogenesis. Strong predominance of HPV 16 has been reported for all HPV associated cancer sites. Generally, it is estimated that approximately 5.2% of all cancers are associated with oncogenic HPV infection. Currently, there are two vaccines on the market; quadrivalent Silgard® (Gardasil®) and bivalent CervarixTM. Large trials for both vaccines have shown efficacy against HPV related infection and disease. Efficacy has been very high in HPV naive subjects to vaccine related types. While HPV vaccination is currently approved for the prevention of cervical cancer, it also has the potential in the prevention of all HPV associated malignancies. The Czech republic belongs to countries that cover HPV vaccination of girls at the age of 13- 14 years by general health insurance. Overall impact of this vaccination remains to be evaluated. The new issues of the role of HPV in oncogenesis, as well as the potential effect of HPV vaccination against HPV related nongenital cancers are discussed. CONCLUSION: Approximately 5.2% of all human cancers are associated with oncogenic human papillomavirus infection. HPV vaccination against the most risky HPV oncotypes may cause a significant reduction of these cancers mainly in the HPV naive population.

Primary intestinal T-cell and NK-cell lymphomas: a clinicopathological and molecular study from China focused on type II enteropathy-associated T-cell lymphoma and primary intestinal NK-cell lymphoma.

In China, which is a non-endemic area for celiac disease, primary intestinal T-cell and NK-cell lymphomas might comprise heterogeneous subtypes. Both type II enteropathy-associated T-cell lymphoma and primary intestinal NK-cell lymphoma are rarely reported and poorly characterized in China. In this study, we examined the clinicopathological and molecular features of 38 cases of primary intestinal T-cell and NK-cell lymphoma in Chinese patients. Based on these findings, we first classified the patients into an NK-cell group (n=6) and a T-cell group (n=32). In the NK-cell group, the mean age was 37 years. All tumors of the NK-cell group were positive for Epstein-Barr virus encoded mRNA in the majority of tumor cells and were polyclonal according to the results of commercial BIOMED-2 T-cell receptor gene rearrangement assays. The survival in the NK-cell group was significantly worse than that of the T-cell group (P=0.0247). Next, 7 tumors of the T-cell group were considered type II enteropathy-associated T-cell lymphoma, while 24 were considered peripheral T-cell lymphoma, not otherwise specified (NOS). In the type II enteropathy-associated T-cell lymphoma group, the mean age was 55 years. Type II enteropathy-associated T-cell lymphoma tumor cells from all seven patients were monomorphic, medium sized. The survival in the type II enteropathy-associated T-cell lymphoma group was significantly worse than that of the peripheral T-cell lymphoma, NOS group (P=0.0181). Multivariate analysis identified NK-cell phenotype, male gender, and CD8 positivity as factors for poor prognosis in our series of primary intestinal T-cell and NK-cell lymphoma patients. In conclusion, most cases of primary intestinal T-cell and NK-cell lymphoma in China are not associated with celiac disease and could be classified to NK-cell group, type II enteropathy-associated T-cell lymphoma group, and peripheral T-cell lymphoma, NOS group. Each group has distinctive histopathological features with prognostic significance.

Association of prostate stem cell antigen gene polymorphisms with the risk of stomach cancer in Japanese.

A recent whole-genome association study identified a strong association between polymorphisms in the prostate stem cell antigen (PSCA) gene and stomach cancer risk. In this case-control study, we aimed to validate this association, and further to explore environmental factors possibly interacting with PSCA polymorphisms in 708 incident stomach cancer cases and 708 age-sex matched controls. The association between PSCA polymorphisms and Helicobacter pylori infection was also examined. We found that rs2294008 and rs2976392, which were strongly linked to each other (D' = 1.00), were significantly associated with stomach cancer risk. Per allele odds ratio for rs2994008 was 1.40 (95% confidence interval: 1.19-1.65; p = 3.7 x 10(-5)). We found significant interaction with a family history of stomach cancer in first-degree relatives (p-heterogeneity = 0.009). Similar to originally reported association, we found significant heterogeneity between diffuse and intestinal type (p-heterogeneity = 0.007). No association was seen between PSCA polymorphisms and H. pylori infection. In conclusion, PSCA polymorphisms are associated with stomach cancer risk in Japanese. A possible interaction with family history warrants further evaluation.

Clinicopathological analysis of primary intestinal diffuse large B-cell lymphoma: Prognostic evaluation of CD5, PD-L1, and Epstein-Barr virus on tumor cells.

BACKGROUND: Primary intestinal diffuse large B-cell lymphoma (iDLBCL) is rare. In this study, we investigated the clinicopathological features of this disease to further understand the prognostic value of CD5, programmed cell death ligand 1 (PD-L1), and Epstein-Barr virus (EBV) on tumor cells. METHODS: Tumor specimens from 62 patients consecutively diagnosed with primary iDLBCL at a single institution were analyzed. RESULTS: Our series consisted of EBV-positive (EBV+ ) iDLBCL (n = 10), de novo CD5+ iDLBCL (n = 4), and DLBCL, not otherwise specified (DLBCL-NOS; n = 48). Notably, seven of 10 EBV+ cases had treated lymphoma-associated (n = 4) or iatrogenic immunodeficiency (n = 3). Two of 10 EBV+ cases expressed PD-L1 on tumor cells, whereas the remaining eight were positive for PD-L1 on microenvironment immune cells. Only one DLBCL-NOS case had neoplastic PD-L1 expression with a giant cell-rich appearance. Both EBV-harboring and PD-L1 expression on tumor cells, but not CD5, were associated with worse overall survival (OS) in iDLBCL patients receiving rituximab-containing chemotherapy (P = 0.0354, P = 0.0092, and P = 0.1097, respectively). Multivariate analysis identified PD-L1 positivity on tumor cells (P = 0.0106), PD-L1 negativity on microenvironment immune cells (P = 0.0193), and EBV positivity (P = 0.0324) as poor independent prognostic factors for OS. Among iDLBCL cases without any EBV association, CD5 positivity, or neoplastic PD-L1 expression, high PD-L1 expression (≥40%) on microenvironment immune cells predicted an extremely favorable outcome. CONCLUSION: EBV+ iDLBCL mainly comprised immunodeficiency-associated patients, which may highlight the specificity of the intestine. PD-L1 expression on tumor cells or microenvironment immune cells was found to have an opposite prognostic impact in iDLBCL.

Kaposi sarcoma-associated herpesvirus/human herpesvirus 8-associated extracavitary primary effusion lymphoma presenting as multiple lymphomatous polyposis.

Primary effusion lymphoma (PEL) is a distinct clinicopathological entity usually characterized by presentation as a lymphomatous body cavity effusion in the absence of solid tumor mass or dissemination during its clinical course. PEL can also rarely occur as a solid lymphoma involving nodal and extranodal sites and is referred to as extracavitary PEL. Here we report a unique case of extracavitary PEL in a 49-year-old HIV-seropositive patient who presented with vague abdominal pain and 20-lb weight loss. Esophagogastroduodenoscopy and colonoscopy revealed more than 100 broad-based intestinal polyps ranging from 2 mm to 3 cm in size, spreading from the duodenum to the rectum as a typical impression of "intestinal polyposis syndrome." Multiple biopsies demonstrated sheets of large lymphoid cells with characteristic features of extracavitary PEL with strong Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 virus positivity by immunohistochemistry. Extracavitary PEL presenting as distinctive multiple lymphomatous polyposis as manifested in the case has not been described previously.

Altered expression of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) during gastric carcinogenesis and its clinical implications on gastric cancer.

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a 465-kDa catalytic subunit of DNA-PK, a DNA repair apparatus. DNA-PKcs has been reported to be a tumor suppressor, but details of its expression in human cancer are controversial. To determine the protein expression and clinical implications of DNA-PKcs in gastric carcinogenesis and cancer progression, we evaluated its expression status by immunohistochemistry in 122 non-neoplastic gastric mucosa samples, and in 115 gastric adenomas and 564 consecutive gastric cancers. In addition, we evaluated the clinicopathologic characteristics of gastric cancers showing altered DNA-PKcs expression, and performed microsatellite instability (MSI) analysis at BAT-26 and frameshift mutation analysis of DNA-PKcs. DNA-PKcs expression was negative in foveolar epithelium of normal gastric mucosal tissues, but was positive in most Helicobacter pylori-associated gastritis, intestinal metaplasia and gastric adenoma tissues. In gastric cancers, negative expression of DNA-PKcs was found in 114 of the 564 (20.2%) cancers and was significantly associated with intratumoral neutrophils, MSI-high (H) phenotype, tumor progression, and poor patient survival (p<0.05). Frameshift mutations of (A)10 mononucleotide repeats in DNA-PKcs were found in 24.3% of MSI-H gastric cancers and these were associated with negative expression of DNA-PKcs. Although patients with MSI-H gastric cancers were found to have a lower risk of lymph node metastasis, gastric cancers harboring the (A)10 mutation of DNA-PKcs were found to have a higher risk of lymph node metastasis. In conclusion, the expression of DNA-PKcs was found to be altered during gastric carcinogenesis and negative DNA-PKcs expression was associated with gastric cancer progression. The (A)10 frameshift mutation of DNA-PKcs in gastric cancers was a target of defective mismatch repair, and was associated with lymph node metastasis.

Retroviral inclusions in the enteric smooth muscle of a tumor-bearing young chicken.

A 15-cm segment of small intestine from a 7-wk-old broiler chicken presented for slaughter was encased by a firm, white mass. Other tissues were grossly unremarkable. Microscopically, the enteric serosa and peripheral muscularis of this segment of small intestine were replaced by a fibrosarcoma. Numerous linear, intracytoplasmic, eosinophilic inclusion bodies were present in smooth muscle cells of the muscularis of the small intestine, and a few similar inclusions were present in the muscularis of the proventriculus. In the heart, there were rare intracytoplasmic inclusions typical of viral matrix inclusions. Ultrastructurally, inclusion bodies in enteric smooth muscle were viral matrix inclusions, and virions resembling avian retroviruses were present in adjacent intercellular spaces. Polymerase chain reaction (PCR) of the deoxyribonucleic acid (DNA) extracted from tumor tissues indicated the presence of proviral DNA of subgroup J avian leukosis virus. This is the first description of the light microscopic appearance of these viral matrix inclusions in enteric smooth muscle.

Papilloma-pseudovirus eradicates intestinal tumours and triples the lifespan of ApcMin/+ mice.

Inducing tumour-specific adaptive immunity, such as cytotoxic T lymphocyte (CTL) response, can result in promising antitumour effect against several human malignancies, especially in combination with immune checkpoint blockade strategies. However, little is known whether activation of innate immunity can lead to direct tumoricidal effect. Here, we develop a papilloma pseudovirus-based oral immunotherapeutic approach that shows strong tumoricidal effects in the gut, resulting in an almost tripled lifespan of ApcMin/+ mice (an animal model of human intestinal tumorigenesis). Mechanistically, these pseudoviruses activate the NLRP3 and AIM2 inflammasomes, leading to caspase-1-mediated tumour regression that is dependent on neither cytotoxic T lymphocytes nor humoral immune response. Blocking caspase-1 activation abrogated the therapeutic effects of the pseudoviruses. Thus, targeting innate immune sensors in tumours by the pseudoviruses might represent a strategy to treat intestinal tumours.

De Novo Human Herpesvirus 8 Tumors Induced by Rituximab in Autoimmune or Inflammatory Systemic Diseases.

OBJECTIVE: Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma (KS)-associated herpesvirus, is involved in KS and other tumors, including multicentric Castleman's disease and primary effusion lymphoma. Rituximab (RTX) is currently used for the treatment of several autoimmune or inflammatory diseases and humoral organ transplant rejection. De novo HHV-8 tumors induced by RTX used for these indications have not been reported previously. This study was undertaken to evaluate de novo HHV-8 tumors induced by RTX. METHODS: In this retrospective study, we investigated the clinical, virologic, and pathologic features of 5 HIV-negative male patients with HHV-8 tumors induced by RTX therapy. RESULTS: Patients were all immunocompromised by previous treatments, which consisted of steroids and/or immunosuppressive agents, and received RTX for insufficient response, disease progression, or transplant rejection. They developed HHV-8 tumors a median of 4 months after beginning treatment with RTX (range 3-13 months). Four patients had at least 1 risk factor for HHV-8, including a high Fitzpatrick skin phototype (of >3) (n = 3) and homosexuality (n = 1). Four patients developed KS (all 4 had skin lesions and 2 had visceral involvement), and 1 patient developed a solid primary effusion lymphoma. RTX was discontinued in all patients, and immunosuppressants were reduced when feasible. After a median follow-up of 20 months, 2 patients died. Remission of KS was complete in 1 patient and partial in 1 patient, and 1 patient had progression. CONCLUSION: Our findings indicate that patients who have a high skin phototype and are at risk of HHV-8 should be carefully screened for HHV-8 before RTX therapy. The safety of RTX, especially in nonlymphomatous disorders, should be carefully evaluated in patients at risk of HHV-8 tumors.

Primary Intestinal Diffuse Large B-cell Lymphoma in Taiwan Showed a Relative Higher Rate of Perforation and EBV Association.

We retrospectively investigated 59 surgically resected primary intestinal diffuse large B-cell lymphomas (PI-DLBCL) including 31 males and 28 females with a median age of 66. Eleven (19%) tumors were perforated at presentation; 8 (14%) were multicentric. Ileum (n=24; 43%) and ileocecum (n=17; 30%) were most frequently involved. Twenty-one (36%) patients did not receive chemotherapy or radiotherapy including 6 with perforation and died in 0.2 to 7 months. The 1-, 2-, and 5-year overall survival rates were 68.4%, 56.5%, and 50.0%, respectively. Seven (12%) of 59 cases were positive for Epstein-Barr virus (EBV) by in situ hybridization. IGH, BCL2, BCL6, and MYC foci were rearranged in 22%, 3%, 17%, and 7% cases, respectively, with 14% exhibiting gain/amplification at the MYC locus. Perforation (P=0.009), high ECOG PS (≥2) (P=0.018), and no adjuvant chemotherapy (P<0.001) were poor prognostic factors but not immunophenotype including co-expression of bcl-2 and myc, EBV status, or chromosomal aberrations. Perforation and chemotherapy remained significant by multivariate analysis. PI-DLBCL in Taiwan carried a relatively higher rate of perforation, lower frequency of germinal center B-cell phenotype, and higher EBV association as compared with studies from other geographic areas. Furthermore, perforation was a poor prognostic factor.

Pituitary neoplasia induced by expression of human neurotropic polyomavirus, JCV, early genome in transgenic mice.

In recent years, there has been mounting evidence pointing to the association of polyomaviruses with a wide range of human cancers. The human neurotropic polyomavirus, JCV, infecting greater than 75% of the human population produces a regulatory protein named T-antigen which is expressed at the early phase of viral lytic infection and plays a critical role in completion of the viral life cycle. Furthermore, this protein has the ability to transform neural cells in vitro and its expression has been detected in several human neural-origin tumors. To further investigate the oncogenic potential of the JCV early protein in vivo, transgenic mice expressing JCV T-antigen under the control of its own promoter were generated. Nearly 50% of the animals developed large, solid masses within the base of the skull by 1 year of age. Evaluation of the location as well as histological and immunohistochemical data suggest that the tumors arise from the pituitary gland. As T-antigen is known to interact with several cell cycle regulators, the neoplasms were analysed for the presence of the tumor suppressor protein, p53. Immunoprecipitation/Western blot analysis demonstrated overexpression of wild-type, but not mutant p53 within tumor tissue. In addition, co-immunoprecipitation established an interaction between p53 and T-antigen and overexpression of p53 downstream target protein, p21/WAF1. This report describes the analysis of inheritable pituitary adenomas induced by expression of the human polyomavirus, JCV T-antigen in transgenic mice where T-antigen disrupts the p53 pathway by binding to and sequestering wild-type p53. This animal model may serve as a useful tool to further evaluate mechanisms of tumorigenesis by JCV T-antigen.

Features of intestinal T-cell lymphomas in Chinese population without evidence of celiac disease and their close association with Epstein-Barr virus infection.

BACKGROUND: Intestinal T-cell lymphoma (ITCL) is a heterogeneous lymphoid neoplastic group with variable clinical and pathological features. ITCL in oriental countries is different from enteropathy-type intestinal T-cell lymphoma (ETCL) in relation to celiac disease and Epstein-Barr virus (EBV). The objective of this study was to investigate the clinicopathological features, immunophenotype, expression of cytotoxic molecule (TIA-1), T-cell receptor (TCR)-gamma gene rearrangement, and Epstein-Barr virus (EBV) latent infection in primary ITCL without celiac disease in Chinese. METHODS: The clinical data of 42 patients were analyzed, and the patients were followed up. Compared with human reactive lymphoid tissues, in situ hybridization for EBER1/2, polymerase chain reaction for TCR-gamma gene rearrangement, and immunohistochemical staining for immunophenotypes, TIA-1 and EBV latent membrane proteins (LMP-1) were investigated. Survival curves of different clinicopathological features, immuno-phenotypes, expression of LMP1, TCR-gamma gene rearrangement and therapy were analyzed. RESULTS: Three fourths of the patients suffered from ITCL in China were men with a peak age incidence in the 4th decade. Common presenting features included fever and hemotochezia. The prognosis was poor with a median survival of 3.0 months. The lesions were mostly localized in the ileocecum and colon. About 38/42 (90.5%) patients demonstrated pleomorphic medium-sized on large cells. Histological features of celiac disease were rarely seen. All 42 patients with ITCL revealed CD45RO positive. Neoplastic cells partially expressed T-cell differentiated antigens (CD3epsilon, CD4, CD8) and NK cell associated antigen (CD56). The positive frequency of CD3epsilon, CD4, CD8 and CD56 was 28/42 (66.7%), 7/42 (16.7%), 10/42 (23.8%) and 12/42 (28.6%) respectively. Thirty-nine cells (92.9%) expressed TIA-1, but none expressed CD20 and CD68. More than half of the patients (64.3%, 64.3% and 59.5%) revealed TCR-gamma gene rearrangement by three different TCR-gamma primers respectively. EBER1/2 was detected in 41 (97.6%) of the 42 patients. The expression frequency of LMP-1 was 38.1% (16/42). CONCLUSIONS: Primary ITCL without celiac disease in Chinese is a special highly EBV-associated clinicopathological entity. There are few similarities in patients with celiac disease in western countries. A small proportion of primary ITCLs in Chinese and extranodal NK/T-cell lymphoma of nasal type belong to the same spectrum.

Human herpesvirus-8-associated lymphoma of the bowel in human immunodeficiency virus-positive patients without history of primary effusion lymphoma.

This report describes two cases of human herpesvirus-8 (HHV-8)-associated large cell lymphoma of the bowel in human immunodeficiency virus (HIV)-positive men. Immunohistochemistry provides evidence of HHV-8 infection of the lymphoma cells (LNA1+, vIL-6+). In both cases, lymphoma cells were coinfected by the Epstein-Barr virus. One case was of B-cell lineage, but the second one was of null phenotype with isolated expression of the CD3 molecule. However, in the latter case, assessment of B- or T-cell clonality remained elusive. The chief finding for these two cases was the lack of history of primary effusion lymphoma. There was an apparent restriction of the tumor to the large bowel in the first case. For the second case, the bowel tumor was preceded by lymph node and liver involvement. The cases suggest that the incidence of HHV-8 infection in large cell lymphoma arising in the setting of HIV infection (other than primary effusion lymphoma) may be underestimated and that the detection of the viral gene products would be appropriate for greater understanding of the pathogenesis of these tumors. HUM PATHOL 33:846-849.

Viral genotypes and p53 expression in Epstein-Barr virus-associated primary malignant lymphomas of the intestines.

A small number (4% to 6%) of primary malignant lymphomas arising in the intestines express the EBV genome. However, in these tumors, the viral genotype and the role of tumor suppressor gene p53 have not been investigated. We sought to determine what genotype of EBV is frequently involved and whether the expression of p53 is related to these tumors. We used EBER-1 in situ hybridization and polymerase chain reactions (PCRs) for EBNA-1, EBNA-2A, and EBNA-2B to detect latent infection with EBV and to determine the genotype, respectively. In addition, we performed p53 PCR-SSCP (exons 5 through 9) and immunohistochemical analysis for p53. We found that EBV type B was present in 4 of 6 cases (67%); the genotype of the remaining cases could not be determined. The p53 PCR-SSCP indicated normal migration patterns in all malignant lymphomas, despite the fact that the tumor cells were strongly immunostained for p53 protein in 5 of the 6 cases. Thus, our study demonstrates that EBV-associated non-Hodgkin's lymphomas of the intestines in Korea are strongly related to the type B EBV and not to mutations of p53 gene. We suggest that EBV-associated intestinal lymphomas may arise through an interaction between the latent proteins of EBV and the wild-type p53 protein.

HLA antigen expression in enteropathy associated T cell lymphoma.

AIMS: To investigate the occurrence of abnormal patterns of HLA-ABC and HLA-DR expression in enteropathy associated T cell lymphoma and to relate such abnormalities to the Epstein Barr virus (EBV) status of the tumours. METHODS: Eleven enteropathy associated T cell lymphomas were immunostained with HC10 (HLA-ABC heavy chain) and TAL 1B5 (HLA-DR alpha chain) monoclonal antibodies and polyclonal anti-beta 2 microglobulin (beta 2m, the HLA-ABC light chain) antibodies. In situ hybridisation for EBV using EBER probes was performed on all cases. RESULTS: Tumour cells of two of 11 patients were EBER positive. One of these showed partial, and the other, complete loss of beta 2m. HLA-DR expression was undetectable in both patients. Of the remaining nine EBER negative tumours, two were HLA-ABC heavy chain negative or showed only occasional positive cells and five of nine showed partial or complete loss of the HLA-ABC light chain, beta 2m. Seven of the nine cases were either negative for HLA-DR or showed weak expression in a proportion of tumour cells. CONCLUSIONS: These data show that low or absent HLA-ABC and HLA-DR antigen expression occurs commonly in enteropathy associated T cell lymphoma. These abnormal patterns of HLA expression may be associated with escape from immune attack which, in a minority of patients, could be directed against EBV antigens.

Primary angiocentric T-cell intestinal lymphoma with Epstein-Barr virus in a 5-year-old boy.

A case of peripheral T-cell lymphoma affecting the small bowel of a 5-year-old boy is reported. The cells did not form a tumoral mass but infiltrated diffusely, arranged in an angiocentric pattern and associated with numerous ulcers, one of which perforated. Immunohistochemistry proved them to be CD45RO-, CD3-, and CD8-positive. CD20, CD4, and CD56 markers were negative. The presence of EBV in the lymphomatous cells was demonstrated by in-situ hybridization. Polymerase chain reaction study revealed T-cell receptor (TCR) gene rearrangement. Notably the hemophagocytic syndrome present on admission reverted after surgery. The authors are not aware of a previous report of intestinal T-cell lymphoma in a child.

Adult T cell leukemia presenting as multiple submucosal tumors of the intestine: detection of HTLV-I DNA by polymerase chain reaction.

We discuss a 45-year-old man who presented with ileus due to multiple submucosal tumors of the small and large intestines. Emergency operation was performed and histological examination of the tumors revealed pleomorphic cells with helper/inducer T-cell phenotype. Polymerase chain reaction (PCR) analysis using DNA extracted from the paraffin-embedded material showed that the intestinal, jejunal and femoral lymphoma samples contained human T-cell leukemia virus type-I (HTLV-I) DNA. Although no atypical lymphocytes were found in the peripheral blood, a diagnosis of adult T-cell leukemia was made. The PCR analysis of HTLV-I infection using paraffin-embedded materials seems to be useful when we encountered patients with T-cell lymphoma in the gastrointestinal tract.

[Epstein-Barr virus infection and expression of T-cell intracellular antigen-1 (TIA-1) in intestinal T-cell lymphoma].

OBJECTIVE: To study the status of Epstein-Barr virus (EBV) infection and the expression of TIA-1 antigen in 24 cases of intestinal T-cell lymphomas. METHODS: In situ hybridization for EBER1/2; immunohistochemical staining by three step ABC technique for TIA-1, LMP-1, CD30, CD45RO, CD3 AND CD20. 19 cases of intestinal B-cell lymphomas were used for comparison. RESULTS: (1) Of the 24 intestinal T-cell lymphoma cases, 23 were pleomorphic, medium to large cell type, and one cases was small cell type; in 20 of the 24 cases EBER1/2 signals were detected in the tumor cells; in 4 of the 20 EBER1/2 positive cases, tumor cells expressed LMP-1; EBER1/2 was not detected in 19 cases of intestinal B-cell lymphomas. (2) in 23 of the 24 cases, TIA-1 was expressed in most tumor cells, but not in the only case of small cell type; TIA-1 was negative in tumor cells of all 19 cases of intestinal B-cell lymphomas. CONCLUSIONS: A high level of EBV infection was present in this group of intestinal T-cell lymphomas, the expression of TIA-1 may be related to its cell origin. Intestinal T-cell lymphoma may be an EBV-associated extranodal NK/T cell lymphoma.