Changes in the inflammatory microenvironment in premalignant colonic adenomatous polyps: Evidence for immunosurveillance?

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 535-535
Author(s):  
David Mansouri ◽  
James Hugh Park ◽  
Clare Orange ◽  
Emilia M. Crighton ◽  
Paul G. Horgan ◽  
...  
Keyword(s):  
T Cell ◽  
Inflammatory Response ◽  
Adenomatous Polyps ◽  
Observer Agreement ◽  
Cytotoxic T Cell ◽  
Specific Response ◽  
Low Grade ◽  
High Grade ◽  
Early Stage Disease ◽  
Local Inflammatory Response

535 Background: The majority of colorectal cancers develop through the adenoma-carcinoma sequence. Recently, the host inflammatory response has become recognized as a key determinant of outcome. In particular, a pronounced peri-tumoral local inflammatory infiltrate identifies those with a better outcome. The present study aimed to characterize the local inflammatory response in pre-malignant colorectal adenomatous polyps. Methods: Patients with adenomatous polyps removed at colonoscopy as part of a population FOBt screening program were identified from a prospectively maintained database. All polyps were greater than 1cm. Whole slide immunohistochemistry was performed to assess intraepithelial T-cell (CD3+), cytotoxic T-cell (CD8+) and macrophage (CD68+) infiltrate. Inter-observer agreement for assessment of inflammatory cell infiltrate was good or better for CD3+, CD8+ and CD68+staining (Kappa 0.66, 0.66, 0.79 respectively). Results: A total of 207 adenomatous polyps, 107 high-grade (HG), 100 low-grade (LG), from 134 patients were included. Median age was 65 years, 33 (25%) were female and 15 (11%) were taking regular aspirin. Comparing HG and LG polyps, there were more older and female patients in the HG group (p<0.05). There was no difference in location (p=0.222), macroscopic morphology (p=0.445) or aspirin (p=0.377) use between groups. Microscopically, HG polyps were more likely to contain a villous component than LG polyps (65% vs 50%, p<0.05). Overall, high levels of CD3+, CD8+ and CD68+ infiltrate were observed in 68%, 25% and 72% of polyps respectively. Both CD3+ (74% vs 61%, p<0.05) and CD8+ (37% vs 13%, p<0.001) infiltrate was higher in HG polyps compared to LG polyps. There was no association with polyp grade and CD68+infiltrate (74% vs 70%, p=0.540). Conclusions: An increase in local T-lymphocytic infiltrate, but not macrophage infiltrate was identified with progression from low-grade to high-grade dysplasia. This would suggest a specific response to early disease progression confirming increased immunosurveillance. Therefore, such early stage disease may amenable to immunomodulatory treatment.

scholarly journals HPV-16 E7-Specific Cellular Immune Response in Women With Cervical Intraepithelial Lesion Contributes to Viral Clearance: A Cross-Sectional and Longitudinal Clinical Study

2022 ◽  
Vol 12 ◽  
Author(s):  
Lina Zhang ◽  
Xinyi Shi ◽  
Qing Zhang ◽  
Zhilei Mao ◽  
Xiaoyu Shi ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Response ◽  
Hpv Infection ◽  
T Cell Response ◽  
Viral Clearance ◽  
Low Grade ◽  
High Grade ◽  
Cross Sectional ◽  
Intraepithelial Lesion ◽  
Longitudinal Clinical Study

High-risk human papillomavirus (HPV) infection is the cause of almost all cervical cancers. HPV16 is one of the main risk subtypes. Although screening programs have greatly reduced the prevalence of cervical cancer in developed countries, current diagnostic tests cannot predict if mild lesions may progress into invasive lesions or not. In the current cross-sectional and longitudinal clinical study, we found that the HPV16 E7-specific T cell response in peripheral blood mononuclear cells of HPV16-infected patients is related to HPV16 clearance. It contributes to protecting the squamous interaepithelial lesion (SIL) from further malignant development. Of the HPV16 infected women enrolled (n = 131), 42 had neither intraepithelial lesion nor malignancy (NILM), 33 had low-grade SIL, 39 had high-grade SIL, and 17 had cervical cancer. Only one of 17 (5.9%) cancer patients had a positive HPV16 E7-specific T cell response, dramatically lower than the groups of precancer patients. After one year of follow-up, most women (28/33, 84.8%) with persistent HPV infection did not exhibit a HPV16 E7-specific T cell response. Furthermore, 3 malignantly progressed women, one progressed to high-grade SIL and two progressed to low-grade SIL, were negative to the HPV16 E7-specific T cell response. None of the patients with a positive HPV16 E7-specific T cell response progressed to further deterioration. Our observation suggests that HPV16 E7-specific T cell immunity is significant in viral clearance and contributes in protection against progression to malignancy.

scholarly journals Exosomal LGALS9 in the cerebrospinal fluid of glioblastoma patients suppressed dendritic cell antigen presentation and cytotoxic T-cell immunity

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Ming Wang ◽  
Yang Cai ◽  
Yong Peng ◽  
Bo Xu ◽  
Wentao Hui ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
T Cell ◽  
Antigen Presentation ◽  
T Cell Activation ◽  
Antitumor Immunity ◽  
Dynamic Monitoring ◽  
Cytotoxic T Cell ◽  
High Recurrence Rate ◽  
Low Grade ◽  
Cell Immunity

Abstract Glioblastoma multiforme (GBM) is highly invasive, with a high recurrence rate and limited treatment options, and is the deadliest glioma. Exosomes (Exos) have attracted much attention in the diagnosis and treatment of GBM and are expected to address the severe limitations of biopsy conditions. Exos in the cerebrospinal fluid (CSF) have great potential in GBM dynamic monitoring and intervention strategies. Here, we evaluated the difference in the proteome information of Exos from the CSF (CSF-Exos) between GBM patients and low-grade glioma patients, and the correlations between GBM-CSF-Exos and immunosuppressive properties. Our results indicates that GBM-CSF-Exos contained a unique protein, LGALS9 ligand, which bound to the TIM3 receptor of dendritic cells (DCs) in the CSF to inhibit antigen recognition, processing and presentation by DCs, leading to failure of the cytotoxic T-cell-mediated antitumor immune response. Blocking the secretion of exosomal LGALS9 from GBM tumors could cause mice to exhibit sustained DC tumor antigen-presenting activity and long-lasting antitumor immunity. We concluded that GBM cell-derived exosomal LGALS9 acts as a major regulator of tumor progression by inhibiting DC antigen presentation and cytotoxic T-cell activation in the CSF and that loss of this inhibitory effect can lead to durable systemic antitumor immunity.

scholarly journals Epidemiology, clinical and cytological features of lymphoma in Boxer dogs

2019 ◽  
Vol 67 (2) ◽  
pp. 224-240
Author(s):  
Urszula Jankowska ◽  
Dariusz Jagielski ◽  
Michał Czopowicz ◽  
Rafał Sapierzyński
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
Clinical Stage ◽  
T Cell Lymphoma ◽  
Low Grade ◽  
High Grade ◽  
Kiel Classification ◽  
Cytological Features ◽  
Boxer Dogs

The aim of this study was to evaluate the epidemiology, clinical and laboratory characteristics of canine lymphomas as well as some aspects of treatment outcomes. The study was conducted on Boxer dogs with lymphoma diagnosed by cytology and immunocytochemistry (CD3 and CD79 alpha). During the study period, lymphoma was diagnosed in 63 Boxers; 86.8% were T-cell (based on the Kiel classification: small clear cell lymphoma, pleomorphic small cell lymphoma, pleomorphic mixed T-cell lymphoma, pleomorphic large T-cell lymphoma, lymphoblastic lymphoma/acute lymphoblastic leukaemia) and 13.2% were B-cell lymphomas (according to the Kiel classification: B-cell chronic lymphocytic leukaemia, centroblastic/centroblastic polymorphic lymphoma). Overall survival (OS) was significantly longer in dogs with low-grade than with high-grade lymphoma (median OS of 6.8 and 4.7 months, respectively; P = 0.024). OS was not influenced by WHO clinical stage, WHO clinical substage, presence of splenomegaly, early administration of glucocorticoids or the time from the first presentation to the beginning of chemotherapy. There are no significant differences in clinical and laboratory parameters between low-grade and high-grade lymphomas. Boxer dogs are predisposed to T-cell lymphoma, with a predominance of high-grade tumour, especially pleomorphic, mixed small and large T-cell subtype. It is possible that Boxer dogs may respond less favourably to chemotherapy than patients of other breeds.

Bone marrow involvement by non-Hodgkin's lymphoma: the clinical significance of morphologic discordance between the lymph node and bone marrow. Nebraska Lymphoma Study Group.

1990 ◽  
Vol 8 (7) ◽  
pp. 1163-1172 ◽  
Author(s):  
M G Conlan ◽  
M Bast ◽  
J O Armitage ◽  
D D Weisenburger
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
T Cell ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
Large Cell ◽  
Small Cell ◽  
Low Grade ◽  
High Grade ◽  
Lymphoid Aggregates

Bone marrow specimens from 317 patients with non-Hodgkin's lymphoma (NHL) obtained at initial staging were evaluated for the presence of lymphoma or benign lymphoid aggregates. Thirty-two percent (102 patients) had lymphoma in their bone marrow, and 9% had benign lymphoid aggregates. Bone marrow lymphoma was present in 39% of low-grade, 36% of intermediate-grade, and 18% of high-grade lymphomas. The bone marrow was involved in 25% of patients with diffuse large-cell or immunoblastic NHL (ie, diffuse histiocytic lymphoma of Rappaport). Bone marrow involvement did not affect survival of patients with low-grade NHL, but survival was significantly shorter (P = .03) for patients with intermediate- and high-grade NHL with bone marrow involvement. Bone marrow involvement was equally common in B-cell and T-cell NHL (31% v 32%). However, patients with T-cell NHL and bone marrow involvement had shorter survival than B-cell NHL with marrow involvement (P = .02) or T-cell NHL without marrow involvement (P = .05). A high incidence of morphologic discordance between lymph node and bone marrow was observed (ie, 40%), always with a more aggressive subtype in the lymph node than in the bone marrow. Presence of large-cell lymphoma in the bone marrow predicted for short survival. Survival for patients with small-cell lymphoma in their bone marrow did not differ significantly from patients with negative bone marrows. We conclude that bone marrow involvement in large-cell NHL, especially in those of T-cell origin, portends a poor prognosis. However, the subgroup of patients with an aggressive histologic subtype of NHL in a lymph node biopsy and small-cell NHL in the bone marrow do not have a poorer outlook than those without bone marrow involvement.

Dendritic Cells (DC) Generated from AML Blasts Express Leukemia Associated Antigens Eliciting Specific Cytotoxic T Cell Responses in the Autologous Host after DC Vaccination.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1812-1812 ◽  
Author(s):  
Li Li ◽  
Peter Reinhardt ◽  
Iwona Hus ◽  
Jacek Rolinski ◽  
Anna Dmoszynska ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mrna Expression ◽  
Cytotoxic T Cell ◽  
Fish Analysis ◽  
Specific Response ◽  
Proteinase 3 ◽  
Cpg Odn ◽  
Dc Vaccine ◽  
Significant Difference

Abstract Several groups including ours demonstrated the generation of DC from AML blasts (AML-DC). FISH analysis has been employed to assess the origin of AML-DC from AML blasts. For clinical application, this approach is not feasible because of the restriction of AML-DC in number. Therefore we established an alternative system to prove the origin of the AML-DC, using quantitative real-time PCR to test the mRNA expression of the leukemia associated antigens (LAAs) preferentially expressed antigen in melanoma (PRAME), proteinase 3, the receptor for hyaluronic acid mediated motility (RHAMM/CD168) and the Wilms tumor gene 1 (WT-1). An elevated PCR signal for PRAME was detected in 7/12 AML-DC preparations when compared with AML blasts, for RHAMM/CD168 in 6/12 AML-DC preparations, but only in 2/12 respectively 1/12 AML-DC for WT-1 and proteinase 3. All preparations showed a strong expression of at least one of the LAAs examined. The stronger PCR signals after DC generation for PRAME and RHAMM/CD168 characterize these two LAAs as favourable target structures for immunotherapies. AML-DC positive for RHAMM/CD168 mRNA tested also positive for the protein as demonstrated by immunocytochemistry. In PRAME mRNA positive AML-DC, the described PRAME derived decamer epitope peptide ALYVDSLFFL was recognized by specific T cells as proven by chromium-51 release assay, thus proving that the mRNA assessment for RHAMM/CD168 and PRAME has an immunological significance. For five patients, AML-DC were generated under good manufacturing practice (GMP) conditions. 5x10E6 AML-DC were injected s.c. in the vicinity of inguinal lymph nodes four times at a biweekly interval. No severe adverse effects were observed after DC vaccination. One patient with AML FAB M4 required blood transfusions and remained in stable condition for several months, but eventually died from pneumonia 13 months after the DC vaccinations. A 70 year-old women with a secondary AML received a complete course of AML-DC vaccinations. During the period of 4 vaccinations, the blast level dropped from 8% in the PB to 0% and no side effects were noted. Two patients died from cranial hemorrhage after the first vaccination due to thrombocytopenia caused by the AML. One patient is still under DC vaccination. ELISPOT analysis of the first two patients revealed a significant increase in interferon gamma and granzyme B releasing CD8+ T cells recognizing a leukemic blast lysate as well as specifically RHAMM derived peptides, when compared to the initial T cell frequency. Potentiation of such an AML-DC vaccine might become feasible by the addition of adjuvants such as CPG-rich oligodeoxyribonucleotides (CPG-ODN) or lipopolysaccharides (LPS). We therefore investigated the presence of receptors for such adjuvants, i.e Toll-like receptors (TLRs) on AML-DC. Quantitative mRNA expression of TLR-2, 4 and 9 in AML-DC and DC generated of monocytes from healthy volunteers did not display any significant difference. In summary, DC could be generated from AML blasts and preserved or even upregulated LAA expression. DC vaccination was well tolerated and resulted in an enhanced and specific response of cytotoxic T cells. The adequate expression of TLRs renders potentiation of the AML-DC vaccine described here by e.g. CPG-ODN possible.

Morphologic and Phenotypic Features of Concurrent Clonal T-Cell Large Granular Lymphocytic Expansion and Myelodysplastic Syndrome

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2803-2803
Author(s):  
Xiaohui Zhang ◽  
Lynn Moscinski ◽  
John M. Bennett ◽  
Reza Setoodeh ◽  
Deniz Peker ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
T Cell ◽  
Peripheral Blood ◽  
Low Grade ◽  
Gene Rearrangements ◽  
High Grade ◽  
Bone Marrow Cellularity ◽  
Hla Dr ◽  
Marrow Cellularity

Abstract Abstract 2803 Myelodysplastic syndrome (MDS) and T-cell large granular (T-LGL) leukemia are both bone marrow failure disorders. It has been reported in a small number of cases that clonal T-LGL proliferation or leukemia can coincidentally occur with MDS. Also, clonal CD8+/CD57+ effector T cells expansion was detected in as many as 50% of MDS bone marrows [Epling-Burnette, 2007]. How clonal LGL cells that reside in the bone marrow interfere with hematopoiesis remains unclear, particularly in the setting of MDS. We analyzed the clinicopathological features of concomitant MDS and T-LGL, and evaluated bone marrow status for lineage or pan-hypoplasia in these patients. Design: Clinical and pathologic data from patients with a diagnosis of MDS and flow cytometry performed on the peripheral blood between 1/2005 and 12/2009 were reviewed. The concurrent bone marrow biopsies from each patient at the time of flow cytometric analysis were reviewed by two hematopathologists. Bone marrow cellularity, lineage hypoplasia (M:E >5: 1 or <1:2) were documented. Peripheral lymphocyte count and CD3+/CD57+ and CD8+/CD57+ populations by flow cytometry were calculated and T cell gene receptor (TCR) rearrangements were correlated. Results: We performed LGL flow cytometry panel on 76 MDS patients (high grade MDS, n=23; low grade, n=54), as well as TCR gene rearrangements, and identified clonal T-LGL cells in peripheral blood of 37 patients (48.7%), including 15 high grade MDS (40.5%, RAEB-I and RAEB-II), and 22 low grade MDS (59.4%), including RCMD(13), RA(1), RS(1), RCMD-RA(1), RCMD-RS (2), 5q- MDS(1), and MDS unclassifiable(3). The immunophenotype of the T-LGL cells was typically CD3+/CD57+/CD7 dim+/CD5 dim+/CD8+ with variable CD11b,CD11c, CD16, CD56 and HLA-DR. A frequent variant in these MDS patients was CD11b-,CD11c -, CD16+/−, CD56+/−, HLA-DR- and CD62L+.The TCRβ or/and TCRγ gene rearrangements were positive in 35 of the 38 cases (92.1%). The peripheral blood lymphocyte counts were 300–3820 cells/μL (1199±799 cells/μL); the CD3+/CD8+/CD57+ T-LGL cell counts were 30–624 cells/μL (229±154 cells/μL). In comparison, the remaining 39 patients with non-clonal T-LGL included 11 high grade MDS cases, and 28 low grade MDS cases. The peripheral blood lymphocyte counts were 308–2210 cells/μL (1030±461 cells/μL). CD3+/CD57+ cells were 1–425 cells/μL (105±98 cells/μL). There was no identifiable phenotypic features suggestive of clonal T-LGL cells such as dim CD5 and/or dim CD7 with aforementioned aberrant expressions on T-cells, although 7 of the 39 cases had TCRβ or/and TCRγ gene rearrangements. Thirty healthy donors were included for controls with absolute lymphocyte counts of 2136±661 cells/μL and baseline CD3+/CD57+ cells of 162±109 cells/μL. All showed no clonal LGL phenotype and negative TCR gene rearrangements. Since the presence of T-LGL cells may impair bone marrow hematopoiesis, we examined if there are bone marrow status differences between these two groups. All the bone marrows were obtained at diagnosis or not on chemotherapy. The bone marrow cellularity of the MDS patients with clonal T-LGL ranged from <3% to almost 100%, averaging 56%, with 8 cases with dramatic hypocellularity (<3%-20%), while the bone marrow cellularity of the MDS patients without clonal T-LGL ranged from 20% to 90%, averaging 62%, with only 2 cases with mild hypocellularity (20% in 73- and 65-year-old). In addition, among MDS patients with clonal T-LGL cells, 14 of 37 (37.8%; 5 high grade, and 9 low grade) bone marrows had certain lineage hypoplasia, including 3 cases of trilineal hypoplasia, 9 cases of erythroid hypoplasia, and 2 cases of myeloid hypoplasia. In contrast, among 39 MDS patients without T-LGL, there were only 1 bone marrow with trilineal hypoplasia and 3 others with erythroid hypoplasia (10.2%). The difference between the two groups was statistically significant (p=0.004, chi square test). In conclusion, our studies indicate that clonal T-LGL cells expansion is a fairly common finding in high grade as well as low grade MDS. The clonal T-LGL cells have more than one variant immunophenotypes and are typically positive for TCR gene rearrangements. Additionally, we observed that the clonal LGL cells present in MDS bone marrows could be associated with lineage hypoplasia, which, in this respect, might impact clinical treatment. Disclosures: No relevant conflicts of interest to declare.

Long-term follow-up of patients with Barrett esophagus: Progression to high-grade dysplasia and esophageal adenocarcinoma according to histology at presentation.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 20-20 ◽  
Author(s):  
Allon Kahn ◽  
Vishnu Kommineni ◽  
Jonathan Callaway ◽  
Rahul Pannala ◽  
David Fleischer ◽  
...  
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Large Cohort ◽  
High Grade Dysplasia ◽  
Continuous Treatment ◽  
Barrett Esophagus ◽  
Low Grade ◽  
High Grade ◽  
Upper Endoscopy ◽  
Early Stage Disease

20 Background: Esophageal adenocarcinoma (EAC) incidence is rising and prognosis is uniformly poor, even with early stage disease. Barrett esophagus (BE) serves as a premalignant marker for EAC, with an estimated progression of 0.5% per year. Low-grade (LGD) and high-grade dysplasia (HGD) confer a higher risk of progression, providing an opportunity for intervention and surveillance. Aims: To evaluate a large cohort of patients undergoing endoscopic evaluation of BE and thereby better understand the natural history of BE and dysplasia. Methods: A retrospective review of endoscopic databases was conducted for all patients with the diagnosis of BE undergoing upper endoscopy at a tertiary academic medical center from 1991-2010. All endoscopy and accompanying pathology reports were reviewed. Only those patients with 2 biopsies documenting specialized intestinal metaplasia were analyzed. Results: 848 patients underwent upper endoscopy for evaluation of BE. Of these, 674 patients met inclusion criteria, at a mean follow up of 66.6 months. Table 1 depicts the distribution of patients according to their histology at presentation. 22 (3.2%) patients presented with established EAC, while EAC developed in 51 (7.6%). Of patients with HGD, LGD, or no dysplasia (ND) at presentation, EAC ultimately developed in 30.6%, 6.6%, and 2.7%, respectively. EAC developed in 4 patients despite RFA treatment for ND (2) or LGD (2). HGD developed in 6 such patients after treatment for ND (3) and LGD (3). Only 1 patient in each RFA-treated cohort required esophagectomy, while the others cleared dysplasia or EAC with continuous treatment. Conclusions: In this large cohort of patients with Barrett’s esophagus, higher grade of dysplasia at first endoscopy was associated with development of EAC. Continuous surveillance during and after endoscopic treatment is necessary and often results in clearance of dysplasia and EAC. [Table: see text]

scholarly journals Cytogenetic findings in peripheral T-cell lymphomas as a basis for distinguishing low-grade and high-grade lymphomas

Blood ◽  
1994 ◽  
Vol 83 (2) ◽  
pp. 505-511 ◽  
Author(s):  
B Schlegelberger ◽  
A Himmler ◽  
E Godde ◽  
W Grote ◽  
AC Feller ◽  
...  
Keyword(s):  
T Cell ◽  
The Other ◽  
Low Grade ◽  
High Grade ◽  
Angioimmunoblastic Lymphadenopathy ◽  
Prolymphocytic Leukemia ◽  
Anaplastic Lymphoma ◽  
Kiel Classification ◽  
T Cell Lymphomas ◽  
Peripheral T Cell Lymphomas

Abstract Cytogenetic studies on lymph node and skin biopsy specimens and peripheral blood in 104 patients with peripheral T-cell lymphomas (PTL) were compared with histopathologic diagnoses made according to the updated Kiel classification. Low-grade lymphomas presented normal metaphases more frequently than high-grade ones (P < .0001). This difference remained significant if cases with greater than 10% and greater than 50% normal metaphases in unstimulated cultures and in cultures stimulated by different mitogens were compared. On the other hand, high-grade lymphomas more often showed aberrant clones (P < .05), triploid to tetraploid clones (P < .0001), and complex clones with more than four chromosome changes (P < .01). Low-grade PTL showed consistent cytogenetic features. Clones with both inv(14)(q11q32.1) and trisomy 8q, mostly caused by i(8q)(q10), were found in all cases of T-cell chronic lymphocytic leukemia (T-CLL) and T-cell prolymphocytic leukemia (T-PLL). Trisomy 3 was observed only in angioimmunoblastic lymphadenopathy with dysproteinemia (AILD)-type PTL, T-zone lymphoma, and lymphoepithelioid lymphoma. Moreover, the proportion of normal metaphases in these PTL was higher than in the other low-grade PTL (P < .01). On the contrary, T-CLL, T-PLL, and cutaneous T-cell lymphomas (CTCL) showed complex clones (P < .0001), duplications in 6p (P <.01), deletions in 6q (P < .01), trisomy 8q (P < .00001), inv(14) (P < .00001), and monosomy 13 or changes of 13q14 (P < .001) more frequently than the other low-grade PTL. Trisomy 5 and + X predominated in AILD- type PTL. A cytogenetic feature characteristic of AILD-type PTL and CTCL was unrelated clones, which were found in 15% of AILD-type PTL and 17% of CTCL. The only chromosome aberration restricted to a certain high-grade PTL was t(2;5)(p23;q35) in large-cell anaplastic lymphoma. Deletions in 6q, total or partial trisomies of 7q, and monosomy 13 or changes of 13q14 turned out to be significantly more frequent in high- grade than in low-grade lymphomas (P < .01, P < .01, and P < .05, respectively). In summary, the cytogenetic findings in our series of 104 PTL enabled us to distinguish not only between low-grade and high- grade lymphomas but also between various entities of PTL. Thus, the cytogenetic findings paralleled the histopathologic diagnoses made according to the updated Kiel classification.

scholarly journals Primary Non-Hodgkin's Lymphoma of the Intestine: High Prevalence of Epstein-Barr Virus in Mexican Lymphomas as Compared With European Cases

Blood ◽  
1997 ◽  
Vol 89 (2) ◽  
pp. 644-651 ◽  
Author(s):  
Leticia Quintanilla-Martı́nez ◽  
Carmen Lome-Maldonado ◽  
German Ott ◽  
Andreas Gschwendtner ◽  
Evelyn Gredler ◽  
...  
Keyword(s):  
T Cell ◽  
Membrane Protein ◽  
Tumor Cells ◽  
Epstein Barr Virus ◽  
Western Europe ◽  
Latent Membrane Protein ◽  
Low Grade ◽  
High Grade ◽  
Barr Virus ◽  
Epstein Barr

Abstract Recent studies in Western European populations have shown that peripheral T-cell non-Hodgkin's lymphomas (T-NHLs) are associated with Epstein-Barr virus (EBV) in a higher percentage than sporadic B-cell NHL (B-NHLs), and that the frequency of EBV-positivity might be influenced by the primary site of the tumor. Because of the geographic differences in EBV expression in Burkitt's lymphoma (BL) and Hodgkin's disease (HD), and the lack of studies of sporadic NHL from developing countries, we decided to survey the presence of EBV in a series of primary intestinal lymphomas from patients in Mexico and in Western Europe, and to analyze whether EBV status is influenced by tumor phenotype, and geographic or ethnic determinants. Paraffin-embedded tissue from 43 primary intestinal NHLs (19 cases from Mexico and 24 from Western Europe) were examined, including 17 high grade B-NHLs, 9 low grade B-NHLs, and 17 T-NHLs; 6 of which were enteropathy associated T-cell lymphomas. The distribution of histologic subtypes was similar in both groups. The presence of EBV was investigated with a combined approach using a nested polymerase chain reaction technique as well as immunohistochemistry for latent membrane protein-1 and in situ hybridization for EBV early RNA transcripts (EBER 1/2) RNAs. The median age of the Mexican patients was significantly lower than the median age of the European patients (32 v 62 years). This difference was most pronounced in patients with T-cell lymphoma (24 v 63 years). EBER-positive tumor cells were detected in 13 of the 43 (30%) cases of primary intestinal lymphoma, including 5 of 26 sporadic B-NHL (3 high grade and 2 low grade), and 8 of 17 T-NHL, all of which were classified as pleomorphic, medium and large cell. The rates of EBV-positivity were markedly different for European and Mexican cases. Whereas 7 of 7 (100%) T-NHL and 5 of 12 (42%) sporadic B-NHL of Mexican origin were EBER-positive, only 1 of 10 T-NHL and 0 of 14 sporadic B-NHL from Europe showed EBER expression in tumor cells. Latent membrane protein was positive in only 2 of 43 cases, 1 of which was an EBER-negative high grade B-NHL from Mexico that showed intact total mRNA in control hybridization. CD30 expression was found in 4 of 8 EBV-positive T-NHL and in none of the EBV-positive B-NHL. In contrast to European cases, intestinal NHLs from Mexico show a very high frequency of EBV-positivity, which is not limited to T-NHL, but includes a significant proportion of B-NHL. This study strongly suggests that similar to HD and probably BL, there are important epidemiologic differences in EBV association in intestinal T-cell NHL between European and Mexican populations. These differences might be the result of environmental factors, for example, earlier contact with childhood viruses on intestinal lymphomagenesis.

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