A Pilot of a Microdevice For In Situ Candidate Drug Screening in Cutaneous Lesions of T-Cell Lymphoma

2019 ◽  
Author(s):  
Keyword(s):  
T Cell ◽  
Drug Screening ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cutaneous Lesions ◽  
Candidate Drug

Sinonasal T-cell Lymphoma and Wegener's Granulomatosis: Aspects in Early Differential Diagnosis

1996 ◽  
Vol 10 (4) ◽  
pp. 239-246
Author(s):  
Anders Cervin ◽  
Michael Dictor ◽  
Olof Kalm
Keyword(s):  
Differential Diagnosis ◽  
In Situ Hybridization ◽  
T Cell ◽  
Wegener’S Granulomatosis ◽  
Cell Lymphoma ◽  
Wegener's Granulomatosis ◽  
T Cell Lymphoma ◽  
Upper Airways ◽  
Gastrointestinal Complications

The clinical course of 12 patients with sinonasal T-cell lymphoma retrospectively diagnosed using in situ hybridization for Epstein-Barr virus RNA was compared with that of 10 recently treated patients with Wegener's granulomatosis (WG) in the upper airways. In particular, we studied the presenting signs and symptoms of both diseases, which commonly offer a problem in differential diagnosis at the clinical and pathological level. A bimodal age distribution was suggested in both T-cell lymphoma and WG; five patients with T-cell lymphoma developed disease prior to 40 years of age. Four of the 12 lymphoma patients had a history of “chronic rhinitis” for several years before developing mucosal ulcerations, which were initially unilateral, as opposed to the bilateral ulcerations in early sinonasal WG. Two lymphoma patients had swelling of the nasal dorsum and cheek. In contrast to the WG patients, cases of T-cell lymphoma did not exhibit associated clinical signs of arthritis, conjunctivitis, pulmonary lesions, or nephritis in the early stage of the disease. Nine of the patients with T-cell lymphoma presenting as a sinonasal lesion developed disseminated disease, variably including infiltrates in intestine, lung, CNS, and skin. Four of these patients died from gastrointestinal complications of their disease. We conclude that unilateral ulcerative or hemorrhagic polypoid mucosal lesions in the sinonasal area are suggestive of lymphoma rather than WG, and nonspecific symptoms, at least in Western patients, may be present as early as the second or third decade of life. A biopsy specimen containing T lymphocytes positive for the EBV ribonucleoprotein EBER1 on in situ hybridization offers reliable confirmation of T-cell lymphoma and is of differential diagnostic value against WG.

scholarly journals SEROLOGICAL AND MOLECULAR MARKERS OF HERPESVIRUS INFECTIONS IN THE DEBUT OF ANGIOIMMUNNOBLASTIC T-CELL LYMPHOMA

2018 ◽  
Vol 23 (2) ◽  
pp. 77-84
Author(s):  
Dmitriy S. Tikhomirov ◽  
N. G. Chernova ◽  
M. N. Sinitsyna ◽  
Yu. V. Sidorova ◽  
N. G. Yaroslavtseva ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Lymph Node ◽  
T Cell ◽  
Primary Infection ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Herpes Viruses ◽  
High Detection Rate ◽  
Ebv Infection

Background. Angioimmunoblastic T-cell lymphoma (AITL) is the rare lymphoproliferative disorder traditionally thought to be associated with EBV. This original study gives data about serological and molecular markers of herpes viruses in primary AITL patients. Materials and methods. The review includes analysis of clinical and laboratory features of 40 primary AITL patients. Peripheral blood, lymph node, bone marrow and bronco-alveolar aspirate samples were tested by ELISA, PCR and in situ hybridization. Results. Laboratory markers of the acute herpetic infection were detected in 29 (72.0%) out of 40 patients. Primary infection was detected in 8 cases: 6 - primary EBV, 1 - HCMV and 1-EBV and HCMV simultaneously. Anti-HSV 1,2 IgM were observed in 15 (37.5%) patients. EBV small non-coding RNAs (EBER) was positive in 27 (71.1%) out of 38 cases. The comparison of the detection of EBER and markers of acute EBV infection showed good correlation (p<0.001). Patients with EBER-negative lymph node samples (n=11) didn’t have any markers of acute EBV infection. Conversely, 24 of 27 (88.9%) EBER-positive cases accompanied by markers of acute EBV infection: 7 (25.9%) of them held markers of primary infection and 17 (63.0%) - reactivation. A pattern of markers of latent EBV was observed in the rest 3 (11.1%) EBER-positive cases. Conclusion. In primary AITL patients markers of herpetic infections are detected with a high frequency. EBV infection is the most frequent. The high detection rate of IgM HSM 1.2 in primary AITL patients seems to be a characteristic feature of the tumor. Obtained data proved the necessity of laboratory testing for markers of acute herpes viruses, especially in EBER-positive cases.

Erythema multiforme-like cutaneous lesions in monomorphic epitheliotropic intestinal T-cell lymphoma: a rare case report

2016 ◽  
Vol 44 (2) ◽  
pp. 183-188 ◽  
Author(s):  
Kumpol Aiempanakit ◽  
Chitiarpa Amatawet ◽  
Kanokphorn Chiratikarnwong ◽  
Sauvarat Auepemkiate ◽  
Kanita Kayasut ◽  
...  
Keyword(s):  
Case Report ◽  
T Cell ◽  
Erythema Multiforme ◽  
Rare Case ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cutaneous Lesions ◽  
Rare Case Report

Final Results of a Phase II Trial of Belinostat (PXD101) in Patients with Recurrent or Refractory Peripheral or Cutaneous T-Cell Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 920-920 ◽  
Author(s):  
Brad Pohlman ◽  
Ranjana Advani ◽  
Madeleine Duvic ◽  
Kenneth B. Hymes ◽  
Tanin Intragumtornchai ◽  
...  
Keyword(s):  
T Cell ◽  
Median Duration ◽  
Cell Lymphoma ◽  
Stage Iv ◽  
T Cell Lymphoma ◽  
Cutaneous Lesions ◽  
Stage Iv Disease ◽  
Duration Of Response ◽  
Post Infusion ◽  
Grade 3

Abstract Abstract 920 Background: Belinostat is a pan-HDAC inhibitor of the hydroxamate chemical class that is well-tolerated and has shown clinical activity. Methods: Open label, multicenter trial enrolling patients (pts) with peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL) who failed ≥ 1 prior systemic therapy. Pts received 1000 mg/m2 IV belinostat over 30 min on days 1 to 5 of a 3-wk cycle. Primary endpoint was objective response (OR) assessed by IWG criteria for PTCL and by SWAT (cutaneous lesions) and IWG criteria (non-cutaneous lesions) for CTCL. Pruritus in pts with CTCL was assessed using a 10-point scale; relief defined as reduction of pruritus score of ≥ 3 points in pts with baseline score ≥ 3. ECGs were monitored and reviewed centrally (pre-/ post-infusion ECGs on all treatment days in cycle 1, and pre-/ post-infusion ECGs on day 1 of subsequent cycles) to evaluate potential cardiac toxicity. Results: The study enrolled a total of 53 treated pts, including 20 and 29 evaluable pts with a diagnosis of PTCL and CTCL, respectively. The 20 pts with PTCL [10 PTCL-unspecified (PTCL-U), 3 anaplastic large cell lymphoma (ALCL), 3 angioimmunoblastic TCL (AITL), 3 NK/T-cell lymphoma, and 1 subcutaneous panniculitis-like TCL (SPTCL)] had received a median of 3 prior systemic therapies (range 1 – 10), and 40 % of them had stage IV disease. 5/20 (25%) PTCL pts responded with 2 CR (both in patients with PTCL-U) and 3 PR (PTCL-U, AITL, ALCL). The 5 responding pts had a median duration of response of 159+ days (range 1 – 504+). Additionally, SD was observed in 5 pts (2 PTCL-U, 2 NK/T-cell, and 1 ALCL) with median duration of SD of 109+ days (range 80 -185+). The 29 pts with CTCL [15 mycosis fungoides (MF), 7 Sezary syndrome (SS), 5 non MF/SS, 2 unclassified] had received a median of 1 prior skin directed therapies (range 0 – 4) and 3 prior systemic therapies (range 1 – 9), and 55 % of them had stage IV disease. 4/29 (14%) CTCL pts responded with 2 CR (ALCL, MF) and 2 PR (MF, SS). The 4 responding pts had a median duration of response of 273 days (range 48 - 469+). Importantly, time to response was short with a median of 16 days (range 14-35). In addition, SD was observed in 17 pts (10 MF, 3 SS, 2 non MF/SS, 2 unclassified) with current duration of up to 127 days. Pruritus relief (score reduction ≥ 3) was seen in 7 of 14 pts with significant baseline pruritis. Median time to pruritus relief was also short, 16 days (range 7-45). Hematological toxicity was minimal without any grade 4 events (shift from baseline) and only one pt each experiencing grade 3 neutropenia and grade 3 thrombocytopenia, respectively. No grade 3 QTcF prolongation was detected in more than 700 ECGs. Four grade 3/4 drug-related AEs were reported: pruritis, rash/erythema, edema, and adynamic ileus. Conclusions: Belinostat monotherapy is safe, well tolerated, and efficacious in pts with recurrent/refractory T-cell lymphoma with durable remissions in both CTCL and PTCL. These results are the basis for a pivotal study with belinostat monotherapy in pts with PTCL. Disclosures: Advani: Seattle Genetics, Inc.: Research Funding. Duvic:Topotarget: research support for conduct of clinical trial. Fagerberg:TopoTarget A/S: Employment, Equity Ownership. Foss:Eisai : Speakers Bureau.

Analysis of Clinical and Pathological Features of 117 Chinese Cases of Natural Killer/T Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5105-5105
Author(s):  
Rong Liang ◽  
Zhe Wang ◽  
Qun xie Chen ◽  
Xian qing Bai ◽  
Guo qing Yan ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Whole Blood ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Pathological Features ◽  
Pharyngeal Wall ◽  
Ebv Dna ◽  
Clinical And Pathological Features

Abstract Abstract 5105 Objective: To improve the understanding of natural killer (NK)/T cell lymphoma (NK/TCL) with poor prognosis and provide experiential references via a restrospective analysis of the clinical and pathological features. Methods: 117 NK/TCL cases in single center of Northwestern China from April 2009 to April 2012 were retrospectively analyzed on their pathologic diagnosis and clinical manifestations, especially primary sites. Pathologic examinations mainly depended on morphology, immunohistochemisty, In situ hybridizationc and polymerase chain reaction (PCR). Immunohistochemical staining for immunophenotype (LCA, CD3, CD20, CD29a, CD45RO, CD56, TIA-1 and Granzyme B), In situ hybridization for Epstein - Barr virus (EBV) small encoded RNA(EBER) and PCR for the amount of EBV DNA in whole-blood and T-cell receptor (TCR) gene rearrangement were performed respectively. For nasal NK/TCL, combined chemotherapy and radiotherapy were indicated for stage I/II disease. Chemotherapy was the main treatment for stage III/IV NK/TCL. Regimens contained drugs not affected by P-glycoprotein, particularly in combination with L-asparaginase, or pegaspargase. Overall survival (OS) according to clinical characteristics was analyzed. Results: NK/TCL could be diagnosed via its typical clinical symptom, pathological morphology, phenotype and EBER. 117 cases were nasal or extranodal NK/TCL. The median age was 39 years old. The median survival was 11 months. The primary nasal NK/TCL was 95, accounting for 81. 2% (95/117) and their average Ki67 was 78. 34%+21. 6%. Other primary extranodal NK/TCL was 22, accunting for 18. 8%(22/117), as follows: 4 primary posterior pharyngeal wall cases with average Ki67 60%+11. 3%, 4 primary lymph nodes cases with average Ki67 50%+10. 6%, 4 primary skin cases with average Ki67 45%+8. 6%, 3 primary tonsil cases with average Ki67 67. 3%+2. 8%, 1 primary laryngeal case with Ki67 80%, 1 primary liver case with Ki67 was 90%, 1 primary intestinal case with Ki67 80%, 1 primary tongue case with Ki67 66%, 2 primary central nervous system cases with average Ki67 less than 30%, 1 primary testis case with Ki67 56%. It was found that 31 patients with primary liver and intestinal or Ki67 greater than 80% were dead in first year. Patients with primary liver and intestinal had higher Ki67 than patients with primary nasal (P <0. 01). Rate of 2 year(2y) OS of 45 patients with Ki67 from 60% to 80% was 60% as compared to 86. 3% of rate of OS of 33 patients with Ki67 from 30% to 50% (P <0. 05)and 100% of rate of OS of patients with Ki67 less than 30%(P <0. 01). Rate of 2y OS of 8 CD56− patients whose TCR was positive and primary sites were nasal was 100% higher than 67% of 109 CD56+ patients(P <0. 01). It was implied that nasal NK/TCL was of T-cell origin. Rate of 2y OS of 7 EBER− patients was 100% higher than 58% of 110 EBER+ patients(P <0. 01). The EBV–DNA was detected in 42 samples with less than 104 copies/ml in whole blood and rate of 2y OS of these patients was 55%+16%. There were 4 samples with more than 105 copie/ml EBV–DNA in whole blood and CD56+. The rate of 2y OS of these patients was 22%+9%. Conclusion: It was implied that Ki67, CD56, EBER, EBV-DNA and primary site was related with the prognosis of NK/TCL. It was also showed that NK/TCL of T-cell origin had a trend for better survival. However, it needs further and more clinical observation and verification to judge if they could be additional markers for prognostication and clinical stratification to be incorporated in clinical individual management algorithms. Disclosures: No relevant conflicts of interest to declare.

Nasal T-cell lymphoma associated with Epstein-Barr virus infection

1993 ◽  
Vol 107 (5) ◽  
pp. 468-470 ◽  
Author(s):  
J. Dhaliwal ◽  
D. C. Rowlands ◽  
G. Niedobitek ◽  
A. Williams ◽  
A. Das Gupta ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
T Cell ◽  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Epstein Barr Virus Infection ◽  
Barr Virus ◽  
Epstein Barr ◽  
Barr Virus Infection

A case of nasal T-cell lymphoma in a Caucasian male is reported, in which the presence of Epstein-Barr virus within tumour cells was demonstrated by in situ hybridization to the Epstein-Barr virus encoded RNAs EBER-1 and EBER-2.

scholarly journals Aggressive peripheral T-cell lymphomas containing Epstein-Barr viral DNA: a clinicopathologic and molecular analysis

Blood ◽  
1991 ◽  
Vol 77 (4) ◽  
pp. 799-808 ◽  
Author(s):  
IJ Su ◽  
HC Hsieh ◽  
KH Lin ◽  
WC Uen ◽  
CL Kao ◽  
...  
Keyword(s):  
T Cell ◽  
Southern Blot ◽  
Dna Hybridization ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
T Cell Lymphomas ◽  
Ebv Dna ◽  
Epstein Barr ◽  
Peripheral T Cell Lymphomas

Abstract The Epstein-Barr virus (EBV) has been shown to be associated with posttransplant lymphoma, Hodgkin's disease, and T-cell lymphoma, in addition to African Burkitt's lymphoma. In a retrospective study of 56 consecutive cases of T-cell lymphoma, EBV DNA was found by Southern blot and in situ DNA hybridization in 10 (20%) of 50 peripheral T-cell lymphomas, but in none of six cases of T-lymphoblastic lymphoma. Peripheral T-cell lymphomas containing EBV DNA could be subclassified into three categories according to histology and immunophenotypic studies: (1) T-cell lymphoma of the helper phenotype, five cases. Two cases had histologic features resembling angioimmunoblastic lymphadenopathy (AILD). (2) T-cell lymphoma of the cytotoxic/suppressor phenotype, four cases. AILD-like features could also be recognized in two cases. Reed-Sternberg-like giant cells were identified in three cases designated Hodgkin-like T-cell lymphoma. (3) Angiocentric T-cell lymphoma or lymphomatoid granulomatosis in one case, initially affecting the skin and nose; no T-cell subset could be defined. Six of the eight EBV DNA-positive patients tested for serum EBV antibodies had elevated titers of IgG antiviral capsid antigen (greater than 640) and/or early antigen (greater than 10). From combined studies of Southern blot hybridization by using EBV termini fragment probe and in situ DNA hybridization, the EBV genomes appeared to be clonotypically proliferated in the neoplastic T cells. The patients in all three groups usually had prolonged fever preceding the diagnosis, hepatosplenomegaly, an aggressive clinical course, and poor response to chemotherapy; nine died with a median survival of only 8 months. We propose that these EBV-associated aggressive T-cell lymphomas, like human T-cell leukemia/lymphoma virus-positive T-cell lymphoma, have characteristic clinicopathologic features and should be treated as a separate disease entity.

Assessment of FDG-PET Imaging in T-Cell and NK-Cell Lymphomas

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5305-5305
Author(s):  
Juan Chalapud-Revelo ◽  
Pedro Sobrevilla-Calvo ◽  
Cadena-Eumaña Carlos ◽  
Rivas-Vera Silvia ◽  
Lopez-Navarro Omar ◽  
...  
Keyword(s):  
T Cell ◽  
Fdg Pet ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Histological Subtypes ◽  
Cutaneous Lesions ◽  
Nasal Type ◽  
T Cell Lymphomas ◽  
Nasal Region

Abstract BACKGROUND: Malignant T-cell lymphomas are a heterogeneous group of disorders that frequently involve extranodal regions. Treatment and prognosis depend on accurate staging and histological evaluation. PET is widely used in staging and response evaluation of B-cell lymphomas, however, the use of FDG-PET have not been well studied for T-cell and natural killer cell lymphomas, and there is controversy if PET can detect accurately extranodal tumor activity. PATIENTS AND METHODS: We retrospectively evaluated FDG-PET in 38 patients with active T-cells, and T/NK-cells lymphoma diagnosed according to the World Health Organization (WHO) classification, from May 2007 to May 2008. We also evaluated the Standard Uptake values (SUV) according the different subtypes and the accuracy of PET in detecting tumor activity in the skin and nasal region. RESULTS: Histological subtypes included were extranodal NK/T-cell lymphoma nasal type (ENKL, n=12); Anaplastic T-cell lymphoma (ATCL, n=11); peripheral T-cell lymphoma (PTL, n=7); mycosis fungoides and Sezary syndrome (MF/SS, n=5), angioimmunoblastic (An=3). FDG-PET detected a lymphoma lesion in at least one site in 35 out of 38 patients (91%). The positivity rate was high in all histological subtypes ENKL 92%, ATCL 100%, PTL 86%, MF/SS 80%, A 100%. Among 13 patients who had cutaneous lesions only 7 had FDG-avid skin lesions (sensitivity =53.8% and specificity=100%) and among 11 patients with nasal region lesions, 91% had FDG-avid cutaneous lesions (sensibility = 91%, specificity=100%). The SUV Value in the different subtypes is shown in the table and there was not statistical differences between the groups (p= 0.067) Lymphoma N Mean SD(+/−) Range An 3 4.1 1.7 2.7–6 MF/SS 5 4.2 3.0 1.9–8.6 ATCL 11 8.3 5.3 1.6–20.8 PTL 7 3.5 1.6 2.2–6.0 ENKL 12 7.2 4.1 2.2–13.8 Total 38 6.35 4.3 1.6–20.8 CONCLUSIONS: Most of the T and T/NK cell lymphomas were detected by FDGPET. All cases, except one, of ENKL nasal type were FDG-avid, but only half of cutaneous lesions were detected by PET. In the whole T-Cell lymphomas group the mean SUV was 6.35, ATCL had the highest SUV, and we did not find any statistically differences between the groups. We conclude that PET has a high sensitivity for detection of active ENNK nasal type lymphomas and this information should be the basis for designing further studies to assess its value in staging, tumor response and as a prognostic factor.

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