Two cases of angioimmunoblastic T-cell lymphoma with concomitant positive serology for acute Epstein-Barr virus infection

TL) is a rare type of peripheral T-celllymphoma. Epstein-Barr virus (EBV) isknown to be associated with pathogenesisand histological progression of AITL andthe onset of the disease often mimics aninfectious process. Here we describe twocases of patients with serology for acuteEBV infection at the onset of AITL.IntroductionAngioimmunoblastic T-cell lymphom

Роль молекулярно-генетических методов определения Т-и В-клеточной клональности в диагностике злокачественныхлимфом кожи

The article presents the data on the studies contributing to improving the differential diagnostics of T-cell and B-cell cutaneous lymphomas including large-plaque parapsoriasis and T-cell and B-cell cutaneous pseudolymphomas as well as frequency of their transformation into malignant cutaneous lymphomas. There was a study of 101 patients using the polymerase chain reaction method to determine the T-cell and B-cell lymphocyte clonality by genes of g and chains in the T-cell receptor and immunoglobulin heavy chain genes. Monoclonality was determined in 40 of 46 cases in patients with T-cell cutaneous lymphomas and in three of four cases in patients with B-cell cutaneous lymphomas. Monoclonality was revealed in one of 14 cases of large-plaque parapsoriasis and one of two cases of T-cell cutaneous pseudolymphoma. In all of the 24 cases of chronic benign dermatoses, five cases of small-plaque parapsoriasis and ten skin tissue samples obtained from healthy donors, polyclonal lymphocytes were revealed. So, the obtained results make it possible to consider the method to be an important addition in the field of diagnosing lymphoproliferative skin diseases.Приведены данные об исследованиях, способствующих совершенствованию дифференциальной диагностики Т- и В-клеточных лимфом кожи, в том числе с крупнобляшечным парапсориазом, Т- и В-клеточными псевдолимфомами кожи, а также о частоте их трансформации в злокачественные лимфомы кожи. У 101 пациента проведено обследование методом полимеразной цепной реакции с целью определения Т- и В-клеточной клональности лимфоцитов по генам g- и -цепей Т-клеточного рецептора и генам тяжелой цепи иммуноглобулина. У пациентов с Т-клеточными лимфомами кожи моноклональность определялась в 40 из 46 случаев, с В-клеточными лимфомами кожи - в 3 из 4 случаев. Также моноклональность была выявлена в 1 из 14 случаев крупнобляшечного парапсориазам и в 1 из 2 случаев Т-клеточной псевдолимфомы кожи. Во всех 24 случаях хронических доброкачественных дерматозов, 5 случаях мелкобляшечного парапсориаза и 10 биоптатах кожи от здоровых доноров была выявлена поликлональность лимфоцитов. Таким образом, полученные результаты позволяют считать данный метод важным дополнением в диагностике лимфопролиферативных заболеваний кожи

A phase II clinical trial of fludarabine and cyclophosphamide followed by thalidomide for angioimmunoblastic T-cell lymphoma. An NCRI clinical trial. CRUK number C17050/A5320.

Accepted version (12 month embargo

О совершенствовании оказания специализированной медицинской помощибольным злокачественными лимфомами кожи

The authors analyzed the responses from directors of dermatovenerology institutions to a standardized questionnaire with questions about recording patients with malignant cutaneous lymphomas, follow-up care, diagnostics, treatment of patients, cooperation with experts in allied fields. They also revealed defects and problems in the organization of specialized medical aid for patients with malignant cutaneous lymphomas in the territory of the Russian Federation, and developed prospective methods for improvement of aid rendered to patients with malignant cutaneous lymphomas.Проведен анализ ответов руководителей кожно-венерологических учреждений на стандартизованную анкету по вопросам регистрации больных злокачественными лимфомами кожи (ЗЛК), диспансерному наблюдению, диагностике, терапии пациентов, взаимодействию со смежными специалистами. Выявлены недостатки и сложности в организации оказания специализированной медицинской помощи больным ЗЛК на территориях Российской Федерации, разработаны перспективные направления совершенствования помощи больным ЗЛК

Value of the CD8-CD3 ratio for the diagnosis of mycosis fungoides

Histopathological diagnosis of mycosis fungoides is difficult, especially in early lesions that may be indistinguishable from inflammatory dermatoses. Mycosis fungoides is a clonal proliferation of mature epidermotropic CD4+ lymphocytes. The aim of this study was to determine the contribution of the CD8-CD3 ratio to the diagnosis of mycosis fungoides. We retrospectively compared the immunophenotypic characteristics of 30 mycosis fungoides with 28 inflammatory dermatoses. The diagnosis of mycosis fungoides was reinforced in all cases by the presence of a cutaneous dominant T-cell clonal population. To analyze exclusively the lymphocytic infiltrates, CD4, which is also expressed by histiocytes, was not considered. The CD8-CD3 ratio was determined separately in the epidermis and the dermis using two methods, one quantitative and the other semiquantitative. Concordance rates between the two methods were higher in epidermal than dermal infiltrates. The mean CD8-CD3 ratio was significantly lower for mycosis fungoides than control cases, with the difference being greater in the epidermal than the dermal component. Although not absolutely specific, a low CD8-CD3 ratio in the epidermal component of a lymphocytic infiltrate supports the diagnosis of mycosis fungoides. It can be evaluated in routine practice using a semiquantitative approach

c-Maf expression in angioimmunoblastic T-cell lymphoma reflects follicular helper T-cell derivation rather than oncogenesis.

peer reviewe

The Distinct Molecular Signature Of Hepatosplenic T-Cell Lymphoma (Hstl) Identifies Oncogenic Pathways With Potential Therapeutic Relevance

Background: HSTL is a rare entity characterized by an infiltration of bone marrow, spleen and liver tissues by neoplastic gammadelta (gd) -more rarely alphabeta (ab)- T cells. Its pathogenesis is poorly understood. Our purpose was to identify the molecular signature of HSTL and explore molecular pathways implicated in its pathogenesis.Methods: Gene expression profiling and array CGH analysis of 10 HSTL samples (7gd, 3ab), 1 HSTL cell line (DERL2), 2 normal gd samples together with 16 peripheral T-cell lymphoma not otherwise specified (PTCL,NOS) and 7 nasal NK/T cell lymphomas were performed.Results: By unsupervised analysis, ab and gdHSTL clustered together remarkably separated from other lymphoma entities. Compared to PTCL, NOS, HSTL overexpresed genes encoding NK-associated molecules, oncogenes (VAV3) and the Sphingosine-1-phosphatase receptor 5 involved in cell trafficking. Compared to normal gd cells, HSTL overexpressed genes encoding NK-cell and multi drug resistance-associated molecules, transcription factors (RHOB), oncogenes (MAFB, FOS, JUN, VAV3) and the tyrosine kinase SYK whereas genes encoding cytotoxic molecules and the tumor suppressor gene AIM1 were among the most downregulated. By immunohistochemistry, SYK was demonstrated on HSTL cells with expression of its phosphorylated form in DERL2 cells by Western blot. Functional studies using a SYK inhibitor revealed a dose dependent increase of apoptotic DERL2 cells suggesting that SYK could be a candidate target for pharmacologic inhibition. Downexpression of AIM1 was validated by qRT-PCR. Methylation analysis of DERL2 genomic DNA treated by bisulfite demonstrated highly methylated CpG islands of AIM1. Genomic profiles confirmed recurrent isochromosome 7q (n=6/9) without alterations at 9q22 and 6q21 containing SYK and AIM1 genes, respectively.Conclusion: The current study identifies a distinct molecular signature for HSTL and highlights oncogenic pathways which offer rationale for exploring new therapeutic options such as SYK inhibitors. It supports the view of gd and ab HSTL as a single entity