Hepatosplenic alphabeta T-cell lymphoma with myelodysplastic syndrome.
ABSTRACT We describe a patient with hepatosplenic 33 T-cell lymphoma who showed pancytopenia and myelodysplasia. A 35-year-old man was admitted with fever, pancytopenia, and hepatosplenomegaly but with no lymphadenopathy. We also found trilineage myelodysplasia in the bone marrow on his first admission. The patient had high fever and anemia but no evidence of infection and was tentatively treated with prednisolone. This treatment resulted in a transient improvement of the cytopenia and a reduction of spleen size. However, 10 months after the first manifestation, progression of the splenomegaly and fever became apparent, and a splenectomy was performed. The pathologic findings for the spleen showed diffuse and disseminated infiltration of medium- to large-sized T-lymphocytes in the splenic red pulp. These cells were immunohistochemically positive for CD3, CD5, CD7, CD8, CD16, CD56,T-cell receptor 33 (TCR33),T-cell intracellular antigen 1, and granzyme B but were negative for CD4, CD30, CD57, and TCR33. These data suggested a diagnosis of hepatosplenic 33 T-cell lymphoma. A Southern blot analysis revealed gene rearrangement of the TCR 3-chain gene but not the immunoglobulin heavy chain gene in the spleen cells. An in situ hybridization analysis for the Epstein-Barr virus revealed negative results. The patient received 8 courses of combination chemotherapy and achieved a partial remission; however, the dysplastic features of the marrow cells persisted after the partial remission was obtained. Additional treatment with allogeneic bone marrow transplantation resulted in a transient complete remission; however, the patient relapsed 11 months later. Because he had experienced no lymphadenopathy and showed dysplastic features in the bone marrow, the diagnosis was highly dependent on the pathologic findings for the resected spleen.
American Journal of Hematology 10/2014; 89(10). DOI:10.1002/ajh.23783 · 3.48 Impact Factor
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ABSTRACT: Granzymes (gzms) are a group of serine proteases that play an important role in innate and adaptive immunity, blood coagulation, apoptosis and inflammation, but are also connected to atherosclerosis, diabetes, cardiovascular and inflammatory lung diseases, cancer and sepsis. Humans have five granzymes (gzms A, B, H, K and M), which differ in their substrate specificity. It is widely accepted that they are delivered from cytotoxic lymphocytes via perforin into the cytoplasm of target cells where they initiate cell death, modulate cytokine signaling, or inactivate pathogen proteins. However more recent evidence indicates granzymes also act extracellularly in non-cytotoxic processes. Proteomic approaches are directed at mapping granzyme cleavage specificity, identifying substrates and unraveling the (patho-) physiological role of these proteases. These studies have refined our understanding of granzyme species specificity, and collectively uncovered an enormous number of new substrates. However, with the exception of a very few human gzmB substrates supported by independent data (Bid, DNA-PK, PARP, ICAD and procaspase 7), it is presently unclear which are physiologically relevant. This review aims to summarize and analyze the different proteomic approaches used and discuss both their convincing and controversial outcomes. This article is protected by copyright. All rights reserved.PROTEOMICS - CLINICAL APPLICATIONS 06/2014; 8(5-6). DOI:10.1002/prca.201300096 · 2.68 Impact Factor
Article: Gamma-delta t-cell lymphomas[Show abstract] [Hide abstract]
ABSTRACT: Gamma-delta T-cell lymphomas are aggressive and rare diseases originating from gamma-delta lymphocytes. These cells, that naturally play a role in the innate, non-specific immune response, develop from thymic precursor in the bone marrow, lack the major histocompatibility complex restrictions and can be divided in two sub-populations: Vdelta1, mostly represented in the intestine, and Vdelta2, prevalently located in the skin, tonsils and lymph nodes. Chronic immunosuppression, such as in solid organ transplanted subjects, and prolonged antigenic exposure are probably the strongest risk factors for the triggering of lymphomagenesis. Two entities are recognized by the 2008 WHO Classification: hepatosplenic gamma-delta T-cell lymphoma (HSGDTL) and primary cutaneous gamma-delta T-cell lymphoma (PCGDTL). The former is more common among young males, presenting with B symptoms, splenomegaly, and thrombocytopenia, usually with absence of lymph nodal involvement. Natural behaviour of HSGDTL is characterized by low response rates, poor treatment tolerability, common early progression of disease and disappointing survival figures. PCGDTL accounts for less than 1% of all primary cutaneous lymphomas, occurring in adults with relevant comorbidities. Cutaneous lesions may vary, but its clinical behaviour is usually aggressive and long-term survival is anecdotal. Available literature on gamma-delta T-cell lymphomas is fractioned, mostly consisting of case reports or small cumulative series. Therefore, clinical suspicion and diagnosis are usually delayed and therapeutic management remains to be established. This review critically analyzes available evidence on diagnosis, staging, and behaviour of gamma-delta T-cell lymphomas, provides recommendations for therapeutic management in routine practice and discusses relevant unmet clinical needs for future studies.This article is protected by copyright. All rights reserved.European Journal Of Haematology 08/2014; 94(3). DOI:10.1111/ejh.12439 · 2.41 Impact Factor