Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Splenic lymphoma with villous lymphocytes (SLVL) is a rare disorder that comprises less than 1% of lymphoid neoplasms. It is the leukemic counterpart of splenic marginal zone lymphoma (SMZL) and is characterized by splenomegaly, often with no lymphadenopathy, moderate lymphocytosis and villous lymphocytes on peripheral blood smear. Here, we report a case of SLVL in a 56-year-old male with very high leukocyte counts, massive splenomegaly and relatively few leukemic cells with subtle villous projections on the surface. This disorder is often confused with other chronic lymphoproliferative disorders, especially chronic lymphocytic leukemia (CLL) and hairy cell leukemia and should be differentiated from them. We are reporting this case to highlight the diagnostic pitfalls associated with this disorder.
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PMID:Splenic lymphoma with villous lymphocytes. 1841 79

Cyclin-dependent protein kinase 6 (CDK6), in cooperation with cyclin Ds, drives cell cycle progression from G1 to S phase through phosphorylation and subsequent inactivation of retinoblastoma 1 protein. Alteration of this pathway results in both nonhematologic and hematologic malignancies, which include a small subset of B-cell lymphoproliferative disorders (BLPDs). We identified 5 cases of BLPD that carried CDK6 chromosomal translocations and characterized their clinical, pathologic, immunophenotypic, and genetic features. Common clinical characteristics included marked neoplastic lymphocytosis, systemic lymphadenopathy, splenomegaly, and bone marrow involvement. Three patients were diagnosed with low-grade B-cell lymphoma and had an indolent clinical course, and 2 patients (one who transformed to large B-cell lymphoma, and the other who was initially diagnosed with a high-grade B-cell lymphoma) had an aggressive clinical course. Immunophenotypically, the neoplastic B cells expressed CD5, CDK6, and cytoplasmic retinoblastoma 1 protein in all cases, expressed phospho-RB, p27kip1, and cyclin D2 in most cases, and uniformly lacked expression of all other cyclins. In 4 cases, the CDK6 translocation partner was kappa immunoglobulin light-chain gene; and in the fifth case, the CDK6 translocation partner was unknown. These distinct clinicopathologic and cytogenetic features distinguish the CDK6 translocation-associated BLPDs (CDK6-BLPDs) from other mature B-cell lymphomas.
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PMID:Clinicopathologic features of CDK6 translocation-associated B-cell lymphoproliferative disorders. 1914 99

Hairy-cell leukemia is a chronic B-cell malignancy seen in adults. The presenting manifestations consist of splenomegaly, pancytopenia, and characteristic monocyte depletion. The presence in peripheral blood or bone marrow of hairy cells exhibiting the CD19(+) CD20(+) CD25(+) CD11c(+) phenotype establishes the diagnosis. Rarely, patients present with inaugural joint manifestations related either to the hematological malignancy or to immune dysfunction. The resulting polymorphic polyarticular symptoms may cause diagnostic wanderings. Monocytopenia is a valuable diagnostic clue. The identification of hairy cells in the joint fluid establishes the diagnosis of leukemia-related arthritis. The treatment rests on purine analogs. One of the main differential diagnoses is Felty's syndrome, which combines rheumatoid arthritis, splenomegaly, and neutropenia. Felty's syndrome is usually caused by T-cell lymphoproliferative disorders. Among 27 patients with hairy-cell leukemia managed at our institution, 1 presented with joint manifestations. We describe this case.
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PMID:Hairy-cell leukemia with inaugural joint manifestations. 1954 26

Stat6 is a transcription factor that regulates important cellular processes such as proliferation, differentiation, and survival through mediating IL-4 and IL-13 signaling. Importantly, increasing evidence indicates of a role for Stat6 in lymphoproliferative disorders. Mice expressing a constitutively active form of Stat6 (Stat6VT) primarily in T lymphocytes were generated, and it has been recently described that a small percentage (approximately 5%) of these mice develop a spontaneous lymphoproliferative disorder (LPD) resulting in dramatic splenomegaly and altered splenic cell populations. Here, we report that Stat6VT mice housed in a non-pathogen-free environment have an increased incidence (37%) of the LPD. Additionally, examination of the expression of Stat6-regulated genes known to have roles in tumorigenesis demonstrated that there appears to be no one genetic alteration common to lymphocytes from Stat6VT/LPD mice. Interestingly, however, uniform exposure to antigen via immunization resulted in complete abrogation of the LPD in Stat6VT mice.
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PMID:Active immune response protects Stat6VT transgenic mice from developing a lymphoproliferative disorder. 1982 76

Mantle cell lymphoma (MCL) is an aggressive neoplasm with a short survival. Cases with leukaemic MCL and splenomegaly without adenopathies (non-nodal MCL) may have a more indolent course. To gain insights into the biological features underlying this presentation, we investigated the gene expression profile (GEP) and the IGHV mutational status in a cohort of leukaemic MCL cases. Comparison of MCL with other lymphoproliferative disorders (i.e. splenic marginal zone lymphoma, follicular lymphoma, chronic lymphocytic leukaemia) revealed a MCL signature enriched for the following gene categories: mitochondrion, oxidoreductase activity, response to stress, to DNA damage and TP53-pathway. Furthermore, GEP analysis revealed that non-nodal MCL cases were characterized by the down-modulation of the following gene categories: cell projection, actin cytoskeleton organization, cell adhesion (ITGAE, CELSR1, PCDH9) and tumour invasion/progression (PGF, ST14, ETS1, OCIAD1, EZR). Many down-modulated genes were related to the TP53-pathway and to DNA damage response. IGHV status proved unmutated in all nodal and mutated in all non-nodal MCL. Non-nodal leukaemic MCLs display a peculiar clinical presentation, with distinctive biological features, such as mutated IGHV and a transcriptional profile lacking tumour invasion properties, that might contribute to the absence of nodal involvement and to the less aggressive clinical course.
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PMID:Behind the scenes of non-nodal MCL: downmodulation of genes involved in actin cytoskeleton organization, cell projection, cell adhesion, tumour invasion, TP53 pathway and mutated status of immunoglobulin heavy chain genes. 2215 Jan 24

Treatment options for lymphoproliferative disorders, including chronic lymphocytic leukemia (CLL), increasingly are based upon molecular targets, taking advantage of the immense research output over the past several years elaborating genetic abnormalities, downstream signaling, cell-surface immunobiochemistry, and microenvironmental stimuli. The latter targets have been particularly useful for the treatment of multiple myeloma, transforming a previously uniformly, fatal disease to one of a more chronic and potentially curable disorder. Subsequently, new treatment approaches are less likely to be based on the more classic types of cytocidal therapy, which, although successful and essential for the more aggressive disorders that are immediately life-threatening, tend to be less so, with respect to quality of life, risk versus benefit ratio and overall curability for the indolent diseases. Because the majority of newer agents are not available to the clinicians practicing in the community, a number of treatment options developed over the past two decades are capable of significantly improving the quality of life of patients with advanced CLL. The initial clinical approach to the patient should be based on performance status, age, comorbidities, and increasingly on prognostic factors elucidated over the past three decades. Initially, both simple laboratory studies and easily measurable clinical manifestations were used to guide the clinician (lymphocyte count, anemia, thrombocytopenia, enlarging lymph nodes, splenomegaly, hepatomegaly), and clinical staging systems were developed. At present a cadre of biologic factors, including cytogenetic alterations, gene expression profiles with subsequent immunoglobulin abnormalities, and expression of CD38 and Zap-70, are now available and are standard decision-making criteria to treat a patient with CLL. An initial period of observation allows the clinician along with the patient to gather all the information necessary to make an informed treatment decision. Frequently, a "watch and wait" approach, which for CLL does not appear to harm the patient, is the most appropriate decision. Complications of CLL, such as autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura, will lead to treatment at least temporarily in those patients who might otherwise have not needed therapy. Frontline therapy will range from easily administrable single-agents to combination chemoimmunotherapy regimens. Experimental protocols, utilizing "post state of the art" treatments, are available in the form of research protocols at major treatment centers. At the present time, it is premature to recommend bone marrow ablative therapy as initial treatment unless the prognosis appears grave and the patient can withstand the rigors of this approach.
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PMID:Update on chronic lymphocytic leukemia: overview of new agents and comparative analysis. 2349 26

Leishmaniasis is a parasitic infection caused by protozoans classified as Leishmania species. Romania is not considered an endemic country and there are only few reports of sporadic cases in the last 100 years. However, studies suggest that the disease is spreading north. We present the case of a 44 year old female that presented with asthenia, perspirations, vertigo, weight loss and menometrorhagias in small to medium quantity. Clinical exam revealed the presence of splenomegaly and her blood tests indicated she had pancitopenia; differential diagnosis included myeloproliferative or lymphoproliferative disorders, infections that evolve with spleen enlargement, autoimmune-related splenomegaly and hepatic--all tests were negative. She refused the bone marrow aspiration. Three months later, her condition worsened and the menometrorragias became more severe. Bone marrow aspiration revealed the presence of numerous intra and extracellular Leishmania spp. amastigotes. A detailed anamnesis showed that she had worked for six months in Italy as a care-giver nine months ago. She was transferred to Bucharest where she received optimal treatment. However, due to the continuous bleeding, the evolution was unfavourable. This is an alarm sign for physicians that should take into account the fact that, due to population migration and global warming, tropical infectious diseases are becoming more and more common. The signs and symptoms, as well as the treatment in leishmaniasis are reviewed, as well as a brief history of leishmaniasis in Romania.
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PMID:Leishmaniasis--an unusual cause of splenomegaly in Romania. 2474 84

Background. Autoimmune lymphoproliferative syndrome (ALPS) is a genetic disorder of lymphocyte homeostasis due to defects in FAS-mediated apoptosis. ALPS is characterized by childhood onset of chronic lymphadenopathy and splenomegaly, autoimmunity, an expanded population of double-negative T cells (DNTCs), and an increased risk of lymphoma. This propensity for lymphoma in ALPS is not well understood. It is possible that lymphomagenesis in some of these patients may result from Epstein-Barr virus (EBV) infection exploiting the defective T-cell surveillance resulting from impaired FAS-mediated apoptosis. Case Presentation. We report the first case, to our knowledge, of lymphoma in a patient with ALPS that was clinically heralded by progressively increasing EBV viremia. We discuss its practical implications and the possible immune pathways involved in the increased risk for EBV-associated lymphoproliferative disorders in ALPS patients. Conclusion. In patients with ALPS, distinguishing chronic lymphadenopathy from emerging lymphoma is difficult, with few practical recommendations available. This case illustrates that, at least for some patients, monitoring for progressively increasing EBV viremia may be useful.
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PMID:Autoimmune Lymphoproliferative Syndrome and Epstein-Barr Virus-Associated Lymphoma: An Adjunctive Diagnostic Role for Monitoring EBV Viremia? 2537 37

Leishmaniasis is spreading from mediterranean countries to the north of Europe. The Alps are not an endemic region and there are only few reports of sporadic cases. We report the case of a 72 year old male who presented after a syncope with fever, cough and a sacral skin rash. Clinical examination revealed splenomegaly, elevated liver enzymes and pancytopenia; differential diagnosis included myeloproliferative or lymphoproliferative disorders, infections and auto-immune conditions that cause enlargement of the spleen and liver diseases, however, all tests were negative. In (18)FDG PET computerized tomography, pathological and diffuse uptake in the spleen was seen, with mild and homogeneous FDG uptake in the bone marrow and normal tracer uptake elsewhere in the body. Bone marrow aspiration revealed the presence of numerous intra- and extracellular Leishmania amastigotes. Travel history indicated that he had been in Sardinia for a 7-day vacation several months ago. The patient promptly responded to treatment with liposomal amphotericin B. Imported visceral leishmaniasis is likely to be seen more frequently in non-endemic regions and fever, pancytopenia and splenomegaly are diagnostic clues, whereas diagnostic confirmation may be done by detection of Leishmania spp. amastigotes in the bone marrow.
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PMID:Imported visceral leishmaniasis - unexpected bone marrow diagnosis in a patient with fever, pancytopenia, and splenomegaly. 2575 10

Two patients with lymphoproliferative disorders, one with chronic lymphocytic leukemia and the other hairy cell leukemia, developed spontaneous rupture of the spleen during the course of their disease. In both cases, this rare complication occurred during systemic atypical infections with Salmonella Dublin and Candida tropicalis respectively. We suggest that severe infection may sometimes play a decisive role in the development of the splenic rupture in some patients who have splenomegaly due to these disorders.
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PMID:Splenic Rupture in Chronic Lymphoid Disorders: Possible Role of Opportunistic Infections. 2745 99


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