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 an indolent hematological malignancy. Persistent lymphocytosis and splenomegaly usually last for years before patients develop infectious complications. Organ involvement other than spleen and bone marrow is rare in SLVL. We report a case of SLVL-related meningitis occurring in a patient presenting with altered mental status and seizures. CNS involvement was documented by an MRI of the head and by the presence of atypical lymphocytes in the cerebrospinal fluid (CSF). Morphologic examination and immunophenotypic analyses were conducted to determine the nature of atypical lymphocytes in the peripheral blood, spleen, bone marrow and CSF. The patient improved after treatment with a combination of radiation and chemotherapy.
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PMID:Leptomeningeal involvement in a patient with splenic lymphoma with villous lymphocytes. 1215 5

Approximately 20% of mantle cell lymphomas (MCL) present with the blastoid variant associated with poor prognosis. Lactic acidosis complicated with hematologic malignancies is seen infrequently and is associated with a poor outcome. Here we report the case of a patient with the blastoid variant of MCL complicated by lactic acidosis and who achieved complete remission through chemotherapy combined with rituximab therapy. A 77-year-old man presented with peripheral blood lymphoma cells, huge splenomegaly, abdominal and mediastinal lymphadenopathy, and pleural effusion. A bone marrow smear showed an increase in large, abnormal lymphoid cells with oval or round nuclei, distinct nucleoli, and abundant basophilic cytoplasm with vacuolization. Splenic sections also showed massive and diffuse infiltration by these cells. Flow cytometry analysis showed these cells to be positive for CD5, CD19, CD20, and kappa chain and negative for CD10 and CD23. A blastoid variant of MCL was diagnosed from the results of histologic, immunohistochemical (cyclin D1), and cytogenetic (chimeric bcl-1/IgH fusion gene) analyses. The patient recovered from the 2 episodes of severe lactic acidosis for which he had been given chemotherapy, and he achieved complete remission after subsequent chemotherapy combined with rituximab treatment.
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PMID:Blastoid variant of mantle cell lymphoma with lactic acidosis: a case report. 1564 54

The Philadelphia chromosome (Ph)-negative myeloproliferative disorders (MPDs) include essential thrombocythemia (ET), idiopathic myelofibrosis (IMF), and polycythemia vera (PV). All of these disorders are clonal hematologic malignancies originating at the level of the pluripotent hematopoietic stem cell. Recently, activating mutations of the intracellular cytokine-signaling molecule JAK2 have been identified in > 90% of patients with PV and in 50% of those with IMF and ET. In addition, a mutation of the thrombopoietin receptor, MPLW515L, has been documented in some patients with IMF. Both mutations activate JAK-STAT signaling pathways and likely play a role in disease progression. Both ET and PV are associated with prolonged clinical courses associated with frequent thrombotic and hemorrhagic events, and progression to myelofibrosis and acute leukemia. IMF has a much poorer prognosis and is associated with cytopenias, splenomegaly, extramedullary hematopoiesis, and bone marrow fibrosis. Stratification of risk for the development of complications from Ph-negative MPDs has guided the identification of appropriate therapies for this population. Intermediate/high-risk IMF or myelofibrosis after ET or PV is associated with a sufficiently poor prognosis to justify the use of allogeneic stem cell transplantation, which is capable of curing such patients. Reduced-intensity conditioning in preparation for allogeneic stem cell transplantation has permitted older patients with IMF to undergo transplantation with increasing success.
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PMID:Philadelphia chromosome-negative myeloproliferative disorders: biology and treatment. 1722 72

Peripheral blood (PB) is sometimes used in place of bone marrow (BM) for cytogenetic studies during the evaluation of hematologic malignancies. A total of 242 PB cytogenetic studies from adult patients were performed: clinical diagnosis was a myeloid neoplasm in 169 patients (70%), lymphoid or plasma cell neoplasm in 50 (21%), and a benign/reactive cytopenia or leukocytosis in 23 (9%). PB cytogenetic studies resulted in at least two analyzable metaphases in 142 of the 242 study cases (59%); in univariate analysis, this was predicted by the specific clinical diagnosis (P < 0.0001), presence and degree of circulating myeloid progenitor cells or blasts of any lineage (P < 0.0001), higher leukocyte count (P < 0.001), lower platelet count (P = 0.003), lower hemoglobin level (P = 0.002), and presence of palpable splenomegaly (P = 0.002). In multivariable analysis, only the presence of circulating myeloid progenitor cells or blasts sustained significance and this was consistent with the high yield rates seen in primary myelofibrosis (PMF) (80%), post-PV/ET PMF (85%), acute myeloid leukemia (76%), and acute lymphoblastic leukemia (80%) in contrast with the low rates seen in ET (0%) and PV (2%). In 104 cases, BM cytogenetic studies were performed within 1 month of the PB cytogenetic studies; an abnormal BM cytogenetic finding was another independent predictor of a successful PB study (P = 0.002). PB cytogenetic studies are most appropriate in diseases of adults characterized by presence of circulating myeloid progenitors or blasts; the yield otherwise is too small to be cost-effective.
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PMID:Peripheral blood cytogenetic studies in hematological neoplasms: predictors of obtaining metaphases for analysis. 1808 99

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

Recent studies suggest that patients with common variable immunodeficiency (CVID) and low numbers of switched memory B cells have lower IgG levels and higher rates of autoimmune disease, splenomegaly, and granulomatous disease; however, no prior literature has focused exclusively on pediatric cases. We examined the relationship between switched memory B cells and clinical and immunologic manifestations of CVID in a pediatric population. Forty-five patients were evaluated. Patients were categorized as Group I (<5 switched memory B cells/ml, n = 24) or Group II (> or =5 switched memory B cells/mL, n = 21). CD3(+) T-cell counts and CD19(+) B-cell levels were lower among Group I patients. Only those in Group I had meningitis, sepsis, bronchiectasis, granulomatous lung disease, autoimmune cytopenias, or hematologic malignancies. Segregation of pediatric patients into high risk (Group I) and average risk (Group II) may assist in targeting surveillance appropriately.
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PMID:Pediatric common variable immunodeficiency: immunologic and phenotypic associations with switched memory B cells. 2145 41

A 42-year-old white woman, who was a general practitioner referral to the medical team, presented with a 3-day history of left upper quadrant pain; an urgent private ultrasound scan had showed splenomegaly. She was initially admitted with sepsis without an obvious cause but with a differential diagnosis of a haematological malignancy. Her admission blood tests showed a mildly reduced white cell count and low platelets. Her symptoms progressed and she developed right upper quadrant pain. Her blood counts deteriorated showing a disseminated intravascular coagulation (DIC) picture and mildly deranged liver function tests. Blood films were non-diagnostic. A CT scan of the abdomen/pelvis showed splenomegaly and also hepatomegaly and ascites, not seen in her initial ultrasound scan. Multiple cultures of blood/urine/ascites and infective serology were unremarkable.She was transferred to a larger tertiary centre under the care of the surgeons with presumed abdominal sepsis and underwent an open laparotomy, which showed a big firm liver and spleen but no obvious cause for sepsis. The infectious disease team were unable to find a cause, and haematology became involved to investigate the possibility of a haematological malignancy. The patient underwent two bone marrow biopsies, a percutaneous liver biopsy and had flow cytometry of her ascitic fluid, which revealed the diagnosis of a natural killer cell leukaemia. After some slight improvement on steroids, the patient was given cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab (CHOP-R) chemotherapy. The patient had an initial response to chemotherapy, with reduction in ascitic volume and hepatosplenomegaly, and normalisation of her coagulation. This was accompanied by an overall improvement in her physical condition. She had a second cycle of CHOP-R, but unfortunately approximately 2 weeks after that, she deteriorated rapidly. She was too weak for salvage chemotherapy, so she was put on comfort care. She died peacefully.
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PMID:Natural killer cell leukaemia. 2188 53

The BCR-ABL1-negative myeloproliferative neoplasms (e.g., essential thrombocythemia, polycythemia vera, and primary myelofibrosis) are a group of heterogeneous hematologic malignancies that involve a clonal proliferation of hematopoietic stem cells. Thrombosis, bleeding, and transformation to acute leukemia reduce the overall survival of patients with myelofibrosis, a disease typified by progressive splenomegaly and disease-related symptoms such as fatigue, pruritus, and bony pains. Hematopoietic stem cell transplant offers the only potential for cure in a minority of eligible patients, leaving a serious unmet need for improved therapies. Recent advances in our understanding of the pathogenetic mechanisms underlying these diseases have led to an explosion of clinical trials evaluating novel therapies. The discovery of an activating mutation in the Janus-activated kinase 2 (JAK2) gene provided a therapeutic target to downregulate this activated signaling pathway, which influences the phenotype of these diseases. Ruxolitinib (Jakafi; Incyte) is a small-molecule inhibitor of JAK1/2 that has proved to be effective at reducing splenomegaly and ameliorating symptoms in myeloproliferative neoplasms. Based on the results of 2 pivotal randomized phase III clinical trials, ruxolitinib has become the first therapeutic to be approved by the U.S. Food and Drug Administration for treatment of patients with myelofibrosis. Ruxolitinib offers a well-tolerated oral therapeutic option for patients with myelofibrosis with symptomatic splenomegaly and debilitating disease-related symptoms, but it does not seem to be effective at eliminating the underlying hematological malignancy.
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PMID:Ruxolitinib: the first FDA approved therapy for the treatment of myelofibrosis. 2247 18

The spleen represents a major lymphatic and hematologic organ and, as such, is frequently involved in hematologic malignancies. Splenomegaly may constitute the first clinical sign leading to the diagnosis of a hematologic malignancy. Vice versa, the presence, or suspicion of a hematologic malignancy requires investigation of the spleen. In case of splenomegaly of unknown origin, directed history, clinical examination, and laboratory testing including a complete blood count with microscopic investigation of a peripheral blood smear, frequently allow to establish a tentative diagnosis. Whenever possible, further specific testing should be based on a thorough primary evaluation to avoid unnecessary diagnostic procedures. In light of the current diagnostic options, diagnostic splenectomy can usually be avoided to establish definitive diagnosis. Indolent lymphomas (chronic lymphocytic leukaemia, hairy cell leukaemia, splenic marginal zone lymphoma) and myeloproliferative neoplasms (chronic myeloid leukaemia, polycythemia vera, essential thrombocythemia, primary and secondary myelofibrosis) are the most prevalent hematologic malignancies associated with splenomegaly. Therapeutic options are highly differentiated depending on the underlying disease. Apart from very rare exceptions, therapeutic splenectomy can usually be avoided.
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PMID:[The spleen in hematologic malignancies]. 2345 63


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