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A serum multiple monoclonal component (MC) is very rare. We here report 6 patients with 3 MCs. The triple MC was detected in all of them by immunofixation. 2/6 patients did not present hematological or oncological associated disease, while in the remaining 4, Waldenstrom macroglobulinaemia (2 cases), Polycythemia Vera and non-Hodgkin lymphoma were diagnosed. Of the 49 global patients reported in the literature (6 + 43), 64.6% had a lymphoproliferative disorder and only in 3 cases there was no associated disease. Therefore, the detection of such laboratory evidence should propel physicians to a deeper investigation.

Background. Thrombotic microangiopathies (TMA) are relatively rare but severe disorders characterised by non-immune haemolytic anaemia, thrombocytopaenia and organ failure. In patients with metastatic cancer, sporadic forms of TMA can be triggered by chemotherapeutic agents or can occur as complication of malignancy itself or of infections. Case report. Hereby, we report a case of a patient diagnosed with metastatic colorectal cancer who experienced an atypical haemolytic-uraemic syndrome (aHUS) during chemotherapy treatment with FOLFOX6 scheme. The use of eculizumab led to prompt recovery of laboratory parameters that was maintained despite treatment discontinuation due to appearance of pneumonia infectious. Additionally, genetic analyses revealed the presence in heterozygosis of CFH gene polymorphisms associated with aHUS. Conclusion. This case emphasises the importance of considering TMA as a possible diagnosis in patients with cancer presenting with haemolytic non-immune mediate anaemia and thrombocytopaenia associated with worsening of renal function. Prompt diagnosis is crucial for the requirement of its specific treatment that can impact on long-term outcome and prognosis.

A double monoclonal component (MC) detected in the serum and/or urine represents a very rare occurrence (2-6% of monoclonal gammopathies). In this study, we report 34 patients with double serum MCs, focusing on the associated diseases. The diagnosis was made using high-resolution serum protein electrophoresis and immunofixation. Of the 1214 patients with monoclonal gammopathies, 49 had a double MC but only 34 (2.8%) were included in our study. A double MC was associated with hematological malignancies in 20/34 cases. Based on our experience, a double MC is more often associated with other diseases, especially an oncohematological one.

A female patient with non-Hodgkin lymphoma who tested positive for surface antigen of the hepatitis B virus and negative for hepatitis B core antibody experienced a reactivation of occult HBV infection 20 months after rituximab discontinuation despite lamivudine prophylaxis covering the 4 months of rituximab administration and the subsequent 12 months. © 2012 Springer-Verlag.

Primary lymphoma of the female genital tract is very rare. We report the case of a 36-year-old woman who was referred to our hospital because of an indeterminate Pap smear test. The colposcopy showed a thickening of the posterior vaginal wall and various irregular ulcerated nodular lesions. Histological examination, immunohistochemistry and the staging procedures were conclusive of diffuse large B-cell lymphoma of the vagina, stage IEA. Complete remission was achieved after 6 cycles of immunopolychemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). No relapse has occurred during a follow-up of 71 months. Moreover, we reviewed the 62 previously reported cases of primary extranodal non-Hodgkin’s lymphoma of the vagina, focusing on clinicopathological and therapeutic aspects, to better characterize this unusual disease.

The numb chin syndrome (NCS) is characterized by facial numbness along the distribution of the mental branch of the trigeminal nerve. Most cases of this syndrome that are not dental in origin have been associated with malignant tumors or diffuse metastatic disease, particularly with underlying lymphoproliferative diseases and breast cancer. NCS can appear together with other signs of neoplastic dissemination or constitute the presenting symptom of the disease. The appearance of this mental nerve neuropathy should be considered as a significant symptom for clinicians, and investigations to detect a possible cancer should be mandatory. We report 12 patients with the NCS as the presenting and isolated symptom of a generalized malignancy.

Background: Increased plasma levels of fibrinogen are been associated with an increased risk of cardiovascular accident. We aimed at verifying whether the changes of fibrinogen levels are associated with red blood cell (and/or hemoglobin) concentration. Methods: A group of 381 carefully selected healthy volunteers (219 male and 162 female), aged from 18 to 101 years, were enrolled in this study. Fasting blood samples were taken and all measurements (fibrinogen plasma level, whole blood viscosity, hemoglobin concentration, hematocrit value, red blood cell and white blood cell count, platelet count, glucose, total cholesterol and triglycerides plasma concentration, and C-reactive protein level) were obtained with standardized methodology using appropriate equipment, procedures, and controls. Results and Conclusions: In the male but not in the female group, plasma fibrinogen concentration inversely correlated with hemoglobin (P * 0.0001) and hematocrit value (P * 0.01). In a post hoc analysis, plasma fibrinogen level inversely correlated with hemoglobin in the subgroup of the 93 premenopausal women and directly correlated with age and inversely correlated with platelet count in the subgroup of the 69 postmenopausal women. Results of multiple regression analysis revealed that in all the subjects, except in the postmenopausal women, hemoglobin level is an independent predictor of fibrinogen plasma level. Considering the physiopathologic role of increased plasma fibrinogen concentration and the scarcity of pharmacologic approaches to decrease its level, these findings could be important in designing a preventive therapy of cardiovascular disease

The authors describe an unusual case (a 79-year-old woman) of secondary extramedullary plasmacytoma (EMP) involving the duodenum. While all the previously reported cases of duodenal involvement by EMP (namely 20 cases) were characterized by the presence of ulcerative masses or ischemic necrotic lesions, in our case EMP led to the unusual finding of several non-polypoid lesions with a depressed central area. The final diagnosis was multiple myeloma IgA lambda, stage II A, with secondary duodenal EMP. To our knowledge this is the first report showing duodenal involvement by EMP with the aspect of multiple non-polypoid lesions.

PLoS one 10(1), 1-17 (2015). doi:10.1371/journal.pone.0116468, Published by PLoS, Lawrence, Kan.

Imatinib mesylate (IM) therapy leads to a complete cytogenetic response (CCyR) in 75-90% of Chronic Myeloid Leukemia (CML) patients in chronic phase, but only a small percentage of patients achieve complete molecular response (CMR). Very little is known about IM discontinuation. We report the case of a 20-years-old male patient in chronic phase CML who maintained undetectable BCR/ABL mRNA levels, despite IM discontinuation over a period of 15 months after achieving CMR. Our patient reached CCyR and CMR after 3 and 6 months of IM treatment, respectively. We also reviewed the published literature concerning cases of IM discontinuation.

We describe an unusual case (a 79-year-old woman) of secondary extramedullary plasmacytoma (EMP) involving the duodenum. While all the previously reported cases of duodenal involvement by EMP (namely 20 cases) were characterized by the presence of ulcerative masses or ischemic necrotic lesions, in our case EMP led to the unusual finding of several non-polypoid lesions with a depressed central area. The final diagnosis was multiple myeloma IgA lambda, stage II A, with secondary duodenal EMP. To our knowledge this is the first report showing duodenal involvement by EMP with the aspect of multiple non-polypoid lesions.

A 56-year-old woman presented with dyspnea and a large swelling in the upper vestibular region (Figure 1 A), appeared 6 weeks before and continuing to grow up. Physical examination suggested pleural effusion, subsequently confirmed by chest X-ray (Figure 1 B). Complete blood cell count and biochemistry values were all within normal ranges, excepting for LDH (2620 IU/L) and β(2) -microglobulin (9.4 mg/L).

Aims To evaluate changes in Hepatitis C Virus (HCV) RNA both in plasma and Peripheral Blood Mononuclear Cells (PBMC) in onco-haematological patients. Patients and methods 8 consecutive anti-HCV/HCV RNA-positive patients with onco-haematological diseases (5 with B-cell Non-Hodgkin Lymphoma and 3 with chronic lymphocytic leukaemia) were observed during chemotherapy and after its discontinuation. All were naive to chemotherapy. HCV RNA was sought by Real Time Polymerase Chain Reaction in Light Cycler 1.5 in plasma and PBMC samples collected before, during and after chemotherapy. Results An increase in HCV RNA of at least 1.5 log IU/mL in plasma and 1.1 log IU/ml in PBMC was observed in all 7 patients undergoing Rituximab-based chemotherapy; these patients showed a hepatic flare after discontinuation, life-threatening in one with cirrhosis. Also the 8th patient had cirrhosis, but was treated with Rituximab-sparing chemotherapy and did not show any increase in HCV RNA or a hepatic flare. Conclusion Rituximab-based chemotherapy favours an increase in HCV RNA in onco-haematological patients; this is followed by a hepatic flare, possibly immune-mediated and life threatening in cirrhotic patients.

The aim of the study was to evaluate clinical and virological differences in HBV reactivation between patients with overt and occult HBV infection. Twenty-three consecutive patients with symptomatic HBV reactivation occurring during or after immunosuppressive therapy were enrolled in a retrospective study: 10 with reactivation of overt HBV infection (overt group) and 13 of occult HBV infection (occult group). Twenty-one patients were treated with nucleot(s)ide analogues after HBV reactivation. Regimens including rituximab or fludarabine were administered more frequently in the occult group (61% vs. 31%, respectively). HBV reactivation was severe frequently in the overt (40%) and occult groups (38.4%). Patients in the overt group showed higher HBV-DNA titers (1.1×10 8±1.4×10 8 vs. 5.1×10 5±6.8×10 5IU; P

Nearly 25% of non-Hodgkin lymphomas (NHLs) arise in extranodal locations. The involvement of soft tissue by NHL is uncommon. Primary extranodal NHL of the skeletal muscle is even rarer. The authors report a 49-year-old man with a 3-month history of progressive asymmetry of the face caused by swelling in the right cheek with paresthesia and burning. He underwent an excisional biopsy of the lesion. Histologic examination, immunohistochemistry and cytogenetic analysis were performed. The final diagnosis was primary large B-cell NHL of the masseter muscle, stage IEA. Rituximab-cyclophosphamide, epirubicin, vincristine and prednisone regimen was started. Restaging procedures after immunopolychemotherapy showed no evidence of disease. No relapse has occurred during a follow-up of 72 months. Although primary muscle lymphoma represents a rare entity, it can involve every muscle. Thus, when patients present with cheek swelling, physicians should always consider the possibility of lymphoma. The authors also reviewed the published literature concerning primary muscle lymphoma. © 2011 Lippincott Williams &Wilkins.

Monoclonal components (MCs) are frequently detected in the sera of patients with B-cell malignancies, by techniques that are getting more and more sensitive. Only few chronic lymphocytic leukemia (CLL) patients with multiple serum paraproteins are reported in the literature.In this case report we present a 71-year-old woman with CLL and serum MCs. Immunofixation was performed on agarose film using anti-sera monospecific for the heavy and light chains of human immunoglobulins (anti-gamma, -alpha, -mu, -delta, -epsilon, -kappa, -lambda). Serum free light chains (FLCs) were quantified nephelometrically. Immunofluorescence analysis was performed using fluorochrome-conjugated goat antibodies specific for human mu, gamma or alpha immunoglobulin heavy chains and K or lamda light chains.Immunofixation revealed two different MCs (IgGlambda + lambda light-chains) in the serum and only one MC (lambda light chains) in concentrated urine. Serum lamda FLCs were 206 mg/L. The bone marrow aspiration and biopsy revealed a 38 % interstitial and nodular infiltration of mature small lymphocytes expressing IgG lambda surface immunoglobulins CD 19, CD20, CD5, and CD23, with negative BCL-1, t(11, 14) and cyclin D1. The plasma cells were less than 1%. Final diagnosis was CLL (Rai stage I) with IgG lamda plus lamda serum paraproteins. Three years later, the patient died because of myocardial infarction after a follow-up period with no need for CLL therapy.Our hypothesis is that the double MC may be the result of an unbalanced immunoglobulin chain synthesis by the leukemic B-cell clone, resulting in IgGlamda and excess of lambda FLCs.

Background: Because the ubiquitin-proteasome pathway (UPS) is required for activation of nuclear factor kappa beta (NFkB), a transcription factor that regulates inflammatory genes, we evaluated the UPS activity, NFkB activation, and tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, in ischemic specimens of diabetic myocardium and relate them to the glycemic control (HbA1c), oxidative stress (nitrotyrosine, a modified amino acid produced by reactive O2), and cardiac outcome (echocardiographic parameters). Moreover, the role of UPS, NFkB, and TNF-alpha in the cardiac tissue injury of acute ischemia/reperfusion (I/R) was evaluated in streptozotocin (STZ)-hyperglycemic rats. Finally, this study aimed to elucidate whether an intervention on UPS with bortezomib, an inhibitor of UPS, may counteract the extensive myocardial infarction and increased inflammatory reaction into the hyperglycemic myocardium. Methods: Ventricular biopsy specimens from 16 nondiabetic and 18 type 2 diabetic patients presenting with unstable angina who underwent coronary artery bypass were collected during coronary bypass surgery. Ejection fraction (EF); myocardial performance index (MPI), which measures both systolic and diastolic function, immunostaining, and cardiac levels of nitrotyrosine; UPS activity; NFkB; and TNF-alpha were investigated in both ischemic human myocardium and heart tissue from STZ-hyperglycemic rats subject to a myocardial ischemia/reperfusion procedure. Results: We found that diabetic patients had higher MPI (P

We report a case of primary non-Hodgkin lymphoma of the breast as third metachronous neoplasm in the same patient. Primary non-Hodgkin lymphoma of the breast occurred about 2 years after endometrial cancer and 1 year after bladder cancer. The patient underwent quadrantectomy with level I-II axillary lymph nodes dissection plus rituximab-cyclophosphamide, doxorubicin, vincristine, prednisone chemotherapy. Patient's health status gradually got worse and 11 months after surgery the patient died.

The evaluation of tongue swellings often represents a diagnostic challenge, because of the wide spectrum of benign and malignant possible lesions. We report a case of a patient presenting a tongue mass. An incisional biopsy was performed. Diagnosis of primary Mantle Cell non-Hodgkin’s Lymphoma of the tongue was made by histological, immunohistochemical and cytogenetic studies. Our patient was treated with Rituximab–Cyclophosphamide, Epirubicine, Vincristine, Prednisone polychemotherapy plus Rituximab as single agent maintenance. Complete remission was achieved and no relapse has occurred during a follow-up of 53 months. We emphasize the importance of including also NHL in differential diagnosis of a tongue mass.

Myeloid sarcoma (MS) is a localized extramedullary mass of immature granulocytic cells that usually occurs in patients with acute myeloid leukemia (AML) or myeloproliferative disorders. It may rarely precede peripheral blood or bone marrow involvement, presenting a diagnostic challenge. Although MS may be found in any location, an intraoral occurrence is rare. In this report we describe a rare case of a patient with nonleukemic MS of the maxillary gingiva. The histologic specimen was first interpreted as non-Hodgkin's lymphoma. The correct diagnosis was reached after extensive immunohistologic studies. The malignant cells were myeloperoxidase positive, lysozyme positive, CD45+, CD68+, CD3-, CD10-, CD19-, CD20-, CD30-, CD34-, CD56-, CD79a-, S100-, and chloroacetate esterase negative. Induction therapy with FLAND (fludarabine, Ara-C, mitoxantrone, and dexamethasone) was started, but the patient did not achieve a remission. Some weeks later, the patient presented pleural effusion and paralysis of the seventh cranial nerve on the left side. She died a few days later. The present case indicates the importance of a correct initial diagnosis for adequate therapy, which is often delayed because of a high misdiagnosis rate. If the MS is treated without intensive chemotherapy for AML as soon as possible, the prognosis will be poor.

B-cell chronic lymphocytic leukemia (B-CLL) is characterized by a progressive accumulation of long-lived and well-differentiated clonal B-lymphocytes in peripheral blood, lymphoid tissue and bone marrow. Although B-CLL pathogenesis is not entirely understood, the progressive increase in lymphocyte counts coupled with the very low proportion of proliferating cells suggests that B-CLL may be primarily determined by defective apoptosis. Consistently, freshly analyzed CLL B-cells express very low levels of membrane CD95, one of the best-known receptors involved in triggering apoptosis. In this study, CD95 upregulation on CLL B-cells was induced by culturing clonal B-cells in the presence of supernatants from preactivated autologous T-lymphocytes. Intracellular cytokine staining of preactivated autologous T-lymphocytes using monoclonal antibodies (moAbs) specific for Th1 or Th2 cytokines, namely interleukin (IL)-2, IL-4, IL-5, IL-10 and interferon (IFN)-gamma, showed these cells to be positive for IL-2 and IFN-gamma. Blocking experiments using moAbs specific for IL-2 and/or IFN-gamma revealed that CD95 upregulation on CLL B-cells was mainly driven by IFN-gamma. However, CD95-expressing CLL B-cells were demonstrated to be resistant to CD95-mediated apoptosis, thus arguing against strategies aimed at exploiting CD95-mediated apoptosis for immunotherapy of B-CLL.

We describe the case of a 60-year-old woman with a delayed hemolytic transfusion reaction (DHTR). She had a history of an ulcerative colitis, blood transfusion because of rectal bleeding, and surgical removal of descendent and sigmoid colon. At admission, laboratory data showed Hb 6.3 g/dL, reticulocytes 120 x 10(9)/L, serum total bilirubin 1.2 mg/dL (direct bilirubin: 0.2 mg/dL). Pretransfusion antibody screening procedures were positive. A monospecific autoanti-Jk(a) and three alloantibodies (anti-c, -E, -K) were identified by immunohematologic studies. The patient received two units of crossmatch compatible concentrated red blood cells. Six days later biochemical serum values showed Hb 6.2 g/dL, LDH 975 I.U./L and total bilirubin 2.95 mg/dL (direct 0.35 mg/dL). Crossmatches with red cell suspension of transfused blood units and a post-transfusion serum were repeatedly positive. Laboratory tests showed the presence of anti-S alloantobody in the serum and eluate. Moreover, pre-transfusion serum of the patient was retrospectively retested: anti-S was not detected. These data suggested a DHTR. The present case is unusual and interesting because of the association of a rare autoanti-Jk(a), non responsible for anemia, and four alloantibodies of which anti-S involved in a DHTR.

The case of a patient with an extranodal non-Hodgkin lymphoma and three M-components (IgGkappa + IgGlambda + IgMlambda) in the serum is described. Three separate populations of M-component producing cells have been identified. Since a kappa-->lambda chain switch is not demonstrated, the synthesis of IgGkappa and IgGlambda by two distinct clones is obvious. IgMlambda and IgGlambda M-components are synthesized by two different plasma cell populations that could represent two unrelated cell clones or, alternatively, two subclones originated by a common precursor. After chemotherapy the IgGlambda M-component is replaced by heavy gamma chains without evidence of lambda light chains.

We report a rare case of a patient with multiple myeloma who developed hyperamylasemia not associated to hyperamylasuria and without symptoms of pancreatic or salivary disease. This condition suggested the occurrence of macroamylasemia, consisting of macromolecules of amylase bound with immunoglobulins, which are not filtered by the kidneys. Hyperamylasemia was not present at the diagnosis of myeloma and appeared at the relapse of the disease, simultaneously with the appearance of an additional gamma-chain oligoclonal component, suggesting a possible role of these chains in producing macroamylasemia. To our knowledge, this is the first report of macroamylasemia in a patient with multiple myeloma.

The development of a IgGk monoclonal gammopathy after a phase of bone marrow aplasia following chemotherapy is described in a patient suffering from biphenotypic acute leukemia (BAL). Paraprotein was followed by the relapse of the disease and disappeared during a further chemotherapy. Paraprotein could have been caused by an additional chemotherapy-induced genetic mutation or by a dysfunction in T-B cooperation observed in the phase of reconstitution of the immune system after medullar aplasia.

In the present study, β-endorphin and met-enkephalin were tested for their antiplatelet activity in human platelet-rich plasma (PRP). Blood samples were obtained from 15 healthy subjects. The results of the study show that these two endogenous opioids (200 pg/ml final concentration) reduce platelet aggregation when it is induced by ADP at low dose (0.5 μM). It is likely due to conformational changes on the platelet membrane that cause a non-specific decreased susceptibility to platelet-aggregating agonists. Am. J. Hematol. 68:1–3, 2001. © 2001 Wiley-Liss, Inc.

Twenty-seven subjects suffering from peripheral occlusive arterial disease (POAD, clinical stage II-III according to Fontaine) were enrolled in this study to evaluate the effect of oxygen-ozone therapy upon hemorheological parameters and hemoglobin-oxygen affinity in patients with POAD. All patients underwent a major ozonized autohemotransfusion consisting of the slow reinfusion of 100 ml of autologous blood, previously exposed to a O(2)-O(3) mixture in a glass box for 10 min. Whole blood viscosity, erythrocyte filterability, hematocrit, and fibrinogen levels were assessed at the basal time and 30 min after the reinfusion of ozonized blood. At the same time p50 standard (p50std) values (an indicator of hemoglobin-oxygen affinity) and plasma values of malonyl dialdehyde (MDA, an indicator of lipid peroxidation) were evaluated. At the baseline, patients had significantly higher ( p0.05- p0.001) whole blood viscosity, MDA, and p50std values and significantly lower blood filterability ( p0.01) as compared with 20 matched healthy volunteers (controls). Thirty minutes after the end of a major autohemotransfusion, whole blood viscosity significantly decreased ( p0.01). This was accompanied by a significant fall in plasma fibrinogen level ( p0.01) with no change in hematocrit. Blood filterability, MDA plasma level, and p50std values increased significantly at the same time ( p0.01- p0.005). The 2,3-DPG value did not change significantly. No significant changes occurred when the same patients received a non-ozonized autohemotransfusion (control test). In conclusion, ozonized autohemotransfusion may be useful to improve both the poor rheological properties of the blood and the oxygen delivery to tissues in patients suffering from POAD.

Context.—C1 inhibitor (C1-INH) is an α2-globulin that blocks esterolytic activity of the first component of the classic complement cascade. The α-granules of normal human platelets also contain C1-INH, which is expressed on the platelet surface during platelet secretion in healthy patients, but it is clearly reduced in patients with hereditary angioedema (HAE).Objective.—To evaluate the effects of in vivo C1-INH concentrate infusion on platelet responsiveness and coagulation system activity in patients with HAE.Design.—Assessment of the platelet activity and plasma levels of C1-INH, activated factor XII (XIIa), and prothrombin fragment F1.2 (F1.2) before and after infusion of 15 U/kg of C1-INH concentrate.Patients.—In 6 patients (4 men and 2 women), HAE was diagnosed according to the accepted clinical and laboratory criteria.Measurements.—Platelet aggregation (final concentrations: adenosine diphosphate, 0.5, 1.25, and 2.5μM; collagen, 5 μg/mL), C1-INH antigen (radial immunodiffusion), C1-INH activity (chromogenic substrates), and XIIa and F1.2 (enzyme-linked immunosorbent assay).Results.—After C1-INH infusion, we observed a prompt increase of C1-INH level and a slow return toward its plasma preinfusion values within 4 to 7 days, a significant decrease of both adenosine diphosphate– and collagen-induced platelet aggregation versus preinfusion values (maximum after 1–2 days; P < .001), and a rapid decrease of high basal values of XIIa and F1.2 in 30 and 120 minutes, respectively.Conclusions.—These data show a role of C1-INH in the control of platelet activity and that its deficiency increases platelet aggregability and plasma levels of XIIa and F1.2 in patients with HAE.