The importance of bone marrow infiltration patterns in multiple myeloma seen on magnetic resonance imaging-Case report and imaging perspective.

Non-secretory multiple myeloma (NSMM) is an extremely rare variant of multiple myeloma (MM) and accounts for a maximum of 5% of all myeloma cases. This variant of MM usually represents a diagnostic challenge to the clinician because of the absence of detectable monoclonal immunoglobulin on serum or urine electrophoresis. We present the case of a 34-year-old Caucasian male who presented to the emergency department with pain in the lumbar area secondary to a fall and who was eventually diagnosed with non-secretory multiple myeloma after the radiologist initially pointed out a discrete "salt and pepper" infiltration of the spine seen on magnetic resonance imaging (MRI) although the spine computed tomography (CT) performed initially showed no suspicious lesions for malignancy. The final diagnosis was obtained after a positive bone marrow biopsy together with the presence of malignant lesions seen on the spine MRI. This case points out the importance of different bone marrow involvement patterns seen on MRI and other useful sequences the radiologist could use to better discriminate between normal marrow reconversion and malignant infiltration.

Whole-body diffusion-weighted magnetic resonance imaging and apparent diffusion coefficient values as prognostic factors in multiple myeloma.

Multiple myeloma (MM) is a neoplasm of the B lymphocytes characterized by the uncontrolled proliferation of a plasmocyte clone. Magnetic resonance imaging (MRI) remains the most sensitive and specific imaging method for the detection of bone marrow infiltration, before macroscopic bone changes are visible, with evidence that the detection rate and overall performance of MRI could be enhanced by applying diffusion-weighted imaging (DWI). The aim of our research was to evaluate whether measuring apparent diffusion coefficient (ADC) values in newly diagnosed patients with MM could be a prognostic factor for the course of the disease and to ascertain whether there is any correlation with other prognostic factors in MM. A retrospective study was performed on a group of 32 patients with newly diagnosed MM that underwent at least two whole-body (WB)-MRIs; one before and one after induction therapy. Patients with advanced stage of disease showed an increased ADC value: Stage 2 vs. stage 1 (1.162 vs. 0.289, P=0.033), respectively, stage 3 vs. stage 1 (0.867 vs. 0.289, P=0.041). In addition, ADC values were inversely correlated with survival time: r=-0.641, P<0.001. According to the multivariate linear regression model, we observed that for every point of ADC value (before treatment) the survival was decreased/reduced by 14.5 months. Moreover, bortezomib therapy predicted an increase in the survival length/duration by 7.9 months. Our regression equation proved to be a good fit for the model, explaining 57.8% of survival duration (adjusted R2=0.578). In conclusion, the negative prognostic factors associated with WB-MRI are represented by high ADC values before treatment (for every point of ADC the survival was decreased by 14.5 months) and focal/diffuse marrow involvement.

High Carbohydrate Diet Is Associated with Severe Clinical Indicators, but Not with Nutrition Knowledge Score in Patients with Multiple Myeloma.

Although the survival rate of patients diagnosed with multiple myeloma has doubled over the last few decades, due to the introduction of new therapeutic lines and improvement of care, other potential contributors to the therapeutic response/relapse of disease, such as nutrient intake, along with nutrition knowledge, have not been assessed during the course of the disease. The purpose of this research was to assess nutrition knowledge and diet quality in a group of patients with a diagnosis of multiple myeloma. Anthropometric, clinical and biological assessments and skeletal survey evaluations, along with the assessment of nutritional intake and general nutrition knowledge, were performed on 61 patients with a current diagnosis of multiple myeloma. A low carbohydrate diet score was computed, classified in tertiles, and used as a factor in the analysis. Patients in tertiles indicative of high carbohydrate or low carbohydrate intake showed significant alteration of clinical parameters, such as hemoglobin, uric acid, albumin, total proteins, beta-2 microglobulin, percentage of plasmacytes in the bone marrow and D-dimers, compared to patients in the medium carbohydrate intake tertile. Nutrition knowledge was not associated with clinical indicators of disease status, nor with patterns of nutrient intake. Better knowledge of food types and nutritional value of foods, along with personalized nutritional advice, could encourage patients with MM to make healthier decisions that might extend survival.

Influence of novel gallium complexes on the homeostasis of some biochemical and hematological parameters in rats.

The aim of this study was to detect possible homeostasis changes in some biochemical and hematological parameters after the administration of gallium (Ga) complexes C (24) and C (85) on an experimental animal model (Wistar strain rats). In order to observe chronobiological aspects, a morning (m) and an evening (e) animal series were constituted. Further on, each series were divided into three groups: control (C), experimental I (EI), and experimental II (EII). Both Ga complexes were solubilized in a carrier solution containing polyethylene glycol (PEG) 400, water, and ethanol. Animals of the C groups received the carrier solution by intraperitoneal injection, those from the EI groups received the solubilized C(24) gallium complex, and those of the EII groups received the solubilized C(85) gallium complex. At the end of the experiment, blood and tissue samples were taken and the following parameters were determined: serum concentration of the nonprotein nitrogenous compounds (uric acid, creatinine, and blood urea nitrogen), hematological parameters (erythrocytes, hemoglobin, leukocytes, and platelets), and the kidney tissue concentration of three essential trace elements (Fe, Cu, and Zn). With the exception of uric acid, the results revealed increased concentrations of the nonprotein nitrogenous compounds both in the morning and in the evening experimental groups. Hematological data showed increased levels of erythrocytes, hemoglobin, and leukocytes and decreased platelet levels in the experimental group given the C(24) gallium complex in the morning (EI-m) group; increased levels of leukocytes and decreased levels of the other parameters in the experimental group given the C(24) gallium complex in the evening (EI-e) group; and increased levels of all hematological parameters in the experimental groups receiving the C(85) gallium complex in the morning (EII-m) group and in the evening (EII-e) group. Decreased kidney tissue concentrations of metals were found in all the experimental groups. Fe levels were significantly decreased in the EI-m receiving the C(24) gallium complex and EII-m which received the C(85) gallium complex and in the EII-e group which received the C(85) gallium complex. In the EI-e group which received the C(24) gallium complex, a significant decrease of Cu concentration was reported.

The characterization of PDGFR-alpha and PDGFR-beta expression in malignant non-Hodgkin lymphoma.

PDGF receptors play an important role in tumor progression as being part of a group of receptors that are expressed along the membrane of tumor cells. The aim of this study was to evaluate the PDGF receptor expression in follicular and diffuse forms of non-Hodgkin malignant lymphoma. We evaluated 38 biopsy fragments from patients diagnosed with malignant non-Hodgkin lymphoma. We noticed the distribution of PDGFR-alpha and -beta in tumor cells and the immunoreactivity was quantified as the percentage of positive tumor cells. We noticed the presence of score 3, more than 30% of tumor cells positive, for PDGFR-alpha and PDGFR-beta in 50% and 75% cases of follicular non-Hodgkin lymphoma. For diffuse malignant non-Hodgkin lymphomas, score 3 was noted in 23.52% of cases for PDGFR-alpha and 35.29% of cases for PDGFR-beta. This may represent an important therapeutic target in patients who do not respond to conventional therapy, but further research is needed for a careful evaluation of benefits and side effects of PDGFR inhibitors.

Heterogeneity of malignant non-Hodgkin lymphoma-associated blood vessels.

The present study described for the first time a high heterogeneity of blood vessels in non-Hodgkin lymphomas (nHL). The tumor blood vessels were highlighted with CD105÷smooth muscle actin (SMA) and CD34/SMA double immunostaining. For both follicular and diffuse types of lymphomas, more than 85% of CD34/SMA positive vessels were of immature and intermediate type. A percent of 96.54 from CD105/SMA assessed blood vessels were of activated and mature activated types with high expression of CD105 on endothelial cells of newly formed blood vessels. Our results suggest that these types of vessels are potential therapeutic targets for antivascular therapy.

Mast cells contribute to the angiogenesis in non-Hodgkin lymphoma. An immunohistochemical study based on the relationship with microvessel density.

Only few data are available in the literature concerning angiogenesis in hematological malignancies. Non-Hodgkin lymphoma classified on the base of molecular profile is frequently characterized by unpredictable behavior that seems to be related to tumor cells and also to the tumor microenvironment. The tumor microenvironment contains blood vessels and a large variety of cells that can play an important role to the progression of angiogenesis and tumor growth. From these, mast cells have been shown to be a source of angiogenic factors. The aim of this work was to investigated the relationships between mast cells and blood vessels in non-Hodgkin lymphoma and reactive lymphoid tissue from three different anatomical sites. Using double immunostaining method CD34/mast cell tryptase we noticed that mast cell density was significantly lower in the follicular lymphoma than in diffuse type lymphoma. The morphology of vessels, the presence of pillars and splitting suggested that intussusceptions is the main mechanism of angiogenesis. In the cases with primary lymphoma of the spleen, we found few mast cells and a high number of blood vessels. Our data suggest that lymphoma-associated angiogenesis is driven in part by the tumor microenvironment, and particularly, by mast cells. On the other hand, our results support the organ-specific tumor-associated angiogenesis in malignant non-Hodgkin lymphoma.

B-cell transcription factors Pax-5, Oct-2, BOB.1, Bcl-6, and MUM1 are useful markers for the diagnosis of nodular lymphocyte predominant Hodgkin lymphoma.

In some instances, the overlap in morphologic features and antigen expression between nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and classical Hodgkin lymphoma (cHL) can cause confusion in the diagnosis. In these cases, the transcription factors (TFs) B-cell specific activator protein (BSAP)/Pax-5, octamer binding protein-2 (Oct-2), B-lymphocyte-specific co-activator BOB.1/OBF.1, Bcl-6 protein and multiple myeloma-1/interferon regulatory factor-4 (MUM1/IRF-4) may aid in clarifying the diagnosis. Twenty-two cases of NLPHL were studied for the immunohistochemical expression of Pax-5, Oct-2, BOB.1, Bcl-6 protein and MUM1/IRF-4. Our results sustain the usefulness of the selected set of TFs to diagnose and distinguish NLPHL from cHL since Pax-5, Oct-2, BOB.1 and Bcl-6 are consistently expressed by lymphocyte predominant (LP) cells and reported by others to be often unexpressed in Hodgkin and Reed-Sternberg cells. By contrast, MUM1/IRF-4 protein scored negative in the majority of LP cells, but is reported to be expressed in almost all cases of cHL. Thus, although the expression of transcription factors is very heterogeneous, their simultaneous implementation for positive and differential diagnosis may be useful.