Irena Seili-Bekafigo

Combined evaluation of bone marrow aspirate and biopsy is superior in the prognosis of multiple myeloma

BackgroundEstimation of plasma cell infiltrates in bone marrow aspirates (BMA) and bone marrow biopsy (BMB) is a standard method in the diagnosis and monitoring of multiple myeloma (MM). Plasma cell fraction in the bone marrow is therefore critical for the classification and optimal clinical management of patients with plasma cell dyscrasias. The aim of the study was to compare the percentage of plasma cells obtained by both methods with the patient clinical parameters and survival.MethodsThis retrospective study included BMA and BMB of 59 MM patients. The conventional differential count was determined in BMA to estimate the percentage and cytologic grade of plasma cells. The pattern of neoplastic infiltration and percentage of plasma cells were estimated on CD138 immunostained BMB slides microscopically and by computer-assisted image analysis (CIA).ResultsSignificantly higher values of plasma cell infiltrates were observed in pathologist (47.7 ± 24.8) and CIA (44.1 ± 30.6) reports in comparison with cytologist analysis (30.6 ± 17.1; P < 0.001 and P < 0.0048, respectively). BMB assessment by pathologist counting and using CIA showed strongest correlation (r = 0.8; P < 0.0001). Correlation was also observed between the pathologist and cytologist counts (r = 0.321; P = 0.015) as well as comparing the percentage of plasma cells in BMA and CIA (r = 0.27; P = 0.05). Patients with clinical stage I/II had a significantly lower CIA plasma cell count than those with clinical stage III (P = 0.008). Overall survival was shorter in patients with more than 25% of atypical plasma cell morphology estimated in BMA (P = 0.05) and a higher percentage of tumor cell infiltrates estimated by the pathologist and CIA (P = 0.0341 and P = 0.013, respectively).ConclusionStudy results suggested the combined analyses to be useful as a routine procedure to achieve more accurate and informative diagnostic data.

Assessment of Bone Marrow Fibrosis and Angiogenesis in Monitoring Patients With Multiple Myeloma

The aim of our study was to emphasize the importance of accurate and standardized techniques for detailed monitoring of the microenvironment in multiple myeloma (MM). Bone marrow fibrosis, angiogenesis, and plasma cell infiltrates in bone marrow biopsy (BMB) samples at the time of diagnosis and on completion of therapy were analyzed for 42 patients with newly diagnosed MM. Computerized image analysis was used for all slides stained with anti-CD138 and anti-CD34. The patients with fibrosis in pretreatment BMB samples had significantly higher microvessel density (MVD) and plasma cell infiltrates. In posttreatment BMB samples, nonresponders had a significantly higher frequency and grade of fibrosis and higher values of MVD, total vascular area, and plasma cell percentage. The overall survival of nonresponders and patients with increased marrow fibrosis in posttreatment BMB samples was significantly shorter. The obtained results confirm that complex morphologic examination of the bone marrow microenvironment during the monitoring of MM can provide better prognostic significance.

Plasma Levels of Osteopontin and Vascular Endothelial Growth Factor in Association with Clinical Features and Parameters of Tumor Burden in Patients with Multiple Myeloma

The aim of this pilot study was to determine the plasma levels of osteopontin (OPN) and vascular endothelial growth factor (VEGF) and find possible association between them and main clinical features and parameters of tumor burden in patient with multiple myeloma (MM). Plasma levels of OPN and VEGF were determined in 44 newly diagnosed MM patients and 24 healthy persons by ELISA method. These values were compared with the presence of anemia, renal dysfunction, and bone lesions as myeloma related clinical manifestations and with serum beta-2 microglobulin and Durie-Salmon clinical stage as prognosticators related to tumor mass. The value of OPN was significantly higher in MM patients with evident bone lesions (P = 0.03) and there was also a positive correlation with serum beta-2 microglobulin (r = 0.366; P = 0.04). Furthermore, patients with lower Durie-Salmon stage had significantly lower OPN and VEGF levels (P = 0.05; P = 0.04, resp.). Our preliminary results found positive association between plasma level of OPN, tumor burden, and bone destruction. Further analysis should provide information about the possible use of OPN as useful clinical biomarker for monitoring bone disease and tumor mass, as well as a prognostic factor, or a possible target for pharmacological intervention.

Angioimmunoblastic lymphadenopathy with dysproteinemia following doxycycline administration

Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is a primary lymphoproliferative T-cell disorder, currently classified as a peripheral T-cell non-Hodgkins lymphoma. AILD is characterized by generalized lymphadenopathy, hepatosplenomegaly, immunological abnormalities, polyclonal hypergammaglobulinemia and anemia. We report a case of AILD in an 80-year-old male who presented with a generalized pruritic maculopapular eruption and fever following doxycycline administration. The maculopapular rash progressed to formation of confluent nodules, plaques and finally erythroderma with lymphadenopathy and hepatosplenomegaly. Blood analysis revealed an elevated erythrocyte sedimentation rate and polyclonal hypergammaglobulinemia. Lymph node biopsy showed almost complete effacement of the nodal architecture with diffuse proliferation of small vessels forming an arborizing network, surrounded by atypical lymphocytes, usually CD3+ CD4+ and occasionally CD3 + CD8+. There were also larger cells (immunoblastic shape) that displayed CD20 positively, some scattered plasma cells, and eosinophils. Histology of a cutaneous lesion showed spongiosis and infiltration of the epidermis by atypical lymphocytes with large hyperchromatic nuclei, perivascular dermal lymphocytic infiltrate (CD3+) mixed with plasma cells and occasional large immunoblasts (CD20+). During hospitalization the patient developed hemolytic anemia (Coombs positive) and lung metastases. The prognosis of AILD is generally poor, with a median survival of less than 20 months. Our patient died two and a half months after the diagnosis was made due to sepsis caused by Staphylococcus aureus isolated in hemoculture.

Plasma Levels of Monocyte Chemotactic Protein-1 Are Associated with Clinical Features and Angiogenesis in Patients with Multiple Myeloma

The aim of this pilot study was to determine the plasma levels of monocyte chemotactic protein-1 (MCP-1) and possible associations with angiogenesis and the main clinical features of untreated patients with multiple myeloma (MM). ELISA was used to determine plasma MCP-1 levels in 45 newly diagnosed MM patients and 24 healthy controls. The blood vessels were highlighted by immunohistochemical staining, and computer-assisted image analysis was used for more objective and accurate determination of two parameters of angiogenesis: microvessel density (MVD) and total vascular area (TVA). The plasma levels of MCP-1 were compared to these parameters and the presence of anemia, renal dysfunction, and bone lesions. A significant positive correlation was found between plasma MCP-1 concentrations and TVA (p = 0.02). The MCP-1 levels were significantly higher in MM patients with evident bone lesions (p = 0.01), renal dysfunction (p = 0.02), or anemia (p = 0.04). Therefore, our preliminary results found a positive association between plasma MCP-1 levels, angiogenesis (expressed as TVA), and clinical features in patients with MM. However, additional prospective studies with a respectable number of patients should be performed to authenticate these results and establish MCP-1 as a possible target of active treatment.

Deskriptivna i funkcionalna definicija jezgrice – put prema terapiji raka

Modern tumour therapy should be target specific and comprehensive. Recent clinical trials test small molecular inhibitors of transcription of ribosomal genes and activators of apoptosis. We treatise on models of activation of the suppressors of tumour growth acting in the nucleolar domain. Tumour cells demonstrate a disordered protein regulation and mutation of P53 gene which codes for a suppressor of growth. Therapy is guided by pathogenesis. Modern disease definition is based on etiopathogenesis of cell stress, wherein participate numerous organelles, including the nucleolus. Nucleus and nucleolus are forms seen on light microscopy. This presentation focuses on the description of the visible correlate of the notion of “nucleolus”. Further to this, acid non-histone proteins which gather around the transcriptional machinery of RNA polymerase I are described, and the significance of their visualisation towards the alteration of the definition of nucleolus is pointed out. Besides being a particle within the nucleoplasm and a subnuclear organelle, the nucleolus is visualized through its functional structures – the AgNORs. The AgNOR proteins have a role in nucleolar stress. The aim of this article is to discuss the nucleolar stress.

The Bethesda system for reporting thyroid cytopathology – our first experiences

Citoloska punkcija stitnjace nezamjenjiva je dijagnosticka metoda u procjeni rizika za malignitet u cvorovima stitnjace. Bethesda klasifikacija citoloskih nalaza stitnjace nastala je 2007. godine kao rezultat analize velikog broja podataka prikupljenih iz razlicitih ustanova i sadrži sest kategorija. Za svaku kategoriju procijenjen je rizik za malignitet i usvojene preporuke za daljnji postupak s pacijentom, a ujednacena je i terminologija u citoloskim nalazima. Primjenjuje se u Sjedinjenim Americkim Državama i vecini europskih zemalja uz neke nacionalne modifikacije. Prikazani su također i prvi rezultati njene primjene na Odjelu za opcu citologiju Klinickog bolnickog centra Rijeka u 2015. godini.