Multimodal Image Analysis of Chronic Leukemic Lymphoproliferative Disorders and the Hypothesis of »Single« and »Multiple« Programmed Stops in the Development of Typical and Atypical Forms of Leukemias and Lymphomas

The study consisted of morphometric analysis, assessment of the argyrophilic nucleolar organization region (AgNOR) characteristics, and image cytometry (ICM) in different tumor mass compartments: bone marrow (BM), peripheral blood (PB) and lymph nodes (LN) from patients with chronic leukemic lymphoproliferative disorders. A total of 71895 cells were analyzed on SFORM PC (VAMSTEC, Zagreb). Correlation between morphometric, AgNOR and ICM characteristics revealed the cells with low proliferative activity to possess small, homogeneous AgNOR, with the majority of cells in the peak of DNA histogram. The cells with high proliferative activity had inhomogeneous AgNOR, mostly containing greater DNA content than peak cells, pathologic mitoses (DNA>4N), or the majority of cells were in the S-phase of the cell cycle. Cells with medium proliferative activity and annular AgNOR were in-between. Analysis of different tumor mass compartments showed that lymphatic cells with the affinity to accumulate in BM regularly exhibited low proliferative activity (a lower percentage of cells in SFC and highest percentage of cells in the peak of the G0/G1 phase). The cells in LN exhibited the characteristics of proliferative cells (an increased number of AgNOR, larger and more proliferative inhomogeneous AgNOR, and lowest percentage of cells in the G0/G1 phase). The migration of cells from BM to LN and between lymph nodes occurred through PB (there were cells with low and high proliferative activity: a higher proportion of cells in SFC and at the same time in the G0/G1 phase of the cell cycle). Analysis of cell size and proliferative activity in different compartments of tumor mass revealed that the cells in BM and PB did not differ substantially according to size and proliferative activity, while an inverse pattern was observed between PB and LN. As small cells are inactive and larger cells more proliferative, the analysis quite unexpectedly showed the PB cells to be largest and most inactive, in contrast to LN where the cells were smallest and most active. The »single« and »multiple programmed stops« have been hypothesized in the development of typical forms of leukemias and lymphomas and atypical forms of subacute and subchronic leukemias. Differentiation impairment may occur at any stage, and different »stop« locations result in different morphology and affinity to accumulation in bone marrow, peripheral blood and lymph nodes

Emphysematous cystitis: a non-specific presentation

Emphysematous cystitis is a rare but serious urinary tract infection characterized by the presence of gas in the bladder wall and lumen, caused by gas-forming bacteria. This condition can lead to damage to the bladder wall, with possible rupture, sepsis, and death if left untreated. It is most commonly seen in older female patients and diabetics with multiple comorbidities

Serum Immunoglobulins in non-Hodgkin’s Lymphoma Patients

Serum proteins and immunoglobulin (Ig) findings in 119 non-Hodgkin’s lymphoma (NHL) patients were analysed. Out of them 96 (81%) patients had B non-Hodgkin lymphoma (B-NHL), and 23 (19%) T-NHL. Indolent type of NHL was more frequent (77 patients, 65%), then aggressive type of NHL (42 patients, 35%). Most patients had normal serum protein concentration, the increased protein concentration was seen in 17% of patients while decreased concentration was noticed in 7% of patients. Hypoalbuminaemia was more frequent (43%) then hyperalbuminaemia (1%). In contrast to albumin, low levels of other protein fractions (alpha1-, alpha2-, and beta-globulin) were rather rare (0.6%, 4%, and 3% of patients, respectively) and high levels were frequent (23%, 37%, and 8%, respectively). Polyclonal hyperimmunoglobulinaemia was more frequent finding than hypoimmunoglobulinaemia. In 29% patients higher IgG level and in 25% patients higher IgA level were found. IgM hypoimmunoglobulinaemia (22%) was more frequent than IgG (11%) and IgA (8%) hypoimmunoglobulinaemia. M-spike in serum protein electrophoresis was found in 11 (7%) patients. The statistically significant association was not found between serum Ig concentration and lymphoma malignancy grade as well as between serum Ig concentration and immunologic origin of lymphoma. T-NHL patients have more often IgA concentration level above or under normal values than B-NHL patients (p<0.05)

Diffuse Large B-cell Lymphoma in Patient after Treatment of angioimmunoblastic T-cell Lymphoma

Relatively few cases of Epstein-Barr (EBV)-positive B-cell lymphomas arising in patients with angioimmunoblastic T-cell lymphoma (AITL) have been reported. We report a case of AITL in which diffuse large B-cell lymphoma arose 13 months after the initial diagnosis of AITL. In a 36-year-old female patient, evaluated for moderate leukocytosis, peripheral and abdominal lymphadenopathy AITL was diagnosed in March 2008, based on results of fine-needle aspiration cytology (FNAC) of the enlarged cervical and supraclavicular lymph nodes.The diagnosis was also confirmed by immunophenotyping and histopathology of the cervical lymph nodes. The patient initially recieved FED chemotherapy (fludarabine, cyclophosphamide, dexamethasone) followed by elective autologous hematopoietic stem cell transplantation. In April 2009 the patient was hospitalized because of fever, pancytopenia, hyperbilirubinemia and peripheral lymphadenopathy. The FNAC of the enlarged cervical lymph nodes was performed again, but this time the smears were composed of polymorphous population of lymphocytes with the predomination of large cells, CD20+ on immunocytochemical stains. The immunophenotyping confirmed a predomination of monoclonal mature B-cells. Patient had high number of EBV DNA copies in plasma and serologic testing revealed increased titers of EBV VCA IgG and EBV EBNA IgG. CHOP-R chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab) was then administered, resulting in good partial response of the disease. Reduced intensity allogeneic stem cell transplantation performed thereafter, resulted in complete remission of the disease. AITL is a rare lymphoproliferative disorder in which the neoplastic T-cells represent the minority of the lymph node cell population and almost all cases harbor EBV-infected B-cells. Various authors postulated that immunodeficiency in AITL patients together with immunosupresive effects of cytotoxic drugs, may be responsible for EBV-induced proliferation of latently or newely EBV-infected B-cells with eventual clonal selection and progression to aggressive B-cell lymphoma

Primary Gastrointestinal non-Hodgkin Lymphoma in Adults: Clinicopathologic and Survival Characteristics

Primary non-Hodgkin lymphomas of gastrointestinal tract (PGI-NHL) are the most common extranodal lymphomas with an increasing incidence. The incidence, clinicopathologic characteristics, treatment and survival were assessed in 39 successive, newly diagnosed PGI-NHL patients (23 male and 16 female) treated at »Merkur« University Hospital. The aim of the study was to precisely evaluate their characteristics and compare them with the results reported from other similar studies. The most common site of PGI-NHL was stomach (n=29, 74%), followed by small intestine (n=5, 13%), and colon and rectosigmoid (n=5, 13%). According to the Ann Arbor classification, 34 (87%) patients had stage IE and IIE, and five patients (12%) stage IIIE and IVE. According to World Health Organization (WHO) classification, 29 (87%) patients had diffuse large B-cell lymphoma (DLCBL), two had mantle cell lymphoma, and seven (18%) had marginal zone B-cell lymphoma-mucosa associated tissue (MALT). Twenty-six (66%) patients underwent surgical resection followed by chemotherapy, ten (26%) were treated with chemotherapy alone, and three (8%) were treated surgically. Complete remission was achieved in 28 (72%) and partial remission in seven (18%) patients. Four (10%) patients had progressive disease. In our patients, the major prognostic factor for outcome was the stage of disease. Patients with localized lymphoma (stage IE and IIE) had a significantly longer overall survival: 85% at five years and 65% at ten years. Patients with extended disease (stage IIIE and IVE) had overall survival less than 33%. The prognostic power of erythrocyte sedimentation rate (ESR), total protein, serum albumin, LDH concentration and activity was analyzed. Of these parameters, only LDH had a statistically significant effect on overall survival. In conclusion, our patient group was comparable to other literature reports on PGI-NHL patients according to clinicopathologic characteristics. Disease stage and LDH were the only parameters that had a statistically significant effect patient survival

Multimodal Image Analysis of Chronic Leukemic Lymphoproliferative Disorders and the Hypothesis of »Single« and »Multiple« Programmed Stops in the Development of Typical and Atypical Forms of Leukemias and Lymphomas

The study consisted of morphometric analysis, assessment of the argyrophilic nucleolar organization region (AgNOR) characteristics, and image cytometry (ICM) in different tumor mass compartments: bone marrow (BM), peripheral blood (PB) and lymph nodes (LN) from patients with chronic leukemic lymphoproliferative disorders. A total of 71895 cells were analyzed on SFORM PC (VAMSTEC, Zagreb). Correlation between morphometric, AgNOR and ICM characteristics revealed the cells with low proliferative activity to possess small, homogeneous AgNOR, with the majority of cells in the peak of DNA histogram. The cells with high proliferative activity had inhomogeneous AgNOR, mostly containing greater DNA content than peak cells, pathologic mitoses (DNA>4N), or the majority of cells were in the S-phase of the cell cycle. Cells with medium proliferative activity and annular AgNOR were in-between. Analysis of different tumor mass compartments showed that lymphatic cells with the affinity to accumulate in BM regularly exhibited low proliferative activity (a lower percentage of cells in SFC and highest percentage of cells in the peak of the G0/G1 phase). The cells in LN exhibited the characteristics of proliferative cells (an increased number of AgNOR, larger and more proliferative inhomogeneous AgNOR, and lowest percentage of cells in the G0/G1 phase). The migration of cells from BM to LN and between lymph nodes occurred through PB (there were cells with low and high proliferative activity: a higher proportion of cells in SFC and at the same time in the G0/G1 phase of the cell cycle). Analysis of cell size and proliferative activity in different compartments of tumor mass revealed that the cells in BM and PB did not differ substantially according to size and proliferative activity, while an inverse pattern was observed between PB and LN. As small cells are inactive and larger cells more proliferative, the analysis quite unexpectedly showed the PB cells to be largest and most inactive, in contrast to LN where the cells were smallest and most active. The »single« and »multiple programmed stops« have been hypothesized in the development of typical forms of leukemias and lymphomas and atypical forms of subacute and subchronic leukemias. Differentiation impairment may occur at any stage, and different »stop« locations result in different morphology and affinity to accumulation in bone marrow, peripheral blood and lymph nodes

Primary Gastrointestinal non-Hodgkin Lymphoma in Adults: Clinicopathologic and Survival Characteristics

Primary non-Hodgkin lymphomas of gastrointestinal tract (PGI-NHL) are the most common extranodal lymphomas with an increasing incidence. The incidence, clinicopathologic characteristics, treatment and survival were assessed in 39 successive, newly diagnosed PGI-NHL patients (23 male and 16 female) treated at »Merkur« University Hospital. The aim of the study was to precisely evaluate their characteristics and compare them with the results reported from other similar studies. The most common site of PGI-NHL was stomach (n=29, 74%), followed by small intestine (n=5, 13%), and colon and rectosigmoid (n=5, 13%). According to the Ann Arbor classification, 34 (87%) patients had stage IE and IIE, and five patients (12%) stage IIIE and IVE. According to World Health Organization (WHO) classification, 29 (87%) patients had diffuse large B-cell lymphoma (DLCBL), two had mantle cell lymphoma, and seven (18%) had marginal zone B-cell lymphoma-mucosa associated tissue (MALT). Twenty-six (66%) patients underwent surgical resection followed by chemotherapy, ten (26%) were treated with chemotherapy alone, and three (8%) were treated surgically. Complete remission was achieved in 28 (72%) and partial remission in seven (18%) patients. Four (10%) patients had progressive disease. In our patients, the major prognostic factor for outcome was the stage of disease. Patients with localized lymphoma (stage IE and IIE) had a significantly longer overall survival: 85% at five years and 65% at ten years. Patients with extended disease (stage IIIE and IVE) had overall survival less than 33%. The prognostic power of erythrocyte sedimentation rate (ESR), total protein, serum albumin, LDH concentration and activity was analyzed. Of these parameters, only LDH had a statistically significant effect on overall survival. In conclusion, our patient group was comparable to other literature reports on PGI-NHL patients according to clinicopathologic characteristics. Disease stage and LDH were the only parameters that had a statistically significant effect patient survival

SKIN SIDE - EFFECTS OF HYDROXYUREA THERAPY

Kod hematološkog bolesnika, kožne promjene mogu biti dio kliničke slike u trenutku postavljanja dijagnoze ili napredovanja bolesti koji se oćituju kožnim iniltratima, posljedica infekcije ili nuspojave terapije. hidroksiureja je peroralni citostatik uz kojeg se mogu pojavljivati dermatološke nuspojave čak i i nekoliko godina od početka liječenja. Prikazujemo bolesnicu s ulkusima potkoljenica nastalima u tijeku terapije hidroksiurejom. Važno je na vrijeme prepoznati kožne promjene vezane uz hidroksiureju jer je ukidanje navedenog citostatika u takvom slučaju kurativno.Hematology patients can have wounds as part of the initial presentation of the disease, as a result of infection, side effects of therapy, or disease progression with skin iniltration. hydroxyurea is an oral cytotoxic drug with known cutaneous side effects that can appear years after treatment initiation. here we present a case of a female patient who developed crural ulcerations during hydroxyurea treatment. It is very important to recognize the wound related to hydroxyurea treatment because drug discontinuation is usually curative

SKIN SIDE - EFFECTS OF HYDROXYUREA THERAPY

Kod hematološkog bolesnika, kožne promjene mogu biti dio kliničke slike u trenutku postavljanja dijagnoze ili napredovanja bolesti koji se oćituju kožnim iniltratima, posljedica infekcije ili nuspojave terapije. hidroksiureja je peroralni citostatik uz kojeg se mogu pojavljivati dermatološke nuspojave čak i i nekoliko godina od početka liječenja. Prikazujemo bolesnicu s ulkusima potkoljenica nastalima u tijeku terapije hidroksiurejom. Važno je na vrijeme prepoznati kožne promjene vezane uz hidroksiureju jer je ukidanje navedenog citostatika u takvom slučaju kurativno.Hematology patients can have wounds as part of the initial presentation of the disease, as a result of infection, side effects of therapy, or disease progression with skin iniltration. hydroxyurea is an oral cytotoxic drug with known cutaneous side effects that can appear years after treatment initiation. here we present a case of a female patient who developed crural ulcerations during hydroxyurea treatment. It is very important to recognize the wound related to hydroxyurea treatment because drug discontinuation is usually curative

Value of Fine-Needle Aspiration Cytology in Diagnosis of Hodgkin’s Lymphoma and Anaplastic Large Cell Lymphoma: One Centre Experience

The aim of the study was to determine the value and limitations of cytology in diagnosis of Hodgkin’s lymphoma (HL) and anaplastic large cell lymphoma (ALCL) as well as differentiation between these two entities. We analysed the FNA cytodiagnoses and histopathological reports, as well as treatment and survival in 89 newly diagnosed consecutive patients with these lymphomas treated in our clinical department. These patients (40 male, 49 female; age range 16–93 years; 44 in clinical stages I–II; 38 with B symptoms) were diagnosed and treated during a period of 64 months (1.1. 2004–1.5.2009). The FNA cytodiagnoses were available in 86 patients and the pathohistological diagnoses were available in 84 patients. Cytology revealed 65 classic HL, 18 ALCL and three patients in which diagnosis was not informative. Among 65 FNA cytodiagnoses of HL, comparison with histopathology was made in 61 cases and the histopathological diagnoses were as follows: 56 (91.8%) HL; three ALCL; one diffuse large B cell lymphoma and one marginal zone B cell lymphoma. In the group of 18 FNA cytodiagnoses of ALCL eight patients (53.3%) had definitive diagnosis of ALCL (either as T-cell or O type), five (33.3%) of HL and in three cases a histopathological diagnosis could not be made. These results confirm the value of FNA in diagnostic procedure in patients with HL and ALCL, especially in HL group of patients. Since we have an almost uniform group of patients according to therapeutic approach, we did univariate analyses and found out that patients with FNA cytodiagnoses of HL, younger than 55 years, with early stage of the disease and without B symptoms had significantly longer overall survival (OS). FNA cytodiagnosis has clinical relevance in differentiation between HL and ALCL