Histological Characteristics of Malignant Tumours

Najveći broj zloćudnih tumora potječe od jedne jedine zloćudno promijenjene stanice - tzv. monoklonalne zloćudne stanice. Međutim, naslijeđena genska nestabilnost zloćudnih stanica, utjecaji mikrookoliša i makrookoliša vrlo brzo dovode do bioloških različitosti, tj. fenotipskih i genskih promjena zloćudnih stanica i njihovih metastaza, tj. heterogenosti zloćudnih stanica. Upravo je heterogenost zloćudnih stanica osnova teorije o nastanku metastaza prema kojoj samo najotpornije i najsposobnije stanice mogu preživjeti, pa se zato metastaziranje može shvatiti kao kompeticija između subpopulacija tumorskih stanica u kojoj su stanice primarnog tumora pobjednice i nastavljaju život u metastazi. Pojednostavnjenom definicijom morfološko se razlikovanje dobroćudnih od zloćudnih tumora osniva na određivanju stupnja sličnosti tumora “roditeljskomu” tkivu, tj. tkivu podrijetla tumora. Tako definirani dobroćudni tumori histološki, citološki i dijelom funkcionalno gotovo u cijelosti odgovaraju “roditeljskomu” tkivu. Dobroćudnost tumora potvrđuju i dodatna obilježja: neinvazivni rast, često stvaranje vezivne kapsule koja odvaja tumor od okolnoga zdravog tkiva, a najvažnije je obilježje da nema sklonosti metastaziranju.Almost all cancers originate from the malignant transformation of a single cell - clonal origin of tumours. However, the inherent genetic instability of malignant phenotype influenced also by micro- and macroenviromental factors, leads to subpopulations of malignant cells with diverse biological characteristics and variations in their metastatic potential - tumour heterogenesity. The tumour heterogenesity has led to the concept that at each point in metastatic process only the most viable cells survive. Therefore, the metastatic process can be considered as a competition in which a population of cells within the primary malignant tumor ultimately prevails as a metastasis. Simple morphological classification is based upon resemblance to parent tissue. Benign tumours in general resemble cytologically, histologically and very frequently functionally the parent tissue. Furthermore many begnin tumours are circumscribed by connective tissue capsule, however some are not (i. e. Polyps, hepatic adenoma, etc). Nevertheless, the definition of benign tumours is based in their inability to invade adjacent tissue and to metastasize

The place and role of serologic methods in detecting Helicobacter pylori infection

The aim of the study was to determine the place and role of serologic methods in detecting Helicobacter pylori (H. pylori) infection, on the basis of estimated enzyme-linked immunosorbent assay (ELISA) and complement fixation test (CFT) sensitivity and specificity. A total of 549 patients were included in the study. ELISA and CFT as serologic methods were compared with invasive methods (rapid urease test--CLO test, culture, histology). The sensitivity of serologic methods was above 90%, and their specificity was around 80%. Study results confirmed the value, reliability and usefulness of serologic methods in the detection of H. pylori infection

Histological Characteristics of Malignant Tumours

Najveći broj zloćudnih tumora potječe od jedne jedine zloćudno promijenjene stanice - tzv. monoklonalne zloćudne stanice. Međutim, naslijeđena genska nestabilnost zloćudnih stanica, utjecaji mikrookoliša i makrookoliša vrlo brzo dovode do bioloških različitosti, tj. fenotipskih i genskih promjena zloćudnih stanica i njihovih metastaza, tj. heterogenosti zloćudnih stanica. Upravo je heterogenost zloćudnih stanica osnova teorije o nastanku metastaza prema kojoj samo najotpornije i najsposobnije stanice mogu preživjeti, pa se zato metastaziranje može shvatiti kao kompeticija između subpopulacija tumorskih stanica u kojoj su stanice primarnog tumora pobjednice i nastavljaju život u metastazi. Pojednostavnjenom definicijom morfološko se razlikovanje dobroćudnih od zloćudnih tumora osniva na određivanju stupnja sličnosti tumora “roditeljskomu” tkivu, tj. tkivu podrijetla tumora. Tako definirani dobroćudni tumori histološki, citološki i dijelom funkcionalno gotovo u cijelosti odgovaraju “roditeljskomu” tkivu. Dobroćudnost tumora potvrđuju i dodatna obilježja: neinvazivni rast, često stvaranje vezivne kapsule koja odvaja tumor od okolnoga zdravog tkiva, a najvažnije je obilježje da nema sklonosti metastaziranju.Almost all cancers originate from the malignant transformation of a single cell - clonal origin of tumours. However, the inherent genetic instability of malignant phenotype influenced also by micro- and macroenviromental factors, leads to subpopulations of malignant cells with diverse biological characteristics and variations in their metastatic potential - tumour heterogenesity. The tumour heterogenesity has led to the concept that at each point in metastatic process only the most viable cells survive. Therefore, the metastatic process can be considered as a competition in which a population of cells within the primary malignant tumor ultimately prevails as a metastasis. Simple morphological classification is based upon resemblance to parent tissue. Benign tumours in general resemble cytologically, histologically and very frequently functionally the parent tissue. Furthermore many begnin tumours are circumscribed by connective tissue capsule, however some are not (i. e. Polyps, hepatic adenoma, etc). Nevertheless, the definition of benign tumours is based in their inability to invade adjacent tissue and to metastasize

Prognostic Markers and Gene Abnormalities in Subgroups of Diffuse Large B-cell Lymphoma: Single Center Experience

Aim To explore the association between FOXP1, BCL2, and BCL6 gene expression in diffuse large B-cell lymphoma tumor cells and their association with the presence of FOXP3 lymphocytes. Methods Samples of lymph nodes from 53 patients with newly diagnosed diffuse large B-cell lymphoma were taken at the time of the diagnosis and immunostained for CD10, MUM1, BCL6, BCL2, FOXP1, and FOXP3. Fluorescent in situ hybridization analysis was used for the detection of FOXP1, BCL2, and BCL6 gene abnormalities. The χ2 test was used for data analysis. Results FOXP1 protein was detected in 28 cases, genetic abnormalities involving the FOXP1 locus were found in 19 cases, and both were present in 13 cases (χ2 =7.157; P = 0.028). FOXP3 positive cells were detected in 37 cases. There was a significant relationship between BCL2 expression and FOXP1 genetic abnormalities (χ2 =5.858; P = 0.016) and between BCL2 expression and BCL2 genetic abnormalities (χ2=6.349; P = 0.012). There was also an association between BCL6 and FOXP1 genetic abnormalities (χ2 =8.497; P = 0.004). Conclusion Association was observed between additional FOXP1 gene copies and BCL2 protein expression as well as changes on both FOXP1 and BCL2 genes in samples of our DLBCL patients.. FOXP3 positive cells showed no association with presence of any of analyzed proteins considered as a prognostic markers in DLBCL neither with changes of their genes

The Place and Role of Serologic Methods in Detecting Helicobacter Pylori Infection

The aim of the study was to determine the place and role of serologic methods in detecting Helicobacter pylori (H. pylori) infection, on the basis of estimated enzyme-linked immunosorbent assay (ELISA) and complement fixation test (CFT) sensitivity and specificity. A total of 549 patients were included in the study. ELISA and CFT as serologic methods were compared with invasive methods (rapid urease test – CLO test, culture, histology). The sensitivity of serologic methods was above 90%, and their specificity was around 80%. Study results confirmed the value, reliability and usefulness of serologic methods in the detection of H. pylori infection

"Double hit" lymphoma or secondary MYC translocation lymphoma?

Chromosomal translocations that juxtapose different genes required for proliferation and differentiation are frequently associatedwith hematologic neoplasms. A term "double hit" lymphoma refers to a group of mature B-cell malignancies that harbor MYC rearrangement accompanied with another translocation commonly found in lymphomas (i.e. IGH/BCL2). A complex karyotype with multiple abnormalities and very aggressive course of disease are additional characteristics of this group. The response to currently available treatment regimens is unsatisfying, thus reported overall survival of these patients is usually very short. Today, the precise mechanisms of "double hit" lymphoma development are still unclear, although several possible pathways have been proposed in the literature. Similar oncogenic chain of events was also observed in another common hematological malignant neoplasm – multiple myeloma. MYC translocation as a secondary pathogenic phenomenon has been demonstrated in multiple myeloma, as well as complex cytogenetics and very aggressive course of the disease. Therefore, secondary translocation involving MYC gene might be a potential marker of aggressive neoplasms emerging from different cells of origin, and united under the umbrella of "MYC-plus" malignancies. That concept might, in the future, result in a novel therapy, targeting this distinct, but not unique cytogenetic aberration

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)

CLINICAL FEATURES IN DLBCL AND TRANSLOCATION BCL2/c-MYC “DOUBLE HIT” LYMPHOMA

Difuzni B velikostanični limfom (DLBCL) je klasificiran kao limfom različitog entiteta i pomoću genske ekspresije proteina klasificiran je u tri podskupine. Cilj ovog rada je da pojasni kliničke, biološke, imunofenotipske i citogenetske značajke DLBCL s translokacijom t(14;18) i 8q24/c-MYC. Jedanaest bolesnika s DLBCL s dvostrukom translokacijom praćeno je u razdoblju od 2000. do 2009. god. Obilježja tih bolesnika uključuju morfološke, imunohistokemijske i citogenetske analize. Svi bolesnici imaju agresivna obilježja, prisutnost B simptoma (64 %), opće stanje bolesnika prema ECOG ljestvici ≥2 (55 %), povišenu aktivnost serumske laktat dehidrogenaze (73 %), klinički stadij III i IV (82 %), ekstranodalnu zahvaćenost bolesti (73 %), IPI ≥2 (73 %). Parcijalna remisija je postignuta kod 73 %, svi su bolesnici (73 %) umrli u kratkom roku. Bolesnici su liječeni CHOP i sličnim protokolima (COP, CVP, CNOP) uz dodatak Mabthere. Učinjena je imunofenotipizacija te određena ekspresija biljega CD20, CD3, CD10, Bcl6 i MUM1. u svih je učinjena citogenetska analiza ⌠fluorescentna hibridizacija in situ - FISH)⌡i nađene su kompleksne kariotipske promjene. Tako smo analizirali prisutnost gena BCL2, BCL6 i c-MYC, osam bolesnika je imalo translokacije gena BCL2 i c-MYC, dok je troje imalo translokaciju gena BCL6 i c-MYC. Usprkos provedenoj adekvatnoj terapiji, prognoza bolesnika je loša. Medijan preživljenja tih bolesnika je 1,85 godina. Zaključujemo da je DLBCL s BCL2 i c-MYC preuređenjem podskupina limfoma s vrlo lošim preživljenjem. Prisutnost tih dviju translokacija ima agresivan klinički tijek.Diffuse large B-cell lymphoma (DLBCL) is classified as lymphoma and various entities using the gene expression of proteins are classified into three groups. The aim of this study was to clarify the clinical, biological, immunophenotypic and cytogenetic features of DLBCL with translocation t (14; 18) and 8q24/c-MYC. Eleven DLBCL patients with dual translation were monitored during the 2000-2009 period. The characteristics of these patients included morphological, immunohistochemical and cytogenetic analysis. Study results showed that all patients had aggressive characteristics, presence of B symptoms (64%), general patient condition according to ECOG scale ≥2 (55%), elevated serum lactate dehydrogenase activity (73%), clinical stage III and IV (82%), extranodal involvement of the disease (73%), and IPI ≥2 (73%). Partial remission was achieved in 73% of all patients and all patients (73%) died within a short time. Patients were treated with CHOP and similar protocols (COP, CVP, CNOP), with the addition of MabThera. Immunophenotyping was performed and determined expression of the CD20, CD3, CD10, BCL6 and MUM1 markers. The cytogenetic analysis/fluorescence in situ hybridization revealed complex karyotype changes. Thus, we analyzed the presence of BCL2, BCL6 and c-MYC genes and found eight patients to have BCL2 and c-MYC translocation genes, while three had translocation of the BCL6 and c-MYC genes. Despite appropriate therapy, the patient prognosis is poor. The median survival in these patients was 1.85 years. DLBCL with BCL2 and c-MYC rearrangement of the subgroups of lymphoma is associated with very poor survival. The presence of these two translocations has an aggressive clinical course

CLINICAL FEATURES IN DLBCL AND TRANSLOCATION BCL2/c-MYC “DOUBLE HIT” LYMPHOMA

Difuzni B velikostanični limfom (DLBCL) je klasificiran kao limfom različitog entiteta i pomoću genske ekspresije proteina klasificiran je u tri podskupine. Cilj ovog rada je da pojasni kliničke, biološke, imunofenotipske i citogenetske značajke DLBCL s translokacijom t(14;18) i 8q24/c-MYC. Jedanaest bolesnika s DLBCL s dvostrukom translokacijom praćeno je u razdoblju od 2000. do 2009. god. Obilježja tih bolesnika uključuju morfološke, imunohistokemijske i citogenetske analize. Svi bolesnici imaju agresivna obilježja, prisutnost B simptoma (64 %), opće stanje bolesnika prema ECOG ljestvici ≥2 (55 %), povišenu aktivnost serumske laktat dehidrogenaze (73 %), klinički stadij III i IV (82 %), ekstranodalnu zahvaćenost bolesti (73 %), IPI ≥2 (73 %). Parcijalna remisija je postignuta kod 73 %, svi su bolesnici (73 %) umrli u kratkom roku. Bolesnici su liječeni CHOP i sličnim protokolima (COP, CVP, CNOP) uz dodatak Mabthere. Učinjena je imunofenotipizacija te određena ekspresija biljega CD20, CD3, CD10, Bcl6 i MUM1. u svih je učinjena citogenetska analiza ⌠fluorescentna hibridizacija in situ - FISH)⌡i nađene su kompleksne kariotipske promjene. Tako smo analizirali prisutnost gena BCL2, BCL6 i c-MYC, osam bolesnika je imalo translokacije gena BCL2 i c-MYC, dok je troje imalo translokaciju gena BCL6 i c-MYC. Usprkos provedenoj adekvatnoj terapiji, prognoza bolesnika je loša. Medijan preživljenja tih bolesnika je 1,85 godina. Zaključujemo da je DLBCL s BCL2 i c-MYC preuređenjem podskupina limfoma s vrlo lošim preživljenjem. Prisutnost tih dviju translokacija ima agresivan klinički tijek.Diffuse large B-cell lymphoma (DLBCL) is classified as lymphoma and various entities using the gene expression of proteins are classified into three groups. The aim of this study was to clarify the clinical, biological, immunophenotypic and cytogenetic features of DLBCL with translocation t (14; 18) and 8q24/c-MYC. Eleven DLBCL patients with dual translation were monitored during the 2000-2009 period. The characteristics of these patients included morphological, immunohistochemical and cytogenetic analysis. Study results showed that all patients had aggressive characteristics, presence of B symptoms (64%), general patient condition according to ECOG scale ≥2 (55%), elevated serum lactate dehydrogenase activity (73%), clinical stage III and IV (82%), extranodal involvement of the disease (73%), and IPI ≥2 (73%). Partial remission was achieved in 73% of all patients and all patients (73%) died within a short time. Patients were treated with CHOP and similar protocols (COP, CVP, CNOP), with the addition of MabThera. Immunophenotyping was performed and determined expression of the CD20, CD3, CD10, BCL6 and MUM1 markers. The cytogenetic analysis/fluorescence in situ hybridization revealed complex karyotype changes. Thus, we analyzed the presence of BCL2, BCL6 and c-MYC genes and found eight patients to have BCL2 and c-MYC translocation genes, while three had translocation of the BCL6 and c-MYC genes. Despite appropriate therapy, the patient prognosis is poor. The median survival in these patients was 1.85 years. DLBCL with BCL2 and c-MYC rearrangement of the subgroups of lymphoma is associated with very poor survival. The presence of these two translocations has an aggressive clinical course

ORBITAL AMYLOIDOSIS

Background. Authors want to present echographic characteristics of two stages of development of bilateral orbital involvement in primary systemic amyloidosis in 10-year follow-up of a case.Methods. A 65-year old white female with 10-year-long history of orbital involvement in primary systemic amyloidosis presented to us with large nasal left upper palpebro-bulbar mass that produced lateral displacement of the globe, marked reduction of ocular motility in all directions and ptosis covering the pupil. Direct and transbulbar echography, pathohistological analysis, and immunohistochemistry were used to confirm the diagnosis of amyloid. The mass was partially removed and the lid reconstructed.Results. The echographic examination of the orbits performed in 1990 showed an epibulbar and parabulbar low-reflectivity orbital mass in the upper temporal part of the right orbit. A widened right lateral rectus muscle of low reflectivity was also documented. Ten years later direct echography of the medial part of the left upper lid discloses palpebral extension of the orbital mass. It has irregular, inhomogeneous, medium to high reflectivity with rough granular structure and calcifications. Transbulbar echography revealed changes in both orbits. There is widening of the orbital fat echo with the higher reflectivity. All extraocular muscles are enlarged, including insertions. The widest is the right lateral rectus muscle. The muscle sheaths are thickened, widened with easily detected higher inner reflectivity than in the muscle itself. There is irregular, inhomogeneous, medium to high reflectivity of the muscles with scarce calcification.Conclusions. The initial stage of orbital amyloidosis is characterized with low reflectivity. Ten years later, the mass reflectivity inhomogeneously increased and calcifications developed.</p