Cervical HPV type-specific pre-vaccination prevalence and age distribution in Croatia.

The main etiological factor of precancerous lesion and invasive cervical cancer are oncogenic human papillomaviruses types (HPVs). The objective of this study was to establish the distribution of the most common HPVs in different cervical lesions and cancer prior to the implementation of organized population-based cervical screening and HPV vaccination in Croatia. In this study, 4,432 cervical specimens, collected through a 16-year period, were tested for the presence of HPV-DNA by polymerase chain reaction (PCR) with three sets of broad-spectrum primers and type-specific primers for most common low-risk (LR) types (HPV-6, 11) and the most common high-risk (HR) types (HPV-16, 18, 31, 33, 45, 52, 58). Additional 35 archival formalin-fixed, paraffin embedded tissue of cervical cancer specimens were analyzed using LiPA25 assay. The highest age-specific HPV-prevalence was in the group 18-24 years, which decreased continuously with age (P<0.0001) regardless of the cytological diagnosis. The prevalence of HR-HPV types significantly increased (P<0.0001) with the severity of cervical lesions. HPV-16 was the most common type found with a prevalence (with or without another HPV-type) of 6.9% in normal cytology, 15.5% in atypical squamous cells of undetermined significance, 14.4% in low-grade squamous intraepithelial lesions, 33.3% in high-grade squamous intraepithelial lesions, and 60.9% in cervical cancer specimens (P<0.0001). This study provides comprehensive and extensive data on the distribution of the most common HPV types among Croatian women, which will enable to predict and to monitor the impact of HPV-vaccination and to design effective screening strategies in Croatia.

Follicular and mantle cell lymphoma characteristics present simultaneously in the same lymph node.

Follicular lymphoma is composed of clonal germinal center B cells. It shows a follicular pattern lacking mantle zones, with a network of interfollicular dendritic cells. Transformation to more aggressive lymphomas is documented, but the only connections to mantle cell lymphoma are described cases of composite lymphoma consisting of these 2 entities. We discuss here a case of a lymph node harboring CD20, CD10, BCL2, BCL6, cyclin D1, CD5, Ki67, and SOX11 with CD21, showing an almost intact network of dendritic cells in one part of a lymph node, and CD20, CD5, SOX11, BCL6, cyclin D1, CD10, Ki67, and CD21 cells restricted to the mantle area in another part of the same lymph node. Both parts of the lymph node had BCL2 rearrangement, a lack of t(11:14)(q13;q32), the presence of SOX11 expression, and the same clonal band. The described case suggests heterogenous development of small cell lymphomas and indicates the possibility of differentiation regression.

[Acute plastic bronchitis--case report]. / Akutni odljevni bronhitis--prikaz bolesnika.

Plastic bronchitis is a rare disorder characterized by formation and sometimes dramatic expectoration of bronchial casts. It may occur at any age, but most published cases refer to pediatric population. We report a case of an 81-year-old man hospitalized at intensive care unit, who presented with the appearance of plastic bronchitis type I. He had profuse expectoration of several pieces, a few cm long and up to 1 cm wide, of wormlike reddish-brownish "tissue". Histologically, it was a slimy purulent secretion with abundant fibrin and blood and with cytopathic effect of herpes virus. The pathogenesis of plastic bronchitis is not clear.

Gene expression in formalin-fixed paraffin-embedded lymph nodes.

Elucidation of molecular pathways involved in development of human lymphoma requires efficient methods for tackling gene expression in lymph nodes. Expression studies of transcription factors in these malignancies facilitate understanding the changes occurring in neoplastic transformation and lymphoma development. Excised lymph nodes are routinely fixed in formalin and embedded in paraffin for diagnosis and stored in many hospitals' pathology archives. These tissues represent a precious resource for research since they allow retrospective studies to cover a broad range of human lymphoma even the less frequent types. Reverse transcription polymerase chain reaction (RT-PCR) is a commonly used method for gene expression analysis and a reproducible protocol for RNA isolation from lymph nodes is an inevitable requirement for these studies. However, formalin fixation and paraffin-embedding interfere with the quality of RNA especially when isolated from lymph nodes being the most fragile lymphatic tissues. We present here a simple and fast method for RNA isolation from formalin-fixed paraffin-embedded lymph nodes that can be successfully applied for RT-PCR as well as for quantitative RT-PCR analysis. We tested diverse isolation reagents and combined a range of factors in order to get a high quality RNA for retrospective studies of gene expression in human lymphoma samples. Our modified method of RNA extraction from FFPE provides superior yields and purity based on qPCR data.

Lymphomatoid granulomatosis in a 23-year-old man--cytological and histological typing and rapid response to steroid and cyclophosphamide combination therapy.

Lymphomatoid granulomatosis (LG) is currently called as extranodal angiocentric and angiodestructive immunoproliferative disorder with various degrees of histological differentiation and disease severity. Histological grading and clinical manifestations are due to number of atypical large EBV + B-lymphatic cells. We report the case of a 23-year-old man clinically presented with fever, sweating, and physical intolerance, and bilateral pulmonary infiltrates of nodular type and destructive changes on the chest X-ray, previously treated with antituberculotics for 1.5 month. As the disease showed progression, diagnostic procedures extended to transbronchial lung biopsy and percutaneous fine needle aspiration with cytological and histological analysis of collected specimens, all being not conclusive enough. LG was confirmed by open lung biopsy, followed by induction of corticosteroids and cyclophosphamide therapy. Very good clinical, functional and radiomorphologic improvement was achieved in a few weeks, and remission of disease maintained in long term follow-up.

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.

Primary mediastinal large B-cell lymphoma: a single-center study of clinicopathologic characteristics.

Primary mediastinal large B-cell lymphoma (PMLBCL) is a subset of LBCL with unique clinicopathologic features. Some studies have raised the question of differences in biological features and clinical course among patients from different parts of the world. We conducted a retrospective clinicopathologic analysis of 24 patients with PMLBCL from a single center in Croatia. We also conducted the first investigation of the frequency of lymphotropic viruses human herpesvirus 6 (HHV-6) and HHV-8 in lymphoid lesions of this disease. The clinical characteristics of the patients were as expected, with high International Prognostic Index scores, elevated serum lactate dehydrogenase (LDH) levels, and bulky disease being adverse prognostic factors. Only 6 patients (25%) showed CD30 expression, and Bcl-6 protein expression was, in our series, prognostically favorable (P = .0401). One patient's tumor had detectable HHV-6 genome sequence, but no HHV-8 sequences were detected in any tumors. Two thirds of the patients received CHOP chemotherapy (cyclophosphamide, hydroxydaunomycin, vincristine, and prednisone) with a relatively low complete remission rate (43.8%; median follow-up, 33.8 months). This study confirmed the moderate preponderance among PMLBCL patients of young females with B symptoms and elevated LDH levels. The CHOP regimen proved effective as first-line therapy only in patients with limited disease. Therefore, other third-generation chemotherapy protocols may be considered for treatment, especially in patients with bulky and advanced disease.

[Lymphangioleiomyomatosis]. / Limfangiolejomiomatoza.

Lymphangioleiomyomatosis (LAM) is a progressive and usually fatal interstitial lung disease characterized by an abnormal smooth-muscle proliferation in the lung and axial lymphatics. It affects almost exclusively young women of childbearing age. The presenting features most commonly include dyspnea, symptoms of pneumothorax and cough. Less commonly patients can present with chest pain, pleural or pericardial effusion and lymphedema. Our patient, a 41-year-old woman, complained mainly of fatigue that had lasted for 2 months and finally became febrile and dispneic, especially when lying down. Pulmonary diagnostic procedures revealed several multicystic destruction of lung parenchyma. There was also respiratory insufficiency with O2 saturation of 87% and lung diffusion capacity reduced to 48%. The retroperitoneum was filled with neoplastic mass as shown on an abdominal CT scan. Pathohistologic analysis of retroperitoneal mass together with the radiologic finding of the lungs correlated with the diagnosis of LAM. The patient was prescribed corticosteroid therapy, which led to rapid clinical improvement. After making a definite diagnosis, the patient was recommended further treatment with medroxyprogesterone. This case shows that LAM, although rare, can present a diagnostic problem to clinicians and should always be considered as one of the diagnostic possibilities in young women with nonspecific pulmonary symptoms.

Diffuse large B-cell lymphoma and its variants.

According to the World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues, diffuse large B-cell lymphoma comprises about 40% of adult cases of non-Hodgkin s lymphoma. It consists of the following morphological variants: 1) centroblastic (with or without multilobulated nuclei); 2) immunoblastic (>90% of immunoblasts); 3) T cell/histiocytes rich; and 4) anaplastic. Rare morphological variants plasmablastic type, mediastinal (thymic) diffuse large B-cell lymphoma, intravascular, and primary effusion B-cell lymphoma are considered distinct variants of diffuse large B-cell lymphoma due to their unique topographic presentation and clinical behavior, as well as immunophenotypic and genetic characteristics. T-cell/histiocyte-rich B-cell lymphoma is morphologically characterized by up to 25% of large neoplastic B cells and 75-90% of reactive, non-neoplastic T cells. Mediastinal (thymic) diffuse large B-cell lymphoma is considered a subtype of diffuse large B-cell lymphoma arising in the mediastinum, with distinctive morphological, immunohistochemical, genotypic, and clinical features. Mediastinal diffuse large B-cell lymphoma is an aggressive disease with poor outcome, which probably originates from thymic B cells at the terminal stage of differentiation. During the 1997-2001 period, 720 patients were diagnosed with non-Hodgkin s lymphoma in our institution. Out of 101 (14%) patients with diffuse large B-cell lymphoma, 17 had T-cell-rich B-cell lymphoma and their median survival was less than 20 months, with no difference regarding sex, bone marrow involvement, CD30 positivity, or histiocytic component of the tumor. Twenty out of 101 patients had mediastinal B-cell lymphoma and their median survival was 21 months, with sex or degree of necrosis of the involved lymph node having no impact on survival. We studied the frequency of bcl-2 gene rearrangement in fusion with immunoglobulin receptor gene of t(14;18) and found no such event among 20 of our patients with mediastinal diffuse large B-cell lymphoma. Despite extensive efforts and constant progress in our understanding of non-Hodgkin s lymphoma pathogenesis, the diffuse large B-cell lymphoma group remains heterogeneous entity awaiting further pathological and clinical stratification.

[Morphology of gastritis and Helicobacter pylori infection]. / Morfoloska slika gastritisa i infekcije Helicobacterom pylori.

Helicobacter pylori infection almost invariably results in chronic gastritis. The Sydney System (1990) emphasised the importance of combining topographical, morphological and etiological aspects in attempt to make clinical useful diagnosis of chronic gastritis. The aims of revised Sydney System in Houston (1994), Texas, were to improve terminology of chronic gastritis emphasising distinction between nonatrophic and atrophic gastritis, and in addition to determinate special forms of gastritis. The special forms of gastritis were described and diagnostic criteria were provided. Principles and grading of histological division of Sydney System were only slightly modified, grading being improved by the provision of a visual scale. Endoscopy and histological findings of 1062 patients from University Hospital Merkur were compared to evaluate the value of endoscopic division of Sydney System, and the modified grading proposed by Houston classification. There was no correlation between endoscopic and histological findings. Localisation of inflammatory cells was either 1) superficial or 2) diffuse in the mucosa, respectively. In Helicobacter pylori positive patients the most common finding was chronic active gastritis, and in Helicobacter pylori negative superficial and inactive chronic gastritis.

[Gastric ulcer and Helicobacter pylori infection]. / Zelucani ulkus i infekcija Helicobacterom pylori.

Helicobacter pylori infection and the use of non-steroidal anti-inflammatory drugs (NSAID) are considered to be the two major risk factors implicated in the development of gastric ulcer. Helicobacter pylori infection related chronic gastritis is known to be the underlying condition which may lead to gastric ulcer. Development of gastric ulcer as the consequence of underlying chronic gastritis is caused by many factors. Treating Helicobacter pylori infection entails the healing of gastric ulcer, it concomitantly prevents recurrences and complications of gastric ulcer, primarily bleeding, and changes the natural course of gastric ulcer disease. Continuation of antisecretory maintenance treatment beyond ulcus healing and eradication of Helicobacter pylori infection is only indicated in risk groups. Patients with gastric ulcer caused by NSAID use are managed with antisecretory therapy.

[Helicobacter pylori and malignant diseases of the stomach]. / Helicobacter pylori i maligne bolesti zeluca.

The association between Helicobacter pylori infection and gastric malignancies, cancer and MALT lymphoma, has been suggested through several lines of evidence during the last decade. Although unresolved issues still cast doubts on the real weight of these association, in the sequence of events that leads to gastric cancer or lymphoma, Helicobacter pylori appears to play a prominent role in the very initial steps as causative agent of chronic gastritis. The subsequent events in the sequence--atrophy, intestinal metaplasia, dysplasia and cancer are multifactorial involving environmental agents, host response and characteristics of the bacterial strain itself. Recognition of the causal role of Helicobacter pylori infection in the cancer induction theoretically presents tools for its prevention. The ongoing studies will show in the future whether eradication or prevention of infection are followed by a reduction in risk of cancer. Lymphomas arising from gastric mucosa-associated lymphoid tissue (MALT) may be a clonal evolution starting from the infection. In low-grade gastric MALT lymphoma cure of the infection induces complete remission in the majority of patients. Longer follow-up investigations are necessary to determine if remissions indicate a cure of the disease.