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There have been some relevant changes in the diagnosis and treatment of breast cancer to implement the updating of the 2016 recommendations made during the 3rd national consensus conference on the disease. Following a wide interdisciplinary consultation, the present recommendations have been finalized after their public discussion at the 4th Hungarian Breast Cancer Consensus Conference. The recommendations cover non-operative, intraoperative and postoperative diagnostics, the determination of prognostic and predictive markers and the content of the cytology and histology reports. Furthermore, it touches some special issues such as the current status of multigene molecular markers, the role of pathologists in clinical trials and prerequisites for their involvement, some relevant points about the future. The most important changes include the integration of the TNM 8th edition, the WHO classification of breast tumors 5th edition, the ASCO/CAP HER2 assessment guidelines from 2018, and the Yokohama terminology for cytology reporting; a more detailed text on tumor-infiltrating lymphocytes and size determination after neoadjuvant therapy and a broader discussion of molecular tests.

Our objective was to develop an electromagnetic tumor therapy device in a consortial cooperation between Semmelweis University and Oncotherm Ltd., to provide data and contribute to the development of the next generation of devices through preclinical, clinical and developmental modules via in vivo, in vitro studies, and patient treatments. Our numerous preclinical studies support the efficacy of mEHT. Clinical treatments were performed in 181 patients with inoperable and/or oligometastatic solid tumors. The protocols were developed, an international guideline was completed, and the planned steps of device development were realized. By optimizing previous selective RF techniques based on recent research findings, we can provide the most modern evidence-based treatment in the future.

Modulated electro-hyperthermia (mEHT) is a non-invasive treatment modality of cancer where electric field generated by 13.56 MHz radiofrequency can selectively accumulate in malignant tumors compared to adjacent normal tissues. This effect is based on the metabolic shift in cancer cells which upregulates glycolysis even under oxygenated conditions (Warburg effect), resulting in elevated lactate and ion concentration. The concomitant increased permittivity can induce dielectric polarization and rotational friction of dipole molecules resulting in elevated core temperature, which can be controlled at 42 °C with the treating instrument. Complementary application of loco-regional mEHT can improve the efficiency of chemo-, radio- and recently molecular targeted therapies based on increasing local perfusion and xenobiotic concentration, resolving tumor hypoxia and improved immune surveillance supported by high-fever range hyperthermia. We earlier showed that mEHT has its own tumor inhibiting/destructing effect, however, its mechanism had not been clarified. In this project we have investigated the molecular mechanism of action of mEHT treatment using in vitro and in vivo models of colorectal adenocarcinoma.

There have been relevant changes in the diagnosis and treatment of breast cancer to implement the updating of the 2010 recommendations made during the 2nd national consensus conference on the disease. Following a wide interdisciplinary consultation, the present recommendations have been finalized after their public discussion at the 3rd Hungarian Consensus Conference on Breast Cancer. The recommendations cover non-operative and intraoperative diagnostics, the work-up of operative specimens, the determination of prognostic and predictive markers and the content of the cytology and histology reports. Furthermore, it touches some special issues such as the current status of multigene molecular markers, the role of pathologists in clinical trials and prerequisites for their involvement, some relevant points about the future.

Unlabelled: In the process of regeneration following colon inflammation mesenchymal stem cells (MSC) of bone marrow origin may also take part besides their local counterparts. These cells migrate in the colon epithelium where they may contribute to epithelial regeneration or form progeny for keeping up local stem cell pool. MSC cells probably leave circulation around lymphoid aggregates to then migrate into nearby crypts. During migration they change their phenotype upon the influence of local microenvironment., Aims: In this study epithelial migration and transition of bone marrow stem cells were examined. Samples from normal healthy individuals and from aspecific inflammation were used. The possible role of lymphoid aggregates in the epithelial regeneration was also studied., Materials and Methods: Samples of normal colon (2) and those showing mild aspecific colitis (3) from female patients who were initially transplanted with male bone marrow were studied. First we detected gender chromosomes with fluorescent in situ hybridization (FISH) and the samples were archived with digital scanning. Then CD45 and cytokeratin (CK) double immunofluorescent reactions (IF) were made followed by digitalization again. Digitalized samples were estimated simultaneously with virtual microscopy (Mirax Viewer)., Results: Significant elevation of CD45 negative/Y-FISH positive potential MSCs were found in crypts locating to the neighborhood of lymphoid aggregates (1,075%) compared with both normal (0,027%, p = 0,002) and mild colitis (0,045%, p = 0,004) samples., Conclusion: Local stem cells probably have enough regeneration capacity in case of minor inflammation. However, in aspecific inflammation the number of MSCs contributing to epithelial regeneration was elevated, suggesting their facilitated contribution to the repair process with less probable forming of local stem cell progeny.

Stroma cells with the microenvironment around them have primary role in the regulation of inflammation processes, conformation of tumors and development of metastasis. Myofibroblasts have essential role in inflammation processes and in the regeneration of encompassed tissue. Molecules produced by them operate the cells of the immune system and effect the proliferation of epithelium. Tumors can activate myofibroblasts which can lead to uncontrolled epithelium proliferation across production of changed and increased regulation ligands (such as cytokines, chemokines, chemotactic and other growth factors) and activation of stem cell. This process could lead piling of uncontrolled epithelial cells and can impact later on conformation of tumors. In this study we present an overview about of myofibroblasts and their roles in inflammation and neoplastic processes.

Whether a breast carcinoma is HER2-positive or -negative has a significant impact on its treatment. The most common method of evaluating the HER2 status of breast tumors is immunohistochemistry. Preliminary data suggest that the proportion of HER2-positive tumors in Hungary shows a wide range from laboratory to laboratory, and overall it just reaches the bottom levels of the incidence reported in the literature (12% 3+ and 11% 2+ cases). A 3-round quality-control test was implemented on a voluntary and anonymous basis. Participating laboratories had to immunostain and evaluate 4 tumor samples per circulation, according to their daily routine. The authors of the present article gave an expert opinion in all cases, and this was compared with the individual laboratories' evaluation and the real FISH-controlled HER2 status of the samples. On the basis of the participants' and experts' evaluation 22/218 and 21/218 HER2 3+ cases were underscored, corresponding to an underevaluation rate of 10%. As most samples were from HER2-positive tumors, overscoring was less common (1%), but reached 5% (individual laboratories' evaluation) or 7% (expert evaluation) when the 2+ scoring of negative cases was also considered. Each case was discussed interactively with the participants and technical advise was also given when deemed necessary. The evaluation of the HER2 status of breast cancers gives reliable results only if adequate quality control measures are implemented, and this study was an important step in this respect.

The four main aspects of applied medical information technology, which change the traditional systems of the entire health service are signal and data processing, digital modelling and interface optimisation. The information technology serving individual clinical specialties including clinical histopathology is changing at each of the four levels resulting in transformation of the communication paradigms. The object of investigation in histopathology is the digital slide, which is accessible throughout the world with no time or geographical limits. It permits the digital modelling of routine histological and/or cytological slide and it also allows measurements by using image analysis or stereology software packages. The electronic slide can be viewed, examined and diagnosed on a computer connected to a microscope, a new interface in diagnostic histopathology. This study describes the main theoretical and practical aspects, including challenges, of digital pathology and it also discusses the conditions required for successful information management. It reviews the experiences of the last one and half decades gained in the field of pathological information technology in Hungary including its main episodes and milestones of development. Introducing its present state, this paper describes the concept and the mode of investigation of the digital slide. It shows the development and use of a virtual microscope in Hungary. Based on know-how including the British experience this review describes the possible uses of digital slides, which by improving communication could have a positive effect on the entire health care system. It summarises the possible and necessary components of a digital pathology laboratory, which may include the new Slide Archive and Communication System (SACS). Using experimental data it mentions the possibility of generating primary digital pathological sample and producing the so called optical biopsy with no need for removing tissue from the patient.

Deletion analysis of the dystrophin gene (Xp21) was carried out by examinations of the most frequently deleted 18 exons (3., 4., 6., 8., 12., 13., 17., 19., 43., 44., 45., 47., 48., 49., 50., 51., 52. and 60. exon) and the muscle specific promoter in 42 Duchenne and Becker muscular dystrophy (DMD/BMD) affected patients with multiple polymerase chain reaction (PCR). 22 (52%) of 42 patients were found to have one or more exon deletions. 9% BMD patients (milder allelic form) were found in the deletion group versus 35% in the non deletion group. This method seems to be useful for prenatal genetic diagnosis in the family of deletion patients.

In a 81-years old man synchronous triple cancers (prostate, kidney and lung) were found at autopsy. The poorly differentiated prostatic adenocarcinoma metastasized to the clear cell carcinoma of the right kidney and to its solitary lung metastasis. The "neoplasm to neoplasm" metastasis and the "metastasis in metastasis" was confirmed by immunohistochemistry.

Authors examined cells participating in intimaproliferation in transplantation arteriopathy ultrastructurally in needle and wedge biopsy material from 40 transplanted kidneys, and immunohistochemically in 10 cases. In early biopsies--even in two control kidneys--it could be observed that the smooth muscle cells of media are in direct contact with endothel cells by their small processes. Processes can fulfil a receptor function and can transmit endothel noxa to smooth muscle cells. Smooth muscle cells of media react to endothel damage caused by rejection with migration to intima and during this period they are transformed to myofibroblasts (myointimal cells). In the mean time inflammatory cells (mainly macrophages, helper and cytotoxic cells in lower number) from the lumen infiltrate the intima, and mediators, enzymes released from them can inspire smooth muscle cells to further proliferation, migration to intima and transformation to myofibroblast. To effect of mediators (gamma interferon) released from inflammatory cells, the myointimal cells during rejection will press out 2nd class transplantation antigens (HLA-DR), and as vicious circle it further aggravates immune reply to graft, causing vascular damage, intimaproliferation.

This study was undertaken to evaluate the number of the immunoglobulin producing cells in the lamina propria of the small intestine by immunocytochemical techniques, using peroxidase-antiperoxidase (PAP) complex in normacid patients with CSBS. 25 patients were studied including 13 patients with bacterial overgrowth, where the bacterial concentration was higher than 10(4) colony forming units/ml, and 12 subjects with normal bacterial concentration, served as control. The patients with CSBS were treated with antibiotics according to the antibiotic resistance. After treatment the luminal bacterial concentrations was lower than 10(4) cfu/ml in 7 of 13 patients (CSBS I. group). In 6 patients the bacterial concentration remained high (CSBS II. group). The immunoglobulin producing cells were determined in biopsy specimens taken from the lower part of duodenum. The number of the IgA and IgM producing immunocytes was significantly decreased only in the CSBS II. group. Our results show that temporary immunological alterations may play an important role in the mechanism of the recurrent CSBS.

Case of ceruminal adenocarcinoma is reported. Tumor was diagnosed in advance stage, and within a month following diagnosis it caused death. Tumor started from right auditory canal, undermined the pyramidal bone and infiltrated great part of right side of base of skull, narrowing great foramen to a certain extent. Metastasizes were only the right of dura. Besides electron microscopic studies, authors performed the immune-histochemical and lectin-histochemical examination of tumor the first time.

7 gastrinomes and 1 gastrin-producer complex carcinoma-carcinoid tumor were examined by light and electron microscopical-method and by immunohistochemical method. In six cases, the tumor was in the pancreas or in the wall of duodenum; in two cases its localisation was of extra-gastroenteropancreatic (liver, lymph node). All patients developed Zollinger-Ellison syndrome, three patients bled and one had diarrhea. One patient had other tumors, besides gastrinome, which were characteristic of MEN-I syndrome. By immunohistochemical methods all tumors proved to be gastrin and neuron-specific-enolase positive. In four cases somatostatin positivity, in some cases glucagon, pancreatic polypeptide, S-100 protein, keratin and carcinoembryonal antigen positivity were detected. Relation could not be detected between other polypeptide hormones, produced besides gastrin, and biological behaviour of tumor and clinical symptoms.

The composition of the cellular infiltrate in 42 needle and wedge biopsies of transplanted kidneys was investigated immunohistochemically. The various inflammatory cell populations were examined in different rejection types and cyclosporin-A nephrotoxicity (CsAN) as well as in different locations in the graft (perivascular and intertubular area, tubular epithelium, glomeruli) separately. There was generally a Th cell predominance except the most unfavorable rejection type, the acute vascular rejection (AVR), where the Tc cells outnumbered all other infiltrating cell populations. The most macrophages too were detected in AVR. The high proportion of plasma cells in chronic rejection indicate an important role of the humoral immune response in this type of rejection, and could also be used as a differential diagnostic sign versus CsAN.

By the immunohistochemical demonstration of SR calcium ATPase and myoglobin a fibre classification method was developed. Fast fibres showed intense, while slow fibres weak SR calcium ATPase reactivity. Immunohistochemical reaction of myoglobin characterized the oxidative metabolic state of fibres similar to the succinate dehydrogenase (SDH) reaction. By means of SR calcium ATPase and myoglobin immunohistochemistry fibres were classified as slow oxidative (SO), fast oxidative glycolytic (FOG) and fast glycolytic (Fg) groups. The SR calcium ATPase activity of the different fibres varied in the FG greater than FOG greater than SO order, while myoglobin immunoreactivity in the FOG greater than SO greater than FG order. Both proteins studied preserved their antigenicities in Bouin's fixative or in formol-acetate and paraffin embedding. The light microscopic immunogold-silver method was found suitable also for electron microscopy. The silver intensification of small particle-size (5 nm) gold conjugate results in a reaction with the joint advantages of high sensitivity and optimal visibility. The described immunohistochemical method proved to be suitable for the retrospective differentiation of human biopsy materials.

Authors have studied in apostematous pyelonephritis induced by the ligation of the ureter and the intravenous injection of E coli bacteria the localization and elimination with time of the pathogen. The pathogen was demonstrated by light and electron microscopy, its parietel antigen was localized with the light microscopic peroxidase antiperoxidase and post-embedding electron microscopic immunogold techniques. Two days after inoculation the suppurative inflammation of tubulo-interstitial foci was observed; in the capillaries, interstitium, and tubuli, free and phagocyted bacteria were encountered. In the interstitium, in the proximal tubuli and in the capillary space of some glomeruli bacterial groups were observed. Intracapillary bacteria were attached by their outer wall to the surface of endothelial cells. In the tubuli this adherence occurred with pili or with the outer layer of bacterial wall. From the seventh day after inoculation macrophages containing PAS-positive globuli appeared in the interstitium. Under the electron microscope these globuli proved to be features composed of myelin figures of phagolysosomal origin. Globuli and the myelin figures possessed an E. coli antigenicity. Thirteen weeks after inoculation E. coli antigen positivity was found in the cytoplasm of inflammatory cells in the tubular walls and in the suppurative cylinders, The organism was apparently unable to eliminate the materials derived from the pathogenic microorganisms.

Authors studied with immunohistochemical methods the immunoglobulin content of plasma cells during the rejection of renal grafts, in different rejections, in Cyclosporin-A nephro-toxicity and in chronic interstitial nephritis, as a comparison. By far the most plasma cells occurred in chronic rejection, containing more than 80% IgG. Whereas great majority of plasma cells were IgG positive in chronic interstitial nephritis. Probably, in chronic rejection a special, secondary type humoral immune reaction has a significant role in addition to cellular immune mechanisms.