Malignus emlotumor? Gyulladásos emloelváltozás? Ritka benignus kórkép?

Case-report: Rosai-Dorfman disease, also known as sinus histiocytosis with massive lymphadenopathy is a rare, benign non-Langerhans cell histiocytosis, that typically involves the lymph nodes, but may also involve extranodal sites. We present a 58- years- old female patient who complained of a palpable mass in her left breast surrounded by 15-20 livid cutaneous lesions, resembling malignant breast cancer with cutaneous metastasis. Despite of core biopsy of the tumor and excisional biopsy one of the lesions, correct diagnosis of RDD was achieved only by complete pathological examination of the whole lesion after surgical excision. Conclusion: Rosai-Dorfman disease confined to the breast is extremely rare, that clinically may mimic breast cancer.

[Pulmonary histiocytic sarcoma]. / A tüdo histiocytás sarcomája.

Histiocytic sarcoma is an uncommon hematological malignancy. Its occurrence in the lung is very rare. Due to the small number of cases and the clinical and pathological features of the disease, the diagnosis can be challenging. Its optimal treatment is not yet known, in locally confined cases - depending on the location and size - surgical removal is part of complex oncotherapy. We report the case of a 52-year-old man with a tumor of central localization in the left lung. Pulmonectomy was performed. Histology verified histiocytic sarcoma of the lung. An overview of clinical features of the entity is presented in connection with our case report. Orv Heti. 2023; 164(34): 1350-1357.

[Rare case of primary pulmonary myxoid sarcoma]. / Primer myxoid tüdosarcoma ritka esete.

Mesenchymal tumors of the lungs are rare, mostly aggressive, with a high metastatic rate, representing only 0.013-1.1% of all pulmonary malignancies. Primary pulmonary myxoid sarcoma is an extremely rare type of lung sarcoma and stands as a separate entity in the 2015 WHO classification, characterized by EWSR1-CREB fusion gene. So far, 37 myxoid sarcoma cases have been reported. We offer an overview of the most important characteristics of pulmonary myxoid sarcoma and differential diagnosis, while reviewing the reported cases. We present the case of a 47-year-old patient with pulmonary myxoid sarcoma, who was diagnosed with a right central pulmonary mass, showing rapid endobronchial progression, complicated by empyema. EWSR1 gene translocation could not be detected. During chemotherapy, tumor progression occurred. Molecular genetic examinations revealed MET gene exon 14 skipping mutation, based on which tyrosine-kinase inhibitor treatment was administered. Pulmonary myxoid sarcoma can be classified as a nonvascular, spindle cell entity of mesenchymal tumors, with the characteristic EWSR1-CREB1 gene translocation. The male-female ratio is similar, with a slightly higher incidence in middle-aged women (1.5 : 1). Patients' average age is 44 years; with predilection in the right upper lobe (62%), or endobronchially (85%). Without specific symptoms, diagnosis is often cumbersome. Immunohistochemical methods, typical hystological image and molecular genetic tests confirm the diagnosis. Pulmonary myxoid sarcoma is a rare entity, without specific symptoms. In our case, myxoid sarcoma was complicated by empyema, which was drained. Because of advanced stage, surgical resection was not an option. Radical surgery offers the best results, in inoperable cases therapeutic recommendations for sarcomas are the guiding principles. Our case belongs to the rare group of myxoid sarcomas, where MET activating mutation was detected, making it eligible for targeted treatment. Orv Hetil. 2023; 164(27): 1077-1083.

Mucocele-like lesions of the breast - A radiological and clinicopathological analysis.

INTRODUCTION: Mucocele-like lesions (MLL) of the breast are rare entities which are considered to harbor uncertain malignant potential. Current UK guidelines recommend vacuum assisted excision (VAE) of all such lesions regardless of whether they display epithelial atypia. This study sought to review the key histological and radiological features of MLLs and compare their differing outcomes based on the presence of epithelial atypia. METHODS: Pathology records of a single breast cancer screening center were retrospectively searched for all biopsy diagnosed MLLs over an 11-year period. Upgrade rates to malignancy (positive predictive values) were calculated by reviewing histology from the initial core biopsy and comparing with the corresponding excision specimen. Radiological images were simultaneously reviewed to provide radiological-pathological correlation. RESULTS: Three of 11 patients (27.3%) with atypical MLLs on biopsy had malignant outcomes at excision, compared with only 1 of 36 patients (2.8%) with non-atypical MLLs. The majority of MLLs (93%) were identified as microcalcifications on mammographic imaging. No specific radiological features were predictive of malignancy. CONCLUSIONS: Our data suggest that MLLs without atypia are potentially overtreated with current protocols and could be managed conservatively with radiological follow up. Radiological-pathological correlation is essential.

Hip-flask defense: An experimental study in the Hungarian population.

Toxicology tests and medical expert opinions are part of routine work in drunk driving cases in both domestic and international practice. The greatest challenge to forming an opinion is that the perpetrator claims to have consumed alcohol after the act of driving. To determine the time of consumption, it is essential to establish whether the alcohol in the body was in the absorption phase or in the elimination phase when the sample was collected. In domestic practice, breath alcohol content can be measured several times, two blood samples can be collected, and both blood and urine samples can be taken almost simultaneously. A recent Swedish study showed that taking a single blood sample and two urine samples allows for a more accurate examination of consumption after the fact. This study aimed to examine the applicability of such model to the domestic environment. We conducted a controlled drinking experiment involving 15 Hungarian casual drinker volunteers aged 18-25 years who consumed different amounts of alcohol at specified times while providing regular breath alcohol measurements as well as blood and urine samples. These measurement results provided accurate information about the changes in alcohol metabolism compared to the time of drinking and allowed us to draw the necessary conclusions, offering further evidence that alcohol metabolism can vary significantly between different ethnic groups. The results showed that the absorption and excretion of ethyl alcohol in the volunteers were much faster than those in the current Hungarian standards used in practice. In conclusion, the comparison of blood and urine samples collected between 60 min and 120 min cannot be considered suitable for establishing the fact of drinking after driving in Hungarian practice, and a local model is needed.

Traumatic Axonal Injury: A Case Report.

A 17-year-old prisoner was found unconscious during a morning check. The previous night, he had been struck on the chin multiple times by one of the other inmates. The patient remained unconscious and eventually died after nearly 1.5 months of care. The primary task of the forensic pathological examination was to investigate the events leading to his death; therefore, it was necessary to examine whether there was a connection between the abuse and eventual death. In our case, the key element was the repetitive, mild-to-moderate force in abuse, resulting in grade I traumatic diffuse axonal damage. Due to progressive brain edema, aspiration subsequently developed, which eventually resulted in irreversible hypoxic damage of the brain.

Three-year Trends in Diagnosis of B3 Breast Lesions and Their Upgrade Rates to Malignant Lesions.

BACKGROUND: B3 breast lesions are a heterogeneous group with uncertain malignant potential and, as such, provide a source of diagnostic difficulty. We calculated the prevalence of B3 lesions at our center along with the upgrade rates (positive predictive value) to in situ or invasive malignancy. MATERIALS AND METHODS: We searched our pathology database over a 3-year period to include all B3 biopsies. The subsequent excision for each biopsy was reviewed, and the rate of upgrade was calculated by subtype. These results were compared against data published in large United Kingdom studies. RESULTS: A total of 9206 breast biopsies were identified, of which 614 (6.7%) were classified as B3. Lesions displaying epithelial atypia were the most common subtype of lesion, with a prevalence of 39.6%. Lesions displaying epithelial atypia were upgraded to malignancy in 35.7% of cases. Among non-atypical cases, papillary lesions were the most common diagnosis (32.1%) with an upgrade rate of 2%. In situ lobular neoplasia (10.4%) was the third most frequently encountered diagnosis, and was upgraded to malignancy in 10.9% of cases. The upgrade rate in the remaining non-atypical lesions was invariably low (0%-2.6%). CONCLUSIONS: Herein, we have shown an overall B3 rate in keeping with published data, whereas lesions displaying epithelial atypia showed upgrade rates to malignancy comparable with that of large United Kingdom studies. In our study, lesions without epithelial atypia showed very low rates of upgrade. A wide range of upgrade rates is seen in cases of lobular neoplasia, which highlights the need for uniformity of nomenclature and reporting within this subtype to accurately ascertain the true risk of upgrade associated with these lesions.

Time-dependent changes in kidney histopathology in ethylene glycol poisoning.

Ethylene glycol (EG) may be acutely toxic following ingestion. In fatal cases, microscopic examination of urine and kidney specimens can establish a post-mortem diagnosis of EG poisoning. We describe the main renal histopathologic changes during different stages of EG poisoning, which might be helpful when dating the EG poisoning itself. A single-centre retrospective study conducted on all EG poisoning cases demonstrated that in an early stage of EG poisoning, fine dust-like crystals were deposited to the tubular cell basement membrane, followed by internalisation of calcium oxalate crystals into the epithelial cells. Later, the crystals formed larger aggregates within the epithelial cells. As the changes became advanced, pronounced tubular epithelial damage occurred, with detachment of epithelial cells from the basement membrane. In the final stage, coarse calcium oxalate crystals were recognised in the tubular lumen, with cellular debris from damaged epithelial cells. Our study shows that the time-dependent histological changes described follow the clinical stages of EG poisoning and may therefore provide a rough estimate of the time of EG ingestion before death.

A single-centre review of suspected sudden infant death cases.

This study aimed to establish the number of deaths in infants under 1 year of age that were being reported for medico-legal examination at a single large academic centre in Hungary, as well as the method of these investigations with special emphasis on histopathology, ancillary techniques and the adherence of our current practice to international recommendations. A single-centre, retrospective audit was conducted on all suspected sudden infant death cases. After the review there were eight infectious background sudden infant death syndrome (SIDS) cases, infectious respiratory tract disease in 14 cases, cardiac septal tumour in one case, and hepatic, possibly metabolic, disorder in one case. Our study has highlighted that even in a single institution there is a huge heterogeneity of approaches which needs standardisation. A reclassification of infant cases according to the San Diego definition resulted in a decreased number of SIDS cases in our material. The San Diego definition and related international recommendations were found to be practical and the classification provides a guide to the standardisation of current practice.

[Analysis of death certificates in postmortem examination waivers]. / Halottvizsgálati bizonyítványok adatainak elemzése nem boncolt elhunytak esetén.

INTRODUCTION AND AIM: The practices of autopsies and waivers in three Hungarian counties subject to the same statutory framework in a 5-year interval have been examined, with special attention to cases of non-natural death. METHOD: The summary data included in the post mortem examination certificates, for the years between 2006 and 2010, in a breakdown according to counties, covering all cases of death were analysed. The work was assisted by a Java-based software programme. RESULTS: In terms of the waiving of autopsies, a comparison of the three counties revealed significant differences. The persons who issue waivers from the performance of autopsies also vary across the counties. In case of deaths caused by accidents, no autopsy was performed in 844 cases. Similar situation was found in case of various identified and non-identified injuries, which were entered as the direct cause of death in 28 cases, as well as road traffic accidents entered in 32 cases and the unidentified consequences of road traffic accidents, which we found in 26 cases. No autopsy was performed in 25 cases of deaths assumed to be suicides and in one homicide. CONCLUSIONS: The Hungarian laws follow the recommendation of the Committee of Ministers to Member States of the Council of Europe, and provide that in all cases where the death is due to non-natural causes or the possibility of non-natural causes is raised, an autopsy should be performed. In this given legal context it is unclear how autopsies in the cases of death due to homicides, suicides and accidents as detailed above could possibly be dispensed with. The purpose of this paper was to provide a baseline study on the current practice of certification. The findings could be used in the course of governmental reviews for the purpose of drawing up recommendations. Orv. Hetil., 2016, 157(52), 2082-2087.

Comparison of dual-color dual-hapten brightfield in situ hybridization (DDISH) and fluorescence in situ hybridization in breast cancer HER2 assessment.

The most optimal method for assessing HER2 status is still subject to controversy as far as the type of assay used, the optimal method to perform, and the costs of each assay are concerned. The current study was done as a validation study prior to setting up a clinical HER2 testing service using the new commercial dual-color dual-hapten brightfield in situ hybridization (DDISH), but it was felt that our experience may be of interest to other laboratories considering setting up HER2 diagnostic facilities. One hundred and five patients diagnosed with invasive breast cancer were selected. PathVysion FISH and DDISH assays were carried out. Concordance correlation coefficients showed near perfect agreement in average HER2 and centromere-specific signal counts per cell and in HER2/CEN17 ratios between the PathVysion and the DDISH assays, and also the Kappa measure showed near perfect agreement between the two assays (Kappa=0.8712, P<0.0001). Statistical analysis confirmed that the two assays are comparable in terms of detection of HER2 gene amplification and suggests its utilization in routine HER2 diagnostics.

Impact of chromosome 17 centromere region assessment on HER2 status reported in breast cancer.

Recent studies have indicated that polysomy 17 is a rare event in breast cancer, and polysomy is usually mimicked in FISH analysis by gain or amplification of the centromere covered by the chromosome 17 centromere probe. To estimate the impact of chromosome 17 centromere assessment on routine practice, we conducted a retrospective re-classification study. Four hundred and five consecutive cases were selected. The original molecular pathology reports were available. Centromere 17 copy counts were ignored in the reassessment. Altogether, nineteen (4.69%) discrepant cases were found, from which five (1.23%) were considered originally non-amplified but had an HER2 copy number >6. Therefore, we reclassified them as HER2-amplified, while fourteen (3.46%) cases were originally considered amplified with 6 or fewer HER2 signals/cell. The discrepant cases found in our reassessment study would require further high-resolution genetic analysis to resolve the disagreement. On the other hand, our result also highlights that for the vast majority of breast cancer cases traditional FISH examination is still adequate to reach the correct diagnosis. This diagnostic gap must be filled by more sophisticated genetic examinations. Moreover, upcoming HER2 guidelines should consider the aid that high-resolution karyotyping can give to the diagnostic algorithm.

Comparison of Pathvysion and Poseidon HER2 FISH assays in measuring HER2 amplification in breast cancer: a validation study.

AIMS: The current study was done as a validation study prior to setting up a clinical HER2 testing service using the new commercial Poseidon HER2 fluorescence in situ hybridisation (FISH) assay. However, it was felt that the experience of the authors of this study may be of interest to other laboratories when considering setting up a HER2 diagnostic facility. METHODS: 122 patients who had been diagnosed with invasive breast cancer were selected. Immunolabelling with HercepTest, PathVysion and Poseidon FISH assays were carried out using tissue microarray blocks. RESULTS: Concordance correlation coefficients showed near perfect agreement in average HER2 and centromere specific signal counts per cell and in the HER2/CEP17 ratios between the PathVysion and the Poseidon FISH assays. In addition, the kappa measure showed perfect agreement (kappa 0.9441, p<0.0001), and if only 2+ cases were considered there was substantial agreement (kappa 0.7671, p=0.0006), between the two assays. The sensitivity and the specificity of the Poseidon FISH kit were calculated to be 95.2% and 100%, respectively, whereas the positive predictive value (PPV) and negative predictive value (NPV) were 100% and 99%, respectively. With regard to the ability to presume HER2 polysomy, the Poseidon FISH kit had a sensitivity of 93.3% and a specificity of 99.1%, with PPV and NPV of 93.3% and 99.1%, respectively, as assessed with PathVysion classification as the reference. CONCLUSIONS: Statistical analysis confirmed that the two FISH assays are comparable in terms of detection of HER2 gene amplification. Proceeding from these findings, the genetic diagnoses obtained with the Poseidon kit can be considered to be as valuable as the results from the Food and Drug Administration approved PathVysion assay, and its utilisation in routine HER2 diagnostics is proposed.

Correlations between the atherosclerotic changes of femoral, carotid and coronary arteries: a post mortem study.

OBJECTIVE: To compare the severity of atherosclerosis in the carotid, coronary and femoral arteries in autopsy findings of stroke patients. METHODS AND RESULTS: 40 patients (age: 75.2 (12.3) years, 21 men, 19 women) were investigated, who died of ischemic stroke. Carotid, femoral and coronary arteries were removed and cut into slices. Atherosclerotic changes were scored and compared. The severity of atherosclerotic changes of the common carotid artery did not correlate with any other arteries. Atherosclerotic parameters of the internal carotid artery correlated with those of the deep femoral and common femoral arteries (r=0.457-0.459; P=0.022-0.028 respectively). We found significant correlations between the deep femoral artery and left anterior descendent coronary arteries (r=0.513; P=0.012). External carotid artery correlated with both the left anterior descendent coronary and deep femoral arteries (r=0.458-0.473 and P=0.028-0.017 respectively). CONCLUSIONS: The severity of atherosclerosis in the external carotid arteries and/or the femoral arteries showed a stronger correlation with the atherosclerosis in the coronaries than that of the common carotid arteries.

Analysis of EGFR gene amplification, protein over-expression and tyrosine kinase domain mutation in recurrent glioblastoma.

Gefitinib and erlotinib are both selective EGFR tyrosine kinase inhibitors (EGFR-TKIs) that have produced responses in a small subgroup of lung cancer patients. The strongest evidence for a role of EGFR in the biology of glioblastoma stems from clinical trials in which 15-20% of recurrent glioblastoma patients experienced significant tumour regression in response to these small-molecule EGFR kinase inhibitors. We examined the protein-kinase domain of the EGFR gene, EGFR protein expression and EGFR gene amplification in 20 cases of recurrent GBMs. EGFR protein over-expression was found in 65% of cases. EGFR protein over-expression was associated with EGFR gene amplification in 35% of cases, and with high polysomy in 15% of cases. No mutations were found in the TK domain of the EGFR gene. Our results confirm that mutations in the kinase domain are absent in recurrent GBM, and this might be a preponderant factor in the lack of major clinical responses of TKIs in GBM, recent studies have suggested that responsiveness to EGFR kinase inhibitors was strongly associated with coexpression of EGFRvIII and PTEN. Further prospective validation of EGFRvIII and PTEN as predictors of the clinical response to EGFR kinase inhibitors in recurrent GBM is strongly anticipated.

An alternative and reliable real-time quantitative PCR method to determine HER2/neu amplification in breast cancer.

The overexpression of HER-2/neu is an independent prognostic factor of clinical outcome of breast cancer, therefore determination of HER-2/neu status is now an integral part of the clinicopathologic workup. The ways of measuring the copy number of the HER-2/neu gene in tumor cells comprise in situ hybridization techniques and real-time polymerase chain reaction (PCR). Quantitative real-time PCR is a relatively new technique for assessing HER-2/neu gene amplification with high sensitivity. However, the HER-2/neu Quantification Kit developed by Roche designed for a LightCycler 1.5 platform had been withdrawn from the commercial market; therefore, we were encouraged to design an alternative LightCycler-based method that offers the desired level of reliability. One hundred breast cancer cases with known HER-2/neu status have been examined with the original Roche developed HER-2/neu Quantification kit and the custom real-time PCR assay. The newly developed, custom PCR showed sensitivity of 91.43%, specificity of 90.63%, and accuracy of 90.91% taking fluorescence in situ hybridization results as the end point. We have described a novel real-time PCR technique for the relative quantification of the HER2/neu gene on a LightCycler 1.5 platform. We have determined that our method is eligible and ideal for the supplement of regular fluorescence in situ hybridization reactions, concerning its high sensitivity and reliability.

A unique biphasic variant of cutaneous fibrous histiocytoma with a storiform pattern and intralesional pigmented melanocytes: "storiform melano-fibrous histiocytoma".

Dermatofibromas (cutaneous fibrous histiocytomas) are common cutaneous neoplasms of mesenchymal origin. They are often associated with epidermal hyperplasia and increased basal layer pigmentation. There have been reports of a spectrum of melanocytic lesions associated with dermatofibromas ranging from junctional nevi to malignant melanomas, some of which may be coincidentally associated. We report a case of a long-standing storiform fibrohistiocytic lesion devoid of cytological atypia, lacking extension into subcutaneous fat, not demonstrating the t(17;22) DFSP translocation yet showing diffuse and strong CD34 immunoreactivity and containing pigmented spindle shaped melanocytic cells admixed with the fibrohistiocytic component. This case raises a nosological debate given the histological, immunophenotypic and cytogenetic findings.

Immunohistochemical antibodies in breast cancer HER2 diagnostics. A comparative immunohistochemical and fluorescence in situ hybridization study.

Overexpression and/or gene amplification of the HER2 oncogene predicts worse prognosis and altered sensitivity to chemotherapy. Trastuzumab is capable of improving prognosis of HER2-positive breast cancer, but for the success of treatment appropriate HER2 testing is essential. Our aim was to determine the value of immunohistochemical (IHC) screening prior to fluorescence in situ hybridization (FISH). We assessed five conventional IHC assays (NCL-CB11, Pathway CB11, CBE356, CBE1, HercepTest) and the novel rabbit monoclonal antibody, RM-4B5, combined with FISH on 199 invasive breast cancer cases. Taking FISH as the endpoint, we calculated sensitivity, specificity, positive and negative predictive values (PPV, NPV) and accuracy for all IHC assays with either taking both 2+/3+ cases or only 3+ cases as IHC positives. With 2+/3+ cases HercepTest showed 100% sensitivity and NPV, while the highest specificity, PPV and accuracy was associated with RM-4B5 (97.36, 80 and 95.34%, respectively). The second highest values belonged to either NCL-CB11 or Pathway CB11. When calculating only with 3+ cases, the results were reversed with increased specificity, PPV and accuracy. Our findings suggest that improving sensitivity by using two parallel IHC reactions might be beneficial; we recommend primarily HercepTest and Pathway CB11. Nevertheless, we may consider performing FISH analysis without prior IHC screening.