Search

Objectives: Haemodynamic determinants of the ratio between pulmonary and systemic flow (Qp/Qs) in partial anomalous pulmonary venous return (PAPVR) are still not fully understood. Indeed, among patients with the same number of lung segments draining anomalously, a great variability is observed in terms of right ventricular overload. The aim of this study was to test the hypothesis that the anatomic site of drainage, affecting the total circuit impedance, independently influences the magnitude of shunt estimated by Qp/Qs. A zero-dimensional lumped parameter mathematical model was developed and validated on a sample of patients., Methods: We developed a zero-dimensional lumped parameter model, using time-varying elastances for heart chambers, RLC Windkessel circuits for the systemic and pulmonary circulations. Patients were categorized into vena cava (VC) type (including left drainage to anomalous vein) and right atrium (RA) type. The mathematical model is a system of ordinary differential equations that are numerically solved by means of the ode15s solver in the MATLAB environment., Results: The model showed an increase of Qp/Qs with the increase of the number of anomalous veins. With the same number of anomalous veins, Qp/Qs was lower in patients with anomalous drainage to the VC as compared with RA. The validation sample consisted of 49 patients (27, 55% females). As predicted by the model, patients with PAPVR with VC type displayed a lower invasive and cardiac magnetic resonance Qp/Qs as compared with drainage to RA: 1.4 (1.2-1.7) and 1.45 (1.25-1.6) versus 2 (1.75-2.1) and 1.9 (1.6-2), P < 0.05. After stratifying for number of lung territories, a lower Qp/Qs was measured in patients with VC PAPVR as compared with RA., Conclusions: In patients with PAPVR, the site of anomalous drainage modulates the Qp/Qs. According to the model, this effect is mediated by the post-capillary impedance of the circuit and significantly decreases with the increase of pulmonary vascular resistances., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Aims: Urothelial carcinoma (UC) demonstrates significant molecular and histologic heterogeneity. The WHO 2022 classification has hinted at adding molecular signatures to the morphologic diagnosis. As morphology and associated molecular repertoire may potentially translate to choices of and response to therapy and relapse rate, broader acceptability of recognizing these key features among uropathologists is needed. This prompted an international survey to ascertain the practice patterns in classical/subtype UC among uropathologists across the globe., Methods and Results: A survey instrument was shared among 98 uropathologists using SurveyMonkey software. Anonymized respondent data were analysed. The response rate was 85%. A majority were in concordance with the profiles of luminal (93%) and basal (82%) types. Opinion on the FGFR3 testing platform was variable. While 95% concurred that TERT promoter mutation is the key driver in UC, 72% had the opinion that APOBEC mutagenesis is the main signature in muscle invasive bladder cancer (MIBC). Uropathologists have divergent opinions on MIBC and ERCC2 mutations. Among the participants, 94% would quantify aggressive micropapillary and sarcomatoid histology, while 88% would reevaluate another transurethral resection of the bladder tumour specimen in nonmuscle invasive tumour with micropapillary, small cell, or sarcomatoid histology. A leading number agreed to specific molecular signatures of micropapillary (93%), plasmacytoid (97%), and small cell (86%) subtypes. Ninety-six percent of participants agreed that a small-cell component portends a more aggressive course and should be treated with neoadjuvant chemotherapy and 63% would perform HER2/neu testing only on oncologist's request in advanced tumours. Ninety percent agreed that microsatellite instability testing, although not a standard protocol, should be considered in young patients with upper tract UC. Eighty-six percent agreed that UC with high tumour mutational burden would be a better candidate for immunotherapy., Conclusion: In the era of precision medicine, enhanced understanding of molecular heterogeneity of UC will contribute to better therapeutic options, novel biomarker discovery, innovative management protocols, and outcomes. Our survey provides a broad perspective of pathologists' perceptions and experience regarding incorporation of histomolecular approaches to "personalize" therapy. Due to variable clinical adoption, there is a need for additional data using uniform study criteria. This will drive generation of best practice guidelines in this area for widespread and consistent clinical utility., (© 2024 John Wiley & Sons Ltd.)

In recent years a significant demand to develop computer-assisted diagnostic tools to assess prostate cancer using whole slide images has been observed. In this study we develop and validate a machine learning system for cancer assessment, inclusive of detection of perineural invasion and measurement of cancer portion to meet clinical reporting needs. The system analyses the whole slide image in three consecutive stages: tissue detection, classification, and slide level analysis. The whole slide image is divided into smaller regions (patches). The tissue detection stage relies upon traditional machine learning to identify WSI patches containing tissue, which are then further assessed at the classification stage where deep learning algorithms are employed to detect and classify cancer tissue. At the slide level analysis stage, entire slide level information is generated by aggregating all the patch level information of the slide. A total of 2340 haematoxylin and eosin stained slides were used to train and validate the system. A medical team consisting of 11 board certified pathologists with prostatic pathology subspeciality competences working independently in 4 different medical centres performed the annotations. Pixel-level annotation based on an agreed set of 10 annotation terms, determined based on medical relevance and prevalence, was created by the team. The system achieved an accuracy of 99.53% in tissue detection, with sensitivity and specificity respectively of 99.78% and 99.12%. The system achieved an accuracy of 92.80% in classifying tissue terms, with sensitivity and specificity respectively 92.61% and 99.25%, when 5x magnification level was used. For 10x magnification, these values were respectively 91.04%, 90.49%, and 99.07%. For 20x magnification they were 84.71%, 83.95%, 90.13%., (© 2024. The Author(s).)

Background: Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced ejection fraction (HFrEF). However, MRAs are often underused because of hyperkalemia concerns., Objectives: The purpose of this study was to assess whether sodium zirconium cyclosilicate (SZC), a nonabsorbed crystal that traps and rapidly lowers potassium, enables MRA use in patients with HFrEF and prevalent hyperkalemia (or at high risk)., Methods: REALIZE-K is a prospective, double-blind, placebo-controlled trial in patients with HFrEF (NYHA functional class II-IV; left ventricular ejection fraction ≤40%), optimal therapy (except MRA), and prevalent hyperkalemia (or at high risk). During the open-label run-in, all participants underwent protocol-mandated spironolactone titration (target: 50 mg daily); those with prevalent (cohort 1) or incident (cohort 2) hyperkalemia during titration started SZC. Participants achieving normokalemia while on spironolactone ≥25 mg daily were randomized to continuing SZC or matching placebo for 6 months. The primary composite endpoint was proportion of participants with optimal response (normokalemia, on spironolactone ≥25 mg daily, no rescue for hyperkalemia [months 1-6])., Results: Of 365 patients (run-in), 202 were randomized. Baseline characteristics included mean age 70 years, prevalent comorbidities (78% estimated glomerular filtration rate <60 mL/min/1.73 m 2 , 38% atrial fibrillation/flutter), high N-terminal pro B-type natriuretic peptide (median 1,136 pg/mL), and high HFrEF therapy use (64% sacubitril/valsartan, 96% beta-blocker, 42% sodium glucose co-transporter 2 inhibitor). At randomization, 78% were receiving spironolactone 50 mg daily., Conclusions: REALIZE-K is the first trial to evaluate whether SZC can enable rapid and safe MRA optimization and long-term continuation in patients with HFrEF and prevalent/high risk of hyperkalemia. (Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients with Symptomatic HFrEF Receiving Spironolactone [REALIZE-K]; NCT04676646)., Competing Interests: Funding Support and Author Disclosures The REALIZE-K trial was funded by AstraZeneca. Drs Kosiborod, Cherney, Connelly, Desai, Guimarães, Kuthi, Lala, Madrini, Merkely, Villota, Squire, Testani, Vaclavik, Verma, Wranicz, and Petrie have received research funding in the form of grants to institutions from AstraZeneca and/or consulting for AstraZeneca. Mr Dahl, Mr Eudicone, and Ms Friberg are employees of, and hold or may hold stock in, AstraZeneca., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Current guidelines recommend considering multiple factors while deciding between cardiac resynchronization therapy with a defibrillator (CRT-D) or a pacemaker (CRT-P). Nevertheless, it is still challenging to pinpoint those candidates who will benefit from choosing a CRT-D device in terms of survival., Objective: We aimed to use topological data analysis (TDA) to identify phenogroups of CRT patients in whom CRT-D is associated with better survival than CRT-P., Methods: We included 2603 patients who underwent CRT-D (54%) or CRT-P (46%) implantation at Semmelweis University between 2000 and 2018. The primary endpoint was all-cause mortality. We applied TDA to create a patient similarity network using 25 clinical features. Then, we identified multiple phenogroups in the generated network and compared the groups' clinical characteristics and survival., Results: Five- and 10-year mortality were 43 (40-46)% and 71 (67-74)% in patients with CRT-D and 48 (45-50)% and 71 (68-74)% in those with CRT-P, respectively. TDA created a circular network in which we could delineate five phenogroups showing distinct patterns of clinical characteristics and outcomes. Three phenogroups (1, 2, and 3) included almost exclusively patients with non-ischemic etiology, whereas the other two phenogroups (4 and 5) predominantly comprised ischemic patients. Interestingly, only in phenogroups 2 and 5 were CRT-D associated with better survival than CRT-P (adjusted hazard ratio 0.61 [0.47-0.80], p < 0.001 and adjusted hazard ratio 0.84 [0.71-0.99], p = 0.033, respectively)., Conclusions: By simultaneously evaluating various clinical features, TDA may identify patients with either ischemic or non-ischemic etiology who will most likely benefit from the implantation of a CRT-D instead of a CRT-P., (© 2023. The Author(s).)

Thyroid-like follicular renal cell carcinoma (TLFRCC), an emerging subtype of renal cell carcinoma, presents diagnostic challenges due to its resemblance to normal thyroid tissue. Here, we report a rare case of TLFRCC in a pediatric patient, a demographic rarely affected by this subtype. Histologically resembling a typical TLFRCC, our case exhibited unique features including post-neuroblastoma development, occurrence in a male teenager, and diffuse MelanA expression, which has not been previously reported in TLFRCC. Comprehensive genomic profiling revealed the EWSR1::PATZ1 fusion, confirming its genetic basis. Due to the advanced tumor stage, the patient received combined immunotherapy, and after a 9-month follow-up, remains tumor-free. Our case broadens the diagnostic spectrum of pediatric renal cell carcinomas, highlighting the importance of comprehensive molecular profiling in rare subtypes such as TLFRCC. Further research is needed to better understand TLFRCC's genetic landscape and optimize therapeutic strategies, especially in pediatric populations with evolving treatment protocols., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Telomerase reverse transcriptase promoter (TERTp) mutations are frequently targeted tumor markers, however, they reside in regions with high GC content, which poses challenges when examined with simple molecular techniques or even with next-generation sequencing (NGS). In bladder cancer (BC), TERTp mutations are particularly frequent, however, none of the available tools have demonstrated efficacy in detecting TERTp mutations via a simple noninvasive technique. Therefore, we developed a novel PCR-based method for the detection of the two most common TERTp mutations and demonstrated its use for the analysis of BC samples. The developed SHARD-PCR TERTp mutation detection technique requires PCR and restriction digestion steps that are easily implementable even in less well-equipped laboratories. Cell lines with known mutational status were utilized for method development. Matching urine and tumor tissue samples from BC patients were analyzed, and the results were validated by next-generation sequencing. Analysis of eighteen urine and corresponding tumor tissue samples by SHARD-PCR revealed perfect matches in sample pairs, which paralleled the corresponding NGS results: fourteen samples exhibited mutations at the -124 position, two samples showed mutations at the -146 position, and no mutations were detected in two samples. Our study serves as a proof-of-concept and is limited by its small sample size, nonetheless, it demonstrates that SHARD-PCR is a simple, economic and highly reliable method for detecting TERTp mutations, which are common in different cancer types. For bladder cancer, SHARD-PCR can be performed with the use of noninvasive samples and could replace or complement currently used techniques., (© 2024. The Author(s).)

Aims: Patients with obesity have an overall higher cardiovascular risk, at the same time obesity could be associated with a better outcome in a certain subgroup of patients, a phenomenon known as the obesity paradox. Data are scarce in candidates for cardiac resynchronization therapy (CRT). We aimed to investigate the association between body mass index (BMI) and all-cause mortality in patients eligible for CRT., Methods: Altogether 1,585 patients underwent cardiac resynchronization therapy between 2000-2020 and were categorized based on their BMI, 459 (29%) patients with normal weight (BMI < 25 kg/m2), 641 (40%) patients with overweight (BMI 25- < 30 kg/m2) and 485 (31%) with obesity (BMI ≥ 30 kg/m2). The primary endpoint was all-cause mortality, heart transplantation, and left ventricular assist device implantation. We assessed periprocedural complications and 6-month echocardiographic response., Results: Normal-weight patients were older compared to patients with overweight or obesity (70 years vs. 69 years vs. 68 years; P ‹0.001), respectively. Sex distribution, ischaemic aetiology, and CRT-D implantation rates were similar in the three patient groups. Diabetes mellitus (BMI < 25 kg/m 2 26% vs. BMI 25- < 30 kg/m 2 37% vs. BMI ≥ 30 kg/m 2 48%; P ‹0.001) and hypertension (BMI < 25 kg/m 2 71% vs. BMI 25- < 30 kg/m 2 74% vs. BMI ≥ 30 kg/m 2 82%; P ‹0.001) were more frequent in patients with overweight and obesity. During the mean follow-up time of 5.1 years, 973 (61%) reached the primary endpoint, 66% in the BMI < 25 kg/m 2 group, 61% in the BMI 25- < 30 kg/m 2 group and 58% in the BMI ≥ 30 kg/m 2 group (log-rank P‹0.05). Patients with obesity showed mortality benefit over normal-weight patients (HR 0.78; 95%CI 0.66-0.92; P = 0.003). The obesity paradox was present in patients free from diabetes, atrial fibrillation, and ischemic events. Periprocedural complication rates did not differ in the three groups (BMI < 25 kg/m 2 25% vs. BMI 25- < 30 kg/m 2 28% vs. BMI ≥ 30 kg/m 2 26%; P = 0.48). Left ventricular ejection fraction improved significantly in all patient groups (BMI < 25 kg/m 2 median ∆ $$ \Delta $$ -LVEF 7% vs. BMI 25- < 30 kg/m 2 median ∆ $$ \Delta $$ -LVEF 7.5% vs. BMI ≥ 30 kg/m 2 median ∆ $$ \Delta $$ -LVEF 6%; P < 0.0001) with a similar proportion of developing reverse remodeling (BMI < 25 kg/m 2 58% vs. BMI 25- < 30 kg/m 2 61% vs. BMI ≥ 30 kg/m 2 57%; P = 0.48); P = 0.75)., Conclusions: The obesity paradox was present in our HF cohort at long-term, patients underwent CRT implantation with obesity and free of comorbidities showed mortality benefit compared to normal weight patients. Patients with obesity showed similar echocardiographic response and safety outcomes compared to normal weight patients., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Prostate cancer stands as the most prevalent malignant tumor among men; with its incidence increasing with advancing age. The spectrum of patient care options for this disease is broad, encompassing approaches such as "active surveillance," definitive radiation therapy, robot-assisted surgery, among others. These diverse modalities afford opportunities for cure or successful management in the majority of cases. It is paramount to underscore that optimal treatment hinges upon a multidisciplinary framework, wherein the coordinated efforts of allied healthcare professionals yield the highest standard of patient care. Hence, it is imperative for pathologists to keep abreast of contemporary processing and specimen collection protocols, as well as the potential necessity of supplementary investigations and their clinical significance. The latest Hungarian guideline on prostate cancer care features a dedicated chapter delineating the pivotal role and responsibilities of pathologists. Through this discourse, we aim to consolidate and disseminate pertinent insights, thereby fostering the continuing enhancement of pathologists' knowledge and elucidating the intricacies of histological processing to our clinical counterparts.

Background: Human pulmonary dirofilariasis (HPD) is rare in Hungary, and it stems from Dirofilaria immitis, mainly transmitted through mosquito bites, with dogs as primary hosts. Despite its prevalence in veterinary settings, human cases are infrequent. Historically, Mediterranean countries report most HPD cases, but sporadic cases occur in temperate European regions. Radiologically, HPD often manifests in a non-specific manner, resembling pulmonary neoplasms, leading to unnecessary surgery and patient distress., Methods: This study presents a notable case series from Hungary, encompassing a 12-year period, documenting 5 instances of HPD with the aim to provide baseline estimate of occurrence for future comparison., Results: Among the patients studied, all were of middle age (median: 52 years, range: 37-69) and exhibited tumor-like lesions, primarily localized to the right lung, necessitating lobectomy or wedge resection. Histological examination consistently revealed a necrotizing granulomatous response characterized by remnants of helminths, without the presence of ovules. Furthermore, rigorous diagnostic procedures excluded other potential infectious agents through specialized staining techniques. Polymerase chain reaction analysis definitively confirmed the diagnosis of HPD in each case., Conclusions: This case series highlights HPD as a seldom zoonosis, with a probable escalation in its occurrence within temperate regions. Therefore, clinicians should maintain a heightened awareness of HPD in the differential diagnosis of pulmonary coin lesions. Early recognition and diagnosis are paramount for appropriate management and prevention of potential complications associated with this increasingly recognized infectious entity., (© 2024. The Author(s).)

Angiosarcoma (AS) of the breast, a rare mesenchymal neoplasm, exhibits distinct forms based on etiological and genetic features. While cases with typical clinical presentation and morphology allow for a straightforward diagnosis, challenges arise when clinical data are scarce, diagnostic material is limited, or morphological characteristics overlap with other tumors, including undifferentiated carcinomas. The trichorhinophalangeal syndrome protein 1 (TRPS1), once regarded as highly specific for breast carcinomas, now faces doubts regarding its reliability. This study explores TRPS1 expression in breast AS. Our investigation revealed that 60% of AS cases displayed TRPS1 labeling, contrasting with the 40% lacking expression. Scoring by four independent readers established a consensus, designating 12/35 ASs as unequivocally TRPS1-positive. However, uncertainty surrounded nine further cases due to a lack of reader agreement (being substantial as reflected by a kappa value of 0.76). These findings challenge the perceived specificity of TRPS1, shedding light on its presence in a noteworthy proportion of breast ASs. Consequently, the study underscores the importance of a comprehensive approach in evaluating breast ASs and expands the range of entities within the differential diagnosis associated with TRPS1 labeling., (© 2024. The Author(s).)

Background: Follicular dendritic cell sarcoma (FDCS) is a rare low-grade tumor of the lymph nodes, but roughly one-third of the cases emerge from extranodal sites, posing diagnostic challenges., Case Presentation: In this report, we present the case of a 59-year-old lady who complained of renal colic. During investigation, a kidney tumor was discovered. A radical nephrectomy was performed, and histological examination identified the tumor as a sarcomatoid renal cell carcinoma. The case was then referred to a genitourinary pathologist for further evaluation. The tumor cells exhibited positive staining for CD21, CD23, somatostatin receptor 2 A, and MDM2 expression. Additionally, MDM2 gene amplification was confirmed by the FISH study. Ultimately, the tumor was diagnosed as a primary renal FDCS. The patient was placed under active oncological surveillance and did not receive any further therapy. Remarkably, after 91 months of follow-up, she remains tumor-free., Conclusion: This case represents a well-documented primary renal FDCS. Our aim in presenting this extremely rare tumor is to enhance awareness and highlight the importance of considering FDCS in the differential diagnosis., (© 2024. The Author(s).)

Introduction: Colorectal tubular adenomas displaying clear cell change are rare entities, with unknown clinical relevance, prognosis, immunohistochemical, and molecular features., Case Presentation: Hereby we report a case of a 43-year-old female patient with a rectosigmoid polyp. Histologically, conventional dysplasia was visible with scattered areas displaying clear cell change. Whole-exome sequencing (WES) was carried out and revealed high tumour mutation burden and 7 pathogenic mutations, including TP53, APC, FGFR4, EHBP1, IL4R, TYR, and ACTN3., Conclusion: Clear cell change may only be present in less than 0.1% of adenomas. Aetiology is not well understood; additionally, few authors suggest autolysis or fixation problems. Our WES resulted in newly found pathogenic mutations, and high mutation burden, proving the lesion's neoplastic origin. Hitherto, neither special stainings nor immunohistochemical markers proved to be useful in the diagnostic process. From a differential diagnostic perspective, enteroblastic differentiation, primary and secondary clear cell adenocarcinoma has to be excluded., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Choosing the optimal device during cardiac resynchronization therapy (CRT) upgrade can be challenging. Therefore, we sought to provide a solution for identifying patients in whom upgrading to a CRT-defibrillator (CRT-D) is associated with better long-term survival than upgrading to a CRT-pacemaker (CRT-P). To this end, we first applied topological data analysis to create a patient similarity network using 16 clinical features of 326 patients without prior ventricular arrhythmias who underwent CRT upgrade. Then, in the generated circular network, we delineated three phenogroups exhibiting significant differences in clinical characteristics and risk of all-cause mortality. Importantly, only in the high-risk phenogroup was upgrading to a CRT-D associated with better survival than upgrading to a CRT-P (hazard ratio: 0.454 (0.228-0.907), p = 0.025). Finally, we assigned each patient to one of the three phenogroups based on their location in the network and used this labeled data to train multi-class classifiers to enable the risk stratification of new patients. During internal validation, an ensemble of 5 multi-layer perceptrons exhibited the best performance with a balanced accuracy of 0.898 (0.854-0.942) and a micro-averaged area under the receiver operating characteristic curve of 0.983 (0.980-0.986). To allow further validation, we made the proposed model publicly available ( https://github.com/tokmarton/crt-upgrade-risk-stratification )., (© 2023. The Author(s).)

Background: Penile melanoma (PM) is a rare tumor, accounting for less than 2% of all penile cancers. PM can occur on the surface of the glans, foreskin, and opening of the urethra. Furthermore, PM primarily affects older individuals and is not associated with sun exposure. Currently, there is no specific staging system for genitourinary tract melanomas, so these tumors are typically staged using the criteria for cutaneous melanoma. Limited data in the literature suggests that PM generally has a poor clinical prognosis., Case Presentation: Here, we describe two cases of PM. The first case affected a 62-year-old male who presented with hematuria and a painful tumor in the distal urethra, leading to a suspicion of penile cancer. The second case involved a 68-year-old male who noticed a rapidly evolving dark spot on his foreskin. Histological analysis confirmed the presence of melanoma in both patients. The tumors showed a diffuse and strong PRAME-positivity and lacked BRAF mutation in both cases. Additionally, the second tumor harbored an activating CKIT mutation. An enhanced PD-L1 expression was observed in both tumors., Conclusions: We presented two rare forms of mucosal melanoma and highlighted the entities in the differential diagnosis. Based on our experience PRAME is a helpful marker for making the diagnosis of PM, and PD-L1 can predict the success of the immunotherapy. We also emphasize the need for an organ-specific staging system for PMs., (© 2023. The Author(s).)

Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare, low-grade, painless tumor of mesenchymal origin. In the current, 5th edition of the World Health Organisation (WHO) 'Classification of tumors: Soft tissue and bone tumors', there is no exact diagnostic genetic alteration defined in MIFS. Hereby we present the case of a 71-year-old female patient, with a medical history of benign essential hypertension, who visited the hospital because of a lesion above her right shin. She perceived the lesion 1.5 years prior to the medical attendance, and she only attended the medical facility because of the development of pain, erosion and papule formation on the skin surface. Microscopically, the lesion had cellular and pleomorphic appearance with nodular structure, and showed honeycomb-like infiltration of the subcutaneous fat tissue. Tumor cell infiltration was visible among the collagen fibers of the dermis. Tumor cells frequently displayed multinuclear morphology with prominent, viral inclusion-like nucleoli and exuberant fibrillary, often vacuolated and ground-glass cytoplasm. With immunohistochemical examination, tumor cells showed multifocal positivity with CD34, CD31, podoplanin (D2-40), cyclin D1, and epithelial membrane antigen (EMA). Furthermore, the tumor cells proved to be diffusely positive with smooth muscle actin (SMA). After meeting all the essential criteria of the current WHO classification, the case was concluded as MIFS, showing high-grade features. According to our experience, an immunohistochemistry panel of podoplanin, ciklin-D1, CD10, EMA, CD34, and CD31 can facilitate the correct conclusion. Our case of MIFS highlights the unusual, focally high-grade features of this complicated, challenging disease. Diffuse SMA positivity is a known, but uncommon feature of these tumors. Orv Hetil. 2023; 164(41): 1637-1641.

Urothelial cell carcinoma is the most common malignant tumor of the urinary tract, which develops in the renal pelvis, ureter, and bladder, and rarely it develops in the ureter. Histologically, urothelial cell carcinoma is categorized into non-invasive and invasive forms. Non-invasive urothelial cell carcinoma has papillary growth, it is usually well differentiated, and has a favorable outcome, while invasive urothelial cell carcinoma infiltratively spreads the organs of origin, it is typically poorly differentiated, and often associated with a poor prognosis. In the case of invasive urothelial cell carcinoma, the clinical course is primarily determined by the depth of invasion, but according to recent data, morphological variants of urothelial cell carcinoma respond differently to oncological treatments, and their biological behavior is also distinct. These subtypes and variants are significantly underdiagnosed in Hungary and internationally because the criteria for histological diagnosis are not clear for many subsets. The latest 2022 WHO classification of urinary tract tumors significantly clarified the definitions of various subtypes and variants. In this paper, utilizing the current classification, we review and explain these subtypes' morphological, immunohistochemical, differential diagnostic, prognostic, and predictive characteristics intending to make them appear as much as possible in everyday diagnostic practice. Also, the work aims to present the individual urothelial cell carcinoma subtypes and variants to the Hungarian community of pathologists, oncologists, and urologists, so that the previously high level of urological oncology care can become even more personalized. Orv Hetil. 2023; 164(40): 1567-1582.

It is acknowledged that nephron develops after bilateral induction of the metanephric mesenchyma and branching ureteric bud (UB), and that nephrogenic rest and Wilms' tumor (nephroblastoma) arises from impaired differentiation of metanephric blastema. The aim of this study was to obtain more information on the involvement of UB derivatives in nephrogenic rest and Wilms' tumor. We applied immunohistochemistry to analyze nephrogenic rests and Wilms' tumors with mixed histology, including regressive and blastemal types. We used antibodies recognizing UB tip cells (ROBO1, SLIT2, RET), principal cells (AQP2), α- and β-intercalated cells (SLC26A4, SLC4A1, ATP6V1B1, ATP6V0D2), and their precursors (CA2). Tubules surrounded by tumorous blastemal cells resembling UB tip were positive for RET, ROBO1, and SLIT2 in Wilms' tumor. Moreover, CA2-positive tubular structures and ATP6V1B1- and ATP6V0D2-positive immature non-α- and non-β-intercalated cells were detected in nephrogenic rest and Wilms' tumor. We suggest that Wilms' tumor is more than nephroblastoma and propose a definition that Wilms tumor is a malignant embryonal neoplasm derived from pluripotential cells of nephrogenic blastema and of ureteric bud tip., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Wilms' tumor (WT) is the most common renal malignancy in children. In diffuse hyperplastic perilobar nephroblastomatosis (DHPLN), nephrogenic rests result in a bulky enlargement of the kidney, a condition considered as a premalignant state before WT. Despite relevant clinical differences between WT and DHPLN, they are often challenging to distinguish based on histology. Molecular markers would improve differential diagnosis, but none are available at present. In our study, we investigated the potential of microRNAs (miRNAs) as such biomarkers, also aiming to shed light on the chronological order of expression changes. Formalin-fixed, paraffin-embedded (FFPE) samples from four DHPLN cases and adjacent healthy tissues were tested using a PCR array containing primers for 84 miRNAs implicated in genitourinary cancer. Expression in DHPLN was compared to WT data available in dbDEMC. Let-7, miR-135, miR-146a-5p, miR-182-5p, miR-183-5p, miR-20b-3p, miR-29b-3p, miR-195-5p and miR-17-5p showed potential to be used as biomarkers to distinguish WT and DHPLN in cases when traditional differential diagnosis is inconclusive. Our study also revealed miRNAs which may play a role in the initial steps of the pathogenesis (at a precancerous stage) and ones which become deregulated later in WT. More experiments are needed to confirm our observations and find new candidate markers.

The lack of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 expression in breast cancer (BC) is the basis for the categorization of the tumour as triple negative breast carcinoma (TNBC). The majority of TNBCs are aggressive tumours with common metastases and decreased expression of markers that could help in identifying the metastatic lesion as of mammary origin. Breast markers, such as gross cystic disease fluid protein-15 (GCDPF-15), GATA binding protein 3 (GATA3), mammaglobin (MGB) and SOX10, are not uniquely specific to BC. Our aim was to evaluate trichorhinophalangeal syndrome type 1 (TRPS1) protein as a breast marker in a series of cytokeratin-5-expressing TNBC, mostly corresponding to basal-like TNBCs, previously characterized for the expression of other breast markers. One hundred seventeen TNBCs in tissue microarrays were immunostained for TRPS1. The cut-off for positivity was ≥ 10%. The reproducibility of this classification was also assessed. TRPS1 positivity was detected in 92/117 (79%) cases, and this exceeded the expression of previously tested markers like SOX10 82 (70%), GATA3 11 (9%), MGB 10 (9%) and GCDFP-15 7 (6%). Of the 25 TRPS1-negative cases, 11 were positive with SOX10, whereas 5 to 6 dual negatives displayed positivity for the other makers. The evaluation showed substantial agreement. Of the five markers compared, TRPS1 seems the most sensitive marker for the mammary origin of CK5-expressing TNBCs. Cases that are negative are most often labelled with SOX10, and the remainder may still demonstrate positivity for any of the 3 other markers. TRPS1 has a place in breast marker panels., (© 2023. The Author(s).)

Renal cell carcinoma (RCC) is the most common malignant kidney tumor. It is not a single entity but an umbrella term for several distinct tumor types. The most prevalent and clinically significant subtype of RCC is clear cell carcinoma, which consists of cells with empty cytoplasm. These tumor cells harbor biallelic loss of the VHL gene, resulting in a pseudohypoxic state that promotes angiogenesis and cellular proliferation. Papillary RCC and chromophobe carcinoma are also common subtypes, with the former displaying a papillary appearance and cMET mutation. The latter is characterized by eosinophilic tumor cells and multiple chromosomal losses. These subtypes are responsible for 90-95% of all kidney cancers in adults. Additionally, rare tumor subtypes with unique immunohistochemical features, genetic abnormalities, or a specific clinical course may be identified. Currently, the RCC subtype only holds prognostic significance, and no treatment is associated with any subtype. However, therapies associated with histological subtypes may emerge in the future, and thus, the diagnosis of RCCs should be made following current recommendations.

Kidney tumors may develop in association with hereditary tumor syndromes. The clinical presentation of these disorders is various, and in some cases, the renal tumor is the first manifestation of the syndrome. Thus, pathologists need to be aware of the gross and histological signs that may suggest the possibility of a tumor syndrome. In this paper, we summarize and illustrate the characteristics of kidney tumors, genetic background along with the extrarenal manifestations in the following diseases: Von Hippel-Lindau syndrome, hereditary papillary renal cell carcinoma syndrome, hereditary leiomyomatosis and renal cell carcinoma syndrome, Birt-Hogg-Dubé syndrome, tuberous sclerosis, hereditary paraganglioma and pheochromocytoma syndrome, and inherited BAP1 tumor syndrome. At the end of the manuscript, we discuss the tumor syndromes with increased risk of Wilms tumors. Such patients require a holistic approach and multidisciplinary care. Our work aims to make those involved in the diagnosis and treatment of kidney tumors aware of these rare diseases that require life-long surveillance. Orv Hetil. 2023; 164(10): 363-375.

Aims: Primary prevention of sudden cardiac death (SCD) in non-ischemic heart failure (HF) patients remains a topic of debate at cardiac resynchronization therapy (CRT) implantation requiring individual risk assessment. Using the Goldenberg SCD risk score, we aimed to predict, which non-ischemic HF patients will benefit from the addition of an implantable cardioverter defibrillator (ICD) to CRT at long-term., Methods: Between 2000 and 2018 non-ischemic HF patients undergoing CRT implantation were collected into our retrospective registry. The Goldenberg risk score (GRS) was calculated by the presence of atrial fibrillation, New York Heat Association (NYHA) class > 2, age > 70 years, blood urea nitrogen > 26 mg/dl and QRS > 120 ms. The primary endpoint was all-cause mortality, heart transplantation or left ventricular assist device implantation., Results: From 667 patients, 347 (52%) underwent cardiac resynchronization therapy-pacemaker (CRT-P), 320 (48%) cardiac resynchronization therapy-defibrillator (CRT-D) implantations. During the median follow up time of 4.3 years, 306 (46%) patients reached the primary endpoint (CRT-D 37% vs. CRT-P 63%; p < 0.001). CRT-D patients were younger (64 vs. 69 years; p < 0.001), infrequently females (26 vs. 39%; p < 0.001), and had a lower ejection fraction (27 vs. 29%; p < 0.01) compared to CRT-P patients. After GRS calculation, patients were dichotomized by low (< 3) and high (≥ 3) scores. CRT-D patients with low GRS showed a mortality benefit compared to CRT-P (HR 0.68; 95% CI 0.48-0.96; p = 0.03), high-risk patients did not (HR 0.84; 95% CI 0.62-1.13; p = 0.26)., Conclusion: In our non-ischemic cohort, patients with low GRS showed a clear long-term mortality benefit by adding ICD to CRT, however, in high-risk patients no further benefit could be observed., Competing Interests: AK receives consulting fees from Medtronic and Biotronik, and receives payment or honoraria for lectures from Novartis, Bayer, Boehringer Ingelheim, Astra Zeneca, Medtronic Biotronik, and Boston Scientific. BM receives grants or has contracts with Abbott, Astra Zeneca, Argint International, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, CSL Behring, Daiichi Sankyo, Cerenis Therapeutics SA DUKE Clinical Institut, Eli Lilly, Medtronic, Novartis, Terumo, St. Jude, Zoll and VIFOR Pharma, and receives lecture fees from Abbott, Astra Zeneca, Biotronik, Boehringer Ingelheim, and Novartis. LG receives lecture fees from Biotronik, Medtronic, Johnson & Johnson Medical, and Abbott outside the submitted work. EZ reports lecture and advisory fees from Biotronik, Medtronic, Boston Scientific, and Zoll Medical, outside the submitted work. RP reports lecture fees from Biotronik, Medtronic, and Abbott outside the submitted work. LM reports lecture fees from Biotronik, Medtronic, and Abbott outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Merkel, Schwertner, Behon, Kuthi, Veres, Osztheimer, Papp, Molnár, Zima, Gellér, Kosztin and Merkely.)

The renal angiomyolipoma (AML) is a benign tumor characteristically composed of fat, smooth muscle tissue, and vessels. We collected AMLs from our nephrectomy database, reclassified them according to their histological appearance, recorded the demographic, clinical, and pathological parameters, and compared them with oncocytoma (RO) and renal cell carcinoma (RCC). Immunohistochemistry was ordered in 41 cases. In 2224 nephrectomies, we found 52 AMLs with a 53 mm median size. The mean age was 52.76. Forty-eight tumors were sporadic, while four were hereditary. The revision resulted in 31 classic, 13 leiomyoma-like, five lipoma-like, two epithelioid, and one AML with epithelial cysts. SMA was diffusely positive, except for the epithelioid type, while MelanA harbored stronger expression than HMB45. AML was more frequent in females and appeared ten and 7 years earlier than RO and RCC, respectively. The follow-up time was 7.42 years, and neither tumor-related death nor relapse occurred. AML is rare in nephrectomies and develops primarily in females in their 50s with an average size of 50-60 mm at the surgery. The histological appearance in order of frequency is classic, leiomyoma-like, lipoma-like, epithelioid, and cystic. The MelanA, HMB45, and SMA immunohistochemistry can support the light-microscopic findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Fejes, Sánta, Jenei, Király, Varga and Kuthi.)

Introduction: End-stage renal disease (ESRD) and acquired cystic kidney disease (ACKD) are known risk factors for renal cell carcinoma (RCC). Hereby, the clinicopathological features of RCCs developed in ESRD were investigated., Methods: A database consisting of 34 tumors from 31 patients with ESRD among 2,566 nephrectomy samples of RCC was built. The demographic, clinical, and follow-up data along with pathological parameters were analyzed. The RCCs were diagnosed according to the current WHO Classification of Urinary and Male Genital Tumors., Results: Twenty-two tumors developed in men and 12 in women, with a median age of 56 years (range: 27-75 years). The causes of ESRD were glomerulonephritis (n = 7), hypertensive kidney disease (n = 6), autosomal dominant polycystic kidney disease (n = 6), chronic pyelonephritis (n = 4), diabetic nephropathy (n = 3), chemotherapy-induced nephropathy (n = 1), and undetermined (n = 4). ACKD complicated ESRD in 12 patients. The following histological subtypes were identified: clear cell RCC (n = 19), papillary RCC (n = 5), clear cell papillary tumor (n = 5), ACKD RCC (n = 3), and eosinophilic solid and cystic RCC (n = 2). The median tumor size was 31 mm (range: 10-80 mm), and 32 tumors were confined to the kidney (pT1-pT2). There was no tumor-specific death during the period of this study. Progression was registered in 1 patient., Conclusion: In our cohort, the most common RCC subtype was clear cell RCC (55%), with a frequency that exceeded international data appreciably (14-25%). The incidence of clear cell papillary tumor and ACKD RCC (14.7% and 8.5%) was lower than data reported in the literature (30% and 40%). Our results indicate a favorable prognosis of RCC in ESRD., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

The morphologic diversity of chromophobe renal cell carcinoma (ChRCC) is well-known. Aside from typical morphology, pigmented adenomatoid, multicystic and papillary patterns have been described. Ten cases of CHRCC composed of small cell population in various percentages were analysed, using morphologic parameters, immunohistochemistry and next-generation sequencing (NGS) testing. Patients were five males and five females, with age ranging from 40 to 78years. The size of tumors ranged from 2.2 cm to 11 cm (mean 5.17 cm). Small cell component comprised 10 to 80% of the tumor volume, while the remaining was formed by cells with classic ChRCC morphology. The immunohistochemical profile of the small cell component was consistent with typical ChRCC immunophenotype, with CD117 and CK7 positivity. Neuroendocrine markers were negative. Mutations of 13 genes were found: DCIER1, FGFR3, JAK3, SUFO, FAM46C, FANCG, MET, PLCG2, APC, POLE, EPICAM, MUTYH and AR. However, only the PLCG2 mutation is considered pathogenic.The small cell variant of ChRCC further highlights and expand upon existing morphologic heterogeneity spectrum. Recognition of small cell variant of CHRCC is not problematic in tumors, where the "classic" CHRCC component is present. However, in limited material (i.e., core biopsy), this may present a diagnostic challenge. Based on the limited follow-up data available, it appears that the small cell tumor component had no impact on prognosis, since there was no aggressive behavior documented.   Awareness of this unusual pattern and applying additional sections to find classic morphology of ChRCC, as well as excluding neuroendocrine nature by immunohistochemistry, may help resolve difficult cases.

Introduction: The COVID-19 (coronavirus disease 2019) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is associated with high mortality rates worldwide. Polymerase chain reaction (PCR) is extensively used for virus detection in both infected patients and deceased persons. PCR, however, gives no information about the localization of the virus in cells and tissues. Detection of spike and nucleocapsid proteins and viral ribonucleic acid (RNA) of the SARS-CoV-2 in situ might provide more information and aid in the discovery of the pathomechanism of cellular damage. There are several commercially available anti-spike and anti-nucleocapsid antibodies used to detect immunohistochemical reactions, though each gives different results. Objective: The goal of the present study was to compare the intensity and specificity of several anti-spike and antinucleocapsid antibodies in different dilutions in four Hungarian university departments. Method: Immunohistochemical reactions were performed on coded slides taken from infected lungs of 3 deceased and placenta samples with appropriate negative controls of formalin-fixed paraffin-embedded tissues, scanned, evaluated unanimously and analysed statistically by the assessors. Results: By comparing the intensity, dilution, background and reproducibility of the different primary antibodies, it was possible to select the antibodies with the best results. Conclusion: The antibodies selected with established dilutions can be used in further studies to detect SARS-CoV-2 proteins in surgical materials and in samples obtained during autopsy.

Patients diagnosed with clear cell renal cell carcinoma (ccRCC) have poor prognosis for recurrence and approximately 30-40% of them will later develop metastases. For this reason, the appropriate diagnosis and the more detailed molecular characterisation of the primary tumour, including its susceptibility to metastasis, are crucial to select the proper adjuvant therapy by which the most prosperous outcome can be achieved. Nowadays, clinicopathological variables are used for classification of the tumours. Apart from these, molecular biomarkers are also necessary to improve risk classification, which would be the most beneficial amongst modern adjuvant therapies. As a potential molecular biomarker, to follow the transcriptional kinetics in ccRCC patients (n=30), we analysed epigenetic changes (γH2A.X, H3K4me 3 , and H3K9me 3 ) and the alterations in the level of RNA polymerase II (RNAPII) by immunohistochemical staining on dissected tissue sections. The variabilities between the tumorous and non-tumorous parts of the tissue were detected using quantitative image analysis by monitoring 30 cells from different positions of either the tumorous or the non-tumorous part of the tissue sections. Data obtained from the analyses were used to identify potential prognostic features and to associate them with the progression. These markers might have a value to predict patient outcomes based on their individual cellular background. These results also support that detection of any alteration in the level of H3K4me 3 , H3K9me 3 , and γH2A.X can account for valuable information for presuming the progression of ccRCC and the clinical benefits to select the most efficient personalised therapy., (Copyright © 2022. Published by Elsevier Inc.)

Routine molecular tumour diagnostics are augmented by DNA-based qualitative and quantitative molecular techniques detecting mutations of DNA. However, in the past decade, it has been unravelled that the phenotype of cancer, as it's an extremely complex disease, cannot be fully described and explained by single or multiple genetic variants affecting only the coding regions of the genes. Moreover, studying the manifestation of these somatic mutations and the altered transcription programming-driven by genomic rearrangements, dysregulation of DNA methylation and epigenetic landscape-standing behind the tumorigenesis and detecting these changes could provide a more detailed characterisation of the tumour phenotype. Consequently, novel comparative cancer diagnostic pipelines, including DNA- and RNA-based approaches, are needed for a global assessment of cancer patients. Here we report, that by monitoring the expression patterns of key tumour driver genes by qPCR, the normal and the tumorous samples can be separated into distinct categories. Furthermore, we also prove that by examining the transcription signatures of frequently affected genes at 3p25 , 3p21 and 9p21.3 genomic regions, the ccRCC (clear cell renal cell carcinoma) and non-tumorous kidney tissues can be distinguished based on the mRNA level of the selected genes. Our results open new diagnostics possibilities where the mRNA signatures of tumour drivers can supplement the DNA-based approaches providing a more precise diagnostics opportunity leading to determine more precise therapeutic protocols., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ujfaludi, Kuthi, Pankotai-Bodó, Bankó, Sükösd and Pankotai.)

A distinct renal tumor has recently been described as "high-grade oncocytic renal tumor" and "sporadic renal cell carcinoma with eosinophilic and vacuolated cytoplasm". The Genitourinary Pathology Society (GUPS) consensus proposed a unifying name "eosinophilic vacuolated tumor" (EVT) for this emerging entity. In this multi-institutional study, we evaluated 19 EVTs, particularly their molecular features and mutation profile, using next-generation sequencing. All cases were sporadic and none of the patients had a tuberous sclerosis complex. There were 8 men and 11 women, with a mean age of 47 years (median 50; range 15-72 years). Average tumor size was 4.3 cm (median 3.8 cm; range 1.5-11.5 cm). All patients with available follow-up data (18/19) were alive and without evidence of disease recurrence or progression during the follow-up, ranging from 12 to 198 months (mean 56.3, median 41.5 months). The tumors were well circumscribed, but lacked a well-formed capsule, had nested to solid growth, focal tubular architecture, and showed ubiquitous, large intracytoplasmic vacuoles, round to oval nuclei, and prominent nucleoli. Immunohistochemically, cathepsin K, CD117, CD10, and antimitochondrial antigen were expressed in all cases. Other positive stains included: PAX8, AE1/AE3 and CK18. CK7 was typically restricted only to rare scattered cells. Vimentin, HMB45, melan-A, and TFE3 were negative in all cases. All tumors showed retained SDHB. All cases (19/19) showed non-overlapping mutations of the mTOR pathway genes: TSC1 (4), TSC2 (7), and MTOR (8); one case with MTOR mutation showed a coexistent RICTOR missense mutation. Low mutational rates were found in all samples (ranged from 0 to 6 mutations/Mbp). Microsatellite instability and copy number variations were not found in any of the 17 analyzable cases. EVT represents an emerging renal entity that shows a characteristic and readily identifiable morphology, consistent immunohistochemical profile, indolent behavior, and mutations in either TSC1, TSC2, or MTOR genes., (© 2021. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)

Clear cell renal cell carcinoma (CCRCC) is well known for intratumor heterogeneity. An accurate mapping of the tumor is crucial for assessing prognosis, and perhaps this can be linked to potential success/failure of targeted therapies. We assembled a cohort of 7 CCRCCs with prominent vasculature and microvascular hyperplasia (ccRCCPV), resembling those seen in high grade gliomas. A control group of classic CCRCC with no variant morphologies was also included. Both groups were analyzed for clinicopathologic, morphologic, immunohistochemical, and molecular genetic features. No statistically significant differences in mRNA expression of studied genes between the two groups were found. Using NGS panel Trusight Oncology 500 (TSO500), only one clinically significant gene mutation, VHL c.263G > A, p. (Trp88Ter), was found. TMB (Tumor Mutation Burden) and MSI (MicroSatellite Instability) were low, and no copy number variations (CNVs) were detected in the study cohort. Prominent microvascular hyperplasia in CCRCC is a rare phenomenon. From molecular genetic point of view, these tumors do not appear to be different from classic CCRCC. Prognostically, they also demonstrated similar clinical behaviors., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Összefoglaló. Bevezetés: A kórboncolás hozzájárul a súlyos akut légzőszervi szindrómát okozó koronavírus-2 (SARS-CoV-2-) fertőzés klinikopatológiai vonatkozásainak megismeréséhez. Célkitűzés: A SARS-CoV-2-fertőzöttek boncolása során gyűjtött tapasztalatok bemutatása. Módszer: Egymást követően boncolt, védőoltásban nem részesült, SARS-CoV-2-fertőzött elhunytak klinikai adatait, makro- és mikroszkópos észleleteit összegeztük; a tüdőkimetszéseket SARS-CoV-2-nukleokapszid-immunfestéssel vizsgáltuk. Eredmények: A boncolást a halálok megállapítására (n = 14), tumorgyanú (n = 9), illetve törvényi kötelezettség (n = 3) miatt végeztük. A fertőzést a klinikai észlelés vagy a boncolás során (n = 4) végzett SARS-CoV-2-nukleinsav-teszt igazolta. A tünetes betegség átlagos hossza 12,9 nap volt. 21 betegnél (medián életkor 69 év; 18 férfi) állt fenn COVID-19-pneumonia, mely 16 esetben önmagában, 4 esetben bakteriális pneumoniával vagy álhártyás colitisszel szövődve okozott halált; 1 antikoagulált pneumoniás beteg heveny retroperitonealis vérzésben halt meg. 3 betegnél a halált disszeminálódott malignus tumor, 1 betegnél coronariathrombosis, 1 mentálisan retardált betegnél pedig pulmonalis emboliás szövődmény okozta. A COVID-19-pneumoniás tüdők nehezek, tömöttek és vörösen foltozottak voltak. Szövettanilag a betegség időtartamától függően diffúz alveolaris károsodás korai exsudativ vagy későbbi proliferativ fázisa látszott atípusos pneumocytákkal; gyakori volt a microthrombosis (n = 7), a macrothrombosis (n = 5), illetve a pulmonalis embolia (n = 4). A SARS-CoV-2-immunfestés pozitívnak bizonyult az esetek 38,5%-ában, dominálóan az exsudativ fázisban. Minden elhunyt társbetegség(ek)ben szenvedett, így magasvérnyomás-betegségben (n = 17), érelmeszesedésben (n = 14), 2-es típusú diabetesben (n = 8), rosszindulatú daganatban (n = 6), krónikus obstruktív tüdőbetegségben (n = 4), elhízásban (n = 3), vesetranszplantáció utáni immunszuppresszióban (n = 3). Következtetés: Az irodalmi adatokkal összhangban, halálos COVID-19-pneumonia túlnyomóan idős, társbetegség(ek)től sújtott férfiakban alakult ki. A boncolási gyakorlatban a SARS-CoV-2-nukleokapszid-immunfestéstől a diffúz alveolaris károsodás korai fázisában várható pozitivitás. Orv Hetil. 2021; 162(45): 1791-1802., Introduction: Autopsy is an important tool for the evaluation of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Objectice: The aim of this study was to present our experience with autopsies of patients diagnosed with SARS-CoV-2 infection., Method: Clinical data, macroscopic and microscopic findings of consecutive postmortems of non-vaccinated SARS-CoV-2 patients are summarized. Lung samples were evaluated with SARS-CoV-2 nucleocapsid immunohistochemistry., Results: Autopsies were performed to determine the cause of death (n = 14), suspected tumours (n = 9) or due to legal obligation (n = 3). SARS-CoV-2 infection was verified by ante mortem (n = 22) and post mortem (n = 4) polymerase chain reaction. The mean duration of symptomatic disease was 12.9 days. Of 21 patients with COVID-19 pneumonia, 16 died of respiratory failure, 4 had additional bacterial pneumonia or Clostridioides difficile infection, and 1 developed hemorrhagic complication (n = 1). Other causes of death included disseminated malignancies (n = 3), coronary thrombosis (n = 1) and pulmonary embolism (n = 1). The affected lungs were heavy and had patchy red appearance. Exudative or proliferative phases of diffuse alveolar damage (DAD) were detected with atypical pneumocytes. Microthrombosis (n = 7), macrothrombosis (n = 5) and pulmonary embolism (n = 4) were frequent. The SARS-CoV-2 immunohistochemical reaction was positive in 38.5% of cases. All patients had co-morbidities, namely, hypertension (n = 17), atherosclerosis (n = 14), diabetes (n = 8), malignancies (n = 6), chronic obstructive pulmonary diseases (n = 4), obesity (n = 3) and immunosuppression after kidney transplantation (n = 3)., Conclusion: Fatal COVID-19 pneumonia occurred mostly in elderly males with co-morbidities. In the autopsy practice, the SARS-CoV-2 nucleocapsid immunohistochemical reaction may confirm the infectious etiology in the early phase of DAD. Orv Hetil. 2021; 162(45): 1791-1802.