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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.

Introduction: The extent of spread through air spaces (STAS) is less investigated among patients with lung adenocarcinoma who underwent sublobar resection. Therefore, we aimed to evaluate the extent of STAS semi-quantitatively, to assess its prognostic impact on overall survival (OS) and recurrence-free survival (RFS), and to investigate the reproducibility of this assessment. Methods: The number of tumour cell clusters and single tumour cells within air spaces was recorded in three different most prominent areas (200x field of view). The extent of STAS was categorized into three groups, and the presence of free tumour cluster (FTC) was recorded. Results: Sixty-one patients were included. Recurrence was more frequent with higher grade (p = 0.003), presence of lymphovascular invasion (p = 0.027), and presence of STAS of any extent (p = 0.007). In multivariate analysis, presence of FTC (HR: 5.89; 95% CI: 1.63–21.26; p = 0.005) and more pronounced STAS (HR: 7.46; 95% CI: 1.60–34.6; p = 0.01) had adverse impact on OS and RFS, respectively. Concerning reproducibility, excellent agreement was found among STAS parameters (ICC range: 0.92–0.94). Discussion: More extensive STAS is an unfavourable prognostic factor in adenocarcinomas treated with sublobar resection. As the evaluation of extent of STAS is reproducible, further investigation is required to gather more evidence.

At present, surgical strategies for breast cancer patients with2 lymph nodes (LN) involved differ from those with no or lower degree of nodal involvement. Preoperative assessment of the axilla is less sensitive in patients with lobular carcinoma (ILC) than patients with other histological tumour types.- A retrospective analysis of axillary staging by palpation, axillary ultrasound (AXUS) and AXUS-guided fine-needle aspiration cytology (FNAC) of 153 patients with ILC diagnosed and operated on between January 2013 and December 2020 was performed. Patients had either sentinel node biopsy or axillary lymph node dissection according to current practice. In period 1, patients had FNAC only when AXUS suggested nodal involvement (n = 106), and in period 2, all ILC patients had axillary FNAC (n = 47).- Of the factors associated with2LNs involvement, logistic regression suggested only AXUS/FNAC based staging as independent variable for all patients. Patients with AXUS-guided FNAC had a significantly higher proportion of true negative and lower proportion of true positive cases in the P2 period (0 vs 55% and 72% vs 11% for2 LNs involvement, respectively; both p 0.0001).- AXUS-guided FNAC of all ILC patients did not result in improved preoperative identification of patients with2 metastatic LNs but increased the false-negative rate of the assessment by producing false-negative results in patients who would not have undergone a biopsy due to negative AXUS findings.

Összefoglaló. Az urachus tumorai és egyéb betegségei ritkák. A 67 éves férfi anamnézisében ismétlődő húgyúti fertőzés szerepelt ciprofloxacinterápiával. Cisztoszkópia során a húgyhólyag felső részének másodlagos érintettségére utaló bullosus nyálkahártya képe mutatkozott. Az ezt követő CT-felvételek alapján az alsó medián hasfallal, húgyhólyaggal, belekkel összefüggő tumor iránydiagnózisát állították fel. A kivizsgálás során kialakuló ileus miatt Hartmann-műtétet végeztek, a tumoros jellegű elváltozás teljes és az érintett szervek részleges eltávolításával. A kórszövettani vizsgálat daganatos elváltozást nem talált, hasi, vélhetően urachuseredetű actinomycosist igazolt: erre az eredetre a lokalizáció és a tünetek közt szereplő köldökváladékozás alapján lehetett gondolni, annak ellenére, hogy urachusmaradványt szövettanilag nem sikerült igazolni a mikroabszcedáló gyulladás által érintett szövetekben. A betegnél amoxicillinterápia indult. Átmeneti, hólyag melletti vizeletcsorgást követően a beteg tünet- és panaszmentesen távozott a kórházból, de 13 nappal később a hasfali seb sterilnek véleményezett szétválása miatt ismét hospitalizálni kellett. Negatív nyomású sebkezelést követően sikerült a hasat ismét zárni. A beteg ismét tünetmentessé vált, és fenntartott antibiotikumkezelés mellett hagyta el a kórházat. Az urachuskörnyéki tumorszerű elváltozások között az actinomycosis lehetőségét is szem előtt kell tartani a differenciáldiagnosztikában. Orv Hetil. 2022; 163(4): 157–160. Summary. Tumours and other diseases of the urachus are rare. A 67-year-old male presented with a history of recurrent urinary tract infection and ciprofloxacin therapy. Cystoscopy suggested secondary involvement of the bullous upper bladder wall. The subsequent CT-based diagnosis was of a tumour infiltrating the lower median abdominal wall, the urinary bladder and bowels. Bowel obstruction developed and this led to partial resection of the involved organs along with a Hartmann’s procedure. Histology revealed no neoplastic conditions, but proved abdominal actinomycosis of probable urachal origin based on the location of the tumour-like lesion and umbilical discharge among the symptoms. Urachal remnants were not identified in the perivesical tissues involved by the microabscess forming inflammation. Amoxicillin therapy was initiated. After a temporary urine leakage from the bladder, the patient became symptomless and was emitted from hospital. After 13 days, he was readmitted because of abdominal wound disruption, which was treated with negative-pressure wound therapy before the abdomen could be closed. At the time of reporting, he is still on amoxicillin, and has become symptomless again. Actinomycosis should be considered in the differential diagnosis of mass lesions of the urachal region. Orv Hetil. 2022; 163(4): 157–160.

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. Summary. 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.

Context.— The International Collaboration on Cancer Reporting (ICCR), supported by major pathology and cancer organizations, aims at the standardization of evidence-based pathology reporting of different types of cancers, with the inclusion of all parameters deemed to be relevant for best patient care and future data collection. Lymph node metastasis is one of the most important prognostic factors in breast cancer. Objective.— To produce a histopathology reporting guide by a panel of recognized experts from the fields of pathology and surgery with elements deemed to be core (required) and noncore (recommended) to report when assessing regional lymph nodes of patients with breast cancer. Data Sources.— Published literature, previous guidelines/recommendations, and current cancer staging principles were the basis of the data set drafted by the expert panel. This was discussed in a series of teleconferences and email communications. The draft data set was then made available for public consultation through the ICCR Web site. After this consultation and ICCR ratification, the data set was finalized. Conclusions.— The ICCR has published a data set for the reporting of surgically removed lymph nodes (including sentinel lymph node biopsy, axillary lymph node dissection, targeted axillary surgery, and lymph node sampling specimens) for breast tumors. This is part of a series of 4 ICCR breast cancer–related data sets. It includes 10 core elements along with 2 noncore elements. This should allow for synoptic reporting, which is more precise, uniform, and complete than nonsynoptic reporting, and leads to improved patient outcomes.

Összefoglaló. Bevezetés: Az állcsonti cysták helytálló diagnosztikája a klinikai, radiológiai és patológiai leletek együttes értékelésével lehetséges. Korábbi munkánk során többször tapasztaltuk a klinikoradiopatológiai kommunikáció és korreláció hiányát, és ez olykor inadekvát diagnózisok felállításához vezetett. Célkitűzés: Célunk ezen kommunikációs probléma mértékének becslése és annak bemutatása, hogy ez a hiányosság hogyan befolyásolhatja a diagnosztikát. Módszer: Korábbi, más célú retrospektív elemzés újraértékelése történt a klinikai (radiológiai) adatközlés, a revízió kapcsán módosuló diagnózisok számszerűsítése céljából, valamint további 3 egyetemi patológiai intézet 10-10 anonimizált leletének vizsgálata az adatközlések vonatkozásában. Eredmények: 2 intézményben 85 odontogen cysta diagnózisakor csupán a betegek életkora, neme volt 100%-osan ismert. A lokalizációra vonatkozó adekvát információ 62%-ban, a méretre vonatkozó csupán 29%-ban fordult elő a szövettani kérőlapokon. Összességében a diagnózist segítő releváns információt csak 52%-ban adtak meg. Az utólagos klinikoradiopatológiai korrelációra törekvő revízió során 38/85 esetben (45%) módosult a végső diagnózis kisebb vagy nagyobb mértékben. A megküldött leletek alapján a klinikai/radiológiai adatok közlése Következtetés: Az odontogen tömlők precíz diagnosztikája mind a klinikai, mind a patológiai oldalról javítást igényel, amelynek egyik része az ilyen irányú képzés lehet. Orv Hetil. 2021; 162(12): 458–467. Summary. Introduction: Proper diagnosis of jaw cysts requires the parallel evaluation of clinical, radiological and histopathological findings. Lack of clinico-radio-pathological correlation can lead to inconsistent diagnoses. Objective: To evaluate the rate of lacking clinico-pathological communication and demonstrate how this may influence diagnostics. Method: Data of a former retrospective analysis were re-evaluated to quantify the lack of clinical data communicated to pathologists and estimate the rate of final diagnoses requiring alteration after review of all available clinical data. 10 anonymized reports on odontogenic cysts from 3 university pathology departments each were analysed for the lack of relevant clinical information. Results: Only the age and gender of patients were documented in 100% for 85 jaw cysts diagnosed in 2 departments of pathology. Adequate information about cyst localization and size were communicated in 62% and 29%, respectively. Overall, information relevant to the diagnosis was given in 52% of the cases. Revision based on clinico-radio-pathological correlation led to alterations of the diagnosis in 38/85 cases (45%). Based on reports from other institutions, the communication of clinical data is estimated to be between versus radicular cyst; a botryoid odontogenic cyst. Conclusion: Proper diagnosis of jaw cysts requires improvements from both pathological and clinical sides, and could probably be improved through education. Orv Hetil. 2021; 162(12): 458–467.

Összefoglaló. Bevezetés: Napjainkban az őrszemnyirokcsomó felkeresésének legelterjedtebb módszere a radioizotópos és kék festékes kettős jelölés, emellett azonban több más jelölés is alkalmazható. Az indociánzöld-fluoreszcencia ígéretes nyirokút-térképezési módszer, mely a találati arányát tekintve – irodalmi adatok alapján – összevethető a radioizotópos módszerrel. Módszer: Osztályunkon 2020. 03. 31. és 2020. 04. 15. között 10, emlőrák miatt operált betegünknél alkalmaztuk az indociánzöld és a kék festékes kettős jelölés módszerét az őrszemnyirokcsomó felkeresésére. Eredmények: A 10 operált betegünknél összesen 17 őrszemnyirokcsomót azonosítottunk és távolítottunk el. 16 őrszemnyirokcsomó jól festődött indociánzölddel (találati arány: 0,94; 95%-os konfidenciaintervallum [CI ]: 0,73–0,99), míg kék festékkel 9 jelölődött (találati arány: 0,53; 95%-os CI: 0,31–0,74). A szövettani feldolgozás során összesen 2 őrszemnyirokcsomó bizonyult áttétesnek, ezek közül 1 kék és fluoreszcens volt, 1 pedig csak kék festékkel jelölődött. Következtetés: Kezdeti, kis esetszámnál nyert tapasztalataink alapján az indociánzöld jelölés emlőrák során végzett őrszemnyirokcsomó-biopszia esetén jól használható kettős jelölési módszer részeként, kék festékkel kiegészítve. A módszer találati aránya, valamint fals negatív aránya irodalmi adatok alapján nem különbözik szignifikánsan a radioizotópos jelölés módszerétől. Orv Hetil. 2021; 162(8): 293–297. Summary. Introduction: The current practice in sentinel lymph node biopsy for breast cancer is the radioisotope and blue dye dual labelling technique, however, other mapping methods are also available. Indocyanine green fluorescence is one of the best alternatives of the standard technique, with detection rates comparable to those of the radioisotope method. Method: Between 31. 03. 2020 and 15. 04. 2020, a total of 10 sentinel lymph node biopsies for breast cancer were performed using the indocyanine green fluorescence and blue dye dual technique. Results: 17 sentinel lymph nodes were detected and removed in total, from which 16 showed explicit fluorescence activity (detection rate: 0.94; 95% confidence interval [CI]: 0.73–0.99), whilst 9 where blue (detection rate: 0.53; 95% CI: 0.31–0.74). During histopathological examination, 2 sentinel lymph nodes proved to be metastatic, from which 1 was fluorescent and blue, the other was blue only. Conclusion: Regarding our early experience based on a small number of patients, indocyanine green fluorescence, used together with blue dye as part of a dual technique, is a usable method for sentinel lymph node mapping. Based on data from the literature, the detection rate and the false-negative rate of the indocyanine green fluorescence method shows no significant difference from the radioisotope mapping technique. Orv Hetil. 2021; 162(8): 293–297.

Syntaxin-1 (STX1) is a recently described highly sensitive and specific neuroendocrine marker. We evaluated the applicability of STX1 as an immunohistochemical marker in pulmonary neuroendocrine neoplasms (NENs). We compared STX1 with established neuroendocrine markers, including insulinoma-associated protein 1 (INSM1). Typical carcinoids (n = 33), atypical carcinoids (n = 7), small cell lung carcinomas ([SCLCs] n = 30), and large cell neuroendocrine lung carcinomas (n = 17) were immunostained using tissue microarray for STX1, chromogranin A, synaptophysin, CD56, and INSM1. Eighty-four of eighty-seven (96.5%) NENs showed STX1 positivity. Carcinoids and LCNECs typically presented a combined strong membranous and weak cytoplasmic staining pattern; cytoplasmic expression was predominately observed in SCLCs. The sensitivity of STX1 was 90% in SCLCs and 100% in typical carcinoids, atypical carcinoids, and large cell neuroendocrine lung carcinomas. The overall sensitivity of STX1 in pulmonary NENs was 96.6%, and the sensitivity of the other markers was as follows: chromogranin A (85.2%), synaptophysin (85.2%), CD56 (92.9%), and INSM1 (97.7%). STX1 was found to be an excellent neuroendocrine marker of pulmonary NENs, with sensitivity and specificity surpassing that of classic markers. We propose a panel of STX1 and INSM1 for the routine immunohistochemical workup of pulmonary NENs.

Aims: Triple-negative breast cancer (TNBC) represents a specific group that lacks the expression of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor-2 and might also lack the expression other breast markers like GATA3, mammaglobin (MG), GCDFP15 (growth cystic disease fluid protein 15), and NYBR1; when this occurs, proving the breast origin of a metastasis is a challenging task. In the present study, we assessed the added value of SOX10 immunohistochemistry to known GATA3, MG, GCDFP15, and NY-BR-1 statuses in a series of CK5-positive primary TNBCs. Methods: Tissue microarrays were made from the formalin-fixed and paraffin-embedded blocks of 120 TNBCs, and 3-4-mm-thick sections were immunostained for SOX10. The cut-off for a positive reaction was at least 10% of tumor cells staining. Results: In our cohort, SOX10 positivity was seen in 82/119 cases, 61, 74, 76, and 82 all of which were GATA3, MG, GCDFP15, and NY-BR-1 negative, respectively. Of the SOX10 negative cases, 12 stained with at least another breast marker. Nevertheless, 25/119 (21%) cases remained negative with all markers assessed. Discussion: SOX10 proved to be the most commonly positive breast marker in our CK5 expressing TNBCs, but the other markers also had some additive value to SOX10.

Odontogenic keratocysts (OKCs) are developmental cysts of the jaws that require proper diagnosis due to their potential for local aggressive growth and recurrences. OKCs have a typical parakeratotic epithelium demonstrating transepithelial cytokeratin 17 (CK17) and basal bcl2 staining on immunohistochemistry (IHC), which distinguishes them from other common jaw cysts. Secondary to inflammation, the epithelial lining may be altered and loses the typical IHC phenotype. The aim of the present study was to analyse a series of consecutive jaw cysts for their expression of CK17 and bcl2 and assess how these IHC stains may help in their diagnosis. All cysts were retrospectively assessed for available clinical, radiological and pathological findings and diagnoses were revised whenever needed. 85 cysts from 72 patients were collected from two departments. The series had 21 OKCs, the remaining non-OKCs included radicular/residual, dentigerous, paradental, lateral periodontal, botryoid odontogenic cysts. OKCs with typical epithelium showed the typical IHC phenotype, which was generally lost in inflammation-associated altered epithelium. Contrarily to earlier descriptions, a wide variety of CK17 positivity was seen in the majority of non-OKCs, including focal transepithelial staining. Basal bcl2 staining was also seen in 16 non-OKCs. These stainings were never as strong in intensity as seen in OKCs. One case was histopathologically identified as OKC due to focally maintained IHC profile. CK17 and bcl2 IHC may help in the diagnosis of OKCs, but must be interpreted with caution and is not a yes or no tool in the diagnostic puzzle. Electronic supplementary material The online version of this article (10.1007/s12253-020-00866-4) contains supplementary material, which is available to authorized users.

Triple-negative breast cancer (TNBC) represents a heterogenous subtype of breast cancer with generally poor prognosis. The prediction of its prognosis remains essential to clinicians in their therapeutical decision-making process. The aim of our study was to compare the validity of three multivariable analysis derived prognostic systems, the Nottingham Prognostic Index (NPI), PREDICT and PrognosTILs (a prognosticator including tumor infiltrating lymphocytes, TILs) in a series of TNBCs. Patients operated on with TNBC at the Department of Surgery, Bács-Kiskun County Teaching Hospital, Kecskemét between 2005 and 2016 were included. Clinical and pathological parameters and follow-up data were collected from medical charts. TILs were assessed retrospectively, following international recommendations. Estimated survivals of PrognosTILs, PREDICT and NPI were recorded and compared with real outcomes. Altogether 136 patients were included in this retrospective study. In univariate Cox analysis, type of surgery, pT, pN, stage, NPI and type of adjuvant therapy were the significant prognostic variables. The multivariate Cox-regression strengthened that NPI is an independent predictor of overall and disease-free survivals in TNBCs. The NPI, PREDICT and PrognosTILs could be compared directly only in a ROC curve analysis: the sensitivities and specificities of these predicting systems are rather similar with area under the curve values falling between 0.7 and 0.8, and NPI having the highest values. Our findings reflect the diverse prognosis of TNBC and highlight the difficulties of predicting its outcome. None of the three multivariable prognosticators is inferior to the others, the NPI can reliably be used for TNBCs.

Absztrakt: Bevezetés: Közleményünkben ismertetjük a 2013–2019 közötti időszakban osztályunkon minimálisan invazív módszerrel (video-assisted thoracic surgery – VATS) elvégzett tüdőlobectomiák során szerzett tapasztalatainkat, eredményeinket. Betegek és módszer: 2013. november 1. és 2019. június 30. közötti időszakban osztályunkon 112 VATS lobectomiát végeztünk. A műtéteket izolált intubációval altatott betegeken elülső behatolás technikával végeztük. 98 betegnél malignus, 9 betegnél benignus elváltozás miatt történtek a műtétek. 10 esetben a műtét utáni szövettani diagnózis metasztázis volt. 78 férfi és 34 nőbetegen végeztük a műtéteket. A betegek átlagéletkora 60,5 (42–63) év volt. Az eltávolított lebenyek megoszlása a következő volt: bal felső: 5, bal alsó: 36, Jobb felső: 15, középső: 11, jobb alsó: 44, pulmonectomia: 1. Eredmények: Műtéti halálozás nem volt. Konverzióra 3 alkalommal kényszerültünk. Az átlagos műtéti idő 150 (70–215) perc volt. Reoperációt 2 betegnél végeztünk, vérzés, légáteresztés miatt. A 112 műtét során 88 betegnél primer tüdőrák, 9 betegnél jóindulatú elváltozás/gyulladás miatt történt a műtét. 10 esetben más szerv tumora miatti metasztázis miatt végeztük a beavatkozásokat. A primer tüdőrák miatt végzett műtétek stádium szerinti megoszlása a szövettani eredmények alapján a következő volt: I.a: 57, I.b: 22, II.a: 6, II.b: 3. A szövettani típus szerinti megoszlás: adenocarcinoma: 52, laphámrák: 23, kissejtes carcinoma: 2, nagysejtes carcinoma: 5, carcinoid: 6 volt. Következtetés: Osztályunkon a szükséges tanuló időszak után a VATS lobectomia megfelelő indikáció szerint rutin műtéti eljárássá vált. Jelenleg mellkasi műtéteink 65%-a, a lobectomiák több mint 50%-a VATS technikával történik. Eredményeink az országos és az irodalmi adatoknak megfelelnek.

The spread through air spaces (STAS) has a main role in local recurrence of stage I lung adenocarcinomas (LAs), therefore its presence might question sublobar resection as a therapeutic option. The aim of our study was to evaluate the distribution of STAS in stage I LAs, to stratify patients according to local recurrence and to identify a group of patients who might be suitable for sublobar surgery. Patients resected with LA were included. The presence of STAS was recorded on hematoxylin eosin stained slides and clinicopathological data were obtained from medical charts. Overall survival (OS) and disease-free survival (DFS) were registered. Statistical methods included Kruskal-Wallis tests, Kaplan-Meier analyses, log-rank tests and Cox-regressions. 292 patients were included. STAS was identified in 38.7% and 95.7% of micropapillary carcinomas showed STAS. Significant correlation was found between STAS and high-grade patterns. Significant differences were found between OS and DFS estimates of STAS0 and STAS1 cases (5-y-OS: 80.0% vs. 68.4%; 5-y-DFS: 71.1% vs. 57.1%). The presence of STAS was associated with unfavorable prognosis in low and intermediate architectural grades, but not in high-grade. Multivariate analysis revealed that architectural grade (HR(OS):2.09; HR(DFS):1.52) and STAS (HR(OS):1.51; HR(DFS):1.48) were independent prognostic markers in stage I LA. Architectural grade combined with STAS was superior to other prognostic grades. The combination of architectural grade and STAS proved to be a prognostic factor that is superior to previously introduced grading systems. Patients having low and intermediate grade LAs without STAS might be eligible for sublobar resection. Electronic supplementary material The online version of this article (10.1007/s12253-020-00855-7) contains supplementary material, which is available to authorized users.

Absztrakt: Bevezetés: Hohenberger 2009-ben a totális mezorectális excízió (TME) elvét átültette a kolonsebészetbe, és az új műtétet komplett mezokólikus excíziónak nevezte el (CME). A CME lényege az érintett kolonszakasz eltávolítása a viszcerális peritoneum sérülése nélkül az ellátó erek centrális lekötésével a viszcerális és parietális fascia közötti embrionális rétegben preparálva. Ez nyitottan és laparoszkóppal is végezhető. Célkitűzés: Válogatás nélküli beteganyagon meggyőződni arról, hogy elvégezhető-e a CME laparoszkóppal hasonló eredménnyel, mint nyílt műtét során. Eredmények: 2016. 09. 01. és 2019. 06. 30. között 156 műtét történt jobb oldali malignus vastagbéldaganat miatt. 143 esetben végeztünk kuratív reszekciót, 63 férfi és 80 nőbetegnél. Az átlagéletkor férfiaknál 71,5 évnek, míg nőknél 73 évnek bizonyult. 84 műtétet laparoszkóppal, 59 műtétet nyitottan végeztünk. Konvencionális műtét 56 esetben, míg CME 87 esetben történt. Az átlagos kolonhossz konvencionális műtétnél 22,34 cm, míg CME esetén 24,97 cm volt (p = 0,18). A nyirokcsomók átlagos száma a hagyományos műtétnél 15,4, míg CME esetén 16,9 volt (p = 0,24). Az átlagos műtéti idő nyitott műtétnél 111, míg laparoszkópos műtétnél 136 perc volt (p = 0,0014), az átlagos ápolási idő pedig a szövődményes esetek nélkül a nyitott csoportban 7,47, míg a laparoszkópos csoportban 5,65 napnak bizonyult (p = 0,0004). Megbeszélés: A korai eredmények alapján az mondható, hogy laparoszkóppal is elvégezhető a műtét hasonló eredményekkel, valamivel rövidebb ápolási idővel.

Absztrakt: Bevezetés: Az őrszemnyirokcsomó-biopszia (SNB) bevezetésével a hónalji blokkdissectiók (ABD) aránya jelentősen csökkent. Az extracapsularis terjedés (ECT) jelenléte az őrszemnyirokcsomókban azonban bizonytalan jelentőségű. Módszer: Retrospektív vizsgálatunkban 635 T1-T2N0M0 klinikai stádiumú emlőrákos beteg adatait elemeztük, akiknél SNB-t végeztünk 2014 és 2018 között. Az esetek 25%-ában (158 beteg) igazolódott őrszemnyirokcsomó- (SN) áttét. Az SN-áttétes betegeinket két csoportra osztottuk aszerint, hogy igazolódott-e az SN-ben ECT, vagy nem. Vizsgálatunk fő célja az volt, hogy elemezzük a masszív (>3) nyirokcsomóáttét arányát az ECT-negatív és -pozitív betegeknél, akiknél ABD történt. Eredmények: Az ECT-negatív csoportba 91/158 beteg (58%), míg az ECT-pozitívba 67/158 beteg (42%) került. Az ECT-negatív betegek 42%-ánál, az ECT-pozitívok 69%-ánál történt ABD. Nem találtunk szignifikáns különbséget a következő változókban: életkor, tumorméret, szövettani típus, grade és lymphovascularis invázió jelenléte, valamint a hormon- és HER2-receptorok arányai között. Amennyiben az SN-ben nem igazolódott ECT, de ABD történt, akkor a pN1-érintettség aránya 82%-os, míg a pN2+pN3 aránya 18%-os volt. Az ECT-pozitív ABD-s csoportban a pN1-érintettség 60%-os volt, míg a pN2+pN3 arány 40%-osnak bizonyult, amely az ECT-negatív csoport kétszerese; ez a különbség szignifikáns (p = 0,038). Következtetések: Az ECT a hónalj masszív nyirokcsomó-érintettség prediktora, ezért ha ECT igazolódik, akkor ez egy olyan tényező, amelyet az ABD-ről való döntésben figyelembe kell venni.

Absztrakt: A rosszul differenciált neuroendocrin tumorok közé tartozik a jól ismert kissejtes carcinoma, valamint a ritka nagysejtes neuroendocrin carcinoma. A két daganat hasonló morfológiai képe, a betegség agresszív viselkedése, illetve a vitatott kezelési ajánlások miatt a diagnózis felállítása és a terápia megválasztása multidiszciplináris megközelítést igényel. Bal oldali fejfájás, hányinger, homályos látás miatt került felvételre az 52 éves nőbeteg. A képalkotó vizsgálat bal occipitalisan, illetve a kisagyban metasztázisra gyanús képletet ábrázolt. Az idegsebészeten mindkét tumort eltávolították. A szövettani vizsgálat neuroendocrin carcinoma agyi áttétét igazolta. A mellkas CT-vizsgálata a bal tüdőben kontrasztanyagot halmozó képletet igazolt. A bronchoszkópos biopsziás minta nagysejtes neuroendocrin carcinomát kórismézett. Posztoperatív koponyabesugárzást és a kissejtes tüdőrák protokollja szerinti kemoterápiát alkalmaztak. Rövidesen progresszió és atelectasia miatt mellkasbesugárzás kezdődött, amelyet ismételt agyi áttétek miatt meg kellett szakítani. A kemoterápiát a nem kissejtes tüdőrák protokollja alapján folytatták. Három hónap után mellkasi progresszió, kisagyi és csontáttétek jelentkeztek. A beteg 14 hónap kezelés után elhunyt. A nagysejtes neuroendocrin carcinoma rossz prognózisú, az esetek 25–50%-ában agyi áttétet adó tüdődaganat. A korai stádiumú nagysejtes neuroendocrin carcinoma esetében a sebészeti kezelés szerepe elsődleges, az adjuváns kemoterápia mérlegelendő. A kemoterápia során a nem kissejtes tüdőrák protokollja az elfogadott, de az irodalmi adatok alapján a kissejtes carcinoma kezelési sémája is mérlegelhető. Orv Hetil. 2020; 161(8): 313–319.

Ductal carcinoma in situ of the breast is a non-obligate precursor of invasive breast cancer, and at its lower risk end might not need treatment, a hypothesis tested in several currently running randomized clinical trials. This review describes the heterogeneity of grading ductal carcinoma in situ (DCIS). First it considers differences between low and high grade DCIS, and then it looks at several grading schemes and highlights how different these are, not only in the features considered for defining a given grade but also in their wording of a given variable seen in the grade in question. Rather than being fully comprehensive, the review aims to illustrate the inconsistencies. Reproducibility studies on grading mostly suggestive of moderate agreement on DCIS differentiation are also illustrated. The need for a well structured, more uniform and widely accepted language for grading DCIS is urged to avoid misunderstanding based misclassifications and improper treatment selection. Electronic supplementary material The online version of this article (10.1007/s12253-019-00760-8) contains supplementary material, which is available to authorized users.

Radiation-induced heart disease (RIHD) is a potential late side-effect of thoracic radiotherapy resulting in left ventricular hypertrophy (LVH) and fibrosis due to a complex pathomechanism leading to heart failure. Angiotensin-II receptor blockers (ARBs), including losartan, are frequently used to control heart failure of various etiologies. Preclinical evidence is lacking on the anti-remodeling effects of ARBs in RIHD, while the results of clinical studies are controversial. We aimed at investigating the effects of losartan in a rat model of RIHD. Male Sprague-Dawley rats were studied in three groups: (1) control, (2) radiotherapy (RT) only, (3) RT treated with losartan (per os 10 mg/kg/day), and were followed for 1, 3, or 15 weeks. At 15 weeks post-irradiation, losartan alleviated the echocardiographic and histological signs of LVH and fibrosis and reduced the overexpression of chymase, connective tissue growth factor, and transforming growth factor-beta in the myocardium measured by qPCR; likewise, the level of the SMAD2/3 protein determined by Western blot decreased. In both RT groups, the pro-survival phospho-AKT/AKT and the phospho-ERK1,2/ERK1,2 ratios were increased at week 15. The antiremodeling effects of losartan seem to be associated with the repression of chymase and several elements of the TGF-β/SMAD signaling pathway in our RIHD model.

Invasive lobular breast carcinoma (ILC) is the second most common breast carcinoma (BC) subtype and is mainly driven by loss of E-cadherin expression. Correct classification of BC as ILC is important for patient treatment. This study assessed the degree of agreement among pathologists for the diagnosis of ILC. Two sets of hormone receptor (HR)-positive/HER2-negative BCs were independently reviewed by participating pathologists. In set A (61 cases), participants were provided with hematoxylin/eosin (HE)-stained sections. In set B (62 cases), participants were provided with HE-stained sections and E-cadherin immunohistochemistry (IHC). Tumor characteristics were balanced. Participants classified specimens as non-lobular BC versus mixed BC versus ILC. Pairwise inter-observer agreement and agreement with a pre-defined reference diagnosis were determined with Cohen's kappa statistics. Subtype calls were correlated with molecular features, including CDH1/E-cadherin mutation status. Thirty-five pathologists completed both sets, providing 4,305 subtype calls. Pairwise inter-observer agreement was moderate in set A (median κ = 0.58, interquartile range [IQR]: 0.48-0.66) and substantial in set B (median κ = 0.75, IQR: 0.56-0.86, p

Histological grade is one of the most important prognosticators of breast cancer which is available for nearly all cases. It also makes part of several multivariable analysis derived combined prognostic profiles despite concerns about its reproducibility. The aims included a reproducibility study of grading in the light of a recently described statistical approach, ONEST (Observers Needed to Evaluate Subjective Tests) and review earlier reproducibility studies in the light of the ONEST analysis. Nine pathologists reviewed 50 core needle biopsies and 50 slides from different excision specimens and recorded the scores for gland (tubule) formation, nuclear pleomorphism and mitotic activity as well as histological grade. Overall percent agreement, Fleiss kappa and the intraclass correlation coefficient (ICC) were used for the analysis of reproducibility. ONEST data and curves were generated from 100 random permutations of the participants. ONEST suggested a minimum of 4 observers for the reliable evaluation of reproducibility for both the scored components and grade in either type of specimen. Our results suggested moderate or moderate to good reproducibility of grading (kappa values of 0.51 for excisions, and 0.54 for biopsies and ICCs of 0.70 and 0.69, respectively) with gland formation being the most and nuclear pleomorphism the worst consistently evaluated feature. In studies with sufficient participants (at least 4) and non-pairwise comparisons in the analysis, the reproducibility of histological grading is fair to moderate, whereas studies with fewer participants or pairwise kappa analysis suggest moderate to almost prefect agreement of the results. ONEST is a valuable complementation of reproducibility analyses.

Background Metabolic syndrome (MetS) refers to a cluster of co-existing cardio-metabolic risk factors, including visceral obesity, dyslipidemia, hyperglycemia with insulin resistance, and hypertension. As there is a close link between MetS and cardiovascular diseases, we aimed to investigate the sex-based differences in MetS-associated heart failure (HF) and cardiovascular response to regular exercise training (ET). Methods High-fat diet-fed male and female APOB-100 transgenic (HFD/APOB-100, 3 months) mice were used as MetS models, and age- and sex-matched C57BL/6 wild-type mice on standard diet served as healthy controls (SD/WT). Both the SD/WT and HFD/APOB-100 mice were divided into sedentary and ET groups, the latter running on a treadmill (0.9 km/h) for 45 min 5 times per week for 7 months. At month 9, transthoracic echocardiography was performed to monitor cardiac function and morphology. At the termination of the experiment at month 10, blood was collected for serum low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol measurements and homeostatic assessment model for insulin resistance (HOMA-IR) calculation. Cardiomyocyte hypertrophy and fibrosis were assessed by histology. Left ventricular expressions of selected genes associated with metabolism, inflammation, and stress response were investigated by qPCR. Results Both HFD/APOB-100 males and females developed obesity and hypercholesterolemia; however, only males showed insulin resistance. ET did not change these metabolic parameters. HFD/APOB-100 males showed echocardiographic signs of mild HF with dilated ventricles and thinner walls, whereas females presented the beginning of left ventricular hypertrophy. In response to ET, SD/WT males developed increased left ventricular volumes, whereas females responded with physiologic hypertrophy. Exercise-trained HFD/APOB-100 males presented worsening HF with reduced ejection fraction; however, ET did not change the ejection fraction and reversed the echocardiographic signs of left ventricular hypertrophy in HFD/APOB-100 females. The left ventricular expression of the leptin receptor was higher in females than males in the SD/WT groups. Left ventricular expression levels of stress response-related genes were higher in the exercise-trained HFD/APOB-100 males and exercise-trained SD/WT females than exercise-trained SD/WT males. Conclusions HFD/APOB-100 mice showed sex-specific cardiovascular responses to MetS and ET; however, left ventricular gene expressions were similar between the groups except for leptin receptor and several stress response-related genes., Highlights Both HFD/APOB-100 males and females developed obesity and hypercholesterolemia; however, only males presented insulin resistance. Exercise training did not change these metabolic parameters significantly.HFD/APOB-100 males showed echocardiographic signs of mild heart failure with thinner walls and dilated ventricles, whereas females developed a starting left ventricular hypertrophy assessed by echocardiography and histology.In response to exercise training, SD/WT males developed increased left ventricular volumes, and females presented physiologic hypertrophy.Exercise-trained HFD/APOB-100 males presented worsening heart failure with reduced ejection fraction. On the contrary, exercise-trained HFD/APOB-100 females reversed the echocardiographic signs of left ventricular hypertrophy.Sex, metabolic syndrome, and exercise training alter the gene expression pattern of the myocardium, which may be involved in the development of sex-specific cardiac alterations in the state of metabolic syndrome or to exercise training.

Uremic cardiomyopathy is characterized by diastolic dysfunction (DD), left ventricular hypertrophy (LVH), and fibrosis. Angiotensin-II plays a major role in the development of uremic cardiomyopathy via nitro-oxidative and inflammatory mechanisms. In heart failure, the beta-3 adrenergic receptor (β3-AR) is up-regulated and coupled to endothelial nitric oxide synthase (eNOS)-mediated pathways, exerting antiremodeling effects. We aimed to compare the antiremodeling effects of the angiotensin-II receptor blocker losartan and the β3-AR agonist mirabegron in uremic cardiomyopathy. Chronic kidney disease (CKD) was induced by 5/6th nephrectomy in male Wistar rats. Five weeks later, rats were randomized into four groups: (1) sham-operated, (2) CKD, (3) losartan-treated (10 mg/kg/day) CKD, and (4) mirabegron-treated (10 mg/kg/day) CKD groups. At week 13, echocardiographic, histologic, laboratory, qRT-PCR, and Western blot measurements proved the development of uremic cardiomyopathy with DD, LVH, fibrosis, inflammation, and reduced eNOS levels, which were significantly ameliorated by losartan. However, mirabegron showed a tendency to decrease DD and fibrosis; but eNOS expression remained reduced. In uremic cardiomyopathy, β3-AR, sarcoplasmic reticulum ATPase (SERCA), and phospholamban levels did not change irrespective of treatments. Mirabegron reduced the angiotensin-II receptor 1 expression in uremic cardiomyopathy that might explain its mild antiremodeling effects despite the unchanged expression of the β3-AR.

Stromal tumour infiltrating lymphocytes (sTILs) are a strong prognostic marker in triple negative breast cancer (TNBC). Consistency scoring sTILs is good and was excellent when an internet-based scoring aid developed by the TIL-WG was used to score cases in a reproducibility study. This study aimed to evaluate the reproducibility of sTILs assessment using this scoring aid in cases from routine practice and to explore the potential of the tool to overcome variability in scoring. Twenty-three breast pathologists scored sTILs in digitized slides of 49 TNBC biopsies using the scoring aid. Subsequently, fields of view (FOV) from each case were selected by one pathologist and scored by the group using the tool. Inter-observer agreement was good for absolute sTILs (ICC 0.634, 95% CI 0.539–0.735, p &lt, 0.001) but was poor to fair using binary cutpoints. sTILs heterogeneity was the main contributor to disagreement. When pathologists scored the same FOV from each case, inter-observer agreement was excellent for absolute sTILs (ICC 0.798, 95% CI 0.727–0.864, p &lt, 0.001) and good for the 20% (ICC 0.657, 95% CI 0.561–0.756, p &lt, 0.001) and 40% (ICC 0.644, 95% CI 0.546–0.745, p &lt, 0.001) cutpoints. However, there was a wide range of scores for many cases. Reproducibility scoring sTILs is good when the scoring aid is used. Heterogeneity is the main contributor to variance and will need to be overcome for analytic validity to be achieved.

Introduction: A subset of breast neoplasia is characterized by features of neuroendocrine differentiation. Positivity for Neuroendocrine markers by immunohistochemistry is required for the diagnosis. Sensitivity and specificity of currently used markers are limited; based on the definitions of WHO Classification of Tumours, 5th edition, about 50% of breast tumors with features of neuroendocrine differentiation express chromogranin-A and 16% express synaptophysin. We assessed the applicability of two novel markers, syntaxin-1 and insulinoma-associated protein 1 (INSM1) in breast carcinomas.Methods: Hypercellular (Type B) mucinous carcinomas, solid papillary carcinomas, invasive carcinomas of no special type with neuroendocrine features and ductal carcinomas in situ of neuroendocrine subtype were included in our study. The immunohistochemical panel included chromogranin A, synaptophysin, CD56, syntaxin-1 and INSM1. The specificity of syntaxin-1 and INSM1 was determined using samples negative for chromogranin A, synaptophysin and CD56.Results: The sensitivity of syntaxin-1 was 84.7% (50/59), with diffuse positivity in more than 60% of the cases. Syntaxin-1 also had an excellent specificity (98.1%). Depending on the definition for positivity, the sensitivity of INSM1 was 89.8% (53/59) or 86.4% (51/59), its specificity being 57.4% or 88.9%. The sensitivities of chromogranin A, synaptophysin and CD56 were 98.3, 74.6 and 22.4%, respectively.Discussion: Syntaxin-1 and INSM1 are sensitive and specific markers of breast tumors with neuroendocrine features, outperforming chromogranin A and CD56. We recommend syntaxin-1 and INSM1 to be included in the routine neuroendocrine immunohistochemical panel.

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.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.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.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).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.

Simple Summary Invasive lobular breast cancer (ILC) is a special type of breast cancer (BC) that was first described in 1941. The diagnosis of ILC is made by microscopy of tumor specimens, which reveals a distinct morphology. This review recapitulates the developments in the microscopic assessment of ILC from 1941 until today. We discuss different concepts of ILC, provide an overview on ILC variants, and highlight advances which have contributed to a better understanding of ILC as a special histologic spectrum of tumors. Abstract Invasive lobular breast cancer (ILC) is the most common special histological type of breast cancer (BC). This review recapitulates developments in the histomorphologic assessment of ILC from its beginnings with the seminal work of Foote and Stewart, which was published in 1941, until today. We discuss different concepts of ILC and their implications. These concepts include (i) BC arising from mammary lobules, (ii) BC growing in dissociated cells and single files, and (iii) BC defined as a morpho-molecular spectrum of tumors with distinct histological and molecular characteristics related to impaired cell adhesion. This review also provides a comprehensive overview of ILC variants, their histomorphology, and differential diagnosis. Furthermore, this review highlights recent advances which have contributed to a better understanding of the histomorphology of ILC, such as the role of the basal lamina component laminin, the molecular specificities of triple-negative ILC, and E-cadherin to P-cadherin expression switching as the molecular determinant of tubular elements in CDH1-deficient ILC. Last but not least, we provide a detailed account of the tumor microenvironment in ILC, including tumor infiltrating lymphocyte (TIL) levels, which are comparatively low in ILC compared to other BCs, but correlate with clinical outcome. The distinct histomorphology of ILC clearly reflects a special tumor biology. In the clinic, special treatment strategies have been established for triple-negative, HER2-positive, and ER-positive BC. Treatment specialization for patients diagnosed with ILC is just in its beginnings. Accordingly, ILC deserves greater attention as a special tumor entity in BC diagnostics, patient care, and cancer research.