The More Extensive the Spread through Air Spaces, the Worse the Prognosis Is: Semi-Quantitative Evaluation of Spread through Air Spaces in Pulmonary Adenocarcinomas

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

Proposal of a grading system for squamous cell carcinoma of the lung — the prognostic importance of tumour budding, single cell invasion, and nuclear diameter

The prognostic markers of lung squamous cell carcinoma (LSCC) are less investigated. The aim of our study was to evaluate tumour budding (TB), minimal cell nest size, nuclear diameter (ND), and spread through air spaces (STAS) among patients with resected LSCC, semi-quantitatively. Furthermore, we aimed to identify a grading system for the best prognostic stratification of LSCC. Patients who underwent surgical resection at the Department of Surgery, University of Szeged between 2010 and 2016 were included. Follow-up data were collected from medical charts. Morphological characteristics were recorded from histologic revision of slides. Kaplan-Meier analysis, log rank test and Cox proportional-hazards model, ROC curve analysis, and intraclass correlation were utilised. Altogether 220 patients were included. In univariate analysis, higher degree of TB, infiltrative tumour border, larger ND, the presence of single cell invasion (SCI) and STAS were associated with adverse prognosis. Based on our results, we proposed an easily applicable grading scheme focusing on TB, ND, and SCI. In multivariate analysis, the proposed grading system (p OS< 0.001, p RFS< 0.001) and STAS (p OS= 0.008, p RFS< 0.001) were independent prognosticators. Compared to the previously introduced grading systems, ROC curve analysis revealed that the proposed grade had the highest AUC values (AUCOS: 0.83, AUCRFS: 0.78). Each category of the proposed grading system has good (ICC: 0.79–0.88) reproducibility. We validated the prognostic impact of TB, SCI, ND, and STAS in LSCC. We recommend a reproducible grading system combining TB, SCI, and ND for proper prognostic stratification of LSCC patients. Further research is required for validation of this grading scheme. © 2023, The Author(s)

TRPS1 expression in cytokeratin 5 expressing triple negative breast cancers, its value as a marker of breast origin

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

Emlőrákok TNM-8 szerinti anatómiai és prognosztikai stádiumainak retrospektív vizsgálata elhunyt, valaha emlőrákos betegek adatai alapján | Evaluation of anatomic and prognostic stages of breast cancer according to the 8th edition of the TNM staging system – Retrospective analysis based on data from deceased patients once diagnosed with breast cancer

Absztrakt: Bevezetés: A tumor-nodus-metastasis (TNM) alapú stádiumbesorolás új, nyolcadik változata a hagyományos T, N és M kategóriákon alapuló anatómiai stádium mellett egy biomarkereket figyelembe vevő prognosztikai stádiumot is definiált emlőrákban. Célkitűzés: A nyolcadik stádiumbesorolásban figyelembe vett prognosztikus változók, valamint az anatómiai és prognosztikai stádiumok megoszlásának vizsgálata elhunyt, de korábban emlőrákkal diagnosztizált beteganyagban a teljes túlélés alapján. Módszer: Retrospektív vizsgálatunkba a 2010 és 2015 között a Bács-Kiskun Megyei Kórházban műtött, reszekciós mintából kórismézett, dokumentált okok miatt elhunyt emlőrákos betegeket vontuk be. A prognosztikus markerek adatait a betegek kórszövettani leleteiből nyertük. Statisztikai modelljeink az egyutas ANOVA, a Dunn-féle post hoc teszt, valamint a Kaplan–Meier-analízis voltak. Eredmények: 303 beteg adatait vizsgálva a legtöbb prognosztikus tényezőben, így az anatómiai és prognosztikai stádiumok vonatkozásában is, szignifikáns különbséget találtunk a tumoros halálozás (n = 168) és a nem tumoros halálozás (n = 135) csoportja között. Ugyancsak szignifikáns különbségeket tudtunk kimutatni egyes pT- és pN-kategóriák, gradusok, ösztrogénreceptor-státuszok között az ötéves teljes túlélés alapján. Vizsgálatunk eredményei szerint az I. és II. stádium kivételével, valamennyi további anatómiai és prognosztikai stádium különbözik a többitől túlélés tekintetében (p<0,001). Kiemelendő, hogy az egységes IV. stádiumú betegségben is adódott túlélésbeli különbség az ösztrogénreceptor-, progeszteronreceptor- és HER2-státuszok alapján determinált betegcsoportok között: a tripla negatív és ösztrogénreceptor-pozitív, HER2-negatív tumorok túlélése ebben a stádiumban is különbözött. Következtetések: Valós túlélési adatokon alapuló elemzésünk szerint az újszerű prognosztikai stádiumok a korábbi anatómiai stádiumokhoz hasonlóan elkülönítik a betegeket teljes túlélésük szerint. Eredményeink validálják az új prognosztikai stádiumbesorolást, de előre is mutatnak a jelenleg egységes IV. stádium tagolása irányában. Orv Hetil. 2017; 158(35): 1373–1381. | Abstract: Introduction: The 8th edition of the Tumor-Node-Metastasis (TNM) based staging of breast cancer introduces a prognostic stage influenced by biomarkers along the traditional T, N and M categories. Aim: To retrospectively assess stage influencing prognostic variables; and the anatomic and prognostic stages on the basis of the overall survival (OS) of a cohort of deceased patients once diagnosed with breast cancer. Method: We included patients with known causes of death certified at the Bács-Kiskun County Teaching Hospital and having a history of breast cancer diagnosed on a resection specimen at the same institution. Prognostic factors were obtained from the histopathological reports. Statistics included one-way ANOVA, Dunn’s post hoc test and Kaplan-Meier curve analyses. Results: The 303 patients grouped as breast cancer related death (n = 168) or unrelated (n = 135) showed significant differences in most stage defining prognostic factors and the anatomic and prognostic stages. Significant differences in 5-year OS were observed between pT and pN categories, histological grades and estrogen receptor statuses. Except for stages I and II, significant differences were found between both different anatomic and prognostic stages (p<0.001). Stage IV is by definition uniform, but we identified survival differences between biomarker based subgroups: triple negative carcinomas had worse OS than estrogen receptor positive and HER2 negative carcinomas. Conclusions: Our analysis based on real survival data suggests that the prognostic stages separate patients according to OS similarly to the anatomic stages. The results validate the prognostic stages, but also suggest that separating stage IV disease according to biomarkers makes sense. Orv Hetil. 2017; 158(35): 1373–1381

A tüdőartériák intimájából kiinduló sarcoma = Intimal sarcoma of pulmonary arteries

Absztrakt: A pulmonalis arterialis intimalis sarcoma ritka, magas mortalitású daganat, mely lokalizációja miatt a pulmonalis embolia, valamint a tüdőgyulladás tünettanát utánozhatja. A diagnózis felállítása és a megfelelő kezelés kiválasztása körül számos kérdés merülhet fel. Egy 46 éves, korábban hereseminoma, pulmonalis embolia, asztma, valamint pollenallergia miatt kezelés alatt álló férfi kontroll mellkasi CT-felvételén bal oldalon a mediastinalis pleurát infiltráló, az arteria pulmonalist teljesen elzáró, összességében 7–8 cm-es térfoglaló folyamatot írtak le. A hörgőbiopsziás mintából orsósejtes tumor diagnózisa született, illetve leiomyoma, leiomyomatosus hyperplasia, illetve leiomyosarcoma lehetőségét vetették fel. A fennálló obstrukció miatt a beteg bal oldali tüdőeltávolításon esett át. A szövettani vizsgálat a pulmonalis artériákban terjedő, orsósejtes daganatot kórismézett, immunhisztokémiailag diffúz SMA- és fokális MDM2-pozitivitással, valamint magas proliferációs aktivitással. A h-caldesmon, az S100 protein, az ERG, valamint a pancitokeratin-immunfestések negatívnak bizonyultak. Fluoreszcens in situ hibridizációval a tumorsejtek mintegy 10%-ában polysomiát, illetve MDM2-amplifikációt lehetett igazolni, aminek alapján a „high-grade” pulmonalis arterialis intimalis sarcoma diagnózisa megerősítésre került. Féléves követés alatt a betegség nem újult ki. A pulmonalis arterialis intimalis sarcoma pontos incidenciája nem ismert. Egyes források szerint a krónikus pulmonalis hypertoniás betegek 1–4%-ánál fordul elő. A tünetek közül a fogyás kelti fel a leginkább a daganatos betegség gyanúját. A képalkotó és a kórszövettani vizsgálatoknak kulcsszerepük van a diagnózis felállításában. A daganat rossz kórjóslata miatt a minél korábbi felismerés és a kemoterápiával kombinált sebészi kezelés javíthatja a túlélési lehetőségeket. Orv Hetil. 2020; 161(6): 232–236. | Abstract: Pulmonary arterial intimal sarcoma is a rare tumour with high mortality. Due to its localisation, the symptoms can mimic pulmonary thromboembolism and pneumonia, therefore assessing the diagnosis and choosing the adequate therapy is never easy. Its therapy mainly consists of surgery combined with radiochemotherapy. A 46-year-old male patient with testicular seminoma, pulmonary embolism, bronchial asthma and pollen allergy in his history had a follow-up thoracic CT. On the left side of the lung, a pleura-infiltrating 7–8 cm lesion, which occluded the pulmonary artery, was described. The first biopsy specimen showed fragments of spindle cell tumour. The primary diagnosis was leiomyoma, leiomyomatous hyperplasia, yet the presence of leiomyosarcoma could not have been ruled out. Due to the arterial obstruction, the patient underwent left sided pulmonectomy. Histological examination showed a tumour mostly composed of spindle cells that were diffusely positive with SMA, focally diffuse with MDM2 immunohistochemistry together with high proliferation activity. h-Caldesmon, S-100, ERG and pancytokeratin expressions were not detected. With fluorescent in situ hybridization 10% of tumour cells showed polysomy and MDM2 amplification. According to the results, high-grade pulmonary arterial intimal sarcoma diagnosis has been made. The precise incidence of pulmonary arterial intimal sarcoma is unknown. Some literature data suggest it can be the cause of chronic pulmonary hypertension in 1–4% of the cases. Weight loss can draw attention to the malignant nature of the disease. Imaging techniques and histology are the gold standard in setting the diagnosis. The prognosis is poor. Early recognition and surgery combined with chemotherapy can prolong survival. Orv Hetil. 2020; 161(6): 232–236

The more the micropapillary pattern in stage I lung adenocarcinoma, the worse the prognosis: a retrospective study on digitalized slides

Although the majority of lung adenocarcinomas show mixed pattern, only the predominant component is taken into account according to the novel classification. We evaluated the proportion of different patterns and their impact on overall survival (OS) and disease-free survival (DFS). Patterns were recorded according to predominance and their proportions were rated and calculated by objective area measuring on digitalized, annotated slides of resected stage I lung adenocarcinomas. Spearman’s rank correlation, Kaplan-Meier models and the log rank test were used for statistical evaluation. Two hundred forty-three stage I adenocarcinoma were included. Lepidic pattern is more frequent in tumours without recurrence (20 vs. 8%), and lepidic predominant tumours have favourable prognosis (OS 90.5%, DFS 89.4%), but proportions above 25% are not associated with improving outcome. Solid and micropapillary patterns are more frequent in patients with recurrence (48 vs. 5% and 13 vs. 4%) and predominance of each one is associated with unfavourable prognosis (OS 64.1%, DFS 56.3% and OS 28.1%, DFS 28.1%, respectively). Above 25%, a growing proportion of solid or micropapillary pattern is not associated with worsening prognosis. In contrast, tumours having micropapillary pattern as secondly predominant form a different intermediate group (OS 51.1%, DFS 57.8%). Our study was based on measured area of each growth pattern on all available slides digitalized. This is the most precise way of determining the size of each component from the material available. We propose using predominant and secondly predominant patterns for prognostic purposes, particularly in tumours having solid or micropapillary patterns. © 2018 Springer-Verlag GmbH Germany, part of Springer Natur