A tüdőrák molekuláris diagnosztikája

Development of the target therapies of lung cancer was a rapid process which fundamentally changed the pathological diagnosis as well. Furthermore, molecular pathology became essential part of the routine diagnostics of lung cancer. These changes generated several practical problems and in underdeveloped countries or in those with reimbursement problems have been combined with further challenges. The central and eastern region of Europe are characterized by similar problems in this respect which promoted the foundation of NSCLC Working Group to provide up to date protocols or guidelines. This present paper is a summary of the molecular pathology and target therapy guidelines written with the notion that it has to be upgraded continuously according to the development of the field

Epidemiologie, prevence a léčba kolorektálního karcinomu dle dostupných českých a mezinárodních dat

Nádory tlustého střeva a konečníku patří mezi nejčastější onkologické diagnózy. V České republice je každoročně nově diagnostikováno téměř 8 500 pacientů s kolorektálním karcinomem a přibližně 3 900 osob tomuto onemocnění každým rokem podlehne. Celková prevalence přesáhne v roce 2012 hranici 55 000 osob. Společenské, etické i ekonomické důsledky vyplývající z takto vysoké zátěže jsou zřejmé. Publikace „Epidemiologie, prevence a léčba kolorektálního karcinomu dle dostupných českých a mezinárodních dat“ přináší ucelený přehled epidemiologické a léčebné zátěže české populace touto chorobou a věnuje se krátkodobým a dlouhodobým predikcím dalšího vývoje. Situace je rovněž hodnocena v mezinárodním srovnání, neboť v hodnotách incidence a mortality kolorektálního karcinomu obsazuje ČR přední příčky evropských i světových statistik. Z mezinárodních studií však také vyplývá pozitivní poznatek, že většině nádorů tlustého střeva a konečníku lze předejít účinnou prevencí. Kromě primární prevence je zde hlavním nástrojem organizovaný populační screening, který je založen na testech krvácení do stolice a na kolonoskopii. Otázkám prevence a výsledkům screeningu kolorektálního karcinomu jsou v publikaci věnovány zvláštní kapitoly. Ačkoli nejnovější data dokládají rostoucí výkonnost českého screeningu, celkově dosažené pokrytí populace bohužel stále není dostatečné. To platí pro včasný záchyt kolorektálního karcinomu obecně, neboť v ČR je setrvale téměř 50 % nových onemocnění diagnostikováno v pokročilých klinických stadiích, a tedy s výrazně sníženou šancí na vyléčení nebo dlouhodobé přežití pacienta. Publikace rovněž hodnotí přežití dosahované u českých pacientů jakožto zásadní ukazatel výsledků léčebné péče, u kterého v posledních 15 letech zaznamenáváme statisticky významné zlepšení. Pravděpodobnost 5letého relativního přežití je u včasně diagnostikovaného kolorektálního karcinomu v klinickém stadiu i vyšší než 88%. Tato čísla opět potvrzují nutnost účinné prevence a posílení screeningu tohoto preventabilního onemocnění. V tomto směru má publikace ambici informovat odbornou i laickou veřejnost, a proto věnuje značný prostor přehledu dostupných informačních zdrojů.The book aims to inform expert and general public about epidemiology of colorectal carcinoma in the Czech Republic and priorities resulting from high population burden for prevention, diagnostics, and treatment of this severe disease. A number of invited experts assess selected information sources that representatively describe performance and quality of preventive programmes and results of CRC treatment in the Czech Republic

Epithelial-myoepithelial tumour of the lung: a case report referring to its molecular histogenesis

Tracheobronchial submucous glands can be considered the pulmonary equivalent of minor salivary glands and therefore they can develop most of the tumours originated in these. Nevertheless, in spite of the wide distribution of this kind of glands along the tracheobronchial tree, pulmonary salivary gland-like neoplasms are not very frequent. Among them, the most frequent are mucoepidermoid and adenoid cystic carcinomas. On the contrary, pulmonary neoplasms showing a mixture of epithelial and myoepithelial elements are extraordinary infrequent, with only 11 cases collected from literature

Intra-tumour heterogeneity is one of the main sources of inter-observer variation in scoring stromal tumour infiltrating lymphocytes in triple negative breast cancer

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 < 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 < 0.001) and good for the 20% (ICC 0.657, 95% CI 0.561–0.756, p < 0.001) and 40% (ICC 0.644, 95% CI 0.546–0.745, p < 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

Reproducibility and predictive value of scoring stromal tumour infiltrating lymphocytes in triple-negative breast cancer : a multi-institutional study

Several studies have demonstrated a prognostic role for stromal tumour infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC). The reproducibility of scoring sTILs is variable with potentially excellent concordance being achievable using a software tool. We examined agreement between breast pathologists across Europe scoring sTILs on H&E-stained sections without software, an approach that is easily applied in clinical practice. The association between sTILs and response to anthracycline-taxane NACT was also examined. Pathologists from the European Working Group for Breast Screening Pathology scored sTILs in 84 slides from 75 TNBCs using the immune-oncology biomarker working group guidance in two circulations. There were 16 participants in the first and 19 in the second circulation. Moderate agreement was achieved for absolute sTILs scores (intraclass correlation coefficient (ICC) = 0.683, 95% CI 0.601-0.767, p-value = 25% (kappa = 0.53) and for LPBC (kappa = 0.49), but poor for sTILs as 10% increments (kappa = 0.24). Increasing sTILs was significantly associated with an increased likelihood of a pathological complete response (pCR) on multivariable analysis. Increasing sTILs in TNBCs improves the likelihood of a pCR. However, inter-observer agreement is such that H&E-based assessment is not sufficiently reproducible for clinical application. Other methodologies should be explored, but may be at the cost of ease of application.Non peer reviewe

Concurrent breast stroma sarcoma and breast carcinoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Breast cancer is one of the most important health problems in the world and affects a great number of women over the entire globe. This group of tumors rarely presents as bilateral disease and, when it does happen, normally occurs within the same histological type. We report a rare case of concurrent bilateral breast cancer with two different histology types, a breast carcinoma and a breast sarcoma, in a 42-year-old woman referred to our hospital.</p> <p>Case presentation</p> <p>A 42-year-old Caucasian woman admitted to our institute in August 1999, presented with a nodule in the left breast of 3.0 × 2.5 cm, and, in the right breast, one of 1.0 cm, suspected of malignancy and with a clinically negative armpit. Biopsies had revealed invasive mammary carcinoma (right breast) and sarcoma (left breast). She was submitted to bilateral modified radical mastectomy. A histological study showed an invasive mammary carcinoma degree II lobular pleomorphic type with invasion of seven of the 19 excised axillary nodes in the right breast and, in the left breast, a sarcoma of the mammary stroma, for which the immunohistochemistry study was negative for epithelial biomarkers and positive for vimentin. Later, she was submitted for chemotherapy (six cycles of 75 mg/m²5-fluorouracil, epirubicin and cyclophosphamide) followed by radiotherapy of the thoracic wall and axillary nodes on the left. Hormone receptors were positive in the tumor of the right breast, and tamoxifen, 20 mg, was prescribed on a daily basis (five years) followed by letrozole, 2.5 mg, also daily (five years). She presented no sign of negative evolution in the last consultation.</p> <p>Conclusion</p> <p>The risk of development of bilateral breast cancer is about 1% each year within a similar histological type, but it is higher in tumors with lobular histology. In this case, the patient presented, simultaneously, two histologically distinct tumors, thus evidencing a rare situation.</p

Staining Performance of ALK and ROS1 Immunohistochemistry and Influence on Interpretation in Non–Small-Cell Lung Cancer

Selection of nonesmall-cell lung cancer patients for treatment relies on the detection of expression of anaplastic lymphoma kinase (ALK) and ROS proto-oncogene 1 (ROS1) protein by immunohistochemistry (IHC). We evaluated staining performance for different IHC protocols and laboratory characteristics, and their influence on ALK and ROS1 interpretation during external quality assessment schemes between 2015 and 2018. Participants received five formalin-fixed, paraffin-embedded cases for staining by their routine protocol, whereafter at least two pathologists scored them simultaneously under a multihead microscope and awarded a graded expert staining score (ESS) from 1 to 5 points based on staining quality. European Conformity in Vitro Diagnostic kits (such as D5F3) revealed a better ALK ESS compared with laboratory-developed tests. ESS was indifferent to the applied antibody dilution or a recent protocol change. Lower ESSs were observed for higher antibody incubation times and temperatures. ESS for various ROS1 protocols were largely similar. Overall, for both markers, ESS improved over time and for repeated external quality assessment participation but was independent of laboratory setting or experience. Except for ROS1, ESS positively correlated with laboratory accreditation. IHC stains with lower ESS correlated with increased error rates in ALK and ROS1 interpretation and analysis failures. Laboratory characteristics differently affected staining quality and interpretation, and laboratories should assess both aspects, and less common protocols need improvement in staining performanc

Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-naïve patients with triple-negative breast cancer

Background: In the absence of prognostic biomarkers, most patients with early-stage triple-negative breast cancer (eTNBC) are treated with combination chemotherapy. The identification of biomarkers to select patients for whom treatment de-escalation or escalation could be considered remains an unmet need. We evaluated the prognostic value of histopathologic traits in a unique cohort of young, (neo)adjuvant chemotherapy-naïve patients with early-stage (stage I or II), node-negative TNBC and long-term follow-up, in relation to stromal tumor-infiltrating lymphocytes (sTILs) for which the prognostic value was recently reported. Materials and methods: We studied all 485 patients with node-negative eTNBC from the population-based PARADIGM cohort which selected women aged &lt;40 years diagnosed between 1989 and 2000. None of the patients had received (neo)adjuvant chemotherapy according to standard practice at the time. Associations between histopathologic traits and breast cancer-specific survival (BCSS) were analyzed with Cox proportional hazard models. Results: With a median follow-up of 20.0 years, an independent prognostic value for BCSS was observed for lymphovascular invasion (LVI) [adjusted (adj.) hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.49-3.69], fibrotic focus (adj. HR 1.61, 95% CI 1.09-2.37) and sTILs (per 10% increment adj. HR 0.75, 95% CI 0.69-0.82). In the sTILs &lt;30% subgroup, the presence of LVI resulted in a higher cumulative incidence of breast cancer death (at 20 years, 58%; 95% CI 41% to 72%) compared with when LVI was absent (at 20 years, 32%; 95% CI 26% to 39%). In the ≥75% sTILs subgroup, the presence of LVI might be associated with poor survival (HR 11.45, 95% CI 0.71-182.36, two deaths). We confirm the lack of prognostic value of androgen receptor expression and human epidermal growth factor receptor 2 -low status. Conclusions: sTILs, LVI and fibrotic focus provide independent prognostic information in young women with node-negative eTNBC. Our results are of importance for the selection of patients for de-escalation and escalation trials.</p