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Small cell lung carcinoma (SCLC) is a high grade neuroendocrinne tumour accounting for approximately 15 % of lung cancers. It is characterised by early relapse and low survival rate. The treatment has remained unchanged for decades. Histological and cytological characteristics are summarised in brief, along with genetic alterations of the tumour. A new molecular subtype classification is presented according to the expression of transciptional factors ASCL1 (SCLC-A), NEUROD1 (SCLC-D), POU2F3 (SCLC-P) and YAP1 (SCLC-Y). These subtypes represent different ways of tumorigenesis, and the distinct genomic alterations may offer new therapeutic strategies.

Histopathological pattern of progressive pulmonary fibrosis could be seen in many different fibrotic lung interstitial diseases. Exact diagnosis is crucial for precise therapy, moreover, different diseases have different prognosis. The most important disorders in this group are idiopatic pulmonary fibrosis and fibrotic hypersensitivity pneumonitis, and their separation is crucial because of totally different treatment of the patients. The aim of this review is to sum up the most important characteristics of usual interstitial pneumonia, histopathological pattern of idiopatic pulmonary fibrosis, and fibrotic hypersensitivity pneumonitis and provide a practical work-up for precise diagnostics of these diseases in the frame of effectively cooperating multidisciplinary team.

Giant cell fibroblastoma is a rare locally aggressive tumor of subcutaneous mesenchymal tissue, occurring mostly on the trunk in young individuals with maximal incidence in the first decade of life. Local recurrences of giant cell fibroblastoma are common if marginally excised, however, distant metastases do not occur. Giant cell fibroblastoma was labelled as a juvenile variant of dermatofibrosarcoma protuberans (DFSP) due to quite frequent combination of both lesions, morphological similarities, identical immunoprofile, and shared gene fusion t(17;22) COL1A1-PDGFB. In this paper, we report a case of a young man with a slowly growing subcutaneous tumor in the groin. The tumor was excised and histological examination identified a mesenchymal tumor with variable cellularity, presence of multinucleated giant cells and pleomorphic spindle cells, which lined pseudovascular or angiectoid spaces. The CD34 immunohistochemistry showed strong positivity in all of these cells, whereas ERG was positive only in endothelial cells in true vessels. These findings led to a suspicion on giant cell fibroblastoma. Because of its borderline malignant behaviour and positive surgical margins, the lesion was subsequently reexcised. The molecular analysis identified the transcription product of gene fusion COL1A1-PDGFB and thus, final diagnosis was confirmed. The article includes review of the literature and brief historical overview of giant cell fibroblastoma concept as an unique entity.

Evaluation of tumor infiltrating lymphocytes (TIL) is gaining importance in many cancers not only because of their prognostic, but also predictive significance. One of the tumors in which the evaluation of TIL is of prognostic importance and has potential predictive impact on the modification of treatment procedures is breast cancer, especially its so-called triple negative, and HER2 positive variants.The aim of this review is to provide an overview of the issue of TIL evaluation in breast cancer, focusing not only on the clinical significance of this evaluation, but especially on the methodological aspects of evaluation and standardized reporting of the results.

Molecular classification of endometrial carcinoma is becoming an important part of the diagnostic process with direct therapeutic implications. Recent international guidelines, including the joint ESGO-ESTRO-ESP recommendation, include the molecular classification into standard diagnostic algorithms. Molecular testing of endometrial carcinomas is also recommended in the latest (5th) edition of the WHO classification of Female Genital Tumors. Due to the need to implement these recommendations in practice, representatives of four professional societies of Czech Medical Association of J. E. Purkyně (Czech Oncological Society, Oncogynecological Section of the Czech Gynecological and Obstetrical Society, Society of Radiation Oncology, Biology and Physics, and the Society of Czech Pathologists) organized a meeting focused on this topic. The result of this meeting is a joint recommendation for molecular testing of endometrial carcinoma in routine diagnostic practice in the Czech Republic.

Molecular testing of tumor tissue for the detection of somatic aberrations using NGS is increasingly gaining significance in routine practice. The technical aspects of testing are standardized and currently do not pose a problem. However, the situation is evolving very rapidly regarding the indication of testing, which depends on the sometimes rapidly developing medical knowledge and needs in clinical practice. In order to implement NGS testing in practice and arrange its reimbursement by the health care system, first it is necessary to reach an agreement on the level of professional societies concerning the definition of priority and medically clearly justified areas in which molecular testing has a clear impact on therapeutical choices. The next step is to reach an agreement with the health insurance companies regarding NGS testing. The aim of this article is to provide an overview of the issue of routine tumor tissue testing using the NGS method covered by public health insurance, with a summary of the current situation in the Czech Republic. Only the testing of somatic aberrations in solid tumors performed at pathology departments is discussed. The issue of testing in haemato-oncological centres is not the subject of this review.

Thoracic frozen section biopsies including lungs, pleura and mediastinum have crucial role in differential diagnosis of solitary lesions of the lungs and mediastinum. There is a significant difference in patient´s therapeutical management, if the patients suffer from lung primary malignant tumour, metastasis or non-malignant lesion. In this review, we summarize the usefulness of frozen section biopsies in thoracic surgery and provide 5-years of experiences with thoracic frozen section biopsies performed at the Department of Pathology and Molecular Medicine of Thomayer Hospital in Prague. Keywords: frozen section - lung - mediastinum.

We report the case of a 54-year-old female with dedifferentiated carcinoma of the ovary. Grossly, both ovaries were affected by a tumor of up to 25 mm (right ovary) and 220 mm (left ovary) in diameter. Microscopically, the tumors of both ovaries showed features of well differentiated endometrioid carcinoma with mucinous differentiation. Moreover, in the left ovary there was an undifferentiated solid component consisting of larger cells. Immunohistochemically, the undifferentiated component showed diffuse vimentin positivity and focal expression of cytokeratin 18. Other markers examined including PAX8, estrogen receptors and progesterone receptors were all negative. Dedifferentiated carcinomas consist of an undifferentiated epithelial component and a component of endometrioid carcinoma of FIGO grade 1 or 2. Clinically, they represent aggressive tumors with unfavorable prognosis mostly occurring in the endometrium. To the best of our knowledge, thus far only 6 cases arising in the ovary have been reported in the literature.

The aim of the retrospective part of the study was a) to select an optimal clone of immunohistochemical (IHC) antibody against the ALK protein with specificity and sensitivity high enough to use this antibody as a screening method for selecting non-small cell lung cancer (NSCLC) cases for fluorescence in situ hybridization (FISH) testing of ALK gene rearrangement and b) to determine the diagnostic yield of "small" biopsies i.e. endobronchial, transbronchial and transthoracic biopsies and cytoblocks for ALK gene rearrangement testing. The best IHC method of ALK protein detection (clone D5F3, dilution 1:100, Cell Signaling Technology, Danvers, MA, USA) was then verified in prospective routine testing of patients with NSCLC. ALK status was correlated with tumor morphology and clinical data. In the retrospective part of the study, 170 EGFR-nonmutated cases of NSCLC were IHC and FISH tested. In the prospective part, 557 cases of NSCLC were tested by IHC and 76 by FISH. There were 8/154 (5.2%) cases with ALK gene rearrangement detected in the retrospective part and 24/557(4.3 %) in the prospective part. Sensitivity and specificity of the best IHC method were 100 % and 99 % in the retrospective part and 100 % and 80 % in the prospective part. The diagnostic yield of "small" biopsies was between 74 - 80 % retrospectively, depending on IHC variant, and 88 % prospectively. No case with ALK gene rearrangement detected prospectively had EGFR mutation. A high diagnostic yield confirms that ALK status testing can be used in this type of specimen. A prevalence of 5.2 % in the retrospective part (EGFR-nonmutated cases) and 4.3 % in the prospective part (without known EGFR mutation status), tumor morphology (solid and acinar type, mucinous type or at least partial mucin production (extra- and/or intracellular) as well as lower average age and male/female ratio of patients with ALK positive tumors in the prospective part (57.5 y vs. 65.2 y, 8 men and 16 women vs. 336 men and 197 women) are consistent with global data.

The group of non-small cell lung carcinomas includes tumors that are variable at the clinical, histopathological and molecular levels. Advances in the understanding of molecular pathology of lung adenocarcinomas in particular led to changes in their histopathological classification and treatment. Patients diagnosed with lung adenocarcinoma harboring specific mutations benefit from the administration of specific targeted therapy. Analysis of EGFR gene mutations and ALK rearrangement in lung adenocarcinomas are already routinely performed and are closely related to the indication for the administration of tyrosinkinase inhibitors. Besides EGFR mutations and ALK rearrangement there are also available other potential markers for analyzing, e.g. b-raf - BRAF, ROS1. Moreover, immunotherapy needs standardization of detection of crucial molecules, namely PD-L1. The aim of this review is to summarize the role of the most relevant molecules that could also serve as the therapeutic target for practicing pathologists.

In this case report the authors describe histomorphological findings of acute lung injury with laboratory-confirmed influenza type A(H1N1) pneumonia leading to the death of a 30 year-old unvaccinated man after 27 days of hospitalisation. Histologically all three types of acute lung injuries were unusually present (diffuse alveolar damage, acute interstitial pneumonia, organizing pneumonia) in different phases of resorption and reparation with transition to extensive fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a primary fibrosing pulmonary process. Due to the ineffectiveness of current therapeutic strategies and unfavorable prognosis, IPF is the most serious example of idiopathic interstitial lung diseases (ILD). Etiology and pathogenesis of this disorder have not been fully clarified yet; but it is anticipated, that the fibroproliferation is caused by the imbalance of reparative and immunologic processes in the genetically predisposed patients. Radiologically and histopathologically, IPF is characterized by specific pattern called usual interstitial pneumonia (UIP), however, this pattern is not fully typical in all cases, and, moreover, it could be seen in other ILD´s, e.g. chronic hypersensitivity pneumonitis, asbestosis, autoimmune connective tissue diseases and many others as well. The final diagnosis of IPF is a consensual result of multidisciplinary team composed of pulmologist, pathologist and radiologist. IPF was an incurable disease with prognosis worse than cancer till the year 2011, when antifibrotic drugs decelerating a progression of this disease have been introduced. Earlier and correct diagnosis of IPF is the most important issue for the patients because they could be effectively treated and thus, prolonging their survival as much as possible.

Diffuse interstitial lung disorders include more than 200 different syndroms affecting the space between epithelial basal membrane and endothelial cells. Histopathological investigation of the lung tissue is one of the crucial parts of the multidisciplinary team approach for the investigation of these disorders. The aim of this review is a brief characterization of the pattern of the main subtypes of lung tissue damage.

There are many different interstitial lung diseases associated with smoking. This short review describes officially recognized disorders (desquamative interstitial pneumonia, respiratory bronchiolitis and pulmonary Langerhans´cells histiocytosis) and entities with uncertain relationship to smoking, which have recently been published in the literature. Histopathological pictures and differential diagnosis of smoking-related diseases of the lungs are discussed.

Brief review of histopathology of non-tumor pulmonary diseases with nodular or granulomatous morphology. Differential diagnosis of infections, sarcoidosis, vasculitides with a granulomatous component and selected pneumoconioses is presented.

Brain and spinal cord autopsies aimed at neuropathological diagnosis of the causes of dementia and motor abnormalities are of increasing importance. Neuropathological brain examination is often the only diagnostic modality capable of definitive diagnosis of a neurodegenerative disease and thus serves as invaluable feedback for clinicians and biochemical and imaging diagnostics. The brain and spinal cord autopsy is performed following a standardized protocol and its goal is to sample all diagnostically relevant structures. Subsequent diagnostics are then done using standard and special histologic stainings, however state-of-the-art diagnostics can be achieved only using immunohistochemical methods. The purpose of the article is to provide the pathologists with a brief and practical guideline for brain and spinal cord autopsy when diagnosis of a neurodegenerative disease is suspected.

The group of non-small cell lung carcinomas includes tumors that are variable at the clinical, histopathological and molecular levels. Advances in the understanding of molecular pathology of lung adenocarcinomas in particular has led to changes in their histopathological classification and treatment. Patients diagnosed with lung adenocarcinoma harboring specific mutations benefit from the administration of specific targeted therapy. Therefore, pathologists closely involved in the diagnostics of lung tumors significantly contribute to the diagnostic-therapeutical algorithm. Analysis of EGFR gene mutations in lung adenocarcinomas is already routinely performed and the presence of activating mutations in EGFR is the main indication for the administration of tyrosinkinase inhibitors. Besides EGFR mutations, EML4-ALK rearrangement is also being analysed and there is potential in analysing BRAF mutations as well. The aim of this review is to summarize the role of the most relevant molecules that also serve as the therapeutic target for practicing pathologists.