Apart from pulmonary disease, acute kidney injury (AKI) is one of the most frequent and most severe organ complications in severe coronavirus disease 2019 (COVID-19). The SARS-CoV‑2 virus has been detected in renal tissu...Apart from pulmonary disease, acute kidney injury (AKI) is one of the most frequent and most severe organ complications in severe coronavirus disease 2019 (COVID-19). The SARS-CoV‑2 virus has been detected in renal tissue. Patients with chronic kidney disease (CKD) before and on dialysis and specifically renal transplant patients represent a particularly vulnerable population. The increasing number of COVID-19 infected patients with renal involvement led to an evolving interest in the analysis of its pathophysiology, morphology and modes of virus detection in the kidney. Meanwhile, there are ample data from several autopsy and kidney biopsy studies that differ in the quantity of cases as well as in their quality. While the detection of SARS-CoV‑2 RNA in the kidney leads to reproducible results, the use of electron microscopy for visualisation of the virus is difficult and currently critically discussed due to various artefacts. The exact contribution of indirect or direct effects on the kidney in COVID-19 are not yet known and are currently the focus of intensive research.
In addition to pneumology and pathology, radiology is an essential discipline in the interdisciplinary diagnosis of interstitial lung diseases (ILDs). The gold standard for diagnosis of ILD is computed tomography. Diagno...In addition to pneumology and pathology, radiology is an essential discipline in the interdisciplinary diagnosis of interstitial lung diseases (ILDs). The gold standard for diagnosis of ILD is computed tomography. Diagnostic findings are based on specific radiological signs such as interlobular septal thickening and nodular changes. From these signs and their distribution within the lung, radiological patterns can be derived, e.g., usual interstitial pneumonia, nonspecific interstitial pneumonia, or organizing pneumonia. Various differential diagnoses result from the radiological pattern, which can then be further limited in an interdisciplinary manner with the clinic and pathology and, if necessary, trigger further diagnostics.The visual assessment of interstitial lung changes requires experience and training and is nevertheless error-prone with high inter- and intraobserver variabilities. Recently, therefore, computer-aided analysis of ILDs has been increasingly promoted. These computer programs analyze the density distribution of the lung parenchyma using parameters such as mean lung density, skewness, and kurtosis thus enabling the quantification and assessment of the course of disease. Furthermore, texture analysis and artificial intelligence are used to characterize parenchymal changes and differentiate between regions of ground glass, reticulation, and honeycombing. Modern dual-energy CT methods allow a combined, regional recording of both the morphology and the function and provide information about regional ventilation and perfusion.
A 54-year-old patient with a history of pulmonary tuberculosis and occupational exposure to dust in early adulthood presented with symptoms of coughing with sputum, weight loss, occasional night sweats, and thoracic pain...A 54-year-old patient with a history of pulmonary tuberculosis and occupational exposure to dust in early adulthood presented with symptoms of coughing with sputum, weight loss, occasional night sweats, and thoracic pain. Non-necrotizing granulomatosis in lung and lymph-node biopsies indicated sarcoidosis. Combined immunosuppressive therapy did not lead to an improvement. An atypical lung resectate with fibroinflammatory changes and obliterative endothelialitis may finally lead to the diagnosis of IgG4-associated lung disease with a bronchovascular pattern of involvement. The question discussed here is whether this is a coexistence of IgG4-associated lung disease with sarcoidosis or the spectrum of one disease.
Although typical histological findings of tuberculosis are well known, the diagnosis of nonmicrobiologically proven tuberculosis with the instruments available to pathology is challenging. Indeed, necrotizing epithelioid...Although typical histological findings of tuberculosis are well known, the diagnosis of nonmicrobiologically proven tuberculosis with the instruments available to pathology is challenging. Indeed, necrotizing epithelioid cell granulomatosis is typical for tuberculosis, but it is also seen in a number of different infectious or noninfectious lung diseases. The tools of microscopy and molecular pathology are suitable for confirming the diagnosis or paving the way to a differential diagnosis, but molecular pathology applied to formalin-fixated and paraffin-embedded material is limited. This should be openly communicated to the referring clinician. After interdisciplinary re-evaluation of the findings, an alternative solution to confirm the diagnosis must therefore be found if the additional examinations are negative.
In the diagnosis of mycobacterioses, microbiological examination with culture and antibiogram, possibly in combination with molecular biological testing of the fresh material, still represents the gold standard. However,...In the diagnosis of mycobacterioses, microbiological examination with culture and antibiogram, possibly in combination with molecular biological testing of the fresh material, still represents the gold standard. However, these methods are not available for formalin-fixed paraffin-embedded (FFPE) material or other fixed samples. For this reason, the first step in pathology is to attempt microscopic pathogen detection (ZN/Fite/rhodamine-auramine). Subsequently, molecular pathological examination for the detection of mycobacterial gene sequences should also be considered mandatory today. Although this has clear limits due to the material, it is nevertheless well suited, if carried out correctly, to detect a mycobacterial infection or make it unlikely. A negative result may favor an alternative diagnosis but does not completely rule out mycobacteriosis.For the therapy of tuberculosis or nontuberculous mycobacterial (NTM) disease, the reliable detection of the species and the determination of resistance is of utmost importance. With regard to therapy, the clinician cannot afford to make a false diagnosis. In case of doubt, a rebiopsy for sampling native material, particularly for microbiological testing, should be discussed.
The spectrum of pulmonary granulomatoses is wide and includes infectious and noninfectious entities, each with very different therapeutic consequences. The first step of histological examination discriminates between nec...The spectrum of pulmonary granulomatoses is wide and includes infectious and noninfectious entities, each with very different therapeutic consequences. The first step of histological examination discriminates between necrotizing and non-necrotizing granulomatosis. After this, an infectious cause of the granulomatosis has to be excluded by special histological stains and molecular-pathologic methods, if necessary. Diagnosis also includes clinical, radiological, and microbiological findings. The process of pathological examination should be standardized as described.
The detection of Mycobacterium tuberculosis complex DNA by PCR using formalin-fixed paraffin-embedded material has become an integral part of molecular-pathological diagnostics. We describe an approach that enables the d...The detection of Mycobacterium tuberculosis complex DNA by PCR using formalin-fixed paraffin-embedded material has become an integral part of molecular-pathological diagnostics. We describe an approach that enables the detection of contamination by using Mycobacterium szulgai as a positive control, contributing to the reduction of false-positive results.
Organizing pneumonia (OP) describes a histological pattern of acute or subacute lung damage. Clinically, patients present with cough, fever, and dyspnea. A distinction is made between idiopathic or cryptogenic organizing...Organizing pneumonia (OP) describes a histological pattern of acute or subacute lung damage. Clinically, patients present with cough, fever, and dyspnea. A distinction is made between idiopathic or cryptogenic organizing pneumonia (COP) and secondary organizing pneumonia (OP). In COP, neither clinical/radiological nor histological causes can be determined. It is classified as an interstitial idiopathic pneumonia (IIP) according to the criteria of the American Thoracic Society (ATS) and the European Respiratory Society (ERS). Secondary organizing pneumonia has a known triggering mechanism, such as infectious agents, certain medications, or concomitant symptoms of other primary pulmonary diseases and diseases of other organ systems. Common to both forms is the histological picture of intra-alveolar mesenchymal buds. These are myofibroblast proliferates that branch out along the alveolar spaces. They are usually accompanied by a moderate interstitial and alveolar, chronic, and macrophage-rich inflammatory cell infiltrate. The most important differential diagnosis is common interstitial pneumonia (UIP). It also shows fibroblast proliferates, which are, however, located in the interstitium. The correct classification of an IIP as a COP by means of clinical, radiological, and histological findings is essential, since the COP, in contrast to the UIP, responds very well to corticosteroids and therefore has an excellent prognosis compared to the UIP. The course of secondary organizing pneumonia depends on the respective underlying disease. Here it is important for the pathologist to correctly identify potential accompanying histological characteristics in order to be able to provide clues to a possible cause of OP.
BACKGROUND: Pandemics lead to new challenges for healthcare systems and a subsequent shift of the scientific focus, which can partially be seen in alterations in scientific publication activity. OBJECTIVES: Follow-up on...BACKGROUND: Pandemics lead to new challenges for healthcare systems and a subsequent shift of the scientific focus, which can partially be seen in alterations in scientific publication activity. OBJECTIVES: Follow-up on the global publication activity within the course of the COVID-19 pandemic in a comparison of national contexts with regards to local infection rates and the involvement of the discipline of pathology. MATERIALS AND METHODS: Comparative analysis of the number of publications in the PubMed® database concerning COVID-19 with respect to publication type, date and place of publication, affiliation to an institute of pathology, and correlation with the number of SARS-CoV‑2 infections over the same timeframe. RESULTS: After an initial peak with regards to the number of publications in the months of May and June 2020, a slight decrease was observed, followed by another increase starting in August/September 2020. Further, the time between data collection and publication contracted to approximately 3-4 months. Countries faced with early SARS-CoV‑2 infections published promptly, even though there was no overall association between the number of publications and COVID-19 case numbers. On average, 4% of authors were affiliated to an institute of pathology, with a steady increase of this percentage within the course of the pandemic. CONCLUSIONS: COVID-19 altered global publication activity by providing for an unprecedented number of publications combined with an acceleration of publication times irrespective of the geographical location and overall case numbers.
BACKGROUND: Gastric carcinomas often measure more than 5 cm at primary diagnosis. Predictive biomarker testing is usually carried out on tissue biopsies, which do not represent the entire tumor biology and intratumoral h...BACKGROUND: Gastric carcinomas often measure more than 5 cm at primary diagnosis. Predictive biomarker testing is usually carried out on tissue biopsies, which do not represent the entire tumor biology and intratumoral heterogeneity. OBJECTIVES: The aim of this study was to explore gastric cancer's intratumoral heterogeneity and its impact on the evaluation of predictive and prognostic biomarkers. MATERIALS AND METHODS: The study cohort consisted of approximately 500 patients with therapy-naive adenocarcinomas of the stomach or the esophagogastric junction. The following biomarkers were determined: HER2, MET, Ki67, PD-L1/PD‑1, VISTA, EBV-status, and PIK3CA. RESULTS: All examined biomarkers were influenced by gastric cancer's intratumoral heterogeneity. Tissue biopsies might carry the risk of sampling errors, which may significantly hamper adequate tumor classification in a clinical setting. CONCLUSIONS: Our findings unravel issues of tumor heterogeneity in gastric cancer. Biomarker diagnostics on tissue biopsies should be carried out on at least five biopsies of different tumor areas. If possible, biomarker diagnostics should be repeated on resection specimens. Tissue microarrays should no longer be used for research studies of gastric cancer.
Lymphangioleiomyomatosis (LAM) is a rare lung disease that mostly occurs in female patients. A total of 200-400 people are assumed to be infected in Germany. A sporadic form and a form associated with the tuberous sclero...Lymphangioleiomyomatosis (LAM) is a rare lung disease that mostly occurs in female patients. A total of 200-400 people are assumed to be infected in Germany. A sporadic form and a form associated with the tuberous sclerosis complex (TSC) can be separated. Mutations of the TSC‑1 and TSC‑2 genes are relevant. Morphologically, pulmonary multicysts and marginal micronodal proliferations of LAM cells are characteristic. Combinations with renal angiomyolipoma are typical and, in cases with TSC glioma, facial angiofibroma and ungual fibroma are seen. Prognosis is favorable (10-year survival: 80%) and with the use of mTORC1 inhibitors it could be improved. Lung transplantation can be considered in some cases.
Interstitial lung disease (ILD) is the most frequent organ manifestation in rheumatic autoimmune disease. Depending on the underlying autoimmune disease, differently pronounced affections of small airways, interstitial p...Interstitial lung disease (ILD) is the most frequent organ manifestation in rheumatic autoimmune disease. Depending on the underlying autoimmune disease, differently pronounced affections of small airways, interstitial parenchyma, and vessels are found. The group of rheumatic autoimmune diseases mainly includes connective tissue diseases (CTDs), also known as collagen vascular diseases, such as rheumatoid arthritis (RA), systemic sclerosis, (SSc), systemic lupus erythematosus, primary Sjögren's syndrome, idiopathic inflammatory myositis (IIM), and interstitial pneumonia with autoimmune features (IPAF). Frequency and manifestations of parenchymal lung disorders are described clinically, radiologically, and morphologically in these entities. For the precise diagnosis and for the differentiation between the wide range of parenchymal disorders with known possible cause or with unknown origin, also called unclassifiable or idiopathic interstitial pneumonias (IIPs), high resolution computed tomography (HRCT) findings represent the diagnostic gold standard. A transbronchial biopsy, surgical biopsy, or cryobiopsy will be used in unclassifiable findings to confirm a definitive histological confirmation. A precise diagnosis of these ILDs is crucial since the different pathologies that encompass ILD have different therapeutic options. In this sense, the participation of a pneumologist, rheumatologist, radiologist, and pathologist become essential in the multidisciplinary evolution of ILD.
Transplantation of solid organs and hematopoietic stem cells represents an important therapeutic option for a variety of end-stage pulmonary diseases, aggressive hematopoietic neoplasms, or severe immunodeficiencies. Alt...Transplantation of solid organs and hematopoietic stem cells represents an important therapeutic option for a variety of end-stage pulmonary diseases, aggressive hematopoietic neoplasms, or severe immunodeficiencies. Although the overall survival following transplantation has generally improved over recent decades, long-time survival of lung and stem-cell transplant recipients is still alarmingly low with an average 5‑year survival rate of only 50-60%. Chronic allo-immunoreactions in general and pulmonary allo-immunoreactions with subsequent fibrosis in particular are major reasons for this poor outcome. Comparable patterns of fibrotic lung remodeling are observed following both lung and hematopoietic stem-cell transplantation. Besides the meanwhile well-established obliterative and functionally obstructive remodeling of the small airways - obliterative bronchiolitis - a specific restrictive subform of fibrosis, namely alveolar fibroelastosis, has been identified. Despite their crucial impact on patient outcome, both entities can be very challenging to detect by conventional histopathological analysis. Their underlying mechanisms are considered overreaching aberrant repair attempts to acute lung injuries with overactivation of (myo-) fibroblasts and excessive and irreversible deposition of extracellular matrix. Of note, the underlying molecular mechanisms are widely divergent between these two morphological entities and are independent of the underlying clinical setting.Further comprehensive investigations of these fibrotic alterations are key to the development of much-needed predictive diagnostics and curative concepts, considering the high mortality of pulmonary fibrosis following transplantation.
Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic progressive fibrosing nonreversible interstitial lung disease of largely unknown origin. In high-resolution computer tomography (HRCT) and histopathology...Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic progressive fibrosing nonreversible interstitial lung disease of largely unknown origin. In high-resolution computer tomography (HRCT) and histopathology it presents with a UIP pattern. To diagnose IPF, (i) an ILD of known origin must be excluded (e.g., hypersensitivity pneumonitis, lung involvement in autoimmune or other systemic disease, and drug-induced ILD) and either (ii) the presence of a UIP pattern in HRCT or (iii) specific combinations of HRCT and histopathology is necessary. The diagnosis of IPF requires interdisciplinary collaboration and a structured procedure. The updated S2k guideline focuses on the IPF diagnostic process and describes the criteria of a UIP pattern in HRCT and histopathology that are differentiated into the categories "UIP pattern," "probable UIP pattern," "indetermined for UIP," and "alternative pattern." Depending on the anamnestic, clinical and serologic findings, HRCT, and - if acquired - histomorphology features, an algorithm to diagnose the IPF is recommended. If a UIP pattern in HRCT is present, IPF can still be diagnosed without further bioptic examination. Additionally, recommendations for the use of surgical lung biopsy (SLB), transbronchial lung biopsy, and the relatively new transbronchial lung cryobiopsy (TBLC) procedure are provided. In contrast to the international guideline, the S2k guideline group evaluated TBLC based on recent studies to be advantageous compared to the SLB, as the diagnostic value and the side-effect rate was assessed to be acceptable and more patients with progressed ILD can be biopsied by TBLC. It is therefore expected that by using TBLC the rate of unclassifiable ILDs can be reduced.
Pulmonary drug reactions are a relatively common factor causing interstitial pulmonary disease. Histological findings of pulmonary drug reactions can mimic other conditions such as various forms of idiopathic interstitia...Pulmonary drug reactions are a relatively common factor causing interstitial pulmonary disease. Histological findings of pulmonary drug reactions can mimic other conditions such as various forms of idiopathic interstitial pneumonia such as nonspecific interstitial pneumonia, organizing pneumonia, diffuse alveolar damage, or usual interstitial pneumonia. The correct diagnosis is important since a causal therapy is possible by stopping the administration. A stringent correlation between dose/time of administration and the type of reaction exists for only a few drugs. An increased risk of drug side effects can arise from known reactions to that specific drug, the patient's history, the type of underlying disease, genetic polymorphisms, occupational factors, and interactions with other drugs. The identification of a pulmonary drug reaction is a difficult task that can often only be solved in an interdisciplinary manner, for which in rare cases a lung biopsy is necessary. Pathology then has to identify histomorphological reaction patterns to exclude other causes and correlate findings with clinical data. In most cases, however, the diagnosis of a drug reaction will be by exclusion.