The current edition of the WHO classification of thyroid tumors (2017) contains a number of very relevant changes with considerable consequences for the diagnostic assessment of thyroid specimens. This applies to both th...The current edition of the WHO classification of thyroid tumors (2017) contains a number of very relevant changes with considerable consequences for the diagnostic assessment of thyroid specimens. This applies to both the histomorphological examination of surgical specimens and the preoperative fine needle biopsy (FNB). In addition, molecular pathological examinations are becoming increasingly important in the diagnosis of thyroid tumors. Changes affect practically all areas of thyroid tumor diagnostics. Some of these changes have far-reaching consequences that justify a comprehensive commentary and query of the knowledge acquired in the form of this CME article.
Hommerding O, Allory Y, Argani P
… +25 more, Bismar TA, Bubendorf L, Canete-Portillo S, Chaux A, Chen YB, Cheng L, Cubilla AL, Egevad L, Gill AJ, Grignon DJ, Hartmann A, Hes O, Idrees MT, Kao CS, Knowles MA, Looijenga LHJ, Lotan TL, Pritchard CC, Rubin MA, Tomlins SA, Van der Kwast TH, Velazquez EF, Warrick JI, Williamson SR, Kristiansen G
Comprehensive understanding of molecular principles in cancer and the diversification of oncological therapy promise individual therapeutic concepts, which have not yet found their way into urogenital cancer therapy. In...Comprehensive understanding of molecular principles in cancer and the diversification of oncological therapy promise individual therapeutic concepts, which have not yet found their way into urogenital cancer therapy. In March 2019 the International Society of Urogenital Pathology (ISUP) therefore held a consensus conference on recommendations for molecular diagnostics of genitourinary tumors, which were published in five separate manuscripts and are summarized in this article.In preparation for the conference, a comprehensive survey of current practices for molecular testing of urogenital tumors was carried out by members of the ISUP. At the conference, the results and the corresponding background information were presented by five working groups and recommendations for action for diagnostics were developed. An agreement between 66% of the conference participants was defined as consensus.
We report on a 72-year-old male patient suffering from weight loss, diarrhea, and epigastric pain. By means of endosonographic ultrasound, a well-circumscribed tumor mass was found in the gastric wall, suggesting a gastr...We report on a 72-year-old male patient suffering from weight loss, diarrhea, and epigastric pain. By means of endosonographic ultrasound, a well-circumscribed tumor mass was found in the gastric wall, suggesting a gastrointestinal stromal tumor (GIST). Biopsies were taken and processed for standard histopathological analysis. The microscopy revealed uniform, small, round cells with central nuclei and prominent cell borders embedded in vascularized stroma. Immunohistochemistry demonstrated the expression of actin, but showed negativity for cytokeratin, CD34, CD117, DOG‑1, desmin, and CD45. The tumor was diagnosed as a gastral glomus tumor. The diagnosis was confirmed in the wedge resection specimen. Gastral glomus tumors are rare intramural tumors of the stomach. GIST and neuroendocrine tumor (NET) present the main differential diagnoses. Especially with regard to the epithelioid variant of GIST, clear separation can be difficult. Besides standard histological examination, immunohistochemistry and molecular analysis can be helpful since gastral glomus tumors do not obtain c‑Kit- or PDGFRα mutations. Based on the fact that this tumor most commonly shows a benign biological behavior, the prognosis of gastral glomus tumors is favorable.
Diffuse interstitial lung disease of infancy (chILD) shows a spectrum of disease substantially different from that of adults. Established classification systems divide chILD into conditions that are more prevalent in inf...Diffuse interstitial lung disease of infancy (chILD) shows a spectrum of disease substantially different from that of adults. Established classification systems divide chILD into conditions that are more prevalent in infancy and conditions that occur at any age. The classification is based on a multidisciplinary approach including clinical, radiological, genetic, and histological findings. Lung biopsies become necessary if other diagnostic investigations have not identified a precise chILD or if severe or refractory respiratory distress of unknown cause is present. As the majority of pediatric lung biopsies will be received first by pathologists outside of specialist centers this review summarizes relevant clinical and histological findings of chILD.
Hypersensitivity pneumonia (HP), also called exogenous allergic alveolitis, is a chronic interstitial pneumonia induced by a hypersensitivity reaction to an identified or unidentified antigen in exposed and susceptible i...Hypersensitivity pneumonia (HP), also called exogenous allergic alveolitis, is a chronic interstitial pneumonia induced by a hypersensitivity reaction to an identified or unidentified antigen in exposed and susceptible individuals that may progress to terminal lung fibrosis. The diagnosis of HP presents a diagnostic challenge. Though therapeutically important, it may be particularly difficult to differentiate fibrotic HP, historically termed chronic HP, from idiopathic pulmonary fibrosis (IPF) or interstitial lung disease associated with connective tissue diseases (CTD-ILD). Multidisciplinary discussion and thus a synoptic evaluation of all findings is firmly established as the gold standard diagnostic approach in interstitial lung diseases including HP. Nonetheless, the high interobserver variability between experts from the individual disciplines (pulmonology, radiology, and pathology) and between experienced multidisciplinary teams in assessing the diagnostic probability of HP has highlighted the need for widely accepted guidelines.The present review summarizes pathology-relevant aspects of the new ATS/JRS/ALAT clinical practice guideline for the diagnosis of HP in adults.
A prerequisite for all HER2 directed therapies is the demonstration of HER2 receptor protein overexpression and/or gene amplification by in situ hybridization (ISH). ASCO and CAP have published several HER2 test guidelin...A prerequisite for all HER2 directed therapies is the demonstration of HER2 receptor protein overexpression and/or gene amplification by in situ hybridization (ISH). ASCO and CAP have published several HER2 test guidelines over the past 15 years for both breast and gastric cancer. The latest version for breast cancer (2018) focuses on special issues of ISH related to the definitions of special diagnostic groups (1-5). The guidelines for gastroesophageal adenocarcinoma (2017), essentially based on ToGA trial data, are now also being used for other tumors such as pancreas, gallbladder, and non-small-cell lung cancer. For colorectal cancer, a modified testing procedure has been proposed. Recently, besides overexpression and amplification, a third type of HER gene alteration, namely mutation, has gained much interest. Next-generation sequencing (NGS) allows detection of both amplification and mutation of the HER2 gene providing new options of therapy especially in the case of activating mutations.
AIM: The focus of these five studies was on human clear cell, glycogen-storing lesions of the liver and kidney, which pertain to preneoplastic lesions of hepatocellular carcinoma and renal cell carcinoma in animal models...AIM: The focus of these five studies was on human clear cell, glycogen-storing lesions of the liver and kidney, which pertain to preneoplastic lesions of hepatocellular carcinoma and renal cell carcinoma in animal models of diabetes-associated carcinogenesis. MATERIAL AND METHODS: Noncirrhotic hepatic and renal tissue of humans, rats, and mice were analyzed with histology, immunohistochemistry, electron microscopy, and molecular biologic methods. RESULTS: In humans, clear cell lesions often occur in noncirrhotic liver and renal tissue. They resemble preneoplastic lesions of experimental hepato- and nephrocarcinogenesis regarding glycogen storage, increased proliferative activity, upregulation of glycolysis and de novo lipogenesis (lipogenic phenotype), and activated protooncogenic signaling pathway of AKT/mTOR. In two models of murine hepatocarcinogenesis, the important role of the transcription factor ChREBP as a "metabolic oncogene" was characterized. CONCLUSION: In these studies, the significance of small glycogen storing parenchymal alterations for carcinogenesis in human noncirrhotic liver and kidney was demonstrated due to their already present metabolic and molecular alterations. Therefore, they have to represent indicator lesions for an increased risk of carcinogenesis. Activation of the protooncogenic pathway AKT/mTOR as well as the transcription factor ChREBP and the manifestation of the lipogenic phenotype are crucial during the processes of carcinogenesis.
Primary vaginal carcinoma is rare. There are two pathogenetic pathways, one associated with HPV high-risk infection and another one with inactivation of p53. Vaginal Paget's disease is rare and mostly associated with vul...Primary vaginal carcinoma is rare. There are two pathogenetic pathways, one associated with HPV high-risk infection and another one with inactivation of p53. Vaginal Paget's disease is rare and mostly associated with vulvar disease or represents intravaginal spread of associated locoregional cancer. Diagnostic vaginal biopsies should be examined by step sections on H&E. Sentinel lymph nodes should be processed completely using ultrastaging. Morphology-based prognostic factors with good clinical evidence are tumour stage and lymph node status. Molecular markers are not currently relevant for treatment decision and prognosis.
Colorectal carcinomas are the second most common cancer and cause of cancer death in Germany for both men and women. Different aspects of morphological, immunohistochemical, and molecular pathological prognostic factors...Colorectal carcinomas are the second most common cancer and cause of cancer death in Germany for both men and women. Different aspects of morphological, immunohistochemical, and molecular pathological prognostic factors of colorectal carcinomas and their precursors were investigated. We demonstrated the prognostic relevance and importance of a precise classification of pericolonic tumor deposits (PTDs) in the pT category of the TNM classification. Furthermore, we demonstrated that patients with regional lymph node metastases after neoadjuvant chemoradiotherapy (nCRT) in rectal carcinomas with ypN0 status do not have a worse prognosis than patients without signs of preoperative lymph node metastases.Molecular pathological examinations of so-called serrated colorectal fibroblastic polyps as possible precursor lesions of colorectal carcinomas showed that their epithelial area represents a true neoplastic component and thus allows for their consideration in the context of a risk assessment for colorectal carcinomas.
This paper briefly summarizes the late-breaking session "Pathology and COVID-19" that took place at the virtual congress of the German Society of Pathology on June 6, 2020. The lectures tackled a broad variety of aspects...This paper briefly summarizes the late-breaking session "Pathology and COVID-19" that took place at the virtual congress of the German Society of Pathology on June 6, 2020. The lectures tackled a broad variety of aspects, including the German Registry for COVID-19 autopsies (DeRegCOVID), the detection methods of SARS-CoV‑2 in pathological material, the typical lung findings in severe COVID-19 cases, the distinct (micro)vascular changes and the cardiac and gastrointestinal involvement in COVID-19. In summary, in this first scientific meeting in German pathology on the COVID-19 pandemic, it became clear that pathologists in Germany, Austria and Switzerland have reacted very quickly to the pandemic and have established an autopsy program that has led to medically highly relevant findings.
The CT and MRI scans of a 70-year-old male patient revealed a mass in the pancreatic head and a 2.8-cm peripancreatic lymph node. Under steroid therapy the mass did not show regression. Finally, a pancreatoduodenectomy w...The CT and MRI scans of a 70-year-old male patient revealed a mass in the pancreatic head and a 2.8-cm peripancreatic lymph node. Under steroid therapy the mass did not show regression. Finally, a pancreatoduodenectomy was performed. Histologically, Rosai-Dorfman disease (RDD) was diagnosed. RDD is a rare histiocytic disorder with usually nodal but sometimes also extranodal involvement. Herein we report a rare case of extranodal RDD with intrapancreatic localization.
COVID-19 disease is a systemic inflammatory viral reaction starting with the viral phase followed by the inflammatory phase. The first phase is rather mild and asymptomatic with only a small subset of infected patients t...COVID-19 disease is a systemic inflammatory viral reaction starting with the viral phase followed by the inflammatory phase. The first phase is rather mild and asymptomatic with only a small subset of infected patients turning into the inflammatory phase with high mortality. Patients with pre-existing cardiovascular diseases and cardiovascular risk factors pose a considerably higher risk to develop severe or lethal COVID-19 disease course. COVID-19 affects not only the epithelial cells of the lung parenchyma via ACE2, but also endothelial cells across the whole body thus leading to generalized endothelial damage and inflammation, so-called endotheliitis. The histological morphology of endotheliitis comprises the accumulation of lymphocytes, plasma cells and macrophages beneath the endothelial cells and within the perivascular spaces. Endothelial cells play an important role in the regulation of vascular tone and the maintenance of vascular homeostasis. Endotheliitis thus can shift the vascular equilibrium towards more pronounced vasoconstriction with subsequent organ ischemia, inflammation with associated tissue edema and a procoagulant state. Patients with pre-existing endothelial dysfunction (male sex, smoking, hypertension, diabetes, obesity, and established cardiovascular disease) are particularly vulnerable and have adverse outcomes in COVID-19. This is a rationale for approaches to stabilize the endothelium. Most of these findings have been established from autopsies since the outbreak of the pandemic.
In contrast to other tumour entities such as lung carcinoma, melanoma or gynaecological and gastrointestinal tumours, the routine application of mutation analyses using high-throughput sequencing via next-generation sequ...In contrast to other tumour entities such as lung carcinoma, melanoma or gynaecological and gastrointestinal tumours, the routine application of mutation analyses using high-throughput sequencing via next-generation sequencing (NGS) has not yet been widely established in haematopathology, especially not in lymphomas.Here we describe our experience with the use and routine implementation of a lymphoma NGS panel primarily developed for research purposes.In addition to a discussion of the steps necessary for transferring such a panel into the routine framework of an accredited institute, we show by the comprehensive workup of 80 investigations and the presentation of several case studies how the panel was able to guide us to the correct diagnosis and how it also provided clinicians with indications for possible tailored therapy options.Even if NGS does not (yet) have to be routinely applied in lymphoma diagnostics for every case, a respectively dedicated NGS panel offers the advantage of having an additional option in the case of difficult differential diagnostic considerations or uncertainties as well as at the request of the treating oncologist to identify potential targets for tailored treatment of the patients.
BACKGROUND: Testicular type II germ cell tumours (GCTs) are an exemplar of a curable cancer and the most common malignancy in males aged ≤35 years. Even in metastatic stages, about 70% of patients can be cured by cisplat...BACKGROUND: Testicular type II germ cell tumours (GCTs) are an exemplar of a curable cancer and the most common malignancy in males aged ≤35 years. Even in metastatic stages, about 70% of patients can be cured by cisplatin-based chemotherapy and multimodal treatments. For patients failing platinum-based standard therapy, prognosis is poor and novel biomarkers and therapeutic options are urgently needed. OBJECTIVES: Discussion of desired histopathological information to guide urologists' and oncologists' decision making in the treatment of male GCTs. MATERIAL AND METHODS: A narrative review of histopathological key features of male GCT tissue samples for clinical decision making. RESULTS: Histopathological workup is crucial to identify (i) a GCT origin in cancers of unknown primary based on isochromosome 12p (i(12p)) detection, (ii) the different type II GCT subtypes, and (iii) risk factors, i.e. lymphovascular or rete testis invasion, among others. Proper histopathological diagnosis is indispensable for guideline-endorsed, histology-driven, and risk-adapted treatment decisions, hereby helping to maintain treatment success while reducing the therapeutic burden and potential long-term sequelae of multimodal treatments. For refractory patients failing standard treatment options, prognosis remains poor and, so far, neither predictive or prognostic biomarkers nor novel therapeutic targets have been established. CONCLUSIONS: Close interaction and interdisciplinary discussion of histopathologic and radiologic findings and established risk factors including serum tumour markers is crucial for successful treatment including intensified strategies, where necessary, or prevention of overtreatment, where possible.
In 2022 the new in vitro diagnostic regulation (IVDR) of the European Union will come into full effect. This complex regulatory framework aims at a stricter regulation and monitoring of industrial diagnostic assay produc...In 2022 the new in vitro diagnostic regulation (IVDR) of the European Union will come into full effect. This complex regulatory framework aims at a stricter regulation and monitoring of industrial diagnostic assay production. The IVDR defines many new methodological requirements and includes an additional entirely new focus on the clinical validity of diagnostic assays as well as a novel tighter vigilance system. Although not the core of the regulation, the whole field of laboratory developed tests (LDTs) is also subject to fundamental restructuring within this regulatory framework. The respective requirements are broad and will pose many challenges to assay developers and users in pathology. The many new aspects of LDT production and use must be properly addressed to avoid a bottleneck in diagnostic assay availability. In this article, the impact of the different aspects of the IVDR on European pathology laboratories will be discussed.
The impact of liquid biopsies on the analysis of molecular alterations of circulating tumor DNA (ctDNA) has recently increased. PIK3CA is one of the most frequently mutated genes in breast cancer and the expected approva...The impact of liquid biopsies on the analysis of molecular alterations of circulating tumor DNA (ctDNA) has recently increased. PIK3CA is one of the most frequently mutated genes in breast cancer and the expected approval of targeted PIK3CA therapy based on the results of the SOLAR1 trial is likely to lead to the use of liquid biopsies as another promising testing strategy in breast cancer patients who can benefit from a targeted therapy.Choosing an appropriate method for the detection of activating PIK3CA mutations should include factors like sensitivity, specificity, and limit of detection. The test should at least meet the parameters of the assay used in the drug approval study.If carefully used, PIK3CA mutation detection with liquid biopsies can then be a useful addition to standard tissue diagnostics.