Pathologie (Heidelberg, Germany)最新文献

Hepatocellular carcinoma (HCC) usually arises on the background of liver cirrhosis. Common risk factors include chronic hepatitis B/C, alcohol abuse, metabolic dysfunction-associated steatotic liver disease (MASLD), and genetic disorders. Annually, 1-8% of cirrhotic patients develop HCC. According to the S3 guideline, biannual screening via ultrasound is recommended. In cirrhotic livers, high-grade dysplastic nodules (HGDN) are recognized as definite precursor lesions with high malignant transformation potential. According to the updated S3 guideline, HCC diagnosis in cirrhosis is primarily based on imaging (CT, MRI, or contrast-enhanced ultrasound): for lesions ≥ 2 cm, a typical enhancement pattern in one modality suffices; for 1-2 cm, two concordant imaging methods are required. Biopsy is only recommended in diagnostically unclear cases. In non-cirrhotic livers, however, histopathological confirmation via biopsy is mandatory due to insufficient specificity of imaging.Histologically, HCC is characterized by architectural distortion, nuclear atypia, and loss of the reticulin fiber network (Gomori stain). If malignancy criteria are inconclusive in biopsy, an immunohistochemical panel including Glypican‑3, HSP70, and glutamine synthetase can be used-expression of at least two markers strongly supports HCC diagnosis. Molecular analysis of hTERT promoter mutations may provide additional diagnostic value.Foci of altered hepatocytes (FAH) are considered putative early precursor lesions in both cirrhotic and non-cirrhotic human livers. They show increased glycogen and/or lipid accumulation, activation of the PI3K/AKT/mTOR pathway, and metabolic shifts resembling early preneoplastic changes observed in experimental hepatocarcinogenesis.

Large gland lesions of the prostate encompass a spectrum of entities from benign histoanatomic variation to invasive high-grade carcinoma. Despite overlapping morphologic features, accurate diagnosis is critical because the clinical management of these lesions varies from no additional follow-up to possible definitive resection or radiotherapy. This manuscript provides a concise overview of large gland lesions with a focus on practical diagnostic features and clinical significance. Where necessary, a brief historical perspective is included as many of these entities have diagnostic and molecular criteria which are still being established. Unfortunately, controversies and lack of consensus within urologic subspecialty groups have made this a challenging topic for the broader pathologist community. This paper serves as a snapshot of our current understanding of the spectrum of intraductal lesions of the prostate and their mimics.

Neuroendocrine (NE) cells in the prostate are part of the diffuse NE system and are found in both the normal prostate and acinar adenocarcinomas, occasionally exhibiting Paneth cell-like morphology.NE cells produce peptide hormones and biogenic amines that influence the differentiation and growth of the prostate glands through paracrine signaling; however, they do not show proliferative activity and lack androgen receptors (AR).Prostate tumors with NE differentiation are classified into five groups: (1) acinar adenocarcinomas with partial NE differentiation, detectable only by immunohistochemistry, (2) adenocarcinomas with Paneth cell-like differentiation, (3) NE tumors/carcinoids (NET), (4) small cell NE carcinomas (SCNEC), and (5) large cell NE carcinomas (LCNEC).The significance of partial and Paneth cell-like differentiation in adenocarcinomas remains under discussion and plays a minor role in routine diagnostics. NETs are extremely rare and appear to behave similarly to NETs of the gastrointestinal tract. In contrast, SCNECs and LCNECs are aggressive tumors with important clinical relevance, as they have a poor prognosis and require aggressive treatment.Therapy-associated neuroendocrine prostate carcinomas (t-NEPC) are recognized as a distinct entity for the first time in the WHO classification (5th edition, 2022). It arises through transdifferentiation via epigenetic changes following androgen deprivation and is characterized by AR loss and high proliferation, among other features. As with primary NE carcinomas, aggressive therapy is indicated. Therefore, a follow-up biopsy is recommended for castration-resistant progressive prostate cancer to confirm this aggressive phenotype.

Infectious colitis comprises histologically a spectrum from normal mucosa to severe inflammation with ulceration. In many cases, a diagnosis is made microbiologically or virologically. Nevertheless, histology still plays an important role, given its potential time and cost-advantages as well as its possibility to provide a statement on differential diagnoses, leading to different therapeutic treatment strategies (anti-infective drugs, surgery, immunosuppressive agents). The pathologists' role is especially important in three scenarios: 1) The infectious agent is directly visible by light microscopy. 2) The infection shows a specific or diagnostic morphological feature. 3) The infection shows a nonspecific histological inflammation pattern and must be distinguished from important differential diagnoses, most notably chronic inflammatory bowel diseases. In this article, examples from all three diagnostic groups, their diagnostic criteria and, differential diagnosis are discussed.

The grossing and reporting of radical prostatectomy specimens are key issues in pathology. Consensus conferences have defined clear guidelines for UICC/TNM-relevant parameters, while the extent of embedding remains controversial. Various embedding protocols, such as the Bonn protocol, enable efficient processing with consistent diagnostic significance. The increasing use of standardized diagnostic schemes, such as those developed by the International Collaboration on Cancer Reporting (ICCR), can ensure (international) comparability of diagnoses. This paper explains the criteria for embedding and reporting with a particular focus on prognostically relevant findings such as the differentiation between pT2 and pT3 tumors.

Background: Trophoblast surface antigen 2 (Trop-2) is a surface antigen that can be targeted by novel antibody-drug conjugates (ADCs). Here we report on the systematic evaluation of Trop‑2 expression and the determination of the biomarker in solid tumors as part of expanded protein diagnostics within the molecular tumor board (MTB) in Freiburg.

Methods: The pan-cancer cohort examined comprises 50 patients from the Comprehensive Cancer Center Freiburg who were enrolled in the MTB and additionally received a Trop‑2 IHC staining that was performed using formalin-fixed and paraffin-embedded tissue samples. Utilizing the H‑score, the samples were categorized into negative-, low-, moderate-, or high-expressing tumors. Additionally, mass spectrometry (MS)-based proteomics was performed on 22 tissue samples and used for correlation analysis with IHC expression levels.

Results: Trop‑2 expression was negative in 16%, low in 20%, moderate in 18%, and high in 46% of the assessed cases. The Trop‑2 IHC scores showed a positive correlation with MS-based protein intensities (Pearson correlation coefficient 0.48). Treatment recommendation for Trop‑2 ADC was given in 61% and Trop‑2 ADC was considered as the best therapeutic option in 20%.

Discussion: The evaluation of Trop‑2 expression might be helpful for personalized treatment recommendations in the off-label setting as well as ranking strategies for personalized therapeutic options within the MTB. The positive correlation between Trop‑2 IHC scores and MS-based protein intensities validates the IHC and demonstrates the promise of multi-omics assessment of therapeutic biomarkers.

Despite advances in imaging diagnostics, the histological confirmation of suspected carcinoma through prostate core needle biopsy remains essential for therapy planning. Diagnosis is based on established morphological criteria such as architectural disturbances, cellular atypia, and the loss of the basal cell layer. In addition to the most common acinar prostate carcinoma, various subtypes and rare histological patterns exist, which must be differentiated from benign mimickers. Immunohistochemical methods support diagnostic accuracy but should be carefully interpreted in the context of morphology. Tumor extent in core biopsy specimens should preferably be reported in millimeters. Diagnostic uncertainties can be coded as atypical small acinar proliferation (ASAP) or atypical intraductal proliferation (AIP) to facilitate appropriate clinical interpretation.