Osteoclastic giant cells represent a common cellular component of lesions arising in bone. Highlighting this morphological finding, the current WHO classification of bone tumors defines a diagnostic group comprising aneurysmal bone cyst, giant cell tumor of bone and non-ossifying fibroma, which may display morphologic similarities while being distinct with regard to molecular and biological features. Starting with these tumors - putting a focus on lesions arising in bone - this article gives a survey of other (chondrogenic and osteogenic) tumors that frequently contain osteoclastic giant cells, which may, particularly in small biopsies, enter differential diagnosis. Overlapping features with selected giant cell-containing soft tissue tumors, which may be of differential diagnostic relevance in daily routine, are discussed.

Over the last 20 years, numerous technical innovations have been introduced to the histopathology laboratory, providing tools for improved standardization and occupational safety. Digital tracking serves as a backbone accompanying the workflow from labeling cassettes and slides to the final steps of preparation of whole slide images and archiving blocks and sections. Multifunctional devices eliminated time consuming manual work prone to mistakes and loss of materials. At present, collaborative robots take over manual work that was considered to be exclusive to humans. The advent of these new technologies is expected to ameliorate the increasing staffing shortage in the laboratory and on the side of histopathologists as well.

The 2020 WHO Classification defines the spindle cell, epithelioid, and myxoid variants as subtypes of uterine leiomyosarcomas (LMS). Presence of cellular atypia (size variation of polymorphic nuclei > 2-3:1), tumor cell necroses, and mitotic count (usually ≥ 10 MF/10 HPF) are still the key features for diagnostic separation from uterine leiomyomas. Preanalytic variables, staining quality, as well as intralesional geographic distribution may affect the mitotic count. Smooth muscle tumors of uncertain malignant potential (STUMP) still exist as a not yet well-characterized diagnostic entity. Immunohistochemical stains against p16, p53, Ki-67, and WT‑1 may aid differential diagnosis in selected cases. Diagnostic molecular pathology is not yet relevant for diagnosis.

Given the rapid developments, there is no doubt that artificial intelligence (AI) will substantially impact pathological diagnostics. However, it remains an open question if AI will primarily be another diagnostic tool, such as immunohistochemistry, or if AI will also be able to replace human expertise. Most current studies on AI in histopathology deal with relatively simple diagnostic problems and are not yet capable of coping with the complexity of routine diagnostics. While some methods in molecular pathology would already be unthinkable without AI, it remains to be shown how AI will also be able to help with difficult histomorphological differential diagnoses in the future.

Predictive immunochemistry is a time-, tumor sample- and cost-efficient method for testing the increasing number of predictive biomarkers in advanced non-small cell lung cancer (NSCLC). Immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded (FFPE) tumor tissue has an established role in detecting PD-L1 expression and in ALK, ROS1, and more recently NTRK testing. Cytology specimens as a source for predictive biomarker testing in NSCLC is very important as up to 40% of all NSCLC are diagnosed by cytology alone.Despite the established role of cytology in lung cancer diagnosis, no commercial IHC assays have been validated for cytology specimens.FFPE cell blocks (CB) are the most straightforward cytology preparation for predictive immunocytochemistry (ICC) as the results are valid using protocols standardized for FFPE histology. But CB are not always available.With non-CB cytology specimens being less standardized than FFPE histology and with considerable preanalytical variability, rigorous cytology-specific ICC protocol optimization, validation, and quality control are required. With this prerequisite, predictive ICC, most commonly performed on Papanicolaou-stained cytology specimens, is robust and reliable on non-CB preparations. This valuable material should not be underutilized for predictive biomarker testing, as this would put patients at risk of unnecessary repeat sampling. This review highlights preanalytical, analytical, and postanalytical aspects that may influence ICC results and summarizes the published data on predictive ICC for PD-L1, ALK, and ROS1 in NSCLC.

Pediatric liver tumors are very rare tumors and account for less than 1% of all childhood malignancies. By far the most common tumors are hepatoblastomas. This review discusses epithelial malignant childhood liver tumors, with particular attention to the morphology of the different hepatoblastoma subtypes. In addition, other malignant liver tumors such as the so-called hepatocellular tumor NOS and the second-most common childhood liver tumor, the hepatocellular carcinoma, are discussed. In addition to the typical morphological characteristics, the immunohistochemical and molecular aspects are also be presented, which can help to distinguish these entities with often overlapping morphology.

Uterine sarcomas are a heterogeneous group of rare malignancies. Mostly (40-50%), they are leiomyosarcomas, followed by endometrial stromal sarcomas (ESS), low-grade (LG) and high-grade (HG), as well as undifferentiated sarcoma of the uterus (UUS) and adenosarcomas (AS). Other, non-organ-specific tumours such as NTRK-rearranged spindle cell neoplasia, perivascular epithelioid cell tumour (PEComa) and inflammatory myofibroblastic tumour (IMT) are extremely difficult to differentiate.In the most recent WHO classification, endometrial stromal tumours are subdivided as follows: benign, expansively growing endometrial stromal nodule (ESN) with sharp demarcation, the histologically similar-looking LG-ESS with infiltrative growth, the highly malignant HG-ESS and, as a diagnosis of exclusion, the highly aggressive UUS lacking specific lines of differentiation. LG-ESS can be differentiated from HG-ESS in most cases histomorphologically and immunohistochemically, but molecular investigations are necessary in individual cases. HG-ESS can be divided into 4 subtypes (YWHAE/NUTM2 fusion low-grade component, YWHAE/NUTM2 fusion high-grade component, ZC3H7B-BCOR fusion or BCOR-ITD) on the basis of molecular findings. Prognostically unfavourable factors in AS are severe sarcomatous overgrowth, deep myometrial invasion, high-grade histology and lymphatic vessel invasion. Tumours with NTRK fusion are immunohistochemically positive for S100 and TRK. PEComas express cathepsin K and HMB45, as well as TFE3 when translocation is present. Almost every IMT shows an alteration in the ALK gene In the case of overlapping morphology and simultaneous therapeutic and prognostic relevance, it is becoming increasingly important to verify or confirm the suspected histomorphological diagnosis by immunohistochemical and possibly molecular investigations.

The assessment of kidney biopsies is mainly confined to specialized centres. However, sometimes a kidney biopsy is submitted to a general pathologist, and in addition peritumorous renal parenchyma in tumour nephrectomies can have concomitant non-neoplastic renal disease. Here we present a survey of inflammatory and immunologic changes in all renal compartments, which may in part indicate the need of prompt therapeutic intervention such as in vasculitis, glomerulonephritis and interstitial nephritis. It is important to take into account that renal involvement of vasculitis is mainly centred in glomeruli and only to a much lesser extent in arteries, and that the frequently observed interstitial inflammation very often is an epiphenomenon of another primary kidney disease and not an independent disease process. Typical renal patterns of injury are emphasised.

Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent chronic liver diseases with a rising incidence in industrial countries. This is accompanied by an increased prevalence for NAFLD-associated liver cirrhosis and an increased risk for developing hepatocellular carcinoma. The current gold standard in the diagnostics is a liver biopsy. The histopathological evaluation is performed through semiquantitative scoring. To optimize the standardization and quantification of the existing scoring systems, in the coming years procedures with artificial intelligence, such as deep learning models could be used. Fields of application could be the supplementation of conventional histopathological diagnostics, the identification of new predictive parameters for estimating the prognosis and the prediction of a possible response to treatment.

Multiprobe fluorescence in situ hybridization (FISH) still remains the gold standard for clarifying inconclusive atypia in urinary cytology in daily routine practice. The Paris Classification System (The Paris System, TPS) provides an important basis for the specific indication of FISH and emphasizes the importance of morphological correlation for an integrative approach to diagnosis. Next-generation sequencing technology in urinary specimens, which is highly sensitive for simultaneous detection of multiple genetic alterations, is also likely to play a diagnostic role in the near future.