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Purpose: Melanocytic nevi in lymph nodes (NNs) are an important histological differential diagnosis of initial sentinel lymph node (SN) metastasis in melanoma. Our aim was to associate NN in SNs with clinicopathologic features and survival rates in 1, 250 patients with SN biopsy for melanoma., Methods: To compare patients with present and absent NN, we used Fisher's exact test, Mann-Whitney U test, and multivariate logistic regression models in this retrospective observational study based on a prospectively maintained institutional database., Results: NN prevalence in axillary, cervical, and groin SNs was 16.5%, 19.4%, and 9.8%, respectively. NN were observed in combination with all growth patterns of melanoma, but more frequently when the primary was histologically associated with a cutaneous nevus. We observed a decreasing NN prevalence with increasing SN metastasis diameter. Multiple logistic regression determined a significantly increased NN probability for SNs of the neck or axilla, for individuals with ≥ 50 cutaneous nevi, midline primary melanomas, and for individuals who reported non-cutaneous malignancies in their parents. Cancer in parents was also significantly more frequently reported by melanoma patients who had more than 50 cutaneous nevi. In SN-negative patients, NN indicated a tendency for slightly lower melanoma-specific survival., Conclusions: We found a highly significant association between NN diagnosis and multiple cutaneous nevi and provided circumstantial evidence that cutaneous nevi in the drainage area of lymph nodes are particularly important. The trend toward lower melanoma-specific survival in SN-negative patients with NN suggests that careful differentiation of SN metastases is important., (© 2022. The Author(s).)

The oculomotor system can initiate remarkably accurate saccades towards moving targets (interceptive saccades) the processing of which is still under debate. The generation of these saccades requires the oculomotor centers to have information about the motion parameters of the target that then must be extrapolated to bridge the inherent processing delays. We investigated to what degree the information about motion of a saccade target is available in the lateral intra-parietal area (area LIP) of macaque monkeys for generation of accurate interceptive saccades. When a multi-layer neural network was trained based on neural discharges from area LIP around the time of saccades towards stationary targets, it was also able to predict the end points of saccades directed towards moving targets. This prediction, however, lagged behind the actual post-saccadic position of the moving target by ~ 80 ms when the whole neuronal sample of 105 neurons was used. We further found that single neurons differentially code for the motion of the target. Selecting neurons with the strongest representation of target motion reduced this lag to ~ 30 ms which represents the position of the moving target approximately at the onset of the interceptive saccade. We conclude that-similarly to recent findings from the Superior Colliculus (Goffart et al. J Neurophysiol 118(5):2890-2901)-there is a continuum of contributions of individual LIP neurons to the accuracy of interceptive saccades. A contribution of other gaze control centers (like the cerebellum or the frontal eye field) that further increase the saccadic accuracy is, however, likely., (© 2021. The Author(s).)

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.

Background: Technical advancement and availability of high-throughput analysis has advanced molecular subtyping of most cancers. Thus, new possibilities for precision oncology have emerged., Aim: Therefore, we aimed to collect data regarding availability and use of next generation sequencing (NGS) for urothelial cancer within the uropathology working group of the German Society of Pathology., Methods: We collected data by questionnaires and additionally asked for sequencing results of bladder cancers in the participating institutions., Results: A total of 13 university-affiliated institutes of pathology took part in the survey. All university institutes offer NGS-based molecular panel diagnostics and provide panels covering between 15 and 170 genes. Altogether, only 20 bladder cancers were sequenced in routine diagnostics and for 10 cancers potential targeted treatment options were available., Discussion: So far, despite availability of NGS diagnostics at university institutes of pathology, only few bladder cancer samples have been sequenced. Based on current data from the molecular subtyping of bladder cancers, we recommend a step-by-step protocol with basic immunohistochemistry analysis and subsequent subtype-dependent analyses, e.g., alterations of the fibroblast growth factor receptors (FGFR) or comprehensive gene panel analyses.

Today, tumour classification has been expanded due to immunohistochemical and molecular-pathological analyses due to corresponding patterns/profiles of protein and gene expression. The latter analyses often include growth factors and their ligands, intracellular signalling pathways, DNA-binding proteins, and oncogenes and suppressor genes, thus functionally including primarily the regulation of growth including angiogenesis and apoptosis as well as the induction of metastases to adhesion and migration disorders. Based on observations that testicular tumours often show microcalcifications, possibly due to impaired calcium metabolism, we focused on calcium-dependent transmembrane proteins, particularly cadherins, in the search for new tumour markers and therapeutic targets. N‑cadherin is expressed differently in the various subtypes of germ cell tumours and is useful in N‑cadherin-positive germ cell tumours as a novel therapeutic targeting structure, particularly in cisplatin resistance, due to functional analysis. In the tumours of the sex cord stroma beta-catenin and the transcription factor SOX-9 give a clear classification of these tumours. Thus, morphological investigations prove to be pilot experiments to purposefully narrow the spectrum of functionally important proteins and thus to establish promising new differential diagnostic markers or target structures.

The mediastinum is among the most frequent anatomic region in which germ cell tumors (GCT) arise, second only to the gonads. Mediastinal GCT (mGCT) account for 16 % of all mediastinal neoplasms. Although the morphology and (according to all available data) the molecular genetics of mediastinal and gonadal GCT are identical, a number of unique aspects exist. There is a highly relevant bi-modal age distribution. In pre-pubertal children of both sexes, mGCT consist exclusively of teratomas and yolk sac tumors. The prognosis is generally favorable with modern treatment. In post-pubertal adults, virtually all patients with malignant mGCT are males; the prognosis is more guarded and depends (among other factors) on the histological GCT components and is similar to GCT in other organs. So-called somatic type malignancies (i. e. clonally related, non-germ cell neoplasias arising in a GCT) are much more frequent in mGCT than in other organs, and the association between mediastinal yolk sac tumors and hematological malignancies, such as myelodysplasias and leukemias, is unique to mediastinal tumors. The prognosis of GCT with somatic type malignancies is generally dismal.

According to the World Health Organization (WHO) classification Leydig cell tumors, Sertoli cell tumors and granulosa cell tumors of the testes belong to the group of sex cord-stromal tumors. These tumors most frequently occur sporadically but in rare cases can be associated with syndromes. These tumor entities show characteristic morphological changes, which in combination with specific immunohistochemical markers facilitate the diagnosis. Recent results of molecular pathological investigations, especially beta-catenin mutation analysis, allow a better categorization of these tumor entities.

The group of non-seminomatous germ cell tumors can be morphologically and therapeutically distinguished from the group of seminomas. The group of non-seminomatous germ cell tumors includes embryonal carcinoma, yolk sac tumor, choriocarcinoma and teratoma. All entities can occur rarely in pure form or much more commonly in mixed germ cell tumors consisting of more than one histological type. The non-seminomatous germ cell tumors are also characterized by the appearance of an isochromosome 12p, i(12p) and arise from a common precursor lesion called intratubular germ cell neoplasia of the unclassified type (ITGCNU). Various immunohistochemical markers are used to distinguish the different tumor components in addition to morphological characteristics.

According to the World Health Organization (WHO) classification from 2004, sex cord gonadal stromal tumors are divided into Leydig cell tumors, Sertoli cell tumors, granulosa cell tumors, tumors of the thecoma-fibroma group, incompletely differentiated sex cord gonadal stromal tumors, mixed forms of sex cord gonadal stromal tumors and tumors containing both germ cell and sex cord gonadal stromal elements. These tumors can appear sporadically or in combination with hereditary syndromes. To diagnose these rare tumors the combination of characteristic morphological aspects and various immunohistochemical markers is useful. Latest investigations demonstrate the potential role of mutation analyses in the diagnosis of this heterogeneous group of tumors.