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Aims: Porocarcinoma is a malignant sweat gland tumour differentiated toward the upper part of the sweat duct and may arise from the transformation of a preexisting benign poroma. In 2019, Sekine et al. demonstrated the presence of YAP1::MAML2 and YAP1::NUTM1 fusions in most poromas and porocarcinomas. Recently, our group identified PAK2‐fusions in a subset of benign poromas. Herein we report a series of 12 porocarcinoma cases harbouring PAK1/2/3 fusions. Methods and Results: Five patients were male and the median age was 79 years (ranges: 59–95). Tumours were located on the trunk (n = 7), on the thigh (n = 3), neck (n = 1), or groin area (n = 1). Four patients developed distant metastases. Microscopically, seven cases harboured a benign poroma component and a malignant invasive part. Ductal formations were observed in all, while infundibular/horn cysts and cells with vacuolated cytoplasm were detected in seven and six tumours, respectively. In three cases, the invasive component consisted of a proliferation of elongated cells, some of which formed pseudovascular spaces, whereas the others harboured a predominant solid or trabecular growth pattern. Immunohistochemical staining for CEA and EMA confirmed the presence of ducts. Focal androgen receptor expression was detected in three specimens. Whole RNA sequencing evidenced LAMTOR1::PAK1 (n = 2), ZDHHC5::PAK1 (n = 2), DLG1::PAK2, CTDSP1::PAK1, CTNND1::PAK1, SSR1::PAK3, CTNNA1::PAK2, RNF13::PAK2, ROBO1::PAK2, and CD47::PAK2. Activating mutation of HRAS (G13V, n = 3, G13R, n = 1, Q61L, n = 2) was present in six cases. Conclusion: Our study suggests that PAK1/2/3 fusions is the oncogenic driver of a subset of porocarcinomas lacking YAP1 rearrangement. [ABSTRACT FROM AUTHOR]

Merkel cell carcinoma (MCC) is an aggressive skin cancer frequently caused by genomic integration of the Merkel cell polyomavirus (MCPyV). MCPyV‐negative cases often present as combined MCCs, which represent a distinctive subset of tumors characterized by association of an MCC with a second tumor component, mostly squamous cell carcinoma. Up to now, only exceptional cases of combined MCC with neuroblastic differentiation have been reported. Herein we describe two additional combined MCCs with neuroblastic differentiation and provide comprehensive morphologic, immunohistochemical, transcriptomic, genetic and epigenetic characterization of these tumors, which both arose in elderly men and appeared as an isolated inguinal adenopathy. Microscopic examination revealed biphasic tumors combining a poorly differentiated high‐grade carcinoma with a poorly differentiated neuroblastic component lacking signs of proliferation. Immunohistochemical investigation revealed keratin 20 and MCPyV T antigen (TA) in the MCC parts, while neuroblastic differentiation was confirmed in the other component in both cases. A clonal relation of the two components can be deduced from 20 and 14 shared acquired point mutations detected by whole exome analysis in both combined tumors, respectively. Spatial transcriptomics demonstrated a lower expression of stem cell marker genes such as SOX2 and MCM2 in the neuroblastic component. Interestingly, although the neuroblastic part lacked TA expression, the same genomic MCPyV integration and the same large T‐truncating mutations were observed in both tumor parts. Given that neuronal transdifferentiation upon TA repression has been reported for MCC cell lines, the most likely scenario for the two combined MCC/neuroblastic tumors is that neuroblastic transdifferentiation resulted from loss of TA expression in a subset of MCC cells. Indeed, DNA methylation profiling suggests an MCC‐typical cellular origin for the combined MCC/neuroblastomas. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Merkel cell carcinoma (MCC) is a highly aggressive skin cancer associated with integration of Merkel cell polyomavirus (MCPyV). MCPyV‐encoded T‐antigens (TAs) are pivotal for sustaining MCC's oncogenic phenotype, i.e., repression of TAs results in reactivation of the RB pathway and subsequent cell cycle arrest. However, the MCC cell line LoKe, characterized by a homozygous loss of the RB1 gene, exhibits uninterrupted cell cycle progression after shRNA‐mediated TA repression. This unique feature allows an in‐depth analysis of the effects of TAs beyond inhibition of the RB pathway, revealing the decrease in expression of stem cell‐related genes upon panTA‐knockdown. Analysis of gene regulatory networks identified members of the E2F family (E2F1, E2F8, TFDP1) as key transcriptional regulators that maintain stem cell properties in TA‐expressing MCC cells. Furthermore, minichromosome maintenance (MCM) genes, which encodes DNA‐binding licensing proteins essential for stem cell maintenance, were suppressed upon panTA‐knockdown. The decline in stemness occurred simultaneously with neural differentiation, marked by the increased expression of neurogenesis‐related genes such as neurexins, BTG2, and MYT1L. This upregulation can be attributed to heightened activity of PBX1 and BPTF, crucial regulators of neurogenesis pathways. The observations in LoKe were confirmed in an additional MCPyV‐positive MCC cell line in which RB1 was silenced before panTA‐knockdown. Moreover, spatially resolved transcriptomics demonstrated reduced TA expression in situ in a part of a MCC tumor characterized by neural differentiation. In summary, TAs are critical for maintaining stemness of MCC cells and suppressing neural differentiation, irrespective of their impact on the RB‐signaling pathway. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Sebaceous gland carcinomas are rare malignant cutaneous adnexal tumors with sebocytic differentiation. The typical predilection area is the head and neck region, where sebaceous gland carcinomas are the most common malignant adnexal tumors of the skin. According to their localization a distinction is made between periocular and extraocular sebaceous gland carcinomas. Muir‐Torre syndrome (MTS) should always be ruled out if it is suspected. In terms of prognosis, sebaceous gland carcinomas are potentially aggressive tumors with a clear tendency to recur and metastasize. Only small extraocular sebaceous gland carcinomas that have been completely resected have a very good prognosis. Sebaceous gland carcinomas most frequently metastasize lymphogenously to regional or distant lymph nodes; organ metastasis occurs less frequently. Periocular sebaceous gland carcinomas have a higher metastasis rate (up to 15%) than extraocular sebaceous gland carcinomas (up to 2%). Complete micrographically controlled surgery (MCS) of the primary tumor is the therapy of first choice, regardless of periocular or extraocular localization. Adjuvant or therapeutic radiotherapy may be considered. There is currently no established standard therapy for advanced, inoperable, or metastatic sebaceous gland carcinomas. Local procedures and systemic therapies such as chemotherapy or immunotherapy can be considered. The procedure should be determined individually by an interdisciplinary tumor board. Close follow‐up care is recommended for these potentially aggressive carcinomas. [ABSTRACT FROM AUTHOR]

Purpose/objectives: Due to the coronavirus disease 2019 (COVID‐19) pandemic, undergraduate education shifted towards online‐only formats from April 2020 until July 2021. Previous research indicated a negative effect on students' competence development, and it remains unclear whether blended learning concepts could provide compensation. Therefore, the present study aimed to compare pre‐ to post‐pandemic students' performance in standardized baseline (BL) and final exams (FE), as well as the associated knowledge gain (KG) in three consecutive undergraduate blended learning‐based oral radiology courses (C1‐3). Methods: Ninety‐four students participated during two pre‐pandemic semesters (October 17–July 18), and ninety‐eight students during two post‐pandemic semesters (October 21–July 22). Before the pandemic, conventional face‐to‐face lectures were combined with an oral radiology platform. Two years into the COVID‐19 pandemic, additional video‐based e‐learning modules were adopted from the pandemic online‐only curriculum. In each semester, skills and KG were assessed by conducting standardized BL and FE. Students' performance in BL, FE, and the associated KG during pre‐pandemic semesters was compared to post‐pandemic semesters. Results: In post‐pandemic courses, students showed significantly lower BL scores, whereas KG was significantly higher in post‐ compared to pre‐pandemic semesters (27.42% vs. 10.64%, p < 0.001, respectively). FE scores in C1 significantly improved from pre‐ to post‐pandemic semesters. Conclusions: Within the limitations of our study, the lower BL scores confirmed the negative effect of the pandemic on competence development. Blended learning concepts seem to compensate for this effect and enable students to return to pre‐pandemic levels. Future studies are needed to assess the additional impact of video‐based e‐learning modules. [ABSTRACT FROM AUTHOR]

Introduction: Blended learning seems to be an effective teaching concept in oral radiology. During the COVID‐19 pandemic, blended learning shifted towards online‐only learning. The aim of the present study was to compare the effectiveness of pandemic online‐only and pre‐pandemic blended learning in three consecutive oral radiology courses (C1, C2 and C3) and to examine whether additional video‐based e‐learning modules (VBLMs) had a positive impact on undergraduate students' performance during pandemic semesters. Materials and Methods: Data from 205 undergraduate dental students participating either in a blended learning or an online‐only learning concept were analysed. Pre‐pandemic blended learning comprised face‐to‐face seminars and access to an oral radiology platform (ORP). Pandemic online‐only learning comprised online seminars, access to the ORP and additional VBLMs (two VBLMs for C1, four VBLMs for C2 and six VBLMs for C3). Through standardised e‐exams at the beginning and end of each semester, performance in final exams and knowledge gain were compared between the two groups. Results: No significant differences in scores in final exams (p =.11) and knowledge gain (p =.18) were found when comparing the pre‐pandemic and pandemic groups. On course level, however, students receiving a lower number of VBLMs performed significantly worse in final exams (C1: p <.01, C2: p =.02) and showed inferior knowledge gain (C2: p <.01) during the pandemic. Conclusions: Within the limitations of the study, the present investigation confirmed that pandemic online‐only learning involving VBLMs might be as effective as pre‐pandemic blended learning. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Actinic keratosis (AK) are common lesions in light‐skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence‐based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was updated and expanded by the topics cutaneous squamous cell carcinoma in situ (Bowen's disease) and actinic cheilitis. The guideline is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office‐based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC. A separate guideline exists for patients and their relatives. In this part, we will address aspects relating to epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This article discusses a case report of a 75-year-old man with metastatic Merkel cell carcinoma (MCC) that was refractory to anti-PD-1 and anti-PD-L1 monotherapy. The patient showed a durable response to combined immunotherapy with ipilimumab (anti-CTLA-4) plus nivolumab (anti-PD-1). This case is the first to demonstrate a complete response to this combination therapy in a patient who did not respond to PD-L1 and PD-1 monotherapy. The findings suggest that the addition of a CTLA-4 inhibitor may enhance the anti-tumoral immunological response in MCC. [Extracted from the article]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Merkel cell carcinoma (MCC, ICD‐O M8247/3) is a rare, malignant, primary skin tumor with epithelial and neuroendocrine differentiation. The tumor cells share many morphologic, immunohistochemical, and ultrastructural features with cutaneous Merkel cells. Nevertheless, the cell of origin of MCC is unclear. MCC appears clinically as a reddish to purple spherical tumor with a smooth, shiny surface and a soft to turgid, elastic consistency, usually showing rapid growth. Spontaneous and often complete regressions of the tumor are observed. These likely immunologically‐mediated regressions explain the cases in which only lymph node or distant metastases are found at the time of initial diagnosis and why the tumor responds very well to immunomodulatory therapies even at advanced stages. Due to its aggressiveness, the usually given indication for sentinel lymph node biopsy, the indication of adjuvant therapies to be evaluated, as well as the complexity of the necessary diagnostics, clinical management should already be determined by an interdisciplinary tumor board at the time of initial diagnosis. [ABSTRACT FROM AUTHOR]

Background: Initial lymphatic vessels do not have a continuous basement membrane. Therefore, the ability of lymphatic endothelial cells (LECs) to produce extracellular matrix (ECM) has received little attention. Untreated lymphedema is a chronic disease that progresses to massive fibrosclerosis in advanced stages. Expansion of the intercellular space and fibrosclerosis cause hypoxia, which also affects the LECs. Results: We studied the expression of genes in human LECs in vitro by RNA sequencing, analyzed the effects of hypoxia (1% O2) vs. normoxia (21% O2), and focused on ECM genes. LECs express fibrillin‐1 and many typical components of a basement membrane such as type IV, VIII, and XVIII collagen, laminin β1, β2, and α4, perlecan, and fibronectin. Under hypoxia, we found significant upregulation of expression of genes controlling hydroxylation of procollagen (PLOD2, P4HA1), and also cross‐linking, bundling, and stabilization of collagen fibrils and fibers. Also striking was the highly significant downregulation of elastin expression, whereas fibulin‐5, which controls the assembly of tropoelastin monomers, was upregulated under hypoxia. In the dermis from genital lymphedema, we observed significant PLOD2 expression in initial lymphatics. Conclusions: Overall, hypoxia results in the picture of a dysregulated ECM production of LECs, which might be partly responsible for the progression of fibrosclerosis in lymphedema. Key Findings: Initial lymphatics do not produce a continuous basal lamina, nevertheless, lymphatic endothelial cells (LECs) express numerous ECM genes including collagen IV, V, VIII, XVIII, laminin, perlecan, fibronectin and fibrillin.RNASeq analyses show that LECs express approx. 16.800 genes. We observed significant regulation of 162 genes after 4 days of hypoxia (1% pO2). 13% (21 genes) of the hypoxia‐regulated genes are connected to the ECM.It is very likely that hypoxia is a crucial factor in the development of fibrosis in chronic lymphedema (LE), and our data suggest that hypoxic LECs can contribute to fibrosclerosis during LE progression. [ABSTRACT FROM AUTHOR]

Objectives: Long‐term follow‐up observations of zirconia implants are rare. This study aimed at evaluating the clinical performance of two‐piece zirconia implants in the posterior jaws over 9 years. Materials and Methods: Sixty partially edentulous patients were treated with two‐piece zirconia implants. In eight no primary stability could be achieved. Fifty‐two patients received the final restoration (i.e., cemented fibreglass abutments and all‐ceramic crowns). After 2 years, 2 implants failed and 4 dropouts were recorded. The remaining 46 patients with one target implant each were recalled at 9 years. Besides implant survival, clinical parameters at the implant level (plaque index–PI, bleeding on probing–BOP, probing depth–PD, mucosal recession–MR) were recorded and compared with previously collected data. Mechanical and technical complications were assessed. Results: Thirty patients responded. The mean observation period was of 111.1 ± 2.2 months. One implant was lost. Data recorded from the remaining 29 implants were analysed. PI values increased overtime. Mean BOP and PD remained unchanged during follow‐up. No additional cases of peri‐implantitis were recorded over the 10 diagnosed during the first 2 years of follow‐up. No significant changes in mean MR values were detected over time, with 65% of the all included implants exhibiting no recession at 9 years and all the others, but one, a maximum MR of 1 mm. Three technical and 6 mechanical complications occurred in 7 patients between 2‐ and 9‐years (6.9% and 20.7%, respectively, at patient level). Conclusion: Within the limitations of the present study, a high survival rate was registered. Albeit frequent mechanical and technical complications, two‐piece zirconia implants could represent a valid solution for the replacement of single teeth in the posterior jaws. [ABSTRACT FROM AUTHOR]

Zusammenfassung: Das Kaposi‐Sarkom (KS) ist eine seltene, maligne, von lymphatischen Endothelzellen ausgehende, multilokuläre Gefäßerkrankung, die vor allem Haut und Schleimhäute, aber auch das lymphatische System und innere Organe wie den Gastrointestinaltrakt, die Lunge oder die Leber befallen kann. Fünf epidemiologische Subtypen des KS mit variablem klinischem Verlauf und unterschiedlicher Prognose werden unterschieden, die in spezifischen Populationen vermehrt auftreten: (1) klassisches KS, (2) iatrogenes KS bei Immunsuppression, (3) endemisches (afrikanisches) lymphadenopathisches KS, (4) epidemisches, HIV‐assoziiertes KS und mit einem Immunrekonstitutions‐Inflammations‐Syndrom (IRIS) assoziiertes KS und (5) KS bei Männern, die Sex mit Männern haben (MSM) ohne HIV‐Infektion. Diese interdisziplinäre Leitlinie fasst aktuelle praxisrelevante Empfehlungen zu Diagnostik und Therapie der verschiedenen Formen des KS zusammen. Die in dieser Kurzleitlinie genannten Empfehlungen werden in der Langfassung der Leitlinie (Online‐Version des JDDG) detaillierter ausgeführt. [ABSTRACT FROM AUTHOR]

Summary: Kaposi's sarcoma (KS) is a rare, malignant, multilocular vascular disease originating from lymphatic endothelial cells that can primarily affect the skin and mucous membranes, but also the lymphatic system and internal organs such as the gastrointestinal tract, lungs or liver. Five epidemiological subtypes of KS with variable clinical course and prognosis are distinguished, with increased incidence in specific populations: (1) Classical KS, (2) Iatrogenic KS in immunosuppression, (3) Endemic (African) lymphadenopathic KS, (4) Epidemic, HIV‐associated KS and KS associated with immune reconstitution inflammatory syndrome (IRIS), and (5) KS in men who have sex with men (MSM) without HIV infection. This interdisciplinary guideline summarizes current practice‐relevant recommendations on diangostics and therapy of the different forms of KS. The recommendations mentioned in this short guideline are elaborated in more detail in the extended version of the guideline (online format of the JDDG). [ABSTRACT FROM AUTHOR]

Detailed examination of tumor components is leading‐edge to establish personalized cancer therapy. Accompanying research on cell‐free DNA, the cell count of circulating tumor cells (CTCs) in patient blood is seen as a crucial prognostic factor. The potential of CTC analysis is further not limited to the determination of the overall survival rate but sheds light on understanding inter‐ and intratumoral heterogeneity. In this regard, commercial CTC isolation devices combining an efficient enrichment of rare cells with a droplet deposition of single cells for downstream analysis are highly appreciated. The Liquid biopsy platform CTCelect was developed to realize a fully‐automated enrichment and single cell dispensing of CTCs from whole blood without pre‐processing. We characterized each process step with two different carcinoma cell lines demonstrating up to 87 % enrichment (n = 10) with EpCAM coupled immunomagnetic beads, 73 % optical detection and dispensing efficiency (n = 5). 40 to 56.7 % of cells were recovered after complete isolation from 7.5 ml untreated whole blood (n = 6). In this study, CTCelect enabled automated dispensing of single circulating tumor cells from HNSCC patient samples, qPCR‐based confirmation of tumor‐related biomarkers and immunostaining. Finally, the platform was compared to commercial CTC isolation technologies to highlight advantages and limitations of CTCelect. This system offers new possibilities for single cell screening in cancer diagnostics, individual therapy approaches and real‐time monitoring. [ABSTRACT FROM AUTHOR]

Objectives: To assess the clinical performance of an equine‐derived collagen‐containing bone block (CXBB) for lateral alveolar ridge augmentation and staged implant placement. Material and Methods: A total of n = 16 patients (16 implants) had received a modified surgical protocol for lateral ridge augmentation using a size‐adapted rigidly fixed CXBB and contour augmentation. After 26 weeks of submerged healing, the primary endpoint was defined as the final ridge width (RW26) sufficient to place an adequately dimensioned titanium implant at the respective sites. Secondary outcomes included the gain in ridge width (RWg) and the need for secondary grafting. Clinical outcomes (bleeding on probing—BOP, probing depth—PD, and mucosal recession—MR) were assessed at implant loading and after a median observation period of 12.3 months. Results: In all patients (n = 16) investigated, RW26 allowed for a successful placement of an adequately dimensioned titanium implant at respective sites exhibiting mean RWg values of 5.09 ± 1.07 mm. A soft tissue dehiscence was noted in one patient (6.3%), and a secondary grafting was needed in two patients (12.5%) The changes in mean BOP, PD, and MR values at V9 amounted to 10.23 ± 30.11%, 0.14 ± 0.80 mm, and −0.01 ± 0.04 mm, respectively. Conclusions: CXBB may represent a feasible approach for lateral alveolar ridge augmentation and two‐stage implant placement. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of the present survey is to give an update of European experts' opinion on infection control and prevention in dentistry during second wave of pandemic. The secondary aim was to analyze how experts' opinion changed in the light of the new scientific evidence since the first wave. Material & Methods: An anonymous online 14‐item questionnaire was sent to a total of 27 leading academic experts in Oral (and Maxillofacial) Surgery from different European countries, who had completed a previous survey in April‐May 2020. The questionnaire covered the topics of dental setting safety, personal protective equipment (PPE), and patient‐related measures to minimize transmission risk. Data collection took place in November‐February 2020/21. Results: 26 experts participated in the follow‐up survey. The overall transmission risk in dental settings was scored significantly lower compared to the initial survey (p <.05), though the risk associated with aerosol‐generating procedures (AGP) was still considered to be high. Maximum PPE was less frequently recommended for non‐AGP (p <.05), whereas the majority of experts still recommended FFP2/FFP3 masks (80.8%), face shields or goggles (88.5%), gowns (61.5%), and caps (57.7%) for AGP. Most of the experts also found mouth rinse relevant (73.1%) and reported to be using it prior to treatment (76.9%). No uniform opinion was found regarding the relevance of COVID‐19 testing of staff and patients. Conclusion: With the continuation of dental care provision, transmission risk has been scored lower compared to the first wave of pandemic. However, high risk is still assumed for AGP, and maximum PPE remained advised for the respective treatments. [ABSTRACT FROM AUTHOR]

A human cell line of neuroblastic tissue, which was believed to have been lost to science due to its unavailability in public repositories, is revived and reclassified. In the 1970s, a triple set of neuroblastoma (NB) cell lines became available for research as MYCNamplified vs nonamplified models (CHP-126/-134 and CHP-100, respectively). Confusingly, CHP-100 was used in subsequent years as a model for NB and, since the 1990s, as a model for neuroepithelioma and later as a model for Ewing's sarcoma (ES), which inevitably led to non-reproducible results. A deposit at a bioresource center revealed that globally available stocks of CHP-100 were identical to the prominent NB cell line IMR-32 and CHP-100 was included into the list of misidentified cell lines. Now we report on the rediscovery of an authentic CHP-100 cell line and provide evidence of incorrect classification during establishment. We show that CHP-100 cells carry a t(11;22)(q24;q12) type II EWSR1-FLI1 fusion and identify it as a classic ES. Although the question of whether CHP-100 was a virtual and never existing cell line from the beginning is now clarified, the results of all relevant publications should be considered questionable. Neither the time of the cross-contamination event with IMR-32 is known nor was the final classification as a model for Ewing family of tumors available with an associated short tandem repeat profile. After a long road of errors and confusion, authentic CHP-100 is now characterized as a type II EWSR1-FLI1 fusion model 44 years after its establishment. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate peri‐implant tissue dimensions following nonsurgical (NS) and surgical therapy (S) employing different decontamination protocols of advanced ligature‐induced peri‐implantitis in dogs. Material & Methods: Peri‐implantitis defects (n = 5 dogs, n = 30 implants) were randomly and equally allocated in a split‐mouth design to NS or S treatment using either an Er:YAG laser (ERL), an ultrasonic device (VUS), or plastic curettes + local application of metronidazole gel (PCM), respectively. Horizontal bone thickness (hBT) and soft tissue thickness (hMT) were measured at different reference points: (v0) at the marginal portion of the peri‐implant mucosa (PM); (v1) at 50% of the distance from PM to bone crest (BC); (v2) at the BC; (v3) at the most coronal extension of the bone‐to‐implant contact. Vertical peri‐implant tissue height was calculated from PM to BC. Results: All of the treatment groups showed a gradual hMT increase from v0 to the v2 reference point, followed by a reduction from v2 to the v3 region. The S‐VUS subgroup tended to be associated with higher hMT values at the v0 region than the NS‐VUS subgroup (0.44 mm versus 0.31 mm). PM‐BC distance varied from 2.22 to 2.83 mm in the NS group, and from 2.07 to 2.38 in the S group. Conclusion: Vertical and horizontal peri‐implant tissue dimensions were similar in different treatment groups. [ABSTRACT FROM AUTHOR]

The relevance of Hedgehog signaling in Merkel cell carcinoma has only been addressed by a few studies with conflicting results. Thus, we aimed to establish the expression of Hedgehog signaling molecules in Merkel cell carcinoma to characterize causes of aberrant expression and to correlate these findings with the clinical course of the patients. Immunohistochemistry was performed for Sonic, Indian, Patched 1 (PTCH1) and Smoothened on patients' tumor tissue. Respective mRNA expression was analyzed in 10 Merkel cell carcinoma cell lines using quantitative real‐time polymerase chain reaction. PTCH1 sequencing and DNA methylation microarray analyses were carried out on tumor tissues as well as cell lines. PTCH1 immunoreactivity in Merkel cell carcinoma was similar to that of basal cell carcinomas, which both significantly differed from PTCH1 immunoreactivity in healthy skin. Most PTCH1 mutations found were synonymous or without known functional impact. However, on average, the promoter regions of both PTCH1 were hypomethylated independently from PTCH1 gene expression or Merkel cell polyomavirus status. PTCH1 and GLI1/2/3 genes were differently expressed in different cell lines; notably, there was a significant correlation between GLI2 and PTCH1 mRNA expression. Similar to PTCH1 protein expression in patient tissues, PTCH1 gene expression in Merkel cell carcinoma cell lines is highly variable, but due to the similar methylation pattern across Merkel cell carcinoma cell lines, effects other than methylation seem to be the reason for the differential expression and PTCH1 appears to be upregulated by GLI as a classical Hedgehog target gene. [ABSTRACT FROM AUTHOR]

Objectives: The current COVID-19 outbreak in conjunction with the need to provide safe dental treatments and the limited knowledge on the efficacy of protective measures has posed dentists into a challenging situation. Therefore, the present article aimed at collecting experiences and recommendations of frontline clinical experts on critical aspects of dental treatment provision during pandemic. Material & Methods: From a total of 32 European countries, one leading academic expert in Oral and Maxillofacial Surgery or Oral Surgery per country was asked to participate in an anonymous online 10-item survey on COVID-19 covering the topics of safety of dental settings, personal protective equipment (PPE), and patient-related measures to reduce transmission risk. Data collection took place from April 12th to May 22nd, 2020. Results: A total of 27 experts from different European countries completed the survey. The transmission risk of SARS-CoV-2 in dental settings for aerosol-generating procedures was considered high by all experts except two. For aerosol-free and aerosol-generating procedures, more than 80% of the experts recommended face protection and caps for every single treatment. For aerosol-generating procedures, additional measures (FFP2/FFP3 masks and gowns) were suggested by the vast majority of the experts. To reduce transmission risk, all experts recommended limiting aerosol-generating procedures and reducing the number of patients in waiting areas as well as hand hygiene for the patients. Conclusion: The limitation of aerosol-generating procedures along with the usage of adequate personal protection equipment was considered to be crucial to protect dental healthcare providers and patients, thus reducing the transmission risk of COVID-19. [ABSTRACT FROM AUTHOR]

Direct comparisons of the incidence and survival of cutaneous vs mucocutaneous genital squamous cell carcinomas (SCCs) are lacking even though they may bring important insights. We aimed to compare incidence rates and survival of cutaneous and mucocutaneous genital SCCs head‐to‐head, using the same source population, cancer registry methodology and statistical methods in a population of predominantly white Caucasian descent. Using data (2007‐2015) from the population‐based cancer registry of North Rhine‐Westphalia, (population of 18 million people), we estimated age‐specific and age‐standardized (old European standard) incidence rates and age‐standardized relative 5‐year survival of SCC with the period approach for the period 2012 to 2015. Overall, 83 650 SCC cases were registered. The age‐standardized incidence rates (per 100 000 person‐years) of cutaneous SCCs were 36.5 (SE 0.17) and 17.0 (SE 0.11) among men and women, respectively, with corresponding rates for mucocutaneous genital skin, 1.3 (SE 0.03) and 4.5 (SE 0.06) for men and women, respectively. In all age groups, incidence rates of mucocutaneous genital SCCs were higher in women than men. Men had higher cutaneous SCC incidence at all nongenital subsites than women, with the exception of the lower extremities. Five‐year relative survival was considerably lower for mucocutaneous genital SCCs (men: 71%, women: 75%), especially of the scrotal skin (67%) and labia majora (62%) than for SCC of nongenital skin (men: 93%, women: 97%). Given their relatively high incidence together with a lower survival probability, future studies are warranted to establish therapies for advanced mucocutaneous genital SCC, such as immune checkpoint inhibition. What's new? Cutaneous and mucocutaneous genital squamous cell carcinoma (SCC) have distinct risk factors. In particular, unlike cutaneous SSC, mucocutaneous disease affects skin not chronically exposed to ultraviolet radiation. Incidence and survival differences between these diseases are largely unexplored. Here, analyses of cancer registry data from North Rhine‐Westphalia show that genital skin SCCs comprise a substantial proportion of SCCs of the body surface, especially in women. Five‐year relative survival was significantly lower for SCC of mucocutaneous genital skin than non‐genital skin SCC. The relatively high incidence and reduced survival of mucocutaneous genital SCC warrant further investigation for underlying mechanisms and potential therapies. [ABSTRACT FROM AUTHOR]

Background: To assess the influence of ridge preservation procedures on the healing of extraction sockets under antiresorptive therapy. Material and Methods: A total of 10 Dutch Belted rabbits were randomly allocated to either the intravenous administration of amino‐bisphosphonate (zoledronic acid) (Za) (n = 5) or a negative control group (no Za [nZa]) (n = 5). At 6 months, the mandibular and maxillary molars were extracted and the four experimental sites randomly allocated to the following subgroups: (a) socket grafting using a collagen‐coated natural bone mineral (BOC) + primary wound closure, (b) coronectomy (CO), or (c) spontaneous healing + primary wound closure (SP). Za medication was continued for another 4 months. Histomorphometrical analyses considered, for example, crestal hard tissue closure of the extraction site (C) and mineralized tissue (MT) formation. Results: Za‐SP was associated with an incomplete median C (31.76% vs 100% in nZa‐SP) and signs of bone arrosion along the confines of the socket. BOC had no major effects on increases in C and MT values in the Za group. CO commonly resulted in an encapsulation and partial replacement resorption of residual roots by MT without any histological signs of osteonecrosis. Conclusions: (a) Za‐SP was commonly associated with a compromised socket healing and signs of osteonecrosis, (b) BOC had no major effect on socket healing in the Za group, and (c) CO at noninfected teeth might be a feasible measure for the prevention of a Za‐related osteonecrosis of the jaw. [ABSTRACT FROM AUTHOR]

Spitzoid neoplasms are a challenging group of cutaneous melanocytic proliferations. They are characterized by epithelioid and/or spindle‐shaped melanocytes and classified as benign Spitz nevi (SN), atypical Spitz tumors (AST), or malignant Spitz tumors (MST). The intermediate AST category represents a diagnostically challenging group since on purely histopathological grounds, their benign or malignant character remains unpredictable. This results in uncertainties in patient treatment and prognosis. The molecular properties of Spitzoid lesions, especially their transcriptomic landscape, remain poorly understood, and genomic alterations in melanoma‐associated oncogenes are typically absent. The aim of this study was to characterize their transcriptome with digital mRNA expression profiling. Formalin‐fixed paraffin‐embedded samples (including 27 SN, 10 AST, and 14 MST) were analyzed using the NanoString nCounter PanCancer Pathways Panel. The number of significantly differentially expressed genes in SN vs. MST, SN vs. AST, and AST vs. MST was 68, 167, and 18, respectively. Gene set enrichment analysis revealed upregulation of pathways related to epithelial–mesenchymal transition and immunomodulatory‐, angiogenesis‐, hormonal‐, and myogenesis‐associated processes in AST and MST. A molecular signature of SN vs. MST was discovered based on the top‐ranked most informative genes: NRAS, NF1, BMP2, EIF2B4, IFNA17, and FZD9. The AST samples showed intermediate levels of the identified signature. This implies that the gene signature can potentially be used to distinguish high‐grade from low‐grade AST with a larger study cohort in the future. This combined histopathological and transcriptomic methodology is promising for prospective diagnostics of Spitzoid neoplasms and patient management in dermatological oncology. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Actinic keratoses (AKs) are common lesions in light‐skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence‐based framework for clinical decision making, the guidelines for actinic keratosis and cutaneous squamous cell carcinoma were developed using the highest level of methodology (S3) according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF). The guidelines are aimed at dermatologists, general practitioners, ENT specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office‐based settings as well as other medical specialties involved in the diagnosis and treatment of patients with AKs and cSCC. The guidelines are also aimed at affected patients, their relatives, policy makers and insurance funds. In the second part, we will address aspects relating to epidemiology, etiology, surgical and systemic treatment of cSCC, follow‐up and disease prevention, and discuss AKs and cSCC in the context of occupational disease regulations. [ABSTRACT FROM AUTHOR]

Zusammenfassung: Aktinische Keratosen (AK) sind häufige Hautveränderungen bei hellhäutigen Menschen mit dem Potenzial, in ein kutanes Plattenepithelkarzinom (PEK) überzugehen. Beide Erkrankungen können mit erheblicher Morbidität verbunden sein und stellen eine große Krankheitslast insbesondere in der älteren Bevölkerung dar. Um eine evidenzbasierte, klinische Entscheidungsfindung zu unterstützen, wurde die Leitlinie "Aktinische Keratose und Plattenepithelkarzinom der Haut" auf der Methodikebene S3 nach dem Regelwerk der AWMF entwickelt. Die Leitlinie richtet sich dabei an Dermatologen, Allgemeinmediziner, HNO‐Ärzte, Chirurgen, Onkologen, Radiologen und Strahlentherapeuten in Klinik und Praxis sowie an andere medizinische Fachgebiete, die sich mit der Diagnose und Behandlung von Patienten mit AK und PEK befassen. Die Leitlinie richtet sich auch an betroffene Patienten, deren Angehörige, politische Entscheidungsträger und Versicherungsgesellschaften. In diesem Teil behandeln wir die Themen Diagnostik, Interventionen bei AK, Versorgungsstrukturen und Qualitätsindikatoren. [ABSTRACT FROM AUTHOR]

Summary: Actinic keratoses (AK) are common lesions in light‐skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence‐based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was developed using the highest level of methodology (S3) according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF). The guideline is aimed at dermatologists, general practitioners, ENT specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office‐based settings as well as other medical specialties involved in the diagnosis and treatment of patients with AK and cSCC. The guideline is also aimed at affected patients, their relatives, policy makers and insurance funds. In the first part, we will address aspects relating to diagnosis, interventions for AK, care structures and quality‐of‐care indicators. [ABSTRACT FROM AUTHOR]

Damage to the critical anatomic structures during dental implant placement can lead to serious complications, including intra- or postoperative bleeding, hematoma formation, or varying degrees of neurosensory alteration. These complications usually occur when the anatomic features of the major blood vessels and their anastomoses, neurovascular bundles, and alveolar ridge contour are not properly investigated prior to the surgery. Therefore, having proper knowledge of specific anatomic factors is key to avoiding intra- and postsurgical complications. The aim of the current review is to summarize the anatomic structures and their variations in the mandible and maxilla as contributing risk factors in implant therapy. [ABSTRACT FROM AUTHOR]

Objectives: To assess the short‐term clinical outcomes of lateral alveolar ridge augmentation using autogenous tooth roots (TR) and autogenous bone blocks (AB). Material and Methods: A total of n = 23 patients (23 implants) were available for the analysis. Each subject was allocated to lateral ridge augmentation using either (a) healthy autogenous tooth roots (e.g., retained wisdom or impacted teeth; n = 13) or (b) cortical autogenous bone blocks harvested from the retromolar area (n = 10). Clinical parameters (e.g., bleeding on probing—BOP, probing pocket depth—PD, mucosal recession—MR, clinical attachment level—CAL) were recorded at (V8) and after 26 ± 4 weeks (V9) of implant loading. Results: TR and AB groups were associated with comparable (p > 0.05) changes in mean BOP (−23.0 ± 34.3%; −11.75 ± 24.9%), PD (−0.03 ± 0.14 mm; −0.1 ± 0.29 mm), MR (0.0 ± 0.0 mm; 0.0 ± 0.0 mm) and CAL (−0.03 ± 0.14 mm; −0.1 ± 0.29 mm) values. The regression analysis failed to reveal any significant correlations between changes in BOP and PD values and the initial as well as the ridge width measured at 26 weeks. Conclusions: TR and AB were associated with comparable clinical short‐term outcomes. [ABSTRACT FROM AUTHOR]

Merkel cell carcinoma (MCC), an aggressive neuroendocrine skin tumor, is a polyomavirus‐induced human cancer. To study the causal relationship of MCC carcinogenesis with the integrated Merkel cell polyomavirus (MCPyV) in detail, well‐characterized MCC cell lines are needed. Consequently, in the current study, we established and characterized six MCPyV‐positive MCC cell lines. Microarray‐based comparative genomic hybridization revealed a stable genome carrying only a limited number of chromosomal gains and deletions. All cell lines expressed MCC markers Keratin‐20 and neuron‐specific enolase as well as truncated MCPyV‐encoded large T antigen (LT). For five cell lines, we were able to identify the MCPyV‐integration sites in introns of different genes. The LT‐truncating stop codon mutations and integration sites were affirmed in the respective clinical patient samples. Inverse PCR suggested that three of the cell lines contained MCPyV genomes as concatemers. This notion was confirmed for the two cell lines with known integration sites. Importantly, our observation of distinct stop codon mutations in cell lines with concatemeric MCPyV integration indicates that these LT‐truncating mutations occur before integration. In summary, we provide the detailed characterization of six MCPyV‐positive MCC cell lines, which are likely to serve as valuable tools in future MCC research. What's new? The first human cancer identified to be caused by a polyomavirus was Merkel cell carcinoma (MCC). To study the causal relationship of MCC carcinogenesis with the integrated Merkel cell polyomavirus (MCPyV) in detail, well‐characterized MCC cell lines are needed. Here, the authors established and characterized six Merkel cell polyoma virus (MCPyV)‐positive MCC cell lines. The data provide a work of reference for future MCC research and also suggest that in MCPyV‐driven carcinogenesis the prerequisite MCPyV‐LT truncating stop codon mutations occur before viral integration. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Merkel cell carcinoma (MCC, ICD‐O M8247 / 3) is a rare malignant primary skin tumor with epithelial and neuroendocrine differentiation. The neoplastic cells share many morphological, immunohistochemical and ultrastructural characteristics with Merkel cells of the skin. The diagnosis of MCC is rarely made on clinical grounds. Histological and immunohistochemical studies are usually required to confirm the clinical suspicion. Given the frequent occurrence of occult lymph node metastasis, sentinel lymph node biopsy should be performed once distant metastasis has been ruled out by cross‐sectional imaging. Primary tumors without evidence of organ metastases are treated with complete surgical excision with appropriate surgical margins. Radiation therapy should be considered at all stages of the disease. For advanced MCC that is no longer amenable to curative treatment by surgery or radiation therapy, there is currently no established systemic therapy for which an improvement in recurrence‐free survival or overall survival has been demonstrated in a prospective randomized trial. However, immunotherapy using PD‐1/PD‐L1 blockade seems to be superior to chemotherapy. Various factors warrant that further diagnostic and therapeutic interventions be determined by an interdisciplinary tumor board. These factors include the tumor's aggressiveness, the frequent indication for sentinel lymph node biopsy along with the frequent occurrence in the head and neck region, the potential indication for adjuvant radiation therapy as well as the complexity of the required diagnostic workup. [ABSTRACT FROM AUTHOR]

Objectives: To assess the feasibility of using autogenous tooth roots (TR) for a lateral augmentation of deficient extraction sockets and two‐stage implant placement. Material and Methods: A total of 15 patients were recruited to perform a simultaneous, lateral augmentation of deficient (i.e., thickness of the buccal bone < 0.5 mm or buccal dehiscence‐type defects) fresh extraction sockets using the respective non‐retainable but non‐infected teeth (n = 15). After 26 weeks of submerged healing, the primary endpoint was defined as the crestal ridge width (mm) (CW26) being sufficient to place an adequately dimensioned titanium implant at the respective sites. Results: The surgical procedure could be accomplished in n = 14 patients. Soft tissue healing was uneventful in all patients. CW26 at visit 6 allowed for a successful implant placement in all patients (e.g., 14/14). Mean CW26 values amounted to 10.85 ± 2.71 mm (median: 8.5). The change (4.89 ± 2.29 mm) in CW compared to baseline was statistically significant (p < 0.001). Conclusions: The usage of TR may represent a feasible approach for lateral augmentation of deficient extraction sockets and two‐stage implant placement. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To assess and compare the efficacy and safety of autogenous tooth roots (TR) and autogenous bone blocks (AB) for lateral alveolar ridge augmentation and two‐stage implant placement. Material and Methods: A total of 30 patients in need of implant therapy and lateral ridge augmentation were allocated to parallel groups receiving either (a) healthy autogenous tooth roots (e.g. retained wisdom or impacted teeth) (n = 15) or (b) cortical autogenous bone blocks harvested from the retromolar area. After 26 weeks of submerged healing, the primary endpoint was defined as the crestal ridge width (mm) (CW26) being sufficient to place an adequately dimensioned titanium implant at the respective sites. Results: Soft tissue healing was uneventful in both groups. CW26 at V isit 6 allowed for a successful implant placement in all patients of both TR (15/15) and AB groups (15/15). Mean CW26 values amounted to 10.06 ± 1.85 mm (median: 11.0) in the TR and 9.20 ± 2.09 mm (median: 8.50) in the AB group, respectively. The difference between both groups did not reach statistical significance (p = 0.241). Conclusions: TR may serve as an alternative graft to support lateral alveolar ridge augmentation and two‐stage implant placement. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the influence of the width of keratinized mucosa (KM) on the development and resolution of experimental peri‐implant mucositis lesions at abutments with different microstructures in humans. Material and methods: In a randomized, controlled study, a total of 28 patients had received 28 target implants exhibiting a KM ≥2 mm. These were randomly connected with either partially microgrooved‐ (test) (n = 15) or machined (control) (n = 13) healing abutments. The study protocol included a wound healing period (WH) following implant placement (12 weeks), a plaque exposure phase (EP) of 21 days (EPd21) and a resolution phase (RP) including visits at 2, 4, and 16 weeks (RPw2; RPw4; RPw16) following plaque removal. Linear regression analyses were used to analyze the relationship between the width of KM and clinical outcomes (i.e., modified plaque index [mPI], modified gingival index [mGI], bleeding on probing [BOP], and probing depth [PD]). Results: Mean and median KM values (end of WH) were 5.9 ± 2.6 and 5.0 mm (min: 2 mm; max: 10 mm; interquartile range: 5 mm) at test‐ and 5.5 ± 2.6 and 4.0 mm (min: 3 mm; max: 11 mm interquartile range: 4 mm) at control abutments. The linear regression analysis revealed significant correlations between the width of KM and mPI (test: RPw2; control: RPw16), mGI (test: RPw16), BOP (both: RPw16), and PD (test: RPw16; control: EPd21, RPw2, RPw4, RPw16) scores. Conclusion: The width of KM (≥2 mm) had some effects on the development (i.e., at 21 days) and resolution of experimental peri‐implant mucositis lesions at both abutment types. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To assess the onset, progression and resolution of experimentally induced peri‐implant mucositis lesions at abutments with different microstructures in humans. Material & Methods: In a randomized, controlled, interventional two‐centre study, a total of 28 patients had received 28 target implants and were randomly allocated to either partially microgrooved (test) or machined (control) healing abutments. The study was accomplished in three phases, including a wound healing period (WH) following implant placement (12 weeks), a plaque exposure phase (EP—21 days) and a resolution phase (RP—16 weeks). Clinical (e.g. bleeding on probing—BOP), immunological (MMP‐8) and microbiological (DNA counts for 11 species) parameters were evaluated. Results: The incidence of peri‐implant mucositis at EPd21 was comparable in both test and control groups (60.0% versus 61.5%), but markedly lower at control abutments after a nonsurgical treatment and reconstitution of oral hygiene measures at RPw16 (46.7% versus 15.4%). At any follow‐up visit (i.e. EP and RP), clinical parameters, MMP‐8 levels and DNA counts of major bacterial species were not significantly different between both groups. Conclusion: The onset, progression and resolution of experimental peri‐implant mucositis lesions were comparable in both groups. [ABSTRACT FROM AUTHOR]