Acceptability of virtual reality to screen for dementia in older adults.

BACKGROUND: Early detection of dementia and cognitive decline is crucial for effective interventions and overall wellbeing. Although virtual reality (VR) tools offer potential advantages to traditional dementia screening tools, there is a lack of knowledge regarding older adults' acceptance of VR tools, as well as the predictors and features influencing their adoption. This study aims to (i) explore older adults' perceptions of the acceptability and usefulness of VR diagnostic tools for dementia, and (ii) identify demographic predictors of adoption and features of VR applications that contribute to future adoption among older adults. METHODS: A cross-sectional study was conducted involving community-dwelling older adults who completed online questionnaires covering demographics, medical history, technology acceptance, previous usage, and perceived usefulness and barriers to VR adoption. Multiple linear regression was employed to assess relationships between sociodemographic factors, prior technology use, perceived ease, usefulness, and intention to adopt VR-based diagnostic tools. RESULTS: Older adults (N = 77, Mage = 73.74, SD = 6.4) were predominantly female and born in English-speaking countries. Perceived usefulness of VR applications and educational attainment emerged as significant predictors of the likelihood to use VR applications for dementia screening. Generally, older adults showed acceptance of VR applications for healthcare and dementia screening. Fully immersive applications were preferred, and older adults were mostly willing to share electronic information from screening with their healthcare providers. CONCLUSIONS: The field of research on VR applications in healthcare is expanding. Understanding the demographic characteristics of populations that stand to benefit from healthcare innovations is critical for promoting adoption of digital health technologies and mitigating its barriers to access.

Building digital solutions to support brain health prescribing in primary care: Where to begin?

National and international policy goals on healthy ageing and dementia risk reduction are yet to be fully realised in community healthcare settings. Disease modification strategies through lifestyle and social interventions are viable, evidence-based solutions to reduce age-related disease burden. However, prescribing lifestyle interventions targeting dementia risk in primary care remains deficient. Using digital technologies to support older individuals and healthcare professionals through formal health checks and lifestyle management is likely to enable shared understanding and consequences of personalized care and treatment options. These tailored solutions may bridge the translation gap and support healthy ageing.

Exploring the usability of the virtual reality module LEAF CAFÉ: a qualitative think-aloud study.

BACKGROUND: The global healthcare system faces increasing strain from our ageing population, primarily due to the growing prevalence of age-related health conditions such as dementia. While modern healthcare technology offers potential solutions, it frequently lacks user-friendliness for older adults. Virtual Reality (VR) has emerged as a promising tool for diagnosing cognitive impairment, offering innovative solutions where traditional methods may fall short. This study explores older adults' perspectives on the usability of a newly designed VR module for cognitive assessment. METHODS: During a 100-min session, participants were asked to engage and complete recall and recognition tasks within the VR module (think-aloud approach) and provide feedback upon completion (semi-structured interviews). Audio materials were transcribed for analysis and recordings of the users' interactions with the module were annotated to provide additional context. These combined textual data were analysed using content coding and thematic analysis to identify themes that reflect how participants used the module's features and what features are desirable to support that process better. RESULTS: Participants (N = 10; Mean age = 73.3, SD = 7.53, range = 65-83 years) perceived the VR module as user-friendly and endorsed its potential as a cognitive screener due to its engaging and immersive nature. Older adults highlighted three key aspects of the module: the usefulness of the platform's ability to offer a comprehensive and reliable evaluation of an individual's cognitive abilities; the need to present concise and relevant content to optimise engagement and use; and the importance of overcoming barriers to support implementation. Suggested game improvements centred on food recognition and adjusting difficulty levels. Barriers to implementation included technology challenges for older adults and concerns about the game's suitability for everyday scenarios. Participants stressed the need for reliable implementation strategies, proposing locations such as libraries and advocating for home-based screening. CONCLUSION: Continued improvements in accessibility suggest that VR tools could help with diagnosing cognitive impairment in older adults. Using a simulated environment to assess cognitive status might fill the gap between current diagnostic methods, aiding treatment planning and early intervention. However, these findings should be approached cautiously, as more research is needed to fully grasp the potential impact of VR tools in this context.

Passive monitoring of avian habitat on working lands.

Intensive agricultural landscapes pose a challenge to wildlife managers, policymakers, and landowners hoping to increase the diversity of desired wildlife species, such as grassland birds, which require urgent conservation action. In intensive agricultural landscapes, like those of the Midwestern United States, most land area is privately owned and operated and managed primarily for production. Thus, conducting ecological research in intensive agricultural landscapes requires collaborative approaches aimed at farm owners and operators. Recent advances in acoustic data collection and high-resolution habitat mapping, including low-cost acoustic recorders and satellite remote sensing, may be well positioned to address this challenge by enabling expanded assessments and monitoring of wildlife populations and habitats across regions. This study examined fine-grained habitat characteristics and their relationship with avian biodiversity in intensive agricultural landscapes at 44 agricultural sites across the state of Iowa. Passive acoustic monitoring and manual identification of bird species allowed for measurement of vocalizing bird richness. High-resolution mapping of noncrop vegetation provided detailed information on small noncrop vegetation habitat complexes within row-crop agriculture. Measures of image texture provided characterizations of compositional heterogeneity within noncrop vegetation. General linear Poisson modeling demonstrated robust associations between noncrop vegetation and vocalizing bird richness, yet variation in grassland bird richness was not well predicted by noncrop vegetation. Noncrop vegetation texture demonstrated potential as a predictor of vocalizing bird richness, though not better than or when combined with noncrop vegetated area, indicating it may not be an independent measure of habitat quality. Passive acoustic monitoring resulted in useful data at 44 out of 60 originally selected sites, with some lost to failed recorders and/or collaboration issues. Challenges remain in detecting habitat characteristics that promote grassland birds in row crop landscapes. Working toward probabilistic research design across privately owned working landscapes and incorporating more detailed management practice information would improve the transferability of this approach to farmland management and policy.

Membranous NECTIN-4 Expression Frequently Decreases during Metastatic Spread of Urothelial Carcinoma and Is Associated with Enfortumab Vedotin Resistance.

PURPOSE: The antibody-drug conjugate enfortumab vedotin (EV) releases a cytotoxic agent into tumor cells via binding to the membrane receptor NECTIN-4. EV was recently approved for patients with metastatic urothelial carcinoma (mUC) without prior assessment of the tumor receptor status as ubiquitous NECTIN-4 expression is assumed. Our objective was to determine the prevalence of membranous NECTIN-4 protein expression in primary tumors (PRIM) and patient-matched distant metastases (MET). EXPERIMENTAL DESIGN: Membranous NECTIN-4 protein expression was measured (H-score) by IHC in PRIM and corresponding MET (N = 137) and in a multicenter EV-treated cohort (N = 47). Progression-free survival (PFS) after initiation of EV treatment was assessed for the NECTIN-4-negative/weak (H-score 0-99) versus moderate/strong (H-score 100-300) subgroup. The specificity of the NECTIN-4 IHC staining protocol was validated by establishing CRISPR-Cas9-induced polyclonal NECTIN-4 knockouts. RESULTS: In our cohort, membranous NECTIN-4 expression significantly decreased during metastatic spread (Wilcoxon matched pairs P < 0.001; median H-score = 40; interquartile range, 0-140), with 39.4% of MET lacking membranous NECTIN-4 expression. In our multicenter EV cohort, absence or weak membranous NECTIN-4 expression (34.0% of the cohort) was associated with a significantly shortened PFS on EV (log-rank P < 0.001). CONCLUSIONS: Membranous NECTIN-4 expression is frequently decreased or absent in mUC tissue. Of note, the clinical benefit of EV strongly depends on membranous NECTIN-4 expression. Thus, our results are of highest clinical relevance and argue for a critical reconsideration of the current practice and suggest that the NECTIN-4 receptor status should be determined (ideally in a metastatic/progressive lesion) before initiation of EV. See related commentary by Aggen et al., p. 1377.

Stability of antibacterial Te(IV) compounds: A combined experimental and computational study.

Inorganic Te(IV) compounds are important cysteine protease inhibitors and antimicrobial agents; AS-101 [ammonium trichloro (dioxoethylene-O,O')tellurate] is the first compound of a family with formula NH4[C2H4Cl3O2Te], where a Te(IV) centre is bound to a chelate ethylene glycol, and showed several protective therapeutic applications. This compound is lacking in stability performance and is subjected to hydrolysis reaction with displacement of the diol ligand. In this paper, we report the stability trend of a series of analogues complexes of AS-101 with generic formula NH4[(RC2H3O2)Cl3Te], where R is an alkyl group with different chain length and different electronic properties, in order to find a correlation between structure and stability in aqueous-physiological conditions. The stability was studied in solution via multinuclear NMR spectroscopy (1H, 13C, 125Te) and computationally at the Density Functional Theory level with an explicit micro solvation model. The combined experimental and theoretical work highlights the essential role of the solvating environment and provides mechanistic insights into the complex decomposition reaction. Antimicrobial activity of the compounds was assessed against different bacterial strains.

Mapping the HLA Ligandome of Colorectal Cancer Reveals an Imprint of Malignant Cell Transformation.

Immune cell infiltrates have proven highly relevant for colorectal carcinoma prognosis, making colorectal cancer a promising candidate for immunotherapy. Because tumors interact with the immune system via HLA-presented peptide ligands, exact knowledge of the peptidome constitution is fundamental for understanding this relationship. Here, we comprehensively describe the naturally presented HLA ligandome of colorectal carcinoma and corresponding nonmalignant colon (NMC) tissue. Mass spectrometry identified 35,367 and 28,132 HLA class I ligands on colorectal carcinoma and NMC, attributable to 7,684 and 6,312 distinct source proteins, respectively. Cancer-exclusive peptides were assessed on source protein level using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein analysis through evolutionary relationships (PANTHER), revealing pathognomonic colorectal carcinoma-associated pathways, including Wnt, TGFß, PI3K, p53, and RTK-RAS. Relative quantitation of peptide presentation on paired colorectal carcinoma and NMC tissue further identified source proteins from cancer- and infection-associated pathways to be overrepresented merely within the colorectal carcinoma ligandome. From the pool of tumor-exclusive peptides, a selected HLA-ligand subset was assessed for immunogenicity, with the majority exhibiting an existing T-cell repertoire. Overall, these data show that the HLA ligandome reflects cancer-associated pathways implicated in colorectal carcinoma oncogenesis, suggesting that alterations in tumor cell metabolism could result in cancer-specific, albeit not mutation-derived, tumor antigens. Hence, a defined pool of unique tumor peptides, attributable to complex cellular alterations that are exclusive to malignant cells, might comprise promising candidates for immunotherapeutic applications.Significance: Cancer-associated pathways are reflected in the antigenic landscape of colorectal cancer, suggesting that tumor-specific antigens do not necessarily have to be mutation-derived but may also originate from other alterations in cancer cells. Cancer Res; 78(16); 4627-41. ©2018 AACR.

The t(14;18) translocation is absent from endothelial and follicular dendritic cells of follicular lymphoma (FL) and shows heterogeneous presence in preserved FL mantle zones.

BACKGROUND: The translocation t(14;18)(q32;q21) is the genetic hallmark of follicular lymphoma (FL) and can be observed in 85-90% of cases. Whether the translocation is restricted to cells with germinal center B-cell phenotype or can be observed in other cell types of the microenvironment remains debated. Of interest, cases of associated histiocytic and dendritic cell sarcomas arising in the background of FL have been shown to be clonally related and carry the t(14;18), suggesting a "transdifferentiation" of the malignant FL clone into a neoplasm of a different hematopoietic lineage. METHODS: We analyzed the presence of the t(14;18)(q32;q21) as a surrogate marker of the malignant clone in cells of the FL microenvironment using combined fluorescence immunophenotyping and interphase cytogenetics targeting the BCL2 gene locus. In addition to non-lymphoid cells in FL, we analysed FL with preserved IgD+ mantle zones and cases of in situ follicular neoplasia (ISFN) to investigate whether cells of non-germinal center B-cell phenotype are part of the malignant clone. RESULTS: Six (40%) of 15 manifest FL cases with preserved IgD+ mantle zones did not harbour the t(14;18)(q32;q21) translocation. In all t(14;18) + FL cases, follicular dendritic cells and endothelial cells lacked the t(14;18) translocation. 2/9 FL revealed t(14;18)- IgD+ mantle zone B-cells. In the seven ISFN cases, the t(14;18) translocation was strictly confined to germinal center cells. CONCLUSIONS: The t(14;18) translocation in follicular lymphoma is limited to B-cells. The origin of IgD+ mantle cells is heterogeneous, in the majority of cases belonging to the neoplastic clone, whereas a minority of cases of manifest FL show nonneoplastic mantle zones, similar to ISFN.

Next generation sequencing of the clonal IGH rearrangement detects ongoing mutations and interfollicular trafficking in in situ follicular neoplasia.

Follicular lymphoma (FL) is characterized genetically by a significant intraclonal diversity of rearranged immunoglobulin heavy chain (IGH) genes and a substantial cell migration activity (follicular trafficking). Recently, in situ follicular neoplasia (ISFN), characterized by accumulations of immunohistochemically strongly BCL2-positive, t(14;18)+ clonal B cells confined to germinal centers in reactive lymph nodes, has been identified as a precursor lesion of FL with low risk of progression to manifest FL. The extent of ongoing somatic hypermutation of rearranged IGH genes and interfollicular trafficking in ISFN is not known. In this study we performed an in depth analysis of clonal evolution and cell migration patterns in a case of pure ISFN involving multiple lymph nodes. Using laser microdissection and next generation sequencing (NGS) we documented significant intraclonal diversity of the rearranged IGH gene and extensive interfollicular migration between germinal centers of the same lymph node as well as between different lymph nodes. Furthermore, we identified N-glycosylation motifs characteristic for FL in the CDR3 region.

Expression of SOX11, PAX5, TTF-1 and ISL-1 in medulloblastoma.

The aim of our study was to evaluate the immunohistochemical expression of SOX11, PAX5, TTF-1 and ISL-1 in medulloblastoma (MB) to investigate their diagnostic usefulness. METHODS: Immunohistochemical expression of PAX5 (two antibodies: Dako, DAK-Pax5; and BD, clone 24), TTF-1 (Dako, 8G7G3/1), SOX11 (CL0142; Abcam) and ISL-1 (1 H9, Abcam) was analyzed using the h-score and Remmele score in 25 cases of MB. RESULTS: There were 18 MBs of classic and 7 of desmoplastic type. SOX11 was strongly expressed in all tumors. The expression of PAX5 was higher and more frequent in a case of DAK-Pax5 clone (25/25) than clone 24 (6/25). ISL-1 was positive in 11 (44%) and TTF-1 in 3 (12%) cases. ISL-1 expression correlated positively (p<0.001), while TTF-1 correlated negatively with the age of patients (p=0.039). PAX5 expression correlated with ISL-1 (p=0.039) and showed a trend toward higher expression in the desmoplastic subtype (p=0.069). CONCLUSIONS: SOX11 is strongly and robustly expressed in MBs. PAX5 expression pattern differs substantially among two antibody clones. TTF-1 and ISL-1 is associated with the age of patients.

Hemangiopericytoma/solitary fibrous tumor of the greater omentum: A case report and review of the literature.

INTRODUCTION: Hemangiopericytoma (HPC) has been first described in 1942 by Stout as a tumor originating from the capillary surrounding pericytes. It is known to occur in any anatomical site, especially the extremities and retroperitoneum. PRESENTATION OF CASE: We describe a case of a 24year old patient presenting with lower abdominal pain due to a tumor of the greater omentum, the patient was treated by conventional laparotomy with tumor resection and the histological evaluation confirmed the diagnosis Hemangiopericytoma/Solitary fibrous tumor (HPC/SFT). The patient has regularly followed-up with periodic imaging for the last 4 years, with no recurrences. DISCUSSION AND CONCLUSION: According to our knowledge, HPC rarely develops in the greater omentum, only 20 cases were described in the literature. Primary surgical resection is the treatment of choice. There is no benefit of radiation or systemic chemotherapy. Angiogenic inhibitors represent promising systemic therapeutic concepts.

A retrospective international study on primary extranodal marginal zone lymphoma of the lung (BALT lymphoma) on behalf of International Extranodal Lymphoma Study Group (IELSG).

Primary lymphoma of the lung is a rare entity. Clinical features, optimal treatment, role of surgery and outcomes are not well defined, and the follow-up is variable in published data. Clinical data of 205 patients who were confirmed to have bronchus mucosa-associated lymphoid tissue lymphoma from December 1986 to December 2011 in 17 different centres worldwide were evaluated. Fifty-five per cent of the patients were female. The median age at diagnosis was 62 (range 28-88) years. Only 9% had a history of exposure to toxic substances, while about 45% of the patients had a history of smoking. Ten per cent of the patients had autoimmune disease at presentation, and 19% patients had a reported preexisting lung disease. Treatment modalities included surgery alone in 63 patients (30%), radiotherapy in 3 (2%), antibiotics in 1 (1%) and systemic treatment in 128 (62%). Patients receiving a local approach, mainly surgical resection, experienced significantly improved progression-free survival (p = 0.003) versus those receiving a systemic treatment. There were no other significant differences among treatment modalities. The survival data confirm the indolent nature of the disease. Local therapy (surgery or radiotherapy) results in long-term disease-free survival for patients with localized disease. Systemic treatment, including alkylating-containing regimens, can be reserved to patients in relapse after incomplete surgical excision or for patients with advanced disease. Copyright © 2015 John Wiley & Sons, Ltd.

Impact of tumour volume on prediction of progression-free survival in sinonasal cancer.

BACKGROUND: The present study aimed to analyse potential prognostic factors, with emphasis on tumour volume, in determining progression free survival (PFS) for malignancies of the nasal cavity and the paranasal sinuses. PATIENTS AND METHODS: Retrospective analysis of 106 patients with primary sinonasal malignancies treated and followed-up between March 2006 and October 2012. Possible predictive parameters for PFS were entered into univariate and multivariate Cox regression analysis. Kaplan-Meier curve analysis included age, sex, baseline tumour volume (based on MR imaging), histology type, TNM stage and prognostic groups according to the American Joint Committee on Cancer (AJCC) classification. Receiver operating characteristic (ROC) curve analysis concerning the predictive value of tumour volume for recurrence was also conducted. RESULTS: The main histological subgroup consisted of epithelial tumours (77%). The majority of the patients (68%) showed advanced tumour burden (AJCC stage III-IV). Lymph node involvement was present in 18 cases. The mean tumour volume was 26.6 ± 21.2 cm(3). The median PFS for all patients was 24.9 months (range: 2.5-84.5 months). The ROC curve analysis for the tumour volume showed 58.1% sensitivity and 75.4% specificity for predicting recurrence. Tumour volume, AJCC staging, T- and N- stage were significant predictors in the univariate analysis. Positive lymph node status and tumour volume remained significant and independent predictors in the multivariate analysis. CONCLUSIONS: Radiological tumour volume proofed to be a statistically reliable predictor of PFS. In the multivariate analysis, T-, N- and overall AJCC staging did not show significant prognostic value.

Analysis of incomplete excisions of basal-cell carcinomas after breadloaf microscopy compared with 3D-microscopy: a prospective randomized and blinded study.

Basal-cell carcinomas may show irregular, asymmetric subclinical growth. This study analyzed the efficacy of 'breadloaf' microscopy (serial sectioning) and three-dimensional (3D) microscopy in detecting positive tumor margins. Two hundred eighty-three (283) tumors (51.2%) were put into the breadloaf microscopy group; 270 tumors (48.8%) into the 3D microscopy group. The position of any detected tumor outgrowths was identified in clock face fashion. The time required for cutting and embedding the specimens and the examination of the microscopic slides was measured. Patient/tumor characteristics and surgical margins did not differ significantly. Tumor outgrowths at the excision margin were found in 62 of 283 cases (21.9%) in the breadloaf microscopy group and in 115 of 270 cases (42.6%) in the 3D microscopy group, constituting a highly significant difference (p < 0.001). This difference held true with incomplete excision of fibrosing (infiltrative/sclerosing/morpheaform) tumors [32.9% in the breadloaf microscopy group and 57.5% in the 3D microscopy group (p = 0.003)] and also with solid (nodular) tumors [16.1 and 34.2%, respectively (p < 0.001)]. The mean overall examination time required showed no important difference. In summary, for detection of tumor outgrowths, 3D microscopy has almost twice the sensitivity of breadloaf microscopy, particularly in the situation of aggressive/infiltrative carcinomas.

TLR signaling-induced CD103-expressing cells protect against intestinal inflammation.

BACKGROUND: Toll-like receptor (TLR) expression in patients with inflammatory bowel disease is increased when compared with healthy controls. However, the impact of TLR signaling during inflammatory bowel disease is not fully understood. METHODS: In this study, we used a murine model of acute phase inflammation in bone marrow chimeric mice to investigate in which cell type TLR2/4 signal induction is important in preventing intestinal inflammation and how intestinal dendritic cells are influenced. Mice were either fed with wild-type bacteria, able to initiate the TLR2/4 signaling cascade, or with mutant strains with impaired signal induction capacity. RESULTS: The induction of the TLR2/4 signal cascade in epithelial cells resulted in inflammation in bone marrow chimeric mice, whereas induction in hematopoietic cells had an opposed function. Furthermore, feeding of wild-type bacteria prevented disease; however, differing signal induction of bacteria had no effect on lamina propria dendritic cell activation. In contrast, functional TLR2/4 signals resulted in increased frequencies of CD103-expressing lamina propria and mesenteric lymph node dendritic cells, which were able to ameliorate disease. CONCLUSIONS: The TLR-mediated amelioration of disease, the increase in CD103-expressing cells, and the beneficial function of TLR signal induction in hematopoietic cells indicate that the increased expression of TLRs in patients with inflammatory bowel disease might result in counterregulation of the host and serve in preventing disease.

Occupancy of red-naped sapsuckers in a coniferous forest: using LiDAR to understand effects of vegetation structure and disturbance.

Red-naped sapsuckers (Sphyrapicus nuchalis) are functionally important because they create sapwells and cavities that other species use for food and nesting. Red-naped sapsucker ecology within aspen (Populus tremuloides) has been well studied, but relatively little is known about red-naped sapsuckers in conifer forests. We used light detection and ranging (LiDAR) data to examine occupancy patterns of red-naped sapsuckers in a conifer-dominated system. We surveyed for sapsuckers at 162 sites in northern Idaho, USA, during 2009 and 2010. We used occupancy models and an information-theoretic approach to model sapsucker occupancy as a function of four LiDAR-based metrics that characterized vegetation structure and tree harvest, and one non-LiDAR metric that characterized distance to major roads. We evaluated model support across a range of territory sizes using Akaike's information criterion. Top model support was highest at the 4-ha extent, which suggested that 4 ha was the most relevant scale describing sapsucker occupancy. Sapsuckers were positively associated with variation of canopy height and harvested area, and negatively associated with shrub and large tree density. These results suggest that harvest regimes and structural diversity of vegetation at moderate extents (e.g., 4 ha) largely influence occurrence of red-naped sapsuckers in conifer forests. Given the current and projected declines of aspen populations, it will be increasingly important to assess habitat relationships, as well as demographic characteristics, of aspen-associated species such as red-naped sapsuckers within conifer-dominated systems to meet future management and conservation goals.

Three dimensional (3D) histology in daily routine: practical implementation and its evaluation.

BACKGROUND: The continuous evaluation of the edges of a tumor by means of three-dimensional (3D) histology often appears complicated and require the surgeon and dermatopathologist to work together closely. We present clear rules that allow communication between all parties involved and then verify their application in daily routine. METHODS: Tissue processing, interpretation of results, as well as communication between the surgeon and the dermatopathologist are based on an algorithm with the aid of exact times and embedding cassettes, which allow precise topographic orientation. We evaluated the use of this method in daily clinic practice, taking into account 947 operated basal cell carcinomas in regard to the development of recurrent tumors. RESULTS: At a median follow-up of 47 months, 10 of the 947 operated basal cell carcinomas (1.1 %) recurred. Sclerodermiform basal cell carcinomas and basal cell carcinomas which could not be curatively resected (R0 resection) during the initial surgery showed a significantly higher recurrence rate (p < 0.05 and p < 0.001). CONCLUSIONS: Standardized rules for dealing with excised tissue allow an effective application of 3D histology in daily clinical practice. 3D histology results in low recurrence rates. Sclerodermiform basal cell carcinomas which could not be curatively resected (R0 resection) were identified as a risk group for the development of recurrent tumors.

Thymoma with loss of keratin expression (and giant cells): a potential diagnostic pitfall.

Due to its profound therapeutic consequences, the distinction between thymoma and T-lymphoblastic lymphoma in needle biopsies is one of the most challenging in mediastinal pathology. One essential diagnostic criterion favouring thymoma is the demonstration of increased numbers of keratin-positive epithelial cells by immunohistochemistry. Loss of keratin expression in neoplastic epithelial cells could lead to detrimental misdiagnoses. We here describe a series of 14 thymic epithelial tumours (11 type B2 and B3 thymomas, 3 thymic carcinomas) with loss of expression of one or more keratins. Cases were analysed for expression of various keratins and desmosomal proteins by immunohistochemistry and immunofluorescence and compared with 45 unselected type B thymomas and 24 thymic carcinomas arranged in a multitissue histological array. All 14 cases showed highly reduced expression of at least one keratin, three cases were completely negative for all keratins studied. Of the 14 cases, 13 showed strong nuclear expression of p63. Expression of desmosomal proteins was preserved, suggesting intact cell contact structures. Loss of expression of broad-spectrum-keratins and K19 was observed in 3 and 5 % of unselected thymomas and in 30 and 60 % of thymic carcinomas. A proportion of keratin-depleted thymomas contained giant cells, reminiscent of thymic nurse cells. Loss of keratin expression in type B2 and B3 thymomas is an important diagnostic pitfall in the differential diagnosis with T-lymphoblastic lymphoma and can be expected in 5 % of cases. A panel of epithelial markers including p63 is warranted to ensure correct diagnosis of keratin-negative mediastinal tumours.