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BackgroundThe validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD™) is a standardized severity assessment for use in clinical trials and registries for atopic dermatitis (AD).ObjectivesTo investigate the reliability, validity, responsiveness and within-patient meaningful change of the vIGA-AD.MethodsData were analysed from adult patients with moderate-to-severe AD in the BREEZE-AD1 (N = 624 patients; NCT03334396), BREEZE-AD2 (N = 615; NCT03334422) and BREEZE-AD5 (N = 440; NCT03435081) phase III baricitinib clinical studies.ResultsAcross studies, test-retest reliability for stable patients showed moderate-to-good agreement [range of Kappa values for Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD), 0·516-0·639; for Eczema Area and Severity Index (EASI), 0·658-0·778]. Moderate-to-large correlations between vIGA-AD and EASI or body surface area (range at baseline, 0·497-0·736; Week 16, 0·716-0·893) supported convergent validity. Known-groups validity was demonstrated vs. EASI and PGI-S-AD (vIGA-AD for severe vs. moderate EASI categories at baseline, P

BackgroundThe Itch Numeric Rating Scale (NRS), Skin Pain NRS, and Atopic Dermatitis Sleep Scale (ADSS) are self-administered patient-reported outcome (PRO) instruments developed to assess symptoms in patients with atopic dermatitis (AD). The objective of this study was to evaluate the psychometric properties (reliability, validity, and responsiveness) and interpretability thresholds of these PROs using data from three pivotal Phase 3 studies in adults.MethodsBREEZE-AD1, BREEZE-AD2, and BREEZE-AD5 evaluated the safety and efficacy of baricitinib in adults with moderate-to-severe AD. Clinician-reported outcomes and other PROs commonly assessed in patients with AD were used to estimate meaningful changes and evaluate test-retest reliability, convergent and divergent validity, known-groups validity, responsiveness, and meaningful change thresholds (MCTs) of the Itch NRS, Skin Pain NRS, and ADSS.ResultsThe test-retest reliability of the Itch NRS, Skin Pain NRS, and ADSS was evidenced by generally large intraclass correlation coefficients (> 0.7) in stable groups of patients between baseline and Week 1 and Weeks 4 and 8. Moderate-to-large correlations (r > 0.4) at baseline and Week 16 were generally observed between each measure and other PROs measuring the same concept, supporting convergent validity. Small-to-moderate correlations with clinician-reported outcomes demonstrated divergent validity. Each instrument was able to distinguish between known groups of disease severity as assessed using other indicators of AD severity. The responsiveness of the Itch NRS, Skin Pain NRS, and ADSS scales was demonstrated through significant differences in their change scores from baseline to Week 16 between categories of change in another PRO also from baseline to Week 16. Thresholds for interpreting meaningful change were estimated as - 4.0 for the 0-10 Itch and Skin Pain NRS items; - 1.25 for the 0-4 ADSS Items 1 and 3 and; - 1.50 for the 0-29 ADSS Item 2, these equivalent to moderate degrees of change.ConclusionsResults of this study demonstrate that the psychometric properties of the Itch NRS, Skin Pain NRS, and ADSS are good to excellent. These findings support the use of these instruments in daily assessment of AD symptoms in adults with moderate-to-severe AD. Trial registration ClinicalTrials.gov numbers: NCT03334396, NCT03334422, and NCT03435081.

BackgroundAlopecia areata (AA) is characterized by hair loss that can affect the scalp and body. This study describes the psychosocial burden of AA.MethodsParticipants diagnosed with AA who had experienced ≥50% scalp hair loss according to the Severity of Alopecia Tool (SALT) were identified by clinicians. A semi-structured interview guide, developed with expert clinician input, included open-ended questions to explore patients' experiences of living with AA. Data were thematically analyzed to identify concepts and relationships.ResultsParticipants (n = 45, 58% female, mean age 33.3 years [range 15-72], mean SALT 67.2 [range 0-100]) described the AA diagnosis as "devastating". Both males and females reported emotional and psychological impacts of AA including feeling sad/depressed (n = 21), embarrassed/ashamed (n = 10) and angry/frustrated (n = 3). Patients felt helpless (n = 5) due to the unpredictability of disease recurrence, and anxious (n = 19) about judgement from others. Many patients avoided social situations (n = 18), which impaired relationships and increased isolation. Coping strategies included concealment of hair loss through wigs or make-up, although fear of the displacement of these coverings also caused anxiety and the avoidance of activities that could result in scalp exposure (n = 22). Some patients became more accepting of AA over time, which lessened the emotional impact, though efficacious treatment was still desired. A conceptual framework was developed, and a conceptual model was created to depict the relationship between the physical signs/symptoms and the associated psychosocial effects of AA.ConclusionAA impairs patients' emotional and psychological wellbeing, relationships and lifestyles. Greater disease awareness and effective treatments are needed.

BackgroundEyebrow and eyelash hair loss and nail damage-in addition to scalp hair loss-are important signs/symptoms of alopecia areata (AA) to patients and deserve assessment in AA clinical trials.ObjectivesOur objective was to develop clinician-reported outcome (ClinRO) and patient-reported outcome (PRO) measures and accompanying photoguides to aid in the assessment of AA-related eyebrow, eyelash and nail signs/symptoms.MethodsIterative rounds of qualitative, semi-structured interviews were conducted with US expert dermatologists and North American patients with AA. Patients with eyebrow, eyelash and nail involvement were purposefully sampled. Interview transcripts were qualitatively analyzed.ResultsDermatologists (n = 10) described eyebrow and eyelash loss as concerning for affected patients and, along with nail appearance, as deserving assessment. Dermatologist data informed the development of single item, 4-point Likert-type ClinRO and PRO measures of current eyebrow loss, eyelash loss and nail appearance and a PRO measure of eye irritation. Patients (n = 45, age 15-72 years) confirmed the importance and relevance of these signs/symptoms. Interim revision resulted in measures that were understood by and relevant to patients. Dermatologists (n = 5) and patients (n = 10, age 21-54 years) participated in the development of the eyebrow, eyelash and nail photoguides and confirmed that they included photos that appropriately represented different severity levels and were helpful to derive and standardize ratings across raters.ConclusionsThe ClinRO and PRO measures for eyebrow, eyelash and nail appearance, with their accompanying photoguides and the PRO Measure for Eye Irritation provide clear and meaningful assessments of outcomes important to patients with AA.

We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10-8), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10-9). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10-6) than in HPV-negative (OR = 0.75, P = 0.16) cancers.

ObjectiveClinically validated biomarkers for neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis (SWN) have not been identified to date. The biomarker working group's goals are to (1) define biomarker needs in NF1, NF2, and SWN; (2) summarize existing data on biomarkers in NF1, NF2, and SWN; (3) outline recommendations for sample collection and biomarker development; and (4) standardize sample collection and methodology protocols where possible to promote comparison between studies by publishing standard operating procedures (SOPs).MethodsThe biomarker group reviewed published data on biomarkers in NF1, NF2, and SWN and on biobanking efforts outside these diseases via literature search, defined the need for biomarkers in NF, and developed recommendations in a series of consensus meetings.ResultsWe describe existing biomarkers in NF and report consensus recommendations for SOP and a minimal clinical dataset to accompany samples derived from patients with NF1, NF2, and SWN in decentralized biobanks.ConclusionsThese recommendations are intended to provide clinicians and researchers with a common set of guidelines to collect and store biospecimens and for establishment of biobanks for NF1, NF2, and SWN.

Oral squamous cell carcinoma (OSCC) is typically considered a differential diagnosis for subgemmal neurogenic plaque (SNP), but the co-occurrence of both adjacent lesions is exceedingly rare. Here is a report on a 47-year-old female patient: The patient complained of severe pain in the posterior third of her tongue. Upon intraoral examination, multiple soft, reddish, rounded papules were observed. An incisional biopsy was performed, resulting in a histopathological diagnosis of SNP and lymphoid tissue hyperplasia. Local measures were implemented to prevent trauma in the affected area. However, the symptoms did not subside, and they shifted to the middle third of the tongue. A new erythematous lesion was noticeable adjacent to where the SNP had been removed. A second biopsy confirmed the histopathological diagnosis of OSCC. Subsequently, the patient was referred to oncology services. While SNP typically causes severe pain, its occurrence in early OSCC is rare. When these conditions are associated, pain may serve as the initial indicator of malignancy. [ABSTRACT FROM AUTHOR]

A 79-year-old female patient with a history of Hashimoto's thyroiditis complained of a painless nodule in her palate that had been present for the past two years. An intraoral examination revealed a nodule in the center of the palate with normal mucosal coloring. Following an incisional biopsy, the histological examination showed an infiltration of diverse neoplastic cells, predominantly lymphoid, arranged in a vaguely nodular pattern, interspersed with dense connective tissue. Immunohistochemical analysis confirmed the presence of positive cells for CD20, BCL2, Lambda, and Ki67. The diagnosis was MALT B-cell lymphoma, and the patient was subsequently referred to a hematologist-oncologist for treatment. Mucosa-associated lymphoid tissue (MALT) lymphoma is a subtype of non-Hodgkin lymphoma originating from B cells in the extranodal marginal zone. MALT B-cell lymphoma is often associated with autoimmune diseases. The occurrence of a primary oral MALT lymphoma in a patient with Hashimoto's thyroiditis is uncommon. According to the literature, if diffuse large B-cell lymphoma or thyroid cancer has been ruled out, adjuvant therapy is typically sufficient for these patients.. [ABSTRACT FROM AUTHOR]

Carcinoma Ex Pleomorphic Adenoma (CXPA) is a rare salivary gland neoplasm that typically arises from a pre-existing pleomorphic adenoma (PA). We present the case of a 69-year-old male patient who was referred for evaluation of a lesion in the hard palate that had been present for over 40 years, with a previous diagnosis of PA. Upon intraoral examination, a well-defined, asymptomatic nodule was identified in the hard palate region. An incisional biopsy was performed. Histopathological examination revealed a malignant neoplasm of glandular origin characterized by the proliferation of myoepithelial and ductal cells, displaying ovoid, fusiform, or plasmacytoid morphology. At the periphery of the lesion, an area with histologically benign components of PA and hyalinization was evident. Immunohistochemical analysis demonstrated positivity for CK7, S100, VIM, and p63, while AML testing yielded negative results. Despite its low incidence and unclear pathogenesis, it is crucial to consider CXPA in the differential diagnosis of neoplasms of glandular origin. [ABSTRACT FROM AUTHOR]

Desmoplastic ameloblastoma (DA) is a rare odontogenic tumor of epithelial origin that differs from the classic ameloblastoma in terms of its anatomical distribution and clinical presentation. This variant accounts for an incidence ranging from 4 to 13% among other ameloblastoma variants. Here, we present a case of a 51-year-old female patient, who is a non-smoker and non-alcoholic, and sought evaluation for a bone defect in the right anterior mandible. Imaging examinations revealed a mixed and multilocular lesion. Histopathological examination demonstrated small islands and cords of odontogenic epithelium surrounded by desmoplastic reaction. Based on these findings, the diagnosis of desmoplastic ameloblastoma was established. Desmoplastic ameloblastoma should be considered as a possible differential diagnosis for lesions exhibiting a radiographic appearance that is mixed, with both radiopaque and radiolucent aspects and ill-defined borders. DA represents a distinct variation among ameloblastomas, characterized by unique clinicoradiographic and histopathological features. Accurate diagnosis of this variant contributes to a better understanding of the clinical and biological behavior of desmoplastic ameloblastoma, which is still not fully elucidated. [ABSTRACT FROM AUTHOR]

A 65-year-old woman with a complaint of a gingival lesion sought treatment at our clinic. She had been using Malvona® mouthwash, which had caused a burning sensation. Intraoral examination revealed a brownish lesion with a smooth surface and fibrous consistency in the upper posterior vestibular and palatine gingiva. Additionally, ulcers were observed in the buccal mucosa. We discontinued the use of the mouthwash and prescribed chlorhexidine 0.12% to be used twice a day. During the patient's follow-up visit, the brownish lesion remained, but the ulcers had resolved. Our primary diagnostic suspicion was melanoma, and incisional biopsies were performed on both the vestibular and palatine gingiva. Histopathological and immunohistochemistry examinations (MelanA, HMB45, and S100) confirmed the diagnosis of melanoma. The patient was referred for treatment, which involved surgical intervention alone. Oral melanoma is an exceptionally rare and aggressive neoplasm in the oral cavity, making early diagnosis crucial for prognosis. Oral pigmentations are often overlooked, highlighting the importance of performing biopsies in cases of suspicious lesions.. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the histomorphologic presentation and the expression of stem cell-related markers in a series of oral solitary fibrous tumors (SFTs).Study Design: Histopathological variables and the expression of the standard stem cell markers CD34 and CD99, used for SFT diagnosis, as well as STAT6 were evaluated in 13 oral SFTs. The expression of the cancer stem cell markers CD44, ALDH1, Bmi-1, and Nanog and the tumor suppressor gene p16Ink4a were also investigated.Results: The majority of oral SFTs were circumscribed and characterized by a proliferation of spindle cells arranged in a hyalinized stroma. Only 2 oral SFTs showed >4 mitoses/10 high-power fields. Hypercellularity as well as nuclear and cellular pleomorphism were classified as low and moderate in most of the oral SFTs. All oral SFTs were positive for CD34, STAT6, CD44, ALDH1, Bmi-1, and p16Ink4a. CD99 and Nanog expression was observed in 11 and 10 oral SFT cases, respectively.Conclusion: We suggest that STAT6 and ALDH1 have relevant diagnostic value. The expression of CD44, ALDH1, Bmi-1, and Nanog, which is observed in cancer stem cells, may confer advantages to oral SFT cells. [ABSTRACT FROM AUTHOR]

Abstract Background Meningiomas may occur either as familial tumors in two distinct disorders, familial multiple meningioma and neurofibromatosis 2 (NF2), or sporadically, as either single or multiple tumors in individuals with no family history. Meningiomas in NF2 and approximately 60% of sporadic meningiomas involve inactivation of the NF2 locus, encoding the tumor suppressor merlin on chromosome 22q. This study was undertaken to establish whether genomic profiling could distinguish familial multiple meningiomas from sporadic solitary and sporadic multiple meningiomas. Methods We compared 73 meningiomas presenting as sporadic solitary (64), sporadic multiple (5) and familial multiple (4) tumors using genomic profiling by array comparative genomic hybridization (array CGH). Results Sporadic solitary meningiomas revealed genomic rearrangements consistent with at least two mechanisms of tumor initiation, as unsupervised cluster analysis readily distinguished tumors with chromosome 22 deletion (associated with loss of the NF2 tumor suppressor) from those without chromosome 22 deletion. Whereas sporadic meningiomas without chromosome 22 loss exhibited fewer chromosomal imbalance events overall, tumors with chromosome 22 deletion further clustered into two major groups that largely, though not perfectly, matched with their benign (WHO Grade I) or advanced (WHO Grades II and III) histological grade, with the latter exhibiting a significantly greater degree of genomic imbalance (P < 0.001). Sporadic multiple meningiomas showed a frequency of genomic imbalance events comparable to the atypical grade solitary tumors. By contrast, familial multiple meningiomas displayed no imbalances, supporting a distinct mechanism for the origin for these tumors. Conclusion Genomic profiling can provide an unbiased adjunct to traditional meningioma classification and provides a basis for exploring the different genetic underpinnings of tumor initiation and progression. Most importantly, the striking difference observed between sporadic and familial multiple meningiomas indicates that genomic profiling can provide valuable information for differential diagnosis of subjects with multiple meningiomas and for considering the risk for tumor occurrence in their family members.

Abstract Background Oral squamous cell carcinoma (OSCC) is a frequent neoplasm, which is usually aggressive and has unpredictable biological behavior and unfavorable prognosis. The comprehension of the molecular basis of this variability should lead to the development of targeted therapies as well as to improvements in specificity and sensitivity of diagnosis. Results Samples of primary OSCCs and their corresponding surgical margins were obtained from male patients during surgery and their gene expression profiles were screened using whole-genome microarray technology. Hierarchical clustering and Principal Components Analysis were used for data visualization and One-way Analysis of Variance was used to identify differentially expressed genes. Samples clustered mostly according to disease subsite, suggesting molecular heterogeneity within tumor stages. In order to corroborate our results, two publicly available datasets of microarray experiments were assessed. We found significant molecular differences between OSCC anatomic subsites concerning groups of genes presently or potentially important for drug development, including mRNA processing, cytoskeleton organization and biogenesis, metabolic process, cell cycle and apoptosis. Conclusion Our results corroborate literature data on molecular heterogeneity of OSCCs. Differences between disease subsites and among samples belonging to the same TNM class highlight the importance of gene expression-based classification and challenge the development of targeted therapies.