Invisible dermatosis, diagnostic discrepancy between the general pathologist and dermatopathologist.

BACKGROUND: Many clinically indicated skin biopsies show minimal histological changes referred to as "invisible dermatoses." They pose a challenge to general pathologists and dermatopathologists. This study determines the discrepancy between the general pathologists' diagnosis and the dermatopathologist's diagnosis and helps define a pathway for reaching the correct diagnosis. METHODS: In total, 81 skin cases were selected from a tertiary hospital pathology department. They were diagnosed by general pathologists as "no specific diagnosis," or "minimal pathologic changes." These cases were reviewed carefully and diagnosed by a dermatopathologist. His diagnoses were compared with the original diagnoses. RESULTS: Out of the 81 cases, 43 cases (53%) were reported by the dermatopathologist to have a specific diagnosis while 38 cases (46.9%) remained nonspecific. Both inflammatory and neoplastic diagnoses of potential clinical significance were made in the first group of 43 cases. The remaining 38 cases with nonspecific results were due to inadequate biopsy, inactive lesions or inadequate clinical data. CONCLUSION: "Invisible dermatoses" describes skin diseases with clinically evident but histologically hidden changes. They are difficult cases for general pathologists and dermatopathologists to diagnose. Hence, it is important to be aware that minor changes on a skin biopsy do not mean it is disease-free.

The histological spectrum of tubulo-reticular inclusion positive renal biopsies: a tertiary hospital experience and review of the literature.

AIM: To identify the underlying diseases with TRI-positive kidney biopsies, and describe the histological pattern and spectrum of TRI-positive kidney biopsies. METHODS: A retrospective analysis of all patients' chart that underwent renal biopsy at King Saud University Medical City between 2012 and 2017 was done. Kidney biopsies that indicated a positive result for tubuloreticular inclusions (TRI's) on electron microscopy were reviewed and the underlying disease and histological pattern was extracted. RESULTS: Of 1,473 native kidney biopsies reviewed, 96 (6.5%) were TRI-positive. Of the 96 TRI-positive kidney biopsies, 87 (90.6%) were TRI-positive lupus nephritis (LN); of which 10 (11.5%) were Class V, 49 (56.3%) were active LN, and 28 (32.2%) were inactive LN. The underlying diseases of the nine non-LN TRI-positive cases included diabetic nephropathy, connective tissue disorders, immune complex mediated Glomerulonephritis (GN), acute thrombotic microangiopathy, rhabdomyolysis, and Wegener's disease. CONCLUSION: LN is a very common finding in TRI-positive kidney biopsies. Active LN and chronic LN are the more common classes of TRI-positive LN kidney biopsies, than pure membranous (Class V) LN. TRI positive kidney biopsies without LN are commonly found in diabetic nephropathy, connective tissue disorders and immune mediated GN's. This study highlights this finding in our patients cohort in opposition to what has been reported in the literature.

Reproducibility of Assessment of Lepidic (Noninvasive) Patterns in Lung Adenocarcinoma With Cytokeratin Immunostain Compared With Hematoxylin and Eosin and the Proposed New International Association for the Study of Lung Cancer (IASLC) Algorithm.

Introduction: Lepidic growth is considered noninvasive in lung nonmucinous adenocarcinoma, whereas other patterns are invasive. Considerable interobserver variability in assessing "invasion" has been reported. We assessed the utility of cytokeratin 7 (CK7) stain and recently proposed International Association for the Study of Lung Cancer criteria to improve assessment of noninvasion in lung adenocarcinoma. Methods: Four pathologists (two staff, two trainees) assessed 158 hematoxylin and eosin (HE)- and CK7-stained slides of 108 pT1N0-2 nonmucinous lung adenocarcinoma cases. Scoring took place in four rounds. First, sections were independently scored for percentage of noninvasive or probable noninvasive and invasive or probable invasive patterns. Second, after a consensus scoring algorithm for CK7 was formulated, the slides were rescored. Subsequent third-round scoring was conducted only on HE slides using the 2023 International Association for the Study of Lung Cancer proposed criteria, and fourth-round scoring on both HE and CK7 slides simultaneously. Intraclass correlation coefficient (ICC) was calculated for each round. Recurrence-free survival was assessed using Cox proportional hazards regression methods. Results: In the first two rounds, interobserver concordance was consistently higher with CK7 (ICC range = 0.44-0.6) than HE (range = 0.24-0.49) scores. The IASLC proposed algorithm improved ICC of HE scores to 0.60 (95% confidence interval: 0.52-0.67), and round 4 HE and CK7 combined improved ICC to 0.75 (95% confidence interval: 0.70-0.80). Continuous measures of averaged noninvasive and probable noninvasive scores on HE were associated with improved recurrence-free survival (hazard ratio: 0.83-0.86). Conclusions: CK7 staining consistently increased interobserver concordance in assessment of invasive versus noninvasive patterns than HE. Combining CK7 with the 2023 IASLC criteria for morphologic features of invasion may further improve the interobservers' concordance for the recognition of lepidic growth in nonmucinous lung adenocarcinoma.

In vivo CRISPR screens identify a dual function of MEN1 in regulating tumor-microenvironment interactions.

Functional genomic screens in two-dimensional cell culture models are limited in identifying therapeutic targets that influence the tumor microenvironment. By comparing targeted CRISPR-Cas9 screens in a two-dimensional culture with xenografts derived from the same cell line, we identified MEN1 as the top hit that confers differential dropout effects in vitro and in vivo. MEN1 knockout in multiple solid cancer types does not impact cell proliferation in vitro but significantly promotes or inhibits tumor growth in immunodeficient or immunocompetent mice, respectively. Mechanistically, MEN1 knockout redistributes MLL1 chromatin occupancy, increasing H3K4me3 at repetitive genomic regions, activating double-stranded RNA expression and increasing neutrophil and CD8+ T cell infiltration in immunodeficient and immunocompetent mice, respectively. Pharmacological inhibition of the menin-MLL interaction reduces tumor growth in a CD8+ T cell-dependent manner. These findings reveal tumor microenvironment-dependent oncogenic and tumor-suppressive functions of MEN1 and provide a rationale for targeting MEN1 in solid cancers.

PD-L1 assessment in cytology samples predicts treatment response to checkpoint inhibitors in NSCLC.

BACKGROUND: Testing for tumor programmed death ligand-1 (PD-L1) expression was initially developed with histology specimens in non-small cell lung cancer (NSCLC). However, cytology specimens are widely used for primary diagnosis and biomarker studies in clinical practice. Limited clinical data exist on the predictiveness of cytology-derived PD-L1 scores for response to immune checkpoint inhibitor (ICI) therapy. METHODS: We reviewed all NSCLC specimens clinically tested at the University Health Network (UHN) for PD-L1 with 22C3pharmDx, from 01/2013 to 04/2021. Treatment outcomes in patients treated with single agent ICI therapy were reviewed and compared according to cytology- and histology-derived PD-L1 scores. RESULTS: We identified 494 and 1942 unique patients with cytology- and histology-derived tumor proportion scores, respectively, during the study period. Informative testing rates were 95 % vs 98 % for cytology and histology, respectively. Clinical data were available for 152 patients treated with single agent ICI: 61 cytology and 91 histology. Overall response rates (ORR) were similar for cytology and histology (36 % vs 34 %; p = 0.23), as well as median progression free survival (PFS) (4.9 vs 4.2 months; p = 0.99) and overall survival (23.4 vs 19.7 months; p = 0.99). The results remained similar even after adjusting for PD-L1 expression levels and line of ICI treatment (PFS HR 1.15; 95 %CI 0.78-1.70; p = 0.47). CONCLUSIONS: Treatment outcomes to single agent ICI based on cytology-derived PD-L1 scores were comparable to histology controls. Our results support PD-L1 biomarker testing on both cytology and histology specimens.

Case report of intra-articular synovial sarcoma in the hip joint.

Synovial sarcoma is a type of soft tissue sarcoma that commonly occurs around large joints. However, primary intra-articular synovial sarcoma is considered an extremely rare variant of synovial sarcoma. We present a case of synovial sarcoma arising from the hip joint in a 17-year-old female patient. Clinical, radiographic, magnetic resonance imaging and histopathology findings are described. The patient underwent neoadjuvant chemoradiation therapy followed by right hemipelvectomy, and there was no local recurrence in the subsequent follow ups. Unfortunately, the patient had pleural metastasis, and she was treated with palliative chemotherapy. To the best of our knowledge, there is only one published case report in the English literature on intra-articular synovial sarcoma from the hip joint.

Corrigendum to "Case report of intra-articular synovial sarcoma in the hip joint" [Radiology Case Reports 15 (2020) 1256-1260].

[This corrects the article DOI: 10.1016/j.radcr.2020.05.026.].

Topical corticosteroids knowledge, attitudes, and practices of primary care physicians.

OBJECTIVES: To assess knowledge, attitudes, and practices of primary care physicians (PCPs) toward topical corticosteroids (TCs). Methods: A cross-sectional, 53-item questionnaire based study on TCs was conducted among PCPs in Riyadh, Kingdom of Saudi Arabia between January and March 2015. A maximum score of 30 was calculated for the knowledge portion. Results: Out of 420 PCPs, 336 responded (80%). Most participants (89.6%) reported prescribing TCs. The mean knowledge score was 17.14 (SD=5.48). Only 39% PCPs correctly identified that there are 7 or 4 TCs potency groups (2 different classification systems). The MBBS/MD and diploma-certified physicians scored lower than board-qualified PCPs (p less than 0.05). Family medicine physicians scored higher than general practitioners (GPs) (p less than 0.05). Hospital-based PCPs scored better than private practice PCPs (p less than 0.05). Moreover, those who felt somewhat comfortable (32.5%) in treating dermatology patients were more knowledgeable (p less than 0.05). Lastly, 76.5% of physicians were interested in attending courses on dermatologic therapies.  Conclusion: Knowledge of TCs among PCPs was inadequate. Targeted educational interventions delivered by dermatologists are recommended.