Novoa, Roberto A.

AbstractBackgroundThe reliability to non‐invasively identify features of inflammatory dermatoses by reflectance confocal microscopy (RCM) remains unknown. Lack of formal training among RCM readers can result in inconsistent assessments, limiting clinical utility. Specific consensus terminology with representative images is necessary to ensure consistent feature‐level interpretation among RCM readers.Objectives(1) Develop a glossary with representative images of RCM features of cutaneous acute graft‐versus‐host disease (aGVHD) for consistent interpretation among observers, (2) assess the interobserver reproducibility among RCM readers using the glossary, and (3) determine the concordance between RCM and histopathology for aGVHD features.MethodsThrough an iterative process of refinement and discussion among five international RCM experts, we developed a glossary with representative images of RCM features of aGVHD. From April to November 2018, patients suspected of aGVHD were imaged with RCM and subsequently biopsied. 17 lesions from 12 patients had clinically and pathologically confirmed cutaneous aGVHD. For each of these lesions, four dermatopathologists and four RCM readers independently evaluated the presence of aGVHD features in scanned histopathology slides and 1.5 × 1.5 mm RCM submosaics at 4 depths (blockstacks) respectively. RCM cases were adjudicated by a fifth RCM expert. Interobserver reproducibility was calculated by mean pairwise difference (U statistic). Concordance between modalities was determined by fraction of assignments with agreement.ResultsWe present a glossary with representative images of 18 aGVHD features by RCM. The average interobserver reproducibility among RCM readers (75%, confidence interval, CI: 71–79%) did not differ significantly from dermatopathologists (80%, 76–85%). The concordance between RCM and histopathology was 59%.ConclusionsBy using the glossary, the interobserver reproducibility among RCM readers was similar to the interobserver reproducibility among dermatopathologists. There was reasonable concordance between RCM and histopathology to visualize aGVHD features. The implementation of RCM can now be advanced in a variety of inflammatory conditions with a validated glossary and representative image set.

AbstractBackgroundAppropriate use criteria (AUC) provide patient‐centered physician guidance in test selection. An initial set of AUC was reported by the American Society of Dermatopathology (ASDP) in 2018. AUC reflect evidence collected at single timepoints and may be affected by evolving evidence and experience. The objective of this study was to update and expand AUC for selected tests.MethodsRAND/UCLA (RAND Corporation [Santa Monica, CA]/University of California Los Angeles) methodology used includes the following: (a) literature review; (b) review of previously rated tests and previously employed clinical scenarios; (c) selection of previously rated tests for new ratings; (d) development of new clinical scenarios; (e) selection of additional tests; (f) three rating rounds with feedback and group discussion after rounds 1 and 2.ResultsFor 220 clinical scenarios comprising lymphoproliferative (light chain clonality), melanocytic (comparative genomic hybridization, fluorescence in situ hybridization, reverse transcription polymerase chain reaction, telomerase reverse transcriptase promoter), vascular disorders (MYC), and inflammatory dermatoses (periodic acid‐Schiff, Gömöri methenamine silver), consensus by panel raters was reached in 172 of 220 (78%) scenarios, with 103 of 148 (70%) rated “usually appropriate” or “rarely appropriate” and 45 of 148 (30%), “appropriateness uncertain.” Limitations: The study design only measures appropriateness. Cost, availability, test comparison, and additional clinical considerations are not measured. The possibility that the findings of this study may be influenced by the inherent biases of the dermatopathologists involved in the study cannot be excluded.ConclusionsAUC are reported for selected diagnostic tests in clinical scenarios that occur in dermatopathology practice. Adhering to AUC may reduce inappropriate test utilization and improve healthcare delivery.

BACKGROUND. Cutaneous erythema and histopathology features in patients post allogeneic hematopoietic cell transplantation (HCT) are nonspecific, making it difficult to distinguish acute graft-versus-host disease (aGVHD) from engraftment syndrome, drug reactions, viral infections, and other etiologies. Biopsies from different locations on the same patient frequently differ in aGVHD grade, and serial biopsies of a single lesion are not possible. Proper biopsy site selection, timing, and serial noninvasive microscopic monitoring may improve our understanding and management of aGVHD. In this study, we tested the feasibility of noninvasive reflectance confocal microscopy (RCM) to detect key histopathology features of cutaneous aGVHD. STUDY POPULATION. We enrolled 11 patients with high clinical suspicion of cutaneous aGVHD, as determined by a transplant physician. In total, 16 lesions of cutaneous aGVHD-affected site were imaged by RCM (6x6 mm2en face images at four different depths) and subsequently biopsied (4x4 mm punch biopsy). 9 out of 11 patients had only skin involvement, and 2 patients had skin and gut aGVHD. 5 patients had >50% body surface area (BSA) affected, 1 had 18-50% BSA, and 5 had <18% BSA. 8 out of 11 patients required systemic corticosteroids and 3 patients received topical corticosteroids. All patients were imaged before starting treatment. METHODS. We used a clinical confocal microscope (Vivascope 1500, Caliber I.D.), which enables real-time evaluation of epidermal and superficial dermal tissue at sub-cellular resolution. Four reflectance confocal microscopists blinded to histopathology independently evaluated the presence or absence of 18 RCM features1. Concurrently, four dermatopathologists blinded to clinical and confocal information determined the presence or absence of 19 histopathology features, as well as the Lerner aGVHD grade. A histologic feature was determined as "present" in a lesion when marked by most experts (expert vote) or resolved by a fifth expert in case of a disagreement among four experts. The reflectance confocal microscopist vote was then correlated to the dermatopathologist expert vote for 17 overlapping features. We also evaluated the interrater variability among microscopists and among dermatopathologists. RESULTS. The main aGVHD features by Lerner grade had > 88% correlation between RCM and histopathology: (1) basal vacuolar change, (2) presence of dyskeratotic keratinocytes, and (3) dermal inflammation. By contrast, dyskeratotic cells and inflammation at the adnexal structures had <50% correlation. This may be attributed to the fact that more adnexal structures are typically visible in the 6x6 mm2 RCM horizontal tissue view compared to vertical section histopathology. We found a similar interrater variability among RCM experts (70%) and dermatopathologists (68%). CONCLUSIONS. In this pilot study, we show that noninvasive label-free RCM of skin enables detection of the main Lerner grade features of cutaneous aGVHD. We found a similar interrater variability among reflectance confocal microscopists and among dermatopathologists who each independently evaluated the presence or absence of a list of aGVHD features. Future studies can build on this work to evaluate the feasibility of RCM to determine cutaneous aGVHD grade, as well as distinguish between rash due to aGVHD and drug reactions. ACKNOWLEDGEMENT. This work was supported in part by Career Development Award Number IK2 CX001785 from the United Sates Department of Veterans Affairs Clinical Science R&D (CSRD) Service. Saknite I, Gill M, Alessi-Fox C, Byrne M, Jagasia M, Gonzalez S, Ardigo M, Tkaczyk ER. Features of cutaneous acute graft-versus-host disease by reflectance confocal microscopy. Br J Dermatol (2019). Disclosures Christi: Caliber I.D.: Employment, Equity Ownership. Byrne:Karyopharm: Research Funding. Jagasia:Kadmon: Consultancy; Incyte: Consultancy; Janssen: Research Funding. Tkaczyk:Incyte: Consultancy.

BackgroundAppropriate use criteria (AUC) provide physicians guidance in test selection, and can affect health care delivery, reimbursement policy and physician decision‐making.ObjectivesThe American Society of Dermatopathology, with input from the American Academy of Dermatology and the College of American Pathologists, sought to develop AUC in dermatopathology.MethodsThe RAND/UCLA appropriateness methodology, which combines evidence‐based medicine, clinical experience and expert judgment, was used to develop AUC in dermatopathology.ResultsWith the number of ratings predetermined at 3, AUC were developed for 211 clinical scenarios involving 12 ancillary studies. Consensus was reached for 188 (89%) clinical scenarios, with 93 (44%) considered “usually appropriate,” 52 (25%) “rarely appropriate” and 43 (20%) “uncertain appropriateness.”LimitationsThe methodology requires a focus on appropriateness without comparison between tests and irrespective of cost.ConclusionsThe ultimate decision of when to order specific test rests with the physician and is one where the expected benefit exceeds the negative consequences. This publication outlines the recommendations of appropriateness—AUC for 12 tests used in dermatopathology. Importantly, these recommendations may change considering new evidence. Results deemed “uncertain appropriateness” and where consensus was not reached may benefit from further research.