Context.— The adoption of digital capture of pathology slides as whole slide images (WSI) for educational and research applications has proven utility. Objective.— To compare pathologists' primary diagnoses derived from WSI versus the standard microscope. Because WSIs differ in format and method of observation compared with the current standard glass slide microscopy, this study is critical to potential clinical adoption of digital pathology. Design.— The study enrolled a total of 2045 cases enriched for more difficult diagnostic categories and represented as 5849 slides were curated and provided for diagnosis by a team of 19 reading pathologists separately as WSI or as glass slides viewed by light microscope. Cases were reviewed by each pathologist in both modalities in randomized order with a minimum 31-day washout between modality reads for each case. Each diagnosis was compared with the original clinical reference diagnosis by an independent central adjudication review. Results.— The overall major discrepancy rates were 3.64% for WSI review and 3.20% for manual slide review diagnosis methods, a difference of 0.44% (95% CI, −0.15 to 1.03). The time to review a case averaged 5.20 minutes for WSI and 4.95 minutes for glass slides. There was no specific subset of diagnostic category that showed higher rates of modality-specific discrepancy, though some categories showed greater discrepancy than others in both modalities. Conclusions.— WSIs are noninferior to traditional glass slides for primary diagnosis in anatomic pathology.

BackgroundH Syndrome is an autosomal recessive disorder characterized by cutaneous hyperpigmentation, hypertrichosis, and induration with numerous systemic manifestations. The syndrome is caused by mutations in SLC29A3, a gene located on chromosome 10q23, which encodes the human equilibrative transporter 3 (hENT3). Less than 100 patients with H syndrome have been described in the literature, with the majority being of Arab descent, and only a few from North America.Case presentationHere we report five pediatric patients from three medical centers in the United States who were identified to have H syndrome by whole exome sequencing. These five patients, all of whom presented to pediatric rheumatologists prior to diagnosis, include two of Northern European descent, bringing the total number of Caucasian patients described to three. The patients share many of the characteristics previously reported with H syndrome, including hyperpigmentation, hypertrichosis, short stature, insulin-dependent diabetes, arthritis and systemic inflammation, as well as some novel features, including selective IgG subclass deficiency and autoimmune hepatitis. They share genetic mutations previously described in patients of the same ethnic background, as well as a novel mutation. In two patients, treatment with prednisone improved inflammation, however both patients flared once prednisone was tapered. In one of these patients, treatment with tocilizumab alone resulted in marked improvement in systemic inflammation and growth. The other had partial response to prednisone, azathioprine, and TNF inhibition; thus, his anti-TNF biologic was recently switched to tocilizumab due to persistent polyarthritis. Another patient improved on Methotrexate, with further improvement after the addition of tocilizumab.ConclusionH syndrome is a rare autoinflammatory syndrome with pleiotropic manifestations that affect multiple organ systems and is often mistaken for other conditions. Rheumatologists should be aware of this syndrome and its association with arthritis. It should be considered in patients with short stature and systemic inflammation, particularly with cutaneous findings. Some patients respond to treatment with biologics alone or in combination with other immune suppressants; in particular, treatment of systemic inflammation with IL-6 blockade appears to be promising. Overall, better identification and understanding of the pathophysiology may help devise earlier diagnosis and better treatment strategies.

The mitotic rate (MR) of malignant melanoma (MM) refers to the number of mitoses per square millimeter. Studies have suggested that it is an independent prognostic variable predicting survival in patients with MM, and it was recently included in the American Joint Committee on Cancer (AJCC) recommendations for diagnosis and treatment of MM. The AJCC melanoma staging committee recommends using the "hot-spot" approach to determine the MR, whereby it is reported as the maximum dermal mitotic figures identified in a 1-mm area of the melanoma. The AJCC has recommended that the MR be determined in all melanomas, irrespective of Breslow depth or other features. We aimed to quantify the MR in MM ≤1 mm in thickness and to identify statistical associations between the MR, Breslow depth, and Clark level. In addition, we hoped to identify practical issues in determining the MR via the hot-spot technique. We conducted a prospective study to determine the MR, Breslow depth, and Clark level in MM ≤1 mm in thickness. Seven melanomas were identified with epidermal mitoses only (7.4%). Sixteen melanomas had dermal mitoses (16.8%); of these, the majority (75.0%) contained only one mitotic figure. Seventy-nine melanomas had no dermal mitoses (83.2%). Seven lesions (7.4%) demonstrated multiple mitoses; 4 with ≥2 dermal mitoses/mm and 3 with multiple epidermal mitoses. We conclude that thin MM with >1 mitosis/mm is rare and discuss practical and theoretical issues with determining the MR using the hot-spot approach.

BACKGROUNDMelanoma in situ (MIS) can have poorly defined borders and subclinical extension that makes margin control challenging. Reflectance confocal microscopy (RCM) is a promising noninvasive technique that can be used to assess subclinical spread.OBJECTIVETo optimize surgical margins of histology-proven MIS using RCM mosaics.MATERIALS AND METHODSProspective review of 22 patients with histology-proven MIS who underwent RCM margin mapping prior to staged excision, between August 1, 2018, and August 13, 2020, at the Department of Dermatology, University of New Mexico, School of Medicine.RESULTSTwenty patients (91%) had tumor clearance on the first stage using a 3-mm surgical margin after confocal margin mapping.CONCLUSIONReflectance confocal microscopy margin mapping using the mosaic device tends to clear MIS in one stage, and the use of the handheld device may improve the accuracy for difficult anatomic areas. Current Procedural Terminology codes for RCM do not reflect the time required and complexity of the procedure. Reflectance confocal microscopy margin mapping prior to excision has the potential to decrease the number of stages needed for melanoma removal, reduce treatment time, and cost.

No abstract