Evaluation of the proliferation marker Ki-67 in gliomas: Interobserver variability and digital quantification.

BACKGROUND: The Ki-67 Labelling Index (LI) is used as an ancillary tool in glioma diagnostics. Interobserver variability has been reported and no precise guidelines are available. Nor is it known whether novel digital approaches would be an advantage. Our aim was to evaluate the inter- and intraobserver variability of the Ki-67 LI between two pathologists and between pathologists and digital quantification both in whole tumour slides and in hot spots using narrow but diagnostically relevant intervals. METHODS: In samples of 235 low and high grade gliomas, two pathologists (A and B) estimated the Ki-67 LI (5-10% intervals) for whole tumour slides and for hot spots. In 20 of the cases intraobserver variability was evaluated. For digital quantification (C) slides were scanned with subsequent systematic random sampling of viable tumour areas. A software classifier trained to identify positive and negative nuclei calculated the Ki-67 LI. The interobserver agreements were evaluated using kappa (κ) statistics. RESULTS: The observed proportions of agreement and κ values for Ki-67 LI for whole tumour slides were: A/B: 46% (κ = 0.32); A/C: 37% (κ = 0.26); B/C: 37% (κ = 0.26). For hot spots equivalent values were: A/B: 14% (κ = 0.04); A/C: 18% (κ = 0.09); B/C: 31% (κ = 0.21). CONCLUSIONS: Interobserver variability was pronounced between pathologists and for pathologists versus digital quantification when attempting to estimate a precise value of the Ki-67 LI. Ki-67 LI should therefore be used with caution and should not be over interpreted in the grading of gliomas. Digital quantification of Ki-67 LI in gliomas was feasible, but intra- and interlaboratory robustness need to be determined.

Two patients with localised hyperhidrosis of the hand based on functional and structural abnormalities of sweat glands.

A 14-year-old girl and a 30-year-old woman presented with localised hyperhidrosis on the dorsal hand and wrist, respectively, provoked by different stimuli such as physical activity and minor trauma to the skin. The skin was seemingly normal in both patients where an iodine-starch test revealed a well-demarcated area of hyperhidrosis. Following histopathological examination, the diagnosis was unilateral localised hyperhidrosis in both cases; one with normal histology and one with a nevus sudoriferous. Both patients were successfully treated with botulinum toxin type A. The 30-year-old woman additionally used low-dose propantheline bromide periodically and experienced long-term remission on this therapy. Hyperhidrosis may embarrass and interfere with patients' school and careers, and it is therefore important to tailor an effective individual treatment.

Atypical Hand, Foot, and Mouth Disease Caused by Coxsackievirus A6 in Denmark: A Diagnostic Mimicker.

Since 2008, outbreaks of atypical hand, foot, and mouth disease (HFMD) in children and adults have been reported worldwide. The majority of these outbreaks are caused by a new lineage of Coxsackie virus A6 (CV-A6) presenting a more severe clinical phenotype than the classical childhood HFMD caused by CV-A16. Between June 2014 and January 2016, 23 cases of atypical HFMD disease presented at a Dermatology Department at a regional University Hospital in Denmark. Patients were referred by general practitioners and dermatologists with a variety of clinical diagnoses, including eczema herpeticum, vasculitis, syphilis, dermatophytid, erythema multiforme and Stevens-Johnson syndrome. Three adults and 3 children required hospitalization due to extensive skin involvement and fever. All reported patients had laboratory-confirmed enterovirus infection. This study demonstrated an upsurge in atypical HFMD caused by CV-A6 in the Region of Southern Denmark and that atypical HFMD can be difficult to diagnose clinically as it may mimic other severe skin diseases.