Interobserver concordance in visual assessment of Ki67 immunohistochemistry in surgical excision specimens from patients with lymph node-negative breast cancer.

PURPOSE: This study aimed to determine the interobserver concordance of two methods for proliferation assessment in breast cancer using Ki67 immunohistochemistry. METHODS: Ki67 was independently assessed in randomly selected tumour samples from patients with lymph node-negative breast cancer using two different methods: either cell counting or visual estimation of hot spot areas. For hot spot cell counting, positive and negative cell numbers were recorded for total cell counts of 300-500, 500-800 and 800-1000 cells. Visual estimation involved allocation of a score from 1 to 5 using a visual scale to estimate percentage positivity. Interobserver agreement for hot spot counting was calculated using a two-way fixed effects intraclass correlation model, and by using Cohen's kappa measure for visual assessment. Prognostic concordance between the two methods was also calculated using Cohen's kappa. RESULTS: Samples from 96 patients were included in this analysis. Interobserver agreement for hot spot cell counting was excellent (> 0.75) across all three cell count ranges, with correlation coefficients of 0.88 (95% CI 0.84-0.92), 0.87 (95% CI 0.82-0.91) and 0.89 (95% CI 0.85-0.92), respectively. Interobserver agreement with visual estimation was greatest for hot spots compared with areas of intermediate or low proliferation, with kappa scores of 0.49, 0.42 and 0.40, respectively. Both assessment methods demonstrated excellent prognostic agreement. CONCLUSIONS: Interobserver and prognostic concordance in Ki67 immunohistochemistry assessments was high using either hot spot cell counting or visual estimation, further supporting the utility and reproducibility of these cost-efficient methods to assess proliferation.

Histologic Assessment of Lichenoid Dermatitis Observed in Patients With Advanced Malignancies on Antiprogramed Cell Death-1 (anti-PD-1) Therapy With or Without Ipilimumab.

Lichenoid drug reaction is a common adverse reaction in patients taking immune-modulatory agents such as antiprogramed cell death (PD-1) and cytotoxic T lymphocyte antigen-4 agents. The authors describe the clinical and histologic features of lichenoid drug reaction in 20 biopsies from 15 patients on anti-PD-1 agents and 9 biopsies from 7 patients on anti-PD-1 plus ipilimumab therapy. Clinically, all except 2 patients presented with discrete, violaceous exanthematous papules to plaques. The lichenoid inflammation in the majority (18 of 29 biopsies) was florid although histology was quite heterogeneous. Nevertheless, there was frequent involvement of the superficial follicular epithelium and acrosyringium, and also a propensity to blister that occurred in approximately 20% of the biopsies. Occasional patients had disease closely resembling lichen planus, although all of these biopsies had some atypical features for lichen planus such as parakeratosis. Dermal eosinophils were common particularly in those with mild inflammation. The lichenoid reaction was responsive to topical steroid or oral systemic treatment in general, and the anti-PD-1 agent had to be ceased in only one patient.