Intra- and Interobserver Reproducibility Assessment of PD-L1 Biomarker in Non-Small Cell Lung Cancer.

Purpose: Reliable and reproducible methods for identifying PD-L1 expression on tumor cells are necessary to identify responders to anti-PD-1 therapy. We tested the reproducibility of the assessment of PD-L1 expression in non-small cell lung cancer (NSCLC) tissue samples by pathologists.Experimental Design: NSCLC samples were stained with PD-L1 22C3 pharmDx kit using the Dako Autostainer Link 48 Platform. Two sample sets of 60 samples each were designed to assess inter- and intraobserver reproducibility considering two cut points for positivity: 1% or 50% of PD-L1 stained tumor cells. A randomization process was used to obtain equal distribution of PD-L1 positive and negative samples within each sample set. Ten pathologists were randomly assigned to two subgroups. Subgroup 1 analyzed all samples on two consecutive days. Subgroup 2 performed the same assessments, except they received a 1-hour training session prior to the second assessment.Results: For intraobserver reproducibility, the overall percent agreement (OPA) was 89.7% [95% confidence interval (CI), 85.7-92.6] for the 1% cut point and 91.3% (95% CI, 87.6-94.0) for the 50% cut point. For interobserver reproducibility, OPA was 84.2% (95% CI, 82.8-85.5) for the 1% cut point and 81.9% (95% CI, 80.4-83.3) for the 50% cut point, and Cohen's κ coefficients were 0.68 (95% CI, 0.65-0.71) and 0.58 (95% CI, 0.55-0.62), respectively. The training was found to have no or very little impact on intra- or interobserver reproducibility.Conclusions: Pathologists reported good reproducibility at both 1% and 50% cut points. More adapted training could potentially increase reliability, in particular for samples with PD-L1 proportion, scores around 50%. Clin Cancer Res; 23(16); 4569-77. ©2017 AACR.

Novel therapeutic option for orbital atypical lymphoid hyperplasia.

Ocular lymphoid tumours represent a spectrum of lymphoproliferative disease and can be subdivided into benign or reactive lymphoid hyperplasia, indeterminate or atypical lymphoid proliferations and malignant lymphoma. Treatment options include a wait and watch approach, systemic steroids, local radiotherapy or systemic chemotherapy. We describe a case of bilateral atypical lymphoid hyperplasia treated successfully with combination immunotherapy and radiotherapy. A 60-year-old lady presented with proptosis and left supra-orbital mass and was diagnosed to have bilateral atypical lymphoid hyperplasia. She had extensive extraocular facial infiltrates but no other sites of involvement on staging investigations. She was treated with eight doses of rituximab 375 mg/m² at weekly intervals with a good partial response, followed by consolidative radiotherapy. Rituximab may be an effective treatment adjunct/alternative for patients with atypical lymphoid hyperplasia of the orbit, particularly where widespread lesions preclude the use of initial radiotherapy.

Schwannoma with tentorial attachment in the cerebellopontine angle mimicking a meningioma.

Intracranial schwannoma not associated with the cranial nerves is rare. It is also an intriguing neoplasm since the Schwann cell is not native to the central nervous system. To date only four cases of intracranial schwannoma arising from the tentorium have been reported. We present a 49-year-old woman who harboured a schwannoma with a tentorial attachment in the right cerebellopontine angle and describe the relevant clinical, radiological and pathological findings. In addition, we briefly review the main hypotheses for the origin of this neoplasm and highlight its resemblance to meningioma and inclusion as a differential diagnosis.

Correlation between macroscopic changes of arthrosis and the posterior cruciate ligament histology in the osteoarthritic knee.

BACKGROUND: There is ongoing debate about the role of the posterior cruciate ligament (PCL) in total knee arthroplasty. Advocates of PCL retention cite better soft tissue balance and improved proprioception, whereas opponents report late flexion instability. The results of knee replacement are similar whether the PCL is retained or sacrificed. The aim of the present study was to examine the PCL for histological changes that would infer its competence and correlate these with changes easily observed by the operating surgeon. METHODS: A prospective study of 50 osteoarthritic knees was performed. RESULTS: Histology of the PCL showed changes secondary to degeneration and trauma. In most of the ligaments examined, arteriosclerosis and fibrosis were present. Half of the PCL examined showed perineural fibrosis, myxoid change and hyalinization. These changes, although very frequent, did not correlate well to the changes observed in either the anterior or PCL, or in the overall severity of osteoarthrosis. CONCLUSIONS: Posterior cruciate ligaments usually show degenerative and chronic traumatic change of varying degrees on histology. The changes are not predictable from inspection of the knee at surgery. The frequency of these changes suggests that many osteoarthritic PCL are of indifferent quality and the surgeon should consider this when choosing the style of knee replacement.

Cimetidine prevents suppression of delayed hypersensitivity in an animal model of haemorrhagic shock.

BACKGROUND: Cimetidine reverses immunosuppression following trauma, however, its effect on pure haemorrhagic shock is unknown. METHODS: Mice sensitized by injection of sheep red blood cells (SRBCs), were subjected to cardiac puncture and randomized to a control group-A (n=11) and three shock groups (35% of blood volume extracted): group-S had no treatment (n=16), group-CP received cimetidine 50mg/kg intraperitoneally (n=16), group-CW received oral cimetidine (200mg/kg per day, n=16). After 5 days, animals were challenged by injection of SRBCs into the foot-pad of the right hind paw (same volume of saline was injected into left paw). Foot-pad thickness ratios (FPTRs) were determined at 16 and 40 h, and inflammatory response was assessed histologically. RESULTS: At 16 h, FPTRs were greater in group-CW than group-S (P=0.01). There were no differences at 40 h. More animals in groups-CP and -CW had grade 3/4 inflammation, whilst group-S had the least inflammatory response (NS). CONCLUSIONS: Cimetidine prevents suppression of delayed hypersensitivity in this model.