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OBJECTIVES: Programmed death-ligand 1 (PD-L1) is the only approved predictive biomarker for immunotherapy in non-small cell lung cancer (NSCLC). However, predictive PD-L1 immunohistochemistry is subject to interobserver variability. We hypothesized that a pathologist's personality influences the interobserver variability and diagnostic accuracy of PD-L1 immunoscoring.MATERIALS AND METHODS: Seventeen pathologists performed PD-L1 immunoscoring on 50 resected NSCLC tumors in three categories (RESULTS: The overall agreement among pathologists for a series of 47 tumors was substantial (kappa = 0.63). Of these, 23/47 (49%) tumors were entirely negative or largely positive, resulting in a kappa value of 0.93. The remaining 24/47 (51%) tumors had a PD-L1 score around the cutoff value, generating a kappa value of 0.32. Pathologists with high scores for conscientiousness (careful, diligent) had the least interobserver variability (r = 0.6, p = 0.009). Also, they showed a trend towards higher sensitivity (74% vs. 68%, p = 0.4), specificity (86% vs. 82%, p = 0.3) and percent agreement (83% vs. 79%, p = 0.3), although not significant. In contrast, pathologists with high scores for neuroticism (sensitive, anxious) had significantly lower specificity (80% vs. 87%, p = 0.03) and percent agreement (78% vs. 85%, p = 0.03). Also, a trend towards high interobserver variability (r = -0.3, p = 0.2) and lower sensitivity (68% vs. 74%, p = 0.3) was observed, although not significant. Pathologists with relatively high scores for conscientiousness scored fewer tumors PD-L1 positive at the ≥ 1% cut-off (r = -0.5, p = 0.03). In contrast, pathologists with relatively high scores for neuroticism score more tumors PD-L1 positive at ≥ 1% (r = 0.6, p = 0.017) and ≥ 50% cut-offs (r = 0.6, p = 0.009).CONCLUSIONS: This study is the first to demonstrate the impact of a pathologist's personality on the interobserver variability and diagnostic accuracy of immunostaining, in the context of PD-L1 in NSCLC. Larger studies are needed for validation of these findings.

Purpose Stereotactic body radiotherapy (SBRT) is a highly conformal technique that allows a more accurate irradiation of lung tumors. However, a highly conformal dose distribution may underdose undetected microscopic disease extensions (MDE) near the tumor leading to loco-regional failure in tumor control. The purpose of the current work is to assess the risk of loco-regional failure in SBRT by analyzing pre-treatment scans. Methods and materials A model to predict the risk of occurrence of MDE from pretreatment images was developed based on pathology samples of 47 lung cancer patients. This model was used to assess the outcome of 238 SBRT treatments. Results Patients with high risk of MDE presence showed significantly lower 2-year loco-regional control (82.0% vs. 91.8%) and shorter time to loco-regional failure (8.4 months vs. 20.7 months) than low risk patients. The minimum dose delivered in the volume surrounding the GTV affected the model predictive power. The model remained predictive for patients who received less than 31 Gy in that volume. For patients who received larger doses, the MDE risk classification was not significant. Conclusions The results show that MDEs are, at least partially, responsible of loco-regional failure in highly conformal radiotherapy. This information could be used to optimize dose distributions.

The objective was to define the relationship between histopathological changes after pre-operative chemo-radiotherapy (CRT) and clinical outcome following tri-modality therapy in patients with superior sulcus tumours. A retrospective analysis of tumour material was performed in a series of 46 patients who received tri-modality therapy between 1997 and 2007. Median follow-up was 34 months (5-154). Pathological complete response (pCR) was present in 20/46 tumours (43 %). The most common RECIST score after CRT in patients with pCR was a partial response (PR; 10/17, three unknown), whereas in patients without a pCR, stable disease was the most common (22/26) (p = 0.002). In 26 specimens with residual tumour, this was mainly located in the periphery of the lesion rather than the centre (Spearman's correlation = 0.67, p 0.001). Prognosis was significantly better after a pCR compared to residual tumour (70 % 5-year overall survival vs. 20 %; p = 0.001) and in patients with fewer than 10 % vital tumour cells as compared to those with10 % (65 % 5-year overall survival vs. 18 %; p 0.001). A low mitotic count was associated with a longer disease-free survival (p = 0.02). Complete pathological response and the presence of fewer than 10 % vital tumour cells after pre-operative CRT are both associated with a more favourable prognosis. A modification of the pathological staging system after radiotherapy, incorporating the percentage of vital tumour cells, is proposed.

Non-Hodgkin lymphoma (NHL) of the female genital tract is extremely rare. We report five cases of NHL, which were collected during an 8-year period from the files of the Department of Pathology at the Onze Lieve Vrouwe Gasthuis, Amsterdam. In these five cases, the NHL was clinically not considered and the genital location was the primary site of presentation.

Case report. In November 1988 a 33-year-old homosexual man requested removal of two moles on the neck that he considered disfiguring. Since the patient was 18 years old many moles had appeared, and 29 were removed in 1983 for cosmetic reasons. Histologic examination revealed a slight cellular atypia of melanocytes in two lesions. The other 27 lesions showed no sign of dysplasia or malignancy. The patient had no family history of dysplastic nevi or malignant melanoma. From 1973 onward the patient was homosexually active with multiple partners. His first HIV antibody test was performed in November 1986 and was found to be positive, but he had no clinical evidence of HIV-related disease. Routine hematologic studies revealed moderate thrombocytopenia (40 to 70 X 109/ L). He also had slightly reduced CD4+ lymphocyte count, CD4+/CD8+ ratio, and lymphocyte stimulation. The two moles in the neck were irregularly pigmented macules (about 1 cm in diameter) with a faint red hue and irregular contours. Both lesions were excised with a margin of about 0.5 cm. Both were superficial spreading melanomas, each with a Breslow thickness of 0.50 mm. Further inspection of the skin revealed several other moles suspected of malignancy. Fourteen of~esewere excised during the next 6 months. Microscopically, all were composed of nests and sheets of melanocytes with marked, variable degrees ofatypia (Fig. 1). A Iymphohistiocytic infiltrate, intermingled with melanophages, was present around the lesions. Immunohistochemical staining with S-l00 (Dakopatts, Glostrup, Denmark) and NK1-C3 (Sanbio RV., Uden, The Netherlands), both markers for melanocytic cells, facilitated the