The 1000 Mitoses Project: A Consensus-Based International Collaborative Study on Mitotic Figures Classification.

Introduction. The identification of mitotic figures is essential for the diagnosis, grading, and classification of various different tumors. Despite its importance, there is a paucity of literature reporting the consistency in interpreting mitotic figures among pathologists. This study leverages publicly accessible datasets and social media to recruit an international group of pathologists to score an image database of more than 1000 mitotic figures collectively. Materials and Methods. Pathologists were instructed to randomly select a digital slide from The Cancer Genome Atlas (TCGA) datasets and annotate 10-20 mitotic figures within a 2 mm2 area. The first 1010 submitted mitotic figures were used to create an image dataset, with each figure transformed into an individual tile at 40x magnification. The dataset was redistributed to all pathologists to review and determine whether each tile constituted a mitotic figure. Results. Overall pathologists had a median agreement rate of 80.2% (range 42.0%-95.7%). Individual mitotic figure tiles had a median agreement rate of 87.1% and a fair inter-rater agreement across all tiles (kappa = 0.284). Mitotic figures in prometaphase had lower percentage agreement rates compared to other phases of mitosis. Conclusion. This dataset stands as the largest international consensus study for mitotic figures to date and can be utilized as a training set for future studies. The agreement range reflects a spectrum of criteria that pathologists use to decide what constitutes a mitotic figure, which may have potential implications in tumor diagnostics and clinical management.

Demyelinating pseudotumor.

Demyelinating disease presenting as a solitary contrast-enhancing mass poses a diagnostic challenge for both radiologists and surgical pathologists. We report the cases of two female patients, aged 23 and 37 years, who exhibited the clinical and radiologic features of a space-occupying mass strongly suggestive of neoplasia. In both patients, magnetic resonance imaging showed a ring-enhancing parietal lesion. Intraoperative frozen sections in both patients displayed histologic features strongly suggestive of a glial neoplasm, including marked hypercellularity, a prominent astrocytic component, and easily identifiable mitotic figures. However, permanent sections showed additional and helpful histologic findings that included Creutzfeldt astrocytes and granular mitoses. Subsequent immunostaining showed that the hypercellularity was principally caused by macrophage infiltration (HAM-56 and CD68) and an associated reactive astrocytosis (glial fibrillary acidic protein). Additional confirmatory tests included special stains for myelin (Luxol-fast-blue), which demonstrated focal, sharply marginated loss of myelin, and for axons (silver stain for axons and neurofilament protein immunohistochemistry), which showed relative preservation of axons in areas of myelin loss. Together, the special stains confirmed the demyelinating nature of the lesions. The keys to avoiding misdiagnosing a demyelinating pseudotumor as a diffuse glioma include a general awareness of this potential pitfall, including the radiologic appearance of demyelinating pseudotumors as contrast-enhancing solitary masses that mimic tumor; knowledge of the characteristic histologic features, including Creutzfeldt astrocytes and granular mitoses; and a high index of suspicion for macrophage infiltration combined with a willingness to use appropriate confirmatory immunohistochemical studies in suspicious or uncertain cases. This approach will minimize the chance of misdiagnosis and subsequent use of inappropriate and deleterious therapies.