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.

Assessment of Pathology Domain-Specific Knowledge of ChatGPT and Comparison to Human Performance.

CONTEXT.­: Artificial intelligence algorithms hold the potential to fundamentally change many aspects of society. Application of these tools, including the publicly available ChatGPT, has demonstrated impressive domain-specific knowledge in many areas, including medicine. OBJECTIVES.­: To understand the level of pathology domain-specific knowledge for ChatGPT using different underlying large language models, GPT-3.5 and the updated GPT-4. DESIGN.­: An international group of pathologists (n = 15) was recruited to generate pathology-specific questions at a similar level to those that could be seen on licensing (board) examinations. The questions (n = 15) were answered by GPT-3.5, GPT-4, and a staff pathologist that recently passed their Canadian pathology licensing exams. Participants were instructed to score answers on a 5-point scale and to predict which answer was written by ChatGPT. RESULTS.­: GPT-3.5 performed at a similar level to the staff pathologist, while GPT-4 outperformed both. The overall score for both GPT-3.5 and GPT-4 was within the range of meeting expectations for a trainee writing licensing examinations. In all but one question, the reviewers were able to correctly identify the answers generated by GPT-3.5. CONCLUSIONS.­: By demonstrating the ability of ChatGPT to answer pathology-specific questions at a level similar to (GPT-3.5) or exceeding (GPT-4) a trained pathologist, this study highlights the potential of large language models to be transformative in this space. In the future, more advanced iterations of these algorithms with increased domain-specific knowledge may have the potential to assist pathologists and enhance pathology resident training.

The Significance of Unsampled Microscopic Thyroid Carcinomas in Multinodular Goiter.

Thorough gross examination and appropriate sampling of the thyroidectomy specimens are fundamental to the diagnosis and clinical risk management of patients. This study aims to investigate the frequency and clinical significance of initially unsampled microscopic thyroid carcinomas in total thyroidectomy specimens with presumed benign multinodular thyroid disease. Seventy-two total thyroidectomy specimens belonging to multinodular goiter patients were randomly selected and included in this prospectively designed study. Inclusion criteria were set as no suspicion of malignancy before surgery as well as lack of intra-parenchymal primary thyroid carcinoma after histopathological evaluation of slides generated from initial sampling. Subsequently, the remaining thyroidectomy specimens were submitted for microscopic examination and sign-outs were finalized following the microscopic examination of the entire thyroid tissue. Microcarcinomas, with a maximum diameter of 3.5 mm, were detected in 29 cases (40.2%) after the whole gland sampling. Although most of these tumors were low-risk papillary microcarcinomas confined to the thyroid, one specimen also showed a medullary microcarcinoma measuring 1.5 mm. Three had micrometastatic nodal disease. There was no local recurrence or distant metastatic disease during the follow-up (mean 51.4 months). This study further supports microscopic carcinomas, including papillary microcarcinoma, and medullary microcarcinoma might stay hidden in thyroidectomy specimens. Increased glandular weight, male gender, and advanced age were significant risk factors in the detection of microcarcinomas in this series. While each multinodular thyroidectomy specimen is unique, we recommend dynamic extensive sampling (rather than bare-minimum approach) strategy based on careful gross and initial histologic examination findings as well as by taking into consideration risk factors.

Primary Cutaneous Myxoid Spindle Cell Squamous Cell Carcinoma of the Scalp: A Case Report.

Cutaneous squamous cell carcinomas are the second most frequent type of non-melanoma skin cancer. A 78-year-old man with a slow-growing but large nodular lesion on his scalp presented to the hospital. The nodular lesion was excised. Histologically, the lesion was diagnosed as a primary cutaneous myxoid spindle cell squamous cell carcinoma, which is the subject of this case report. Extracellular mucin production is an even less common finding in SCC. We also aim to discuss the histological and immunohistochemical findings for distinguishing MSC SCC from other primary cutaneous and metastatic spindle cell neoplasms with myxoid stroma.