UNASSIGNED: The present study aimed to investigate whether the presence of mitoses in hyperchromatic crowded groups (HCGs) in cervical cytological specimens can serve as cytological criteria for high-grade squamous intra-epithelial lesions (HSILs).
UNASSIGNED: Various parameters were examined, including the frequency of mitotic figures per high power field (HPF) in Pap, hematoxylin eosin (HE) samples, and PHH3 immunocytochemical (ICC) and immunohistochemical (IHC) analyses.
UNASSIGNED: In the Pap and PHH3-ICC samples, the number of mitotic figures observed in HCGs was significantly higher in HSIL (P < 0.001) compared to other groups. Furthermore, the frequency of observing two or more mitoses was significantly higher in HSIL (Pap: P = 0.002, PHH3-ICC: P < 0.001) than in low-grade squamous intra-epithelial lesions (LSILs). Moreover, a comparison between Pap samples and PHH3-ICC showed that the frequency of two or more mitoses was significantly higher in the PHH3-ICC analysis of HSIL (P = 0.042). Regarding HE and PHH3-IHC samples, counting the number of mitoses in the lower and middle/upper layers of the squamous epithelial layer revealed that HSIL had a significantly higher value (HE: P = 0.0089, PHH3-IHC: P = 0.0002) than LSIL in the middle/upper layers.
UNASSIGNED: Hence, the presence of two or more mitotic figures in HCGs per HPF in cervical cytology indicates a suspicion of HSIL. The detection of mitoses in PHH3-ICC samples is more sensitive and easier to observe than in Pap samples, making it a valuable mitotic marker.

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.

Sinonasal non-intestinal-type adenocarcinoma is a rare but important differential diagnosis in patients presenting with recurrent, unexplained epistaxis. Low-grade types have a more favourable prognosis as opposed to the more aggressive high-grade. Symptoms include nasal obstruction and epistaxis that can last up to 5 years. We report a case of a rare low-grade sinonasal non-intestinal-type adenocarcinoma in a 43-year-old male who is frequently exposed to wood and dust particles. Endoscopy revealed right nasal mass occupying the entire nasal cavity as well as inferior turbinate hypertrophy and mass attached to the nasal septum on computed tomography. Biopsy confirmed the diagnosis and was classified as pT1NX with the presence of mitotic figures, which are more commonly present in the high-grade subtype.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a rare cancer of parafollicular C-cell origin. The International MTC Grading System (IMTCGS) incorporates mitotic activity, the presence of necrosis, and the Ki67 proliferation rate (PR) to classify MTCs as low or high grade. The ability to predict IMTCGS grade in cytology was assessed.
METHODS: MTCs with cytology and subsequent surgical follow-up were reviewed. Cytology slides were reviewed for mitotic figures, apoptoses, and necrosis, and a Ki67 PR was calculated when possible. Findings were correlated with final IMTCGS grade.
RESULTS: Twenty-five MTC fine-needle aspirations (FNAs) were identified, with nine identified as high grade (36%). By using a PR cutoff of 5%, Ki67 on FNA material (Ki67FNA) showed 92% concordance (n = 22 of 24) with surgical Ki67 and a correlation coefficient (R2) of 0.72. Sensitivity and specificity of Ki67FNA for predicting high-grade MTC were 38% and 100%, respectively. Multiple mitotic figures were present in a single slide of 43% (n = 3 of 7) of evaluable high-grade MTCs, whereas only one of 16 low-grade MTCs showed a single mitotic figure. Definitive apoptoses were present in five of seven high-grade MTC FNAs but were absent in 16 low-grade MTCs. The sensitivity and specificity of apoptoses/necrosis on cytology for high-grade MTCs were 71% and 88%, respectively.
CONCLUSIONS: Ki67FNA ≥5% shows low sensitivity but high specificity for predicting high-grade MTC. The presence of multiple mitotic figures in a single slide or definitive apoptotic bodies are both highly suggestive of high-grade MTC, and should warrant a close examination for necrosis and a careful Ki67 PR count.

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BACKGROUND: Fibroblasts and/or collagen fibrils have not been included in previous cytologic grading schemes of canine mast cell tumors (MCTs), and their association with biological behavior is broadly debated.
OBJECTIVE: This study aimed to evaluate the cytologic findings of canine MCT, with emphasis on the microenvironment, and propose a novel cytologic grading system correlated with mortality and histologic grade.
METHODS: Cytology smears of canine cutaneous MCTs were retrospectively reviewed and compared with their histopathologic counterparts using Cohen´s Kappa test. One-year survival rates were also compared with the cytologic and histopathologic variables using Pearson´s correlation test.
RESULTS: From 92 first-occurrence canine cutaneous MCTs, the five features most associated with mortality were selected for a new grading system. The five features were cytoplasmic granulation, fibroblast and/or collagen fibril concentrations, and the presence of mitotic figures, multinucleation, and karyomegaly. Among concordant histopathologic and cytologic cases (ie, the same grades using both systems), mortality rates were 2.6% (1/38) for low-grade and 71.4% (10/14) for high-grade cases (P < 0.001, chi-square). For false-negative and false-positive results, mortality rates were 33% (1/3) and 45% (5/11), respectively (P = 0.707).
CONCLUSIONS: Unlike the Camus cytologic grading system, the present amendment excluded binucleation and included fibroblasts and/ or collagen fibrils, which in higher concentrations were associated with increased survival and a low histopathologic grade. Cytologic grading with the inclusion of fibroblast and collagen fibril concentrations correlated with survival, as did the Camus cytologic and Kiupel histopathologic grades; however, further studies are needed to confirm the prognostic value of this novel cytologic grading scheme.

The mitotic count (MC) is an important histological parameter for prognostication of malignant neoplasms. However, it has inter- and intraobserver discrepancies due to difficulties in selecting the region of interest (MC-ROI) and in identifying or classifying mitotic figures (MFs). Recent progress in the field of artificial intelligence has allowed the development of high-performance algorithms that may improve standardization of the MC. As algorithmic predictions are not flawless, computer-assisted review by pathologists may ensure reliability. In the present study, we compared partial (MC-ROI preselection) and full (additional visualization of MF candidates and display of algorithmic confidence values) computer-assisted MC analysis to the routine (unaided) MC analysis by 23 pathologists for whole-slide images of 50 canine cutaneous mast cell tumors (ccMCTs). Algorithmic predictions aimed to assist pathologists in detecting mitotic hotspot locations, reducing omission of MFs, and improving classification against imposters. The interobserver consistency for the MC significantly increased with computer assistance (interobserver correlation coefficient, ICC = 0.92) compared to the unaided approach (ICC = 0.70). Classification into prognostic stratifications had a higher accuracy with computer assistance. The algorithmically preselected hotspot MC-ROIs had a consistently higher MCs than the manually selected MC-ROIs. Compared to a ground truth (developed with immunohistochemistry for phosphohistone H3), pathologist performance in detecting individual MF was augmented when using computer assistance (F1-score of 0.68 increased to 0.79) with a reduction in false negatives by 38%. The results of this study demonstrate that computer assistance may lead to more reproducible and accurate MCs in ccMCTs.

Currently, canine soft tissue sarcoma (STS) grading is based on histopathology. In humans, several studies have demonstrated concordance between cytologic grading systems for STS and histologic grade. The aim of this study was to correlate several cytologic parameters (smear cellularity, anisokaryosis, nucleolar malignancy score, multinucleation, and the number of mitotic figures per 200 cells) that form part of a human STS cytologic grading system, with histologic grades of canine cutaneous and subcutaneous STS. Three observers (blinded) reviewed the cytologic preparations independently from cases with confirmed histologic diagnoses of STS. A cytologic grading score was assigned for each parameter. Correlations between cytologic grading scores (averaged between observers) and histologic grades were assessed using Spearman\'s correlation coefficient, with statistical significance defined as P < .05. Twenty-one cases were included in the study (10 Grade I STS, nine Grade II STS, and two Grade III STS). The number of mitotic figures (≥3) per 200 cells was the only parameter that showed a significant but weak, positive correlation with histologic grade (rs  = .469; P = .032). No Grade I tumors had ≥3 mitotic figures per 200 cells; however, ≥3 mitotic figures per 200 cells were only observed in 33% of Grade II tumors and 50% (one out of two) of the Grade III tumors. This pilot study suggests that an increased number of mitotic figures seen on cytology might correlate with higher grade STS; however, the sensitivity of this parameter for grading STS appears to be low.

The exact process of the malignant conversion of oral submucous fibrosis (OSF) to oral cancer is not fully understood. This study aimed to detect and analyze E-cadherin expression, p63 expression, and number of mitotic figures, all correlated to cancer development, in ApoTome images of oral tissues to determine the oncogenic potentiality of OSF. ApoTome images of the study groups (6 normal, 16 OSF with dysplasia, and 10 OSF without dysplasia) were recorded. Cytoplasmic and membranous E-cadherin expression, breakages of the cell membrane, and p63 expression were detected in MATLAB 2016b. The number of mitotic figures detected by MATLAB was correlated with the number of chromosomes detected by ImageJ. A Mann–Whitney U test was done to determine a significant difference between the study groups for cytoplasmic and membranous E-cadherin distribution points. Statistical significant differences were found for cytoplasmic E-cadherin distribution between normal and OSF (with dysplasia) (p = 0.0278). There was an increase in mitotic figures, p63 expression, and cytoplasmic E-cadherin expression and a decrease in membranous E-cadherin expression from normal to diseased condition. Hence, automated detection and quantification of E-cadherin, p63, and mitotic figures in ApoTome images of oral biopsies can help in determining the oncogenic potentiality of OSF.

Giant cell-rich osteosarcoma (GCRO) is an exceedingly rare histological variant of conventional primary osteosarcoma. It constitutes about 1%-3% of all osteosarcomas, and is extremely uncommon in the maxillofacial region. The unusual histopathological appearance and the rarity of the lesion poses a great diagnostic challenge. This article aims to present a rare case of GCRO involving the mandible in a 52-year-old male patient.