Automated Nuclear Morphometry: A Deep Learning Approach for Prognostication in Canine Pulmonary Carcinoma to Enhance Reproducibility.

The integration of deep learning-based tools into diagnostic workflows is increasingly prevalent due to their efficiency and reproducibility in various settings. We investigated the utility of automated nuclear morphometry for assessing nuclear pleomorphism (NP), a criterion of malignancy in the current grading system in canine pulmonary carcinoma (cPC), and its prognostic implications. We developed a deep learning-based algorithm for evaluating NP (variation in size, i.e., anisokaryosis and/or shape) using a segmentation model. Its performance was evaluated on 46 cPC cases with comprehensive follow-up data regarding its accuracy in nuclear segmentation and its prognostic ability. Its assessment of NP was compared to manual morphometry and established prognostic tests (pathologists' NP estimates (n = 11), mitotic count, histological grading, and TNM-stage). The standard deviation (SD) of the nuclear area, indicative of anisokaryosis, exhibited good discriminatory ability for tumor-specific survival, with an area under the curve (AUC) of 0.80 and a hazard ratio (HR) of 3.38. The algorithm achieved values comparable to manual morphometry. In contrast, the pathologists' estimates of anisokaryosis resulted in HR values ranging from 0.86 to 34.8, with slight inter-observer reproducibility (k = 0.204). Other conventional tests had no significant prognostic value in our study cohort. Fully automated morphometry promises a time-efficient and reproducible assessment of NP with a high prognostic value. Further refinement of the algorithm, particularly to address undersegmentation, and application to a larger study population are required.

Survivin, ß-catenin, and ki-67 immunohistochemical expression in canine perivascular wall tumors: Preliminary assessment of prognostic significance.

High survivin expression has been correlated with poor outcomes in several canine tumors but not in soft tissue tumors (STTs). Survivin is a target gene of the Wnt/ß-catenin pathway, which is involved in human STT oncogenesis. Immunohistochemistry for survivin, ß-catenin, and Ki-67 was performed on 41 canine perivascular wall tumors (cPWTs), and statistical associations of protein expression and histopathologic and clinical variables with clinical outcomes were investigated. Immunohistochemically, there was nuclear positivity (0.9%-12.2% of tumor cells) for survivin in 41/41 (100%), cytoplasmic positivity (0 to > 75% of tumor cells) for survivin in 31/41 (76%), nuclear positivity (2.9%-67.2% of tumor cells) for ß-catenin in 24/41 (59%), and cytoplasmic positivity (0% to > 75% of tumor cells) for ß-catenin in 23/41 (56%) of cPWTs. All tumors expressed nuclear Ki-67 (2.2%-23.5%). In univariate analysis and multivariate analysis (UA and MA, respectively), every 1% increase of nuclear survivin was associated with an increase of the instantaneous death risk by a factor of 1.15 [hazard ratio (HR) = 1.15; P = .007]. Higher nuclear survivin was associated with grade II/III neoplasms (P = .043). Expression of cytoplasmic survivin, nuclear and cytoplasmic ß-catenin, and nuclear Ki-67 were not significantly associated with prognosis in UA nor MA. Tumor size was a significant prognostic factor for local recurrence in UA [subdistribution HR (SDHR) = 1.19; P = .02] and for reduced overall survival time in MA. According to UA and MA, a unitary increase of mitotic count was associated with an increase of the instantaneous death risk by a factor of 1.05 (HR = 1.05; P = .014). Nuclear survivin, mitotic count, and tumor size seem to be potential prognostic factors for cPWTs. In addition, survivin and ß-catenin may represent promising therapeutic targets for cPWTs.

Mitotic activity: A systematic literature review of the assessment methodology and prognostic value in feline tumors.

Increased proliferation is a driver of tumorigenesis, and quantification of mitotic activity is a standard task for prognostication. This systematic review is an analysis of all available references on mitotic activity in feline tumors to provide an overview of the assessment methods and prognostic value. A systematic literature search in PubMed and Scopus and a nonsystematic search in Google Scholar were conducted. All articles on feline tumors that correlated mitotic activity with patient outcome were identified. Data analysis revealed that of the 42 eligible articles, mitotic count (MC, mitotic figures/tumor area) was evaluated in 39 studies, and mitotic index (MI, mitotic figures/tumor cells) in 3 studies. The risk of bias was considered high for most studies (26/42, 62%) based on small study populations, insufficient details of the MC/MI methods, and lack of statistical measures for diagnostic accuracy or effect on outcome. The MC/MI methods varied between studies. A significant association of MC with survival was determined in 20 of 28 (71%) studies (10 studies evaluated other outcome metrics or provided individual patient data), while 1 study found an inverse effect. Three tumor types had at least 4 studies, and a prognostic association with survival was found in 5 of 6 studies on mast cell tumors, 5 of 5 on mammary tumors, and 3 of 4 on soft-tissue sarcomas. MI was shown to correlate with survival for mammary tumors by 2 research groups; however, comparisons to MC were not conducted. Further studies with standardized mitotic activity methods and appropriate statistical analysis for discriminant ability of patient outcome are needed to infer the prognostic value of MC and MI.

Mitotic activity: A systematic literature review of the assessment methodology and prognostic value in canine tumors.

One of the most relevant prognostic indices for tumors is cellular proliferation, which is most commonly measured by the mitotic activity in routine tumor sections. The goal of this systematic review was to analyze the methods and prognostic relevance of histologically measuring mitotic activity that have been reported for canine tumors in the literature. A total of 137 articles that correlated the mitotic activity in canine tumors with patient outcome were identified through a systematic (PubMed and Scopus) and nonsystematic (Google Scholar) literature search and eligibility screening process. Mitotic activity methods encompassed the mitotic count (MC, number of mitotic figures per tumor area) in 126 studies, presumably the MC (method not specified) in 6 studies, and the mitotic index (MI, number of mitotic figures per number of tumor cells) in 5 studies. A particularly high risk of bias was identified based on the available details of the MC methods and statistical analyses, which often did not quantify the prognostic discriminative ability of the MC and only reported P values. A significant association of the MC with survival was found in 72 of 109 (66%) studies. However, survival was evaluated by at least 3 studies in only 7 tumor types/groups, of which a prognostic relevance is apparent for mast cell tumors of the skin, cutaneous melanoma, and soft tissue tumor of the skin and subcutis. None of the studies using the MI found a prognostic relevance. This review highlights the need for more studies with standardized methods and appropriate analysis of the discriminative ability to prove the prognostic value of the MC and MI in various tumor types. Future studies are needed to evaluate the influence of the performance of individual pathologists on the appropriateness of prognostic thresholds and investigate methods to improve interobserver reproducibility.

A novel dilated contextual attention module for breast cancer mitosis cell detection.

Background and object: Mitotic count (MC) is a critical histological parameter for accurately assessing the degree of invasiveness in breast cancer, holding significant clinical value for cancer treatment and prognosis. However, accurately identifying mitotic cells poses a challenge due to their morphological and size diversity. Objective: We propose a novel end-to-end deep-learning method for identifying mitotic cells in breast cancer pathological images, with the aim of enhancing the performance of recognizing mitotic cells. Methods: We introduced the Dilated Cascading Network (DilCasNet) composed of detection and classification stages. To enhance the model's ability to capture distant feature dependencies in mitotic cells, we devised a novel Dilated Contextual Attention Module (DiCoA) that utilizes sparse global attention during the detection. For reclassifying mitotic cell areas localized in the detection stage, we integrate the EfficientNet-B7 and VGG16 pre-trained models (InPreMo) in the classification step. Results: Based on the canine mammary carcinoma (CMC) mitosis dataset, DilCasNet demonstrates superior overall performance compared to the benchmark model. The specific metrics of the model's performance are as follows: F1 score of 82.9%, Precision of 82.6%, and Recall of 83.2%. With the incorporation of the DiCoA attention module, the model exhibited an improvement of over 3.5% in the F1 during the detection stage. Conclusion: The DilCasNet achieved a favorable detection performance of mitotic cells in breast cancer and provides a solution for detecting mitotic cells in pathological images of other cancers.

Radiographic growth rate as a predictor of aggressiveness of diffuse gliomas without 1p19q codeletion.

OBJECTIVE: The 2021 WHO classification of CNS tumors has refined the definition of adult-type diffuse gliomas without 1p19q codeletion. Nevertheless, the aggressiveness of gliomas is based exclusively on histomolecular criteria performed on a limited sample of the tumor. The authors aimed to assess whether the spontaneous radiographic tumor growth rate is associated with tumor aggressiveness and allows preoperative identification of malignancy grade of adult-type diffuse gliomas without 1p19q codeletion. METHODS: The authors retrospectively reviewed the records of adult patients harboring a newly diagnosed supratentorial diffuse glioma without 1p19q codeletion, with available preoperative MRI follow-up between January 2008 and April 2022. The spontaneous radiographic tumor growth rate was quantified by tumor volume segmentation and regression of the evolution of the mean tumor diameter over time and was compared with clinical, imaging, histomolecular, and survival data. RESULTS: Ninety-six patients were included. The spontaneous radiographic tumor growth rates (mean 17.8 ± 38.8 mm/year, range 0-243.5 mm/year) significantly varied according to IDH1/2 mutation (p < 0.001), grade of malignancy (p < 0.001), and presence of microvascular proliferation (p < 0.001). The spontaneous radiographic tumor growth rate allowed preoperative identification of high-grade cases: 100% of grade 3 and 4 IDH-mutant diffuse astrocytomas had a spontaneous radiographic tumor growth rate ≥ 8.0 mm/year, and 100% of IDH-wild-type glioblastomas had a spontaneous radiographic tumor growth rate ≥ 42.0 mm/year. A spontaneous radiographic growth rate ≥ 8.0 mm/year was an independent predictor of shorter progression-free (p = 0.014) and overall (p = 0.007) survival. A mitotic count threshold ≥ 4 mitoses was the optimal threshold for identifying aggressive IDH-mutant astrocytomas based on spontaneous radiographic tumor growth. CONCLUSIONS: The spontaneous radiographic tumor growth rates could be used as an additional tool to preoperatively screen tumor aggressiveness of adult-type diffuse gliomas without 1p19q codeletion.

Equine sarcoids: A clinicopathologic study of 49 cases, with mitotic count and clinical type predictive of recurrence.

Sarcoids are common mesenchymal neoplasms of horses. Although there are few studies in which sarcoids have been followed over a long period of time, sarcoids are considered locally invasive and have been reported to frequently recur following surgical excision. Currently, no histological features have been identified to predict which sarcoids will recur after excision. The present study comprised 49 sarcoids for which histology sections were available and in which the recurrence status of the case was known. Each sarcoid was excised from a different horse. Overall, 12 of the 49 (24%) sarcoids recurred after surgical excision. Mitotic count (MC), cellularity, necrosis, nuclear pleomorphism, and inflammation of the sarcoids were evaluated histologically. Of these, MC correlated with recurrence. Four of 5 (80%) sarcoids with an MC ≥ 20 in 2.37 mm2 recurred, which was a significantly higher recurrence rate than that of sarcoids with an MC < 20, 8 of 44 cases recurred (18%), P = .0051. Clinical type was also found to correlate with recurrence. Three of 4 (75%) fibroblastic types recurred, which was a significantly higher recurrence rate than that of sarcoids with other clinical types, 9 of 45 cases (18%), P < .001. In addition, univariate Cox regression analysis confirmed fibroblastic type and MC ≥ 20 as significant predictors for recurrence (P = .016 and P = .005, respectively). To the authors' knowledge, this is the first large study examining recurrence rates in sarcoids, and the first time that histological features have been correlated with recurrence.

Ki67 Index in Patnaik Grade 2/Kiupel Low-Grade Canine Cutaneous Mast Cell Tumors with Early Lymph Node Metastasis: A Descriptive Study.

Several studies evaluating Ki67 in canine cutaneous mast cell tumors (cMCTs) have reported its prognostic value when tumors of all histological grades are included. This study aims to evaluate whether the Ki67 index has a predictive value in a homogeneous cohort of G2/LG cMCTs with HN2 lymph nodes (LNs) and to describe the clinical outcome. The second goal was to explore the correlation between the Ki67 index and MC. The medical databases of three institutions were retrospectively searched for dogs undergoing surgical treatment for cMCT and LN extirpation, with a histological diagnosis of G2/LG with HN2 LNs. Information about histological margins, MC, Ki67 index, local recurrence, nodal relapse, distant metastasis, de novo cMCT occurrence and date and cause of death were included. A total of 39 cases were identified. None of these developed local and nodal relapse or metastatic distant disease. Median MC was 1 (0-2). Median Ki67 index was 3.5 (0.7-14.3). Ki67 and MC were not significantly correlated. At the end of the study, 32 (82%) dogs were alive, 7 (18%) dogs were dead from unrelated causes and 4 (10.2%) dogs were lost to follow-up. The median ST was not reached, and the mean was 893 days (104-2241 days). Considering the strict inclusion criteria, dogs affected by G2/LG with HN2 LNs treated with surgery alone may have a good oncologic outcome; the Ki67 index does not have prognostic impact.

Primary Ovarian Leiomyosarcoma Is a Very Rare Entity: A Narrative Review of the Literature.

BACKGROUND: Primary ovarian leiomyosarcoma is a very rare malignancy characterized by unclear management and poor survival. We reviewed all the cases of primary ovarian leiomyosarcoma to identify prognostic factors and the best treatment. METHODS: We collected and analyzed the articles published in the English literature regarding primary ovarian leiomyosarcoma from January 1951 to September 2022, using PubMed research. Clinical and pathological characteristics, different treatments and outcomes were analyzed. RESULTS: 113 cases of primary ovarian leiomyosarcoma were included. Most patients received surgical resection, associated with lymphadenectomy in 12.5% of cases. About 40% of patients received chemotherapy. Follow-up information was available for 100/113 (88.5%) patients. Stage and mitotic count were confirmed to affect survival, and lymphadenectomy and chemotherapy were associated with a better survival rate. A total of 43.4% of patients relapsed, and their mean disease-free survival was 12.5 months. CONCLUSIONS: Primary ovarian leiomyosarcomas are more common in women in their 50s (mean age 53 years). Most of them are at an early stage at presentation. Advanced stage and mitotic count showed a detrimental effect on survival. Surgical excision associated with lymphadenectomy and chemotherapy are associated with increased survival. An international registry could help collect clear and reliable data to standardize the diagnosis and treatment.

Factors Predicting Type I Gastric Neuroendocrine Neoplasia Recurrence: A Single-Center Study.

Type I gastric neuroendocrine neoplasms (gNENs) are associated with atrophic gastritis and have a high recurrence rate, which means frequent endoscopies are required. The objective of this study was to identify factors predicting the local recurrence of type I gNENs. The clinical course and the pathological and biochemical data of patients with type I gNENs treated at Bnai Zion Medical Center between 2006 and 2022 were analyzed retrospectively. Twenty-seven type I gNENs were evaluated. The follow-up period was 41 months (range: 11-288 months). Recurrence of the tumor occurred in 13/27 (48%) patients after 35 months (median (M), interquartile range (IQR): 21-67.5). Serum gastrin levels were significantly higher in patients with recurrent disease versus patients with non-recurrent disease (788 vs. 394 ng/L; p = 0.047), while the Ki-67 index was significantly lower in patients with recurrent disease versus patients with non-recurrent disease (1% vs. 3.5%; p = 0.035). Tumor size, mitotic count, and serum chromogranin A levels did not correlate with recurrence. The present study emphasizes the role of gastrin in the pathogenesis of gNEN recurrence and highlights the debate regarding the ability of the Ki-67 index to predict the clinical course of this disease.

ReCasNet: Improving consistency within the two-stage mitosis detection framework.

Mitotic count (MC) is an important histological parameter for cancer diagnosis and grading, but the manual process for obtaining MC from whole-slide histopathological images is very time-consuming and prone to error. Therefore, deep learning models have been proposed to facilitate this process. Existing approaches utilize a two-stage pipeline: the detection stage for identifying the locations of potential mitotic cells and the classification stage for refining prediction confidences. However, this pipeline formulation can lead to inconsistencies in the classification stage due to the poor prediction quality of the detection stage and the mismatches in training data distributions between the two stages. In this study, we propose a Refine Cascade Network (ReCasNet), an enhanced deep learning pipeline that mitigates the aforementioned problems with three improvements. First, window relocation was used to reduce the number of poor quality false positives generated during the detection stage. Second, object re-cropping was performed with another deep learning model to adjust poorly centered objects. Third, improved data selection strategies were introduced during the classification stage to reduce the mismatches in training data distributions. ReCasNet was evaluated on two large-scale mitotic figure recognition datasets, canine cutaneous mast cell tumor (CCMCT) and canine mammary carcinoma (CMC), which resulted in up to 4.8% percentage point improvements in the F1 scores for mitotic cell detection and 44.1% reductions in mean absolute percentage error (MAPE) for MC prediction. Techniques that underlie ReCasNet can be generalized to other two-stage object detection pipeline and should contribute to improving the performances of deep learning models in broad digital pathology applications.

Counting mitoses in gastrointestinal stromal tumours (GISTs): variable practices in the real-world setting and their clinical implications.

Mitotic count (MC) is an important prognostic indicator in gastrointestinal stromal tumours (GISTs). Though MC evaluation was initially proposed in 50 HPFs, recent international guidelines recommend that MC be performed on 5 mm2 because HPFs may have different areas depending on the ocular field number (FN) of the utilized light microscope. Performing MC on different areas leads to a non-standardized evaluation and erroneous risk stratification. The aim of the study was to audit real-life MC practices with special emphasis on possible risk stratification errors. A survey was administered to Italian pathologists to evaluate the following: method used for MC (5 mm2 versus 50 HPF); FN of the light microscope; prognostic scheme for risk stratification. Based on the results of the survey, 100 GISTs (25/risk class using Miettinen prognostic scheme) were retrieved and MC performed using 5 mm2 versus the corresponding mm2 area sizes of 50 HPFs with variable FNs (18, 20, 22). The survey demonstrated that the majority of pathologists (64.5%) use 50 HPFs with various FNs leading to excessive area size. The most frequently used prognostic scheme is that by Miettinen. Using this prognostic scheme and counting mitoses in 5 mm2 versus 50 HPFs with FNs 18, 20 and 22, a change in risk class was identified ranging from 10 to 41%, depending on FN. In conclusion, this study demonstrates that MC is still frequently performed on 50 HPF, with area sizes exceeding the specified 5 mm2 by far.

Atypical Mitotic Figures Are Prognostically Meaningful for Canine Cutaneous Mast Cell Tumors.

Cell division through mitosis (microscopically visible as mitotic figures, MFs) is a highly regulated process. However, neoplastic cells may exhibit errors in chromosome segregation (microscopically visible as atypical mitotic figures, AMFs) resulting in aberrant chromosome structures. AMFs have been shown to be of prognostic relevance for some neoplasms in humans but not in animals. In this study, the prognostic relevance of AMFs was evaluated for canine cutaneous mast cell tumors (ccMCT). Histological examination was conducted by one pathologist in whole slide images of 96 cases of ccMCT with a known survival time. Tumor-related death occurred in 11/18 high-grade and 2/78 low-grade cases (2011 two-tier system). The area under the curve (AUC) was 0.859 for the AMF count and 0.880 for the AMF to MF ratio with regard to tumor-related mortality. In comparison, the AUC for the mitotic count was 0.885. Based on our data, a prognostically meaningful threshold of ≥3 per 2.37 mm2 for the AMF count (sensitivity: 76.9%, specificity: 98.8%) and >7.5% for the AMF:MF ratio (sensitivity: 76.9%, specificity: 100%) is suggested. While the mitotic count of ≥ 6 resulted in six false positive cases, these could be eliminated when combined with the AMF to MF ratio. In conclusion, the results of this study suggests that AMF enumeration is a prognostically valuable test, particularly due to its high specificity with regard to tumor-related mortality. Additional validation and reproducibility studies are needed to further evaluate AMFs as a prognostic criterion for ccMCT and other tumor types.

How to measure your microscope's HPF. A critical guide for residents.

Counting stuff under the microscope is part of the duties of a surgical pathologist. Many textbooks and articles still report the surface area as the number of high-power fields (HPFs) counted. This is bad, since the area displayed by an HPF varies between two microscopes. It is therefore necessary to express the surface as mm2. This is a how to guide written for the resident who has to measure the HPF of the microscope for the first time. The Resident can either calibrate the microscope with a stage micrometer slide (a small ruler on a glass slide) or compute the surface area of the HPF using the numbers on the eyepiece and the magnification objective. for "10X/22" eyepiece and a "40X" objective, the diameter of the HPF is 22/40 = 0.55 (if no other magnification is present), and the surface is 0.238 mm2. The young resident might then ask: "How far off-target was I when I counted the number of HPFs that the chief resident declared to be correct?" Probably not that much: although legitimate in principle and correct in math, the size of the problem is often overstated since microscopes are not that different after all and because pathology is not just about counting.

Long term trends of breast cancer incidence according to proliferation status.

BACKGROUND: Long-term breast cancer incidence trends according to proliferation status are poorly described. We studied time-trends in breast cancer incidence, using mitotic count and Ki-67 as markers of proliferation. METHODS: Among 83,298 Norwegian women followed for breast cancer occurrence 1961-2012, 2995 incident breast cancers were diagnosed. Ki-67 was assessed using immunohistochemistry on tissue microarrays and mitoses were counted on whole sections. We compared incidence rates according to proliferation status among women born 1886-1928 and 1929-1977, estimating age-specific incidence rate ratios. We performed multiple imputations to account for unknown proliferation status. Mean values of Ki-67 and mitotic counts were calculated, according to age and birth year. We performed separate incidence analyses for HER2+ and triple negative breast cancers. RESULTS: Among women aged 40-69 years, incidence rates of tumours with low-proliferative activity were higher among those born in 1929 or later, compared to before 1929, according to Ki-67 and mitotic count. Incidence rates of tumours with high-proliferative activity were also higher in women born in 1929 or later compared to before 1929 according to Ki-67, but not according to mitotic count. Mean values of Ki-67 and mitotic count varied according to age and birth year. In subtype-specific analyses we found an increase of high-proliferative HER2+ tumours according to Ki-67 in women born in 1929 or later, compared to before 1929. CONCLUSIONS: There has been a temporal increase in both low- and high-proliferative breast cancers.

Predictive Power of MIB-1 vs. Mitotic Count on Progression-Free Survival in Skull-Base Meningioma.

Although meningiomas are mainly non-aggressive and slow-growing tumors, there is a remarkable recurrence rate in a long-term follow-up. Proliferative activity and progression-free survival (PFS) differs significantly among the anatomic location of meningiomas. The aim of the present study was to investigate the predictive power of MIB-1 labeling index and mitotic count (MC) regarding the probability of PFS in the subgroup of skull-base meningiomas. A total of 145 patients were included in this retrospective study. Histopathological examinations and follow-up data were collected. Ideal cut-off values for MIB-1 and MC were ≥4.75 and ≥6.5, respectively. MIB-1 as well as MC were good predictors for PFS in skull-base meningiomas. Time-dependent analysis of MIB-1 and MC in prediction of recurrence of skull-base meningioma showed that their prognostic values were comparable, but different cut-offs for MC should be considered regarding the meningioma's location. As the achievement of a gross total resection can be more challenging in skull-base meningiomas and second surgery implies a higher risk profile, the recurrence risk could be stratified according to these findings and guide decision-making for follow-ups vs. adjuvant therapies.

Mutations in Exons 8 and 11 of c-kit Gene in Canine Subcutaneous Mast Cell Tumors and Their Association with Cell Proliferation.

The prognostic significance of internal tandem duplication (ITD) mutations in exons 8 and 11 of c-kit has been well-described for canine cutaneous mast cell tumors (MCTs), but c-kit mutations have rarely been reported in subcutaneous MCTs. The objective of this study was to identify the prevalence of ITD mutations in exons 8 and 11 of c-kit in canine subcutaneous MCTs and to investigate its association with histologic grade, KIT pattern, and proliferation markers. ITD mutations in exons 8 and 11 of c-kit, mitotic count, Ki67 index, AgNOR number, Ki67xAgNOR score, KIT pattern, and histologic grade (two-tier system) were retrospectively recorded for 216 dogs with subcutaneous MCTs. ITD mutations in exons 8 and 11 of c-kit were detected in 23 (10.6%) and 12 (5.56%) subcutaneous MCTs, respectively. Exon 11 mutations were significantly associated with Kiupel high grade (p < 0.001) and increased mitotic count (p < 0.001) compared to subcutaneous MCTs with no mutations in exons 8 or 11 (p = 0.002) or subcutaneous MCTs with a mutation in exon 8 (p = 0.001). There was no significant association of either c-kit mutation with KIT patterns or proliferation activity. This study identified a higher prevalence of ITD mutations in exons 8 and 11 of c-kit in subcutaneous MCTs than previously reported. Like their cutaneous counterpart, subcutaneous MCTs with exon 11 mutations were more likely to be histologically high grade and have a higher mitotic count, whereas such associations were not observed in subcutaneous MCTs with exon 8 mutations.

The road less travelled: Skeletal muscle invasion in oral squamous cell carcinoma.

Introduction: Oral squamous carcinoma (OSCC) is one of the most challenging global constraint and currently the third most common cancer in India. Malignant cells exhibit anomalous morphological characteristics like increased and abnormal mitosis which might suffice as a prognostic indicator. Skeletal muscles present in close approximation with the oral epithelium are often encountered by the tumor cells of OSCC which is an uncharted territory and might serve as a critical parameter in assessing the outcome of OSCC. Amalgamation of mitotic count and skeletal muscle invasion can put forward cogent paths in discerning the behavior of these lesions. Material & methods: A total of 60 histopathologically diagnosed cases of well, moderately and poorly-differentiated OSCC cases were obtained from the archives. Hematoxylin and eosin-stained slides were examined for Mitotic count and Skeletal muscle invasion. Results: There was a statistically significant increase in Mitotic count from well-differentiated to poorly-differentiated OSCC. Despite the statistically insignificant difference there was a distinct rise of skeletal muscle invasion from well-differentiated to poorly-differentiated OSCC. Conclusion: The rise in mitotic count with increasing grades of OSCC suggests an increase in their proliferation rate. Owing to the marked elevation of skeletal muscle invasion in higher grades of OSCC, we can assume it to be a reliable predictor of aggressiveness and outcome. Further studies with a uniform sample size and site specificity might help in solidifying their role in assessing the prognosis of OSCC.

Evaluation of Tumor Grade and Proliferation Indices before and after Short-Course Anti-Inflammatory Prednisone Therapy in Canine Cutaneous Mast Cell Tumors: A Pilot Study.

Glucocorticoid administration is a common clinical practice that attempts to decrease the inflammation associated with and improve the resectability of canine mast cell tumors (MCTs). However, the impact of neoadjuvant glucocorticoids on the histological features and proliferation indices of canine MCTs is unknown. The objective of this study was to evaluate changes in tumor grade, mitotic count, Ki67, AgNOR, and AgNORxKi67 scores following short-course anti-inflammatory neoadjuvant prednisone in canine patients with MCTs. This was a prospective single-arm pilot study. Client-owned dogs with treatment-naïve cytologically confirmed MCTs were enrolled. Patients underwent an initial incisional biopsy followed by a 10-14-day course of anti-inflammatory prednisone and surgical resection. All histological samples were randomized, masked, and evaluated by a single pathologist. Unstained paired pre- and post-treatment samples were submitted to a commercial laboratory for Ki67 and AgNOR immunohistochemical analysis. There were 11 dogs enrolled with 11 tumors. There were no statistical differences between the pre- and post-treatment histological parameters of mitotic index, Ki67, AgNOR, or Ki67xAgNOR. There were no clinically significant alterations between pre-treatment and post-treatment in the assignment of tumor grades. A short course of anti-inflammatory prednisone does not appear to alter the histological parameters that affect grade determination or significantly alter the proliferation indices in canine MCTs.

Leiomyosarcoma of urinary bladder in a Shih Tzu dog.

A 10-year-old intact male Shih Tzu dog presented with hematuria. Double-contrast cystography revealed a polypoid filling defect at the apex of the urinary bladder. Ultrasonography revealed a heterogeneously hypoechoic intramural mass with minimal vascular flow beneath the submucosal layer. After partial cystectomy, a well-demarcated bladder leiomyosarcoma was diagnosed on histopathology. The patient was alive and well without any clinical signs, recurrence, or metastasis at the 29-month follow-up after the surgical removal of the bladder mass. Leiomyosarcoma should be considered as a differential diagnosis if mass-like lesions are observed in the urinary bladder, although this type of malignancy is rare in canines. Histopathological confirmation is important for predicting prognosis and determining further medical plans.