scholarly journals A large-scale dataset for mitotic figure assessment on whole slide images of canine cutaneous mast cell tumor

2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Christof A. Bertram ◽  
Marc Aubreville ◽  
Christian Marzahl ◽  
Andreas Maier ◽  
Robert Klopfleisch
Keyword(s):  
Mast Cell ◽  
Large Scale ◽  
Region Of Interest ◽  
Mitotic Figure ◽  
Low Grade ◽  
Detection Algorithms ◽  
Large Scale Dataset ◽  
Cutaneous Mast Cell ◽  
Mitotic Figures ◽  
Whole Slide Images

AbstractWe introduce a novel, large-scale dataset for microscopy cell annotations. The dataset includes 32 whole slide images (WSI) of canine cutaneous mast cell tumors, selected to include both low grade cases as well as high grade cases. The slides have been completely annotated for mitotic figures and we provide secondary annotations for neoplastic mast cells, inflammatory granulocytes, and mitotic figure look-alikes. Additionally to a blinded two-expert manual annotation with consensus, we provide an algorithm-aided dataset, where potentially missed mitotic figures were detected by a deep neural network and subsequently assessed by two human experts. We included 262,481 annotations in total, out of which 44,880 represent mitotic figures. For algorithmic validation, we used a customized RetinaNet approach, followed by a cell classification network. We find F1-Scores of 0.786 and 0.820 for the manually labelled and the algorithm-aided dataset, respectively. The dataset provides, for the first time, WSIs completely annotated for mitotic figures and thus enables assessment of mitosis detection algorithms on complete WSIs as well as region of interest detection algorithms.

scholarly journals Variation among Pathologists in Histologic Grading of Canine Cutaneous Mast Cell Tumors

2005 ◽  
Vol 17 (3) ◽  
pp. 245-248 ◽  
Author(s):  
Nicole C. Northrup ◽  
Barry G. Harmon ◽  
Tracy L. Gieger ◽  
Cathy A. Brown ◽  
K. Paige Carmichael ◽  
...  
Keyword(s):  
Mast Cell ◽  
Significant Variation ◽  
Low Grade ◽  
Histologic Grading ◽  
Mast Cell Tumors ◽  
Cutaneous Mast Cell ◽  
Mitotic Figures

Ten veterinary pathologists at 1 veterinary institution independently assigned histologic grades to the same 60 canine cutaneous mast cell tumors (MCTs). There was significant variation among pathologists in grading the MCTs ( P < 0.001). The probability of assigning a low grade was significantly higher for the pathologists in this study who use a published reference for histologic grading of canine cutaneous MCTs that allows subcutaneous MCTs or MCTs with mitotic figures to be included in the low-grade category ( P < 0.0001 and P < 0.0001, respectively).

scholarly journals Stereology in Grading and Prognosis of Canine Cutaneous Mast Cell Tumors

2021 ◽  
pp. 030098582098513
Author(s):  
Mafalda Casanova ◽  
Sandra Branco ◽  
Inês Berenguer Veiga ◽  
André Barros ◽  
Pedro Faísca
Keyword(s):  
Mast Cell ◽  
Clinical Outcome ◽  
Prognostic Value ◽  
Histological Grade ◽  
Intraobserver Variability ◽  
Low Grade ◽  
High Grade ◽  
Mast Cell Tumors ◽  
Cutaneous Mast Cell ◽  
Grade Iii

Canine cutaneous mast cell tumors (ccMCTs) are currently graded according to Patnaik and Kiupel grading schemes. The qualitative and semiquantitative parameters applied in these schemes may lead to inter- and intraobserver variability. This study investigates the prognostic value of volume-weighted mean nuclear volume ([Formula: see text]), a stereological estimation that provides information about nuclear size and its variability. [Formula: see text] of 55 ccMCTs was estimated using the “point-sampled intercept” method and compared with histological grade and clinical outcome. The clinical history of dogs treated with surgical excision alone was available for 30 ccMCTs. Statistical differences in [Formula: see text] were found between grade II ([Formula: see text]= 115 ± 29 µm3) and grade III ccMCTs ([Formula: see text]= 197 ± 63 µm3), as well as between low-grade ([Formula: see text]= 113 ± 28 µm3) and high-grade ccMCTs ([Formula: see text]= 184 ± 63 µm3). An optimal cutoff value of [Formula: see text] ≥ 150 µm3 and [Formula: see text] ≥ 140 µm3 was determined for grade III and high-grade ccMCTs, respectively. In terms of prognosis, [Formula: see text] was not able to predict the clinical outcome in 42% of the cases; however, cases with [Formula: see text]<125 µm3 had a favorable outcome. These results indicate that, despite having limited prognostic value when used as a solitary parameter, [Formula: see text] is highly reproducible and is associated with histological grade as well as with benign behavior.

scholarly journals Ancillary techniques on the evaluation of canine cutaneous mast cell tumors from Brazil

2016 ◽  
Vol 46 (10) ◽  
pp. 1804-1810 ◽  
Author(s):  
Mariana Martins Flores ◽  
Renata Dalcol Mazaro ◽  
Ingeborg Maria Langohr ◽  
Alma Roy ◽  
Keith Strother ◽  
...  
Keyword(s):  
Mast Cell ◽  
Pcr Amplification ◽  
The United States ◽  
Growth Fraction ◽  
Grading System ◽  
Low Grade ◽  
Ki 67 ◽  
Mast Cell Tumors ◽  
Cutaneous Mast Cell ◽  
Exon 11

ABSTRACT: The use of histologic classification by a 2-tier grading system only, immunohistochemistry (IHC) for KIT and Ki-67 and polymerase chain reaction (PCR) for internal tandem duplications (ITD) on exon 11 has improved the prognostication of canine cutaneous mast cell tumors (CCMTs) particularly in the United States. However, these techniques are not commonly used in most Brazilian laboratories. Likewise, no studies, to date, have investigated the occurrence of ITD in CCMTs from the country. Thus, this study tested the 2-tier grading system, the immunohistochemistry for KIT and Ki-67 and the PCR for exon 11 in a group of Brazilian CCMTs with the goal of investigating the applicability of these tests in a Brazilian laboratory. Of the 39 CCMTs, 69.2% (27/39) were identified as low-grade and 30.8% (12/39) as high-grade by a 2-tier grading system. All tumors had a KIT expression pattern II, and 30.6% (11/36) had a high growth fraction (Ki-67). PCR amplification was successful in four of the 11 tumors examined. Two of these (50%) were positive for ITD. This study highlights the importance of using auxiliary techniques in the CCMT evaluation, identifies limitations and confirms the applicability of these methods on a routine diagnostic basis in Brazil. Our results will help to improve the prognostication of CCMTs in Brazilian diagnostic laboratories, encouraging the use of supplementary methods.

scholarly journals Deep learning algorithms out-perform veterinary pathologists in detecting the mitotically most active tumor region

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marc Aubreville ◽  
Christof A. Bertram ◽  
Christian Marzahl ◽  
Corinne Gurtner ◽  
Martina Dettwiler ◽  
...  
Keyword(s):  
Deep Learning ◽  
Ground Truth ◽  
Mitotic Count ◽  
Mitotic Figure ◽  
Two Stage ◽  
Data Set ◽  
Area Selection ◽  
Tumor Region ◽  
Cutaneous Mast Cell ◽  
Mitotic Figures

Abstract Manual count of mitotic figures, which is determined in the tumor region with the highest mitotic activity, is a key parameter of most tumor grading schemes. It can be, however, strongly dependent on the area selection due to uneven mitotic figure distribution in the tumor section. We aimed to assess the question, how significantly the area selection could impact the mitotic count, which has a known high inter-rater disagreement. On a data set of 32 whole slide images of H&E-stained canine cutaneous mast cell tumor, fully annotated for mitotic figures, we asked eight veterinary pathologists (five board-certified, three in training) to select a field of interest for the mitotic count. To assess the potential difference on the mitotic count, we compared the mitotic count of the selected regions to the overall distribution on the slide. Additionally, we evaluated three deep learning-based methods for the assessment of highest mitotic density: In one approach, the model would directly try to predict the mitotic count for the presented image patches as a regression task. The second method aims at deriving a segmentation mask for mitotic figures, which is then used to obtain a mitotic density. Finally, we evaluated a two-stage object-detection pipeline based on state-of-the-art architectures to identify individual mitotic figures. We found that the predictions by all models were, on average, better than those of the experts. The two-stage object detector performed best and outperformed most of the human pathologists on the majority of tumor cases. The correlation between the predicted and the ground truth mitotic count was also best for this approach (0.963–0.979). Further, we found considerable differences in position selection between pathologists, which could partially explain the high variance that has been reported for the manual mitotic count. To achieve better inter-rater agreement, we propose to use a computer-based area selection for support of the pathologist in the manual mitotic count.

scholarly journals A retrospective study on prophylactic regional lymphadenectomy versus nodal observation only in the management of dogs with stage I, completely resected, low-grade cutaneous mast cell tumors

2021 ◽  
Author(s):  
Silvia Sabattini ◽  
Matti Kiupel ◽  
Riccardo Finotello ◽  
Damiano Stefanello ◽  
Eugenio Faroni ◽  
...  
Keyword(s):  
Mast Cell ◽  
Stage I ◽  
Low Grade ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Mast Cell Tumors ◽  
Regional Lymphadenectomy ◽  
Significant Difference ◽  
Cutaneous Mast Cell ◽  
Prophylactic Lymphadenectomy

Abstract Background. While lymphadenectomy of metastatic 27 lymph nodes (LNs) has been associated with improved outcome, the clinical utility of prophylactic lymphadenectomy in dogs with stage I cutaneous mast cell tumors (cMCTs) remains a controversial topic. To assess the therapeutic role of lymphadenectomy of uninvolved regional LNs, the long-term outcome of cMCT-bearing dogs with cytologically negative and surgically unresected regional LNs (observation only, OO) was compared with that of dogs with a surgically resected and histologically negative regional LNs (prophylactic regional lymphadenectomy, PRL).Results. A retrospective analysis of 64 dogs with a low-grade, completely resected stage I cMCT was performed: (54.7%) dogs were subjected to OO and 29 (45.3%) underwent PRL. Dogs were monitored for a median of 813 and 763 days in the OO group and PRL group, respectively. The number of dogs undergoing MCT progression was significantly higher in the OO group (P = 0.028) and curve comparison revealed a tendency to a better time to progression in the PRL group (P = 0.058). No significant difference in survival time (P = 0.294) was observed between dogs in the OO and PRL groups.Conclusions. Our results showed that lack of immediate lymphadenectomy was associated with a higher risk for tumor progression. This preliminary judgement, reinforced by the findings that lymphadenectomy was well tolerated in all cases, and that histopathology provides the definitive assessment of the nodal pathological status, may suggest that prophylactic lymphadenectomy is indicated in the management of stage I MCTs. Larger prospective studies are warranted for generating clinical evidence of this latter hypothesis.

scholarly journals Immunohistochemical and molecular profiling of CD 117, Oct-4, and Sox-2 in canine cutaneous mast cell tumor of the crossbred dogs in Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand

2021 ◽  
pp. 2646-2654
Author(s):  
Sirilak Meesuwan ◽  
Dettachai Ketpun ◽  
Prapruddee Piyaviriyakul ◽  
Kasem Rattanapinyopituk ◽  
Pattharakrit Theewasutrakul ◽  
...  
Keyword(s):  
Mast Cell ◽  
Study Finding ◽  
Cell Tumor ◽  
Low Grade ◽  
Mrna Levels ◽  
High Grade ◽  
Rt Pcr ◽  
Cd 117 ◽  
Mast Cell Tumor ◽  
Cutaneous Mast Cell

Background and Aim: CD 117 (c-KIT) internal tandem duplication (ITD), octamer-binding transcription factor 4 (Oct-4), and sex-determining region Y-box 2 (Sox-2) may govern the oncogenicity and aggressiveness of canine cutaneous mast cell tumor (MCT) in the crossbred dogs. Thus, a comprehension of this matter may help us establishing a novel platform to treat the disease in those dogs. However, evidence has lacked so far. Thus, this study aimed to survey CD 117 ITD, Oct-4, and Sox-2 expressions and their relations to the 2-tier grading in a group of Thai crossbreed dogs. The study was done using polymerase chain reaction (PCR), Reverse transcription PCR (RT-PCR), and immunohistochemistry. Materials and Methods: Thirty-three MCT specimens graded by the 2-tier histopathology grading were collected from the crossbred and purebred dogs. CD 117 ITD was detected by conventional PCR and immunohistochemistry. While, Oct-4 and Sox-2 expression levels were determined at the protein and mRNA levels by immunohistochemistry and RT-PCR, respectively. The expression magnitude of each parameter was then related to the grades and breeds. Results: About 60.61% of specimens were low grade, while 39.39% were high grade. CD 117 ITD was not detected in all specimens. A significant increase of Oct-4 expression was found in the high-grade, crossbred dogs. Meanwhile, Sox-2 expressions were increased both in the purebred and crossbred dogs with high-grade MCT. Conclusion: The study finding has indicated that the level of Sox-2 expression may be a useful tumorigenic and prognostic biomarker because it correlates to the 2-tier grades but not dog breeds.

scholarly journals Grading Cutaneous Mast Cell Tumors in Cats

2018 ◽  
Vol 56 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Silvia Sabattini ◽  
Giuliano Bettini
Keyword(s):  
Mast Cell ◽  
Case Series ◽  
Surgical Excision ◽  
Skin Neoplasms ◽  
Grading System ◽  
Low Grade ◽  
Tumor Diameter ◽  
High Grade ◽  
Mast Cell Tumors ◽  
Cutaneous Mast Cell

Cutaneous mast cell tumors (cMCTs) account for approximately 20% of skin neoplasms in cats. As there is no grading system for these tumors, prognosis is difficult to estimate. Although the typical presentation is a benign tumor that can be cured by surgical excision, a small but important proportion of feline cMCTs is biologically aggressive and can spread to local lymph nodes, precede the onset of disseminated cutaneous disease, or be associated with visceral involvement. A number of macroscopic and histologic features were retrospectively evaluated in cases of feline cMCTs treated with surgical excision with or without medical therapy. Cats were divided into 2 groups based on the clinical outcome. Group 1 included cats alive with no mast cell tumor–related disease at 1000 days from surgery; group 2 included cats developing histologically confirmed metastatic or cutaneous disseminated disease. The criteria allowing the best differentiation between the groups were used to develop a grading scheme. Groups 1 and 2 were composed by 48 (76%) and 15 (24%) cases, respectively. Tumors were classified as high grade if there were >5 mitotic figures in 10 fields (400×) and at least 2 of the following criteria: tumor diameter >1.5 cm, irregular nuclear shape, and nucleolar prominence/chromatin clusters. According to this scheme, the 15 (24%) high-grade cMCTs had significantly reduced survival time (median, 349 days; 95% CI, 0–739 days) as compared with the 48 low-grade tumors (median not reached; P < .001). Further studies are warranted to validate this grading system and test reproducibility on a larger case series.

Differences in the proteome of high-grade versus low-grade canine cutaneous mast cell tumours

2012 ◽  
Vol 194 (2) ◽  
pp. 210-214 ◽  
Author(s):  
P. Schlieben ◽  
A. Meyer ◽  
C. Weise ◽  
A. Bondzio ◽  
R. Einspanier ◽  
...  
Keyword(s):  
Mast Cell ◽  
Low Grade ◽  
High Grade ◽  
Grade Versus ◽  
Cutaneous Mast Cell

scholarly journals Occurrence and distribution of canine cutaneous mast cell tumour characteristics among predisposed breeds

2019 ◽  
Vol 63 (1) ◽  
pp. 141-148 ◽  
Author(s):  
Anna Śmiech ◽  
Wojciech Łopuszyński ◽  
Brygida Ślaska ◽  
Kamila Bulak ◽  
Agnieszka Jasik
Keyword(s):  
Mast Cell ◽  
Genetic Background ◽  
Clinical Course ◽  
Reference Group ◽  
Low Grade ◽  
Histological Grading ◽  
Skin Tumours ◽  
Cutaneous Mast Cell ◽  
Tumour Characteristics ◽  
Labrador Retrievers

Abstract Introduction: Breed predisposition to cutaneous mast cell tumours (MCT) in a population of dogs in Poland affected by various skin tumours was assessed, and the distribution of MCT characteristics such as histological grading, sex, age, and location, in predisposed breeds was evaluated. Material and Methods: The retrospective epidemiological study included 550 dogs affected by cutaneous MCTs with a reference group of 2,557 dogs diagnosed with other skin tumours. Results: A univariable logistic regression analysis was performed to determine the odds ratios (ORs) with 95% confidence intervals. The risk of high-grade MCTs was the highest for Shar-Peis (OR: 26.394) and American Staffordshire Terriers (OR: 2.897). Boxers (OR: 6.619), Labrador Retrievers (OR: 2.630), French Bulldogs (OR: 2.050), Golden Retrievers (OR: 1.949), and American Staffordshire Terriers (OR: 2.592) were mainly affected by low-grade MCTs. The high risk of MCT was calculated to be at the age of 4–6 years for Labrador Retrievers (OR: 2.686) and 7–10 years for Boxers (OR: 2.956) and French Bulldogs (OR: 9.429). MCTs were significantly more often located on the trunk in French Bulldogs (OR: 4.680), American Staffordshire Terriers (OR: 2.520), and Labrador Retrievers (OR: 1.948). There was no statistically significant correlation between gender and the occurrence of MCTs in the breeds. Conclusions: The breed-predicated differences in the clinical course of MCTs suggest a genetic background for the tumours.

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