Mitotic Count in Canine Cutaneous Mast Cell Tumours – Not Accurate but Reproducible

2020 ◽  
Vol 174 ◽  
pp. 143
Author(s):  
C.A. Bertram ◽  
M. Aubreville ◽  
C. Gurtner ◽  
A. Bartel ◽  
S.M. Corner ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mitotic Count ◽  
Cutaneous Mast Cell

scholarly journals Computer-Assisted Mitotic Count Using a Deep Learning-based Algorithm Improves Inter-Observer Reproducibility and Accuracy in canine cutaneous mast cell tumors

2021 ◽  
Author(s):  
Christof A Bertram ◽  
Marc Aubreville ◽  
Taryn A Donovan ◽  
Alexander Bartel ◽  
Frauke Wilm ◽  
...  
Keyword(s):  
Mast Cell ◽  
High Performance ◽  
Ground Truth ◽  
Mitotic Count ◽  
Computer Assisted ◽  
Malignant Neoplasms ◽  
Mast Cell Tumors ◽  
Computer Assistance ◽  
Phosphohistone H3 ◽  
Cutaneous Mast Cell

The mitotic count (MC) is an important histological parameter for prognostication of malignant neoplasms. However, it has inter- and intra-observer discrepancies due to difficulties in selecting the region of interest (MC-ROI) and in identifying/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, the computer-assisted review by pathologists may ensure reliability. In the present study we have compared partial (MC-ROI preselection) and full (additional visualization of MF candidate proposal 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 MF and improving classification against imposters. The inter-observer 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 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 prove that computer assistance may lead to a more reproducible and accurate MCs in ccMCTs.

scholarly journals Computerized Calculation of Mitotic Count Distribution in Canine Cutaneous Mast Cell Tumor Sections: Mitotic Count Is Area Dependent

2019 ◽  
Vol 57 (2) ◽  
pp. 214-226 ◽  
Author(s):  
Christof A. Bertram ◽  
Marc Aubreville ◽  
Corinne Gurtner ◽  
Alexander Bartel ◽  
Sarah M. Corner ◽  
...  
Keyword(s):  
Mast Cell ◽  
High Power ◽  
Ground Truth ◽  
Mitotic Count ◽  
Automated Image Analysis ◽  
High Power Field ◽  
Borderline Cases ◽  
Area Selection ◽  
Cutaneous Mast Cell ◽  
Mitotic Figures

Mitotic count (MC) is an important element for grading canine cutaneous mast cell tumors (ccMCTs) and is determined in 10 consecutive high-power fields with the highest mitotic activity. However, there is variability in area selection between pathologists. In this study, the MC distribution and the effect of area selection on the MC were analyzed in ccMCTs. Two pathologists independently annotated all mitotic figures in whole-slide images of 28 ccMCTs (ground truth). Automated image analysis was used to examine the ground truth distribution of the MC throughout the tumor section area, which was compared with the manual MCs of 11 pathologists. Computerized analysis demonstrated high variability of the MC within different tumor areas. There were 6 MCTs with consistently low MCs (MC<7 in all tumor areas), 13 cases with mostly high MCs (MC ≥7 in ≥75% of 10 high-power field areas), and 9 borderline cases with variable MCs around 7, which is a cutoff value for ccMCT grading. There was inconsistency among pathologists in identifying the areas with the highest density of mitotic figures throughout the 3 ccMCT groups; only 51.9% of the counts were consistent with the highest 25% of the ground truth MC distribution. Regardless, there was substantial agreement between pathologists in detecting tumors with MC ≥7. Falsely low MCs below 7 mainly occurred in 4 of 9 borderline cases that had very few ground truth areas with MC ≥7. The findings of this study highlight the need to further standardize how to select the region of the tumor in which to determine the MC.

scholarly journals HSP32 and HSP90 Immunoexpression, in Relation to Kit Pattern, Grading, and Mitotic Count in Canine Cutaneous Mast Cell Tumors

2016 ◽  
Vol 54 (2) ◽  
pp. 222-225 ◽  
Author(s):  
M. Romanucci ◽  
M. Massimini ◽  
A. Ciccarelli ◽  
D. Malatesta ◽  
L. Bongiovanni ◽  
...  
Keyword(s):  
Mast Cell ◽  
Histological Grade ◽  
Tumor Grade ◽  
Mitotic Count ◽  
Immunohistochemical Expression ◽  
Mast Cell Tumors ◽  
Great Heterogeneity ◽  
Poorly Differentiated ◽  
Cutaneous Mast Cell

Literature data indicate heat shock protein (Hsp) 32 and 90 as potential molecular targets in canine neoplastic mast cells (MCs). However, their immunoexpression patterns in canine mast cell tumors (MCTs) have not been investigated. Thus, the aim of this study was to evaluate the immunohistochemical expression of Hsp32 and Hsp90 in 22 canine cutaneous MCTs, in relation to KIT immunolabeling pattern, histological grade, and mitotic count. All cases showed cytoplasmic labeling of Hsp90, variably associated with nuclear and/or membranous labeling. Relationships of Hsp90 or Hsp32 immunolabeling with KIT pattern, mitotic count, and tumor grade were not observed. However, the reduced Hsp32 immunoexpression observed in most grade III/high-grade MCTs suggests a tendency toward a loss of immunosignal in poorly differentiated MCs. The great heterogeneity in extent and distribution of Hsp90 immunoexpression among the different MCT cases may also partially explain the difficulties in predicting the in vivo biologic activity of Hsp90 inhibitors on canine MCTs.

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 RETRACTED ARTICLE: Cutaneous mast cell tumor (Mastocytoma): Cyto- histopathological and haematological investigations

2014 ◽  
Vol 9 (1) ◽  
Author(s):  
Ehsan Hosseini ◽  
Behnam Pedram ◽  
Ali Mohammad Bahrami ◽  
Mohammad Hossein Jaberi Moghaddam ◽  
Javad Javanbakht ◽  
...  
Keyword(s):  
Mast Cell ◽  
Cell Tumor ◽  
Mast Cell Tumor ◽  
Retracted Article ◽  
Cutaneous Mast Cell

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.

Effects of Skin Mast Cells on Bleeding Time and Coagulation Activation at the Site of Platelet Plug Formation

1998 ◽  
Vol 79 (04) ◽  
pp. 843-847 ◽  
Author(s):  
Petteri Kauhanen ◽  
Petri Kovanen ◽  
Timo Reunala ◽  
Riitta Lassila
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Thrombin Generation ◽  
Bleeding Time ◽  
Normal Skin ◽  
Urticaria Pigmentosa ◽  
Primary Hemostasis ◽  
Cell Accumulation ◽  
The Mean ◽  
Cutaneous Mast Cell

SummaryWe studied the effects of stimulated skin mast cells on bleeding time and thrombin generation which was measured using prothrombin fragment F 1+2 (F 1+2) and thrombin-antithrombin-III-complex (TAT). In 10 patients with urticaria pigmentosa (chronic cutaneous mast cell accumulation) the mean bleeding time was significantly prolonged in wounds made on urticaria pigmentosa lesions vs. normal skin (460 ± 34 vs. 342 ± 27 s, p = 0.005). In 10 atopic subjects skin incisions were made on prick-tested sites 30, 60, 120 and 240 min after administration of an allergen (acute mast cell stimulation), histamine or vehicle. The mean bleeding time was significantly prolonged at all time points, being maximal at 120 min (60% prolonged) in wounds made on allergen-stimulated skin areas (p <0.01) compared with histamine or vehicle sites. Administration of allergen or histamine lowered the TAT concentration in the bleeding-time blood. Furthermore, TAT and F 1+2 levels in the bleeding-time blood were lower at 60, 120 and 240 min after allergen or histamine application in comparison with samples collected at 30 min. We conclude that skin mast cells can regulate primary hemostasis by prolonging bleeding time and by inhibiting thrombin generation.

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