Proposal of a 2-Tier Histologic Grading System for Canine Cutaneous Mast Cell Tumors to More Accurately Predict Biological Behavior

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.

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Histologic Grading of Canine Cutaneous Mast Cell Tumors: Is There a Good System?

Journal of Veterinary Science & Medical Diagnosis ◽

10.4172/2325-9590.1000e101 ◽

2012 ◽

Vol 01 (01) ◽

Author(s):

Adam W. Stern

Keyword(s):

Mast Cell ◽

Good System ◽

Histologic Grading ◽

Mast Cell Tumors ◽

Cutaneous Mast Cell

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The Relevance of CD117-Immunocytochemistry Staining Patterns to Mutational Exon-11 inc-kitDetected by PCR from Fine-Needle Aspirated Canine Mast Cell Tumor Cells

Veterinary Medicine International ◽

10.1155/2014/787498 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 9

Author(s):

A. Sailasuta ◽

D. Ketpun ◽

P. Piyaviriyakul ◽

S. Theerawatanasirikul ◽

P. Theewasutrakul ◽

...

Keyword(s):

Mast Cell ◽

Needle Aspiration ◽

Biological Behavior ◽

High Grade ◽

Fine Needle ◽

Mast Cell Tumors ◽

Diagnosis And Prognosis ◽

Cutaneous Mast Cell ◽

Exon 11 ◽

Two Parameters

Canine cutaneous mast cell tumors (MCT) are the lethal skin tumors. The biological behavior of the MCT cells is quite varied and unpredictable. Almost MCT dogs usually require a rapid diagnosis and therapy. However, MCT diagnosis and prognosis are still dependent on histopathology which is rather inconvenient, time-consuming, painful, and harmful for some cases. Indeed, MCT can be easily accessible using fine-needle aspiration (FNA). In this study, our biopsy specimens were classified as low- and high-grade MCT based on the novel 2-tier histopathologic grading system. We have demonstrated the usage of fine-needle aspirated MCT cells (FNA-MCT cells) from these specimens as a primary cell source to study the distribution of CD117-immunocytochemistry (CD117-ICC) staining patterns and the frequency of internal tandem duplication- (ITD-) mutant exon-11 ofc-kit. The result has substantially shown that there were three staining patterns identified in the cells. Only paranuclear pattern was significantly increased in the cells from high-grade MCT. Altogether, the ITD-mutant exon-11 was also detectable only in these cells. Therefore, the result has supported our hypothesis that there was an increased opportunity to observe a higher CD117-ICC staining pattern and exon-11 mutation in high-grade MCT; even these two parameters may not precisely indicate a histopathological grade.

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Comparison of 2- and 3-category histologic grading systems for predicting the presence of metastasis at the time of initial evaluation in dogs with cutaneous mast cell tumors: 386 cases (2009–2014)

Journal of the American Veterinary Medical Association ◽

10.2460/javma.246.7.765 ◽

2015 ◽

Vol 246 (7) ◽

pp. 765-769 ◽

Cited By ~ 37

Author(s):

Damiano Stefanello ◽

Paolo Buracco ◽

Silvia Sabattini ◽

Riccardo Finotello ◽

Chiara Giudice ◽

...

Keyword(s):

Mast Cell ◽

Initial Evaluation ◽

Histologic Grading ◽

Mast Cell Tumors ◽

Grading Systems ◽

Cutaneous Mast Cell

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Variation among Pathologists in the Histologic Grading of Canine Cutaneous Mast Cell Tumors with Uniform Use of a Single Grading Reference

Journal of Veterinary Diagnostic Investigation ◽

10.1177/104063870501700606 ◽

2005 ◽

Vol 17 (6) ◽

pp. 561-564 ◽

Cited By ~ 49

Author(s):

N. C. Northrup ◽

E. W. Howerth ◽

B. G. Harmon ◽

C. A. Brown ◽

K. P. Carmicheal ◽

...

Keyword(s):

Mast Cell ◽

Histologic Grading ◽

Mast Cell Tumors ◽

Cutaneous Mast Cell ◽

Is Value

Ten veterinary pathologists independently assigned histologic grades to the same 60 canine cutaneous mast cell tumors using the Patnaik classifications. The degree of agreement in grading among the pathologists was compared with the degree of agreement among the same pathologists in a previous study, in which each pathologist used the reference for grading that he/she uses routinely. Mean agreement improved significantly from 50.3% to 62.1% with uniform use of the Patnaik classifications ( P = 0.00001), suggesting that there is value in uniform application of a single grading scheme for canine cutaneous mast cell tumors. Agreement among pathologists was still not 100%, suggesting that a more objective grading scheme should be developed and that other histologic indicators of prognosis should be investigated.

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Expression of Ki67, BCL-2, and COX-2 in Canine Cutaneous Mast Cell Tumors

Veterinary Pathology ◽

10.1177/0300985812447829 ◽

2012 ◽

Vol 50 (1) ◽

pp. 110-121 ◽

Cited By ~ 42

Author(s):

M. Vascellari ◽

M. Giantin ◽

K. Capello ◽

A. Carminato ◽

E. M. Morello ◽

...

Keyword(s):

Mast Cell ◽

Health Status ◽

Mortality Rate ◽

Protein Expression ◽

Tumor Grade ◽

Grading System ◽

High Grade ◽

Mast Cell Tumors ◽

Cox 2 ◽

Cutaneous Mast Cell

The expression of Ki67, BCL-2, and COX-2 was investigated in 53 canine cutaneous mast cell tumors (MCTs) by immunohistochemistry and quantitative real time polymerase chain reaction (qPCR) to evaluate their prognostic significance and the association with the histologic grading and the mitotic index (MI). MCTs were graded according to the Patnaik grading system and the novel 2-tier grading system proposed by Kiupel. The numbers of mitotic figures/10 high-power fields (MI) were counted. Both grading systems were significantly associated with prognosis. The Patnaik grading was of limited prognostic value for grade 2 MCTs, with 23% being associated with mortality. The concordance among pathologists was strongly improved by the application of the 2-tier grading system, and 71% of high-grade MCTs were associated with a high mortality rate. MI and Ki67 protein expression were significantly associated with grading and survival. No significant association between BCL-2 protein expression and either grading system or health status was observed. BCL-2 mRNA expression was significantly higher in grade 2 than in grade 1 MCTs, while no statistically significant differences were detected between low- and high-grade MCTs. The increased BCL-2 mRNA level was significantly associated with increased mortality rate. The COX-2 protein expression was detected in 78% of the MCTs investigated. However, neither association with the tumor grade nor with the health status was observed. COX-2 mRNA was significantly up-regulated in MCTs compared to surgical margins and control skin tissue, but it was neither associated with tumor grade nor with survival.

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Grading Cutaneous Mast Cell Tumors in Cats

Veterinary Pathology ◽

10.1177/0300985818800028 ◽

2018 ◽

Vol 56 (1) ◽

pp. 43-49 ◽

Cited By ~ 3

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.

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

Journal of Veterinary Diagnostic Investigation ◽

10.1177/104063870501700305 ◽

2005 ◽

Vol 17 (3) ◽

pp. 245-248 ◽

Cited By ~ 42

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).

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