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

Northrup, Nicole C.; Harmon, B. G.; Gieger, Tracy L.; Brown, Cathy A.; Carmichael, K. Paige; García, Anapatricia; Latimer, Kenneth S.; Munday, John S.; Rakich, Pauline M.; Richey, Lauren; Stedman, Nancy; Cheng, An‐Lin; Howerth, Elizabeth W.

doi:10.1177/104063870501700305

Cited by 60 publications

(61 citation statements)

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“…18 Predicting the behavior of grade II MCTs has proven to be difficult, and this problem is confounded by the fact that despite specific guidelines for determination of grade (i.e., the Patnaik system), there is significant variation in grade assignment among pathologists. 21 Over the past several years, attempts have been made to improve the characterization of cutaneous MCTs in order to better predict biologic behavior and therefore provide guidelines for therapeutics. For example, as previously discussed, Ki-67, PCNA, and AgNOR staining have been used as surrogate markers of proliferation in cutaneous MCTs, and some studies have demonstrated that they do correlate with biologic behavior.…”

Section: Discussionmentioning

confidence: 99%

“…18 While tumor grade is often used to determine prognosis, there is widespread disagreement on standardization of grading, as evidenced by a recent publication in which there was significant variation among 10 pathologists in the grading of the same set of 60 MCTs. 21 There are several other characteristics of canine MCTs that may contribute to potential outcome. It has been suggested that MCTs that develop in the oral cavity, nail bed, and inguinal, preputial, and perineal regions behave in a more malignant fashion regardless of histologic grade, although definitive proof for this is lacking.…”

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confidence: 99%

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Mitotic Index Is Predictive for Survival for Canine Cutaneous Mast Cell Tumors

et al. 2007

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Abstract. Mitotic index (MI) is an indirect measure of cell proliferation that has been demonstrated to be a strong predictor of outcome for several human and canine cancers. The purpose of this study was to evaluate the utility of MI as a predictor of biologic behavior and survival in dogs with cutaneous mast cell tumors (MCTs). Medical records from 148 dogs with histologically confirmed MCTs were reviewed. Information regarding tumor grade, local recurrence, metastatic disease, date of death/last follow-up, and outcome was obtained. The region of the tumor with the highest overall mitotic activity was chosen for evaluation, and the MI value was defined as the number of mitotic figures/10 high-power fields (4003, 2.7 mm 2 ). A Cox proportional hazards regression model was used to compare MI with survival data. A Mann-Whitney test was used to compare MI on the basis of the development of local recurrence and metastatic disease. The MI correlated directly with tumor grade (P , .0001). The median survival time for dogs with an MI #5 was significantly longer (70 months) than for those with an MI .5 (2 months), regardless of grade (P , .001). For grade II tumors with an MI #5, the median survival time (MST) was 70 months, compared with 5 months for those with an MI .5 (P , .001). For grade III tumors with an MI #5, the MST was not reached, compared with ,2 months for those with an MI .5 (P , .001). In conclusion, MI is a strong predictor of overall survival for dogs with cutaneous MCTs and should be included as a prognostic indicator when determining therapeutic options.

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confidence: 99%

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Mitotic Index Is Predictive for Survival for Canine Cutaneous Mast Cell Tumors

et al. 2007

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“…1 Additionally, the PS is influenced by subjective interobserver variations. 4,6,7 To improve concordance among pathologists and reduce the prognostic uncertainty of the intermediate grade in the PS, a 2-tier histologic grading system was proposed in 2011 by Kiupel et al 4 According to the Kiupel system (KS), the diagnosis of a high-grade (HG) MCT is characterized by any of the following criteria: at least 7 mitotic figures in 10 highpower fields (HPFs), at least 3 multinucleated cells in 10 HPFs, at least 3 bizarre nuclei in 10 HPFs, and karyomegaly. 4 All other tumors are considered low grade (LG).…”

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Histologic Grading of Canine Mast Cell Tumor

et al. 2014

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Mast cell tumor (MCT) is a common canine cutaneous neoplasm with variable biological behavior. A 2-tier histologic grading system was recently proposed by Kiupel et al to reduce interobserver variation and eliminate prognostic uncertainty of the Patnaik system. This study compared the ability of these 2 grading systems to predict survival in a cohort of dogs with MCTs. However, surgical margins were unknown, and the risk of developing new/metastatic MCTs was not studied. Histologic grade was assessed according to both systems for 137 surgically resected cutaneous MCTs. The relationship between grade and survival was evaluated. According to the Patnaik system, 18 MCTs (13.1%) were classified as grade I, 83 (60.6%) as grade II, and 36 (26.3%) as grade III. Grade III was associated with a poorer prognosis (P < .001), but no significant difference between grades I and II was detected. Grading according to the Patnaik system was based on consensus grading among 3 pathologists, and interobserver variability was not considered. All grade I MCTs were low grade in the Kiupel system, and all grade III were high grade. Among grade II, 71 (85.6%) were low grade, and 12 (14.4%) were high grade, with a 1-year survival probability of 94% and 46%, respectively (P < .001). The 2-tier system had a high prognostic value and was able to correctly predict the negative outcomes of some grade II MCTs. Data also confirm that histologic grading cannot predict biological behavior of each MCT and should be supplemented with molecular methods for more accurate prognostication.Keywords dog, skin, mast cell tumor, histologic grade, prognosis Mast cell tumors (MCTs) are the most common cutaneous tumors in dogs, accounting for 16% to 21% of all skin neoplasms. Canine MCTs vary widely in their biological behavior, ranging from nearly benign to highly invasive and metastatic.

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“…40 Although histologic grades have been shown to be significantly associated with prognosis, 2,40 the ambiguity of intermediate-grade tumors 55,67 and the marked degree of interobserver variation, with as low as 50% agreement between pathologists in some studies, have led to questioning of the relevance of the current histologic grading system. 23,36,37 The propensity for uncontrolled cellular proliferation is a hallmark of cancer, 17 and as such, measures of cellular proliferation have been used extensively to prognosticate both human 14,18,19,41,46,47,63,64 and veterinary neoplastic diseases. 1,3,20,22,24,26,29,34,49,52,53,56 In veterinary medicine, the most commonly used methods to evaluate cellular proliferation include proliferating cell nuclear antigen (PCNA) and Ki67 immunostaining and argyrophilic nucleolar organizing region (Ag-NOR) histochemical staining.…”

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Cellular Proliferation in Canine Cutaneous Mast Cell Tumors: Associations with c-KIT and Its Role in Prognostication

et al. 2007

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Abstract. Canine cutaneous mast cell tumor (MCT) is a common neoplastic disease in dogs. Due to the prevalence of canine MCTs and the variable biologic behavior of this disease, accurate prognostication and a thorough understanding of MCT biology are critical for the treatment of this disease. The goals of this study were to evaluate and compare the utility of the proliferation markers Ki67, proliferating cell nuclear antigen (PCNA), and argyrophilic nucleolar organizing region (AgNOR) as independent prognostic markers for canine MCTs and to evaluate the use of these markers in combination, as each marker assesses different aspects of cellular proliferation. An additional goal of this study was to evaluate the associations between cellular proliferation and c-KIT mutations and between cellular proliferation and aberrant KIT protein localization in canine MCTs. Fifty-six MCTs treated with surgical excision alone were included in this study. Each MCT was evaluated for Ki67 expression, PCNA expression, and KIT protein localization using immunohistochemistry; for AgNOR counts using histochemical staining; and for the presence of internal tandem duplication c-KIT mutations using polymerase chain reaction amplification. In this study, increased Ki67 and AgNOR counts were both associated with significantly decreased survival. On the basis of these results, we recommend that the evaluation of cellular proliferation, including evaluations of both Ki67 expression and AgNORs, should be routinely used in the prognostication of canine MCTs. Additionally, the results of this study show that MCTs with aberrant KIT protein localization or internal tandem duplication c-KIT mutations are associated with increased cellular proliferation, further suggesting a role for c-KIT in the progression of canine MCTs.

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

Cited by 60 publications

References 6 publications

Mitotic Index Is Predictive for Survival for Canine Cutaneous Mast Cell Tumors

Mitotic Index Is Predictive for Survival for Canine Cutaneous Mast Cell Tumors

Histologic Grading of Canine Mast Cell Tumor

Cellular Proliferation in Canine Cutaneous Mast Cell Tumors: Associations with c-KIT and Its Role in Prognostication

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