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There are two grading systems in common use for canine cutaneous MCTs; the Patnaik and Kiupel systems (Patnaik et al. 1984; Kiupel et al. 2011).

The grading system developed by Patnaik and colleagues is based on histomorphologic features, including cellularity, cell morphology, invasiveness, mitotic activity, and stromal reaction and is prognostic for survival. Well‐differentiated (grade I) MCTs account for 26–55% of all MCTs, intermediate differentiated (grade II) MCTs account for 25–59% of MCTs, and poorly differentiated (grade III) MCTs account for 16–40% of MCTs (Murphy et al. 2006). Tumor grade is the most consistent prognostic indicator for biological behavior and survival time in cutaneous MCTs across multiple studies (Turrel et al. 1988; Patnaik et al. 1984; Thamm et al. 1999). Higher tumor grade is associated with higher risk of metastasis, lower local control rates, and shorter survival times. Grade II MCTs are the most common grade identified and have the widest range of biological behavior compared to the other two grades. Most dogs diagnosed with grade II MCT will have a good prognosis; however, there is a subset of these patients that will develop metastases and have decreased survival time. Grade III MCTs have an aggressive clinical behavior and poor survival time compared to grade I or II MCTs, with a reported median survival time for dogs with grade III MCTs of 224–257 days and a metastatic rate of 55–96% (Bostock 1986; Hume et al. 2011).

There is significant variation in grading of MCTs between pathologists using the Patnaik grading scheme. In one study, 10 veterinary pathologists independently graded the same 60 cutaneous MCTs using the Patnaik grading system (Northrup et al. 2005). Agreement was 62.1% with most variation in classification was between grade I and grade II and grade II and grade III tumors.

The limitations of the Patnaik grading system prompted development of novel grading systems using mitotic index, argyrophilic nucleolar organizer regions (AgNOR), and Ki67 proliferation markers to help differentiate between grade II MCTs with a poor and good prognosis (Maglennon et al. 2008; Romansik et al. 2007; Scase et al. 2006).

A two‐tier grading system for MCTs proposed by Kiupel et al. (2011) has been validated and widely adopted by veterinary pathologists and MCTs are frequently reported with grading according to both these systems. The Kiupel system uses mitotic figures, multinucleated, bizarre nuclei, and karyomegaly for grading criteria. Kiupel graded high‐grade MCTs are significantly associated with shorter time to metastasis or new tumor development, and shorter survival time. The median survival time was less than four months for high‐grade MCTs but more than two years for low‐grade MCTs.

Dogs with high‐grade Kiupel and Grade III Patnaik MCTs were significantly more likely to have metastases (mainly lymph node metastases) at the time of initial diagnosis than low‐grade or Grade II or I MCTs (Krick et al. 2009; Weishaar et al. 2014). Combining histologic grade with clinical stage information provides a more accurate biological behavior prediction than either parameter alone (Stefanello et al. 2015). Prognosis should not rely solely on histologic grade, regardless of the grading system used, but should also consider the results of clinical staging. Dogs with Stage 1 high‐grade tumors treated surgically can have a prolonged survival time (Moore et al. 2020).