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CHAPTER 81   Selected Neoplasms in Dogs and Cats   1329


              Given the fact that mast cells produce a variety of bioac-  More recently, a group of pathologists proposed establish-
            tive (mainly vasoactive) substances, dogs with MCTs may be   ing a two-tier grading system for canine MCTs, using a low-
  VetBooks.ir  evaluated because of diffuse swelling (i.e., edema and inflam-  grade and high-grade designation (Kiupel et al., 2011).
                                                                 A group of 28 pathologists from 16 institutions evaluated
            mation around a primary tumor or its metastatic lesion),
            erythema, or bruising of the affected area. These episodes
                                                                 Interestingly, when grading the tumors using the original
            may be acute, and they may occur during or shortly after   95 MCTs from dogs treated by surgical resection alone.
            exercise or exposure to cold weather. Percutaneous FNA of   three-tier  system,  concordance  among  pathologists  was
            an unexplained subcutaneous swelling in dogs should always   approximately 60% to 65% for grades 1 and 2 tumors and
            be performed as part of the workup.                  75% for grade 3 tumors. Using the newer two-tier grading
              A “typical” MCT is a dermoepidermal, dome-shaped, alo-  system, there was a 98.6% consistency among six patholo-
            pecic, and erythematous lesion (Fig. 81.7). However, as dis-  gists.  Along with this,  the MST for dogs  with low-grade
            cussed in previous paragraphs, MCTs rarely have a typical   tumors was 23 months, compared with approximately 4
            appearance. A clinical feature that may aid in the diagnosis   months for dogs with high-grade tumors. This newer grading
            of a MCT is the Darier sign, which is the erythema and wheal   scheme, overall, has been shown to decrease inter-pathologist
            that form after the tumor is slightly traumatized (i.e., scraped,   variation as well as provide strong correlations with overall
            compressed, aspirated, etc.).                        survival, MCT-associated mortality, and risk of metastasis.
              As discussed in Chapter 74, MCTs are easily diagnosed   However, other authors have questioned whether this
            on cytology (see  Fig. 74.8). Most dogs with MCTs have a   grading system correlates well with survival times (Stefanello
            normal,  although  eosinophilia  (sometimes  marked),  baso-  et al., 2015).
            philia,  mastocythemia, neutrophilia, thrombocytosis, or   In some cases, special stains may be required to identify
            anemia (or a combination of these) may be present. Serum   the typical intracytoplasmic granules in poorly differentiated
            biochemistry abnormalities are uncommon.             neoplasms. The mitotic index is of prognostic relevance in
              From a histopathologic standpoint, MCTs were tradition-  dogs with MCTs, so it should be provided by the pathologist
            ally classified using the Patnaik grading system into three   (Romansik et al., 2007). In addition to the grading of the
            categories: well differentiated (grade 1), moderately differen-  tumor, the pathologist should provide the clinician with
            tiated (grade 2), and poorly differentiated (grade 3). Several   information regarding the completeness of the excision. A
            studies have shown that dogs with grade 1 tumors treated   dog with an incompletely excised MCT is rarely cured by the
            with surgery alone have longer survival times than identi-  initial surgical procedure and requires either a second
            cally treated dogs with grade 3 tumors, mainly because well-  surgery, irradiation of the affected area, or chemotherapy.
            differentiated neoplasms are easier to resect and have a lower   Markers  of  proliferation,  such  as AgNOR  (argyrophilic
            metastatic potential (i.e., most tumors in dogs with systemic   nucleolar organizing region) and Ki-67, have been used
            mast cell disease are grade 3).                      prognostically in some studies, and are now offered by
                                                                 several commercial  laboratories.  In these studies,  high
                                                                 AgNOR and Ki-67 scores were associated with a shorter time
                                                                 to relapse and MSTs. We do not routinely use these stains to
                                                                 plan treatment of dogs with MCTs.
                                                                   From a molecular standpoint, approximately 20% to 30%
                                                                 of canine MCTs have internal tandem duplications in exons
                                                                 11 and 12 of c-kit; c-kit is the stem cell growth factor recep-
                                                                 tor, and its mutation results in immortalized clones that do
                                                                 not undergo apoptosis (Jones et al., 2004). Mutations in c-kit
                                                                 are more common in high-grade tumors and have been asso-
                                                                 ciated with decreased MST and disease-free interval (DFI),
                                                                 and a higher risk of local recurrence, metastasis, and MCT-
                                                                 related mortality.

                                                                 Biologic Behavior
                                                                 The biologic behavior of canine MCTs can be summed up in
                                                                 one word: unpredictable. Even though several criteria may
                                                                 help in establishing the biologic behavior of these neoplasms,
                                                                 they rarely apply to an individual dog (i.e., they may be
                                                                 meaningful from the statistical viewpoint; however, they are
                                                                 not always representative in a specific patient).
                                                                   In general, solitary cutaneous MCTs that are termed low-
            FIG 81.7                                             grade (Kiupel) or grade 1 (Patnaik) have a low metastatic
            Dermoepidermal, dome-shaped lesion in the pinna of a   potential and low potential for systemic dissemination.
            Boxer. The cytologic diagnosis was mast cell tumor.   However, the clinician may encounter a dog with several
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