Page 632 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition
P. 632

610   PART IV    Specific Malignancies in the Small Animal Patient



          TABLE 28.3     Criteria Used for Histologic Grading of Malignancy in Feline and Canine Mammary Carcinomas
                                                                                                      b
                                                                                        MITOSES/10 HPFS
  VetBooks.ir  Tubule Formation a    Nuclear Pleomorphism a                          Canine          Feline
            Tubule formation >75% of the
              specimen: 1 point      Uniform or regular small nucleus and occasional nucleoli: 1 point  0–9: 1 point  0–8: 1 point
            Moderate formation of tubular   Moderate degree of variation in nuclear size and shape, hyperchromatic   10–19: 2 points  9–17: 2 points
              arrangements (10%–75% of the   nucleus, and presence of nucleoli (some of which can be prominent):
              specimen) admixed with areas   2 points
              of solid tumor growth: 2 points
            Minimal or no tubule formation   Marked variation in nuclear size and hyperchromatic nucleus,    >19: 3 points  >17: 3 points
              (<10%): 3 points         often with one or more prominent nucleoli: 3 points

            a In complex and mixed tumors, the percentage of tubular formation and the nuclear pleomorphism are evaluated only in the malignant component. In malignant myoepithelioma tubular formation is 2
            b HPF, High-power field. The fields are selected at the periphery or the most mitotically active parts of the sample (including also myeopithelial cells if part of the tumor). Diameter of the field of view = 0.55
                                   2
                       2
            mm; area = 0.237 mm ; 10 HPFs = 2.37 mm . The mitotic count has to be proportional to the field diameter.

           TABLE 28.4A     Tumor Grade Based on Histologic       TABLE 28.4B     Newly Proposed Histologic Grading
                        Score from Table 28.3 in Cats and                     System for Invasive Mammary
                        Dogs 133,134,136,137,210                              Carcinoma in Cats
            Total Score           Grade of Malignancy             Lymphovascular Invasion            Points
            3–5                   I (low)                         Present                            1
                                  Well differentiated
                                                                  Absent                             0
            6–7                   II (intermediate)                        a
                                  Moderately differentiated       Nuclear Form                       Points
            8–9                   III (high)                      ≤5% Abnormal                       0
                                  Poorly differentiated           >5% Abnormal                       1
                                                                  Mitotic Count (mitoses per 10 HPFs) b  Points
                                                                  ≤62                                0
         is poorly differentiated (Table 28.4a,b). Tumor grade has been found
         to provide consistent and reliable prognostic information in both cats   >62                1
         and dogs. 82,129,130,132–135  More recently, details on how to perform   Histologic Grade   Sum of Points
         grading, particularly in MGTs with myoepithelial or mesenchymal
         components 136  and on how to standardize the mitotic count, 137    Grade I (low, well differentiated)  0
         have been published. In addition to the grading system, informa-  Grade II (intermediate, moderately differentiated)  1
         tion regarding vascular/lymphatic invasion, surrounding stromal
         invasion, LN involvement, and tumor type may also predict behav-  Grade III (high, poorly differentiated)  2–3
         ior. 13,29,65,130,131,135,138,139  Specifically for histotypes, 131  dogs carry-  a Abnormal nuclear form includes any deviation from smooth nuclear contour or round/oval
         ing adenosquamous (median survival time [MST] of 18 months),   nuclear shape such as clefting, angularity, corrugation, or ameboid morphology assessed
         comedo- (MST of 14 months), solid (MST of 8 months), and   at high power (40–60× objective) in the least differentiated and/or most invasive portions
         anaplastic (MST of 3 months) carcinomas experienced the worst   of the tumor. The number of nuclei exhibiting the abnormal nuclear form is estimated and
         prognosis. Prolonged survival was observed for complex carcinoma   expressed as a percentage of the total number of nuclei within any given field.
                                                                  Cumulative number of mitoses in 10 consecutive high-power fields (HPFs) in the most
                                                                  b
         and simple tubular carcinoma, whereas a more than 10-fold higher   mitotically active area with a microscope field diameter of 0.53 mm (40× objective). 218
         risk of tumor-related death was associated with certain other types
         such as simple tubulopapillary carcinoma, intraductal papillary car-
         cinoma, and carcinoma and malignant myoepithelioma. Carcino-
         sarcomas and sarcomas are typically not graded via this system, but   Clinical Prognostic Factors
         the majority tend to be biologically aggressive tumors and associated
         with a very poor long-term survival. 135,138          The three prognostic factors that are most consistently reported
            MGTs in dogs represent a wide histologic spectrum with both   to be associated with prognosis include tumor size, LN involve-
         benign and malignant lesions originating from different tissue   ment, and World Health Organization (WHO) stage (modified
         types or a combination of tissues. Many dogs present with several   and original). These are the only factors that will be discussed here.
         different tumors and tumors of different types and can as such
         represent a rather daunting histopathologic picture; prognosis is   Tumor Size
         determined by the most aggressive tumor and decisions regarding   According to MacEwen et al, dogs with tumor volume larger than
         adjuvant treatments should be based on the largest or the most   40 cc (approximately 3.4 cm in diameter) have a statistically signif-
         aggressive histology. In many cases, the most aggressive tumor is   icant worse outcome than smaller tumors, both in terms of remis-
                  15
         the largest.                                          sion and survival. 140  Other investigators have classified tumors as
   627   628   629   630   631   632   633   634   635   636   637