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CHAPTER 3  The Pathology of Neoplasia  65



            TABLE 3.2     Histologic Features of Hyperplasia and Benign and Malignant Neoplasia
             Histologic Feature    Hyperplasia       Benign Neoplasia           Malignant Neoplasia
  VetBooks.ir  Tissue demarcation  Blends with normal   Expansive and/or compressive, possibly   Invasive, infiltrative, unencapsulated, poorly
                                     tissue
                                                      encapsulated, well demarcated
                                                                                  demarcated
             Organization/architecture of   Retention of normal    Fairly uniform, typically some retention    Moderately to markedly haphazard, loss of normal
               cell population       tissue architecture  of normal architecture  architecture
             Cellular differentiation  Normal        Well differentiated        Moderately to poorly differentiated or undiffer-
                                                                                  entiated
             Cell and nuclear pleomorphism  None     Minimal                    Moderate to marked
             Cellular and nuclear atypia  None       Minimal to none            Moderate to marked; binucleated, multinucleated,
                                                                                  karyomegalic, or bizarre nuclei may be observed
             Anisocytosis/anisokaryosis  None        Minimal to none            Moderate to marked
             Nucleoli              Normal, indiscernible  Normal, typically indiscernible  Prominent, large and/or multiple
             Mitotic figures       Typically low     Typically low a            Typically high a
             Necrosis              None              Minimal to none            Moderate to marked
             Stromal reaction      None              None                       Scirrhous or desmoplastic response b
             Vascular invasion (blood or   Not present  Not present             Potential to exist
               lymphatic vasculature)
             a Exceptions exist; see Table 3.3.
             b Especially as can be seen with squamous cell and transitional cell carcinoma.





             Histopathologic features that distinguish benign from malig-  chemotherapy, or a combination thereof) because histopathologic
           nant neoplasia were introduced in the earlier section Terminology   features of treatment-associated tissue responses can be difficult
           and in Table 3.2. Ultimately, malignancies typically are charac-  to distinguish from overt neoplasia. This may be especially true
           terized by invasive growth with effacement of normal tissue and   after RT, which can induce the formation of bizarre reactive cells,
           poor organization of the tumor tissue itself. Cellular features of   including fibroblasts (radiation atypical fibroblasts), that display
           malignancy include increased cellular and nuclear pleomorphism;   many features of malignancy, although these cells are not neoplas-
           increased  anisocytosis  and  anisokaryosis;  increased  and variable   tic.  Inflammation,  fibrovascular  proliferation,  and  EC and/or
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           nuclear:cytoplasmic  ratio; presence of binucleated, multinucle-  epithelial hyperplasia are other possible treatment-associated tis-
           ated, and/or karyomegalic cells or bizarre nuclei; abnormal nuclear   sue responses that may preclude or obscure an appropriate assess-
           chromatin; increased number of mitotic figures; bizarre mitotic   ment of neoplasia. If tumor cells are identified, the clinician may
           figures; and abnormal, large, prominent and/or multiple nucleoli.   wish to know if these cells are viable, dead, or rendered viable but
           Increased necrosis also is recognized as a feature of malignancy.   sterilized (reproductively dead) by RT or chemotherapy. Although
           Unequivocal intravascular  (hematogenous  or lymphogenous)   the latter is not possible with routine microscopy, the presence of
           invasion, histologic evidence of lymph node (LN) involvement,   mitotic figures in the tumor cell population would indicate repli-
           or widespread metastasis (confirmed by submission of multiple   cative potential.
           lesions at various sites) conclusively establish malignancy, regard-
           less of other histopathologic features. 2,5,14        Mitotic Figures
             In some tumors the histopathologic features do not correlate
           with expected biologic behavior. Examples include canine cutane-  Mitotic figures (MFs) are observable, quantifiable tumor-associ-
           ous histiocytoma, benign plasmacytoma, and pleomorphic feline   ated histopathologic features that have been proven to be a reliable
           cutaneous MCT. 15–17  These typically display some histologic fea-  prognostic indictor for some tumors. The terminology, methodol-
           tures of malignancy but clinically are benign. Histologically low-  ogy of acquisition, and reporting of MFs, however, has varied over
           grade yet biologically high-grade FSAs of the canine oral cavity   the years and thus is addressed here to provide the clinician with
           have benign histologic features but are clinically malignant.    some insight and guidance when interpreting the MF information
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           Similarly, bronchial carcinomas in cats retain organized epithe-  provided in the pathology report.
           lial  structures composed of  well-differentiated,  ciliated,  pseu-  A MF provides visual confirmation of an actively dividing cell,
           dostratified columnar epithelium even at distant metastatic sites,   specifically in mitosis. Mitosis occurs during the M-phase when
           including the digit, eye, heart, and kidneys.  In these instances   replicated chromosomes of the cell are separated into two sepa-
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           knowledge of the clinical history and tumor behavior is essential   rate nuclei and, ultimately, cytokinesis gives rise to two separate
           to distinguish benign from malignant neoplasia.       cells. Mitotic stages are divided into prophase, prometaphase,
             Challenges may also be encountered during evaluation for pos-  metaphase, anaphase, and telophase, any of which may be visual-
           sible recurrence after therapy (surgery, radiation therapy [RT],   ized on routine microscopic evaluation, and all are considered
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