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700   PART IV    Specific Malignancies in the Small Animal Patient



          TABLE 33.3     Histologic and Immunophenotypic Characteristics of Common Canine Non-Hodgkin’s Lymphomas in
                      Relative Order of Frequency
  VetBooks.ir  Subtype       Typical Location   Histologic Architecture  Cellular Features  Immunophenotype +  +
                             Usually multicentric
            Diffuse large B-cell
                                                Diffuse
                                                                                           CD1 , CD20 , CD21 , CD45 ,
                                                                                              +
                                                                   Large cells; round nuclei; one
                                                                                                   +
              (DLBCL)          lymphadenopathy                       (central) or multiple nucleoli;   CD79a , Pax5 , MHCII ,
                                                                                                      +
                                                                                                           +
                                                                                                 +
                                                                     high mitotic rate; “starry sky”   CD18 low
                                                                     appearance
                                                                                              +
                                                                                                   –
                                                                                                             +
                                                                                                        –
            Peripheral T-cell   Usually multicentric   Diffuse     Variable size (small to large);   CD3 , CD79a , CD21 , CD45 ,
                                                                                               +
              lymphoma-not     lymphadenopathy                       irregular nuclei, variable   CD5 , CD4 , CD8 ,
                                                                                                         +/–
                                                                                                    +/–
              otherwise specified                                    chromatin, prominent nucleoli;   CD18 high , TCRαβ
              (PTCL-NOS)                                             varied mitotic activity
            Marginal zone    Nodal (nMZL) or splenic   Nodular/ follicular  Mostly intermediate- sized cells-   CD1 , CD20 , CD21 , CD45 ,
                                                                                              +
                                                                                                            +
                                                                                                       +
                                                                                                   +
                                                                                                 +
                lymphoma (MZL)  (sMZL) or extranodal                 abundant pale cytoplasm;   CD79a , MHCII , CD18 inter-
                                                                                                      +
                               mucosal                               irregular nuclei with peripher-  mediate
                                                                     alized chromatin and a single
                                                                     central nucleolus; rare mitotic
                                                                     figures (except nMZL)
                                                                                                       +
                                                                                                  +
                                                                                                           +
                                                                                              –
            T-zone lymphoma   Usually multicentric   Nodular, paracortical,   Small to intermediate- sized   CD45 , CD3 , CD5 , CD21 ,
              (TZL)            Lymphadenopathy    progressing to diffuse  cells; moderate amount of   CD4 / , CD8 +/–
                                                                                               + –
                                                                     pale cytoplasm; oval to ellipti-
                                                                     cal nuclei with sharp, shallow
                                                                     indentations; nucleoli and
                                                                     mitotic figures are sparse
            Precursor lymphoma a  Multicentric and/or   Diffuse and/or leukemia  Intermediate-sized cells; round   If T-cell: CD45 , CD34 / ,
                                                                                                         + –
                                                                                                    +
                                                                                               +/–
                               leukemia                              nuclei; scant Cytoplasm; high   CD5 , CD3 / , CD4 , CD8 –
                                                                                                          +/–
                                                                                                    + –
                                                                                                     +
                                                                     mitotic rate          If B-cell: CD45 , CD18 ,
                                                                                                          +
                                                                                                + –
                                                                                                            +/–
                                                                                                       +
                                                                                             CD34 / , CD79a , CD21 ,
                                                                                             CD20 +/–
                                                                                                   +
                                                                                                              +
                                                                                                        +
                                                                                              +
            Mantle cell lymphoma   Splenic white pulp  Nodular/ follicular  Small to intermediate- sized   CD20 , CD21 , CD45 , CD79a ,
              (MCL)                                                  cells; scant cytoplasm; round   MHCII +
                                                                     nuclei with dense chromatin,
                                                                     inconspicuous nucleoli; varied
                                                                     mitotic rate
                                                                                                   +
                                                                                              +
                                                                                                        +
                                                                                                              +
            Follicular lymphoma  Lymphadenopathy, solitary   Nodular/ follicular  Mixed—mostly small cells with   CD20 , CD21 , CD45 , CD79a ,
                               or multiple                           clear cytoplasm, pale chroma-  MHCII +
                                                                     tin, and inconspicuous nucleoli
                                                                     (centrocytes) with fewer large
                                                                     cells with dark blue cytoplasm,
                                                                     vesicular nuclei, and 1–3
                                                                     nucleoli (centroblasts)
            a Precursor lymphoma includes lymphoblastic B- or T-cell lymphomas and B- or T-cell acute leukemias.
            Adapted with permission from Seelig DM, Avery AC, Ehrhart EJ, Linden MA. The comparative diagnostic features of canine and human lymphoma. Vet Sci. 2016;3: Epub ahead of print. https://doi.
            org/10.3390/vetsci3020011; and Burkhard MJ, Bienzle D. Making sense of lymphoma diagnostics in small animal patients. Vet Clin North Am Small Anim Pract. 2013;43:1331-1347.

         results can occur with clonality assays. For example, cells from   molecular techniques, although helpful for diagnosis, could
         a dog with lymphoma may be negative for clonality if the   also have utility in detecting relapse and in determining more
         clonal segment of DNA is not detected with the PCR prim-  accurate clinical stage and so-called “molecular remission rates”
         ers used, mutation of the primer site has occurred, there are   because they are more sensitive than standard cytologic assess-
         background  nonneoplastic  lymphocytes  (noise)  within  the   ment of peripheral blood, bone marrow, or LNs. 
         tumor, the malignant cells are natural killer (NK) cells (rare),
         or the malignant cells are present in too low a frequency to   Other Immunohistochemical and
         be  detected. False positives  occur  rarely in some  infectious   Immunocytochemical Assessments
         diseases (e.g., ehrlichiosis and leishmaniasis). In these cases, a   Assessments of several markers of multidrug resistance and
         diagnosis should be made only after considering the results of   apoptotic pathways (e.g., P-glycoprotein, p53, Bcl-2 proteins)
         all the diagnostic tests, including histologic/cytologic evalua-  have been evaluated in dogs with lymphoma 29,30,174,196,197 ;
         tion, immunophenotyping, and clonality studies in conjunc-  however, their clinical significance and utility have not been
         tion with signalment and physical examination findings. These   established. 
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