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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.