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Immunophenotyping of canine large-cell lymphoma (LCL) for B-cell and T-cell surface antigens is commonly performed to better predict the clinical outcome. Expression of surface antigen CD3 is associated with T-cell malignancies; surface antigen CD20 is expressed on B cells. However, a small subset of canine LCLs expresses both CD3 and CD20 (CD3+/CD20+); this form of lymphoma remains poorly defined at the molecular level. In a retrospective study, we aimed to better characterize immunophenotypic properties and antigen receptor clonality of CD3+/CD20+ LCL. We selected formalin-fixed, paraffin-embedded tissues from 10 cases of CD3+/CD20+ LCL and breed-matched controls of peripheral large T-cell lymphoma (PTCL) and diffuse large B-cell lymphoma (DLBCL). Using PCR for antigen receptor rearrangement (PARR), we identified monoclonal T-cell receptor gamma (TCRγ) rearrangements in all CD3+/CD20+ cases. Three of 10 cases had monoclonal rearrangements in the immunoglobulin heavy chain (IgH), supportive of cross-lineage rearrangement. There was no significant difference in the frequency of antigen receptor rearrangement between CD3+/CD20+ and PTCL cases. In comparison with DLBCL, CD3+/CD20+ LCL had TCRγ rearrangement more frequently and IgH rearrangement less frequently, respectively. Immunolabeling of the B-cell marker PAX5 occurred less frequently in all CD3+/CD20+ LCL cases compared to the DLBCL controls. Immunolabeling for BCL-2 was robust, regardless of immunophenotype. Nuclear Ki67 positivity was variable in CD3+/CD20+ cases, indicating a heterogeneity in proliferation. Overall, cases of canine CD3+/CD20+ LCL had properties similar to PTCL, suggesting a similar histogenesis of these 2 subsets., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

T-cell-rich, large B-cell lymphoma (TCRLBCL) is the most commonly diagnosed type of lymphoma in horses. Here we describe the clinical signs, neuropathology, immunohistochemistry (IHC), and PCR for antigen receptor rearrangement (PARR) analysis results of a TCRLBCL in the brain of an 8-y-old male Quarter Horse that was euthanized after acute anorexia, tremors, head pressing, falling, blindness, incoordination, and seizures. Autopsy revealed a firm, smooth, pale-yellow mass that expanded both lateral ventricles and the adjacent subcortical white matter. Histologically, the mass consisted of a densely cellular neoplasm composed of large, CD79+ neoplastic B-lymphocytes admixed with sheets of small, CD3+ reactive T-lymphocytes, Iba1+ histiocytes, MUM1+ plasma cells, and rare eosinophils supported by a fine fibrovascular stroma. Formalin-fixed, paraffin-embedded tissue scrolls were retrieved and subjected to PARR analysis, which revealed a clonal reaction in the immunoglobulin gene and a polyclonal reaction for the T-lymphocyte receptor gene, consistent with a neoplastic B-lymphocyte and reactive T-lymphocyte proliferation. The diagnosis of TCRLBCL was suspected histologically and confirmed based on IHC and PARR analysis.

Canine diffuse large B-cell lymphoma (cDLBCL) is characterized by high mortality and clinical heterogeneity. Although chemo-immunotherapy improves outcome, treatment response remains mainly unpredictable. To identify a set of immune-related genes aberrantly regulated and impacting the prognosis, we explored the immune landscape of cDLBCL by NanoString. The immune gene expression profile of 48 fully clinically characterized cDLBCLs treated with chemo-immunotherapy was analyzed with the NanoString nCounter Canine IO Panel using RNA extracted from tumor tissue paraffin blocks. A Cox proportional-hazards model was used to design a prognostic gene signature. The Cox model identified a 6-gene signature ( IL2RB , BCL6 , TXK , C2 , CDKN2B, ITK ) strongly associated with lymphoma-specific survival, from which a risk score was calculated. Dogs were assigned to high-risk or low-risk groups according to the median score. Thirty-nine genes were differentially expressed between the 2 groups. Gene set analysis highlighted an upregulation of genes involved in complement activation, cytotoxicity, and antigen processing in low-risk dogs compared with high-risk dogs, whereas genes associated with cell cycle were downregulated in dogs with a lower risk. In line with these results, cell type profiling suggested the abundance of natural killer and CD8+ cells in low-risk dogs compared with high-risk dogs. Furthermore, the prognostic power of the risk score was validated in an independent cohort of cDLBCL. In conclusion, the 6-gene-derived risk score represents a robust biomarker in predicting the prognosis in cDLBCL. Moreover, our results suggest that enhanced tumor antigen recognition and cytotoxic activity are crucial in achieving a more effective response to chemo-immunotherapy.

A 17-y-old Rocky Mountain gelding was presented to the Virginia-Maryland Veterinary Teaching Hospital because of a 4-wk history of anorexia, weight loss, lethargy, and fever of unknown origin. Abdominal ultrasound revealed lymphadenomegaly of the abdominal and colonic lymph nodes, thickening of the wall of the large colon, and a mass associated with the large colon. The horse was euthanized given a poor prognosis. On autopsy, an ~20-cm diameter mass was found within the mesocolon between the right ventral and right dorsal colon. The mass had invaded through the colonic walls and formed a fistula between the 2 involved lumina. On histologic evaluation, the mass consisted of small numbers of large neoplastic lymphocytes, numerous small lymphocytes, and many foamy macrophages. A diagnosis of T-cell-rich, large B-cell lymphoma was made based on immunohistochemical staining for CD79a, CD3, and Iba1; concurrent infection with equid herpesvirus 5 was confirmed with in-situ hybridization (ISH). To our knowledge, neither a trans-colonic fistula resulting from alimentary lymphoma in a horse nor detection of intralesional equid herpesvirus 5 in equine alimentary lymphoma by ISH has been reported previously.

Expression of interferon regulatory factor 4 (IRF4)/multiple myeloma oncogene-1 (MUM1) in peripheral T-cell lymphoma (PTCL) in people is associated with a poorer survival outcome compared to cases of PTCL lacking MUM1 expression. The aim of this study was to determine whether MUM1 is expressed in canine peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). For comparison, the presence of MUM1 antigen was also investigated in canine diffuse large B cell lymphoma (DLBCL). Nine cases of PTCL-NOS and 9 cases of DLBCL diagnosed by a commercial veterinary diagnostic laboratory were selected. Positive immunohistochemical labeling for MUM1 was observed in PTCL-NOS (2 out of 9 cases) and DLBCL (3 out of 9 cases). These findings suggest that a subset of neoplastic T and B lymphocytes can express MUM1. The role of MUM1 in the biological behavior and outcome of canine lymphoma (CL) requires further investigation on a larger number of cases.

The most common subtype of lymphoma in the dog is diffuse large B-cell lymphoma (DLBCL). The remaining forms of B-cell lymphoma in dogs are categorized as small-to-intermediate in size and include marginal zone, follicular, mantle cell, and small-cell lymphocytic lymphoma. Marginal zone lymphoma and follicular lymphoma have readily identifiable unique histologic features while other forms of small B-cell lymphoma in the dog are poorly described by histopathology. Forty-seven cases of nodal small B-cell lymphoma identified by flow cytometry (small cell size based on forward scatter) with concurrent histopathology were reviewed. These cases fell into 3 histologic subtypes: marginal zone lymphoma, follicular lymphoma, and a diffuse form of small B-cell lymphoma with consistent features. As a descriptive term, we refer to the latter subtype as diffuse small B-cell lymphoma (DSBCL) until it can be further characterized by gene expression profiling and other molecular tools. Clinical presentation of DSBCL was compared to cases of histologically confirmed DLBCL and clinical follow-up was obtained for 22 of the 27 cases of DSBCL. This subset of diffuse small B-cell lymphoma had an overall median survival of 140 days. The expression of CD21, class II MHC and CD25 by flow cytometry did not differ between DSBCL and the other histologic subtypes of small cell B-cell lymphoma making histopathology the only current method of classification.

A 12-y-old, castrated male Pomeranian dog was presented because of mandibular lymph node (LN) enlargement. Physical examination and a complete blood count revealed generalized lymphadenopathy and moderate lymphocytosis. Fine-needle aspirate cytology revealed expansion of medium lymphocytes in the right mandibular LN and expansion of large lymphocytes in the left popliteal LN. Flow cytometry identified 2 aberrant lymphocyte populations in both LNs, namely a CD5+CD45- T-cell population, and a large CD21+ B-cell population. Flow cytometry of the peripheral blood revealed an identical population of aberrant CD45- T cells. The patient was diagnosed with concurrent T-zone lymphoma and leukemia, and B-cell lymphoma. Multi-agent chemotherapy was instituted, and serial clinical and flow cytometric analysis revealed complete remission of the neoplastic B cells, but persistence of the neoplastic T cells and persistent lymphadenopathy. This case affirms the diagnostic value of flow cytometry and reveals a unique limitation of the RECIST criteria.

An 8-y-old spayed female Beagle dog was presented with peripheral lymphadenomegaly. Lymph node cytology and flow cytometry led to the diagnosis of large B-cell lymphoma (LBCL). We detected minimal percentages of LBCL cells in peripheral blood and bone marrow samples. However, a monomorphic population of neoplastic cells different from those found in the lymph node was found in the bone marrow. T-cell acute lymphoblastic leukemia was suspected based on flow cytometric immunophenotyping. PCR for antigen receptor rearrangement (PARR) revealed clonal rearrangement of both B-cell and T-cell receptors, and the presence of both neoplastic clones in the lymph node, peripheral blood, and bone marrow. The dog was treated with multi-agent chemotherapy but died 46 d following diagnosis. Tumor staging and patient classification are needed to accurately establish a prognosis and select the most appropriate therapeutic protocol.

Lymphoma is among the most common cancer in dogs. Diffuse large B-cell lymphoma (DLBCL) is the predominant type, accounting for up to half of all cases. Definitive diagnosis of DLBCL relies on cytologic evaluation with immunophenotyping, or histopathology and immunohistochemistry when needed. A rapid and specific molecular test aiding in the diagnosis could be beneficial. Noncoding microRNAs (miRNAs) are regulators of gene expression involved in a variety of cellular processes, including cell differentiation, cell cycle progression, and apoptosis. Not surprisingly, miRNA expression is aberrant in diseases such as cancers. Their high stability and abundance in tissues make them promising biomarkers for diagnosing and monitoring diseases. This study aimed to identify miRNA signatures of DLBCL to develop ancillary molecular diagnostic tools. miRNA was isolated from formalin-fixed, paraffin-embedded lymph node tissue from 22 DLBCL and 14 nonneoplastic controls. Relative gene expression of 8 tumor-regulating miRNAs was achieved by RT-qPCR (reverse transcriptase quantitative polymerase chain reaction). The results showed downregulation of the let-7 family of miRNAs and miR-155 , whereas miR-34a was upregulated in DLBCL compared to the controls. We demonstrated that the combination of expression levels of miR-34a and let-7f or of let-7b and let-7f achieved 100% differentiation between DLBCL and controls. Furthermore, let-7f alone discriminated DLBCL from nonneoplastic tissue in 97% of cases. Our results represent one step forward in search of a rapid and accurate ancillary diagnostic test for DLBCL in dogs.

A 7-y-old mixed-breed male dog was presented with a history of generalized lymphadenopathy. Fine-needle aspirates of the enlarged peripheral lymph nodes were suggestive of lymphoma. Histologic examination of a retromandibular lymph node was suggestive of high-grade, medium large-cell lymphoma. Immunohistochemistry revealed concurrent expression of CD3 and CD20. The co-localization of the 2 antigens was confirmed by immunofluorescence. PCR for antigen receptor gene rearrangements (PARR) detected clonal rearrangements for both T-cell receptor gamma and B-cell receptor. The final diagnosis was CD3-CD20-positive anaplastic lymphoma with cross-lineage rearrangement.

A 4-year and 10-month old female Pembroke Welsh Corgi presented with an enlarged right popliteal lymph node, and a histopathological diagnosis of nodal marginal zone lymphoma (nMZL) was made. After resection of the lymph node, follow-up observation was continued without chemotherapy. At 22 months after initial presentation, the dog developed enlargement of peripheral lymph nodes, and the histopathological diagnosis was late-stage nMZL. Multidrug chemotherapy induced clinical complete remission, but the tumor relapsed with enlargement of peripheral and abdominal lymph nodes 42 months after initial presentation. Second-round multidrug chemotherapy induced complete clinical remission again; however, the tumor relapsed with lymphadenopathy 47 months after initial presentation. The dog died 59 months after initial presentation, and postmortem examination revealed generalized lymphadenopathy; the histopathological diagnosis was diffuse large B-cell lymphoma (DLBCL). Polymerase chain reaction for antigen receptor gene rearrangements revealed that the nMZL and DLBCL samples were derived from the same B-lymphocyte clone.

Lymphoma is the most common intestinal neoplasm in horses, but its clinical-pathological features are poorly characterized. Primary intestinal lymphoma was diagnosed in 20 horses on biopsy samples and further confirmed by postmortem examination in 16 cases. Lymphoma was found in the small intestine in 12 of 20 (60%), in the colon in 5 of 20 (25%), and in both small and large intestines in 3 of 20 (15%) cases. Gross findings included thickening of the intestinal wall (45%), mural nodules or masses (30%), and both thickening and nodules (10%). Cases were classified according to the human World Health Organization classification as enteropathy-associated T-cell lymphoma (EATL) type 1 (40%), EATL type 2 (45%), and T-cell-rich large B-cell lymphoma (TCRLBCL) (15%). With respect to histologic grade, 70% of cases were grade 1 and 30% were grade 2. Of EATLs, the infiltrate was mucosal only (12%), mucosal and submucosal (53%), or transmural (35%). EATL1 was submucosal to transmural (2/8 and 6/8), EATL2 was mucosal to submucosal (3/9 and 6/9), and TCRLBCL was always transmural. Epitheliotropism was present in most EATLs and characterized by single-cell infiltrates within the epithelium in EATL1 and intraepithelial clusters or plaques in EATL2. Median survival was 25 days for EATL1, 90 days for EATL2, and 187.5 days for TCRLBCL; differences were not statistically significant. Of the EATLs, grade 1 had a median survival of 60 days and grade 2 had a median survival of 25 days; differences were not statistically significant.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma in dogs. We evaluated Ki67 immunoexpression and mitotic index (MI) in dogs diagnosed with DLBCL and treated with a 19-wk CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) protocol. Twenty-nine lymph node samples from dogs diagnosed with DLBCL were analyzed for Ki67 immunostaining, and positive cells present in 1 cm 2 were counted in a grid reticle for comparison of survival times above and below the means. The Ki67 mean was 107, and the MI mean was 21. There was a significant ( p < 0.05) difference in median survival time between Ki67 immunostaining above and below the mean, with no difference in MI groups. Ki67 values >107 positive cells per 5 HPF counted in a grid reticle were associated with shorter survival times in dogs with DLBCL treated with a 19-wk CHOP-based protocol.

Lymphoma has been described in individual cases for goats but not systematically characterized in a larger cohort. This study aimed to subtype caprine lymphoma based on topographic and subgross distribution, immunophenotype, and cellular morphology following the World Health Organization classification system for hematopoietic tumors in domestic animals. Fifteen caprine lymphoma cases were assessed with 6 submitted as biopsy and 9 for postmortem examination. Goats were predominantly young adult (median 3 years) and dwarf breeds (Pygmy and Pygora). The sexes were similarly represented. Nuclear size was measured relative to red blood cells (RBCs) and then adjusted for species-specific differences and designated small (<3× RBCs), intermediate (3-4× RBCs), or large (>4× RBCs). Using immunohistochemistry, 11 of 15 (73%) goats had T-cell lymphoma (TCL; CD3 positive, CD79α negative) and 4 of 15 (27%) had B-cell lymphoma (BCL; CD79α positive, CD3 negative). A multicentric distribution was most common. TCL generally involved the thoracic cavity and/or neck, suggestive of thymic origin or homing. TCLs were further classified as lymphoblastic lymphomas (3/11; 27%), large granular lymphocyte lymphoma (1/11; 9%), diffuse small lymphocytic lymphomas (3/11; 27%), or peripheral/mature T-cell lymphoma (PTCL) not otherwise specified (4/11 [36%], of which 3 were high grade and 1 intermediate grade). In 1 goat with PTCL, lymph nodes had either paracortical expansion or diffuse infiltrates suggesting transition from nodular to diffuse PTLC. BCLs were classified as diffuse large B-cell lymphoma (2/4; 50%) or B-cell lymphocytic lymphoma intermediate type (2/4; 50%). In contrast to dogs and horses, lymphomas in goats are predominantly TCL and frequently involve the mediastinum.

Cutaneous lymphoma is a common skin neoplasm of pet rabbits in Europe but is rarely reported in pet rabbits in North America. These neoplasms have not been previously characterized, nor has the cause for the apparent predilection for cutaneous lymphoma in European pet rabbits compared with North American pet rabbits been investigated. In this retrospective study, the authors morphologically and immunohistochemically characterized 25 cutaneous lymphomas in European pet rabbits according to the World Health Organization classification. Tumors were classified as diffuse large B cell lymphomas, with 14 lymphomas exhibiting a centroblastic/centrocytic subtype and 11 tumors exhibiting a T cell-rich B cell subtype. To investigate a potential viral etiology of these lymphomas, 3 diffuse large B cell and 3 T cell-rich B cell lymphomas were evaluated by polymerase chain reaction for retroviral and herpesviral genes. Neither virus was detected. In contrast to other domestic animals, cutaneous lymphomas in European pet rabbits were highly pleomorphic and frequently contained multinucleated giant cells. Unexpectedly, the second most common subtype was T cell-rich B cell lymphoma, a subtype that is rare in species other than horses. Based on a limited number of samples, there was no support for a viral etiology that would explain the higher incidence of lymphoma in European pet rabbits compared with American pet rabbits. Further investigation into genetic and extrinsic factors associated with the development of these tumors is warranted.

A 12-year-old Persian cat was examined for a firm swelling of the right tarsal region and enlargement of the corresponding right popliteal lymph node. Cytologic evaluation demonstrated a population of malignant cells consistent with large cell lymphoma. Necropsy revealed a multi-lobulated subcutaneous mass involving the tarsus with some extension into adjacent deep muscular tissue. Histologically, the mass was composed of round cells with eosinophilic cytoplasm and pleomorphic anisokaryotic nuclei. Evidence of articular and nodal infiltration by these cells was observed. Differential diagnoses included synovial sarcoma and histiocytic sarcoma. Neoplastic cells were negative for cytokeratin, CD79a, and CD3 and positive for CD18, vimentin, lysozyme, and alpha-1-antitrypsin, most consistent with a diagnosis of histiocytic sarcoma. This is the first report of a histiocytic sarcoma involving a joint of a cat. The final diagnosis was based on the light microscopic appearance in combination with the immunohistochemical stains.

A 12-year-old Appaloosa gelding was referred to the Texas Veterinary Medical Center with a history of chronic diarrhea and weight loss. At necropsy, numerous oval, craterlike ulcers were observed throughout the small intestine. Histologically, these lesions were composed of a neoplastic proliferation of round cells with intracytoplasmic phosphotungstic acid-hematoxylin-positive granules. The tumor cells stained positively for the CD3 antigen and negatively for a B-cell marker. A diagnosis of large granular lymphoma was based on the morphologic and immunohistochemical characteristics of the neoplasm. The postmortem presentation of this case depicted unusual multifocal, ulcerative lymphomatous lesions throughout the small intestine without involvement of the regional lymph nodes. The histologic and ultrastructural morphology of the neoplastic lymphocytes was similar to that in previously reported cases of abdominal equine large granular lymphomas, but in this case the neoplasm was restricted to the small intestine.

The recent application of neuroimaging techniques in veterinary neurology has led to the accurate localization of many types of intracranial lesions but has also created a clinical need, particularly with brain tumors, for a specific intraoperative diagnosis. For human brain tumors, a smear technique has been used successfully for many years to provide an extremely rapid, highly accurate intraoperative diagnosis. In similar smear preparations of intracranial lesions, obtained either by computed tomography (CT)-guided stereobiopsy or from a craniotomy, we have described distinguishing cytologic features of some primary spontaneous nervous system tumors in 80 dogs and 13 cats. A final diagnosis was confirmed by evaluation of paraffin-embedded sections from the same sample and, when appropriate, by immunocytochemical staining. Preliminary findings indicate that, in dogs and cats, this procedure is useful for rapid, accurate intraoperative diagnosis of many primary nervous system tumors. The distinguishing features of the canine and feline tumors bear a remarkably close resemblance to their human counterparts.

This report describes six cases of feline large granular lymphocyte lymphoma identified by light microscopy on the basis of their characteristic azurophilic granulation in Giemsa-stained plastic sections and by electron microscopy on the basis of their typical granules. Although the granules of all the tumor cells were negative for peroxidase activity, they all demonstrated chloroacetate-esterase and acid phosphatase activity. All the tumors reacted with cross-reacting antibodies against the CD3 antigen (epsilon chain) and did not react with a cross-reacting monoclonal antibody directed against epitopes on cytoplasmic domains of the CD20 antigen. Three tumors had a positive reaction with a monoclonal human CD57-like antibody. This is highly suggestive of either a cytotoxic T cell or a natural killer cell origin of the neoplasias. In three cats, although other abdominal organs were affected to a variable extent, the main neoplastic lesions were localized in the gastrointestinal tract and the jejunal lymph nodes. In contrast, in the other three cats, organ involvement was more widespread, affecting the lung (two), myocardium (two), precardiac mediastinum (one), salivary gland (one), and spinal cord (one); in addition, leukemia was present in two of these cats. The data presented indicate that tumors made up of large granular lymphocytes occur more frequently in cats than previously assumed and that they share many characteristic features with specific subtypes of clonal disorders of large granular lymphocytes in humans.

Gross lesions, microscopic appearance, and immunophenotyping are reported in a retrospective study of 31 cases of equine malignant lymphoma. Immunohistochemical studies were performed on archived formalin-fixed, paraffin-embedded tissues. Monoclonal antibodies to surface glycoprotein BLA.36 and intracytoplasmic domains of mb-1 and B29 were used to document the presence of B lymphocytes in the equine tumors. Polyclonal antibody to CD3 and monoclonal antibodies to T-lymphocyte markers CD3 and CD5 revealed the presence of variable numbers of T cells within the equine lymphomas. The neoplastic component of the equine lymphomas was determined through morphologic evaluation, immunophenotyping, and the use of proliferation markers Ki-67 and proliferating cell nuclear antigen. Equine malignant lymphomas were composed of a heterogeneous cell population. Most tumors contained B and T lymphocytes. Twenty-four horses had diffuse lymphomas derived from B lymphocytes. Thirteen of these lymphomas contained primarily neoplastic B lymphocytes. Eleven additional cases of diffuse large B-cell lymphoma contained from 40% to 80% nonneoplastic T lymphocytes and were classified as T-cell-rich, large B-cell lymphomas. This is the first description of T-cell-rich, B-cell lymphoma in the horse. Six tumors with a diffuse architecture were derived from T lymphocytes. Four T-cell tumors were large-cell tumors, 1 was a small-cell tumor, and in 1 tumor the size of the cells could not be determined accurately because of autolytic change in the tissues. One diffuse large-cell lymphoma did not react with either B- or T-cell markers.

A prospective analysis of 38 cases of bovine lymphoma was performed. Thirty-five of the lymphomas were considered enzootic because of serologic or molecular biologic association with the bovine leukemia virus (BLV). The three remaining cases were in cattle < 1 year of age and were not associated with BLV and hence were considered sporadic lymphomas. Utilizing the national cancer Institute Working Formulation for the morphologic classification of human non-Hodgkin's lymphoma, 54.3% (19/35) of the enzootic lymphomas were classified as the diffuse large cleaved cell type. The cells of the 35 enzootic lymphomas expressed a consistent immunophenotype represented by MHCII+, gamma-heavy chain+, and lambda-light chain+; this constellation of markers indicated a mature B-cell phenotype. The three sporadic lymphomas failed to express MHCII antigen despite the presence of other B-cell antigens. There was no correlation between morphologic cell type and immunophenotype in these bovine lymphomas.

A retrospective histologic study was made of 1,198 cases of bovine lymphoma using the National Cancer Institute Working Formulation for human non-Hodgkin's lymphoma. This classification scheme was found to be readily applicable to bovine lymphoma. Most of the cell types described in the National Cancer Institute Working Formulation occurred in this series of bovine lymphomas, but the distribution of cell types varied markedly compared to that of human beings. Eighty-nine percent (1,067/1,198) of bovine lymphomas were high-grade tumors. The diffuse large cell type and its cleaved variant comprised 65.9% of all bovine lymphomas. Similar to the dog, but in marked contrast to human beings where at least 34% of non-Hodgkin's lymphomas were follicular, follicular tumors were found to be extremely rare in cattle (0.3% or 4/1,198). The prevalence of cell types varied significantly between the enzootic and sporadic lymphomas. The cleaved variant of the diffuse large cell type constituted 38% (406/1,072) of enzootic lymphomas versus 14% (18/126) of sporadic lymphomas. The mitotic index (100 x oil immersion field, 175 microns in diameter) of enzootic lymphomas (3.72 +/- 0.06, mean +/- standard error) was significantly greater than the mitotic index of sporadic lymphomas (2.82 +/- 0.17). We concluded that the cleaved variant of the diffuse large cell type with high mitotic index is characteristic of enzootic lymphoma. This characteristic high-grade cell type may be a consequence of the viral etiology of the enzootic form of bovine lymphoma.

Malignant lymphoma occurred in six Macaca arctoides from a colony of 83 animals during a 30-month period. The cells of two neoplasms had T cell markers. Concurrent disease processes included atypical mycobacterial disease in four macaques and progressive multifocal leukoencephalopathy in one.

Clinicopathological findings of three different neoplastic conditions involving the spinal cord and nerve roots in three dogs are described. One sarcomatous intra-medullary tumor closely associated with the vasculature was classified as a reticulum cell sarcoma of the spinal cord. The second case had massive and widespread neoplastic proliferation of reticulohistiocytic cells around the perineurinal vessels of many spinal nerve roots. The process was classified as a primary neoplastic reticulosis of the spinal roots. Multiple highly malignant tumors, infiltrating the spinal cord were found in one thoracic and several lumbosacral spinal nerve roots in the third case. These were considered to be anaplastic neurofibrosarcomas because of high collagen content, intact nerve fibers, whorl formation, and the tendency to palisade in some areas.

Immunoreactive lysozyme was readily detectable in canine histiocytic disorders including systemic histiocytosis, malignant histiocytosis and granulomatous panniculitis. Lysozyme was less reliable as a histiocytic marker in cutaneous histiocytoma; forty percent of these tumors were negative for lysozyme expression. The marked heterogeneity in lysozyme expression in cutaneous histiocytoma may indicate that a proportion of these tumors show relatively primitive histiocytic differentiation and do not express lysozyme. Alternatively, this same proportion may exhibit a phenotype akin to cutaneous Langerhans cells which do not contain lysozyme. Lysozyme was not detectable in the tumor cells in lymphomatoid granulomatosis, atypical cutaneous histiocytoma, and histiocytic lymphosarcoma. Other evidence that these three disorders do not represent true histiocytic proliferative disorders is discussed.