Lymphocytosis and lymphadenopathy in a dog arising from two distinct lymphoid neoplasms

A 10-year-old intact male Golden Retriever was presented to The Ohio State University Veterinary Medical Center for acute, non-painful facial swelling of the right mandibular region. On physical examination, the right mandibular swelling was found to represent marked lymphadenopathy of the submandibular lymph node. At this time, marked lymphadenopathy of the prescapular and popliteal lymph nodes was also appreciated. The CBC showed a moderate leukocytosis (38.4 × 10⁹ cells/L, reference interval [RI] 4.8-13.9 × 10⁹ cells/L) characterized by a moderate lymphocytosis (28.4 × 10⁹ cells/L, RI 1.0-4.6 × 10⁹ cells/L). Evaluation of peripheral blood and enlarged prescapular and popliteal lymph nodes revealed two morphologically different populations of homogeneous lymphocytes, with the lymphocyte population in the lymph nodes being distinct from that in the blood smear. Flow cytometry of peripheral blood revealed CD45-, CD5+, CD4-, CD8-, variably CD21+ neoplastic lymphocytes compatible with T-zone lymphocytes due to the absence of CD45 expression. Flow cytometry of the lymph node aspirate indicated a distinct population of CD21+ lymphocytes consistent with a B-cell phenotype along with a smaller proportion of the T-zone lymphocytes observed in the blood confirming the presence of two distinct populations of neoplastic lymphocytes, one involving T cells, and the other involving B cells.     

Paraneoplastic hypereosinophilia in a dog with intestinal T-cell lymphoma

A 9-year-old, intact male Doberman Pinscher was examined because of anorexia and weakness. Results of a CBC showed severe, microcytic, hypochromic anemia with mild eosinophilia (2944 cells/microL, reference interval 100-1250/microL) and thrombocytosis. Hypoferremia, hypoferritinemia, and a positive fecal occult blood test supported a diagnosis of iron deficiency anemia secondary to chronic intestinal hemorrhage. Abdominal ultrasound evaluation showed a thickened small intestinal loop, of which representative specimens were obtained during exploratory laparotomy. Histologically, the intestinal wall was infiltrated by a neoplastic population of large, round, lymphoid cells with vesicular chromatin, 1 or more prominent nucleoli, and a high number of mitotic figures. The cells were closely admixed with mature eosinophils, but were negative for metachromatic granules with toluidine blue. Immunohistochemically, tumor cells were positive for CD3, and negative for CD21, Pan B, and CD79a. A diagnosis of intestinal T-cell lymphoma was made. Chemotherapy was begun, with 30 mg/m;2 of doxorubicin administered intravenously every 3 weeks. Eosinophil concentration was 880/microL 2 weeks after surgery (on day 15 after presentation) but increased markedly to 62,914/microL on day 30, 62,400/microL on day 37, and 39,444/microL on day 58 after presentation. An association between hypereosinophilia and T-cell lymphoma is well established in human patients, in whom production of IL-5 by neoplastic T cells has been demonstrated. Hypereosinophilia has been reported only rarely with intestinal lymphoma in cats and horses, and with T-cell lymphoma in dogs.     

Morphologic, immunohistochemical, and molecular characterization of hepatosplenic T-cell lymphoma in a dog

A 13-year-old neutered male Jack Russell Terrier (Parson Russell Terrier) was presented to the Texas Veterinary Medical Center with a history of lethargy, depression, vomiting, and fever. The dog had mildly regenerative anemia, severe thrombocytopenia and low antithrombin activity. Marked splenomegaly was found on physical examination and imaging studies, and malignant round cell neoplasia and marked extramedullary hematopoiesis were diagnosed on aspirates of the spleen. The dog underwent exploratory laporatomy and splenectomy. Because of a rapid decline in clinical condition postsurgery, the dog was euthanized. Splenic and hepatic biopsies were submitted for histopathologic evaluation. A neoplastic population of round cells was found throughout the splenic parenchyma and within hepatic sinusoids. The neoplastic cells stained strongly positive for CD3 (T-cell marker) and were negative for CD79a (B-cell marker) and lysozyme (histiocytic marker). A diagnosis of T-cell lymphoma was confirmed by assessment of T-cell clonality using canine-specific polymerase chain reaction-based techniques. Although expression of the gammadelta T-cell receptor was not evaluated, this case shares many similarities with a rare syndrome in humans known as hepatosplenic gammadelta T-cell lymphoma.     

B‐cell intestinal lymphoma with Mott cell differentiation in a 1‐year‐old miniature Dachshund

Abstract: A 1‐year‐old intact female miniature Dachshund was presented with hematochezia, vomiting, and diarrhea of more than 1‐week duration. An abdominal mass was palpated, which at exploratory surgery was found to be a 7‐cm‐long thickened section of ileum. The thickened ileum was resected. Impression smears revealed numerous small‐ to medium‐sized lymphocytes, with a smaller number of cells resembling Mott cells. The Mott‐like cells contained multiple pale vacuoles that were positive for periodic acid‐Schiff (PAS) in wet‐fixed smears, consistent with Russell bodies. Histologic evaluation of the surgically excised ileum revealed 2 populations of neoplastic lymphoid cells. The majority were uniform medium‐sized lymphocytes with hyperchromatic oval or round nuclei and inconspicuous nucleoli. The remaining cells resembled Mott cells, which contained several PAS‐positive eosinophilic globules in the cytoplasm, occasionally compressing the nucleus. The majority of neoplastic cells stained positively for vimentin, CD20, CD79a, and Pax‐5, but were negative for CD3 and lysozyme; 43.5% of cells stained positively for Ki‐67. The Mott cells were strongly positive for immunoglobulin but were negative for Pax‐5. Using electron microscopy, a homogenous substance of intermediate electron density was observed frequently in the cisternae of rough endoplasmic reticulum in the cytoplasm of the Mott cells, and rarely in the perinuclear cisternae of the lymphoid cells, corresponding to the site of immunoglobulin staining. Monoclonal rearrangement of immunoglobulin heavy‐chain (IgH) gene was observed by PCR testing for lymphocyte–antigen receptor rearrangement. The morphologic features, immunophenotype, and IgH gene rearrangement verified the lymphoid cells were neoplastic (mature cell type) and had a B‐cell phenotype, with evidence of immunoglobulin production and differentiation into Mott cells. This case was unusual because of the age of the dog and because most intestinal lymphomas are T‐cell phenotype. The Mott cell morphology also differed from typical mature B‐cell lymphoma types and may be a unique B‐cell lymphoma variant.     

Anterior uveitis as an atypical presentation of large granular lymphoma in a caracal (Caracal caracal)

An 11-year-old, female, spayed caracal (Caracal caracal) presented with a 3-month history of intermittent anorexia, vomiting, and weight loss. At examination, bilateral anterior uveitis with anisocoria was present. Further examination under general anesthesia revealed the anterior chamber of the right eye contained copious amounts of thick fibrin, hypopyon, and hyphema obscuring the ventral pupil margin and ventral iris. Aqueous paracentesis revealed a cytologic diagnosis of large granular lymphoma. Additional antemortem diagnostics (computed tomography, ultrasound with fine needle aspiration, and cytology) confirmed the diagnosis of multicentric large granular lymphoma with associated intestinal perforation. Necropsy and histopathology confirmed multicentric large granular lymphoma in the right eye, jejunum, mesenteric lymph nodes, and right kidney. Large granular lymphoma in nondomestic felids is likely rare since it has not been previously reported, but should be considered as a differential in any felid species with anterior uveitis or when lymphoma is considered. In the case of this caracal, the use of aqueous paracentesis with cytology was a powerful diagnostic.     

Lymphoma with cutaneous involvement in three domestic rabbits (Oryctolagus cuniculus)

Three domestic rabbits ( Oryctolagus cuniculus ) with cutaneous lymphoma are described. Two rabbits were young (7 weeks and 1 years) and were euthanized within 1 week of showing clinical signs. Lymphoma was found in the skin and internal organs. The third rabbit was 9.5 years of age, and lived for more than 1 year after diagnosis. No response was seen to either 2 months of alpha-interferon administration or a 2.5-week course of isotretinoin treatment. After 1 year the rabbit died suddenly; the owner refused necropsy. Immunologic stains of the tumour in all three rabbits showed T cells to be the lymphoma cell type.     

A case of hemophagocytic syndrome progressing into large granular lymphoma in a dog

A 12‐year‐old castrated male mixed breed dog was presented with anorexia, lethargy, intermittent vomiting, diarrhea, and weight loss. Clinicopathologic and imaging abnormalities included pancytopenia, icterus, and splenomegaly with multiple minute hypoechogenic nodules. Bone marrow (BM) smears revealed 2.5% hemophagocytic macrophages. In addition, an increased number of small to intermediate lymphocytes (16.3%) and plasma cells (3.2%) were recognized in the BM smears. More than 80% of the lymphocytes contained multiple small intracytoplasmic magenta granules. Histopathologic findings of the spleen revealed hemophagocytosis. Large granular lymphocytes (LGLs) were not found on the liver cytology or splenic histopathology at this time. PCR for antigen receptor rearrangement (PARR) analysis showed a clonal reaction in the T‐cell receptor ? (TCR?) gene in the BM sample. The dog was diagnosed with hemophagocytic syndrome (HPS). The dog was maintained in good condition with immunosuppressive therapy. However, the dog developed hepatic LGL lymphoma 7 months later. At this time, PARR analysis showed a clonal TCR? gene rearrangement in the hepatic LGL lymphoma samples. The BM and liver sample clonal rearrangements showed 100% homology, indicating that the small to intermediate granular lymphocytes in the BM at the HPS stage had progressed to hepatic LGL lymphoma. To our knowledge, this is the first report of canine secondary HPS caused by the occurrence of a BM LGL lymphoma clone that progressed to hepatic LGL lymphoma.     

MRI characteristics of ventral vertebral venous plexus occlusion due to lymphoma in a large breed dog

Intravascular lymphoma is a rare presentation of lymphoma with a predilection to the central nervous system (CNS). A 9-year-old male-neutered Collie presented with a 3-month history of lymphadenopathy and a 6-day history of an acute onset, progressive, painful, symmetrical L4-S3 myelopathy. Magnetic resonance imaging revealed multifocal extradural spinal cord compressions from L3 to L6 secondary to a bilaterally enlarged and occluded ventral vertebral venous plexus (VVVP). Histopathology revealed low-grade lymphoma within the venous plexus in the lumbar vertebral column, tracheobronchial lymph nodes, and tonsils. Intravascular lymphoma should be considered a differential diagnosis for enlarged VVVP causing compression of the spinal cord.     

Radiotherapy in the management of localized mucocutaneous oral lymphoma in dogs: 14 cases

Oral mucocutaneous lymphoma is rare in dogs. Surgery and chemotherapy do not usually provide effective long-term control. The objective of this study was to retrospectively evaluate survival of dogs with localized oral lymphoma treated with radiation therapy. The medical database of three institutions was searched for dogs with diagnosis of oral lymphoma treated with radiotherapy. Dogs with evidence of systemic disease were excluded. Survival was calculated with the Kaplan-Meier method and prognostic variables analysed with log-rank test. Fourteen dogs were included in the study. Mean survival was 1129 days [95% confidence interval (CI) 711-1546] with median survival of 770 days. The overall response of radiotherapy was 67% (five complete and three partial responses). A survival advantage was seen in dogs with no evidence of lymph node metastasis (P = 0.002) and that achieved a complete response to radiation therapy (P = 0.013). Radiation therapy was a well-tolerated and effective treatment for localized oral lymphoma.     

Canine nodal marginal zone lymphoma: Descriptive insight into the biological behaviour

Canine nodal marginal zone lymphoma (nMZL) is classified as an indolent lymphoma. Such lymphomas are typified by low mitotic rate and slow clinical progression. While the clinical behaviour of canine splenic MZL has been described, characterized by an indolent course and a good prognosis following splenectomy, there are no studies specifically describing nMZL. The aim of this study was to describe the clinical features of and outcome for canine nMZL. Dogs with histologically confirmed nMZL undergoing a complete staging work‐up (including blood analysis, flow cytometry [FC] on lymph node [LN], peripheral blood and bone marrow, imaging, histology and immunohistochemistry on a surgically removed peripheral LN) were retrospectively enrolled. Treatment consisted of chemotherapy or chemo‐immunotherapy. Endpoints were response rate (RR), time to progression (TTP) and lymphoma‐specific survival (LSS). A total of 35 cases were enrolled. At diagnosis, all dogs showed generalized lymphadenopathy. One‐third was systemically unwell. All dogs had stage V disease; one‐third also had extranodal involvement. The LN population was mainly composed of medium‐sized CD21+ cells with scant resident normal lymphocytes. Histology revealed diffuse LN involvement, referring to “late‐stage” MZL. Median TTP and LSS were 149 and 259 days, respectively. Increased LDH activity and substage b were significantly associated with a shorter LSS. Dogs with nMZL may show generalized lymphadenopathy and an advanced disease stage. Overall, the outcome is poor, despite the “indolent” designation. The best treatment option still needs to be defined.     

Differences in the geographic distribution of lymphoma subtypes in Golden retrievers in the USA

The purpose of this cross‐sectional study was to examine differences in the geographic distribution of two distinct subtypes of canine lymphoma (CL), B‐cell lymphoma (BCL) and T‐zone lymphoma (TZL), in the USA while accounting for heritable risks associated with the outcome of disease through inclusion of only one breed of dog. This study included 454 Golden retrievers and associations between geographic areas of the USA and the phenotypic variant of lymphoma were examined using multivariable logistic regression. There was a detectable difference in the geographic distribution of BCL and TZL with dogs in the Northeast [odds ratio (OR) = 3.4, 95% confidence interval (CI) = 1.6–7.0] and East North Central regions (OR = 12.1, 95%CI = 3.6–40.5) being more likely to be diagnosed with TZL as compared to dogs in the Mountain region of the USA. The finding of non‐random geographic distribution of lymphoma subtypes suggest that environmental risk factors may contribute to the development of different types of CL.     

Canine cutaneous epitheliotropic T‐cell lymphoma: a review

Cutaneous epitheliotropic T‐cell lymphoma in the dog is a rare neoplastic condition with unknown aetiology. The dermatitis is characterized by infiltration of neoplastic T lymphocytes with a specific tropism for the epidermis and the adnexal structures. The different clinical and histological forms (mycosis fungoides, pagetoid reticulosis and Sézary syndrome) are reviewed. The disease in the dog resembles the human syndrome, but in 80% of the canine cases, neoplastic cells are CD4^?/CD8⁺ versus CD4⁺/CD8^? in 90% of the human patients. Prognosis is poor with a survival time from few months to 2 years. Treatments frequently have a low efficacy. New protocols using lomustine may improve the poor prognosis of the disease.     

CHEMOTHERAPY FOLLOWED BY ABDOMINAL CAVITY IRRADIATION FOR FELINE LYMPHOBLASTIC LYMPHOMA

Combination chemotherapy is standard care for feline lymphoma, although clinically relevant improvements in remission duration are unlikely to result from manipulations of chemotherapy agents alone. Lymphopoietic tissues generally are sensitive to radiation, and support for chemoradiotherapy as a treatment for lymphoma is found in both humans and dogs. The goal of this prospective pilot study was to determine the normal tissue tolerance to 15 Gy total abdomen fractionated radiation therapy following induction chemotherapy in cats with lymphoblastic lymphoma. Eight cats with lymphoblastic gastrointestinal or multicentric lymphoma confined to the abdominal cavity were treated with a 6‐week combination chemotherapy protocol followed 2 weeks later by whole‐abdomen radiation therapy consisting of 10 daily fractions of 1.5 Gy. Treatment was well tolerated; renal insufficiency documented in one cat at the start of radiation therapy progressed to stable chronic renal failure. One cat not in complete remission at the time of radiation therapy relapsed 2 weeks later, one cat with multicentric lymphoma relapsed with hepatic large granular lymphoma, and one cat was euthanatized 3 weeks following completion of radiation therapy for other reasons; no evidence of lymphoma or radiation toxicoses was identified on post mortem evaluation. The remaining five cats remain in remission at least 266 days after starting therapy; median remission duration has not been reached (range, >266 to >1332 days). Results of this study suggest that 15 Gy total abdomen fractionated radiation therapy after induction chemotherapy is tolerated satisfactorily. This protocol is suitable for further testing to quantify efficacy.     

RADIOTHERAPY WITH AND WITHOUT CHEMOTHERAPY FOR LOCALIZED LYMPHOMA IN 10 CATS

A retrospective study was undertaken to determine the efficacy of radiotherapy with and without chemotherapy for treatment of localized lymphoma in 10 cats. Tumor location included nasal cavity (3 cats), retrobulbar area (3 cats), mediastinum (1 cat), subcutaneous tissue (1 cat), maxilla (1 cat) and mandible (1 cat). Six cats were treated with radiation alone and 4 cats also received chemotherapy during and/or after radiotherapy. Complete remission was achieved locally in 8 of 10 cats, whereas 2 cats had partial remission. Five of the 6 cats treated with radiotherapy alone achieved complete remission. Overall mean and median remission times for the 8 cats with complete remission were 123 weeks and 114 weeks, respectively (range 4 to 277 weeks). Three of the 8 cats have been in complete remission for more than 131 weeks and are still alive. Three cats achieving complete local remission developed lymphoma outside the radiation field. One cat had recurrence at the site of irradiation. Results of the retrospective study suggest that radiotherapy with and without chemotherapy may be effective for the treatment of localized lymphoma in the cat.     

Presumptive precursor-targeted immune-mediated anemia concurrent with gastrointestinal lymphoma in a cat

A 10-year-old spayed female mixed-breed cat presented with progressive nonregenerative anemia. Clinicopathological abnormalities included severe nonregenerative anemia (packed cell volume [PCV]: 7%, aggregate reticulocytes: 1.12 × 10³/µl) and a hypoechogenic mass well-localized in the stomach. Bone marrow (BM) smears revealed increased particle hematopoietic cellularity with decreased myeloid:erythroid (M:E) ratios, no dysplasia of any lineage, and presence of erythroid precursors phagocytized by macrophages. The cat was diagnosed with presumptive precursor-targeted immune-mediated anemia (PIMA). The stomach mass was consistent with CD 20 positive T-cell lymphoma. The lymphoma was completely resected via surgery, and the PIMA was cured by immunosuppressive therapy. On day 410, both diseases have not recurred without medications. This is the first report of feline PIMA and concurrent gastrointestinal lymphoma.     

Marginal zone lymphoma in a dog

A 13-year-old spayed female American Cocker Spaniel was presented for evaluation of a cough and weight loss. Physical exam revealed generalized lymphadenopathy. The patient was diagnosed with marginal zone lymphoma (MZL) on histopathology of an extirpated lymph node. This report demonstrates an unusual case of a pleomorphic neoplastic population documented on cytologic evaluation that had moncytoid features and peripheral blood involvement; a previously undocumented IgG1 monoclonal gammopathy was also an interesting feature of this canine MZL. The patient did not undergo chemotherapy for lymphoma and was euthanized over 4 years after the initial presentation.