Renal T-cell lymphoma with cerebral metastasis in a dog with chronic canine ehrlichiosis

A renal T-cell lymphoma with exclusive cerebral metastasis was diagnosed in a 5-year-old Staffordshire bull terrier bitch euthanased for aggression. This is the first recorded case of primary renal lymphoma in a dog. Immune suppression, due to chronic canine monocytic ehrlichiosis, may account for the unusual primary site and metastatic pattern of the tumour.     

A retrospective study of 61 cases of spontaneous canine epistaxis (1998 to 2001)

OBJECTIVES: To determine the prevalence and identify possible clinicopathologic indicators of the diseases associated with canine epistaxis. METHODS: The medical records of 61 dogs with epistaxis were reviewed. RESULTS: Systemic diseases, diagnosed in fifty-six dogs, included canine leishmaniasis in twenty-three dogs, canine monocytic ehrlichiosis in twenty-two, concurrent canine leishmaniasis and canine monocytic ehrlichiosis in six, rodenticide toxicity in two and primary immune-mediated thrombocytopenia, suspected oestrogen toxicity and systemic arterial hypertension in one dog each. Intranasal diseases were documented in the remaining five dogs, including transmissible venereal tumour in three dogs, and nasal adenocarcinoma and nasal aspergillosis in one dog each. Mucosal pallor and a generalised bleeding tendency were significantly more common among dogs with canine monocytic ehrlichiosis compared with those with canine leishmaniasis, whereas the opposite was true for peripheral lymphadenomegaly. Also, dogs with canine monocytic ehrlichiosis presented with pancytopenia more frequently compared with those with canine leishmaniasis; in the latter dogs, the median values of haematocrit, leucocyte and platelet counts and serum total protein concentrations were higher. CLINICAL SIGNIFICANCE: Canine leishmaniasis and canine monocytic ehrlichiosis are the leading causes of canine epistaxis in Greece. Mucosal pallor, bleeding tendency and pancytopenia are more likely to be indicative of canine monocytic ehrlichiosis, as opposed to peripheral lymphadenomegaly and hyperproteinaemia in canine leishmaniasis.     

Genetic characterization of Anaplasma (Ehrlichia) platys in dogs in Spain

This paper reports the first genetic characterization of Anaplasma (Ehrlichia) platys in Spain from a naturally infected dog. The dog presented clinical signs compatible with canine ehrlichiosis. After DNA extraction and PCR amplification, 16S rRNA gene and citrate synthase gene ( gltA) of this agent were amplified. The GenBank accession number for the nucleotide sequence of the 16S rRNA gene of this strain is AY530806. The A. platys strains registered in France and Japan showed the highest similarity to the 16S rRNA gene sequence obtained from the Spanish strain. In the amplification of the gltA gene, a 1443 bp fragment was obtained, and three nucleotide differences were detected in comparison with other strains sequences. These data confirm the presence of A. platys in a dog showing clinical signs compatible with ehrlichiosis in Spain.     

Parathyroid hormone-related protein (PTHrP) produced by dog lymphoma cells

Parathyroid hormone-related protein (PTHrP) was investigated in a canine lymphoma case with hypercalcemia by means of immunoradiomentric assay (IRMA) and molecular analysis. The plasma calcium level of the patient dog was 13.7 mg/dl. The PTHrP concentration examined by IRMA was 6.1 pmol/L in the plasma sample from the dog, but it was undetectable (< 1.1 pmol/L) in plasma samples from 4 lymphoma cases without hypercalcemia or 5 normal dogs. The PTHrP concentration examined in the culture supernatant of the lymphoma cells from this case was 1.3 pmol/L, whereas those of the lymphoma cells from a lymphoma case without hypercalcemia was undetectable. PTHrP mRNA was clearly detected not only in the lymphoma cells from this dog with hypercalcemia but also in lymphoma cells from 4 lymphoma cases without hypercalcemia and 2 canine lymphoma cell lines.     

Progression of an orbital T-cell rich B-cell lymphoma to a B-cell lymphoma in a dog

An 11-year-old Shetland Sheepdog was presented for exophthalmos caused by a locally extensive, poorly defined mass located behind the right eye. The primary orbital mass was identified by light microscopy and immunohistochemistry as a T-cell rich B-cell lymphoma (TCRBCL) composed predominantly of BLA.36-positive large neoplastic lymphoid cells admixed with fewer CD3- and CD79a-positive small lymphocytes. The dog was treated for lymphoma, but 6 months after presentation it was euthanatized for suspected hepatic and gastrointestinal metastasis. Gross findings revealed an enlarged liver with multiple well-demarcated, randomly distributed 0.1-1.5-cm white nodules, five firm white submucosal jejunal nodules, and ileocecal, mediastinal, and hilar lymphadenopathy. Metastatic liver lesions consisted of sheets of monomorphic large neoplastic lymphoid cells that effaced and expanded portal and centrilobular zones. These cells were morphologically similar to the large neoplastic cells of the original orbital tumor and were CD3-negative and variably BLA.36-positive, consistent with B-cell lineage. Similar cells comprised the jejunal nodules and effaced the lymph nodes. The progression of TCRBCL to a diffuse B-cell lymphoma in this case is consistent with reported human cases and has not been previously reported in the dog.     

Counterimmunoelectrophoresis (immunoelectroosmosis) and serum electrophoretic pattern in serologic diagnosis of canine blastomycosis

Counterimmunoelectrophoresis (CIEP) with blastomyces and histoplasma antigens was used in a serologic study of 181 dogs clinically suspected of having blastomycosis and of 8 dogs with confirmed blastomycosis or histoplasmosis. Thirteen of the 181 dogs, positive by CIEP, were euthanatized, and the diagnosis was confirmed by cultivation and/or microscopic detection of Blastomyces dermatitidis. Additional CIEP-positive dogs were confirmed by staining of aspirates collected in vivo. Radiographic support for the diagnosis was reported in 4 other dogs in which histoplasmosis was excluded by a negative CIEP with histoplasma antigen. The precipitating antibody may disappear during the course of the disease, as it did in 1 dog treated with amphotericin B, but not cured. This dog reverted from CIEP-positive to CIEP-negative within 17 months of treatment (with a weak reaction after 10 months of treatment). The CIEP-detectable antibody was present only in 1 dog without a confirmation by histopathologic findings or cultivation among 24 well-documented cases and 181 total tested sera. The CIEP was more sensitive and specific than was the gel-diffusion precipitin test, eliminated the problems of anticomplementarity that often affected the results of complement-fixation tests with canine sera, and served well in detecting dogs with blastomycosis. Electrophoretic pattern of sera from CIEP-positive dogs with blastomycosis showed a decrease in albumin and an increase in alpha 2- and often in beta- and gamma-globulins, with a substantial decrease of the albumin/globulin ratio.     

Primary lymphoma of the uterine horn in a Lhasa Apso dog

Primary lymphomas of the canine female genital tract are uncommon tumours. A 9-year-old intact female Lhasa Apso dog presenting with a closed pyometra underwent an ovariohysterectomy (OHE), and the hyperplastic uterine horn along with multiple follicular cysts on the right ovary was examined by histological analysis. Severe infiltration of medium-sized lymphocytes with strong positive immunoreactivity for CD79a and numerous anaplastic features was detected in the unilateral uterine horn, and the dog was diagnosed as having extranodal marginal zone B-cell lymphoma (MZBCL). The present case reports an extremely rare occurrence of primary lymphoma involving the uterine horn in a dog and describes histological characteristics of the tumour for definite diagnosis.     

Immunophenotypic comparison of blood and lymph node from dogs with lymphoma

Peripheral blood and lymph node tissue from 12 dogs with lymphoma was immunophenotyped. Additionally, the bone marrow was immunophenotyped in 6 dogs. The lymphomas were characterized as B-cell in 11 dogs and T-cell in 1 dog. Immunophenotypic patterns in the peripheral blood and bone marrow were variable. The trend in dogs with B-cell lymphoma was normal to increased percentage of IgG-positive cells, decreased percentage of pan-T-positive cells, decreased percentage of CD4-positive cells, and decreased CD4/CD8 ratio. Simultaneous immunophenotyping of lymph node, blood and bone marrow cannot be recommended routinely without further studies to document its value as an independent prognostic indicator. However, it is potentially useful for tumor staging and monitoring remission, especially in lymphoma patients with a leukemic phase.     

Primary central nervous system B-cell lymphoma in a young dog

This report describes a primary central nervous system B-cell lymphoma in a 3-year-old intact female Maltese dog. Canine primary central nervous system lymphomas constitute about 4% of all intracranial primary neoplasms, but comprehensive histopathologic classifications have rarely been carried out. This is the first report of this disease in a young adult dog.     

Development of high-grade B-cell lymphoma concurrent with T-cell chronic lymphocytic leukemia in a dog

Second malignancies are frequent complications in human patients with chronic lymphocytic leukemia (CLL). However, the clinical details and outcome of this phenomenon were unclear in their canine counterparts. Here, we report a dog with high-grade lymphoma concurrent with T-cell CLL. A 10-year-old male golden retriever presented with lymphadenopathies. The lymph nodes contained large-sized lymphocytes, raising suspicion of high-grade lymphoma. Meanwhile, small lymphocytic lymphocytosis in the peripheral blood was consistent with CLL. Interestingly, molecular biological analyses revealed that CLL cells were of the T-cell type, whereas lymphoma cells were of the B-cell type. Chemotherapy using the L-VCA short protocol was effective for 155 days, but the dog died on day 194 after diagnosis, despite rescue therapies.     

Primary malignant lymphoma of the urinary bladder in a dog: longterm remission following treatment with radiation and chemotherapy

Primary (extranodal) malignant lymphoma limited exclusively to the urinary bladder is an extremely rare disorder in both humans and animals and has to be differentiated from malignant lymphoma cases where a systemic (multicentric) lymphoma has spread to the bladder. We report a case of a 3-year old female spayed mixed breed dog presenting with gross haematuria and dysuria and diagnosed with a primary B-cell high-grade lymphoma of the urinary bladder without involvement of any other site. After treatment with a combination of hypofractionated external beam radiation and cytotoxic chemotherapy, rapid and complete remission of the tumor occurred. At present the dog is alive and has been in remission for 52 months.     

The brown dog tick Rhipicephalus sanguineus and the dog as experimental hosts of Ehrlichia canis

Adult Rhipicephalus sanguineus ticks efficiently transmitted Ehrlichia canis to susceptible dogs for 155 days after detachment as engorged nymphs from a dog in the acute phase of ehrlichiosis. Adult ticks that had similarly engorged on a dog in the chronic phase of ehrlichiosis failed to transmit E canis to susceptible dogs. Infected but unfed adult ticks may be of greater importance than the chronically infected carrier dog as a natural reservoir of E canis.     

Identification of serum biomarkers for canine B-cell lymphoma by use of surface-enhanced laser desorption-ionization time-of-flight mass spectrometry

OBJECTIVE: To identify biomarker proteins for B-cell lymphoma in canine serum by use of surface-enhanced laser desorption-ionization time-of-flight (SELDI-TOF) mass spectrometry and build classification trees with multiple biomarkers that have high sensitivity and specificity for that tumor type. SAMPLE POPULATION: Sera from 29 dogs with B-cell lymphoma and 87 control dogs (approx equal numbers of healthy dogs, dogs with malignant cancers other than B-cell lymphoma, and dogs with various nonneoplastic diseases or conditions). PROCEDURES: Serum samples were fractionated chromatographically and analyzed via SELDI-TOF mass spectrometry. Peak amplitudes of the spectra from the 2 sample groups were compared to identify potential biomarker peaks, and classification trees were built by use of computer software to detect patterns formed by multiple biomarkers among SELDI data sets. RESULTS: Several biomarker protein peaks in canine serum were identified, and a classification tree was built on the basis of 3 biomarker protein peaks. With 10-fold cross-validation of the sample set, the best individual serum biomarker peak had 75% sensitivity and 86% specificity and the classification tree had 97% sensitivity and 91% specificity for the classification of B-cell lymphoma. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of biomarker proteins identified in canine serum, classification trees were constructed, which may be useful for the development of a diagnostic test for B-cell lymphoma in dogs. Further investigation is needed to determine whether these biomarkers are useful for screening susceptible dog populations or for monitoring disease status during treatment and remission of B-cell lymphoma in dogs.     

Inactivation of the p16 cyclin-dependent kinase inhibitor in high-grade canine non-Hodgkin's T-cell lymphoma

The significance of p16/Rb tumor suppressor pathway inactivation in T-cell non-Hodgkin's lymphoma (NHL) remains incompletely understood. We used naturally occurring canine NHL to test the hypothesis that p16 inactivation has specific pathologic correlates. Forty-eight samples (22 T-cell NHL and 26 B-cell NHL) were included. As applicable, metaphase- or array-based comparative genomic hybridization, Southern blotting, promoter methylation, and Rb phosphorylation were used to determine the presence, expression, and activity of p16. Fisher's exact test was used to test for significance. Deletion of p16 (or loss of dog chromosome 11) was restricted to high-grade T-cell NHL (lymphoblastic T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified). These were characterized by a concomitant increase of tumor cells with Rb phosphorylation at canonical CDK4 sites. Rb phosphorylation also was seen in high-grade B-cell NHL (diffuse large B-cell lymphoma and Burkitt-type lymphoma), but in those cases, it appeared to be associated with c-Myc overexpression. The data show that p16 deletion or inactivation occurs almost exclusively in high-grade T-cell NHL; however, alternative pathways can generate functional phenotypes of Rb deficiency in low-grade T-cell NHL and in high-grade B-cell NHL. Both morphologic classification according to World Health Organization criteria and assessment of Rb phosphorylation are prognostically valuable parameters for canine NHL.     

Epitheliotropic cutaneous lymphoma (mycosis fungoides) in a dog

A seven-year-old castrated male Yorkshire terrier dog was presented for a recurrent skin disease. Erythematous skin during the first visit progressed from multiple plaques to patch lesions and exudative erosion in the oral mucosa membrane. Biopsy samples were taken from erythematous skin and were diagnosed with epitheliotropic T cell cutaneous lymphoma by histopathology and immunochemical stain. In serum chemistry, the dog had a hypercalcemia (15.7 mg/dl) and mild increased alkaline phosphatase (417 U/l). Immunohistochemistry was performed to detect parathyroid hormone-related peptide (PTH-rP) in epitheliotropic cutaneous lymphoma tissues but the neoplastic cells were not labeled with anti-PTH-rP antibodies. The patient was treated with prednisolone and isotretinoin. However, the dog died unexpectedly.     

Orthovoltage radiotherapy of primary lymphoma of bone in a dog

A 1 1/2-year-old castrated Boxer with a progressive left forelimb lameness of 1 month's duration had a solitary immunoblastic B-cell lymphoma of the proximal portion of the ulna. This primary lymphoma of bone was successively treated with orthovoltage radiation (45 Gy divided into 10 fractions over 22 days). The dog gradually regained normal gait function and did not develop any local recurrence over 34 months. In dogs, primary lymphoma of bone is a rare primary bone tumor, and the ulna is an unusual location for extranodal lymphoma. Local administration of radiation appears to be an effective treatment, allowing retention of normal function.     

Etoposide (VP-16)

A retrospective analysis was performed of the effect of VP-16 (etoposide) in the treatment of 13 dogs with lymphoma. Twelve dogs had achieved partial (two) and complete (ten) responses to combination chemotherapy, but all were out of remission at the time of the trial. One dog had not previously had chemotherapy. There was minimal response to VP-16 chemotherapy in the 13 dogs studied, and only two of 13 dogs had some response to treatment. For one dog, complete and partial remission durations were one and three months, respectively. In another dog, there was partial remission of eight days. There were no responses in the other 11 dogs. The most serious adverse reaction after administration of VP-16 was an acute pruritic cutaneous reaction that occurred in 11 of the 13 dogs, which may have been associated with the vehicle of VP-16, polysorbate 80. Results showed that VP-16 has minimal activity for treatment of dogs with lymphoma that have experienced relapses after treatment with other anti-cancer drugs. More trials are needed with higher dosages and the oral form of the drug, which does not contain polysorbate 80.     

Disseminated histoplasmosis in dogs: 12 cases (1981-1986)

Diarrhea, intestinal blood loss, anemia, and lethargy were predominant clinical findings in 12 dogs with disseminated histoplasmosis. Young dogs were affected most commonly, with 6 dogs being 1 to 3 years old. A diagnosis of disseminated histoplasmosis was established on the basis of histologic or cytologic detection of Histoplasma organisms in intestinal or rectal mucosa in 7 dogs, in circulating leukocytes in 5 dogs, in bone marrow in 3 dogs, and in multiple tissues at necropsy in 1 dog (4 dogs had Histoplasma organisms detected in greater than 1 site). Anemia was detected in 10 dogs (PCV less than 20% in 3 dogs), and the anemia was inadequately regenerative or nonregenerative in 7. Hypoalbuminemia was detected in 9 dogs, and serum albumin concentrations were low (less than 1.0 g/dl) in 4 of the 9 dogs. Of 5 dogs treated with ketoconazole, 2 were in remission for greater than or equal to 1 year. Corticosteroid therapy may have exacerbated the disease in 4 dogs. Histoplasma infection of multiple organs was detected in 5 necropsied dogs.     

Tumor staging in a Beagle dog with concomitant large B-cell lymphoma and T-cell acute lymphoblastic leukemia

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.