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.     

Implications of the RhoA/Rho associated kinase pathway and leptin in primary uterine inertia in the dog

The underlying functional and molecular changes in canine primary uterine inertia (PUI) are still not clarified. Leptin (Lep) and obesity negatively affect uterine contractility in women, partly mediated by the RhoA/Rho associated kinase pathway, affecting myometrial calcium sensitization. We hypothesized that increased uterine Lep/Lep receptor (LepR) or decreased RhoA/Rho associated kinase expression contributes to PUI in dogs, independent of obesity. Dogs presented for dystocia were grouped into PUI (n = 11) or obstructive dystocia (OD, still showing strong labor contractions; n = 7). Interplacental full-thickness uterine biopsies were collected during Cesarean section for relative gene expression (RGE) of RhoA, its effector kinases (ROCK1, ROCK2), Lep and LepR by qPCR. Protein and/or mRNA expression and localization was evaluated by immunohistochemistry and in situ hybridization. RGE was compared between groups by one-way ANOVA using body weight as covariate with statistical significance at P < 0.05. Uterine ROCK1 and ROCK2 gene expression was significantly higher in PUI than OD, while RhoA and Lep did not differ. LepR RGE was below the detection limit in five PUI and all OD dogs. Litter size had no influence. Lep, LepR, RhoA, ROCK1, ROCK2 protein and/or mRNA were localized in the myometrium and endometrium. Uterine protein expression appeared similar between groups. LepR mRNA signals appeared stronger in PUI than OD. In conclusion, lasting, strong labor contractions in OD likely resulted in downregulation of uterine ROCK1 and ROCK2, contrasting the higher expression in PUI dogs with insufficient contractions. The Lep-LepR system may affect uterine contractility in non-obese PUI dogs in a paracrine-autocrine manner.     

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.     

Monitoring of large B-cell lymphoma and T-zone lymphoma in a dog via flow cytometry

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.     

Cutaneous lymphoma in a juvenile dog

Abstract: An 18-month-old male Doberman Pinscher was referred to the Veterinary Medical Teaching Hospital of the College of Veterinary Medicine for an erythemic nodular mass on the right forelimb. The mass was diagnosed as cutaneous lymphoma, based on cytologic examination of a mass aspirate and histopathology. Using immunohistochemistry the neoplastic cells were positive for CD3 but negative for CD79a, E-cadherin, and pancytokeratin, confirming their origin as T lymphocytes. No tumor recurrence was noted 18 months after surgery. To our knowledge, this is the first report of a solitary nodular form of cutaneous lymphoma in a young dog.     

The role of rituximab in the treatment of canine lymphoma: an ex vivo evaluation

Targeting the CD20 receptor that is common to many B-cell Non-Hodgkin's Lymphoma subtypes in people, rituximab is a chimeric monoclonal antibody which has significantly improved disease-free survival rates compared with the use of cytotoxic agents alone. This study evaluated ex vivo canine B cell binding and depletion by rituximab with flow cytometric technique as possible proof of concept for treatment of canine lymphoma. Despite immunohistochemistry supporting CD20 expression, rituximab did not bind or deplete canine B cells and it is unlikely that it will be added to the armamentarium of treatment options for canine lymphoma.     

Mucosa-associated lymphoid tissue lymphoma of the third eyelid conjunctiva in a dog

A 4-year-old, neutered female Cocker Spaniel was presented to the veterinary clinic for protrusion of the left third eyelid. When the third eyelids from both eyes were everted, lobulated masses were present on the bulbar surface. The left third eyelid had a larger protrusion. There was no apparent associated ocular or systemic involvement. The tumor of left third eyelid was removed and referred for histological examination. Histologically, there were proliferations of lymphoid follicles surrounded by lymphoid cells forming a marginal zone. Those lymphoid cells occasionally infiltrated into conjunctival epithelium. A few apoptotic bodies with karyopyknotic and karyorrhexic nuclei were observed in the germinal center of lymphoid follicles. Mitotic figures were rare. On immunohistochemistry, tumor cells expressed CD79a but not CD3. A diagnosis of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) of the third eyelid was established based on the histological and immunophenotypical features. At the 1-year follow-up, there was no evidence of recurrence of the mass at the area of excision of the left third eyelid and the remaining tumor of the right third eyelid was still a similar size. The dog still showed no significant findings, except those of the tumor, and no evidence of systemic involvement. To the authors' knowledge, this is the first reported case of MALT lymphoma of the third eyelid in a dog.     

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.     

Mastitis caused by Mycobacterium kansasii infection in a dog

A 2‐year, 7‐month‐old female Chihuahua was admitted for a mammary mass measuring one cm in diameter. The dog had a history of demodicosis for 4 months and showed signs of pseudopregnancy at the time of the visit. Cytologic examination of an aspirate of the mass revealed a large number of macrophages containing nonstaining bacterial rods, which were acid‐fast in a Ziehl–Neelsen stain, suggesting mycobacterial infection. Histologic examination of the mass revealed a pyogranulomatous mastitis characterized by an infiltration with macrophages containing acid‐fast bacteria. Mycobacterium kansasii was subsequently cultured and identified by PCR. Surgical excision of the mass resulted in the growth of other dermal masses, but antimycobacterial treatment with rifampin and clarithromycin resolved these masses within 1 month. Three months after discontinuation of the treatment, similar organisms were found in aspirates of the enlarged bilateral inguinal lymph nodes by cytologic examination. Despite antimycobacterial treatment for another 4 months, there was no improvement and demodicosis also recurred. The dog eventually died of lymphoma 5 months after the relapse of mycobacterial infection. Although M kansasii is considered an important pathogen for pulmonary and cutaneous disease in people, there is only one report in a dog with an infection in a pleural effusion. As both adult‐onset demodicosis in dogs as well as mycobacterial infection in people have been associated with T‐lymphocyte deficiency, the M kansasii infection in this dog may have been associated with a condition of immune compromise.     

Primary lymphoma of the prostate in a dog

A case of primary lymphoma of the prostate is reported in a nine-year-old crossbred dog. The lesion was treated with cytotoxic drugs, however, the dog was euthanased because of inadequate response. This is the first recorded case of primary prostatic lymphoma in the dog.     

Primary mesenteric root osteosarcoma in a dog

Abstract: A 10‐year‐old spayed female Boxer‐mix was presented with a history of several weeks of soft stools, straining to defecate, inappetance, and lethargy and several days of hematochezia, melena, and dyschezia. Physical examination findings included mild tachycardia and tense cranial abdomen. CBC results indicated moderate mature neutrophilia. Ultrasonographic examination of the abdomen revealed a large mass with complex echogenicity in the cranial abdomen, likely associated with the intestines. Cytologic examination of a fine‐needle aspirate revealed a population of round, stellate, and spindle‐shaped cells arranged individually and in aggregates with occasional cells embedded in an eosinophilic extracellular matrix. The cytologic interpretation was malignant mesenchymal neoplasm with osteosarcoma being the primary differential. Surgical exploration of the abdomen revealed a 10‐cm‐diameter mass located at the intestinal mesenteric root. The mass occluded blood flow to portions of the gastrointestinal tract. The dog was euthanized due to the nonresectable nature of the tumor. Histopathologic examination revealed an expansile poorly demarcated mesenchymal neoplasm composed predominantly of spindloid and pyriform cells, occasionally embedded in a matrix compatible with osteoid. The diagnosis was extraskeletal osteosarcoma of the intestinal mesenteric root, only rarely reported in dogs.     

Unicentric extranodal lymphoma of the upper eyelid conjunctiva in a dog

A case of conjunctival lymphoma in a 4-year-old Siberian husky is reported. A large red mass protruding from the conjunctiva of the upper eyelid of the right eye was present. Irritation, blepharospasm and epiphora were revealed on initial ophthalmic examination. After anti-inflammatory treatment, surgery was performed. Histologically, the mass consisted of large polygonal cells with a high nucleus to cytoplasm ratio, moderate amounts of slightly eosinophilic cytoplasm, pleomorphic nuclei with vesicular chromatin and prominent multiple nucleoli. Mitotic figures were frequent. Approximately 70% of the neoplastic cells were CD3 positive and CD79alpha negative. On the basis of histologic and immunohistochemical findings, a diagnosis of intermediate-grade, diffuse large-cell lymphoma with T-cell immunophenotype was made. The surgical area healed uneventfully and, although chemotherapy was not received, after 12 months the dog exhibited no recurrence. To the authors' knowledge, this is the first report of unicentric extranodal conjunctival lymphoma in a dog.     

Influence of chemotherapy for lymphoma in canine parvovirus DNA distribution and specific humoral immunity

In man, the combination of cancer and its treatment increases patients’ susceptibility to opportunistic infections, due to immune system impairment. In veterinary medicine little information is available concerning this issue. In order to evaluate if a similar dysfunction is induced in small animals undergoing chemotherapy, we assessed the complete blood count, leukocytic, plasma and fecal canine parvovirus (CPV) viral load, and anti-CPV protective antibody titers, in dogs with lymphoma treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) protocol, before and during chemotherapy.There was no evidence of decreased immune response, either at admission or after two chemotherapy cycles, indicating that the previously established immunity against CPV was not significantly impaired, supporting the idea that immunosuppression as a result of hematopoietic neoplasms and their treatment in dogs requires further investigation and conclusions cannot be extrapolated from human literature.     

Gamma delta T‐cell large granular lymphocyte lymphoma in a dog

A 2‐year and 6‐month‐old female neutered Labrador Retriever with Horner syndrome, megaesophagus, and a mediastinal mass was referred to the Queen Mother Hospital for Animals of the Royal Veterinary College. A large granular lymphocyte (LGL) lymphoma was diagnosed on cytology; flow cytometric analysis revealed a γδ T‐cell phenotype (CD3+, CD5+, CD45+, TCRγδ+, CD4?, CD8?, CD34?, CD21?). Chemotherapy was started with a combination of lomustine, vincristine, procarbazine, and prednisolone, followed by bleyomicin. Euthanasia was elected by the owners, due to progressive deterioration and lack of quality of life, 28 days after diagnosis. This is the first cytologic and immunophenotypic characterization of a canine γδ T‐cell lymphoma with LGL morphology and probably of mediastinal origin. The role of chemotherapy in delaying the disease progression remains unknown.     

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.     

Treatment of cutaneous T-cell lymphoma with dacarbazine in a dog

Abstract Epitheliotropic cutaneous T-cell lymphoma in a Lhasa Apso dog treated with dacarbazine is reported. Clinical disease consisted of a 4 × 4-cm ulcerated mass over the mandibular symphysis and bilateral lymphadenopathy of the submandibular lymph nodes. Skin biopsy sections were díagnostic for epitheliotropic cutaneous T-cell lymphoma, and immunohistochemistry staining for the CD3 antigen was positive. Tissue samples were submitted for chemosensitivity testing and dacarbazine was shown to be 60% effective. Treatment with dacarbazine resulted in total clinical remission. The dog remains disease free 1 year after treatment. Résumé— Les auteurs décrivent un cas de lymphome cutané T épithéliotrope chez un Lhassa Apso traitéà la dacarbazine. Le tableau clinique était caractérisé par la présence d'une masse ulcérée de 4 × 4 cm sur la symphyse mandibulaire et par une adénopathie bilatérale des ganglions sous mandibulaires. Les biopsies posèrent le díagnostic de lymphome cutané T et l'immunomarquage fut positif pour l'antigène CD3. Des prélèvements tissulaires fürent soumis à des tests de chimiosensibilité et la dacarbazine se révéla efficace à 60%. Le traitement à la dacarbazine entraina une rémission clinique totale. Le chien ne présente pas de récidive un an après le traitement. [Lemarié, S. L., Eddlestone, S. M. Treatment of cutaneous T-cell lymphoma with dacarbazine in a dog. (Traitement d'un lymphome cutané T à la dacarbazine chez un chien.) Veterinary Dermatology 1997; 8 : 41–46.] Resumen Se describe el tratamiento con dacarbazina de un linfoma cutáneo epiteliotrópico de células T en un Lasha Apso. La presentación clinica consistia en una masa ulcerada de 4 × 4 cm por encima de la sinfisis mandibular y linfadenopatia bilateral de los ganglios linfáticos submandibulares. El estudio histológico cutáneo permitió un díagnóstico de linfoma cutáneo epiteliotrópico de celulas T, con positividad inmunohistoquimica al antigeno CD3. Se remitieron muestras tisulares para pruebas de quimiosensibilidad, en las que la dacarbazina mostró una efectividad del 60%. El tratamiento con dacarbazina llevó a una remisión clinica total. El perro sigue sano un año después del tratamiento. [Lemarié, S. L., Eddlestone, S. M. Treatment of cutaneous T-cell lymphoma with dacarbazine in a dog. (Tratamiento del linfoma cutáneo de celulas T con dacarbazina en un perro.) Veterinary Dermatology 1997; 8 : 41–46.] Zusammenfassung— Es wird über eine epitheliotropes kutanes T-Zell-Lymphom bei einem Lhasa Apso berichtet, das mit Dacarbazin behandelt wurde. Die klinische Erkrankung bestand in einer 4 × 4 cm großen ulzerierten Masse über der Symphyse der Mandibula sowie einer bilateralen Lymphadenopathie der submandibulären Lymphknoten. Die Hautbiopsien ergaben die Diagnose epitheliotropes kutanes T-Zell-Lymphom, die immunohistochemische Färbung auf CD3-Antigen fiel positiv aus. Die Gewebsproben wurden einer Chemosensitivitätsprobe unterzogen und Dacarbazin erwies sich zu 60% wirksam. Die Behandlung mit Dacarbazin führte zu einer vollständigen klinischen Remission. Der Hund blieb frei von Krankheitssymptomen seit einem Jahr nach der Behandlung. [Lemarié, S. L., Eddlestone, S. M. Treatment of cutaneous T-cell lymphoma with dacarbazine in a dog. (Die Behandlung eines kutanen T-Zell-Lymphom mit Dacarbazin bei einem Hund.) Veterinary Dermatology 1997; 8 : 41–46.]     

Genetic homogenisation of birth weight in rabbits: Indirect selection response for uterine horn characteristics

A divergent selection experiment on within-litter homogeneity of birth weight in rabbits was carried out at the INRA experimental farm at Auzeville. The two lines were created by selecting breeding does and bucks from the female strain AGP22 bred at the Grimaud Frères Sélection Company. This involved a new model incorporating a genotypic value for the mean of individual birth weight and a genotypic value for the environmental variance. This new “trait” was modelled in the usual infinitesimal framework, giving estimated breeding values for environmental variability. There was a favourable selection response with a significant difference in within-litter standard deviation of birth weight between the lines selected for increasing (HOM) or decreasing (HET) homogeneity. At the end of the third generation, 31 females from the HOM line and 33 from the HET line were sacrificed to collect the uterine horns and measure their initial length (L1) and their length after elongation with a weight of 50 g (L2) and then 70 g (L3). The length in the homogeneous line was significantly greater, whatever the weight (L1: + 1.3 cm, P = 0.02; L2:  + 2.8 cm P < 0.001; L3:  + 4.2 cm, P < 0.001). The absolute and the relative elongations were significantly higher in the HOM line. There was no significant effect of the line on the number of ova shed, the weight of the ovary, or the weight of the uterine horns. It is concluded that the divergence between lines for the within-litter homogeneity of birth weight is at least partly due to the characteristics of the genital tract, i.e. the length and capacity for elongation of the uterine horn.     

Characterization of lymphocyte populations by flow cytometry in a calf with sporadic juvenile lymphoma

A 2-month-old Angus heifer was presented to Washington State University Veterinary Teaching Hospital for generalized peripheral lymphadenopathy and mild anorexia. Results of a CBC revealed marked lymphocytosis consisting primarily of large, atypical lymphocytes with cleaved, reniform nuclei. A presumptive diagnosis of sporadic juvenile lymphoma was made. To confirm these findings, a prescapular lymph node was submitted for histopathology, immunochemistry, and flow cytometric analysis. Peripheral blood also was analyzed by flow cytometry. Phenotypic characterization of lymph node and peripheral blood cell populations verified the calf had the B-cell form of sporadic juvenile lymphoma. The results of this investigation expand the phenotypic characterization of neoplastic lymphocytes in sporadic juvenile lymphoma.     

Pyometra with inguinal herniation of the left uterine horn and omentum in a Beagle dog

Objective: To describe a unique case of pyometra with inguinal herniation of the left uterine horn and omentum. Case summary: A 7‐year‐old, 19 kg, intact female Beagle dog presented for surgical treatment of presumptive pyometra and biopsy of a caudal abdominal mass in the left inguinal mammary gland region. Ventral midline celiotomy was performed, and a distended, fluid‐filled uterus with passage of the distal aspect of the left uterine horn through the left vaginal process into the inguinal canal was identified. The patient recovered uneventfully following ovariohysterectomy and left inguinal herniorrhaphy. New or unique information provided: This is the first documented report of inguinal herniation of a uterine horn associated with a pyometra.