RADIOGRAPHIC CHARACTERIZATION OF PRIMARY LUNG TUMORS IN 74 DOGS

Primary pulmonary neoplasia is well recognized in dogs and prognosis depends upon the tumor type. The purpose of this retrospective study was to characterize the radiographic appearance of different primary lung tumors with the goal of establishing imaging criteria to separate the different types. Three‐view thoracic radiographs of 74 dogs with histologically confirmed pulmonary anaplastic carcinoma (n = 2), adenocarcinoma (n = 31), bronchioalveolar carcinoma (n = 19), histiocytic sarcoma (n = 21), and squamous cell carcinoma (n = 1) were evaluated. Radiographs were assessed for tumor volume, affected lobe, location within lobe, overall pulmonary pattern, presence of cavitation, mineralization, air bronchograms, lymphadenomegaly, and pleural fluid. Histiocytic sarcomas were significantly larger than other tumor types (271 cm³; P = 0.009) and most likely to be found in the left cranial (38%; 8/21) and right middle (43%; 9/21) lung lobes, whereas adenocarcinomas were most likely to be found in the left caudal (29%; 9/31) lung lobe. Fifty‐seven percent (12/21) of histiocytic sarcomas had an internal air bronchogram. Findings indicate that a large mass in the periphery or affecting the whole lobe of the right middle or left cranial lung lobe with an internal air bronchogram is likely to be an histiocytic sarcoma.     

SKELETAL LESIONS OF HISTIOCYTIC SARCOMA IN NINETEEN DOGS

The purpose of this study was to describe the clinical and radiographic findings in dogs with bone lesions secondary to histiocytic sarcoma. Nineteen dogs with radiographically identified bone lesions that were histologically diagnosed as histiocytic sarcoma were assessed. The medical records, all available radiographs and histologic sections were reviewed retrospectively. Dogs were subcategorized into localized or disseminated histiocytic sarcoma groups. Golden Retrievers or Rottweilers greater than 5 years of age, with a history of lameness or neurologic deficits localized to the spinal cord was the most common presentation. Fifteen of 19 dogs had a radiographically detectable soft tissue mass associated with bone destruction. The bone lesions had aggressive characteristics and the sites of involvement included periarticular bones (n = 11), vertebrae (n = 6), proximal humerus (n = 5), and rib (n = 2). Fifteen of 19 dogs had disseminated histiocytic sarcoma, and four had localized histiocytic sarcoma. All Rottweilers had disseminated histiocytic sarcoma. Histiocytic sarcoma should be considered as a differential diagnosis for aggressive periarticular, vertebral, or proximal humeral bone lesions identified on radiographs. The index of suspicion should be increased in greater than 5-year-old Golden Retrievers and Rottweilers when a soft tissue mass is associated with the bone lesion on radiographs or myelography. Bone involvement with histiocytic sarcoma, and the Rottweiler breed, was associated with the disseminated form of the disease.     

Phase II evaluation of doxorubicin for treatment of various canine neoplasms

One hundred eighty-five dogs with histologically confirmed, measurable malignant tumors were used in a prospective study to determine the response to 2 doses of the anthracycline antitumor antibiotic, doxorubicin. Eighty-three dogs had been refractory to one or more previous treatment modalities (surgery, n = 54; chemotherapy, n = 22; radiation, n = 10; hyperthermia, n = 1; biological response modifier, n = 1). The extent of neoplastic disease was determined immediately prior to and 3 weeks after 2 doses of doxorubicin were administered (30 mg/m2 of body surface area, iv) 21 days apart. Eighty-four percent (n = 157) of the dogs received 2 doses of doxorubicin and were evaluated. Of the 28 dogs ruled ineligible, 4 had serious side effects to the first dose of doxorubicin, and 24 others acquired complications resulting from their malignant tumors. A partial or complete remission was obtained in 41% (64/157) of all evaluable dogs: 26% (11/43) of the dogs with carcinoma, 67% (42/63) of the dogs with lymphoma, and 22% (11/51) of the dogs with sarcoma. Tumors in which there was at least a 50% volume reduction (partial or complete remission) included malignant lymphoma (42/63), fibrosarcoma (1/14), solid follicular thyroid carcinoma (3/13), mammary adenocarcinoma (2/8), hemangiosarcoma (2/8), osteosarcoma (1/6), circumanal carcinoma (3/5), synovial cell sarcoma (2/3), undifferentiated sarcoma (2/3), nasal adenocarcinoma (1/2), liposarcoma (1/2), infiltrating lipoma (1/1), malignant melanoma (1/1), sclerosing mesothelioma (1/1), and neurofibrosarcoma (1/2).(ABSTRACT TRUNCATED AT 250 WORDS)     

Canine hemophagocytic histiocytic sarcoma: a proliferative disorder of CD11d+ macrophages

Histiocytic disorders of dogs include histiocytoma, localized histiocytic sarcoma (HS), disseminated HS (malignant histocytosis), and the reactive histiocytoses: cutaneous and systemic. A common element to these diseases is proliferation of dendritic cells (DC) of either Langerhans cell (epithelial DC) or interstitial DC lineage. In this report, 17 dogs with hemophagocytic HS are described. Breeds affected included Bernese Mountain Dog (6), Golden Retriever (4), Rottweiler (3), Labrador Retriever (2), a mixed-breed dog, and a Schnauzer, which were from 2.5 to 13 years old. The dogs presented with Coombs negative responsive anemia in 16/17 dogs (94%), thrombocytopenia in 15/17 dogs (88%), hypoalbuminemia in 16/17 dogs (94%), and hypocholesterolemia in 11/16 dogs (69%). All dogs died or were euthanized. The clinical course ranged from 2 to 32 weeks (mean 7.1 weeks). Diffuse splenomegaly with ill-defined masses was consistently present. Microscopic lesions were prevalent in spleen, liver, lung, and bone marrow. Metastasis occurred by insidious intravascular invasion with minimal mass formation. Histiocytes were markedly erythrophagocytic and accompanied by foci of extramedullary hemopoiesis. Cytologically, the histiocytes varied from well differentiated to atypical, with atypia more prevalent in spleen than bone marrow. These tumors arose from splenic red pulp and bone marrow macrophages, which expressed major histocompatibility complex class II and the beta2 integrin, CD11d. They had low and/or inconsistent expression of CD1 and CD11c, which are dominantly expressed by canine nonhemophagocytic HS of DC origin. Canine histiocytic proliferative diseases now encompass proliferation of all members of the myeloid histiocytic lineage: Langerhans cells, interstitial DC, and macrophages.     

Evaluation of Serum Ferritin as a Tumor Marker for Canine Histiocytic Sarcoma

Background: Canine histiocytic sarcoma (HS) is an aggressive malignancy. Hyperferritinemia has been documented in dogs with HS and could serve as a tumor marker aiding in diagnosis and treatment. In people, hyperferritinemia is found in inflammatory diseases, liver disease, and hemolysis, and thus may occur in dogs with these conditions. Objective: To determine if serum ferritin concentration is a tumor marker for canine HS. Animals: Dogs with HS (18), inflammatory diseases (20), liver disease (24), immune‐mediated hemolytic anemia (IMHA) (15), and lymphoma (23). Methods: Prospective, observational, cohort study: Serum ferritin concentration was measured at initial diagnosis. Parametric methods were used to compare mean log ferritin concentrations among disease categories. Receiver‐operating characteristic curves and likelihood ratios were used to evaluate serum ferritin concentration as a tumor marker. Results: Varying proportions of dogs with IMHA (94%), HS (89%), liver disease (79%), lymphoma (65%), and inflammatory diseases (40%) had hyperferritinemia. Dogs with IMHA had significantly higher mean ferritin concentration than dogs in all other categories. Dogs with HS had significantly higher mean ferritin concentration than those in the inflammatory disease and lymphoma categories. Mean serum ferritin concentration was not significantly different between dogs with HS and those with liver disease. Decision thresholds were determined to distinguish IMHA and HS from the other diseases associated with hyperferritinemia. Conclusion: Hyperferritinemia is common in dogs with HS and, after IMHA is ruled out, the degree of hyperferritinemia may be useful in differentiating dogs with HS from dogs with inflammatory diseases, liver disease, and lymphoma.     

The diagnosis and prognosis of synovial tumors in dogs: 35 cases

Although synovial cell sarcoma is reported to be the most common neoplasm of the canine synovium, this retrospective study of 35 canine synovial tumors found that the majority were of histiocytic origin. Five (14.3%) synovial cell sarcomas were identified by positive immunohistochemical staining with antibodies to cytokeratin. Eighteen (51.4%) histiocytic sarcomas were identified by cell morphology and immunohistochemical staining with antibodies to CD18. Six (17.1%) synovial myxomas were identified by histologic pattern. The remaining six (17.1%) synovial tumors represented a variety of sarcomas, including two malignant fibrous histiocytomas (actin positive), one fibrosarcoma, one chondrosarcoma, and two undifferentiated sarcomas. Rottweilers were overrepresented in the histiocytic sarcoma category and Doberman Pinschers were overrepresented in the synovial myxoma category. The average survival time was 31.8 months for dogs with synovial cell sarcoma, 5.3 months for dogs with histiocytic sarcoma, 30.7 months for dogs with synovial myxoma, and 3.5 months for dogs with other sarcomas. Among the dogs with follow-up information available, metastatic disease was detected in 25% of dogs with synovial cell sarcoma, in 91% of dogs with histiocytic sarcoma, in none of the dogs with synovial myxoma, and in 100% of dogs with other sarcomas. Immunohistochemical staining for cytokeratin, CD18, and smooth muscle actin is recommended to make the diagnosis and thereby predict the behavior of synovial tumors in dogs.     

Radiographic characterization of enlarged sternal lymph nodes in 71 dogs and 13 cats

In this retrospective study, radiographically enlarged sternal lymph nodes (LNs) were evaluated in 71 dogs and 13 cats for average size, location, and most representative radiographic view. Concurrent clinical diagnoses were also noted and grouped into one of three following categories: neoplastic, inflammatory, or hematologic. There were no statistically significant differences in LN size between lateral views within each species. Enlarged sternal LNs were more cranially positioned in dogs than cats. No statistical difference was noted between right and left laterals, as to on which projection the enlarged sterna lymph nodes was seen best. Neoplastic disease (78.9%) was the most prevalent condition seen in association with LN enlargement in dogs, followed by primary infectious or inflammatory diseases (14.1%) and various hematologic conditions (7.0%). In cats, neoplasia was also most common (69.2%), followed by inflammatory diseases (30.8%). No hematologic conditions were noted in cats. The most common etiologic agent seen concurrently with enlarged sternal LNs in both dogs (33.8%) and cats (38.5%) was malignant lymphoma. The results of this study provide a clinically useful representation of the average size and location of radiographically enlarged sternal LNs for dogs and cats. The diseases represented demonstrate the wide spectrum of potential causes of sternal lymphadenopathy.     

Evaluation of the drug sensitivity and expression of 16 drug resistance-related genes in canine histiocytic sarcoma cell lines

Canine histiocytic sarcoma (HS) is an aggressive tumor type originating from histiocytic cell lineages. This disease is characterized by poor response to chemotherapy and short survival time. Therefore, it is of critical importance to identify and develop effective antitumor drugs against HS. The objectives of this study were to examine the drug sensitivities of 10 antitumor drugs. Using a real-time RT-PCR system, the mRNA expression levels of 16 genes related to drug resistance in 4 canine HS cell lines established from dogs with disseminated HS were determined and compared to 2 canine lymphoma cell lines (B-cell and T-cell). These 4 canine HS cell lines showed sensitivities toward microtubule inhibitors (vincristine, vinblastine and paclitaxel), comparable to those in the canine B-cell lymphoma cell line. Moreover, it was shown that P-gp in the HS cell lines used in this study did not have enough function to efflux its substrate. Sensitivities to melphalan, nimustine, methotrexate, cytarabine, doxorubicin and etoposide were lower in the 4 HS cell lines than in the 2 canine lymphoma cell lines. The data obtained in this study using cultured cell lines could prove helpful in the developing of advanced and effective chemotherapies for treating dogs that are suffering from HS.     

CCNU for the treatment of dogs with histiocytic sarcoma

BACKGROUND: Histiocytic sarcoma is an aggressive neoplasm of dendritic cells that carries a grave prognosis. The efficacy of chemotherapy against this disease is unknown. The purpose of this study was to determine the efficacy of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in dogs with incompletely resected or metastatic histiocytic sarcoma, to describe the clinical characteristics of these dogs, and to identify factors affecting prognosis. HYPOTHESIS: Our hypothesis is that CCNU has activity against canine histiocytic sarcoma and can improve survival in dogs with advanced disease. ANIMALS: Included in analysis are dogs diagnosed with histiocytic sarcoma who had gross measurable or residual microscopic disease and who received CCNU. METHODS: A multi-institutional, retrospective, single-arm cohort study was conducted. Available biopsy samples were tested with an antibody against CD18 when possible to confirm the diagnosis of histiocytic sarcoma. RESULTS: Fifty-nine dogs were treated at 8 institutions. Twenty-three tumor specimens were confirmed to be CD18 positive. Treatment with CCNU at 60 to 90 mg/m2 resulted in an overall response rate of 46% in the 56 dogs with gross measurable disease. All 3 dogs with minimal residual disease experienced tumor relapse but lived 433 days or more after starting CCNU. The median survival of all 59 dogs was 106 days. Thrombocytopenia (< 100,000 platelets/microL) and hypoalbuminemia were found to be negatively associated with prognosis and were predictive of < 1 month survival. CONCLUSIONS AND CLINICAL IMPORTANCE: Results suggest that CCNU is active against canine histiocytic sarcoma and may be useful in the treatment of dogs without negative prognostic factors.     

Localized and disseminated histiocytic sarcoma of dendritic cell origin in dogs

Canine histiocytic proliferative disorders include a wide spectrum of diseases characterized by different biologic behaviors. The etiology and pathogenesis of these diseases are largely unknown. The clinicopathologic, morphologic and immunophenotypic characteristics of canine localized and disseminated histiocytic sarcoma were examined in 39 dogs. Rottweilers, Bernese Mountain Dogs, and retrievers were most commonly affected (79%). Localized histiocytic sarcomas (19 dogs) arose from a single site, and metastatic lesions were observed in draining lymph nodes. Predilection sites were subcutis and underlying tissues on extremities, but tumors occurred in other locations, including spleen, lung, brain, nasal cavity, and bone marrow. Disseminated histiocytic sarcomas (20 dogs), a multisystem disease previously described as malignant histiocytosis, primarily affected spleen, lungs, bone marrow, liver, and lymph nodes. Both localized and disseminated canine histiocytic sarcomas were composed of pleomorphic tumor cell populations. CD1+, CD4-, CD11c+, CD11d-, MHC II+, ICAM-1 +, Thy-1 +/- tumor cells were identified in all snap-frozen samples (31 dogs). This phenotype is characteristic for myeloid dendritic antigen-presenting cell lineage. Hence, canine localized and disseminated histiocytic sarcomas are likely myeloid dendritic cell sarcomas. Dendritic antigen-presenting cells are a heterogeneous cell population with regards to their ontogeny, phenotype, function, and localization. The exact sublineage of the proliferating dendritic antigen-presenting cells involved in canine histiocytic sarcomas remains to be determined. Phenotypic analysis of formalin-fixed tissues from eight dogs was limited by available markers. Morphologic features and the phenotype CD18+, CD3-, and CD79a- were the most useful criteria to indicate likely histiocytic origin.     

Cytopathology of canine lymphomas (100 cases)

Malignant lymphoma is one of the most common malignant tumours occurring in dogs. Fine needle aspiration biopsy (FNAB) is an excellent, specific diagnostic procedure used to assess pathological processes in lymph nodes. The aim of the present study was to conduct a cytopathological analysis of lymphoma in dogs and to analyse some epidemic aspects of occurrence of lymphoma in 100 dogs using Giemsa stained slides. Samples were obtained by fine needle aspiration biopsy, fine needle non-aspiration biopsy, lymph node impression smears and by examination of body cavity effusions. The determination of the type and subtype of tumour was made on the basis of the updated Kiel classification adopted for dogs. Based on cytopathological analysis, the lymphoma was diagnosed in 100 dogs: 44 were female and 56 male. The animals' age ranged from 1.5 year to 15 years (median: 7.5 years), the animals were of different breeds (72% of all dogs belonged to 28 different breeds) and crossbreeds (28%). In 29% of dogs the regional or general lymphadenomegaly was the only clinical sign observed, in remaining cases (71%) at least one abnormality connected to lymphoma was found. Among all diagnosed lymphomas, high-grade lymphomas were more prevalent (86% of all cases) than low-grade lymphomas (14% of all cases). The possibility of boxers having a predisposition to T cell lymphoma development could be also suspected.     

Cytologic–histologic concordance in the diagnosis of neoplasia in canine and feline lymph nodes: a retrospective study of 367 cases

Lymph nodes are frequently sampled in dogs and cats for the diagnosis of primary and metastatic neoplasia. We determined the accuracy of cytologic diagnosis in lymph nodes using histology as the gold standard. Lymph node reports (2001–2011) were retrospectively evaluated and diagnoses were categorized as neoplastic or non‐neoplastic. Lymph nodes from 296 dogs and 71 cats included 157 (42.7%) non‐neoplastic lesions, 62 (16.9%) lymphomas and 148 (40.3%) metastatic neoplasms. Cytology had a sensitivity of 66.6% [95% confidence interval (CI) 60.0–72.8%], specificity of 91.5% (CI 86.3–95.2%), and accuracy of 77.2% (CI 72.6–81.3%) for neoplasia. Likelihood of malignancy with a positive cytologic diagnosis of neoplasia was 93.0%. High proportions of false‐negative results were found in mesenteric T‐cell lymphoma (22/35, 63%, mainly cats), metastatic sarcoma (8/14, 57%) and metastatic mast cell tumour (15/48, 31%, mainly dogs). Factors contributing to discrepancies included well‐differentiated lymphocyte morphology, focal distribution of metastases and poorly defined criteria for metastatic mast cell tumours.     

Acquired cardiac diseases in the dog: a retrospective analysis

To document the frequency of the different acquired cardiac diseases in the referring area of the University of Zurich, records of 474 dogs were retrospectively analysed. Most common were valvular diseases, predominantly atrioventricular valve endocardiosis (49.4%), myocardial diseases, predominantly dilated cardiomyopathy (21.1%), pericardial effusion (12.4%), mainly due to neoplasia or idiopathic pericarditis, and cardiac neoplasia without pericardial effusion (7.0%). Rare to very rare diagnoses were dirofilariosis (2.5%), endocarditis (1.1%, only 2 of these valvular), hypertrophic cardiomyopathy (0.6%) and infectious pericarditis (0.4%). Arrhythmias were found in 145 dogs, mainly tachyarrhythmias, and most commonly associated with dilated cardiomyopathy. Relevant concomitant diseases were tracheobronchial collapse and hyperadrenocorticism in dogs with mitral endocardiosis. Knowing prevalence and causes of the various cardiac and the complicating non-cardiac diseases with clinical similarities is important for formulating diagnosis and differential diagnosis.     

IMAGING CHARACTERISTICS OF INTRATHORACIC HISTIOCYTIC SARCOMA IN DOGS

In this retrospective study, two observers independently reviewed thoracic imaging studies of 39 dogs with confirmed histiocytic sarcoma. The most common findings were intrathoracic lymphadenopathy, identified by the first and second observers in 82.1% and 87.2% of dogs, respectively, and pulmonary masses (74.4% and 82.1%). Right middle lung lobe masses were significantly more common than masses in any other lung lobe (P<0.0013), with the majority having a ventral distribution. Sternal and tracheobronchial lymphadenopathy were significantly more common than cranial mediastinal lymphadenopathy (P‐values of 0.0002 and 0.012, respectively). Interobserver agreement regarding distribution of lymphadenopathy and pulmonary masses was good (κ=0.64 and 0.75, respectively). Other findings included pulmonary nodules, pleural effusion, and abnormal pulmonary patterns. In patients with CT examinations, the majority of masses were mildly to moderately enhancing and heterogeneous, poorly marginated, and bronchocentric. Lymphadenopathy and pulmonary masses are the most common intrathoracic findings in dogs with histiocytic sarcoma, and the strong predilection for the ventral aspect of the right middle lung lube may help to differentiate it from other types of neoplasia.     

Radiotherapy of malignant nasal tumors in 67 dogs

The nasal cavity of 67 dogs with malignant nasal neoplasia was treated with radiation. Preirradiation surgical cytoreduction of the tumor was done in 41 dogs. Fifty dogs were irradiated by use of 10 fractions over 22 days, and 17 dogs were given a similar total dose in 5 fractions over 35 days. The range of survival times (0.5 to 42 months), median survival time (8.5 months), and 1- and 2-year survival rates (38% and 30%, respectively) were better than those expected for other methods of treatment. Serious complications were few (4%). Survival times for dogs were determined on the basis of histologic tumor type and on the basis of megavoltage (cobalt or linear accelerator) vs softer deep radiation (cesium or orthovoltage) treatment, with or without cytoreductive surgery. Survival times of 10 dogs given softer radiation without surgery were shorter than those of 14 dogs that were given softer radiation and had cytoreductive surgery. Survival times of dogs that were given softer radiation and had surgery were similar to those of dogs that were given megavoltage radiation only. Cytoreductive surgery did not improve survival times for dogs that were given megavoltage radiation. Median survival time for 38 dogs with adenocarcinoma was 12 months, compared with 6 months for 14 dogs with squamous cell or undifferentiated carcinoma. Median survival time for 16 dogs with a variety of sarcomas was 11.2 months. Survival times of dogs with adenocarcinoma or sarcoma were significantly better (P less than 0.02 or 0.03) than for dogs with squamous cell or undifferentiated carcinoma. Necropsies were performed on 27 of 58 dogs that died or were euthanatized.(ABSTRACT TRUNCATED AT 250 WORDS)     

RETROSPECTIVE ASSESSMENT OF THORACIC RADIOGRAPHIC FINDINGS IN METASTATIC CANINE HEMANGIOSARCOMA

Twenty-one dogs with histopathologically confirmed hemangiosarcoma were evaluated by thoracic radiography for metastatic disease. All dogs had histopathologic examinations of the lungs within two weeks of thoracic radiography. Fourteen dogs had histopathologic evidence of pulmonary hemangiosarcoma; metastatic disease was detected radiographically in eleven of these dogs. The most common radiographic pattern was that of poorly defined small coalescing nodules (8 dogs); other radiographic patterns included well-circumscribed nodules (3 dogs) and alveolar infiltrates secondary to hemorrhage (2 dogs). Differential diagnoses for diffuse, poorly defined, coalescing pulmonary opacities should include hemangiosarcoma in addition to edema, lymphoma, systemic mycoses, fibrosis, allergy, toxicosis, and carcinomas.     

COMPUTED TOMOGRAPHIC APPEARANCE OF PRIMARY LUNG TUMORS IN DOGS

Canine primary lung tumors typically appear radiographically as a well‐circumscribed solitary mass in the periphery of a caudal lung lobe. Consolidated and diffuse forms of primary lung tumors have also been described. Nineteen dogs with computed tomographic (CT) images of the thorax and a histological diagnosis of primary lung tumor (17 primary carcinomas and two primary sarcomas) were evaluated retrospectively to characterize the CT findings. All primary lung tumors were bronchocentric in origin with internal air bronchograms. The bronchi were typically narrowed, displaced, and often obstructed by the tumor. Eighteen of 19 (95%) of the tumors were solitary and there was one pneumonic/alveolar form. Most solitary tumors were well circumscribed (17/18), located in the central to periphery of the lung (14/18), and in a cranial or caudal lobe (16/19). Most primary lung tumors (11/17) had mild to moderate heterogeneous contrast enhancement. Five of 19 dogs (26%) had evidence of pulmonary metastasis. Internal mineralization (3/19) and tracheobronchial lymphadenopathy (4/19) were also identified. On CT examination, solitary, well circumscribed, bronchocentric masses with internal air bronchograms are consistent with a primary pulmonary tumor in dogs.