Gross, histologic, cytochemical, and immunocytochemical study of medullary thyroid carcinoma in sixteen dogs

The gross, histomorphologic, cytochemical, and immunocytochemical findings in 16 dogs with medullary thyroid carcinoma were evaluated. Grossly, the neoplasms were encapsulated, firm, lobulated, and grey-white to tan. The typical histologic pattern was groups or sheets of round to polygonal cells with fibrovascular stroma, which was thickened and hyalinized in places. Variants of clear cell (two dogs), giant cell (one dog), and oxyphil cell (one dog) types were also seen. In all 16 dogs, Grimelius-stained sections of the neoplasms revealed intracytoplasmic silver granules; ten tumors contained amyloid and four contained mucin. Immunohistochemically, the neoplasms reacted to AE1/AE3 (n = 13), S-100 protein (n = 5), neuron specific enolase (n = 14), synaptophysin (n = 11), calcitonin (n = 16), somatostatin (n = 4), gastrin (n = 7), and serotonin (n = 6). Only one neoplasm was positive for vimentin. None of the neoplasms reacted to antibodies for neurofilaments, thyroglobulin, insulin, glucagon, or adrenocorticotrophic hormone. Eleven neoplasms contained multiple (two to four) peptides, in various combinations. It was concluded that in dogs, gross and histologic features can be used to distinguish medullary thyroid carcinoma from other thyroid malignancies. Cytochemical and immunocytochemical studies with neuron specific enolase, synaptophysin, and calcitonin can be used to establish the diagnosis of medullary thyroid carcinoma in dogs.     

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 intracranial primary neoplasia: 173 cases (1986-2003)

This study investigates the clinical and pathologic findings associated with 173 primary brain tumors in our hospital population of dogs that presented between the years 1986 and 2002. Of the 173 primary brain tumors, 78 (45%) were meningiomas, 29 (17%) were astrocytomas, 25 (14%) were oligodendrogliomas, 12 (7%) were choroid plexus tumors, and 7 (4%) were primary central nervous system lymphomas. Smaller numbers of glioblastomas (n = 5), primitive neuroectodermal tumors (n = 5), histiocytic sarcomas (n = 5), vascular hamartomas (n = 4), and unclassified gliomas (n = 3) were identified. One dog had both a meningioma and an astrocytoma. Most tumors were located within the telencephalon, and seizures were the most common clinical presenting complaint. Of 168 tumors for which a location in the brain was recorded at postmortem examination, 79 were found to involve more than 1 brain division. Other neoplasms unrelated to the primary brain tumor were identified on postmortem examination in 39 dogs (23%). Intrathoracic and intraabdominal neoplasms were present at necropsy in 13 and 24 cases, respectively. Based on the results of this study, thoracic radiographs and abdominal ultrasonography may be indicated to look for extracranial neoplasia prior to advanced imaging of the brain or intracranial surgery.     

Brain Stem Auditory-Evoked Response Abnormalities in 14 Dogs With Confirmed Central Nervous System Lesions

Abnormal brain stem auditory-evoked responses (BAER) were recorded on 14 dogs with brain lesions confirmed by necropsy (n = 13) or magnetic resonance imaging and surgical biopsy (n = 1). Lesions included brain stem or cerebellar tumors (6 dogs), brain stem trauma (1 dog), forebrain tumors (3 dogs), hydrocephalus (2 dogs), granulomatous meningoencephalitis (1 dog), and meningoencephalitis (1 dog). Five affected dogs were comatose at the time of recording. BAER abnormalities could be classified as (1) absence of some or all of waves I to V, (2) increased latencies, with wave V being most frequently affected, or (3) a reduction in the amplitude ratio of waves V/1.     

Management of canine atopic dermatitis using the plant extract PYM00217: a randomized, double-blind, placebo-controlled clinical study

This study evaluated PYM00217, a proprietary blend of plant extracts, in the management of canine atopic dermatitis (AD). One hundred and twenty dogs were diagnosed with perennial AD on the basis of history, clinical signs, a positive test for perennial allergens and elimination of other dermatoses. Exclusion criteria included antimicrobials within 7 days, antihistamines within 14 days, oral/topical glucocorticoids or ciclosporin within 28 days, and parenteral glucocorticoids, essential fatty acids or immunotherapy within 56 days. Flea control, shampoos and ear cleaners were permitted. Dogs with a minimum canine atopic dermatitis extent and severity index (CADESI) of 25 were randomly allocated to receive PYM00217 (100, 200 or 400 mg kg-1 day-1) or placebo for 12 weeks. The mean reductions in CADESI (intention-to-treat population) were 3.9% (placebo; n=29), 4.4% (100 mg kg-1 day-1; n=30), 23.4% (200 mg kg-1 day-1; n=29) and 8.5% (400 mg kg-1 day-1; n=29). The reduction in the 200 mg kg-1 day-1 group was significant (P<0.01). For dogs with a baseline CADESI>or=50, the mean changes were +10.6% (placebo; n=12), +0.6% (100 mg kg-1 day-1; n=14), -29.3% (200 mg kg-1 day-1; n=14) and -3.4% (400 mg kg-1 day-1; n=15). The 200 mg kg-1 day-1 dose was significantly more effective than placebo (P=0.038). No serious adverse effects were reported. Minor adverse effects seen in 10% (placebo and 100 mg kg-1 day-1), 24% (200 mg kg-1 day-1) and 42% (400 mg kg-1 day-1) of cases were mainly minor gastrointestinal disorders and only five cases required cessation of dosing. Two dogs (one in each of the 100 mg kg-1 day-1 and 200 mg kg-1 day-1 groups) refused to eat the medicated food. In conclusion, PYM00217 at 200 mg kg-1 appears to be an effective, palatable and well-tolerated treatment for canine AD.     

Canine cutaneous clear cell adnexal carcinoma: histopathology, immunohistochemistry, and biologic behavior of 26 cases.

Thirty tumors including 27 distinctive cutaneous neoplasms and 3 metastatic tumors from 26 dogs were collected from diagnostic submissions to 3 laboratories. Characteristic histopathologic features included location in the subcutis or dermis (or both); lobular, nodular, and nest-like architecture; and a component of epithelioid cells with clear cytoplasm. Additional features present in most cases included follicular dermal papilla-like structures, low mitotic index, nuclear pleomorphism, necrosis, and mineralization. Cytoplasmic periodic acid Schiff-positivity, which was abolished by pretreatment with diastase, indicated the presence of glycogen in all cases. The oil red O stain did not demonstrate cytoplasmic lipid. Melanin granules, accentuated by the Fontana-Masson method, were observed infrequently. A sparsely cellular mucinous stroma and stromal cartilaginous differentiation were uncommon. By immunohistochemistry, neoplastic cells stained positively for cytokeratin (29 of 29), vimentin (28 of 28), S-100 protein (24 of 29), and melan A (8 of 12); results were negative for smooth muscle actin and calponin in all cases. Clinical follow-up information was obtained on all 26 dogs. One tumor recurred, 1 metastasized to a regional lymph node, and 1 metastasized to regional lymph nodes twice. In another case, possible pulmonary metastasis was noted radiographically. The findings are consistent with a poorly differentiated, low-grade, adnexal carcinoma of the skin. Similar canine cutaneous neoplasms have been reported as "clear-cell hidradenocarcinoma" and "follicular stem cell carcinoma." The authors propose the designation "cutaneous clear cell adnexal carcinoma."     

A case of canine cutaneous clear cell adnexal carcinoma with prominent expression of smooth muscle actin

Cutaneous clear cell adnexal carcinoma was found in the right lip of a 14-year-old male castrated Shih Tzu. Histologically, the tumor mostly consisted of neoplastic cells with clear or vacuolated cytoplasms and contained frequent tubular structures. Neoplastic cells showed coexpression of pan-cytokeratin (CK) and vimentin by double-labeled immunofluorescence staining. In addition, immunohistochemistry revealed that the tumor cells were positive for pan-CK (AE1/AE3, KL1, CAM 5.2), CK-7, CK-8, CK-14, CK-15, CK-18, vimentin and alpha-smooth muscle actin (SMA) with varied intensity and positivity. Among these marker proteins, SMA was positive in 75% of the tumor cells. On the other hand, CK-15, which is a specific marker of follicular stem cells, was expressed in less than 1% of the tumor cells. Based on these findings, the tumor showed diverse differentiation in apocrine sweat glands and the inner and outer root sheaths of hair follicles, indicating the follicular stem cell to be the origin of this tumor.     

Diagnostic efficacy of serum alkaline phosphatase and gamma-glutamyltransferase in dogs with histologically confirmed hepatobiliary disease: 270 cases (1980-1990).

The diagnostic efficacy of serum alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) activities was examined, using the records of 270 dogs initially suspected of having hepatobiliary disease on the basis of history, findings on physical examination, results of baseline screening tests, or any combination of these data. Histologic examination of hepatic tissue was performed in each dog. Sixty-three dogs did not have histologic evidence of hepatobiliary disease and served as the control group. On the basis of diagnosis, dogs were assigned to 1 of 8 groups: dogs with cirrhosis (n = 34), steroid hepatopathy (n = 16), hepatic neoplasia (primary and secondary, n = 36), chronic hepatitis (n = 14), chronic passive congestion (n = 5), hepatic necrosis (n = 17), portosystemic vascular anomaly (n = 35), and cholestasis (extrahepatic bile-duct obstruction and intrahepatic cholestasis, n = 50). Of the 207 dogs with hepatobiliary disease, 29 (14%) had normal ALP and GGT activities, 31 (15%) had normal ALP activity, and 112 (54%) had normal GGT activity. Of the 63 control dogs, 29 (46%) had normal serum ALP and GGT activities, 32 had normal ALP activity (ALP specificity, 51%), and 55 had normal GGT activity (GGT specificity, 87%). The specificity of ALP and GGT in parallel (positive result = result of either test abnormal) was 46%, and in series (positive result = results of both tests abnormal) was 91%. The highest median activities of ALP developed in dogs with cholestasis, steroid hepatopathy, chronic hepatitis, and hepatic necrosis. The highest median activities of GGT developed in dogs with steroid hepatopathy, cholestasis, and hepatic necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glioblastoma multiforme: clinical findings, magnetic resonance imaging, and pathology in five dogs

Although glioblastoma multiforme (GBM), a World Health Organization grade IV astrocytoma, is the most common primary brain tumor in humans, in dogs GBM is relatively rare, accounting for only about 5% of all astrocytomas. This study presents combined clinical, neuroimaging, and neuropathologic findings in five dogs with GBM. The five dogs, aged from 5 to 12 years, were presented with progressive neurologic deficits that subsequent clinical neurologic examination and neuroimaging studies by magnetic resonance imaging (MRI), localized to space occupying lesions in the brain. MRI features of the tumors included consistent peritumoral edema (n = 5), sharp borders (n = 4), ring enhancement (n = 3), heterogenous T2-weighted signal intensity (n = 3), iso- to hypointense T1-weighted images (n = 5), necrosis (n = 5), and cyst formation (n = 2). Two tumors were diagnosed clinically using a computed tomography-guided stereotactic biopsy procedure. At necropsy all the tumors resulted in, on transverse sections, a prominent midline shift and had a variegated appearance due to intratumoral necrosis and hemorrhage. Histologically, they had serpentine necrosis with glial cell pseudopalisading and microvascular proliferation, features which distinguish human GBM from grade III astrocytomas. Immunoreactivity of tumor cells for glial fibrillary acidic protein was strongly positive in all cases, whereas 60% and 40% of the tumors also expressed epidermal growth factor receptor and vascular endothelial growth factor, respectively. These canine GBMs shared many diagnostic neuroimaging, gross, microcopic, and immunoreactivity features similar to those of human GBMs.     

Immunocytochemical differentiation of canine mesenchymal tumors in cytologic imprint preparations

BACKGROUND: Immunocytochemical techniques are a potentially valuable diagnostic tool to support cytologic diagnosis in dogs. However, detailed studies of staining patterns and intensity in cytologic specimens of mesenchymal tumor types are lacking. OBJECTIVE: The aim of this study was to evaluate commercially available antibodies against human proteins for use in the characterization of canine tumors of mesenchymal origin in cytologic samples. METHODS: Immunocytochemical staining was performed on air-dried imprint specimens of biopsies obtained from 103 mesenchymal neoplasms and 14 metastatic lesions from 98 dogs. All specimens were stained with anti-cytokeratin AE1/AE3 and vimentin. Based on the histologic diagnosis, tumors of muscle, endothelial, histiocytic, and melanocytic origin also were stained with cell-specific antibodies. Staining intensity was subjectively graded and the percentage of positive tumor cells was estimated. RESULTS: All mesenchymal tumors and metastases, with the exception of mesotheliomas, were vimentin-positive and cytokeratin-negative; mesotheliomas (n=6) were positive for both vimentin and cytokeratin. Tumors of muscle (n=5), endothelial (n=15), and histiocytic (n=18) origin stained moderately to strongly positive in a majority of tumor cells with desmin, von Willebrand factor, and lysozyme, respectively. Malignant melanomas (n=15) had variable staining and a variable percentage of positive cells with Melan-A and S100. CONCLUSIONS: Our results indicate that immunocytochemical staining of canine cytologic specimens is a reliable and sensitive technique that may be of benefit for the differentiation of poorly differentiated mesenchymal tumors and metastases. Additional study is needed to assess the specificity of immunocytochemical stains in mesenchymal tumors.     

Efficacy of mitoxantrone against various neoplasms in dogs

One hundred twenty-six dogs with histologically confirmed, measurable malignant tumors were evaluated in a prospective study to determine the response to the antineoplastic drug mitoxantrone. Ninety-five dogs had been refractory to one or more treatment modalities (surgery, n = 57; chemotherapy other than mitoxantrone, n = 37; radiation, n = 4; whole body hyperthermia, n = 1). The extent of neoplastic disease was determined immediately before each dose of mitoxantrone was administered (1 to 10 doses, 2.5 to 5 mg/m2 of body surface area, IV) 21 days apart. Each dog was treated with mitoxantrone until the dog developed progressive disease or until the dog's quality of life diminished to an unacceptable level as determined by the owner or attending veterinarian. A partial or complete remission (greater than 50% volume reduction) was obtained in 23% (29/126) of all dogs treated. Tumors in which there was a partial or complete remission included lymphoma (11/32), squamous cell carcinoma (4/9), fibrosarcoma (2/9), thyroid carcinoma (1/10), transitional cell carcinoma (1/6), mammary adenocarcinoma (1/6), hepatocellular carcinoma (1/4), renal adenocarcinoma (1/1), rectal carcinoma (1/1), chondrosarcoma (1/2), oral malignant melanoma (1/12), cutaneous malignant melanoma (1/1), myxosarcoma (1/1), mesothelioma (1/1), and hemangiopericytoma (1/1). Our results indicated that mitoxantrone induces measurable regression in various malignant tumors in dogs.     

Correlation of DNA ploidy to tumor histologic grade, clinical variables, and survival in dogs with mast cell tumors.

By using flow cytometry, a retrospective analysis of the DNA content of 40 primary canine mast cell tumors and seven lymph nodes that contained metastatic mast cell tumor from 44 dogs of various breed, sex, and age was performed on formalin-fixed, paraffin-embedded samples of the tumors and nodes. These samples were chosen according to the following criteria: samples contained sufficient well-preserved tumor tissue in the paraffin block for processing, sufficient patient history data were available, clean and homogeneous cell suspensions were obtained after processing, and interpretable DNA histograms were produced on analysis. The ploidy data obtained were compared with the histopathologic grade, the anatomical site of occurrence, the clinical stage of the tumors, and the survival of the dogs. Over 70% (29/40) of the mast cell tumors were diploid. Three metastatic mast cell tumors in lymph nodes had the same ploidy status as their corresponding primary tumors. In five dogs, mast cell tumors from multiple sites in each dog displayed similar ploidy status. Of 26 dogs evaluated for survival times, 69% (18/26) had diploid tumors and 31% (8/26) had aneuploid tumors. When numbers of diploid versus aneuploid tumors were compared, no significant difference was found between any two grades, clinical stages, or anatomic sites. A significant difference (P = 0.02) was found, however, between aneuploid and diploid tumors when comparing Stage I and non-Stage I disease. The Kaplan-Meier survival plot indicated a tendency towards an increased survival within the first year in dogs with diploid versus aneuploid tumors (P = 0.06).     

p63: a novel myoepithelial cell marker in canine mammary tissues

Several immunohistochemical markers have been used to demonstrate the presence of myoepithelial cells in order to determine their role in the histogenesis of mammary tumors. p63, a recently characterized p53 homologue, is consistently expressed in myoepithelial cells of the human breast; however, no assessment of its immunoreactivity has been reported so far in canine mammary tissues. We investigated p63 immunohistochemical expression, as a novel myoepithelial cell nuclear marker, in 81 samples of normal (n = 2), hyperplastic (n = 11), and neoplastic (n = 68) canine mammary tissues. Myoepithelial phenotype was confirmed by using complementary monoclonal antibodies: alpha-smooth muscle actin, cytokeratin 14, cytokeratin AE1/AE3, and vimentin. p63 expression was observed in 91.4% (74/81) of the samples evaluated. Normal mammary glands, mammary hyperplasias, and benign tumors showed 100% immunoreactivity, with p63 expression restricted to myoepithelial cell nuclei. In general, benign mixed tumors showed a basal cell compartment immunoreactive to p63, with a gradual decrease of its expression during myoepithelial transformation. p63 expression was found in 72% of malignant tumors, allowing myoepithelial or basal cell identification in spindle-cell carcinomas (2/2), tubulopapillary carcinomas (8/9), solid carcinomas (7/10), and carcinosarcomas (1/3). The osteosarcoma analyzed was p63 negative. In our series, stromal components were consistently nonreactive to p63. In conclusion, the present study reveals p63 as a sensitive and highly specific marker of myoepithelial cells in canine mammary tissues, and the authors suggest p63 as an additional marker for defining myoepithelial histogenesis.     

Endostatin and vascular endothelial growth factor concentrations in healthy dogs, dogs with selected neoplasia, and dogs with nonneoplastic diseases

To evaluate the relationship between endostatin and vascular endothelial growth factor (VEGF) in cancers of dogs, circulating concentrations of these 2 tumor-associated markers were measured prospectively in healthy dogs (n = 44), dogs with tumors (n = 54), and dogs with nonneoplastic diseases (n = 42 for endostatin; n = 16 for VEGF). A canine-directed enzyme-linked immunosorbent assay kit was used for determination of endostatin, and a human-directed kit was validated for detection of canine VEGF. Concentrations of endostatin for all dogs were 28-408 ng/mL. Increasing serum endostatin concentration was associated with increasing age (P = .0396). Concentrations of endostatin were not different among groups of dogs (P = .1989) when adjusted for age. Mean endostatin concentrations for all dogs were higher in dogs (P = .0124) with detectable VEGF concentrations. Endostatin concentrations, when corrected for age, were related to decreasing PCV (P = .032) but not white blood cell count (P = .225) or platelet count (P = .1990). Measurable VEGF (> or = 2.5 pg/mL) was detected in 3 (7.0%) of 43 healthy dogs. Dogs with tumors had detectable VEGF in 24 (44%) of 54 dogs, with concentrations ranging from 2.5-274 pg/mL; only 1 dog with a nonneoplastic disease process had detectable VEGF. VEGF concentrations for all dogs after correcting for age, endostatin, and disease categories were associated with increased white blood cell count (P = .0032) and platelet counts (P = .0064) and decreased PCV (P = .0017). Linkage between increased endostatin and VEGF concentrations suggests that similar factors may influence concentrations of these markers. Further evaluation of endostatin and VEGF associations in dogs with tumors may provide information on the extent and progression of the disease.     

Canine digital tumors: a veterinary cooperative oncology group retrospective study of 64 dogs

We compared clinical characteristics and outcomes for dogs with various digital tumors. Medical records and histology specimens of affected dogs from 9 veterinary institutions were reviewed. Risk factors examined included age, weight, sex, tumor site (hindlimb or forelimb), local tumor (T) stage, metastases, tumor type, and treatment modality. The Kaplan-Meier product limit method was used to determine the effect of postulated risk factors on local disease-free interval (LDFI), metastasis-free interval (MFI), and survival time (ST). Outcomes were thought to differ significantly between groups when P < or = .003. Sixty-four dogs were included. Squamous cell carcinoma (SCC) accounted for 33 (51.6%) of the tumors. Three dogs presented with or developed multiple digital SCC. Other diagnoses included malignant melanoma (MM) (n = 10; 15.6%), osteosarcoma (OSA) (n = 4; 6.3%), hemangiopericytoma (n = 3; 4.7%), benign soft tissue tumors (n = 5; 7.8%), and malignant soft tissue tumors (n = 9; 14%). Fourteen dogs with malignancies had black hair coats, including 5 of the 10 dogs with MM. Surgery was the most common treatment and, regardless of the procedure, had a positive impact on survival. None of the patient variables assessed, including age, sex, tumor type, site, and stage, had a significant impact on ST. Both LDFI and MFI were negatively affected by higher T stage, but not by type of malignancy. Although metastasis at diagnosis correlated with a shorter LDFI, it did not have a significant impact on ST. On the basis of these findings, early surgical intervention is advised for the treatment of dogs with digital tumors, regardless of tumor type or the presence of metastatic disease.     

Cytologic evaluation of primary and secondary myelodysplastic syndromes in the dog

Myelodysplastic syndromes are a heterogeneous group of acquired primary and secondary alterations of hematopoietic stem cells that result in cytopenias in blood and cytologic features of dysplasia in blood and/or bone marrow. To better understand the cytologic features that would permit differentiation of primary and secondary forms of myelodysplasia, we reviewed 267 consecutive bone marrow reports from dogs. These reports indicated that 34 dogs (12.7%) had dysgranulopoiesis, dyserythropoiesis, and/or dysthrombopoiesis in >10% of granulopoietic cells, erythroid cells, and/or megakaryocytes, respectively. Thirteen dogs had primary myelodysplastic syndromes, and 21 had secondary myelodysplastic syndromes. Of the 13 dogs with primary myelodysplasia, 4 were subclassified as myelodysplastic syndrome with refractory anemia (MDS-RA), and 9 were subclassified as myelodysplastic syndrome with excess blasts (MDS-EB). Secondary conditions associated with dysplasia in the bone marrow included malignant lymphoma (n = 5), myelofibrosis (n = 3), immune-mediated thrombocytopenia (n = 4), immune-mediated hemolytic anemia (n = 5), multiple myeloma with melphalan administration (n = 1), pyometra with estrogen administration (n = 1), polycythemia vera (n = 1), and thrombopathia (n = 1). MDS-RA was characterized by <5% myeloblasts in bone marrow, normal granulocyte maturation ratio, increased erythroid maturation ratio, and dysplastic changes in >15% of erythroid cells. MSD-EB was characterized by >/=5% myeloblasts in bone marrow, high granulocyte maturation and erythroid maturation ratios, >/=32% dysplastic granulocytes, and the presence of small atypical immature myeloid cells. Secondary myelodysplastic syndromes were characterized by <5% myeloblasts in bone marrow, variable granulocyte maturation and erythroid maturation ratios, and variable dysplastic features. These results indicate that morphology alone cannot be used to distinguish primary and secondary myelodysplastic syndromes in dogs.     

C-kit expression in canine mucosal melanomas

The c-kit receptor is responsible for transmission of promigration signals to melanocytes; its downregulation may be involved in malignant progression of human melanocytic neoplasms. Expression of this receptor has not been examined in normal or neoplastic melanocytes from dogs. In this study, 14 benign dermal and 61 malignant mucosal melanocytic tumors were examined for c-kit (KIT) expression. Sites of the mucosal melanomas were gingiva (not further specified; n = 30), buccal gingiva (n = 6), soft palate (n = 4), hard palate (n = 5), tongue (n = 7), lip (n = 6), and conjunctiva (n = 3). Melan A was expressed in all 14 dermal melanocytomas and in 59 of 61 (96.7%) tumors from oral or conjunctival mucosa, confirming melanocytic origin. C-kit receptor expression was strong and diffuse throughout the cytoplasm in all 14 dermal melanocytomas and was identified in basilar mucosal melanocytes over submucosal neoplasms (27 of 61, 44.3%), junctional (neoplastic) melanocytes (17 of 61, 27.9%), and, less commonly, neoplastic melanocytes of the subepithelial tumors (6 of 61, 9.8%). KIT expression anywhere within the resected melanomas correlated with significantly longer survival. These results suggest that c-kit receptor expression may be altered in canine melanomas and may have potential as a prognostic indicator for mucosal melanomas.     

Canine ovarian neoplasms: a clinicopathologic study of 71 cases, including histology of 12 granulosa cell tumors

In a retrospective study of 71 primary ovarian tumors in the dog, epithelial tumors (46%) were more common than sex cord stromal (34%) and germ cell tumors (20%). There were more adenocarcinomas (64%) than adenomas. Sex cord stromal tumors were equally divided into Sertoli-Leydig (12/24) and granulosa cell tumors (12/24). There were equal numbers (7/14) of dysgerminomas and teratomas among the germ cell tumors. Most teratomas (6/7) were malignant. Most granulosa cell tumors were solid; two were mostly cystic. Patterns included sheets of round and ovoid to spindle-shaped cells separated by thin, fibrovascular stroma; neoplastic cells formed rosettes or Call-Exner bodies. In some areas, neoplastic cells were in cords or columns and formed cyst-like structures. Four granulosa cell tumors were macrofollicular, having cysts lined with granulosa cells. Median ages of dogs with different ovarian neoplasms were similar; all were more than 10 years old, except the dogs with teratoma (mean age, 4 years). Most neoplasms were unilateral (84%), except the Sertoli-Leydig cell tumors, many of which were bilateral (36%). Size of ovarian neoplasms varied (2 cm3 to 15,000 cm3). Twenty-nine percent of neoplasms metastasized; adenocarcinomas (48%) and malignant teratomas (50%) had the highest rates, and distant metastasis was more common in malignant teratoma. Endometrial hyperplasia was in 67% of the dogs; it was most common in dogs with sex cord stromal tumors (95%). Uterine malignancy was not seen in dogs with granulosa cell tumors, although hyperplasia endometrium was in all dogs with this tumor. Cysts in the contralateral ovaries were most common in dogs with sex cord stromal tumors.     

Pituitary tumor size, neurologic signs, and relation to endocrine test results in dogs with pituitary-dependent hyperadrenocorticism: 43 cases (1980-1990).

Pituitary neoplasm was identified in 43 dogs with pituitary-dependent hyperadrenocorticism via necropsy (n = 33), diagnostic imaging with computerized tomography or magnetic resonance imaging (n = 5), or diagnostic imaging and necropsy (n = 5). All dogs had clinical signs and clinicopathologic test results typical of hyperadrenocorticism. Thirty-seven dogs had grossly visible pituitary tumors, and 6 dogs had microscopic pituitary tumors. Fifteen dogs had developed neurologic signs typical of those resulting from an enlarging pituitary mass. Twenty-three dogs had pituitary tumors greater than or equal to 1 cm in diameter. Provocative testing of the pituitary-adrenocortical axis was performed on all dogs. Dogs with grossly visible pituitary tumors and dogs with neurologic signs had significantly (P less than 0.05) higher mean plasma endogenous ACTH concentrations, compared with values from dogs with microscopic tumors and dogs without neurologic signs, respectively. Dogs with grossly visible pituitary tumors and dogs with tumors greater than or equal to 1 cm in diameter had significantly (P less than 0.05) lower adrenocortical responsiveness to exogenous ACTH, compared with dogs with microscopic pituitary tumors and dogs with tumors less than 1 cm in diameter, respectively. Despite these differences, there was overlap between test results among dogs. On the basis of endocrine test results, it would appear difficult to distinguish dogs with pituitary-dependent hyperadrenocorticism and large pituitary tumors from those with pituitary-dependent hyperadrenocorticism and microscopic pituitary tumors prior to onset of neurologic signs.     

Treatment by digital amputation of subungual squamous cell carcinoma in dogs: 21 cases (1987-1988)

Malignant digital tumors were diagnosed in 62 dogs during a 1-year period. Twenty-one (33.9%) of the dogs had subungual squamous cell carcinoma. Each of these dogs had involvement of single digits. Sixteen (76.2%) of the dogs with squamous cell carcinoma were large-breed dogs, and 15 (71.4%) had predominantly black coats. Labrador Retrievers (n = 5, 23.8%) and Standard Poodles (n = 3, 14.3%) were the most commonly represented purebreeds. None of the dogs had evidence of metastases prior to treatment. All 21 tumors were treated by amputation of the involved digit. Histologic evidence of neoplastic bone invasion was found in 15 of the 21 amputated digits (71.4%). Local tumor recurrences were not observed. Only 1 dog developed documented metastatic disease; this dog was euthanatized because of pulmonary metastases 5 months after surgery. At the time of this report, 9 dogs (42.9%) were alive with no evidence of disease (median, 26 months after surgery), and 11 dogs (52.4%) had died or were euthanatized (median, 20 months after surgery). The cause of death in 7 dogs was known to be unrelated to squamous cell carcinoma, and the cause of death in 4 dogs was unknown. The 1-year and 2-year survival rates were 76.2% and 42.9%, respectively.