Perianal malignant melanoma in a dog

Melanocytic tumors are relatively common in dogs and most often occur in the oral cavity, lip, skin, digit, and eye. There are notable differences in the behavior of these tumors, depending on their anatomical location. The majority of oral melanomas and two-thirds of melanomas arising from the digit are malignant, whereas most of melanomas originating from the haired skin are benign. The anus and perianal areas are very uncommon sites for melanocytic tumors in domestic animals except horses, and most of those tumors in horses are malignant. To our knowledge, perianal malignant melanoma has not been reported in the dog and its prognosis is unknown.     

Prognosis after surgical excision of canine melanomas.

One hundred and thirty-four dogs from which melanomas had been excised were studied until death or for at least 2 years after surgery. Seven of 49 (14%) intraoral and lip tumours and 52 of 85 (61%) skin tumours were histologically benign; in spite of this, three of seven (43%) "benign" oral and four of 52 (8%) "benign" skin lesions led to the eventual death of the host. Thirty eight of 42 (90%) dogs with a histologically malignant melanoma of the lip or oral cavity died because of the tumour but only 15 of 33 (45%) with malignant skin melanomas died. Six of 59 (10%) dogs with a tumour of mitotic index 2 or less died from the tumour 2 years after surgery compared to 19 of 26 (73%) dogs having a tumour with a mitotic index of 3 or more.     

Partial Maxillectomy and Premaxillectomy in the Treatment of Oral Neoplasia in the Dog and Cat

Partial maxillectomies were performed in 17 dogs and three cats to accomplish wide excision of oral tumors. The extent of the maxillectomy was dependent on tumor type, location, size, and invasiveness as determined by clinical and radiographic examination and incisional biopsy. The tumor and involved portions of adjacent facial bones, most commonly the maxillary and incisive bones, were removed. The resulting oronasal defect was closed by suturing a labial mucosal flap based on the lip margin to the hard palate mucoperiosteum. The major postoperative complication was partial suture line dehiscence, which occurred in three dogs. All four dogs with benign tumors were free of disease 7 to 34 months postoperatively (median 21.5 months). Of the 13 dogs treated for malignant neoplasia, seven were tumor-free at follow-up times ranging from 3 to 31 months (median 12 months). Five dogs with malignant tumors developed local recurrence 1 week to 10 months postoperatively (median 4.5 months). One cat with a benign tumor and two with malignant tumors were tumor-free at follow-up times of 7, 24, and 27 months. Partial maxillectomy can be effective in treating both benign and malignant oral tumors in dogs and cats.     

Thyroid neoplasms in a colony of beagle dogs

The histologic, clinicopathologic, and epidemiologic features of spontaneous thyroid neoplasms were evaluated in a control population of Beagle dogs. The mean age of thyroid tumor-bearing dogs (16.2 years) as significantly higher than non-tumor-bearing dogs (13.6 years). Thirteen benign and 18 malignant tumors were identified, with the incidence of both tumors increasing rapidly near the mean age of 16.2 years for tumor-bearing dogs. The age-specific incidence of tumors was 1.1% per year at 8 to 12 years, increasing to 4.0% per year by 12 to 15 years and 67% over 17 years of age. Numbers of malignant tumors were greater than benign tumors at an earlier age. Approximately 44% of the malignant tumors metastasized but only 22% resulted in death of the dog. There was no difference in tumor incidence when compared according to sex, if total tumor numbers were considered or if tumors were separated into benign and malignant categories. The age at death of tumor-bearing dogs was not increased significantly by the surgical resection of the thyroid tumors. Of dogs with thyroid tumors, 15% had clinical diagnoses of hypothyroidism, and no dogs with thyroid tumors had diagnoses of hyperthyroidism.     

Effect of substrate selection on indirect immunofluorescence testing of canine autoimmune subepidermal blistering diseases

The detection by indirect immunofluorescence (IIF) of circulating antibodies in the serum of dogs with autoimmune subepidermal blistering diseases (AISBD) was regarded for a long time as an unrewarding tool. It was, however, demonstrated in humans that the sensitivity of IIF assays depended on the selection of the substrates used. The effects of substrate selection on IIF tests was thus studied by examining sera from 12 dogs with AISBD tested against 8 different substrates from 3 different normal dogs. Patients with AISBD suffered from bullous pemphigoid (n = 4 sera), mucous membrane pemphigoid (n = 4 sera), and epidermolysis bullosa acquisita (n = 4 sera). Substrates included canine tongue, canine lip, canine dorsal haired skin, and ventral haired skin. The same 4 substrates were also split with salt splitting technique (using 1 M sodium chloride), in order to cleave the basement membrane within the lamina lucida and to expose the targeted antigens. The strength of the specific fluorescence of each slide was scored after processing for IIF testing with anti-canine IgG polyclonal antibody. Other criteria, such as background fluorescence, easiness of the interpretation, and variations within a same substrate, were also assessed. Intact canine lip and canine salt-split lip demonstrated consistently stronger intensity of fluorescence and a better ease of interpretation. We concluded that the performance of IIF tests with such substrates was a reliable tool for the detection of circulating IgG autoantibodies of canine patients with AISBD.     

Cutaneous epitheliotropic lymphoma with dual CD3 and c‐kit expression in a dog

An 11‐year‐old 8.9‐kg spayed female Boston Terrier was presented for evaluation of a mucocutaneous tumor on the right side of the upper lip that had been biopsied (punch biopsy) by the referring veterinarian. The histologic diagnosis was poorly differentiated round cell tumor involving the submucosa with patchy involvement of the mucosa. On presentation of the dog to Louisiana State University, the tumor was found to involve the mucosa and haired skin surface of the right upper lip. A fine‐needle aspirate of the right mandibular lymph node contained atypical poorly differentiated round cells similar to those in the histologic sections. To further characterize the tumor, immunohistochemical analysis of the tumor on the lip was performed; tumor cells were strongly immunoreactive for both CD3 and c‐kit in a cytoplasmic to membranous pattern, with CD3 expression having a more intense membranous component. The diagnosis was cutaneous epitheliotropic T‐cell lymphoma with co‐expression of CD3 and c‐kit by neoplastic lymphocytes, an unusual finding. As receptor tyrosine kinases can be attractive targets for cancer treatment, expression of these molecular targets in tumors is a promising subject of future research.     

Cell proliferation and expression of connexins differ in melanotic and amelanotic canine oral melanomas

Melanoma is a malignant neoplasm occurring in several animal species, and is the most frequently found tumor in the oral cavity in dogs. Melanomas are classified into two types: melanotic and amelanotic. Prior research suggests that human amelanotic melanomas are more aggressive than their melanotic counterparts. This study evaluates the behavior of canine melanotic and amelanotic oral cavity melanomas and quantifies cell proliferation and the expression of connexins. Twenty-five melanomas (16 melanotic and 9 amelanotic) were collected from dogs during clinical procedures at the Veterinary Hospital of the School of Veterinary Medicine and Animal Science of the University of São Paulo, Brazil. After diagnosis, dogs were followed until death or euthanasia. Histopathology confirmed the gross melanotic or amelanotic characteristics and tumors were classified according to the WHO. HMB45 or Melan A immunostainings were performed to confirm the diagnosis of amelanotic melanomas. Cell proliferation was quantified both by counting mitotic figures and PCNA positive nuclei. Expressions of connexins 26 and 43 were evaluated by immunohistochemistry, qRT-PCR and Western blot. Dogs bearing amelanotic melanomas presented a shorter lifespan in comparison to those with melanotic melanomas. Cell proliferation was significantly higher in amelanotic melanomas. Expressions of Connexins 26 and 43 were significantly reduced in amelanotic melanomas. The results presented here suggest that oral cavity melanotic and amelanotic melanomas differ regarding their behavior, cell proliferation and connexin expression in dogs, indicating a higher aggressiveness of amelanotic variants.     

Morphology and behavior of primary ocular melanomas in 91 dogs

Primary ocular melanocytic neoplasms from 91 dogs were divided into two groups by histologic criteria. Seventy-five were benign and composed of spindle-shaped and large polyhedral melanocytes similar to those of human ocular melanocytomas. Fifty-nine of these originated in the uvea where most resulted in uveitis, glaucoma, or hyphema prior to enucleation. None metastasized. Nineteen melanocytomas were limbal tumors. None metastasized, but three of nine incompletely excised tumors were found within the anterior chamber 2 to 3 years after the initial removal. Sixteen uveal melanocytic neoplasms were histologically malignant. Three had confirmed metastases, all within 3 months of enucleation. Cell type or pattern of growth within the globe were not predictive of biologic behavior. Our data suggest that the mitotic index is the best criterion for histologic identification of ocular melanomas with high metastatic potential. We propose that the classification of primary ocular melanomas be simplified to include only two categories: melanocytoma (benign) and melanoma (potentially malignant). Further behavioral data may justify a grading scheme for melanomas based upon mitotic index.     

Immunohistochemical detection of canine distemper virus in haired skin, nasal mucosa, and footpad epithelium: a method for antemortem diagnosis of infection.

A reliable antemortem diagnostic method is needed for determining infection with canine distemper virus (CDV). The utility of immunohistochemical detection of CDV antigen was examined was examined for samples of nasal and footpad epithelium and haired skin in dogs with and without detectable CDV antigen in the lung and/or brain. Tissues from 57 dogs at risk of CDV infection were tested. Viral antigen was found in the lung and/or brain of 28 dogs. Among these dogs, viral antigen was demonstrated in the epithelial cells of the nasal mucosa in 24 of 27 dogs, in the footpad epithelium in 24 of 26 dogs, and in the haired skin of the dorsal neck in 26 of 27 dogs. Among the 29 dogs without CDV antigen in either the lung or brain, 1 dog had positive staining for viral antigen in the skin and nasal mucosa. Biopsies of haired skin of the dorsal neck, which is relatively simple to sample, can be used for immunohistochemical testing for acute and subacute infection with CDV.     

p53 gene mutations occurring in spontaneous benign and malignant mammary tumors of the dog

Sixty-three cases of benign and malignant canine mammary tumors were analyzed to define the alteration of exons 5-8 for the p53 tumor suppressor gene using polymerase chain reaction direct sequence analysis with paraffin-embedded tissues. Four missense mutations were found in 38 benign mammary tumors (11%), and five missense (one tumor had two missense mutations) and one nonsense mutations were found in 25 mammary carcinomas (20%). These data suggest that the p53 gene alterations might be initiated at an early stage of canine mammary carcinogenesis and p53 mutations might be associated with malignancy. However, there was no evidence of any relationship between the p53 alterations and the histologic types of tumors or breeds of dogs.     

Feline melanoma: a comparative study of ocular, oral, and dermal neoplasms

Melanomas diagnosed in 29 cats over an 11 year period included 19 ocular (16 intraocular, three palpebral), five oral, and five dermal melanomas. Intraocular melanomas involved the ciliary body and iris in 12; the whole eye was involved in four. The average age of cats with intraocular melanomas was 11 years; the female : male ratio was 9 : 7. Histologically, eight intraocular tumors were mixed, six were epithelioid, and two were spindle cell. Ten of 16 cats (62.5%) with intraocular melanomas were killed because of the tumor at a mean of 156 days; four are living with no evidence of disease (average, 255 days). The mean time of death in cats with palpebral melanoma was 409 days. Metastasis occurred in 63% of cats with intraocular melanoma and all cats with palpebral melanoma. Four cats with oral melanoma were killed at a mean of 61 days; all had metastasis. Of five cats with cutaneous melanoma, one was killed with metastasis at 90 days; three cats were alive without evidence of recurrence or metastasis greater than 365 days after surgery. Results of this study indicate that in the cat, ocular melanomas are more common than oral and dermal melanomas, and ocular and oral melanomas are more malignant than dermal melanomas, with higher rates of mortality and metastasis.     

A retrospective study of visceral and nonvisceral hemangiosarcoma and hemangiomas in domestic animals.

Cases of hemangiosarcoma submitted to the Colorado State University Veterinary Diagnostic Laboratory during a 6-year period were reviewed. Visceral hemangiosarcomas represent less than 2% of canine specimens submitted for histologic examination and nonvisceral hemangiosarcoma less than 1%. Most nonvisceral hemangiosarcomas of dogs occur in skin. Hemangiosarcomas are less common in cats and usually occur in skin. They are also rare in other animal species. Animals with nonvisceral hemangiosarcomas are usually mature; dogs and cats average 10 years of age. The tumors develop in many different locations, and there is no sex predilection. A wide variety of dog breeds are affected, but Italian greyhounds, greyhounds, and whippets are overrepresented. Clinical outcomes of 76 cases of nonvisceral hemangiosarcomas in dogs and cats were obtained from submitting veterinarians. Completeness of excision of a tumor is the most important factor that can be used in predicting clinical outcome for an affected dog or cat. In all cases in which the animals were clinically normal for at least 1 year after surgical removal of a nonvisceral hemangiosarcoma, the margins were reported to be free of neoplastic cells. Degree of differentiation, mitotic rate, size of tumor, and presence or absence of epidermal ulceration, mast cells, or solar elastosis did not correlate with clinical outcome.     

Mammary tumor recurrence in bitches after regional mastectomy

Objectives— To investigate the histologic diagnosis and incidence of new mammary tumor growth in the remaining mammary chain tissue after regional mastectomy.
Study Design— Prospective clinical study.
Animals— Female dogs (n=99) that had excision of a single mammary tumor.
Methods— Female dogs that had regional mastectomy to remove a single tumor were followed for ≥1 year postoperatively. Data regarding tumor type, tumor recurrence, and development of metastasis were recorded.
Results— Fifty-seven (58%) dogs developed a new tumor in the ipsilateral mammary chain after the 1st surgery; 77% had repeat surgery. There was no significant correlation between the time to new tumor development and the histologic diagnosis for the 1st and 2nd tumor types. In 31 dogs, the histologic diagnosis for initial and subsequent tumors was identical and there was a significant correlation such that dogs with an initial malignant tumor are likely to develop another malignant tumor ( P =.0089). The histologic classification of the new tumor was likely to be malignant if it was located close to the side where the initial tumor had been removed ( P =.026).
Conclusions— Our results show that 58% of dogs developed a new tumor in the remaining mammary glands of the ipsilateral chain after regional mastectomy for removal of a single tumor.
Clinical Relevance— This should be taken into account when deciding on the surgical management (radical or regional mastectomy) in dogs with single mammary tumors.     

Associations between canine benign and malignant neoplasms

Associations between benign and malignant neoplasms of the dog were quantitatively evaluated. Using histologically confirmed submissions and population-based methodology, canine benign tumors were significantly associated with both the unordered and subsequent development of additional distinct malignancies in the same dogs. A detailed examination of the methods indicated that these results are not likely due to methodologic artifact. The implication is that benign and malignant tumor development are associated and that the occurence of a benign neoplasm is an indicator of a parallel predisposition to malignancy.     

Evaluation of progesterone and estrogen receptor expression in 15 meningiomas of dogs and cats

OBJECTIVE: To evaluate progesterone and estrogen receptor expression in meningiomas of the CNS in dogs and cats. ANIMAL: 8 dogs (1 of which was treated with gestrinone) and 5 cats with intracranial meningiomas and 2 dogs with spinal cord meningiomas; tissue samples were also obtained from 1 clinically normal dog and 1 clinically normal cat. PROCEDURE: Meningioma tissue was obtained during surgery or at necropsy; samples were processed for histologic classification and immunohistochemical evaluation of the proportion of tumor cells with progesterone and estrogen receptors. Correlation among receptor expression, tumor grade, and histologic subtypes was determined. RESULT: Several histologic subtypes of intracranial meningiomas were detected among tissue samples. In the cats, all intracranial meningiomas were benign. Progesterone receptor immunoreactivity was detected in 14 of 15 meningiomas. Progesterone receptor expression was identified in > 80% of cells in 8 intracranial meningiomas (4 dogs and 4 cats) and 2 spinal cord meningiomas. In samples of malignant transitional and granular cell meningiomas in dogs, progesterone receptors were detected in 32 and 4.8% of cells respectively. In 1 cat, 38% of tumor cells had progesterone receptors. In a dog treated with gestrinone, no progesterone receptors were detected in the intracranial meningioma. Estrogen receptors were only detected in the tumor of 1 dog. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate a high proportion of progesterone receptors in cells of meningiomas of the CNS in dogs and cats. Antiprogesterone treatment may have a role in the treatment of unresectable or recurrent meningiomas in dogs and cats.     

Anterior uveal spindle cell tumor in a cat

Purpose To describe a case of anterior uveal spindle cell tumor in a cat with features similar to spindle cell tumor of blue eyed dogs. Methods A 10‐year‐old female spayed domestic short‐haired cat was referred for an iris mass OS. The mass was solitary, nodular, nonpigmented, located medially, and causing dyscoria. A diagnosis of a benign epithelial tumor was suggested by a FNA of the mass. The cat was lost to follow‐up for 2 years, after which time she re‐presented with glaucoma, blindness and grossly evident iridal mass enlargement OS. Transconjunctival enucleation was performed and the globe submitted for histopathology. Results Histopathology of the enucleated globe revealed the superior iris to be infiltrated and effaced by a large population of neoplastic spindle cells. The cells were arranged in streams and bundles and exhibited Antoni‐A and Antoni‐B tissue patterns, which are characteristic of Schwann cell tumors. Mitotic figures were rare and cellular pleomorphism moderate. Immunohistochemical staining was positive for S‐100 protein and glial fibrillary acidic protein (GFAP), and negative for Melan‐A. Interestingly, there was no histological evidence of glaucoma. Conclusions Based on its histopathologic characteristics, this iris tumor was diagnosed as a Schwann cell variant of a peripheral nerve sheath tumor (PNST) closely resembling the spindle cell tumor of blue‐eyed dogs. Anterior uveal PNST has not been previously reported in cats to the authors’ knowledge. The presence of Antoni type A and type B tissue patterns along with immunohistochemical staining may facilitate a diagnosis of PNST and rule out malignant melanoma.     

Soft tissue sarcomas in the African hedgehog (Atelerix albiventris): microscopic and immunohistologic study of three cases.

Three soft tissue tumors from 2 female hedgehogs were examined microscopically and immunohistochemically. Two tumors involved haired skin and the third one was vaginal. Microscopically, the cutaneous tumors had features of malignant peripheral nerve sheath tumor (MPNST), whereas the vaginal tumor was classified only as a spindle cell sarcoma. Immunohistochemically, all 3 tumors were strongly positive for vimentin and strongly to moderately positive for CD10 and neuron-specific enolase but did not stain with antibody to S100 protein, an antigen typically present in human MPNST The cutaneous tumor from hedgehog no. 1 was examined ultrastructurally and the neoplastic cells resembled fibroblasts. Hedgehog no. 1 was euthanized at the time of the biopsy. The outcome of the other hedgehog was unknown.     

Cytomorphologic differentiation of benign and malignant mammary tumors in fine needle aspirate specimens from irradiated female Sprague-Dawley rats.

BACKGROUND: Fine needle aspiration (FNA) offers a rapid and minimally invasive means to distinguish malignant from benign neoplasms. However, few studies have been published regarding the cytopathology of mammary tumors in rats despite widespread use of the rat model for breast cancer formation and inhibition. OBJECTIVE: The purpose of this study was to determine the diagnostic accuracy of FNA cytology and to develop distinguishing cytologic criteria for the diagnosis of radiation-induced benign and malignant mammary tumors in rats. METHODS: In a study of radiation-induced mammary carcinogenesis, 100 Sprague-Dawley rats with cutaneous masses were randomly chosen for FNA. The aspirates were smeared, fixed, and stained with a modified Papanicolaou procedure for diagnostic evaluation. Cytologic and histologic diagnoses (benign vs malignant) were compared, and diagnostic accuracy was calculated using the histologic diagnosis as the criterion standard. FNA smears were scored semiquantitatively on a scale of 1-4 for cellularity, atypia, nuclear size, chromatin pattern, nuclear membrane thickness, nucleoli, and mitoses. The background was evaluated for necrosis, hemorrhage, inflammation, and mucosecretory material. Cytomorphologic features were compared statistically between benign and malignant tumors, based on the histologic diagnosis. RESULTS: The sensitivity of FNA was 92.3% and specificity was 89.4% for the detection of malignancy. However, 14% of specimens, all fibroadenomas by histology, had insufficient cells for cytologic evaluation, for an overall accuracy rate of 78.0%. Malignant tumors had significantly higher scores for all cytomorphologic features, and were significantly more likely to contain cell clusters and necrotic debris. CONCLUSIONS: FNA is an accurate method for differentiating benign and malignant rat mammary tumors.     

Reclassification of small intestinal and cecal smooth muscle tumors in 72 dogs: clinical, histologic, and immunohistochemical evaluation

Objectives— To reclassify canine small intestinal and cecal leiomyoma (LM) and leiomyosarcoma (LMS) into smooth muscle and gastrointestinal stromal tumors (GIST) using histologic and immunohistochemical (IH) analysis and to report clinical findings and survival data.
Study Design— Retrospective review of cases.
Animals— Dogs (n=47) with small intestinal (40 LMS; 7 LM) and 25 dogs with cecal tumors (23 LMS; 2 LM).
Methods— Clinical and survival data were reviewed. Tissue sections were reevaluated for light-microscopic malignancy criteria and examined for expression of SMA, desmin, vimentin, S-100, and CD117 (KIT) by immunohistochemistry.
Results— Reclassification resulted in 2 LM, 9 LMS, 19 GIST, and 17 GIST-like tumors in the small intestine and 23 GIST and 2 GIST-like tumors in the cecum. GIST-like tumors were morphologic and IH identical to GIST but lacked KIT expression. No significant difference in survival was observed for tumor type, location, histologic, or IH characteristics; however, dogs with cecal tumors were significantly older in age, presented more commonly with intestinal perforation and peritonitis, and less commonly with weight loss. Cecal tumors had more histologic malignancy criteria than small intestinal tumors. After excision, 1 and 2 year recurrence-free periods were 80.1% and 67.2% for small intestinal and 83.3% and 61.9% for cecal tumors.
Conclusion— Prognosis for intestinal tumors with histologic smooth muscle appearance is good after excision and not related to tumor type, location, histologic, or IH characteristics.
Clinical Relevance— Clinical importance could not be demonstrated for reclassification, but may be for future treatment, of intestinal smooth muscle or stromal tumors.     

Malignant melanoma of the conjunctiva in a cat

A conjunctival melanoma was diagnosed in an adult domestic cat. The neoplasm was excised without further complications. It is important to differentiate conjunctival melanoma from other types of pigmented ocular neoplasia. In man, conjunctival melanomas are often malignant tumors with potential for metastatic behavior. Although this neoplasm had histologic features of malignancy, no evidence of local recurrence or metastasis has been apparent during the 11-month follow-up period.