Canine inflamed nonepitheliotropic cutaneous T‐cell lymphoma: a diagnostic conundrum

Background –  Cutaneous T‐cell lymphoma (CTCL) in dogs is a heterogeneous disease complex, which consists of nonepitheliotropic (NE) and epitheliotropic forms. These lymphomas are readily recognized by the presence of dominant populations of cytologically atypical lymphocytes. Objective –  The objective of this study was to introduce the key features of inflamed NE‐CTCL, which is easily confused with reactive, inflammatory histiocytic disease. Animals –  Twenty‐four dogs (mean age 7.5 years) presented with inflamed NE‐CTCL. Lesions presented as nodules, plaques or masses. An initial diagnosis of cutaneous reactive histiocytosis (11 dogs) or histiocytic neoplasia (three dogs) was made by primary pathologists. Methods –  Lesions were assessed by histology and immunohistochemistry to detect canine leukocyte antigens. Lesional genomic DNA was extracted and gene rearrangement analysis of the T‐cell receptor γ locus was assessed. Results –  The cutaneous lesions consisted of pleocellular infiltration of the dermis with variable extension into the subcutis. The lesions often surrounded vessels and adnexae. Epitheliotropism was minimal or lacking. Small lymphocytes, plasma cells and intermediate to large, cytologically atypical lymphocytes were scattered between prominent histiocytic infiltrates. Atypical lymphocytes often had marked variation in the intensity of CD3 expression. Molecular clonality analysis of the T‐cell receptor γ locus revealed clonal expansion of T cells in 22 of 23 dogs tested. Conclusion –  The recognition of inflamed NE‐CTCL and its differentiation from cutaneous reactive histiocytosis depends on careful assessment of lymphocyte morphology and immunostaining patterns. Confirmation of the diagnosis is best accomplished by T‐cell antigen receptor gene rearrangement analysis.     

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.     

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.     

Feline progressive histiocytosis

Histiocytic proliferative diseases include reactive and neoplastic proliferations of dendritic cells (DC) or macrophages. Various forms of DC proliferations have been documented in humans and dogs; their etiology is largely unknown. With the exception of a few case reports, histiocytic proliferations have not been characterized in cats. This study summarizes clinical, morphologic, and immunophenotypic features of a feline progressive histiocytosis (FPH) in 30 cats. There was no breed or age predilection. Females were more often affected than males. Solitary or multiple nonpruritic firm papules, nodules, and plaques had a predilection for feet, legs, and face. Lesions consisted of poorly circumscribed epitheliotropic (13/30) and nonepitheliotropic (17/30) histiocytic infiltrates of the superficial and deep dermis, with variable extension into the subcutis. The histiocytic population was relatively monomorphous early in the clinical course. With disease progression, cellular pleomorphism was more frequently encountered. Histiocytes expressed CD1a, CD1c, CD18, and major histocompatibility complex class II molecules. This immunophenotype suggests a DC origin of these lesions. Coexpression of E-cadherin, a feature of cutaneous Langerhans cells, was only observed in 3 cats. FPH followed a progressive clinical course; the lesions, however, were limited to the skin for an extended period of time. Terminal involvement of internal organs was documented in 7 cases. Treatment with chemotherapeutics or immunosuppressive and immunomodulatory drugs was not successful. The etiology of FPH remains unknown. FPH is best considered an initially indolent cutaneous neoplasm, which is mostly slowly progressive and may spread beyond the skin in the terminal stage.     

Localized pulmonary histiocytic sarcomas in Pembroke Welsh Corgi

Nineteen cases of histiocytic sarcomas in Pembroke Welsh Corgi were examined histopathologically. Focal or multiple masses were detected in the lung or in regional lymph nodes, or in both lung and nodes. All neoplastic lesions had common histological features characterized by the proliferation of pleomorphic histiocytic cells combined with various inflammatory cells. Most of the pleomorphic neoplastic cells were immunopositive for human leukocyte antigen (HLA)-DR and Iba-1. The median survival time for all dogs was 133 days. In the present study, several prognostic factors, such as gender, age, single or multiple lesions, lymph node involvement at the time of diagnosis, surgical resection status and additional chemotherapy, were examined, although none of these factors approached statistical significance. Histiocytic sarcoma must be considered in the differential diagnosis of dogs with pulmonary masses, especially in the canine breed.     

Keloidal fibromas and fibrosarcomas in the dog

Sixteen dogs (2-12 years of age) presented with one (n = 15) or two (n = 1) cutaneous nodules (n = 16) or a dermal plaque (n = 1). Intact males (n = 9) and neutered males (n = 4) were more affected than were females (n = 3). Histologically, these lesions were characterized by focal dermal and subcutaneous deposition of thick hyalinized collagen fibers intermingled with fibroblasts, and in 13 of 17 lesions, a variable number of CD18-positive cells were interpreted as reactive macrophages. Fibroblasts in three dogs formed intersecting fascicles, interpreted as evidence of malignant transformation. The terms keloidal fibroma and keloidal fibrosarcoma can be applied to these lesions. Excision was curative in five dogs with keloidal fibroma for which follow-up was available. However, because malignant transformation may occur, wide excision of canine keloidal lesions is warranted.     

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.     

Putative drug-related pemphigus foliaceus in four dogs

Four dogs developed cutaneous lesions following the administration of various antibiotics. Histopathology of the lesions was compatible with pemphigus foliaceus, although apoptotic cells suggestive of erythema multiforme were seen in two cases. In two dogs the lesions resolved after 7.5-8.5 months of immune-suppressive treatment. No recurrence was seen during the follow-up period (3 and 4.5 years). The lesions in the other two dogs resolved within 3 weeks to 3 months following discontinuation of the antibiotic. No recurrence of clinical signs occurred during the follow-up period (1 and 4 years, respectively).     

Histological and immunohistochemical features of cutaneous mast cell tumor in six captive four-toed hedgehogs (Atelerix albiventris)

This report described the histopathological and immunohistochemical features of cutaneous mast cell tumor (MCT) in six hedgehogs. The hedgehogs presented single cutaneous mass with ulcer and crusting. Histologically, the neoplastic lesions were characterized by the proliferation of well-differentiated mast cells (3 cases), and atypical mast cells (3 cases) with one atypical histiocytic morphology. Immunohistochemically, tumor cells were positive for KIT and mast cell tryptase, and were negative for Iba-1. In well-differentiated MCT, all patients were clinically improved and survived more than 365 days after surgical excision, whereas an atypical histiocytic MCT showed aggressive behavior with re-recurrence, and the animal died 115 days after surgery. These findings suggest that, compatible with other animals, well-differentiated MCT has a better prognosis in hedgehogs.     

Systemic Mastocytosis in 16 Dogs

The clinical and pathologic features of systemic mastocytosis in 16 dogs are reported. There was no apparent breed or sex predilection, and the median age at presentation was 9.5 years. In 14 of 16 cases there was a primary cutaneous mast cell tumor (MCT). When cutaneous tumor location was compared with previous reports, there was no association between location and systemic dissemination. The most common presenting signs associated with the cutaneous tumor were regional dissemination, edema, ulceration, and abscessation. They were present in 12 dogs (69%). Signs of systemic illness, including anorexia, vomiting, and diarrhea, were seen in eight dogs (50%). Other than the cutaneous tumors, the most consistent physical and radiographic abnormalities included lymphadenopathy, splenomegaly, and hepatomegaly. Eosinophilia and basophilia were seen in two and five dogs, respectively. Six dogs had increased numbers of mast cells in peripheral blood or buffy coat smears. Five of the nine dogs evaluated had increased numbers of mast cells in bone marrow aspirates. Bone marrow aspiration was superior to both peripheral blood and buffy coat smears in predicting mastocytosis. Coagulation abnormalities were seen in three of five dogs tested. Using a conventional histomorphologic grading system, 10 of 13 (77%) tumors were classified as Grade III or undifferentiated and were overrepresented when compared with previous reports of cutaneous MCTs. Eighty-eight percent of the dogs either died or were euthanatized because of their tumors. Organs commonly involved at necropsy included lymph nodes, spleen, liver, and bone marrow; four dogs had gastroduodenal ulcers.     

Utilization of cytoplasmic lysozyme immunoreactivity as a histiocytic marker in canine histiocytic disorders

Immunoreactive lysozyme was readily detectable in canine histiocytic disorders including systemic histiocytosis, malignant histiocytosis and granulomatous panniculitis. Lysozyme was less reliable as a histiocytic marker in cutaneous histiocytoma; forty percent of these tumors were negative for lysozyme expression. The marked heterogeneity in lysozyme expression in cutaneous histiocytoma may indicate that a proportion of these tumors show relatively primitive histiocytic differentiation and do not express lysozyme. Alternatively, this same proportion may exhibit a phenotype akin to cutaneous Langerhans cells which do not contain lysozyme. Lysozyme was not detectable in the tumor cells in lymphomatoid granulomatosis, atypical cutaneous histiocytoma, and histiocytic lymphosarcoma. Other evidence that these three disorders do not represent true histiocytic proliferative disorders is discussed.     

Multiple cutaneous histiocytomas in a cat

A 15-year-old domestic long haired cat developed nodular cutaneous masses over the right shoulder that were removed surgically. Similar masses developed in multiple cutaneous sites over the following three years. In each case, the lesions were characterized by diffuse dermal infiltration by histiocytic cells with a low mitotic rate and evidence of epidermotropism. The neoplastic population uniformly expressed class II molecules of the Major Histocompatibility Complex, but did not express the T and B lymphoid markers CD3 and CD79. Perivascular aggregates of CD3⁺ T lymphocytes were located at the deep margins of the tumour nodules. The clinical, histopathological and immunohistochemical features of these tumours are consistent with cutaneous histiocytoma. This tumour has not been previously well-documented in the cat.     

Cutaneous actinomycosis and nocardiosis in dogs: 48 cases (1980-1990).

Medical records of 48 dogs with cutaneous actinomycosis or nocardiosis were reviewed. Male, large-breed dogs kept outdoors were overrepresented. The mean age at admission was 3.6 years. Cutaneous swelling (68%), abscesses (65%), draining tracts (48%), fever (36%), and signs of pain (13%) were the most common clinical findings. The cervicofacial area was affected in 48% of the dogs. Abdominal and thoracic wall involvement was less common. Leukocytosis, neutrophilia with left shift, monocytosis, and hyperglobulinemia were common. The diagnosis was confirmed by cytologic examination, bacteriologic culture, or histologic examination. Gram-positive filamentous bacteria were seen in 69% of the fine needle aspirates and in 50% of the biopsy specimens. Actinomyces spp were isolated from cutaneous lesions in 27 (60%) dogs. Nocardia asteroides was isolated from 1 dog. Treatment consisted of surgical debridement, drainage, and administration of antibiotics in 29 dogs (group A) and antibiotics alone in 13 dogs (group B). The infection redeveloped in 10 (42%) group-A dogs and 6 (60%) group-B dogs. Of the 10 group-A dogs with recurrent infection, 6 had resolution after a second surgery and 4 were euthanatized. Of the 6 group-B dogs, 1 had resolution after surgery, 4 were euthanatized or died because of persistent disease, and 1 had an unresolved infection. The combination of surgery and antibiotic treatment appeared to be superior to antibiotic treatment alone in resolving cutaneous Actinomyces and Nocardia infections.     

Multifocal cutaneous histiocytic sarcoma in a young dog and review of histiocytic cell immunophenotyping

A 9‐month‐old male Great Dane had progressive generalized nodular dermatopathy for several months. There were > 100 raised, alopecic, firm, painful nodules throughout the skin. Aspirates from several lesions yielded moderate numbers of irregularly round or polygonal to spindle‐shaped cells with mild to moderate anisocytosis and few inflammatory cells, and the cytologic interpretation was proliferation of mesenchymal or histiocytic cells. On histopathologic examination, nodules were composed of densely packed sheets of round to spindle‐shaped cells with mild anisokaryosis and low mitotic activity. Multifocal histiocytic sarcoma with a spindle‐cell pattern was diagnosed based on morphologic features and intense expression of CD18. Additional immunophenotypic analysis on frozen sections of tissue confirmed the diagnosis of histiocytic sarcoma; expression of CD18, CD45, CD1a, CD11b, and CD11c, limited expression of Thy‐1 (CD90) and CD80, and lack of expression of CD4, CD11d, and CD86 indicated that the cells were likely interstitial dendritic cells; a review of reactive and neoplastic dendritic cells is provided. Based on staging, internal organs were not affected. Sequential treatment with lomustine and doxorubicin failed to prevent progression of the cutaneous lesions, and the dog died 3 months after initial diagnosis. At necropsy, a focus of neoplastic cells was present in one lymph node, but except for skin other organs were not involved. The clinical presentation of histiocytic sarcoma may be unusual, and neoplastic cells may lack overt features of malignancy on cytologic and histopathologic examination. In some instances, immunophenotyping is required to differentiate histiocytic sarcoma from other histiocytic disorders.     

Mortality in a cohort of flat-coated retrievers in the UK

A cohort study of 174 flat-coated retrievers was undertaken to establish the importance of cancer in flat coat mortality in terms of the prevalence of neoplasia in the breed and also the relative effect of cancer on lifespan in relation to other forms of mortality. Dogs aged 2–7 years were recruited in 1996 and followed until 2007. An annual health census was used to collect the data. Two dogs were lost to follow-up and 72 dogs (42%) died from confirmed neoplasia. Twenty dogs (11.6%) died of unconfirmed tumours and 61 (35%) died from non-neoplastic conditions. The cause of death was unknown for 19 dogs. Soft tissue sarcoma (especially histiocytic sarcoma) was the predominant cancer type, affecting 32 dogs (44% of neoplasms). Six dogs died with malignant melanoma and three with lymphoma. Median age at death was 9 years for dogs with tumours (eight for sarcoma patients) and 12 years for non-neoplastic fatalities. The results confirm that soft tissue sarcoma, particularly histiocytic sarcoma, is a major cause of mortality in this breed.     

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.     

Synovial tumours in dogs

The morphological characteristics, breed predispositions, site predilections and behaviour of three of the most common types of synovial tumours were discussed. Synovial histiocytic sarcoma represents 50% of synovial tumours, occurring in breeds predisposed to histiocytic sarcoma, and has a poor prognosis. Their histological appearance is similar to histiocytic sarcomas occurring elsewhere. The stifle is the most common site; dogs with ruptured cranial cruciate ligament are predisposed. Synovial cell sarcoma represents 15% of synovial tumours in dogs. They have non-specific spindle cell morphology, and can only be distinguished using cytokeratin immunohistochemistry, which will label a small percentage of the spindle cells. Amputation is often curative, but metastases can occur. Synovial myxoma represents 20% of synovial tumours in dogs. They have a characteristic morphology of myxomatous nodules filling the joint cavity and sometimes extending into the surrounding tissues, including bone. Labrador Retrievers and Doberman Pinschers are predisposed, and the stifle and digit are the most common sites. Prognosis is good; even with incomplete excision some dogs survive years without progression or metastasis. Histopathological examination of synovial tumours is essential to determine the course of treatment, and prognosis.     

Identification of the most common cutaneous neoplasms in dogs and evaluation of breed and age distributions for selected neoplasms

OBJECTIVE-To identify the most common cutaneous neoplasms in dogs and evaluate breed and age distributions for selected neoplasms. DESIGN-Retrospective epidemiological study. SAMPLE-Records available through the Veterinary Medical Database of dogs examined at veterinary teaching hospitals in North America between 1964 and 2002. PROCEDURES-Information on tumor type and patient breed and age was collected. Incidence and odds ratios with 95% confidence intervals were calculated. RESULTS-Records of 1,139,616 dogs were reviewed. Cutaneous neoplasms were diagnosed in 25,996 of these dogs; records for the remaining 1,113,620 dogs did not indicate that cutaneous neoplasms had been diagnosed, and these dogs were considered controls. The most frequent age range for dogs with cutaneous neoplasms was 10 to 15 years. Lipoma, adenoma, and mast cell tumor were the most common skin tumor types. CONCLUSIONS AND CLINICAL RELEVANCE-Results supported previously reported data regarding cutaneous neoplasia in dogs but provided updated information on the most common skin tumors and on age and breed distributions.     

Systemic histiocytosis of Bernese mountain dogs

A histiocytic proliferative disorder was identified in six closely related Bernese mountain dogs. Clinical signs included anorexia, weight loss, stertorous respiration, and conjunctivitis with marked chemosis. Multiple cutaneous nodules were distributed over the entire body but were especially prevalent in the scrotum, nasal apex, nasal planum, and eyelids. Lesions consisted of perivascular infiltrates of large histiocytes as well as minor populations of lymphocytes, neutrophils, and eosinophils. Histiocytes were further characterized by enzyme histochemistry and electron microscopy. Necropsy examinations of four dogs revealed that the histiocytic infiltrates were widespread and involved skin, lung, liver, bone marrow, spleen, lymph nodes, kidneys, testes, orbital tissues, and others. However, skin and peripheral lymph nodes were more consistently involved. The disease course was punctuated by remissions and relapses not clearly influenced by conventional therapeutic measures. Preliminary results of an experimental therapeutic regimen involving administration of bovine thymic extracts in two dogs are present. The relationship of the disorder to other human and canine histiocytic proliferative disorders is discussed.     

Outcome of dogs with mast cell tumors in the inguinal or perineal region versus other cutaneous locations: 124 cases (1990-2001)

OBJECTIVE: To compare clinical outcome of dogs with cutaneous mast cell tumors (MCTs) in the inguinal or perineal region with outcome for dogs with MCTs in other cutaneous locations. DESIGN: Retrospective study. ANIMALS: 37 dogs with MCTs in the inguinal or perineal region and 87 dogs with MCTs in other cutaneous locations. PROCEDURE: Information obtained from the medical records included sex, breed, age, histologic grade of all tumors, number and location of all tumors, tumor size (ie, diameter of the tumor), completeness of surgical excision, treatments administered in addition to surgery, and outcome. In all dogs, the primary treatment consisted of surgical excision. RESULTS: Disease-free interval and survival time for dogs with MCTs in the inguinal or perineal region were not significantly different from values for dogs with MCTs in other cutaneous locations. Dogs with incompletely excised tumors, dogs with grade III tumors, and dogs that received systemic treatment were 2, 2.5, and 4 times as likely, respectively, to have a relapse. Factors significantly associated with a shorter survival time were age > 8 years, metastatic disease at the time of initial diagnosis, and tumor relapse. CONCLUSIONS AND CLINICAL RELEVANCE: Results of the present study suggest that dogs with MCTs in the inguinal or perineal region do not have a worse prognosis in regard to disease-free interval or survival time than do dogs with MCTs in other cutaneous locations. Treatment recommendations for dogs with cutaneous MCTs should be based on confirmed predictors of biological behavior, such as histologic grade and clinical stage.