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.

Abstract. 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 b2 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.

Abstract. 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.

Data on fifty horses with hereditary equine regional dermal asthenia (HERDA; "hyperelastosis cutis") were collected on clinical, histopathological, ultrastructural and immunohistological findings. All horses were Quarter horses or of Quarter horse ancestry. Pedigree evaluation strongly supported an autosomal recessive mode of inheritance. The most common lesions were seromas/haematomas, open wounds, sloughing skin, and loose, easily tented skin that did not return to its initial position. Definitive diagnosis could not be made via histopathology, although the presence of tightly grouped thin and shortened collagen fibres arranged in clusters in the deep dermis was suggestive of the disease. Trichrome, acid orcein-Giemsa and immunohistochemical stains for collagens I and III showed no consistent abnormalities compared to control horses; an increase in elastic fibres was not a consistent finding. Electron microscopy showed no abnormalities in the periodicity of the collagen bundles; neither orientation nor variation of cross-section diameter of the collagen fibrils differentiated control from affected horses. The diagnosis of HERDA relies on clinical presentation, but may be supported by suggestive (although not pathognomonic) histopathological lesions.

Clinical, morphological and immunohistochemical features of cutaneous lymphocytosis, an uncommon disease histologically resembling well-differentiated malignant lymphoma, were characterized in 23 cats. Clinical outcome was correlated with histomorphology and immunophenotype in an attempt to predict benign vs. malignant behaviour. The disease mainly affected older cats. Lesions were solitary in 61% of cats and often characterized by alopecia (73.9%), as well as erythema, scaling and ulceration. The lateral thorax was most commonly affected (43.5%). Pruritus was frequent (65.2%). Systemic signs included anorexia and weight loss. Morphologically, lesions were characterized by dermal infiltrations of well-differentiated CD3+ T-cells (100%) and aggregates of CD79+ B-cells (64.3%). Cutaneous lymphocytosis is slowly progressive and relatively benign, although in some cats systemic signs led to euthanasia. Four of 12 euthanized cats and one live cat also had lymphoid infiltrates in internal organs. Unfortunately, we were unable to predict clinical outcome by histological and immunohistochemical evaluations of skin lesions.

Twenty horses with pemphigus foliaceus were seen over a period of 15 years in a veterinary medical teaching hospital. Breeds seen were seven quarterhorses, five thoroughbreds, three cross-bred horses, two Arabians and one of each of the following: standardbred, Tennessee walker and warmblood. There was no breed, age or sex predisposition. Nine were mares, ten were geldings and one was a stallion. Ages ranged from 2.5 months to 25 years, with a mean of 8.6 years. Sixteen (80%) of the pemphigus foliaceus horses first exhibited signs between September and February. There was a statistically significant more common occurrence of pemphigus foliaceus during those months. Signs in the four other horses were first noted in March, May or June. Three of those horses were < 13 months of age. Oedema (14/20) and crusts (13/20) were the most common lesions. Pain was present in 9/20 horses, pruritus in 7/20 and pyrexia in 7/20. Follow-up was available for 13 horses. Five of these horses were euthanased. In three horses the reason for euthanasia was laminitis secondary to treatment. Four horses remained lesion-free after medication was discontinued. Two horses required maintenance medication and are doing well at the time of writing.

The medical records of 53 horses with purpura haemorrhagica were reviewed. Seventeen of them had been exposed to or infected with Streptococcus equi, nine had been infected with Corynebacterium pseudotuberculosis, five had been vaccinated with S. equi M protein, five had had a respiratory infection of unknown aetiology, and two had open wounds; the other 15 cases had no history of recent viral or bacterial infection. The horses were between six months and 19 years of age (mean 8.4 years). The predominant clinical signs were well demarcated subcutaneous oedema of all four limbs and haemorrhages on the visible mucous membranes; other signs included depression, anorexia, fever, tachycardia, tachypnoea, reluctance to move, drainage from lymph nodes, exudation of serum from the skin, colic, epistaxis and weight loss. Haematological and biochemical abnormalities commonly detected were anaemia, neutrophilia, hyperproteinaemia, hyperfibrinogenaemia, hyperglobulinaemia and high activities of muscle enzymes. All of the horses were treated with corticosteroids; 42 also received non-steroidal anti-inflammatory drugs and 26 received antimicrobial drugs. Selected cases received special nursing care, including hydrotherapy and bandaging of the limbs. Most of the horses were treated for more than seven days and none of them relapsed. Forty-nine of the horses survived, one died and three were euthanased, either because their severe clinical disease failed to respond to treatment or because they developed secondary complications. Two of the four non-survivors had been vaccinated against S. equi with a product containing the M protein, one had a S. equi infection and the other had a respiratory infection of undetermined aetiology.

Canine epitheliotropic cutaneous T-cell lymphoma (CTCL) is a spontaneous neoplasm of the skin and mucous membranes of aged dogs. The WHO classification of tumours of haematopoietic and lymphoid tissues in human beings recognizes three forms of cutaneous epitheliotropic CTCL: mycosis fungoides (MF), Sézary syndrome and pagetoid reticulosis. In this series of dogs (n = 56), there were 39 cases of MF, 16 cases of pagetoid reticulosis and a single case of Sézary syndrome. Epitheliotropic T cells in CTCL lesions expressed CD8 in 44 of 55 dogs (80%) assessed; neither CD4 nor CD8 was expressed in the remainder. This contrasts with human MF in which alphabeta T-cell receptors (TCR) and CD4 are dominantly expressed. Molecular clonality assessment of canine epitheliotropic CTCL utilizing PCR primers specific for canine TCR gamma (TCRG) was performed. Of the 45 canine cases assessed, TCRG monoclonality was detected in 36 cases (80%). TCR typing of canine epitheliotropic CTCL revealed that TCRgammadelta was expressed in 60% of cases, including all cases of canine pagetoid reticulosis assessed. Either muco-cutaneous junctions or tissues of the oral cavity were the sites of lesions in 32 dogs (57%) with epitheliotropic CTCL. Analysis of the topography of lesions revealed an association with TCR type. If epitheliotropic CTCL lesions occurred in both locations, T cells were more likely to express TCRgammadelta (gammadelta : alphabeta = 2.0). These data establish that canine skin trafficking T cells have a far wider range than previously thought; this includes tongue, gingival, buccal and palatine mucosae.