FC-13 Molecular markers in canine T-cell lymphoma

A previous study described cutaneous lymphocytosis (CL) in 23 cats. The process resembles cutaneous pseudolymphoma in humans, a heterogeneous group of benign reactive proliferations of well-differentiated lymphocytes in the skin of humans. Morphological and immunophenotypic characteristics do not offer reliable criteria to accurately predict the clinical outcome of feline CL or pseudolymphoma in humans. Presence of clonal cell populations is more consistent with a neoplastic process. In a previous study, feline CL lesions (20 cats) were evaluated for clonality using PCR, and only two cats had monoclonal T-cell populations. Because false-negative results may occur, the purpose of this study was to repeat the PCR using a revised primer set based on analysis of additional feline T-cell receptor γ (TCRγ) sequences. DNA was isolated from 29 skin lesions and six internal organs of 20 cats. DNA integrity was assessed by glyceraldehyde-3-phosphate dehydrogenase PCR. Polymerase chain reaction clonality was performed using the revised primer set specific for feline TCRγ, and duplicate samples were evaluated. The PCR products were assessed by heteroduplex analysis. Clonal rearrangement of TCRγ was detected in 14 cats (24 of 35 tissues: 21 of 29 skin lesions and three of six internal organs); eight of these cats are still alive and six were euthanized. Monoclonal populations were seen in three of five cats that had involvement of internal organs. These findings indicate that feline CL is best considered as a slowly progressive process which may be reactive, but often evolves into a low-grade indolent lymphoma.
Funding: George H. Muller Fund for Research in Dermatology.     

FC‐14 Clonality studies of feline cutaneous lymphocytosis

A previous study described cutaneous lymphocytosis (CL) in 23 cats. The process resembles cutaneous pseudolymphoma in humans, a heterogeneous group of benign reactive proliferations of well‐differentiated lymphocytes in the skin of humans. Morphological and immunophenotypic characteristics do not offer reliable criteria to accurately predict the clinical outcome of feline CL or pseudolymphoma in humans. Presence of clonal cell populations is more consistent with a neoplastic process. In a previous study, feline CL lesions (20 cats) were evaluated for clonality using PCR, and only two cats had monoclonal T‐cell populations. Because false‐negative results may occur, the purpose of this study was to repeat the PCR using a revised primer set based on analysis of additional feline T‐cell receptor γ (TCRγ) sequences. DNA was isolated from 29 skin lesions and six internal organs of 20 cats. DNA integrity was assessed by glyceraldehyde‐3‐phosphate dehydrogenase PCR. Polymerase chain reaction clonality was performed using the revised primer set specific for feline TCRγ, and duplicate samples were evaluated. The PCR products were assessed by heteroduplex analysis. Clonal rearrangement of TCRγ was detected in 14 cats (24 of 35 tissues: 21 of 29 skin lesions and three of six internal organs); eight of these cats are still alive and six were euthanized. Monoclonal populations were seen in three of five cats that had involvement of internal organs. These findings indicate that feline CL is best considered as a slowly progressive process which may be reactive, but often evolves into a low‐grade indolent lymphoma. Funding: George H. Muller Fund for Research in Dermatology.     

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.     

Feline pulmonary Langerhans cell histiocytosis with multiorgan involvement

Histiocytic proliferative diseases are uncommon in cats, although recently a progressive histiocytosis of the skin with terminal involvement of internal organs has been described in cats. Here we describe 3 cats (2 males and 1 female) with pulmonary Langerhans cell histiocytosis (PLCH). The cats were euthanized due to progressive respiratory clinical symptoms and deterioration. Macroscopically, extensive, multifocal to confluent, pulmonary masses were evident. Infiltration of pancreas (2 cats), kidneys (1 cat), liver (1 cat), as well as tracheobronchial, hepatosplenic, or mesenteric lymph nodes (2 cats) was observed by gross or microscopic examination. The infiltrating cells had histiocytic morphology with cytologic atypia characterized by anisokaryosis and hyperchromasia regionally within infiltrated tissues. Lesional histiocytes expressed vimentin, CD18, and E-cadherin. Expression of E-cadherin was usually markedly reduced in extra-pulmonary lesions, which is consistent with possible down-regulation of E-cadherin associated with distant migration from the lung. Transmission electron microscopy demonstrated intracytoplasmic organelles consistent with Birbeck's granules of Langerhans cells in the lesional histiocytes in all cats, except in the pancreas of one cat. These findings were compatible PLCH with limited organ involvement of humans. It remains unproven whether feline PLCH represents a reactive or neoplastic cell proliferation.     

Clinical outcome,PDGFRβ and KIT expression in feline histiocytic disorders: a multicentre study

Information about histiocytic disease in cats is limited. The aim of this study was to document clinical findings and outcome in feline histiocytic disorders, and characterize the expression of PDGFRβ and KIT in order to identify potential treatment targets. Morphologically diagnosed feline histiocytic tumours were reviewed and characterized by immunohistochemistry (IHC). Five cases of feline progressive histiocytosis (FPH), eight histiocytic sarcomas (HS) and two haemophagocytic histiocytic sarcomas (HaeHS) were confirmed. PDGFRβ was variably positive in most histiocytic cases, while KIT was negative in all. Clinical presentation, treatment and outcome were also evaluated. Partial responses were recorded in measurable disease with tyrosine kinase inhibitors and lomustine, and radiotherapy achieved long‐term control in some cases. Survival times were shortest in HaeHS and disseminated disease. PDGFRβ, but not KIT, may represent a therapeutic target in feline histiocytic disorders but more studies are needed to investigate other potential treatment targets.     

Clinical, morphological and immunohistochemical characterization of cutaneous lymphocytosis in 23 cats

Abstract   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.     

Cutaneous vascular neoplasia in 15 cats: clinical, morphologic, and immunohistochemical studies.

Seven cases of cutaneous hemangioma and nine of cutaneous hemangiosarcoma were diagnosed from biopsy specimens of 15 Domestic Shorthairs of 5,091 cats that were examined by necropsy or biopsy during the 5-year period from 1 January 1986 through 31 December 1990. All but three cats were male. Tumor cells of both hemangiomas and hemangiosarcomas were immunoreactive for factor VIII-related antigen and for vimentin by the avidin biotin peroxidase complex method. In cats with a median age of 10 years, hemangiomas occurred in skin with pigmented hair in six of seven cases without apparent site predilection. These solitary tumors did not recur after excision although one cat (No. 3) subsequently developed cutaneous hemangiosarcoma at another site. Seven of nine hemangiosarcomas occurred in dermis and subcutis of the head, usually on the pinna. All five hemangiosarcomas of the head, for which cutaneous pigmentation could be determined, occurred in unpigmented skin. Cats with hemangiosarcoma had a median age of 12.5 years at the time of diagnosis. Metastasis has not been documented, but hemangiosarcoma has recurred, from 1 month to 2 years after excision, in 6/7 cats that were studied.     

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.     

Intraepidermal adenocarcinoma in the perianal skin of two cats, a condition resembling human extramammary Paget's disease

In humans, mammary and extramammary Paget's disease is an uncommon to rare manifestation of intraepidermal adenocarcinoma arising from simple epithelium, usually glandular in origin. This report describes two cats with lesions in perianal skin consisting of atypical intraepidermal neoplastic cells. Differential diagnoses included intraepidermal adenocarcinoma, in situ squamous or basal cell carcinoma, junctional amelanotic melanoma, and epitheliotropic tumours of histiocytic or lymphocytic origin. The atypical intraepidermal cells in the cats were immunohistochemically positive for cytokeratin 8/18 (CK8/18), which stains simple (glandular) epithelium. The keratinocytes and basal cells were negative for CK8/18. In addition, the atypical intraepidermal cells were immunohistochemically negative for melanocytic, lymphocytic, and histiocytic markers. The staining results confirmed the atypical intraepidermal cells to be of simple glandular origin, and ruled out other causes of intraepidermal malignancy. In one cat the clinical lesions consisted of a pruritic erythematous eruption surrounding the anus. Another cat presented clinically for an area of irregular anal thickening; this cat had well-regulated diabetes mellitus. The cats were otherwise clinically healthy. The clinical features, histological appearance, and immunohistochemical staining of the skin lesions were consistent with those described for human perianal extramammary Paget's disease. To the authors' knowledge, this is the first report of an intraepidermal adenocarcinoma in a cat or other animal species.     

Canine atopic dermatitis in Greece: clinical observations and the prevalence of positive intradermal test reactions in 91 spontaneous cases.

Atopic dermatitis was diagnosed in a total of 91 dogs by combining the compatible historical evidence and clinical signs with the presence of one or more positive intradermal test reactions well correlated with the exposure to the aeroallergens and the seasonality of the clinical signs. Compared to the general hospital population Yorkshire terriers, Chinese Shar-Peis and cocker spaniels showed a strong predilection. No such predilection was found regarding the sex of the animals. The age of the dogs at the onset of the clinical signs ranged from 2 months to 8 years (median: 2.5 years). Moderate to severe pruritus, noticed in all the 91 dogs, was either localized (29/91) or generalized (64/91) and non-seasonal (43/91), seasonal (19/91) or of unknown seasonality (29/91). The most common cutaneous lesions included erythema, hyperpigmentation, hypotrichosis and crusts; their body distribution was generalized (64%) or localized (36%) with the feet as the most common site of involvement. Five dogs that had unlesional skin were significantly younger and had been pruritic for a shorter period of time compared to the majority of our study population. Otitis externa (43/91) and bacterial pyoderma (30/91) were the most common conditions associated with atopic dermatitis, while the prevalence of Malassezia dermatitis was very low (2/91). Of the other allergic skin diseases flea allergic dermatitis was the most common (29/91) followed by food hypersensitivity (2 out of the 15 dogs tested). The majority of the dogs demonstrated multiple sensitivities to the 50 aeroallergens tested, while domestic mites (77/91), and particularly Dermatophagoides farinae (64/91), were the most commonly implicated. The total number of the positive intradermal test reactions was increasing parallel to the age of the dogs but it was negatively associated with the presence of skin lesions on the carpal and tarsal joints.     

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.     

Cutaneous histiocytosis in dogs

Multifocal cutaneous histiocytic lesions were recognized in 9 dogs. Clinically, the dogs had multiple erythematous plaques or nodules in the skin (1 to 5 cm diameter). Histologically, the lesions were comprised of dermal or pannicular infiltrates of large histiocytic cells, with varying numbers of other inflammatory cells intermixed. By electron microscopy, the cells resembled those of canine cutaneous histiocytoma. The lesions seemed to wax and wane and appeared in new sites, regardless of treatment. The dogs ranged in age from 2 to 13 years; 7 dogs were under 6 years of age. Both sexes and various breeds were represented. An infectious agent could not be identified.     

Retrospective study: the presence of Malassezia in feline skin biopsies. A clinicopathological study

Malassezia spp. dermatitis, a rare disorder in cats, has previously been associated with immune suppression and internal malignancies. This study evaluates the presence and importance of Malassezia spp. in feline biopsy specimens submitted for histopathological examination. Five hundred and fifty haematoxylin and eosin-stained skin biopsy specimens received for histopathological examination between January 1999 and November 2000 were reviewed. Fifteen (2.7%) submissions contained Malassezia organisms in the stratum corneum of the epidermis or follicular infundibulum. Eleven of 15 cats presented with an acute onset of multifocal to generalized skin lesions. All 11 cats were euthanized or died within 2 months of the onset of clinical signs. Seven cats had dermatopathological changes and clinical signs supportive of paraneoplastic alopecia, and three cats had an interface dermatitis suggestive of erythema multiforme or thymoma-associated dermatosis. Histopathological changes were nonspecific in one cat that was euthanized 2 weeks following onset of severe pruritus and alopecia. In three cats, Malassezia spp. were found in localized sites (two chin, one footpads) and appeared inconsequential to their overall health status. One cat had Malassezia spp. in association with cutaneous demodicosis. These findings suggest that Malassezia yeast in dermatopathological specimens from multifocal or generalized lesions should prompt a thorough clinical work-up for internal neoplasia.     

Cutaneous neoplasia in 340 cats.

A total of 340 cases of cutaneous neoplasia were diagnosed in 340 of 3,564 cats that were examined by biopsy or necropsy during a 41-month period from January 1, 1986 through May 31, 1989. Eighteen types of tumor occurred, but four types comprised 77% of the cases. These were basal cell tumor, 89 cases (26%, mean age 10.3); mast cell tumor, 72 cases (21%, mean age 8.6); squamous cell carcinoma, 52 cases (15%, mean age 11.6); and fibrosarcoma, 50 cases (15%, mean age 10.2). For each of these four types of tumors, peak number of cases occurred in cats older than 10 years. Mast cell tumor was the only tumor diagnosed in cats younger than 1 year. The head was the most common site for basal cell tumors, mast cell tumors, and squamous cell carcinomas. The legs were the most common location of fibrosarcomas. Siamese cats had approximately three times as many mast cell tumors as statistically expected, but only one-fourth as many squamous cell carcinomas. Breed predilection for other skin tumors was not apparent. Sex predilection was not detected for any skin tumor.     

Feline eosinophilic granuloma complex(ities): some clinical clarification

PRACTICAL RELEVANCE: The feline eosinophilic granuloma complex (EGC) comprises a group of clinically well recognised but poorly understood dermatoses that are common in cats. In many cases, lesions are severe and can be accompanied by varying degrees of (and sometimes considerable) pruritus and/or pain. In addition, lesions can be chronic and recurrent. It is, therefore, important to achieve a prompt and accurate diagnosis in order to provide optimal, often life-long, treatment for affected cats. PATIENT GROUP: There is no age predisposition or well documented breed predilection for the development of EGC lesions in cats. Some studies have reported a possible female predisposition, but this has not been consistently documented. CLINICAL CHALLENGES: The clinical diagnosis of EGC lesions is usually straightforward, but investigation of the potential underlying aetiology can pose a challenge for the clinician. Information on the indication for various diagnostic tests and their interpretation is lacking, and the tendency for these cases to be managed with chronic medical intervention prior to achieving a definitive diagnosis can further complicate the interpretation of any diagnostic investigation. In addition, successful therapeutic management of these cases can be challenging. Some cats suffer only a single episode of disease that resolves with treatment, while others have recurrent lesions and some of these can be refractory to treatment. The individual variation in both the clinical nature of the disease and the response to therapy could be related to disease severity, but could also be explained by differences in the underlying aetiopathogenesis. EVIDENCE BASE: This article reviews the published literature to discuss the complex aetiology of the EGC and present an overview of the different clinical presentations and diagnosis. A further and particular aim has been to provide some evidence-based recommendations for the management of this unusual group of dermatoses.     

Metastatic digital carcinoma in the cat: a retrospective study of 36 cats (1992-1998)

Thirty-six cats with bronchogenic carcinoma metastatic to the digit were identified. The mean age was 12.7 years, with no breed or sex predilection. Records from 19 cases were available for review. These cats presented with a primary complaint of lameness that involved primarily weight-bearing digits and the third phalanx. None had respiratory signs, despite the presence of pulmonary carcinoma. Course of disease was consistent in the 19 cases, with a mean survival time of 58 days from initial presentation. Amputation of affected digits was rarely palliative due to development of lesions in other digits and progressive nonrespiratory disease.     

Poxvirus infection in the domestic cat: some clinical and epidemiological observations

The clinical findings from 30 cases of feline poxvirus infection in the UK are reviewed and some epidemiological observations described and discussed. In most cases the clinical signs consisted of skin lesions only, although systemic signs were also occasionally seen. Over half the cats had a history of a single recent lesion, assumed to be primary, on the head, neck or a forelimb. Twenty-nine of 30 cats developed more widespread secondary skin lesions. Cat-to-cat transmission was apparently rare. More cases were recognised in the autumn than at other times of the year. The possibility of a wild mammal reservoir of infection 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.     

Use of laser photocoagulation for treatment of cutaneous angiomatosis in one dog and two cats.

One dog and 2 cats were evaluated because of multiple progressively enlarging cutaneous vascular plaques. Biopsies were performed and revealed small well-circumscribed dermal nodules of dilated fully enclosed blood-filled spaces lined by single layers of endothelial cells aligned on thin fibrous walls, with minimal mitotic activity. A diagnosis of cutaneous angiomatosis was made in all 3 animals. Cutaneous angiomatosis is a progressive proliferative lesion of vascular tissue involving the dermis and subcutaneous tissues of dogs and cats. Lasers of selected wavelengths have been used to induce photothermal coagulation of hemoglobin-containing cutaneous lesions in humans; argon-pumped dye and neodymium:yttrium-aluminum-garnet lasers were used to treat the cutaneous lesions in the animals of this report. Laser treatment may provide an alternative to wide surgical resection or limb amputation for management of this condition in veterinary patients.