Comorbidity of ectopic thymoma-associated exfoliative dermatitis and pemphigus foliaceus in a cat

An 8-year-old cat was presented with pruritus, purulent paronychia, scaling, crusting, and spontaneous alopecia. Histopathology revealed intraepidermal neutrophilic pustular acantholytic dermatitis and hyperkeratotic cytotoxic interface dermatitis. No thoracic mass was seen on a lateral radiograph. Ectopic thymoma was discovered on necropsy. This case highlights the necessity for thorough investigation of any case of feline exfoliative dermatitis and pemphigus foliaceus for the presence of thymoma.Key clinical message:Comorbidity of exfoliative dermatitis and pemphigus foliaceus in a cat should prompt a thorough investigation for presence of a thymoma, possibly with advanced imaging techniques.     

Thymoma-associated exfoliative dermatitis in a rabbit

A 5-year-old rabbit with generalized scaling is presented. Multiple skin scrapings and acetate tape impressions were negative for mites and Malassezia. Culture for dermatophytes was also negative. Skin biopsies showed similarities with sebaceous adenitis described in rabbits (absence of sebaceous glands, perifollicular lymphocytic infiltrate at the level of the absent sebaceous glands, lymphocytic mural folliculitis, interface dermatitis). The owners refused any treatment and 2 months later the rabbit was euthanized due to anorexia. At necropsy a mass was found in the anterior mediastinum. Histopathology confirmed a diagnosis of thymoma. A possible paraneoplastic skin disease was suspected, based on similarities with thymoma-associated exfoliative dermatitis in cats.     

Symmetrical alopecia, scaling and hepatitis in a rabbit

A 5-year-old rabbit with inappetence, symmetrical alopecia and skin lesions was examined. No mites or Malassezia were found in skin scrapings and tape impressions and dermatophyte culture was negative. Trial therapy with ivermectin did not reduce skin lesion severity, and euthanasia was performed because of anorexia after 1 month. Histopathology of the skin showed hyperkeratosis, lymphocytic exocytosis, cell-poor interface dermatitis (lymphocytic infiltration and apoptotic cells in basal layer of epidermis), absence of sebaceous glands and lymphocytic mural folliculitis comparable to sebaceous adenitis and thymoma-associated exfoliative dermatitis previously described in rabbits. The liver exhibited an interface hepatitis, comparable to autoimmune hepatitis in man. The occurrence of morphological similarities to exfoliative dermatitis and sebaceous adenitis in rabbits, in association with an autoimmune hepatitis, has not been described before.     

Resolution of exfoliative dermatitis and Malassezia pachydermatis overgrowth in a cat after surgical thymoma resection

A four-year-old, male neutered domestic shorthaired cat was presented with a two-week history of nasal and ocular discharge, generalised exfoliative dermatitis, intense pruritus, polydipsia, polyphagia, weight loss, intermittent hindlimb ataxia and lethargy. Cutaneous populations of Malassezia pachydermatis yeast organisms were found to be elevated. The generalised nature of the disease prompted survey radiography which revealed the presence of a cranial mediastinal mass which was subsequently resected and found to be a thymoma. Within six months of surgery, systemic and cutaneous signs had resolved and yeast counts had returned to normal, suggesting a causal relationship between the thymoma and the skin disease.     

Diagnosis of erythema multiforme associated with thymoma in a dog and treated with thymectomy

A 7 yr old Labrador retriever initially presented for severe halitosis, mild ptylism, and depigmentation of the nasal planum. Erythema multiforme was diagnosed based on clinical signs and dermatopathology. Treatment was initiated but the condition did not resolve. Six months later, the dog was diagnosed with a mediastinal mass. Trucut biopsy was performed and histopathologic diagnosis was consistent with a thymoma. A median sternotomy was performed, the thymoma was excised, and the dog recovered well. Four months postoperatively, there were no longer any obvious erythema multiforme lesions and the skin condition was controlled without medication. Erythema multiforme may be a paraneoplastic disorder associated with thymoma in the dog, similar to thymoma-associated exfoliative dermatitis in the cat. Clinical signs of erythema multiforme may warrant performing thoracic radiographs or thoracic CT to rule out thymoma as an underlying cause.     

Cellular immunophenotyping of exfoliative dermatitis in canine leishmaniosis (Leishmania infantum)

Lymphocyte subsets, major histocompatibility complex (MHC)-II expressing cells and number of amastigotes in the epidermis and dermis were investigated immunohistochemically in 48 dogs with patent leishmaniosis, with or without exfoliative dermatitis (ED) to study the immunopathogenesis of this common cutaneous form of the disease. Skin biopsies were obtained and compared for ED sites (group A, n = 26), normal-appearing skin from the same animals (group B, n = 24), and leishmanial dogs not exhibiting ED (group C, n = 22), and normal controls (group D, n = 22). The CD3+, CD45RA+, CD4+, CD8+ (CD8a+), CD21+, and MHC-II+ cells and leishmania amastigotes were identified immunohistochemically and counted with the aid of an image analysis system. Pyogranulomatous to granulomatous dermatitis, expressed in various histopathological patterns, was noticed in all groups A and B and in half of group C dogs. In the epidermis, the low number of T-cells and their subsets did not differ significantly between groups A and B, but CD8+ outnumbered CD4+ lymphocytes in both groups. MHC-II+ expression on epidermal keratinocytes was intense in the skin with and without lesions from dogs with ED but not in group C dogs. CD3+, CD8+ and MHC-II+ cells were fewer in group C compared to group A and B dogs. In the dermis, CD3+ cells in group A animals were mainly represented by the CD8+. CD45RA+ and CD21+ cells were also seen in high numbers. MHC-II expression, potentially in lymphocytes, fibroblasts, dendritic cells, and macrophages was intense. The numbers of all cellular subpopulations in the dermis were significantly different between the groups, being highest in group A and lowest in group D. In sebaceous adenitis sites, CD4+ outnumbered CD8+ cells in contrast to the neighbouring dermis and the epidermis. The number of CD21+ and CD45RA+ cells was much lower in the inflamed sebaceous glands compared to the dermis. Finally, the number of amastigotes in the normal-appearing skin was significantly higher in the ED dogs (group B) than in those not exhibiting this cutaneous form of the disease (group C).     

Thymoma-associated exfoliative dermatitis with post-thymectomy myasthenia gravis in a cat

Thymoma-associated exfoliative dermatitis was suspected in a cat with a cranial mediastinal mass. The dermatopathy resolved with surgical removal of a thymoma. The cat manifested neurologic signs consistent with myasthenia gravis 7 wk after surgery. Exfoliative dermatitis and post-thymectomy myasthenia gravis in the same cat has not been reported previously.     

Interleukin 4-producing CD4+ T cells in the skin of cats with allergic dermatitis

Lesional skin of cats with allergic dermatitis has a cellular infiltrate and a CD4/CD8 ratio comparable to that in humans with atopic dermatitis. CD4+ helper T cells and in particular cells belonging to the Th2 subset play an important role in disease pathogenesis in humans. We investigated the cytokine pattern of CD4+ T cells in situ, with special emphasis on the putative presence of cells producing interleukin 4 (IL4), in cats with allergic dermatitis. Immunohistochemical procedures were used to determine that CD4+ T cells in lesional and nonlesional skin of cats with allergic dermatitis can produce IL4, as occurs in humans. Lesional and nonlesional skin of cats with allergic dermatitis had significantly more IL4+ T cells (P = 0.001) than did skin of healthy control cats. Double staining indicated that all IL4+ cells were positive for pan-T or CD4 markers. Double labeling for mast cell chymase and IL4 stained primarily different cells. Western blotting demonstrated cross-reactivity between the antibody against human IL4 and a feline recombinant IL4. These results indicate that IL4 is primarily produced by CD4+ T cells and is also present in clinically uninvolved skin, indicating a role in the pathogenesis of allergic dermatitis in cats.     

The Utility of Flow Cytometry for the Diagnosis of Cranial Mediastinal Malignancy in Canine Patients

Introduction:  The most common neoplasms located in the anterior mediastinum in the canine are thymoma and lymphoma. Distinguishing between the two is a diagnostic challenge. Treatment and prognosis for these diseases differs significantly. Thymomas contain a population of normally developing T cells. The majority of these T cells exhibit an immature phenotype, characterized by co‐expression of CD4 and CD8. This phenotype is rarely seen on neoplastic lymphocytes. The purpose of this study was to determine if analysis by flow cytometry could discriminate thymoma from lymphoma based on these cell surface markers.
Methods:  Fine needle aspirates were obtained from ten canine patients with mediastinal masses. Cells were analyzed by flow cytometry using a panel of T and B cell markers.
Results:  Six cases with 10% or greater CD4 + CD8+ cells were diagnosed with thymoma and were confirmed by histopathology. Four cases had fewer than 5% CD4 + CD8+ cells, having lymphocytes expressing CD4 only (3 cases) or CD21, a B cell marker(1 case). These were confirmed as lymphoma by cytology and/or a clonality assay. The sensitivity and specificity of this assay when used in the diagnostic work‐up for suspected thymoma was 100%.
Conclusion:  Flow cytometry may provide important, complementary information in the diagnostic work‐up of the canine patient with a mediastinal mass.     

Mixed Thymoma in a Young Cynomolgus Monkey (Macaca fascicularis)

A mass with a diameter of 1.5 cm was found in the thymus of a 4-year and 3-month-old male cynomolgus monkey. Microscopically, the mass consisted of two different patterns of proliferation, dense or fascicular proliferation of elongated spindle cells in a sporadic storiform pattern and dense proliferation of thymic cortex-like lymphoid cells in which the multifocal pale nests resembling the thymic medulla were distributed. In these pale nests, large dendriform cells sometimes forming Hassall's corpuscles were present. The proliferating spindle cells were positive for cytokeratin. The lymphoid cells in the mass were positive for CD3. We concluded that the mass consisted of the neoplastic thymic epithelium with thymocytes proliferation containing medullary differentiation. The mass was diagnosed as a mixed thymoma according to the WHO classification of thymomas in humans. Mixed thymoma is characterized as a mixture of two types of proliferative lesions, spindle-shaped epithelial proliferation and a lymphocyte predominant lesion with or without medullary differentiation. To the best of our knowledge, this is the first report concerning thymoma in monkeys.     

Malassezia dermatitis in the dog: a retrospective histopathological and immunopathological study of 86 cases (1990–95)

A retrospective histopathological and immunopathological study was conducted on 86 dogs with Malassezia dermatitis. West Highland White terriers, English Setters, Shih Tzus, Basset Hounds, American Cocker Spaniels, spayed females, and castrated males were found to be at increased risk. The histopathological reaction pattern of lymphocytic superficial perivascular to interstitial dermatitis with parakeratotic hyperkeratosis, irregular epidermal hyperplasia, diffuse intercellular oedema and lymphocytic exocytosis was found to be consistent with a diagnosis of Malassezia dermatitis whether yeast were histologically visible (73.3% of the cases) or not (26.7%). Immunopathological studies revealed that 60– > 90% of the inflammatory cells within the epidermis, and 25–75% of those within the dermis were CD3+T lymphocytes, and that the only immunoglobulin-positive cells were dermal plasma cells.     

Morphologic and immunohistochemical features of experimentally induced allergic contact dermatitis in Göttingen minipigs

Many preclinical studies in investigative dermatology are performed preferably in pigs because pig skin is more similar to human skin than is rodent skin. A frequently used model is allergic contact dermatitis (ACD); however, this T-cell-mediated skin condition so far is not well characterized in pigs. The present study is aimed at the evaluation of morphologic and immunohistochemical features of experimentally induced acute ACD in G?ttingen minipigs using 2,4-dinitrofluorobenzene (DNFB) as a hapten. Eight minipigs were sensitized with 10% DNFB and challenged 2 weeks later at different sites with 1% DNFB. In addition to clinical examinations, cutaneous blood flow was quantified by laser Doppler velocimetry (Periflux PF3). These examinations were performed before challenge and 8, 24, 48, and 72 hours after challenge. Skin biopsies were taken at the same time points, fixed, sectioned, and stained with Giemsa for histologic evaluation, or with mouse anti-swine monoclonal antibodies (CD1, CD2, CD4, CD5, CD8, CD25, CD45, MHCII) and with one mouse anti-human monoclonal antibody (CD62E) cross-reacting with swine for immunohistochemical evaluation. Positively stained cells were counted per square millimeter of epidermis and dermis by using a video image analyzing system (Videoplan Kontron). Erythema and cutaneous blood flow peaked at 24 hours. The major epidermal changes most pronounced at 48 hours were acanthosis, spongiosis, intracellular edema, exocytosis, and abscesses mainly containing neutrophils and mononuclear cells (MNC). Perivascular infiltrates of MNC as well as neutrophils and eosinophils were the most significant dermal changes, with peak levels at 24-48 hours. In biopsies taken before challenge, CD1+ dendritic cells were found in similar numbers and locations as MHCII+ cells in the epidermis. In the epidermis the maximum CD1+ cell decrease occurred at 24 hours whereas in the dermis the maximum increase in CD1+ stained cells was seen at 72 hours. The dermal infiltrate (CD2+, CD5+, CD25+, and CD45+) was most dense at 48 hours. Between 8 and 48 hours more CD4+ were present than CD8+, cells, whereas at 72 hours CD4+ and CD8+ cells were similar in numbers. These findings closely resemble changes in human ACD. Therefore, DNFB-induced ACD in G?ttingen minipigs is considered to be an appropriate animal model to study immunopathologic mechanisms and pharmacologic intervention.     

Clinical considerations on canine visceral leishmaniasis in Greece: a retrospective study of 158 cases (1989-1996).

The medical records of 158 dogs with visceral leishmaniasis confirmed cytologically and/or serologically were reviewed. Ages of affected dogs varied from nine months to 15 years, with a male-to-female ratio of 1.3. The most common clinical manifestations of the disease were variable cutaneous lesions such as exfoliative dermatitis and skin ulcerations, chronic renal failure, peripheral lymphadenopathy or lymph node hypoplasia, masticatory muscle atrophy (i.e., chronic myositis), ocular lesions (i.e., conjunctivitis, keratoconjunctivitis sicca, blepharitis, and uveitis), and poor body condition. Ascites, nephrotic syndrome, epistaxis, polyarthritis, and ulcerative stomatitis were seen only in a small number of cases. Clinical splenomegaly was not a common finding. The clinicopathological abnormalities were nonregenerative anemia, hyperproteinemia, glomerular proteinuria, and symptomatic or asymptomatic azotemia. In this study, an indirect immunofluorescence assay's diagnostic sensitivity was found to be higher than that of lymph node aspiration cytology.     

Successful Treatment of Idiopathic Sebaceous Adenitis in a Lionhead Rabbit

A 15-month-old, ovariohysterectomized female Lionhead rabbit was presented with generalized chronic exfoliative dermatitis and patchy alopecia. General physical examination revealed no abnormalities apart from a body condition score of 4 of 9. Ectoparasitic infestation, dermatophytosis, Malassezia dermatitis, epitheliotropic lymphoma, thymoma-associated exfoliative dermatitis, and autoimmune hepatitis-associated exfoliative dermatitis were excluded on the basis of skin scrapings, fungal culture, cutaneous histopathology, thoracic radiography, and the results of hematologic and biochemical analyses. Histopathology of the skin showed orthokeratotic hyperkeratosis, absence of sebaceous glands and mural lymphocytic folliculitis, consistent with sebaceous adenitis. The extent and severity of the skin lesions were scored by the Rabbit Dermatitis Extent and Severity Index adapted from the recently published Canine Atopic Dermatitis Extent and Severity Index–03. Once-daily oral treatment with 5 mg/kg of ciclosporin A dissolved in an equal amount of a medium-chain triglyceride solution (Miglyol 812; Bufa, Uitgeest, The Netherlands) was initiated, but the response to this was poor. Therefore, while maintaining the oral treatment, topical treatment with phytosphingosine products was given. The rabbit's coat was clipped and a phytosphingosine 0.2% microemulsion spray (daily), a phytosphingosine 0.1% shampoo (weekly), and a phytosphingosine 1% spot-on treatment (weekly) were applied. Nine months later, there had been significant hair regrowth on previously hairless areas and the Rabbit Dermatitis Extent and Severity Index confirmed the marked improvement with a 91% reduction in the original score. Serum ciclosporin concentrations were undetectable throughout the treatment period.     

Chronic eosinophilic dermatitis: a manifestation of a multisystemic, eosinophilic, epitheliotropic disease in five horses

A generalized, chronic, progressive, exfoliative dermatitis in five horses is described. Histologically, the lesion is characterized by a superficial and deep perivascular dermatitis which is eosinophil-rich with a marked lymphocytic and plasmacytic component, accompanied by marked acanthosis and hyperkeratosis. More severe cases progress to a lichenoid pattern with the same cellular composition with focal eosinophilic spongiosis and eosinophilic subcorneal pustules. Clinically, the disease is associated with chronic, severe weight loss and is fulminating. The skin lesions are accompanied by lymphoplasmacytic and eosinophilic infiltrates and formation of eosinophilic granulomas in other epithelial organs, most noticeably the pancreas, in which a chronic, fibrosing pancreatitis develops. Other epithelial organs involved to various degrees are salivary glands, the gastrointestinal system, including the oral cavity and esophagus, biliary epithelium and bronchial epithelium. The etiology of this disease is unknown.     

Immunohistochemical study of the inflammatory infiltrate associated with feline cutaneous squamous cell carcinomas and precancerous lesions (actinic keratosis).

The distribution of T lymphocytes (CD3+), B lymphocytes (CD79+), immunoglobulin-containing plasma cells (IgG, IgM and IgA), macrophages (Mac387+) and MHC Class II antigen was analysed in the inflammatory infiltrate associated with cutaneous squamous cell carcinomas (SCC) from 23 cats. Peri-tumoural skin (12 cases) and precancerous lesions of actinic keratosis (nine cases) were also evaluated for the expression of MHC Class II. The results revealed that an abundant inflammatory infiltrate was associated with the majority of SCC. This infiltrate was composed mainly of CD3+ T lymphocytes, B cells (CD79+) and IgG-bearing plasma cells, and the intensity of infiltration increased with the degree of invasiveness of the tumour. The number of CD3+ T cells and CD79+ cells was significantly increased in well-differentiated SCC compared with moderately differentiated tumours, whereas the number of IgM+, IgA+ plasma cells and Mac387+ macrophages was low or moderate and did not change significantly with histologic grade or invasiveness. MHC Class II antigen was expressed by infiltrating lymphocytes and macrophages, and by fibroblasts. A variable number of neoplastic cells (10% to 80%) in 10 SCC, and keratinocytes of basal layers in seven of nine cases of actinic keratosis also expressed MHC Class II, whereas keratinocytes of normal skin were always negative for this antigen. These results suggest that CD3+ T lymphocytes, CD79+ B cells and IgG-bearing plasma cells may participate in down-regulation of tumour growth, since these cell types were particularly numerous in well-differentiated and mildly invasive SCC, as well as in actinic keratosis. The expression of MHC Class II by neoplastic cells could enhance this local anti-tumour immune response.     

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.     

Mixed thymoma in a cow.

A neoplastic mass measuring 25 x 8 x 3 cm was found in the mediastinum of a 10-year-old Holstein cow. The neoplasm was encapsulated, multilobulated, and cystic. Several firm adhesions were present between the neoplasm and the right cranial lung lobe and the ipsilateral side of the pericardial sac. Under microscopic examination, the neoplasm was characterized by solid sheets of spindle epithelial cells (pancytokeratin and high molecular weight cytokeratin positive) subdivided by fibrous trabeculae. Numerous individualized or small aggregates of mature T-cell (CD3 positive) lymphocytes were scattered throughout the neoplastic cell population. Based on the gross, histologic, and immunohistochemical findings, the neoplasm was diagnosed as a mixed thymoma.     

Sézary syndrome in a cat

Sézary syndrome is an uncommon leukemic variant of cutaneous lymphoma in cats. This cat had recurrent dermatitis with erythematous, pruritic plaques. Multiple skin imprints and biopsy samples were obtained over a 6-month period, and histopathological findings were consistent initially with eosinophilic miliary dermatitis and later with erythema multiforme. One week before death, Sézary cells were identified in the peripheral blood that expressed cluster of differentiation (CD)3 and CD8 antigens. Massive infiltration of CD3+ lymphocytes was noted in the skin and multiple internal tissues by histopathological examination. This case demonstrates the difficulty in diagnosing cutaneous lymphoma early in the disease course.