Canine cutaneous epitheliotropic T‐cell lymphoma: a review

Cutaneous epitheliotropic T‐cell lymphoma in the dog is a rare neoplastic condition with unknown aetiology. The dermatitis is characterized by infiltration of neoplastic T lymphocytes with a specific tropism for the epidermis and the adnexal structures. The different clinical and histological forms (mycosis fungoides, pagetoid reticulosis and Sézary syndrome) are reviewed. The disease in the dog resembles the human syndrome, but in 80% of the canine cases, neoplastic cells are CD4^?/CD8⁺ versus CD4⁺/CD8^? in 90% of the human patients. Prognosis is poor with a survival time from few months to 2 years. Treatments frequently have a low efficacy. New protocols using lomustine may improve the poor prognosis of the disease.     

Epitheliotropic cutaneous lymphoma (mycosis fungoides) in a coati

The aim of this report was to present a case of epitheliotropic cutaneous lymphoma (mycosis fungoides) in a coati. The animal was presented for evaluation of a non-pruritic nodule. Although the diagnosis of cutaneous histiocytoma was made histologically, plaques and erosions appeared in new areas of the skin along with rapid deterioration of body condition that led to euthanasia in less than one month following initial presentation. Epitheliotropic cutaneous lymphoma was confirmed with plaque biopsies. Cross-reactivity of a polyclonal antihuman CD3 antibody to coati T lymphocytes was also observed. Apart from skin lesions, only pleuritis was post-mortem diagnosed most likely because of immunosuppression secondarily to malignant neoplasia.     

Lokivetmab improved pruritus in a dog with cutaneous epitheliotropic lymphoma

A 13-year-old spayed female Cavalier King Charles Spaniel presented with chronic swelling and pruritus on the palmar aspect of the left forepaw and on the tail. Cutaneous epitheliotropic lymphoma (CEL) was diagnosed by histopathology and immunocytochemistry. Prednisolone was initially used alone as an alternative treatment for CEL. Despite long-term corticosteroid therapy, the patient’s physiological (pruritus) and dermatological signs (alopecia, erythema, erosion, and ulceration with crust) progressed and showed no evidence of improvement. To address the worsening condition of pruritus, lokivetmab was started in combination with prednisolone. Once on lokivetmab, the pruritus steadily improved and was effective in resolving and maintaining remission. Further investigation on the critical role of IL-31 in the pruritus pathway of dogs with CEL is required.     

Treatment of cutaneous T-cell lymphoma with dacarbazine in a dog

Abstract Epitheliotropic cutaneous T-cell lymphoma in a Lhasa Apso dog treated with dacarbazine is reported. Clinical disease consisted of a 4 × 4-cm ulcerated mass over the mandibular symphysis and bilateral lymphadenopathy of the submandibular lymph nodes. Skin biopsy sections were díagnostic for epitheliotropic cutaneous T-cell lymphoma, and immunohistochemistry staining for the CD3 antigen was positive. Tissue samples were submitted for chemosensitivity testing and dacarbazine was shown to be 60% effective. Treatment with dacarbazine resulted in total clinical remission. The dog remains disease free 1 year after treatment. Résumé— Les auteurs décrivent un cas de lymphome cutané T épithéliotrope chez un Lhassa Apso traitéà la dacarbazine. Le tableau clinique était caractérisé par la présence d'une masse ulcérée de 4 × 4 cm sur la symphyse mandibulaire et par une adénopathie bilatérale des ganglions sous mandibulaires. Les biopsies posèrent le díagnostic de lymphome cutané T et l'immunomarquage fut positif pour l'antigène CD3. Des prélèvements tissulaires fürent soumis à des tests de chimiosensibilité et la dacarbazine se révéla efficace à 60%. Le traitement à la dacarbazine entraina une rémission clinique totale. Le chien ne présente pas de récidive un an après le traitement. [Lemarié, S. L., Eddlestone, S. M. Treatment of cutaneous T-cell lymphoma with dacarbazine in a dog. (Traitement d'un lymphome cutané T à la dacarbazine chez un chien.) Veterinary Dermatology 1997; 8 : 41–46.] Resumen Se describe el tratamiento con dacarbazina de un linfoma cutáneo epiteliotrópico de células T en un Lasha Apso. La presentación clinica consistia en una masa ulcerada de 4 × 4 cm por encima de la sinfisis mandibular y linfadenopatia bilateral de los ganglios linfáticos submandibulares. El estudio histológico cutáneo permitió un díagnóstico de linfoma cutáneo epiteliotrópico de celulas T, con positividad inmunohistoquimica al antigeno CD3. Se remitieron muestras tisulares para pruebas de quimiosensibilidad, en las que la dacarbazina mostró una efectividad del 60%. El tratamiento con dacarbazina llevó a una remisión clinica total. El perro sigue sano un año después del tratamiento. [Lemarié, S. L., Eddlestone, S. M. Treatment of cutaneous T-cell lymphoma with dacarbazine in a dog. (Tratamiento del linfoma cutáneo de celulas T con dacarbazina en un perro.) Veterinary Dermatology 1997; 8 : 41–46.] Zusammenfassung— Es wird über eine epitheliotropes kutanes T-Zell-Lymphom bei einem Lhasa Apso berichtet, das mit Dacarbazin behandelt wurde. Die klinische Erkrankung bestand in einer 4 × 4 cm großen ulzerierten Masse über der Symphyse der Mandibula sowie einer bilateralen Lymphadenopathie der submandibulären Lymphknoten. Die Hautbiopsien ergaben die Diagnose epitheliotropes kutanes T-Zell-Lymphom, die immunohistochemische Färbung auf CD3-Antigen fiel positiv aus. Die Gewebsproben wurden einer Chemosensitivitätsprobe unterzogen und Dacarbazin erwies sich zu 60% wirksam. Die Behandlung mit Dacarbazin führte zu einer vollständigen klinischen Remission. Der Hund blieb frei von Krankheitssymptomen seit einem Jahr nach der Behandlung. [Lemarié, S. L., Eddlestone, S. M. Treatment of cutaneous T-cell lymphoma with dacarbazine in a dog. (Die Behandlung eines kutanen T-Zell-Lymphom mit Dacarbazin bei einem Hund.) Veterinary Dermatology 1997; 8 : 41–46.]     

Epitheliotropic lymphoma (mycosis fungoides) presenting as blepharoconjunctivitis in an Irish setter

An 11-year-old neutered female Irish setter was presented with a six-week history of blepharoconjunctivitis affecting the right eye. A conjunctival biopsy was taken and histopathological examination revealed a heavy cellular infiltrate involving the epithelial and subepithelial tissues. Immunohistochemical staining showed the intraepithelial cell population to uniformly have the phenotype CD3 (T-cell specific marker). A diagnosis of epitheliotropic lymphoma (mycosis fungoides) was made. The use of a synthetic retinoid and topical prednisolone in the management of the case is discussed.     

Epitheliotropic T-cell lymphoma in 2 half-sibling bontebok

We diagnosed epitheliotropic T-cell lymphoma of the forestomachs in 2 aged, half-sibling, zoo-managed bontebok (Damaliscus pygargus pygargus). One bontebok also had mesenteric lymph node and cutaneous involvement. Both animals had a history of chronic abdominal distension and diminished body condition that resulted in euthanasia. At autopsy, both animals had marked ruminal distension with diffusely blunted ruminal papillae and reticular crests. In case 1, there was an increased amount and particle length of the ruminoreticular fibrous material with scant fluid, and a 2-cm diameter focus of cutaneous crusting adjacent to a mammary teat. In case 2, the rumen and reticulum were fluid-distended with decreased fibrous material. Histologically in case 1, the rumen, reticulum, omasum, and skin had intraepithelial nests and sheets of neoplastic small lymphocytes; in case 2, the rumen and reticulum had a similar neoplastic cell population. Immunohistochemically, neoplastic lymphocytes were immunoreactive for CD3 and negative for CD20, confirming the diagnosis of epitheliotropic T-cell lymphoma.     

Epitheliotropic lymphoma in a dog

Despite treatment with steroids, nodular areas of alopecia and erythematous skin lesions persisted in a 9-year-old Irish water spaniel with discoid lupus. Epitheliotropic lymphoma was diagnosed by skin biopsy.     

Cutaneous lymphoma in a juvenile dog

Abstract: An 18-month-old male Doberman Pinscher was referred to the Veterinary Medical Teaching Hospital of the College of Veterinary Medicine for an erythemic nodular mass on the right forelimb. The mass was diagnosed as cutaneous lymphoma, based on cytologic examination of a mass aspirate and histopathology. Using immunohistochemistry the neoplastic cells were positive for CD3 but negative for CD79a, E-cadherin, and pancytokeratin, confirming their origin as T lymphocytes. No tumor recurrence was noted 18 months after surgery. To our knowledge, this is the first report of a solitary nodular form of cutaneous lymphoma in a young dog.     

Epidermotropic Cutaneous T-Cell Lymphoma (mycosis fungoides) in Syrian Hamsters (Mesocricetus auratus). A Report of Six Cases and the Demonstration of T-Cell Specificity

Abstract— Epidermotropic cutaneous T-cell lymphoma was diagnosed in six Syrian hamsters (Mesocricetus auratus) with a generalised dermatosis characterised by pruritus, alopecia and exfoliative erythroderma. Plaques and nodules were evident in one animal. Clinical and histopathological findings were suggestive of mycosis fungoides and electron microscopical investigations in one case were supportive. Immuno-histochemical stains for CD3 antigen were strongly positive in all cases. Résumé— Un lyphome T cutané a été diagnostiqué chez six hamsters de Sibérie (Mesocricetus auratus) avec une dermatose généralisée, caractérisée par un prurit, une alopécle et une érythrodermie exfoliative. Des plaques et des nodules ont été observées sur un animal. Les données cliniques et histopathologiques étaient évocatrices d'un mycosis fungoïdes et les examens en microscopie électronique étaient compatibles dans un cas. Les marquages immuno-histochimiques de l'antigène CD3 étaient très positifs dans tous les cas. Zusammenfassung— Bei sechs Syrischen Goldhamstern (Mesocricetus auratus) wurde ein epidermotropes kutanes T-Zell-Lymphom mit einer generalisierten Dermatose diagnostiziert, die durch Pruritus, Alopezie und eine exfoliative Erythrodermie gekennzeichnet war. Bei einem Tier traten auch Plagues und Knoten auf. Die klinischen und histopathologischen Befunde deuteten auf Mycosis fungoides hin. Elektronenmikroskopische Untersuchungen unterstützten diesen Verdacht in einem Fall. Immunhistochemische Färbungen auf CD3-Antigen waren bei alien Fallen stark positiv. Resumen En un grupo de seis hamsters de siria, (Mesocricetus auratus), se diagnosticó limfoma epidermotrópico cutáneo de linfocitos T, presentando una dermatosis generalizada de tipo pruriginoso, acompañada de alopecia y eritroderma exfoliativo. Las placas y nódulos fueron evidentes en uno de los animales. Los estudios clinicos e histopatológicos indicaron una micosis fungoide, y las investigaciones de microscopía, en uno de los caseos, pareció indicar lo mismo. La tintura inmuno-histoquimica para el antígeno CD3 resultó claramente positiva en todod los casos.     

Unicentric extranodal lymphoma of the upper eyelid conjunctiva in a dog

A case of conjunctival lymphoma in a 4-year-old Siberian husky is reported. A large red mass protruding from the conjunctiva of the upper eyelid of the right eye was present. Irritation, blepharospasm and epiphora were revealed on initial ophthalmic examination. After anti-inflammatory treatment, surgery was performed. Histologically, the mass consisted of large polygonal cells with a high nucleus to cytoplasm ratio, moderate amounts of slightly eosinophilic cytoplasm, pleomorphic nuclei with vesicular chromatin and prominent multiple nucleoli. Mitotic figures were frequent. Approximately 70% of the neoplastic cells were CD3 positive and CD79alpha negative. On the basis of histologic and immunohistochemical findings, a diagnosis of intermediate-grade, diffuse large-cell lymphoma with T-cell immunophenotype was made. The surgical area healed uneventfully and, although chemotherapy was not received, after 12 months the dog exhibited no recurrence. To the authors' knowledge, this is the first report of unicentric extranodal conjunctival lymphoma in a dog.     

Acute tumour lysis syndrome in a dog with B-Cell multicentric lymphoma

A 5-year-old, spayed female German Shepherd dog was admitted to hospital with marked generalised lymphadenomegaly and splenomegaly. A stage Va B-cell multicentric lymphoma was diagnosed on clinical, cytological (lymph node, bone marrow), histological-immunohistochemical (lymph node excision) and imaging grounds. Since no satisfactory remission was achieved using a multi-drug chemotherapy protocol that included cyclophosphamide, vincristine, cytosine arabinoside, prednisolone, and subsequently supplemented by L-asparaginase, it was replaced by another protocol combining vincristine, L-asparaginase, prednisolone, cyclophosphamide and doxorubicin. Soon after the third weekly session of the second protocol, the clinical status of the animal deteriorated suddenly and severely, with a bleeding tendency, jaundice, hyperuricaemia, hyperphosphataemia, azotaemia, hyperbilirubinaemia and, presumptive disseminated intravascular coagulation. There was also complete regression of lymphadenomegaly. This report emphasises the clinicopathological features and the diagnostic peculiarities of the acute tumour lysis syndrome, which occurs uncommonly in dogs.     

Response of canine cutaneous epitheliotropic lymphoma to lomustine (CCNU): a retrospective study of 46 cases (1999-2004)

BACKGROUND: Epitheliotropic lymphoma (ELSA) is an uncommon cutaneous canine malignancy of T lymphocytes. A consensus regarding the therapeutic standard of care is lacking, warranting evaluation of chemotherapeutic agents traditionally employed against canine nodal lymphoma in the treatment of ELSA. HYPOTHESIS: The purpose of this retrospective, multi-institutional study was to evaluate the efficacy of 1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea (CCNU) in the treatment of ELSA. ANIMALS: Forty-six dogs with adequate follow-up and treatment response information. METHODS: All cases were diagnosed histopathologically. Immunohistochemisty (CD3, CD79a) was performed on 42/46 samples. RESULTS: Presenting skin lesions included generalized scales (25/46), plaques or nodules (22/46), mucocutaneous lesions (14/ 46), and corneal involvement (1/46). Lymph node involvement and Sézary syndrome were documented in 7 and 2 dogs, respectively. The median number of CCNU treatments was 4 (range, 1-11), with a median starting dose of 60 mg/m(2) (range, 30-95). Of the 46 dogs, 15 achieved complete remission, 23 achieved partial remission, 5 had stable disease, and 3 had progressive disease, for an overall response rate of 83%. The median number of treatments to achieve a response was 1 (range, 1-6). The overall median duration of response was 94 days (range, 22-282). Sixteen dose reductions were required because of neutropenia (10/46), thrombocytopenia (1/46), anemia (1/46), increased liver enzyme activity (3/46), or unspecified reasons (1/46). CONCLUSIONS AND CLINICAL IMPLICATIONS: Given the high response rate and well tolerated protocol, prospective studies are warranted to investigate the utility of CCNU alone or in multi-agent protocols for the treatment of ELSA.     

Cutaneous T-cell lymphoma with Sézary syndrome in a dog

An 8-year-old female spayed Cocker Spaniel mix breed dog was presented with generalized erythroderma, scaling and alopecia. Radiographs of the thorax demonstrated a discrete lung mass which was aspirated using ultrasound guidance and cytological analysis revealed large abnormal lymphocytes. Similar cells were observed in the peripheral blood and in skin biopsies. The cells in the skin biopsies were epidermotropic, indicative of an uncommon cutaneous lymphoma termed cutaneous T cell lymphoma (CTCL), sometimes also called mycosis fungoides. Immunohistochemical staining of a skin biopsy was positive for the CD3 antigen demonstrating that the lymphocyte infiltrate was of a T-cell lineage. The presence of neoplastic lymphocytes in the epidermis and peripheral blood indicate that this is a rare variant of Cutaneous Epidermotropic Lymphoma (CEL) called Sézary syndrome based on nomenclature used in the human literature. An unusual feature of this dog, not seen in previous cases, was the presence of a discrete neoplastic lung mass.     

Nontraditional treatment of mycosis fungoides in a dog

A 14-year-old Dachshund with plaque-stage mycosis fungoides was treated and kept free of lesions for 25 months, using combination drug therapy of a placental lysate and low-dose prednisone. Mycosis fungoides has a poor prognosis and has had a history of poor response to treatment. Placental lysate with low-dose prednisone may offer an alternate therapeutic regimen in this disease.     

Systemic mycosis due to Aspergillus deflectus in a dog

A 4-year-old, entire female, German Shepherd Dog was referred with a 3-month history of right foreleg lameness that partially responded to nonsteroidal anti-inflammatory and antimicrobial therapy. The bitch lost weight, was polydipsic and had reduced exercise tolerance. On referral, the animal was in poor condition, pyrexic and exhibited moderate pain on full extension of the right shoulder. Blood, urine and joint fluid were obtained and radiographs were taken of the right shoulder and chest. The bitch was lymphopaenic, hyperfibrinogenaemic, hyperglobulinaemic, mildly azotaemic, mildly proteinuric and isosthenuric. Branching fungal hyphae were present in the urine. On radiography, the thorax contained a large ventral mediastinal mass and the humeral head had extensive areas of radiolucency. An aspirate from the right humeroscapular joint exhibited branched fungal hyphae and numerous neutrophils and macrophages. A diagnosis of disseminated mycosis was made and euthanasia was performed. At necropsy, numerous caseating granulomas were present, especially in the kidneys, adrenal glands, heart and lymph nodes. Extensive osteomyelitis involved the head of the right humerus, the sternebrae and the fifth intervertebral disc. Fungal hyphae were detected in sections of granulomas in all affected organs and a diagnosis of disseminated fungal granulomatosis was made. Aspergillus deflectus was readily isolated from affected lymph nodes, but confirming its identity as A deflectus using standard procedures proved difficult. The identity of the fungus was finally confirmed by sequencing part of the 185 rRNA of the isolate. This is the first report in Australia of a disseminated mycosis caused by A deflectus. Previously, the involvement of A deflectus as a cause of disseminated mycosis was limited to 5 cases from the West Coast of the USA, four of which occurred in German Shepherd Dogs.     

Lymphoma with cutaneous involvement in three domestic rabbits (Oryctolagus cuniculus)

Three domestic rabbits ( Oryctolagus cuniculus ) with cutaneous lymphoma are described. Two rabbits were young (7 weeks and 1 years) and were euthanized within 1 week of showing clinical signs. Lymphoma was found in the skin and internal organs. The third rabbit was 9.5 years of age, and lived for more than 1 year after diagnosis. No response was seen to either 2 months of alpha-interferon administration or a 2.5-week course of isotretinoin treatment. After 1 year the rabbit died suddenly; the owner refused necropsy. Immunologic stains of the tumour in all three rabbits showed T cells to be the lymphoma cell type.     

Marginal zone lymphoma in a dog

A 13-year-old spayed female American Cocker Spaniel was presented for evaluation of a cough and weight loss. Physical exam revealed generalized lymphadenopathy. The patient was diagnosed with marginal zone lymphoma (MZL) on histopathology of an extirpated lymph node. This report demonstrates an unusual case of a pleomorphic neoplastic population documented on cytologic evaluation that had moncytoid features and peripheral blood involvement; a previously undocumented IgG1 monoclonal gammopathy was also an interesting feature of this canine MZL. The patient did not undergo chemotherapy for lymphoma and was euthanized over 4 years after the initial presentation.