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1.
BMC Vet Res ; 18(1): 267, 2022 Jul 11.
Article in English | MEDLINE | ID: mdl-35821128

ABSTRACT

BACKGROUND: Cutaneous epitheliotropic T-cell lymphoma is a malignant tumour of the skin already reported in humans, dogs, cats, horses, and other species, but not previously in donkeys. The standard diagnosis is based on clinical, morphological and immunophenotypic data. Differentiation of malignant versus benign proliferation of lymphocytes is crucial; in ambiguous cases T-cell receptor gamma (TRG) molecular clonality should be tested. In the present paper, we report a case of mycosis fungoides diagnosed in a donkey whose diagnosis was based on clinical, histological and immunohistochemical aspects and a positive TRG clonality test. CASE PRESENTATION: A twenty-five-year-old donkey gelding was referred with a mildly pruritic, generalised and severe exfoliative dermatosis. Otherwise, the animal was clinically healthy, though mildly underweight. Dermatological examination revealed severe generalised alopecic and exfoliative dermatitis, occasionally eroded, with high number of large, thin, greyish scales. All mucocutaneous junctions except the hoofs were affected. Ectoparasites and dermatophytes were ruled out. The complete blood count and blood smear evaluation revealed mild normocytic normochromic anemia. The biochemistry panel showed mild hyperproteinemia with albumin within the normal range. Protein electrophoresis showed moderate polyclonal hypergammaglobulinemia. Histological findings were characterised by interface dermatitis with massive exocytosis in the epidermis of a homogenous population of lymphoid cells showing atypia. Clusters of neoplastic cells were present within the epidermis forming Pautrier "microabscesses". These findings are consistent with cutaneous epitheliotropic lymphoma. Immunohistochemical staining revealed uniform labelling of the neoplastic cells for CD3, and lack of expression of CD20 (a B cell lineage associated marker). Molecular clonality PCR (PARR) was performed using equine TRG primers; this revealed a clonal rearrangement in a heavy polyclonal background. Transmission electronic microscopy showed multiple lymphocytes with convoluted or cerebriform nuclei. CONCLUSIONS: This case report provides the first evidence of clinical, histopathological, immunophenotypic features, electron microscopy findings and molecular analysis of a cutaneous epitheliotropic T-cell lymphoma (mycosis fungoides) in a donkey. Our observations suggest that cutaneous T-cell lymphoma should be included in the differential diagnoses of exfoliative dermatitis, even those progressing in a chronic pattern and/or with few or no pruritus.


Subject(s)
Dermatitis, Exfoliative , Equidae , Lymphoma, T-Cell, Cutaneous , Mycosis Fungoides , Skin Neoplasms , Animals , Dermatitis, Exfoliative/veterinary , Lymphoma, T-Cell, Cutaneous/diagnosis , Lymphoma, T-Cell, Cutaneous/pathology , Lymphoma, T-Cell, Cutaneous/veterinary , Male , Mycosis Fungoides/diagnosis , Mycosis Fungoides/pathology , Mycosis Fungoides/veterinary , Receptors, Antigen, T-Cell, gamma-delta , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Skin Neoplasms/veterinary
2.
Vet Dermatol ; 33(6): 559-567, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35876313

ABSTRACT

BACKGROUND: Canine epitheliotropic cutaneous T-cell lymphoma (eCTCL) is thought to represent a disease homologue to human mycosis fungoides (MF). In human MF, neoplastic cells are phenotypically consistent with resident effector memory T cells, a population that remains for an extended period within tissue without circulating. Dogs with eCTCL often present with lesions in multiple locations, raising the question of whether the neoplasm is of the same T-cell subpopulation or not. OBJECTIVES: To characterize the antigen receptor gene rearrangements of lymphocytes from skin and blood of dogs with eCTCL to determine if neoplastic clones are identical. ANIMALS: Fourteen dogs with eCTCL. MATERIALS AND METHODS: Histological and immunohistochemical examination, and PCR for antigen receptor rearrangement (PARR) for T-cell receptor gamma (TRG) performed on multiple cutaneous biopsy samples and blood. RESULTS: All skin biopsies contained cluster of differentiation (CD)3-positive neoplastic lymphocytes. Within individual dogs, all skin biopsies revealed identical TRG clonality profiles, suggesting that the same neoplastic clone was present in all sites. In the blood, a matching clone was found in six of 14 dogs, a unique clone was observed in nine of 14 dogs, and no clone was detected in two of 14 dogs. CONCLUSIONS: These findings show that canine eCTCL lesions in multiple locations harbour the same neoplastic clone, neoplastic lymphocytes do not remain fixed to the skin and instead can circulate via blood, differing clones can be identified in skin versus blood, and circulating neoplastic cells can be detected without lymphocytosis.


Contexte - On pense que le lymphome T cutanĆ© Ć©pithĆ©liotrope canin (eCTCL) reprĆ©sente une maladie homologue au mycosis fongoĆÆde (MF) humain. Dans le MF humain, les cellules nĆ©oplasiques sont phĆ©notypiquement compatibles avec les cellules T mĆ©moire effectrices rĆ©sidentes, une population qui reste pendant une pĆ©riode prolongĆ©e dans les tissus sans circuler. Les chiens atteints d'eCTCL prĆ©sentent souvent des lĆ©sions Ć  plusieurs endroits, ce qui soulĆØve la question de savoir si le nĆ©oplasme appartient ou non Ć  la mĆŖme sous-population de lymphocytes T. Objectifs - CaractĆ©riser les rĆ©arrangements du gĆØne du rĆ©cepteur antigĆ©nique des lymphocytes de la peau et du sang des chiens atteints d'eCTCL afin de dĆ©terminer si les clones nĆ©oplasiques sont identiques. Animaux - Quatorze chiens avec eCTCL. MatĆ©riels et mĆ©thodes - Examen histologique et immunohistochimique, et PCR pour le rĆ©arrangement des rĆ©cepteurs antigĆ©niques (PARR) pour le rĆ©cepteur gamma des lymphocytes T (TRG) effectuĆ©s sur plusieurs Ć©chantillons de biopsie cutanĆ©e et de sang. RĆ©sultats - Toutes les biopsies cutanĆ©es contenaient des amas de lymphocytes nĆ©oplasiques positifs Ć  la diffĆ©renciation (CD)3. Chez les chiens individuels, toutes les biopsies cutanĆ©es ont rĆ©vĆ©lĆ© des profils de clonalitĆ© TRG identiques, suggĆ©rant que le mĆŖme clone nĆ©oplasique Ć©tait prĆ©sent dans tous les sites. Dans le sang, un clone correspondant a Ć©tĆ© trouvĆ© chez six des 14 chiens, un clone unique a Ć©tĆ© observĆ© chez neuf des 14 chiens et aucun clone n'a Ć©tĆ© dĆ©tectĆ© chez deux des 14 chiens. Conclusions - Ces rĆ©sultats montrent que les lĆ©sions eCTCL canines Ć  plusieurs endroits abritent le mĆŖme clone nĆ©oplasique, les lymphocytes nĆ©oplasiques ne restent pas fixĆ©s Ć  la peau et peuvent plutĆ“t circuler par le sang, diffĆ©rents clones peuvent ĆŖtre identifiĆ©s dans la peau par rapport au sang, et les cellules nĆ©oplasiques circulantes peuvent ĆŖtre dĆ©tectĆ© sans lymphocytose.


IntroducciĆ³n- se cree que el linfoma epiteliotrĆ³pico cutĆ”neo de cĆ©lulas T canino (eCTCL) representa una enfermedad homĆ³loga a la micosis fungoide (MF) humana. En la MF humana, las cĆ©lulas neoplĆ”sicas son fenotĆ­picamente consistentes con las cĆ©lulas T de memoria efectoras residentes, una poblaciĆ³n que permanece durante un perĆ­odo prolongado dentro del tejido sin circular. Los perros con eCTCL a menudo presentan lesiones en mĆŗltiples ubicaciones, lo que plantea la cuestiĆ³n de si la neoplasia es de la misma subpoblaciĆ³n de cĆ©lulas T o no. Objetivos- caracterizar los reordenamientos del gen del receptor de antĆ­geno de los linfocitos de la piel y la sangre de perros con eCTCL para determinar si los clones neoplĆ”sicos son idĆ©nticos. Animales- catorce perros con eCTCL. Materiales y mĆ©todos - Examen histolĆ³gico e inmunohistoquĆ­mico, y PCR para el reordenamiento del receptor de antĆ­geno (PARR) para el receptor de cĆ©lulas T gamma (TRG) realizado en mĆŗltiples muestras de biopsia cutĆ”nea y sangre. Resultados- todas las biopsias de piel contenĆ­an linfocitos neoplĆ”sicos positivos para grupos de diferenciaciĆ³n (CD)3. Dentro de perros individuales, todas las biopsias de piel revelaron perfiles de clonalidad de TRG idĆ©nticos, lo que sugiere que el mismo clon neoplĆ”sico estaba presente en todos los sitios. En la sangre, se encontrĆ³ un clon compatible en seis de 14 perros, se observĆ³ un clon Ćŗnico en nueve de 14 perros y no se detectĆ³ ningĆŗn clon en dos de 14 perros. Conclusiones- estos hallazgos muestran que las lesiones de eCTCL canino en mĆŗltiples ubicaciones albergan el mismo clon neoplĆ”sico, los linfocitos neoplĆ”sicos no permanecen fijados a la piel y, en cambio, pueden circular a travĆ©s de la sangre, se pueden identificar diferentes clones en la piel versus la sangre y las cĆ©lulas neoplĆ”sicas circulantes pueden ser identificadas sin presencia de linfocitosis.


Contexto - Acredita-se que o linfoma epiteliotrĆ³pico cutĆ¢neo de cĆ©lulas T canino (eCTCL) representa uma doenƧa anĆ”loga Ć  micose fungoide (MF) humana. Na MF humana, as cĆ©lulas neoplĆ”sicas sĆ£o fenotipicamente consistentes com cĆ©lulas T efetoras de memĆ³ria residentes, uma populaĆ§Ć£o que permanece por um perĆ­odo extenso no tecido sem entrar na circulaĆ§Ć£o. Os cĆ£es com eCTCL frequentemente apresentam lesƵes em mĆŗltiplos locais, levantando a questĆ£o de se a neoplasia Ć© da mesma subpopulaĆ§Ć£o de cĆ©lulas T ou nĆ£o. Objetivos - Caracterizar os rearranjos dos genes receptores de antĆ­genos dos linfĆ³citos da pele e do sangue de cĆ£es com eCTCL para determinar se os clones neoplĆ”sicos sĆ£o idĆŖnticos. Animais - Quatorze cĆ£es com eCTCL. Materiais e mĆ©todos - Exame histolĆ³gico e imunohistoquĆ­mico, e PCR para rearranjo de receptor de antĆ­geno (PARR) para o receptor Gama de cĆ©lulas T (TRG) realizado em mĆŗltiplas amostras de biĆ³psia cutĆ¢nea e sangue. Resultados - Todas as biĆ³psias cutĆ¢neas continham clusters de diferenciaĆ§Ć£o linfĆ³citos T (CD)3- positivos. Entre os indivĆ­duos, todas as biĆ³psias cutĆ¢neas revelaram perfis de clonalidade de TGR idĆŖnticos em seis dos 14 cĆ£es, sugerindo que a mesma cĆ©lula neoplĆ”sica estava presente em todos os locais. No sangue, um clone correspondente foi encontrado em seis dos 14 cĆ£es, um clone Ćŗnico foi observado em nove dos 14 cĆ£es e nenhum clone foi detectado em dois dos 14 cĆ£es. ConclusƵes - Estes achados demonstraram que as lesƵes de eCTCL em mĆŗltiplos locais possuem o mesmo clone neoplĆ”sico, linfĆ³citos neoplĆ”sicos nĆ£o permanecem fixos na pele e podem circular por via sistĆŖmica , diversos tipos de clones podem ser identificados na pele versus sangue, e as cĆ©lulas neoplĆ”sicas circulantes podem ser detectadas sem linfocitose.


Subject(s)
Dog Diseases , Lymphoma, T-Cell, Cutaneous , Mycosis Fungoides , Skin Neoplasms , Dogs , Animals , Humans , Skin Neoplasms/diagnosis , Skin Neoplasms/veterinary , Mycosis Fungoides/pathology , Mycosis Fungoides/veterinary , Lymphoma, T-Cell, Cutaneous/veterinary , Lymphoma, T-Cell, Cutaneous/pathology , Skin/pathology , Biopsy/veterinary , Dog Diseases/pathology
3.
Vet Dermatol ; 28(2): 246-e65, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28133821

ABSTRACT

BACKGROUND: Mycosis fungoides (MF) is an uncommon cutaneous neoplasm in dogs. Treatment options are limited. Total skin electron therapy (TSET) has been suggested as a possible therapy for canine MF. OBJECTIVE: To describe the use of TSET as palliative treatment for MF in a dog. RESULTS: An adult dog, previously diagnosed with nonepidermolytic ichthyosis, was presented with generalized erythroderma, alopecia and erosions. Histopathology revealed a densely cellular, well-demarcated, unencapsulated infiltrate extending from the epidermis to the mid-dermis compatible with MF. The infiltrate exhibited epitheliotropism multifocally for the epidermis, infundibula and adnexa. Due to a lack of response to chemotherapy, TSET was elected. Six megavoltage electrons were delivered using a 21EX Varian linear accelerator. A dose of 6 Gy was delivered to the skin surface and a 100 cm skin to surface distance was used for dog setup. The treatment time for the cranial half treatment was 3 h. The treatment was divided in two sessions (cranial and caudal halves of the body) 15 days apart. Clinical and histopathological complete remission was achieved and the dog was kept in remission with no additional treatments for 19 months before relapse and development of SĆ©zary syndrome. CONCLUSION AND CLINICAL SIGNIFICANCE: To the best of the authors' knowledge, this is the first case reporting the use of TSET for medically refractory canine MF with post treatment follow-up. This case suggests that the use of TSET may be an effective palliative treatment for canine MF.


Subject(s)
Dog Diseases/therapy , Mycosis Fungoides/veterinary , Skin Neoplasms/veterinary , Whole-Body Irradiation/veterinary , Animals , Dog Diseases/radiotherapy , Dogs , Fatal Outcome , Female , Mycosis Fungoides/pathology , Mycosis Fungoides/radiotherapy , Skin Neoplasms/pathology , Skin Neoplasms/radiotherapy
4.
Vet Pathol ; 53(3): 563-6, 2016 May.
Article in English | MEDLINE | ID: mdl-26354309

ABSTRACT

A 14-year-old female spayed Dachshund was presented with generalized scaling, erythema, pruritus, poor quality of hair coat, and progressive weight loss. Cutaneous epitheliotropic T-cell lymphoma (CETCL) was suspected. Skin biopsies were suggestive of CETCL. However, immunohistochemistry revealed the presence of numerous CD20+ and CD3+ cells. Clonality assay demonstrated a clonal T-cell receptor gamma rearrangement and a polyclonal IgH gene rearrangement. Double-label immunofluorescence confirmed coexpression of CD3 and CD20 by neoplastic cells. By double immunohistochemistry, neoplastic cells were CD3+ and PAX5-. The results are compatible with a CD3+, CD20+ CETCL. Coexpression of CD20 and CD3 has been recognized in peripheral T-cell lymphomas. Although documented in human CETCL, it has not been reported in canine CETCL. The pathogenetic basis of CD20 expression in mycosis fungoides is explored.


Subject(s)
Antigens, CD20/metabolism , CD3 Complex/metabolism , Dog Diseases/diagnosis , Lymphoma, T-Cell, Cutaneous/veterinary , Mycosis Fungoides/veterinary , Skin Neoplasms/veterinary , Animals , Biopsy/veterinary , Dog Diseases/metabolism , Dog Diseases/pathology , Dogs , Epithelium/metabolism , Epithelium/pathology , Female , Fluorescent Antibody Technique/veterinary , Immunohistochemistry/veterinary , Lymphoma, T-Cell, Cutaneous/diagnosis , Lymphoma, T-Cell, Cutaneous/metabolism , Lymphoma, T-Cell, Cutaneous/pathology , Mycosis Fungoides/diagnosis , Mycosis Fungoides/metabolism , Mycosis Fungoides/pathology , Skin/metabolism , Skin/pathology , Skin Neoplasms/diagnosis , Skin Neoplasms/metabolism , Skin Neoplasms/pathology
5.
Vet Dermatol ; 24(6): 628-31, e155, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24118305

ABSTRACT

BACKGROUND: Mycosis fungoides (MF) is the most common form of canine epitheliotropic cutaneous lymphoma, which is characterized by the accumulation of neoplastic CD8(+) T cells. Given that multifocal skin lesions are commonly seen in MF, neoplastic lymphocytes may actively migrate into the blood circulation. HYPOTHESIS/OBJECTIVES: Cytotoxic T cells with a skin-homing phenotype could be increased in the blood circulation of dogs with MF. ANIMALS: Ten dogs with MF and 10 age-matched healthy dogs were included. METHODS: The transcription levels of chemokine receptors, cytokines and cytotoxic markers in peripheral blood of dogs with MF were quantified by real-time RT-PCR. RESULTS: The dogs with MF had lower transcription levels of chemokine receptors associated with skin homing (CCR4), epitheliotropism (CXCR3), lymph node homing (CCR7), a type-1 cytokine (LT-α) and cytotoxic markers (perforin and granzyme B) in the circulation than healthy control dogs (P < 0.05). CONCLUSIONS AND CLINICAL IMPORTANCE: The present results suggest that the number of peripheral cytotoxic T cells with a skin-homing phenotype could be decreased in the peripheral blood of dogs with MF, which might be due to the sequestration of cytotoxic T cells in the lesional skin.


Subject(s)
Biomarkers, Tumor/blood , Cytokines/metabolism , Dog Diseases/metabolism , Mycosis Fungoides/veterinary , Receptors, Chemokine/metabolism , Transcriptome , Animals , Case-Control Studies , Cytokines/genetics , Dog Diseases/blood , Dogs , Gene Expression Regulation, Neoplastic , Mycosis Fungoides/genetics , Mycosis Fungoides/metabolism , Receptors, Chemokine/genetics
6.
J Vet Diagn Invest ; 22(1): 20-9, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20093678

ABSTRACT

In the dog, early-stage epitheliotropic T-cell lymphoma (ETCL) can clinically and histologically mimic a large range of inflammatory dermatoses and often progresses rapidly to a more aggressive tumor stage. Early diagnosis of ETCL is essential to proceed with a specific oncologic therapy that is favorable for the prognosis. In the present study, an improved method for the detection of T-cell receptor gamma (TCRgamma) rearrangement was developed by designing a new set of consensus primers to amplify the different forms of rearranged canine TCRgamma gene sequences by polymerase chain reaction. The amplicons were analyzed by conventional polyacrylamide gel electrophoresis, which requires minimal specific equipment and may be performed in almost every pathology laboratory at low costs. The method proved to be highly specific and sensitive to detect early ETCL in formalin-fixed, paraffin-embedded biopsy specimens, providing an efficient tool for veterinary pathologists to distinguish early neoplastic from reactive cutaneous T-cell infiltrates (tumor-specific marker) or to discriminate T-cell lymphoma from B-cell lymphomas or nonlymphoid neoplasms (T-cell lineage marker). By direct sequencing analysis of amplified TCRgamma gene sequences, ETCL was found to rearrange exclusively the joining (J) 4 region, which suggests specific biology for primary cutaneous T-cell lymphomas. Also, a novel (seventh) functional J region in the TCRgamma gene, localized approximately 2.3 kb upstream of J5, was identified.


Subject(s)
Biopsy/veterinary , Dog Diseases/diagnosis , Mycosis Fungoides/veterinary , Polymerase Chain Reaction/veterinary , Skin/pathology , Animals , DNA/genetics , Dogs , Female , Gene Expression Regulation, Neoplastic/physiology , Genes, T-Cell Receptor gamma/physiology , Male , Mycosis Fungoides/diagnosis , Mycosis Fungoides/metabolism , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Receptors, Antigen, T-Cell, gamma-delta/genetics , Receptors, Antigen, T-Cell, gamma-delta/metabolism
7.
J Small Anim Pract ; 49(4): 204-7, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18086155

ABSTRACT

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.


Subject(s)
Lymphoma, T-Cell, Cutaneous/veterinary , Mycosis Fungoides/veterinary , Procyonidae , Skin Neoplasms/veterinary , Animals , Fatal Outcome , Female , Immunocompromised Host , Immunohistochemistry/veterinary , Lymphoma, T-Cell, Cutaneous/diagnosis , Lymphoma, T-Cell, Cutaneous/pathology , Mycosis Fungoides/diagnosis , Mycosis Fungoides/pathology , Pleurisy/etiology , Pleurisy/veterinary , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , T-Lymphocytes, Regulatory/pathology
8.
J Zoo Wildl Med ; 38(3): 479-82, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17939360

ABSTRACT

A 12-yr-old, intact male squirrel (Sciurus sp.) presented with a 15 mm-by-20 mm area of alopecia and plaque-like dermal thickening over the left caudolateral thorax. Routine diagnostic tests ruled out more common conditions that result in alopecia, such as dermatophytosis and acariasis. A punch biopsy was obtained under anesthesia and submitted for histopathologic evaluation. The diagnosis of epitheliotropic lymphoma was made, and follow-up surgical excision was performed. Histopathologic features were consistent with epitheliotropic lymphoma, and immunohistochemistry confirmed a T-cell origin. There was no local recurrence, new lesions, or evidence of metastasis 10 mo after surgical excision. To our knowledge, to date, epitheliotropic lymphoma has not been described in a squirrel.


Subject(s)
Mycosis Fungoides/veterinary , Sciuridae , Skin Neoplasms/veterinary , Animals , Male , Mycosis Fungoides/epidemiology , Mycosis Fungoides/pathology , Mycosis Fungoides/surgery , Skin Neoplasms/epidemiology , Skin Neoplasms/pathology , Skin Neoplasms/surgery , Treatment Outcome
9.
J Vet Intern Med ; 20(1): 136-43, 2006.
Article in English | MEDLINE | ID: mdl-16496933

ABSTRACT

This retrospective study examined the use of CCNU (1-[2-chloroethyl]3-cyclohexyl-1-nitrosurea) in 36 dogs with epitheliotropic lymphoma. Thirty-one (86%) dogs had the cutaneous form of disease, and 5 (14%) dogs had the oral form of disease. Nineteen (51%) dogs were treated with other chemotherapeutic agents before receiving CCNU. All dogs had detectable disease at the time CCNU therapy was initiated. Dogs received a median starting CCNU dosage of 70 mg/m2 (range, 50-100 mg/m2). The median number of treatments administered was 3 (range, 1-12 treatments). After the initial treatment, the CCNU dosage was adjusted in 9 of 26 (35%) dogs in which CCNU was continued: 7 had dosage reductions, and 2 had dosage escalations. Twenty-eight of 36 (78%) dogs had a measurable response to CCNU for a median duration of 106 days (95% confidence interval [CI], 75-182). Six dogs (17%) had a complete response, including 5 dogs with the cutaneous form and 1 dog with the oral form. Twenty-two dogs (61%) had a partial response, including 20 dogs with the cutaneous form and 2 dogs with the oral form, for a median duration of 88 days (95% CI, 62-170). Toxicoses after CCNU chemotherapy included myelosuppression in up to 29% of the dogs, gastrointestinal signs in up to 22% of the dogs, and liver enzyme activity increases in up to 86% of the dogs. This study demonstrates that CCNU chemotherapy can be considered a reasonable option for the treatment of canine epitheliotropic lymphoma in dogs.


Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Dog Diseases/drug therapy , Lomustine/therapeutic use , Mycosis Fungoides/veterinary , Skin Neoplasms/veterinary , Animals , Antineoplastic Agents, Alkylating/adverse effects , Dogs , Female , Lomustine/adverse effects , Male , Mycosis Fungoides/drug therapy , Retrospective Studies , Skin Neoplasms/drug therapy
10.
J Vet Intern Med ; 20(6): 1389-97, 2006.
Article in English | MEDLINE | ID: mdl-17186855

ABSTRACT

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 SĆ©zary 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.


Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Dog Diseases/drug therapy , Lomustine/therapeutic use , Mycosis Fungoides/veterinary , Skin Neoplasms/veterinary , Animals , Antineoplastic Agents, Alkylating/adverse effects , Dog Diseases/pathology , Dogs , Female , Immunohistochemistry/veterinary , Lomustine/adverse effects , Male , Mycosis Fungoides/drug therapy , Mycosis Fungoides/pathology , Retrospective Studies , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Treatment Outcome
11.
J Vet Sci ; 7(1): 97-9, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16434861

ABSTRACT

A seven-year-old castrated male Yorkshire terrier dog was presented for a recurrent skin disease. Erythematous skin during the first visit progressed from multiple plaques to patch lesions and exudative erosion in the oral mucosa membrane. Biopsy samples were taken from erythematous skin and were diagnosed with epitheliotropic T cell cutaneous lymphoma by histopathology and immunochemical stain. In serum chemistry, the dog had a hypercalcemia (15.7 mg/dl) and mild increased alkaline phosphatase (417 U/l). Immunohistochemistry was performed to detect parathyroid hormone-related peptide (PTH-rP) in epitheliotropic cutaneous lymphoma tissues but the neoplastic cells were not labeled with anti-PTH-rP antibodies. The patient was treated with prednisolone and isotretinoin. However, the dog died unexpectedly.


Subject(s)
Dog Diseases/pathology , Mycosis Fungoides/veterinary , Skin Neoplasms/veterinary , Animals , Dog Diseases/drug therapy , Dogs , Fatal Outcome , Isotretinoin/therapeutic use , Male , Mycosis Fungoides/drug therapy , Mycosis Fungoides/pathology , Prednisolone/therapeutic use , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology
12.
J Invest Dermatol ; 102(2): 227-30, 1994 Feb.
Article in English | MEDLINE | ID: mdl-7906287

ABSTRACT

Canine cutaneous T-cell lymphoma (CTCL) is a morphologic and immunophenotypic simulant of human mycosis fungoides (MF) characterized by an infiltrate of atypical, hyperconvoluted, epidermotropic T cells. To further support our hypothesis that canine MF is a useful model for the study of human CTCL, we have used Southern blotting to search for clonal T-cell proliferations in canine MF. Cellular DNA was extracted from normal dog buffy coat cells (n = 8), lesional canine MF skin (n = 8), canine MF buffy coat cells (n = 7), normal dog skin (n = 3), and normal human buffy coat cells (n = 5), digested with a panel of restriction enzymes and Southern blotted onto nylon membranes. All cases of canine MF were also immunophenotyped with anti-canine monoclonal antibodies to CD4, CD8, CD18, CD45RA, canine class II, T-cell activation antigens, and pan-B-cell antigens. Normal dogs gave reproducible digestion patterns in blood and skin, which differed from the human germline patterns when probed with a human T-cell receptor (TCR), beta chain constant region (C beta) cDNA. Common germline bands between the species included the 3.5-kb Eco RI, 3.4-kb Bam HI, 5.4-kb Sac I. These results confirmed that the TCR-beta gene is evolutionarily conserved between dog and man. Immunostaining revealed that 3/7 cases were CD4+ canine CTCL and 4/7 were CD8+ canine CTCL. Rearranged bands, deletion of germline bands, as well as minor alterations in electrophoretic mobility were observed in lesional DNA from seven of eight cases of canine MF, with at least two restriction digests in each case. Dog rearrangements were best detected with Bgl II, Eco RI, Eco RV, and Sac I, whereas deletions were detected with Bgl II, Sac I, Eco RV, and Bam HI. These studies demonstrate the presence of clonal TCR rearrangement in canine MF, further supporting the similarity of this tumor to human MF and its role as an animal model of CTCL.


Subject(s)
Dog Diseases/genetics , Gene Rearrangement, beta-Chain T-Cell Antigen Receptor/genetics , Lymphoma, T-Cell, Cutaneous/veterinary , Mycosis Fungoides/veterinary , Receptors, Antigen, T-Cell, alpha-beta/genetics , Skin Neoplasms/veterinary , Animals , Antigens, CD/analysis , Biological Evolution , Blotting, Southern , CD18 Antigens , CD4 Antigens/analysis , CD8 Antigens/analysis , DNA, Neoplasm/analysis , DNA, Neoplasm/genetics , Disease Models, Animal , Dogs , Humans , Immunophenotyping , Leukocyte Common Antigens/analysis , Lymphoma, T-Cell, Cutaneous/genetics , Lymphoma, T-Cell, Cutaneous/pathology , Mycosis Fungoides/genetics , Receptors, Antigen, T-Cell, alpha-beta/analysis , Skin Neoplasms/genetics , Skin Neoplasms/pathology , T-Lymphocytes/chemistry , T-Lymphocytes/pathology , T-Lymphocytes/ultrastructure
13.
Cancer Lett ; 64(1): 17-22, 1992 May 30.
Article in English | MEDLINE | ID: mdl-1596872

ABSTRACT

Linoleic acid (LA) administered orally as safflower oil (SFO), which is 76% LA, produced remission in 6 out of 8 dogs with mycosis fungoides (MF). Following each feeding of SFO on 5 successive days to a normal dog peak plasma levels of non-esterified (free) LA in excess of 200 microM were observed. No clinical toxicity was observed from the SFO feedings in the normal or MF animals at the levels of SFO (3 ml/kg) used in these studies. However, a marked rise in white blood cells (WBC) and lymphocytes and a marked transient drop in the serum glutamine transaminases SGOT and SGPT was noted both in the normal and MF animals. These effects of LA may be significant for the remission of MF.


Subject(s)
Dog Diseases/drug therapy , Linoleic Acids/therapeutic use , Mycosis Fungoides/veterinary , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Dog Diseases/pathology , Dogs , Leukocyte Count , Linoleic Acid , Linoleic Acids/administration & dosage , Remission Induction , Safflower Oil/administration & dosage
14.
Arch Dermatol Res ; 287(2): 186-92, 1995.
Article in English | MEDLINE | ID: mdl-7539248

ABSTRACT

In human mycosis fungoides (MF), interactions between LFA-1 (CD11a/CD18) and ICAM-1 (CD54) are involved in lymphocyte adhesion to keratinocytes. The purpose of this study was to evaluate the expression of ICAM-1, beta-2 integrins and class II major histocompatibility complex molecules (MHC II) on keratinocytes and infiltrating lymphocytes in canine MF. Sections of frozen skin biopsy specimens from normal dogs (n = 3) and dogs with MF (n = 17) were evaluated by immunohistochemistry for expression of ICAM-1, beta-2 integrins, and class II MHC molecules. Our results demonstrated that in canine MF, ICAM-1 was expressed variably on epidermal and follicular keratinocytes. The extent of keratinocyte ICAM-1 expression did not correlate with the degree of lymphocyte epithelial infiltration, nor with lymphocyte LFA-1 expression. This was especially evident in cases of Pagetoid reticulosis-like disease in which prominent lymphocyte epidermotropism was not accompanied by keratinocyte ICAM-1 expression. Keratinocyte class II MHC molecule expression did not correlate with keratinocyte ICAM-1 expression. In conclusion, in canine MF, the lack of statistically significant correlations between epithelial lymphocyte infiltration and keratinocyte ICAM-1 expression, and between keratinocyte ICAM-1 and lymphocyte LFA-1 staining, suggests that the LFA-1/ICAM-1 pathway is not the major adhesion mechanism between lymphocytes and keratinocytes. It is suspected that different ligands of the LFA-1 integrin (e.g. ICAM-2) or other adhesion molecules (e.g. CD2/LFA-3, VLA-1) might be involved in the epitheliotropism phenomenon in canine MF. These hypothesis cannot be evaluated in the dog at this time owing to the lack of specific monoclonal antibodies.


Subject(s)
Dog Diseases , Integrins/biosynthesis , Intercellular Adhesion Molecule-1/biosynthesis , Lymphocytes/immunology , Mycosis Fungoides/veterinary , Skin/immunology , Animals , Antibodies, Monoclonal , Biopsy , CD11 Antigens/analysis , CD18 Antigens/analysis , Dogs , Epitopes/analysis , Histocompatibility Antigens Class II/analysis , Humans , Immunoenzyme Techniques , Integrins/analysis , Intercellular Adhesion Molecule-1/analysis , Lymphocyte Function-Associated Antigen-1/analysis , Lymphocytes/pathology , Mycosis Fungoides/immunology , Mycosis Fungoides/pathology , Skin/pathology
15.
J Comp Pathol ; 123(1): 59-63, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10906257

ABSTRACT

This report describes an uncommon case of a cutaneous epitheliotropic T-cell lymphosarcoma with central nervous system (CNS) manifestations in a 9-year-old mixed breed German shepherd dog. The animal had a history of sudden blindness, pyrexia and multifocal areas of hyperaemia in the oral mucosa. A biopsy from the muco-cutaneous junction of the lips led to the diagnosis of an epitheliotropic lymphosarcoma and the animal was humanely destroyed. At necropsy, hyperaemia in the oral mucosa was no longer detectable. In the brain, a mass effacing the optic chiasm and invading the hypothalamic area was found; histological examination revealed lymphoid tumour cell infiltration. In the epithelium of the oral mucosa, intra-epithelial lymphoid tumour cells, sometimes arranged in small clusters (Pautrier's microabscesses), in combination with a mild inflammation in the superficial dermis were observed. Skin and brain tumour cells expressed CD3 antigen, indicating their T-cell origin. This is, to our knowledge, the first report of a cutaneous epitheliotropic lymphosarcoma with CNS metastasis in a dog.


Subject(s)
Dog Diseases/pathology , Hypothalamic Neoplasms/veterinary , Mycosis Fungoides/veterinary , Skin Neoplasms/veterinary , Animals , CD3 Complex/chemistry , Dogs , Fatal Outcome , Hypothalamic Neoplasms/chemistry , Hypothalamic Neoplasms/secondary , Immunoenzyme Techniques/veterinary , Mycosis Fungoides/chemistry , Mycosis Fungoides/pathology , Skin Neoplasms/chemistry , Skin Neoplasms/pathology , T-Lymphocytes/chemistry , T-Lymphocytes/pathology
16.
J Am Vet Med Assoc ; 194(4): 535-7, 1989 Feb 15.
Article in English | MEDLINE | ID: mdl-2537810

ABSTRACT

Mycosis fungoides was initially diagnosed in a 7.5-year-old German Shepherd Dog with generalized canine cutaneous histiocytoma. Lesions resolved without treatment over approximately 16 weeks. The final diagnosis of histiocytoma with 2 histopathologic patterns was obtained by use of a special staining technique for the detection of lysozyme found in histiocytes.


Subject(s)
Dog Diseases/pathology , Histiocytoma, Benign Fibrous/veterinary , Skin Neoplasms/veterinary , Animals , Diagnosis, Differential , Dogs , Female , Histiocytes/pathology , Histiocytoma, Benign Fibrous/pathology , Immunohistochemistry , Muramidase/analysis , Mycosis Fungoides/veterinary , Prognosis , Skin Neoplasms/pathology
17.
J Am Vet Med Assoc ; 198(4): 635-8, 1991 Feb 15.
Article in English | MEDLINE | ID: mdl-1850399

ABSTRACT

A 12-year-old spayed Golden Retriever with mycosis fungoides was treated by use of a chemotherapy protocol that included vincristine. After 16 weekly vincristine injections, the dog began to have signs of peripheral neuropathy. Results of electromyographic examination were consistent with muscle denervation, and motor nerve conduction velocity was depressed. Histologic examination of a common peroneal nerve biopsy specimen revealed severe nerve fiber degeneration. Clinical response and pathologic evidence of improvement were observed after the drug had been discontinued for 2.5 months.


Subject(s)
Dog Diseases/chemically induced , Mycosis Fungoides/veterinary , Peripheral Nervous System Diseases/veterinary , Skin Neoplasms/veterinary , Vincristine/adverse effects , Animals , Dog Diseases/drug therapy , Dogs , Electromyography/veterinary , Female , Mycosis Fungoides/drug therapy , Peripheral Nervous System Diseases/chemically induced , Skin Neoplasms/drug therapy , Vincristine/therapeutic use
18.
J Am Vet Med Assoc ; 185(8): 900-1, 1984 Oct 15.
Article in English | MEDLINE | ID: mdl-6501050

ABSTRACT

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.


Subject(s)
Dog Diseases/drug therapy , Mycosis Fungoides/veterinary , Placenta , Prednisone/therapeutic use , Skin Neoplasms/veterinary , Tissue Extracts/therapeutic use , Animals , Dogs , Drug Therapy, Combination , Male , Mycosis Fungoides/drug therapy , Prednisone/administration & dosage , Skin Neoplasms/drug therapy , Tissue Extracts/administration & dosage
19.
J Am Vet Med Assoc ; 212(4): 550-2, 1998 Feb 15.
Article in English | MEDLINE | ID: mdl-9491164

ABSTRACT

A 17-year-old Quarter Horse mare was examined to determine the cause of a vulvar mass. Differential diagnoses for the swollen, ulcerated tissue included hypersensitivity reaction to insect stings or bites and cutaneous neoplasia. During the next 4 months, the mass enlarged involving the skin of the perineum and ventral aspect of the abdomen with secondary dependent edema of both hind limbs. Histologic examination of biopsy and necropsy specimens revealed changes consistent with a diagnosis of mycosis fungoides (cutaneous T-cell lymphoma). Diagnostic features included invasion of neoplastic lymphocytes into the epidermis and detection of T-cell lineage of neoplastic cells. Location of lesions at a mucocutaneous junction, association with epidermal ulcers, and progressive skin involvement mimic the condition in human beings and other species. Prognosis is poor when the condition is at the tumor stage (invasion of deep tissues).


Subject(s)
Horse Diseases/pathology , Mycosis Fungoides/veterinary , Skin Neoplasms/veterinary , Vulvar Neoplasms/veterinary , Abdomen , Animals , Diagnosis, Differential , Female , Horses , Immunohistochemistry , Mycosis Fungoides/pathology , Skin/pathology , Skin/ultrastructure , Skin Neoplasms/pathology , T-Lymphocytes/ultrastructure , Vulvar Neoplasms/pathology
20.
J Am Vet Med Assoc ; 180(5): 531-6, 1982 Mar 01.
Article in English | MEDLINE | ID: mdl-7061338

ABSTRACT

Cutaneous lymphoma (mycosis fungoides) was diagnosed by multiple biopsies of nonulcerated cutaneous lesions in 13 dogs. The disease was initially characterized by erythema and alopecia of the trunk. Subsequently severe scaling, pruritus, and skin nodules developed. Lymph nodes were usually normal in size during early stages of the disease but became enlarged as the disease became extensive. Four dogs were treated with cytotoxic drugs. Marked improvement of skin lesions occurred in 3 dogs, but treatment did not prevent development of extra-cutaneous lesions.


Subject(s)
Dog Diseases/pathology , Mycosis Fungoides/veterinary , Skin Neoplasms/veterinary , Animals , Cyclophosphamide/therapeutic use , Dog Diseases/drug therapy , Dogs , Female , Lymphocytes/ultrastructure , Male , Mechlorethamine/therapeutic use , Mycosis Fungoides/drug therapy , Mycosis Fungoides/pathology , Mycosis Fungoides/ultrastructure , Prednisolone/therapeutic use , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Skin Neoplasms/ultrastructure , Vincristine/therapeutic use
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