Subcutaneous panniculitis-like T-cell lymphoma: Morphological, immunophenotypical and clonality assessment in six cats.

BACKGROUND: Primary cutaneous lymphoma represents 0.2%-3% of all feline lymphomas, with nonepitheliotropic lymphomas being the most common. In humans and dogs, subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a primary nonepitheliotropic lymphoma with a T-cell phenotype developing in the subcutis and often mimicking inflammation. OBJECTIVE: The aim of this report is to describe pathological, phenotypical and clonal features of SPTCL in cats. ANIMALS: Six cats with SPTCL were included in this study. MATERIALS AND METHODS: Skin biopsies were formalin-fixed, routinely processed and stained. Histological and immunohistochemical investigation for anti-CD18, CD204, CD79a, CD20, CD3, FeLVp27and FeLVgp70 and clonality assessment were performed. RESULTS: Four male and two female domestic shorthair cats, mean age 11.2 years, developed SPTCL in the abdominal (three), inguinal (two) and thoracic (one) regions. Variably pleomorphic neoplastic lymphoid cells were present in the panniculus in percentages, expanding the septa (six of six) and extending into fat lobules in one of six cats. Tumours were associated with elevated numbers of neutrophils (five of six), lesser macrophages (six of six) and variable necrosis (six of six). Neoplastic cells expressed CD3+ (six of six), with clonal T-cell receptor rearrangement detected in five of six cats. CONCLUSIONS AND CLINICAL RELEVANCE: This is the first description of SPTCL in cats. Lesions can be confused with panniculitis, leading to delay in diagnosis and therapy. Awareness of this neoplastic disease is relevant to avoid misdiagnoses and to gain greater knowledge about the disease in cats.

Palliative Radiation Therapy for Treatment of Cutaneous T-cell Lymphoma in a Double Yellow-headed Amazon Parrot (Amazona oratrix).

A 17-year-old captive female double yellow-headed Amazon parrot (Amazona oratrix) was presented to the Kansas State University Zoological Medicine Service (Manhattan, KS, USA) for a 2-month history of a left sided facial swelling. On examination, a red, raised mass was noted on the left side of the face. A whole-body computed tomography scan of the bird was performed to assess the extent of the mass and evaluate the patient for obvious evidence of disseminated disease. No systemic involvement was detected, and the swelling was localized to the cutaneous and subcutaneous tissues overlying the left rhamphotheca. Two punch biopsies were collected, and histopathology was consistent with cutaneous lymphoma, with strong positive CD3 staining congruous with a T-cell origin. Because of a lack of evidence for disseminated disease, the authors elected to pursue localized radiation therapy, and a single fraction of 8 Gray was administered. The swelling had resolved by the time of the recheck examination 4 weeks post-radiation therapy, and the patient remained clinically normal 52 weeks after radiation therapy.

Clinical efficacy of recombinant canine interferon-gamma therapy in dogs with cutaneous epitheliotropic T-cell lymphoma.

BACKGROUND: The antitumour effects of interferon-gamma (IFN-γ) in humans with cutaneous epitheliotropic T-cell lymphoma (CETCL) have been described; however, the efficacy of IFN-γ in dogs has not been investigated. HYPOTHESIS/OBJECTIVES: The aim of this study was to evaluate the efficacy of recombinant canine IFN-γ (rCaIFN-γ) therapy in dogs with CETCL. ANIMALS: Twenty dogs with CETCL recruited from seven veterinary clinics were enrolled in the study. MATERIALS AND METHODS: Fifteen dogs were treated with rCaIFN-γ, and five control dogs were treated with prednisolone. We evaluated survival time, skin lesions (erythema, nodules, ulcers and bleeding), pruritus and general condition (sleep, appetite and body weight). In the rCaIFN-γ group, a questionnaire regarding the therapy was administered to owners after the dogs died. RESULTS: No significant differences existed in the median survival time between the rCaIFN-γ and control groups (log-rank test: p = 0.2761, Wilcoxon's rank sum test: p = 0.4444). However, there were significant differences in ulcer, bleeding, pruritus, sleep, appetite and body weight between the groups (Wilcoxon-Mann-Whitney U-test: p = 0.0023, p = 0.0058, p = 0.0005, p = 0.0191, p = 0.0306 and p = 0.0306, respectively). Two (40%) of five dogs were euthanised in the control group, compared with none in the rCaIFN-γ group. Fourteen questionnaires were collected, and owners reported that they were satisfied with the rCaIFN-γ treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Although the median survival time was not prolonged, rCaIFN-γ could be helpful in maintaining good quality of life for dogs with CETCL.

Disseminated T-cell lymphoma with non-epitheliotropic cutaneous involvement in a cat with erythematous patches and regenerative anemia.

A 14-y-old, castrated male, diabetic, domestic longhaired cat was presented for investigation of anemia. General examination revealed widespread cutaneous erythematous macules and patches. Hematology and bone marrow aspiration revealed severe regenerative anemia and marked erythroid hyperplasia, respectively. Low numbers of intermediate-to-large, atypical lymphocytes were observed in the blood smear and bone marrow aspirates. Various imaging modalities demonstrated a diffuse pulmonary bronchial pattern, multifocal mural thickening of the urinary bladder, splenomegaly, and mild tri-cavitary effusion. Skin biopsies and cytologic examination of the pleural effusion demonstrated round-cell neoplasia consistent with lymphoma. Autopsy confirmed disseminated T-cell lymphoma, mostly affecting the urinary bladder, stomach, lymph nodes, and interscapular subcutis and muscles. Angiocentrism and nerve infiltration were present. The cutaneous erythematous patches, characterized by perivascular neoplastic lymphocytic infiltrates and angiodestruction, were a manifestation of the disseminated lymphoma in this cat, similar to the lesions reported in humans affected by angioimmunoblastic T-cell lymphoma.

Prognostic clinical and histopathological features of canine cutaneous epitheliotropic T-cell lymphoma.

Canine cutaneous epitheliotropic T-cell lymphoma is a neoplasm with heterogeneous clinical and histopathological presentations. Survival times and responses to therapy are variable, and indicators to predict outcomes are lacking. Clinical and histopathological parameters from 176 archival cases from the University of Pennsylvania and University of Bern (2012-2018) were investigated for associations with clinical outcomes. Histopathological evaluation used digitized whole slide images and QuPath software. Cases included 107 female and 69 male dogs from 48 breeds, with a mean age of 10.4 years. Most common clinical signs were erythema (n = 131), crusting (n = 108), and scaling (n = 102). Affected sites were haired skin (n = 159), lip (n = 74), nasal planum (n = 49), and paw pads (n = 48). The median survival time (MST) was 95 days (1-850). Dogs had 4.26-fold and 2.82-fold longer MST when treated with chemotherapy and prednisone, respectively, than when receiving supportive care. Haired skin involvement (hazard ratio [HR]: 2.039, 95% confidence interval [CI]: 1.180-3.523), erosions/ulcers (HR: 1.871, 95% CI: 1.373-2.548), nodules (HR: 1.496, 95% CI: 1.056-2.118), and crusting (HR: 1.454, 95% CI: 1.061-1.994) were clinical parameters predicting poor outcomes, whereas complete posttherapeutic clinical remission (HR: 0.469, 95% CI: 0.324-0.680) and a stable disease (HR: 0.323, 95% CI: 0.229-0.456) were associated with longer survival. Histopathological features associated with the increased risk of death were extensive infiltration of the panniculus (HR: 2.865, 95% CI: 1.565-4.809), mitotic count ≥7/high-power field (HR: 3.027, 95% CI: 2.065-4.439), cell diameter ≥10.0 µm (HR: 2.078, 95% CI: 1.281-3.372), and nuclear diameter ≥8.3 µm (HR: 3.787, 95% CI: 1.647-8.707).

Hamster polyomavirus-associated T-cell lymphomas in Syrian hamsters (Mesocricetus auratus).

Hamster polyomavirus (HaPyV) infection has been associated with lymphomas in Syrian hamsters. In the present study, 14 cases of lymphoma in pet Syrian hamsters were pathologically examined and the involvement of HaPyV was investigated. Among 14 cases, 11 were abdominal and 3 were cutaneous lymphomas. The average ages of hamsters with abdominal lymphoma and cutaneous lymphoma were 7 months (range: 4-12 months) and 14 months (range: 6-23 months), respectively. Histologically, abdominal lymphomas were characterized by the diffuse growth of tumor cells with intermediate or large nuclei, low mitotic rates, the presence of tingible body macrophages, and the T-cell immunophenotype. Furthermore, 4/11 abdominal lymphomas were immunopositive for T-cell intracellular antigen-1, suggesting cytotoxic T-cell lymphomas. Cutaneous lymphomas were diagnosed as nonepitheliotropic T-cell lymphoma. Polymerase chain reaction (PCR) detected HaPyV DNA in 12/14 samples, and a sequence analysis of PCR amplicons confirmed >99% nucleotide identity to the published HaPyV sequences. In situ hybridization (ISH) for HaPyV DNA resulted in diffuse nuclear signals within tumor cells in 10/14 cases. Consistent with previous findings, all HaPyV-associated lymphomas were observed in the abdominal cavity of young hamsters. Polymerase chain reaction and ISH were useful for identifying the involvement of HaPyV in lymphomas, and ISH results indicated the presence of episomal HaPyV in neoplastic lymphocytes. The present study suggests that HaPyV infection is highly involved in abdominal lymphomas in young pet Syrian hamsters in Japan and provides diagnostic information on HaPyV-associated lymphoma.

Evaluation of clonality from multiple anatomic sites in canine epitheliotropic T cell lymphoma.

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 cutané épithéliotrope canin (eCTCL) représente une maladie homologue au mycosis fongoïde (MF) humain. Dans le MF humain, les cellules néoplasiques sont phénotypiquement compatibles avec les cellules T mémoire effectrices résidentes, une population qui reste pendant une période prolongée dans les tissus sans circuler. Les chiens atteints d'eCTCL présentent souvent des lésions à plusieurs endroits, ce qui soulève la question de savoir si le néoplasme appartient ou non à la même sous-population de lymphocytes T. Objectifs - Caractériser les réarrangements du gène du récepteur antigénique des lymphocytes de la peau et du sang des chiens atteints d'eCTCL afin de déterminer si les clones néoplasiques sont identiques. Animaux - Quatorze chiens avec eCTCL. Matériels et méthodes - Examen histologique et immunohistochimique, et PCR pour le réarrangement des récepteurs antigéniques (PARR) pour le récepteur gamma des lymphocytes T (TRG) effectués sur plusieurs échantillons de biopsie cutanée et de sang. Résultats - Toutes les biopsies cutanées contenaient des amas de lymphocytes néoplasiques positifs à la différenciation (CD)3. Chez les chiens individuels, toutes les biopsies cutanées ont révélé des profils de clonalité TRG identiques, suggérant que le même clone néoplasique était présent dans tous les sites. Dans le sang, un clone correspondant a été trouvé chez six des 14 chiens, un clone unique a été observé chez neuf des 14 chiens et aucun clone n'a été détecté chez deux des 14 chiens. Conclusions - Ces résultats montrent que les lésions eCTCL canines à plusieurs endroits abritent le même clone néoplasique, les lymphocytes néoplasiques ne restent pas fixés à la peau et peuvent plutôt circuler par le sang, différents clones peuvent être identifiés dans la peau par rapport au sang, et les cellules néoplasiques circulantes peuvent être détecté sans lymphocytose.

Introducción- se cree que el linfoma epiteliotrópico cutáneo de células T canino (eCTCL) representa una enfermedad homóloga a la micosis fungoide (MF) humana. En la MF humana, las células neoplásicas son fenotípicamente consistentes con las células T de memoria efectoras residentes, una población que permanece durante un período prolongado dentro del tejido sin circular. Los perros con eCTCL a menudo presentan lesiones en múltiples ubicaciones, lo que plantea la cuestión de si la neoplasia es de la misma subpoblación de células T o no. Objetivos- caracterizar los reordenamientos del gen del receptor de antígeno de los linfocitos de la piel y la sangre de perros con eCTCL para determinar si los clones neoplásicos son idénticos. Animales- catorce perros con eCTCL. Materiales y métodos - Examen histológico e inmunohistoquímico, y PCR para el reordenamiento del receptor de antígeno (PARR) para el receptor de células T gamma (TRG) realizado en múltiples muestras de biopsia cutánea y sangre. Resultados- todas las biopsias de piel contenían linfocitos neoplásicos positivos para grupos de diferenciación (CD)3. Dentro de perros individuales, todas las biopsias de piel revelaron perfiles de clonalidad de TRG idénticos, lo que sugiere que el mismo clon neoplásico estaba presente en todos los sitios. En la sangre, se encontró un clon compatible en seis de 14 perros, se observó un clon único en nueve de 14 perros y no se detectó ningún clon en dos de 14 perros. Conclusiones- estos hallazgos muestran que las lesiones de eCTCL canino en múltiples ubicaciones albergan el mismo clon neoplásico, los linfocitos neoplásicos no permanecen fijados a la piel y, en cambio, pueden circular a través de la sangre, se pueden identificar diferentes clones en la piel versus la sangre y las células neoplásicas circulantes pueden ser identificadas sin presencia de linfocitosis.

Contexto - Acredita-se que o linfoma epiteliotrópico cutâneo de células T canino (eCTCL) representa uma doença análoga à micose fungoide (MF) humana. Na MF humana, as células neoplásicas são fenotipicamente consistentes com células T efetoras de memória residentes, uma população que permanece por um período extenso no tecido sem entrar na circulação. Os cães com eCTCL frequentemente apresentam lesões em múltiplos locais, levantando a questão de se a neoplasia é da mesma subpopulação de células T ou não. Objetivos - Caracterizar os rearranjos dos genes receptores de antígenos dos linfócitos da pele e do sangue de cães com eCTCL para determinar se os clones neoplásicos são idênticos. Animais - Quatorze cães com eCTCL. Materiais e métodos - Exame histológico e imunohistoquímico, e PCR para rearranjo de receptor de antígeno (PARR) para o receptor Gama de células T (TRG) realizado em múltiplas amostras de biópsia cutânea e sangue. Resultados - Todas as biópsias cutâneas continham clusters de diferenciação linfócitos T (CD)3- positivos. Entre os indivíduos, todas as biópsias cutâneas revelaram perfis de clonalidade de TGR idênticos em seis dos 14 cães, sugerindo que a mesma célula neoplásica estava presente em todos os locais. No sangue, um clone correspondente foi encontrado em seis dos 14 cães, um clone único foi observado em nove dos 14 cães e nenhum clone foi detectado em dois dos 14 cães. Conclusões - Estes achados demonstraram que as lesões de eCTCL em múltiplos locais possuem o mesmo clone neoplásico, linfócitos neoplásicos não permanecem fixos na pele e podem circular por via sistêmica , diversos tipos de clones podem ser identificados na pele versus sangue, e as células neoplásicas circulantes podem ser detectadas sem linfocitose.

Cutaneous epitheliotropic T-cell lymphoma in a donkey - a case report.

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.

Outcomes and prognostic factors in canine epitheliotropic and nonepitheliotropic cutaneous T-cell lymphomas.

Canine cutaneous lymphoma is an uncommon lymphoma in dogs. Most canine cutaneous lymphoma cases have a T-cell origin. Canine cutaneous T-cell lymphoma (CTCL) is classified into epitheliotropic and nonepitheliotropic cutaneous lymphomas, and each type of lymphoma is subclassified into several histological subtypes. Limited information is available regarding the prognostic significance of clinical variables and histopathological subtypes in dogs with CTCL. This retrospective study aimed to investigate the influence of clinical variables and histopathological subtypes on the prognosis of dogs with CTCL. Forty-six dogs diagnosed with CTCL by histopathological examination were included. Histopathological specimens were reexamined and classified into CTCL subtypes. The influence of the type of skin lesion, histopathological subtype, haematological examination results and treatment response on the overall survival time (OS) was examined. Thirty-one dogs were diagnosed with epitheliotropic CTCL (mycosis fungoides in 28 dogs; pagetoid reticulosis in 3 dogs) and 15 dogs were diagnosed with nonepitheliotropic CTCL (anaplastic large T-cell lymphoma in 6 dogs; peripheral T-cell lymphoma, not otherwise specified, in 9 dogs). The OS of dogs diagnosed with epitheliotropic CTCL (141 days) was significantly shorter than that of dogs diagnosed with nonepitheliotropic CTCL (374 days). As clinical variables, the presence of neoplastic lymphocytes in peripheral blood, thrombocytopenia and initial chemotherapeutic response was related to prognosis. Our results demonstrated that histopathological subtype and several clinical variables were found to influence the prognosis of dogs with CTCL.

Treatment of indolent cutaneous T-cell lymphoma with hypofractionated radiation therapy in three cats.

BACKGROUND: Feline indolent cutaneous T-cell lymphoma (ICL) is an uncommon neoplastic disease. There is currently no consensus on treatment recommendations for ICL. OBJECTIVE: To report the clinical outcome of three cats with ICL treated with hypofractionated electron-beam radiotherapy (RT). ANIMALS: Three privately owned cats with ICL. MATERIALS AND METHODS: Medical records and client surveys were reviewed. A diagnosis of probable ICL was based on history, clinical presentation and histopathological findings, and confirmed using CD3 immunohistochemical analysis and PCR for antigen receptor gene rearrangement (PARR). All cats were treated with hypofractionated RT (four fractions of 8 Gy). RESULTS: All cats presented with skin lesions characterised by erythema and alopecia that were refractory to previous treatment with systemic glucocorticoids. Before hypofractionated RT treatment, lesions were histologically described as having diffuse infiltration of the dermis with CD3+ T cells. Molecular clonality analysis revealed clonal T-cell receptor gamma gene rearrangement. After RT, two cats showed histological improvement defined by decreased infiltration of lymphocytes, with cellular infiltrate present only in the deeper dermis; one cat had near complete histological resolution of lesions with only minimal residual lymphocytes. One cat was determined to have a complete clinical response while the other showed partial responses. No acute adverse effects of radiation were observed; chronic effects included leukotrichia, partial alopecia and mild fibrosis. All clients reported improvement in quality of life for their cats. CONCLUSIONS AND CLINICAL IMPORTANCE: Clinical and histological improvement in these cats suggests that hypofractionated RT can be a useful treatment modality for cats with ICL.

Treatment of canine cutaneous epitheliotropic T-cell lymphoma with oclacitinib: a case report.

Canine cutaneous epitheliotropic T-cell lymphoma (CETL) is associated with a poor prognosis and without consistently beneficial treatment options. This case report describes a 9-year-old Staffordshire bull terrier with CETL treated with oclacitinib (0.7 mg/kg twice daily), resulting in partial remission that was maintained for three months. Further studies are warranted.

Le lymphome cutané T épithéliotrope canin (CETL) est associé à un pronostic faible et sans option thérapeutique bénéfique constante. Ce cas clinique décrit un Staffordshire bull-terrier de 9 ans avec CETL traité avec oclacitinib (0,7 mg/kg deux fois par jour), résultant en une rémission partielle qui s'est maintenue trois mois. Des études supplémentaires sont nécessaires.

El linfoma epiteliotrópico cutáneo de células T canino (CETL) se asocia con un mal pronóstico y sin opciones de tratamiento consistentemente beneficiosas. Este informe de caso describe un Staffordshire bull terrier de 9 años con CETL tratado con oclacitinib (0,7 mg/kg dos veces al día), lo que resultó en una remisión parcial que se mantuvo durante tres meses. Se necesitan más estudios.

O linfoma epiteliotrópico canino de células T (CETL) está associado a um mau prognóstico e sem opções de tratamento consistentemente benéficas. Este relato de caso descreve um Staffordshire bull terrier de 9 anos de idade com CETL tratado com oclacitinib (0,7 mg/kg duas vezes ao dia), resultando em remissão parcial que foi mantida por três meses. Mais estudos são necessários.

Transcriptional Differences between Canine Cutaneous Epitheliotropic Lymphoma and Immune-Mediated Dermatoses.

Canine cutaneous epitheliotropic T-cell lymphoma (CETL) and immune-mediated T-cell predominant dermatoses (IMD) share several clinical and histopathological features, but differ substantially in prognosis. The discrimination of ambiguous cases may be challenging, as diagnostic tests are limited and may prove equivocal. This study aimed to investigate transcriptional differences between CETL and IMD, as a basis for further research on discriminating diagnostic biomarkers. We performed 100bp single-end sequencing on RNA extracted from formalin-fixed and paraffin-embedded skin biopsies from dogs with CETL and IMD, respectively. DESeq2 was used for principal component analysis (PCA) and differential gene expression analysis. Genes with significantly different expression were analyzed for enriched pathways using two different tools. The expression of selected genes and their proteins was validated by RT-qPCR and immunohistochemistry. PCA demonstrated the distinct gene expression profiles of CETL and IMD. In total, 503 genes were upregulated, while 4986 were downregulated in CETL compared to IMD. RT-qPCR confirmed the sequencing results for 5/6 selected genes tested, while the protein expression detected by immunohistochemistry was not entirely consistent. Our study revealed transcriptional differences between canine CETL and IMD, with similarities to human cutaneous lymphoma. Differentially expressed genes are potential discriminatory markers, but require further validation on larger sample collections.

A case report of total skin photon radiation therapy for cutaneous epitheliotropic lymphoma in a dog.

BACKGROUND: Total skin electron beam radiation therapy (TSEBT) is an effective treatment for primary diffuse cutaneous lymphomas in humans. While several techniques exist, they all require significant commitment of staff time and resources. In veterinary medicine, canine-specific techniques and strategies have been adapted and delivered but deemed not "realistically" clinically implementable given the time commitment of over 2.5 h plus per fraction or have been relegated to palliative intent. Leveraging these technologies of helical tomotherapy and 3D printing, we developed and clinically implemented a radiotherapeutic treatment strategy for the management of medically refractory diffuse cutaneous lymphoma in the dog. CASE PRESENTATION: A 13.5-year-old female spayed Bichon Frise presented to the Oncology service at Texas A&M University, College of Veterinary Medicine due to the progression of diffuse cutaneous epitheliotropic lymphoma (CEL) that had failed medical management. Twenty-seven gray were delivered to the patient with a treatment time requirement under 40 min including real time monitoring of anesthesia during setup and treatment. A partial response was noticeable after four fractions and the tumor completely regressed progressively over the entire treated area by the end of therapy. A grade 1 lethargy, fatigue, weight loss, and oral mucositis and grade 2 alopecia, nail/claw changes, pruritus, scaling, anorexia, and diarrhea were noted during treatment. Additionally, a grade 3 thrombocytopenia developed after fraction eight requiring a treatment interruption of 6 weeks and prescription modification prior to treatment continuation and completion. From the beginning of total skin photon radiation therapy (TSPT) treatment until the time of the patient was euthanized unrelated to cutaneous epitheliotropic lymphoma (123 days), only one new lesion on the head was identified and confirmed by histopathology within the treated fields. CONCLUSIONS: The proposed technique is an acceptable alternative to TSEBT that is actually clinically implementable within a palliative or definitive setting and clinical constraints, however further testing and refinement is needed to reduce hematological complications and to confirm and expand on preliminary findings.

Cutaneous epitheliotropic lymphoma in a baboon (Papio spp.): A case report and a brief literature review.

Cutaneous epitheliotropic lymphoma (CEL) has not been reported in non-human primates. We report the first case of CEL in a 9-year-old baboon. The phenotype of the neoplastic cells in this baboon is similar to CEL in humans (CD3+, CD4+, CD8-) and different from dogs (CD3+, CD4-, CD8+).

Canine non-epitheliotropic CD4-positive cutaneous T-cell lymphoma: a case report.

A 5-year-old, spayed female French Bulldog presented with multiple papules on the skin of the scapular area. Histopathological examination of punch biopsy samples revealed dense infiltration of small lymphoid cells in the superficial dermis and in areas surrounding hair follicles. Immunohistochemical analysis indicated that these cells were positive for CD3, CD4, and TCRαß, but negative for CD1c, CD8α, CD8ß, CD11c, CD20, CD45RA, CD90, MHC-II, and TCRγδ. In addition, CD45 was highly expressed, and the proliferation fraction was very low. Molecular clonality of T-cell receptor G chains yielded a clonal result. The skin lesions were surgically excised because they had progressed to the lateral front leg. Postoperative clinical course was favorable, and recurrence was not observed until the dog died in a traffic accident, approximately 1 year later.

Prevalence of CD20+ cutaneous epitheliotropic T-cell lymphoma in dogs: a retrospective analysis of 24 cases (2011-2018) in the USA.

BACKGROUND: Limited information is known about the baseline frequency of canine CD20 positive (+ ) cutaneous epitheliotropic T-cell lymphoma. A single canine case report has been published. OBJECTIVES: To characterize the baseline frequency of CD20+ staining in cases of canine cutaneous epitheliotropic T-cell lymphoma; to assess its values as a prognostic indicator. ANIMALS: Skin biopsies from 24 client-owned animals diagnosed with cutaneous epitheliotropic lymphoma were assessed. METHODS AND MATERIALS: A retrospective review of medical records from 2011 to 2018. Clinical histories and previous histological and immunohistochemical slides were collected from 24 dogs and additional immunohistochemical staining was performed as needed to assess cases of cutaneous epitheliotropic T-cell lymphoma for CD3, CD20, CD79a and PAX5 staining characteristics. Staining characteristics were assessed for their statistical relationship to median survival time. RESULTS: Overall median survival time was 189 days following the onset of clinical signs and 99 days following definitive diagnosis; 54% of cases had CD20+ staining. There was no statistically significant correlation between staining characteristics and median survival time from onset of signs (P = 0.54) or from diagnosis (P = 0.61). CONCLUSIONS AND CLINICAL SIGNIFICANCE: Canine cutaneous epitheliotropic lymphoma has a higher instance of CD20 positivity than documented previously. This indicates that CD20 staining may be unsuitable to differentiate T-cell and B-cell cutaneous epitheliotropic lymphoma. This also may have therapeutic implications with the advent of canine CD20 monoclonal antibody therapies.

Canine and Feline Cutaneous Epitheliotropic Lymphoma and Cutaneous Lymphocytosis.

Cutaneous lymphomas are divided into categories based on histologic evaluation of the skin and location of neoplastic lymphocytes. Epitheliotropic cutaneous lymphoma, also known as cutaneous T-cell lymphoma, is diagnosed when neoplastic lymphocytes show tropism for the epidermis and these cells infiltrate the epidermis and adnexae. In diagnosis of nonepitheliotropic cutaneous lymphoma, neoplastic lymphocytes are found mostly in the dermis and/or subcutis. Neoplastic cells are of either B-cell or T-cell origin. This article focuses on epitheliotropic cutaneous lymphomas and cutaneous lymphocytosis, which is considered a form of indolent lymphoma, in dogs and cats.

T cell-lymphoma in the eyelid of a 9-year-old English Setter.

BACKGROUND: Eyelid tumours are frequently found in dogs, most of these being benign. In case of an ulcerating eyelid tumour, malignancy must be considered. We report a unique case of a low-grade peripheral T-cell lymphoma in the eyelid of a 9-year-old English Setter. CASE PRESENTATION: A 9-year-old Setter presented with a 6-month history of an eyelid ulcer. A malignant eyelid neoplasm was suspected, and the lesion was surgically excised. No other treatment was applied, and 19 months after excision the dog was still well. Histopathology revealed a diffuse lymphocytic infiltrate in the eyelid skin. Ulceration of the epithelium was seen, and the underlying tumour was composed of round and poorly demarcated pleomorphic tumour cells. The cytoplasm was pale and the nuclei heterogeneous. Numerous mitoses were present. The tumour cells stained strongly for CD3. The final diagnosis was a peripheral T-cell lymphoma not otherwise specified (NOS). CONCLUSIONS: This is the first described case of a solitary T-cell lymphoma NOS in the haired eyelid skin in a dog. Lymphoma should be considered in case of a persistent eyelid ulcer and a biopsy should be performed. T-cell lymphoma is generally an aggressive disease; however, indolent cases are well known, and as this case shows, complete excision of a solitary T-cell lymphoma can be curable. Canine cutaneous epitheliotropic T-cell lymphoma is an important differential diagnosis, which must be recognized as the prognosis is very poor and systemic treatment is mandatory. The sub-classification of canine lymphoma is not complete, and further studies are needed to identify lymphoma subgroups and provide treatment guidelines.

Clinical response to isotretinoin and interferon-α of two dogs with cutaneous epitheliotropic T-cell lymphoma: a case report.

BACKGROUND: There is no specific therapy for cutaneous epitheliotropic T-cell lymphoma (CETL). The administration of retinoids in conjunction with interferon-α (IFN-α) in CETL has not been reported in dogs. CASE PRESENTATION: Two dogs (Shih tzu and Miniature pinscher) presented with multiple nodular skin lesions. Histopathological examination revealed diffuse infiltrations of lymphocytes in the epidermis and dermis, with a CD3-positive immunophenotypic profile. Based on the clinical and histopathological examination, CETL was diagnosed. Both dogs were treated with isotretinoin in combination with IFN-α and showed clinical improvement with complete or partial remission. The disease in these dogs was well-controlled for more than 264 days of overall median survival time without any additional clinical signs after initiation of the treatment. In both the cases, the dogs were followed up for 27 months, and 10 months without any evidence of recurrence or metastasis, respectively. CONCLUSIONS: We describe the clinical efficacy of isotretinoin combined with IFN-α in 2 dogs with CETL. Long-term management with isotretinoin combined with IFN-α was effective in treating CETL in these cases.

Phenotypic analysis of mice xenografted with canine epitheliotropic cutaneous T-cell lymphoma cells.

BACKGROUND: In canine epitheliotropic cutaneous T-cell lymphoma (ECTCL), neoplastic cells cause skin lesions and potentially metastasize to lymph nodes, blood and other organs. Murine models are potentially valuable for elucidating the molecular mechanisms responsible for regulation of ECTCL cell migration. HYPOTHESIS/OBJECTIVES: To describe a phenotype of mice xenografted with canine ECTCL cells (EO-1 cells). ANIMALS: Four NOD.CB17-Prkdcscid /J (NOD SCID) mice were used. METHODS AND MATERIALS: EO-1 cells were subcutaneously xenografted into NOD SCID mice. After four weeks, the development of tumour lesions in skin and other organs was investigated. RESULTS: Mice developed skin lesions with metastasis to the lymph nodes, spleen, lung, blood and liver. CONCLUSIONS AND CLINICAL IMPORTANCE: Mice xenografted with EO-1 cells may be useful for studying the pathogenesis of canine ECTCL.