Epitheliotropic Lymphoma Research Articles

Efficacy of verdinexor for the treatment of naïve canine epitheliotropic cutaneous T-cell lymphoma: An open-label pilot study.

Verdinexor (Laverdia-CA1; Dechra Veterinary Products), a selective inhibitor of nuclear export, has been utilised for treatment of non-Hodgkin T-cell lymphoma in dogs. However, the efficacy of verdinexor has not been evaluated for cutaneous epitheliotropic T-cell lymphoma (CETL). To evaluate the efficacy of verdinexor for the treatment of CETL. Eight client-owned animals with CETL. Patients received between 1.28 and 1.45 mg/kg verdinexor per os twice weekly with a minimum of 72 h between doses until disease progression or voluntary withdrawal. Adjunctive therapy with lokivetmab or prednisone was permitted after Day (D)14. Assessment of clinical lesions (canine Response Evaluation Criteria in Solid Tumors [cRECIST v1.0] and novel Canine Epitheliotropic Lymphoma Extent and Severity Index [CELESI]), pruritus (Visual Analog Scale) and treatment efficacy (owner global assessment of treatment efficacy [OGATE]) were evaluated every 14 days for 3 months, then monthly thereafter (mean 70 ± 43.4 days). Seventy-five percent of patients achieved complete response, partial response or stable disease. The mean time to disease progression was 56 ± 41 days. There was a significant reduction (p = 0.026) in total CELESI score when the lowest score for each dog was compared to their score at D0. Verdinexor did not significantly reduce pruritus at any time point (p = 0.45), including when given as a monotherapy or concurrently with lokivetmab ± glucocorticoids. On D28, 75% of owners rated response to treatment as 'fair' to 'excellent'. The most common adverse effects included weight loss, inappetence, vomiting and lethargy. Verdinexor could be considered a safe, palliative treatment for canine CETL.

Spontaneous Lesions of Endangered Geriatric Julia Creek Dunnarts (Sminthopsis douglasi, Archer 1979) with Emphasis in Reproductive Pathology.

Julia Creek dunnarts are an endangered species of carnivorous marsupials and the focus of multiple conservation strategies involving significant resources such as captive breeding programs. Despite the relevance for conservation, no study to date has focused on evaluating geriatric diseases in dunnarts. This study describes the pathology findings in a group of one wild and thirty-five captive-born, mostly geriatric Julia Creek dunnarts that failed to produce offspring over multiple breeding periods. A total of 20 females and 16 males were submitted for a postmortem examination, with ages ranging from 9 to 42 and 12 to 42 months for females and males, respectively. Of these, 10 had unremarkable findings. The most common condition in females was cystic glandular hyperplasia (n = 8), typical of hormonal dysregulation profiles in senescence, particularly hyperestrogenism. Rarely, cutaneous disease represented by unidentified dermal round cell infiltrates was observed in females (n = 2). Primary reproductive hormonal dysregulation was also suspected in males diagnosed with testicular degeneration, aspermatogenesis and/or atrophy (n = 3). Cutaneous round cell infiltrates, possibly compatible with epitheliotropic lymphomas, were seen in males (n = 3), and 2/3 affected males also had concurrent testicular degeneration or atrophy, indicating male sex could be a predictor for lymphoid neoplasia in aged dunnarts, especially in individuals with concurrent testosterone-luteinizing hormone dysregulation as it occurs in gonadectomized animals. The role of an underlying viral etiology is also explored. This study is the first to describe major spontaneous diseases in endangered aged Julia Creek dunnarts, providing an important understanding of senescence and geriatric diseases within a conservation context.

Hamartoma affecting ampullary electroreceptors and epitheliotropic lymphoma in a captive electric eel Electrophorus varii

Few reports are available describing lesions in captive electric eels Electrophorus spp. This report describes 2 types of cutaneous proliferative lesions (i.e. hamartoma and neoplasm) in a captive electric eel. Ampullary electroreceptor hamartomas appeared grossly as 2 discrete, smooth, pink, spherical, cutaneous masses measuring 6 and 18 mm in diameter. Histologically, hamartomas were composed of predominately spindle cells that were separated into lobules by a peripheral rim of polygonal cells. Spindle cells were arranged in vague streams and occasionally whorls within a myxomatous matrix. Polygonal cells arranged in variably sized trabeculae and cords within a pre-existing fibrovascular stroma surrounded the streams of spindle cells. Admixed with the polygonal cell population were multiple mucous glands and alarm cells, similar to those seen in normal regions of epidermis. Histochemical stains confirmed similar components in the normal ampullary electroreceptor as in the hamartomas. Lymphoma was also present, appearing grossly as patchy pitting, erythematous, and thickened areas of the skin affecting the entire animal. Lymphoma was diffusely infiltrating and expanding the epidermis, oral mucosa, and branchial mucosa up to 1.5 mm in thickness. It was composed of an unencapsulated, well-demarcated, moderately cellular neoplasm composed of lymphocytes arranged in small dense sheets and clusters that separated and effaced epidermal cells. This is the first report of lymphoma in an electric eel, and the first report of ampullary electroreceptor hamartoma in any animal species.

Cathepsin W, T-cell receptor-associated transmembrane adapter 1, lymphotactin and killer cell lectin like receptor K1 are sensitive and specific RNA biomarkers of canine epitheliotropic lymphoma.

Cutaneous T-cell lymphoma (CTCL) is an uncommon type of lymphoma involving malignant skin-resident or skin-homing T cells. Canine epitheliotropic lymphoma (EL) is the most common form of CTCL in dogs, and it also spontaneously arises from T lymphocytes in the mucosa and skin. Clinically, it can be difficult to distinguish early-stage CTCLs apart from other forms of benign interface dermatitis (ID) in both dogs and people. Our objective was to identify novel biomarkers that can distinguish EL from other forms of ID, and perform comparative transcriptomics of human CTCL and canine EL. Here, we present a retrospective gene expression study that employed archival tissue from biorepositories. We analyzed a discovery cohort of 6 canines and a validation cohort of 8 canines with EL which occurred spontaneously in client-owned companion dogs. We performed comparative targeted transcriptomics studies using NanoString to assess 160 genes from lesional skin biopsies from the discovery cohort and 800 genes from the validation cohort to identify any significant differences that may reflect oncogenesis and immunopathogenesis. We further sought to determine if gene expression in EL and CTCL are conserved across humans and canines by comparing our data to previously published human datasets. Similar chemokine profiles were observed in dog EL and human CTCL, and analyses were performed to validate potential biomarkers and drivers of disease. In dogs, we found enrichment of T cell gene signatures, with upregulation of IFNG, TNF, PRF1, IL15, CD244, CXCL10, and CCL5 in EL in dogs compared to healthy controls. Importantly, CTSW, TRAT1 and KLRK1 distinguished EL from all other forms of interface dermatitis we studied, providing much-needed biomarkers for the veterinary field. XCL1/XCL2 were also highly specific of EL in our validation cohort. Future studies exploring the oncogenesis of spontaneous lymphomas in companion animals will expand our understanding of these disorders. Biomarkers may be useful for predicting disease prognosis and treatment responses. We plan to use our data to inform future development of targeted therapies, as well as for repurposing drugs for both veterinary and human medicine.

Combining ultrasound radiomics, complete blood count, and serum biochemical biomarkers for diagnosing intestinal disorders in cats using machine learning.

This retrospective analytical observational cohort study aimed to model and predict the classification of feline intestinal diseases from segmentations of a transverse section from small intestine ultrasound (US) image, complete blood count (CBC), and serum biochemical profile data using a variety of machine-learning approaches. In 149 cats from three institutions, images were obtained from cats with biopsy-confirmed small cell epitheliotropic lymphoma (lymphoma), inflammatory bowel disease (IBD), no pathology ("healthy"), and other conditions (warrant a biopsy for further diagnosis). CBC, blood serum chemistry, small intestinal ultrasound, and small intestinal biopsy were obtained within a 2-week interval. CBC and serum biomarkers and radiomic features were combined for modeling. Four classification schemes were investigated: (1) normal versus abnormal; (2) warranting or not warranting a biopsy; (3) lymphoma, IBD, healthy, or other conditions; and (4) lymphoma, IBD, or other conditions. Two feature selection methods were used to identify the top 3, 5, 10, and 20 features, and six machine learning models were trained. The average (95% CI) performance of models for all combinations of features, numbers of features, and types of classifiers was 0.886 (0.871-0.912) for Model 1 (normal vs. abnormal), 0.751 (0.735-0.818) for Model 2 (biopsy vs. no biopsy), 0.504 (0.450-0.556) for Model 3 (lymphoma, IBD, healthy, or other), and 0.531 (0.426-0.589), for Model 4 (lymphoma, IBD, or other). Our findings suggest model accuracies above 0.85 can be achieved in Model 1 and 2, and that including CBC and biochemistry data with US radiomics data did not significantly improve accuracy in our models.

Clinical and Histopathological Features of an Italian Monocentric Series of Primary Small Bowel T-Cell Lymphomas.

The gastrointestinal (GI) tract is the most common extranodal site of occurrence of non-Hodgkin lymphomas. Most GI lymphomas are of B-cell lineage, while T-cell lymphomas are less frequent. The aim of our retrospective study was to depict the clinical-pathological profile of a series of patients affected by intestinal T-cell lymphomas (ITCL) and possibly define hallmarks of these neoplasms. A total of 28 patients were included: 17 enteropathy-associated T-cell lymphomas (EATL), 5 monomorphic epitheliotropic T-cell lymphomas (MEITL), 3 indolent T-cell lymphoproliferative disorders of the gastrointestinal tract (ITCLDGT), and 3 intestinal T-cell lymphomas not otherwise specified (ITCL-NOS). Celiac disease (CD) was diagnosed in around 70% of cases. Diagnosis of EATL showed a significant correlation with CD30 expression, whereas MEITL with angiotropism and CD56 positivity. ITCLDGT cases showed plasma cells infiltration. Peripheral lymphocytosis, the absence of a previous diagnosis of CD, an advanced Lugano clinical stage, and the histological subtype ITCL-NOS were significantly associated with worse survival at multivariate analysis. Our findings about the epidemiological, clinical, and histopathological features of ITCL were in line with the current knowledge. Reliable prognostic tools for these neoplasms are still lacking but according to our results lymphocytosis, diagnosis of CD, Lugano clinical stage, and histological subtype should be considered for patient stratification.

Canine Oral Lymphoma: A Review and 3 Case Studies.

Canine oral lymphoma is an infrequently diagnosed malignancy in dogs and reports in the literature are lacking. Most cases are due to epitheliotropic lymphoma, in which lesions are often multifocal and involve the skin as well as the oral cavity. Epitheliotropic lymphoma is an uncommon form of lymphoma that is characterized by neoplastic T-lymphocyte tropism for epithelial tissues. However, not all cases of oral lymphoma are due to epitheliotropic lymphoma, and B-cell disease is also possible. This article describes very different cases of oral lymphoma in dogs including the history at presentation, examination and radiographic findings, treatments, and outcomes. The cases highlight the variability in signalment, examination findings, and clinical courses that are found with oral lymphoma.

Epitheliotropic cutaneous lymphoma in a Javan silvered leaf monkey (Trachypithecus auratus auratus) and attempted treatment with masitinib

AbstractA 14‐month‐old, female Javan silvered leaf monkey (Trachypithecus auratus auratus) was presented for inguinal circular, erythematous, crusty dermatitis. The animal was bright and alert, and appetite was good. Lesions progressed to the whole abdomen and became ulcerative. Skin biopsies revealed a cutaneous lymphoma and no metastases were detected on computed tomography scan. Anti‐tumoral treatment was attempted with masitinib (50 mg orally every 48 hours), a tyrosine kinase inhibitor. In the absence of improvement of the lesions, as treatment was well tolerated, masitinib dose was increased to 50 mg orally once a day. Effect on the lesions was minimal, clinical condition worsened and the animal died 9 months after initial presentation. Postmortem examination and histopathology confirmed multicentric epitheliotropic CD3+ cutaneous lymphoma. To the authors’ knowledge, this is the first report of cutaneous lymphoma in a langur, and the first attempt of treatment with masitinib in a non‐human primate species. Despite poor response, masitinib treatment appeared safe.

Cutaneous epitheliotropic T-cell lymphoma in ferrets (Mustela putorius furo): 3 cases (2014–2021)

Background : Tumours are commonly encountered in ferrets and lymphoma is the third most common neoplasm in this species. Cutaneous epitheliotropic lymphoma has rarely been described in ferrets. Materials and methods : Inclusion criteria for ferrets in this study were cutaneous lymphoma diagnosed by histopathologic examination. Data collection from affected ferrets presented at the clinic between January 2014 and March 2021 included signalment, medical history, clinical signs, histopathology and immunohistochemistry results, treatments and clinical outcome when available. Results : Three ferrets met the inclusion criteria. They presented with erythematous and crusted lesions on the foot in ferrets 1 and 2, and multiple erythematous papules over the lumbar region in ferret 3. Epitheliotropic T-cell lymphoma was identified by immunohistochemistry in all cases. Chemotherapy was declined in ferret 1 and a medical treatment based on prednisolone, a skin ointment, and spirulina was initiated. Ferret 2 received lomustine and prednisolone. Ferret 3 received chlorambucil, an isotretinoin skin ointment and prednisolone. In all cases, dermatologic symptoms significantly improved or disappeared after 1 to 3 months. Ferret 1 was lost to follow up after 2 months. Ferret 2 discontinued chemotherapy after 7 months and was humanely euthanised 3 months later after recurrence and worsening of its general condition. Ferret 3 died 3 months after diagnosis from an unknown cause. Conclusion and clinical relevance : This case series describes three cases of cutaneous epitheliotropic T-cell lymphoma, with three different treatment plans and illustrates the importance of considering cutaneous epitheliotropic lymphoma as a differential diagnosis in ferrets with dermatologic symptoms.

Intra- and interobserver assessments of intestinal wall thickness and segmentations from transverse sections of feline abdominal ultrasound images.

Measurements of intestinal wall thicknesses from ultrasound imaging (US) are routinely used to support diagnoses of intestinal disorders in cats, however published studies describing observer agreement are currently lacking. The aim of this retrospective, observer agreement study was to quantify inter- and intraobserver repeatability and agreement in the measurement of intestinal wall layer thicknesses and the segmentation of transverse sections of small intestines in US images of 20 cats. Intestinal wall layer thickness measurements of the mucosa, submucosa, muscularis, serosa layer, and total thickness of these layers were performed on five cats with small cell epitheliotropic lymphoma, five with inflammatory bowel disease, and 10 with other conditions. Thickness measurements and the segmentation encompassing the serosa layer were obtained from five observers four times non-sequentially. The average standard deviation in thickness measurements (95% confidence interval) in the mucosa, submucosa, muscularis, serosa, and total thickness were 0.35 (0.07-0.95), 0.24 (0.07-0.52), 0.22 (0.06-0.49), 0.20 (0.05-0.49), and 0.57 (0.11-1.60) mm, respectively. The average intraclass correlation coefficients, which estimates the degree of consistency in thickness measurements and segmentation areas for each observer, ranged from 0.355 to 0.870 and 0.850 to 0.993, respectively. The interclass correlation coefficient, which estimates the degree of consistency when measuring a thickness or segmentation area over all observers ranged from 0.115 to 0.753, and 0.811 to 0.902, respectively. The overall average Dice Coefficient, which estimates the extent of overlap of the segmentations for all observers was 0.957 (0.933 to 0.972). Our results suggest segmentations of small intestines have a higher interobserver agreement than measurements of intestinal wall thicknesses.

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

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. To characterize the antigen receptor gene rearrangements of lymphocytes from skin and blood of dogs with eCTCL to determine if neoplastic clones are identical. Fourteen dogs with eCTCL. 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. 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. 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.

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

BackgroundCutaneous 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 presentationA 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.ConclusionsThis 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.

Isotretinoin treatment of 12 dogs with epitheliotropic lymphoma.

Epitheliotropic lymphoma is an uncommon cutaneous malignancy of T lymphocytes. Limited information is available regarding the treatment and outcome of dogs with this disease. To evaluate the treatment outcome and toxicity profile of isotretinoin in dogs with epitheliotropic lymphoma. Twelve dogs with a diagnosis of epitheliotropic lymphoma were included. A medical database was searched for dogs diagnosed with epitheliotropic lymphoma and treated with isotretinoin between 2010 and 2021. Diagnosis, treatment details and tumour response were recorded for 12 dogs. All lesions resolved in four of 12 (33%) treated dogs. Lesions visibly improved in a further three dogs, giving a response rate of 58%. Two dogs' lesions remained unchanged and three progressed despite therapy. Adverse effects occurred in three dogs (25%), all of which were rapidly resolving or not affecting quality of life. Isotretinoin treatment was a well-tolerated and effective treatment for canine epitheliotropic lymphoma.

Bcl-2 Immunoexpression in Feline Epitheliotropic Intestinal T-Cell Lymphomas.

Lymphoma is the most common malignant hematopoietic neoplasm in domestic felines. Twenty-two cases of feline epitheliotropic duodenal T-cell lymphoma were characterized morphologically and immunohistochemically (CD3, Pax5, Ki-67), and Bcl-2 immunoexpression was established. Most cases were in domestic shorthair cats (88.2%), with a mean age of 11.2 years. All lymphomas were CD3+, with a low-to-moderate expression of Ki-67 (<30%). A correlation between the tumoral pattern of infiltration in the lamina propria and the intraepithelial distribution of the neoplastic lymphocytes was established (p = 0.0155). Intraepithelial nests of neoplastic lymphocytes were predominantly observed in lymphomas with a patchy distribution in the lamina propria, whereas intraepithelial plaques were seen in lymphomas with an obliteration pattern. Bcl-2 was expressed in neoplastic cells in all cases, and a higher expression was associated with increased villous stunting (p = 0.0221), and tended to be present in those cases with increased epithelial damage. The expression of Bcl-2 and the degree of epitheliotropism were correlated with neoplastic progression in epitheliotropic intestinal T-cell lymphomas; those displaying high Bcl-2 immunoexpression showed increased villous stunting and epithelial damage, suggesting that Bcl-2 is overexpressed in advanced tumor stages, and may be used as a predictor of tumoral behavior in feline epitheliotropic intestinal T-cell lymphomas. This entity showed many similarities with human MEITL, so the latter entity should be considered in further lymphoma classifications of domestic animals.

Cover Image

The cover image is based on the Original Article Outcomes and prognostic factors in canine epitheliotropic and nonepitheliotropic cutaneous T-cell lymphomas by Kazushi Azuma et al., https://doi.org/10.1111/vco.12752.

Feline and Canine Cutaneous Lymphocytosis: Reactive Process or Indolent Neoplastic Disease?

Cutaneous lymphocytosis (CL) is an uncommon and controversial lymphoproliferative disorder described in dogs and cats. CL is generally characterized by a heterogeneous clinical presentation and histological features that may overlap with epitheliotropic lymphoma. Therefore, its neoplastic or reactive nature is still debated. Here, we describe clinicopathological, immunohistochemical, and clonality features of a retrospective case series of 19 cats and 10 dogs with lesions histologically compatible with CL. In both species, alopecia, erythema, and scales were the most frequent clinical signs. Histologically, a dermal infiltrate of small to medium-sized lymphocytes, occasionally extending to the subcutis, was always identified. Conversely, when present, epitheliotropism was generally mild. In cats, the infiltrate was consistently CD3+; in dogs, a mixture of CD3+ and CD20+ lymphocytes was observed only in 4 cases. The infiltrate was polyclonal in all cats, while BCR and TCR clonal rearrangements were identified in dogs. Overall, cats had a long-term survival (median overall survival = 1080 days) regardless of the treatment received, while dogs showed a shorter and variable clinical course, with no evident associations with clinicopathological features. In conclusion, our results support a reactive nature of the disease in cats, associated with prolonged survival; despite a similar histological picture, canine CL is associated with a more heterogeneous lymphocytic infiltrate, clonality results, and response to treatment, implying a more challenging discrimination between CL and CEL in this species. A complete diagnostic workup and detailed follow-up information on a higher number of cases is warrant for dogs.

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.

Divergent Effects of EZH1 and EZH2 Protein Expression on the Prognosis of Patients with T-Cell Lymphomas

T-cell lymphomas are highly heterogeneous and their prognosis is poor under the currently available therapies. Enhancers of zeste homologue 1 and 2 (EZH1/2) are histone H3 lysine-27 trimethyltransferases (H3K27me3). Despite the rapid development of new drugs inhibiting EZH2 and/or EZH1, the molecular interplay of these proteins and the impact on disease progression and prognosis of patients with T-cell lymphomas remains insufficiently understood. In this study, EZH1/2 mutation status was evaluated in 33 monomorphic epitheliotropic intestinal T-cell lymphomas by next generation sequencing and EZH1/2 and H3K27me3 protein expression levels were detected by immunohistochemistry in 46 T-cell lymphomas. Correlations with clinicopathologic features were analyzed and survival curves generated. No EZH1 mutations and one (3%) EZH2 missense mutation were identified. In univariable analysis, high EZH1 expression was associated with an improved overall survival (OS) and progression-free survival (PFS) whereas high EZH2 and H3K27me3 expression were associated with poorer OS and PFS. Multivariable analysis revealed EZH1 (hazard ratio (HR) = 0.183; 95% confidence interval (CI): 0.044–0.767; p = 0.020;) and EZH2 (HR = 8.245; 95% CI: 1.898–35.826; p = 0.005) to be independent, divergent prognostic markers for OS. In conclusion, EZH1/2 protein expression had opposing effects on the prognosis of T-cell lymphoma patients.

Monomorphic epitheliotropic intestinal T-cell lymphomas: a case report

BackgroundMonomorphic epitheliotropic intestinal T-cell lymphomas (MEITL) is a rare and aggressive subtype of lymphoma. The most common site of origin is small intestine. Patients are often presented with diagnosis of intestinal perforation with abdominal pain as the main consulting symptoms. Because of the deficiency of specific diagnostic measures and effective management, diagnosis is often confirmed in advanced stage with poor prognosis.Case presentationHere, we introduce a patient who has suffered from abdominal pain and diarrhea, and eventually been diagnosed as Monomorphic epitheliotropic intestinal T-cell lymphomas.ConclusionMEITL is rare in clinical practice with deficiency of early diagnostic measures and poor prognosis. Therefore, any patient with ambiguous gastrointestinal symptoms or perforation of the digestive tract where the primary lesion is difficult to identify should be alert to the possibility of this disease.

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.