Cutaneous T‐cell lymphoma – Sézary syndrome in a Boxer

A 7‐year‐old male Boxer with a 3.5‐year history of atopy and food hypersensitivity was presented with multiple poorly circumscribed nodules and maculae of the skin and tongue, and jaundiced mucosal membranes. Cytologic and histopathologic examination of the skin lesions revealed cutaneous epitheliotropic lymphoma. Cells were CD3⁺ and CD8⁺ in flow cytometry. The CBC showed a moderate leukocytosis with 16% atypical lymphocytes with irregularly cleaved nuclei. Flow cytometric phenotyping of peripheral blood showed an elevated proportion of the CD8⁺ T‐lymphocyte subpopulation, indicating a malignant population of T‐cell origin, and the electropherogram of the PCR antigen receptor rearrangement produced a monoclonal peak for TCRγ. Liver enzyme activities were markedly increased and abdominal ultrasound examination showed increased echogenicity of the liver and enlarged abdominal lymph nodes. Fine‐needle aspirates of the liver confirmed infiltration with lymphocytes exhibiting the same morphology as the cells detected in skin and peripheral blood. Treatment was induced with L‐asparaginase, lomustine, and prednisone. Partial clinical remission of the skin and tongue lesions was achieved within 10 days, and hematologic abnormalities resolved. Despite further treatment with L‐asparaginase and lomustine, the dog relapsed within one month and was euthanized. Presence of malignant lymphocytes in skin, peripheral blood, and liver indicate a rare variant of leukemic cutaneous T‐cell lymphoma, equivalent of Sézary syndrome in a dog. This case report describes the use of flow cytometry as a complementary tool for lymphocyte characterization of skin lesions for the first time.     

Epitheliotropic cutaneous lymphoma (mycosis fungoides) in a dog

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.     

TOTAL SKIN ELECTRON THERAPY TECHNIQUE FOR THE CANINE PATIENT

Cutaneous epitheliotropic T‐cell lymphoma in canine patients is a radiation sensitive tumor but total skin electron therapy is used only rarely. Our purpose was to evaluate dose distribution from a total skin electron therapy technique using 6 MeV electron beams. The treatment was comprised of 12 fields, with the dog in lateral recumbency in a stride position at an extended distance from the source. Uniformity, flatness and symmetry were determined for each beam. The composite percent depth dose profile for all beams was measured in solid water phantoms and skin dose was determined on a canine cadaver using thermoluminescent dosimeters. The resulting d_max of the composite beams was 1 mm and dose variation over the skin was 6.8%, with the extremities having the most uneven dose distribution. Dimensions of the fields were adequate to obtain an effective treatment profile for the entire thickness of canine epidermis and the technique was feasible for clinical application. Individual tailoring of the protocol to deal with hot and cold spots may be necessary and set up will likely involve a significant time commitment for the therapy team.     

Erythrophagocytic low‐grade extranodal T‐cell lymphoma in a cat

Abstract: A 13‐year‐old male castrated domestic shorthair cat was presented to the referring veterinarian with a 2‐month history of weight loss and lethargy. Splenomegaly, hepatomegaly, nonregenerative anemia, neutropenia, and hyperbilirubinemia were noted. Results of testing for feline immunodeficiency virus, feline leukemia virus, Toxoplasma gondii, and Mycoplasma sp. were negative. On cytologic examination of aspirates from the enlarged spleen and liver, a population of erythrophagocytic round cells was observed. Splenectomy and a liver biopsy were done which revealed a population of CD3+/CD79a– erythrophagocytic mononuclear round cells localized in the hepatic and splenic sinusoids. T‐cell PARR (PCR for antigen receptor gene rearrangements) analysis of bone marrow and spleen demonstrated a single band indicative of a clonal proliferation of T cells. Based on the marked splenomegaly, sinusoidal infiltration, lack of lymphadenopathy, and results of cytology, PARR, and immunophenotyping, a diagnosis of low‐grade extranodal T‐cell lymphoma was made. The cat was treated with chlorambucil and prednisolone; clinical and laboratory abnormalities resolved and the cat has remained clinically normal for 2.5 years. To our knowledge, this report documents the first case of an erythrophagocytic T‐cell lymphoma in a cat. The clinicopathologic findings were suggestive of hepatosplenic T‐cell lymphoma, a neoplasm described previously only in humans and dogs.     

Epitheliotropic lymphoma in a squirrel (Sciurus sp.).

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.     

Epitheliotropic cutaneous lymphoma (mycosis fungoides) in a coati

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

Cutaneous epitheliotropic lymphoma with dual CD3 and c‐kit expression in a dog

An 11‐year‐old 8.9‐kg spayed female Boston Terrier was presented for evaluation of a mucocutaneous tumor on the right side of the upper lip that had been biopsied (punch biopsy) by the referring veterinarian. The histologic diagnosis was poorly differentiated round cell tumor involving the submucosa with patchy involvement of the mucosa. On presentation of the dog to Louisiana State University, the tumor was found to involve the mucosa and haired skin surface of the right upper lip. A fine‐needle aspirate of the right mandibular lymph node contained atypical poorly differentiated round cells similar to those in the histologic sections. To further characterize the tumor, immunohistochemical analysis of the tumor on the lip was performed; tumor cells were strongly immunoreactive for both CD3 and c‐kit in a cytoplasmic to membranous pattern, with CD3 expression having a more intense membranous component. The diagnosis was cutaneous epitheliotropic T‐cell lymphoma with co‐expression of CD3 and c‐kit by neoplastic lymphocytes, an unusual finding. As receptor tyrosine kinases can be attractive targets for cancer treatment, expression of these molecular targets in tumors is a promising subject of future research.     

Pulmonary and hepatic eosinophilic granulomas and epistaxis in a horse suggestive of multi‐systemic eosinophilic epitheliotropic disease

Multi‐systemic eosinophilic epitheliotropic disease (MEED) is a relatively uncommon disease characterised by eosinophilic infiltration of more than one organ system, with the skin and gastrointestinal tract most commonly affected. This case report describes a gelding that presented for weight loss, increased respiratory rate and effort and chronic intermittent epistaxis. During post mortem examination diffuse eosinophilic granulomatous lesions were identified in the lung and liver, leading to a diagnosis of MEED. Veno‐occlusive pulmonary remodelling was also discovered, believed to be the cause of the chronic epistaxis and a result of the pulmonary fibrosis and eosinophilic granulomas.     

Epitheliotropic T-cell lymphoma in a guinea pig

A 4-year-old female guinea pig was presented with pruritic, erythematous, hypotrichotic and scaling skin lesions, mainly involving the abdomen and the hindlegs. Clinical abnormalities were limited to the skin, and the guinea pig was otherwise healthy. The dermatological diagnostic work-up excluded ectoparasites, dermatophytosis and an endocrinopathy as differential diagnoses for the pruritus and hair loss. An allergic dermatitis was under investigation when the general and skin condition deteriorated. A neoplastic skin disorder was suspected, and skin biopsies revealed changes consistent with a cutaneous epitheliotropic T-cell lymphoma. Pautrier's microabscesses and immunophenotyped CD3(+) CD79(-) lymphocytes were identified. Owing to the deteriorating condition of the animal and the unknown but most likely poor prognosis of this disease, the guinea pig was euthanized. To the authors' knowledge, this is the first case report of cutaneous epitheliotropic T-cell lymphoma in the guinea pig with characteristic histopathological and immunohistochemical features.     

Epitheliotropic T-cell lymphoma in 2 half-sibling bontebok

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

Epidemiological,pathological and immunohistochemical aspects of 125 cases of feline lymphoma in Southern Brazil

A retrospective study compiling cases of feline lymphoma diagnosed during 12 years (2004‐2016) in Southern Brazil was performed. A total of 125 cases of lymphoma diagnosed in cats were reviewed, and information including age, breed, sex and tumour topography were collected. FeLV and FIV immunohistochemical tests were performed, as well as immunophenotyping of lymphomas. The alimentary form represented the most common presentation (42/125), followed by mediastinal lymphoma (35/125). Out of 125 cases, 79 presented positive retroviral immunostaining in tumour tissue (52 FeLV alone, 14 FIV alone and 13 presented FIV and FeLV co‐infections), 66/125 of the cases were of T‐cell origin and 59/125 of the cases were of B‐cell origin. The median age of cats with T‐cell lymphoma was 120 months (10‐240 months), and 60 months (6‐204 months) for cats with B‐cell lymphoma. The most frequent alimentary tumour presentation was the enteropathy‐associated T‐cell lymphoma (type 1), and the major type of mediastinal tumour observed was diffuse large B‐cell lymphoma. Considering only mediastinal and alimentary lymphomas (n = 77), the prevalence of mediastinal lymphoma in FeLV‐positive cats was 2.21 times higher than the prevalence of this type of tumour in FeLV‐negative cats (P = .036). Mediastinal lymphoma was more frequently observed in younger cats, and the prevalence of mediastinal tumours in these animals was 3.06 times higher than the prevalence of this tumour form in old cats (P = .0125). The present study indicates that retroviral infections still play an important role in the development of feline lymphomas in southern Brazil.     

Canine inflamed nonepitheliotropic cutaneous T‐cell lymphoma: a diagnostic conundrum

Background –  Cutaneous T‐cell lymphoma (CTCL) in dogs is a heterogeneous disease complex, which consists of nonepitheliotropic (NE) and epitheliotropic forms. These lymphomas are readily recognized by the presence of dominant populations of cytologically atypical lymphocytes. Objective –  The objective of this study was to introduce the key features of inflamed NE‐CTCL, which is easily confused with reactive, inflammatory histiocytic disease. Animals –  Twenty‐four dogs (mean age 7.5 years) presented with inflamed NE‐CTCL. Lesions presented as nodules, plaques or masses. An initial diagnosis of cutaneous reactive histiocytosis (11 dogs) or histiocytic neoplasia (three dogs) was made by primary pathologists. Methods –  Lesions were assessed by histology and immunohistochemistry to detect canine leukocyte antigens. Lesional genomic DNA was extracted and gene rearrangement analysis of the T‐cell receptor γ locus was assessed. Results –  The cutaneous lesions consisted of pleocellular infiltration of the dermis with variable extension into the subcutis. The lesions often surrounded vessels and adnexae. Epitheliotropism was minimal or lacking. Small lymphocytes, plasma cells and intermediate to large, cytologically atypical lymphocytes were scattered between prominent histiocytic infiltrates. Atypical lymphocytes often had marked variation in the intensity of CD3 expression. Molecular clonality analysis of the T‐cell receptor γ locus revealed clonal expansion of T cells in 22 of 23 dogs tested. Conclusion –  The recognition of inflamed NE‐CTCL and its differentiation from cutaneous reactive histiocytosis depends on careful assessment of lymphocyte morphology and immunostaining patterns. Confirmation of the diagnosis is best accomplished by T‐cell antigen receptor gene rearrangement analysis.     

T-cell-derived malignant lymphoma in the boxer breed

The boxer breed of dog is at high risk for a variety of neoplasms including lymphoma. In this observational study, tissue sections from boxer dogs with lymphoma were immunostained for T and B lymphocyte distinction, and the results compared with similar studies carried out on lymphoma tissues from temporally selected cohorts of golden retriever and rottweiler dogs. The frequency of T‐cell lymphomas was significantly (P < 0.001 for all comparisons) higher in the boxers than in the rottweilers or golden retrievers. We are unaware of other reports linking immunotype of canine lymphoma with breed; whether other brachycephalic breeds of dogs have a similar preponderance of T‐cell lymphoma awaits further study.     

Clinical characteristics and outcome in dogs with small cell T‐cell intestinal lymphoma

Small cell intestinal lymphoma has not been well characterized in dogs. The objective of this study was to describe clinical characteristics and outcome in dogs with small cell intestinal lymphoma. We hypothesized that affected dogs would have prolonged survival compared with high‐grade gastrointestinal (GI) lymphoma. Pathology records were searched for dogs with histologically confirmed small cell GI lymphoma. Seventeen dogs with confirmed small cell intestinal lymphoma were identified, and clinical and outcome data were retrospectively collected. Histopathology was reviewed by a board‐certified pathologist, and tissue sections were subjected to immunophenotyping and molecular clonality assessment. All dogs had small cell, T‐cell, lymphoma confirmed within various regions of small intestine, with 1 dog also having disease in abdominal lymph nodes. All dogs had clinical signs attributable to GI disease; diarrhoea (n = 13) was most common. Ultrasonographic abnormalities were present in 8 of 13 dogs with abnormal wall layering (n = 7) and hyperechoic mucosal striations (n = 7) representing the most common findings. In total, 14 dogs received some form of treatment. The median survival time (MST) for all dogs was 279 days and the MST for the 14 dogs that received any treatment was 628 days. Dogs with anaemia and weight loss at presentation had significantly shorter survival times and dogs that received a combination of steroids and an alkylating agent had significantly longer survival times. Small cell, T‐cell, intestinal lymphoma is a distinct disease process in dogs, and those undergoing treatment may experience prolonged survival.     

Canine cutaneous epitheliotropic T‐cell lymphoma: a review of 30 cases

This retrospective study reviewed the clinical, histological and immunohistochemical features of 30 European cases of canine cutaneous epitheliotropic T‐cell lymphoma (CETL). The clinical presentation was highly variable and was not associated with the disease subtype. Diffuse erythema (86.6%) with scaling (60%) and focal hypopigmentation (50%) were the most common lesions. The skin was uniformly involved but muco‐cutaneous junctions or mucosae were affected in 50% of cases. The median age at diagnosis was 10 years (SD 2.79, range 4–15) and the median time between onset and final diagnosis was 5 months (SD 3.79, range 0–12). Five cases occurred in Bichon Frises. There was no evidence of a previous history of chronic dermatitis in any cases. Histologically, the follicular epithelium was affected in 86.7% of cases. One case with mainly follicular disease was considered folliculotropic mycosis fungoides (MF), but no follicular mucinosis was observed. Epidermal Pautrier’s microabscesses were uncommon (23.3%). Sweat glands were infiltrated in 70% of cases. Immunohistochemistry confirmed T‐cell neoplasia in all cases. B cells infiltrated as individual cells or formed linear bands or ectopic follicles at the base of the neoplasm. Ki67 labelling revealed a range of proliferation indices but did not correlate with severity. A final diagnosis of classical MF was made in 40% of the dogs, MF d’emblé in 36.7%, generalized Pagetoid reticulosis in 20% and localized Pagetoid reticulosis in one case (Woringer–Kolopp Pagetoid reticulosis). The median survival time after diagnosis was 6 months and this did not change appreciably with therapy (lomustine or prednisolone).     

Immunohistochemical detection of protein gene product 9.5 (PGP 9.5) in canine epitheliotropic T-cell lymphoma (mycosis fungoides)

Protein gene product 9.5 (PGP 9.5), a ubiquitin COOH-terminal hydrolase initially considered specific for neural and neuroendocrine tissues, is expressed in a variety of epithelial and mesenchymal tumors. During immunohistochemical evaluation of a cutaneous epitheliotropic T-cell lymphoma (mycosis fungoides [MF]) in a dog, strong reactivity for PGP 9.5 was observed. This unexpected result prompted us to examine PGP 9.5 immunoreactivity in 13 additional cases of canine mycosis fungoides. All tumors were confirmed as T-cell epitheliotropic lymphoma by histopathology and immunohistochemistry for CD3. Eight of 14 cases were positive for PGP 9.5, with reactivity mainly in the cytoplasm and less commonly in the nucleus. One case had strong reactivity in the cell membrane, sometimes with concurrent paranuclear staining. Immunoreactivity did not correlate with location (epidermal, dermal, and adnexal) of tumor cells. Disease outcome did not vary between PGP 9.5-positive and negative tumors. Although PGP 9.5 immunoreactivity in MF did not predict tumor behavior in these dogs, it has had prognostic value in certain human carcinomas. This unexpected staining of lymphocytes in mycosis fungoides with an antibody to PGP 9.5 demonstrates its presence in nonneuroendocrine tumors and precludes its use as the sole diagnostic marker in discrete cell tumors in the skin.