Emphysematous Cystitis due to Escherichia coli Associated with Prolonged Chemotherapy in a Non‐Diabetic Dog

An 11‐year‐old male Labrador retriever dog with chronic recurrent complicated urinary tract infection due to Escherichia coli and a history of prolonged multi‐drug chemotherapeutic protocol due to lymphoma was diagnosed with emphysematous cystitis. Diagnosis was based on ultrasonographic and radiographic findings. The immunosuppressive effects of the long glucocorticoid treatment were probably the main underlying mechanism involved in the pathogenesis, however, chemotherapy and/or the presence of lymphoma might have also been involved.     

Laboratory findings, histopathology, and immunophenotype of lymphoma in domestic ferrets

Lymphoma is a common tumor in ferrets, but anatomic distribution, histomorphology, immunophenotype, laboratory abnormalities, and response to chemotherapy are incompletely defined. In this study, lymphoma was diagnosed by histopathology of tumor tissue in 29 ferrets ranging in age from 0.8 to 8.5 years, including 12 males and 17 females. Tumors involved the viscera of the abdominal cavity (n = 11), thoracic cavity (n = 1), or abdominal and thoracic cavities (n = 7); the skin (n = 2); or the viscera of both body cavities plus other sites (n = 8). Microscopically, all tumors had diffuse architecture. Assessment by histomorphology and immunophenotype classified tumors as peripheral T-cell lymphoma (n = 17), anaplastic large T-cell lymphoma (n = 5), anaplastic large B-cell lymphoma (n = 4), diffuse large B-cell lymphoma (n = 1), and Hodgkin-like lymphoma (n = 2). Cytologic evaluation of tumor tissue was diagnostic in 11 of 13 cases. Twenty-two of 27 ferrets had anemia, 2 had leukemia, and 5 were neutropenic. Common comorbid disorders were adrenal disease (n = 27) and insulinoma (n = 6). Tumors most frequently involved mesenteric lymph nodes, while enlargement of peripheral lymph nodes was uncommon (n = 3). Ferrets with Hodgkin-like lymphoma had massive enlargement of single lymph nodes. Mean survival of ferrets not immediately euthanized was 5.0 months (T-cell lymphoma) and 8.4 months (B-cell lymphoma). Ferrets treated with chemotherapy survived an average of 4.3 months (T-cell lymphoma, n = 9) or 8.8 months (B-cell lymphoma, n = 4). Results indicate that lymphomas in ferrets most commonly affect abdominal viscera, may be amenable to cytologic diagnosis, are frequently associated with anemia and, in some cases, may be chemosensitive, resulting in relatively long survival times.     

Canine indolent and aggressive lymphoma: clinical spectrum with histologic correlation

Sixty‐three dogs with newly diagnosed lymphoma underwent complete staging and received the same chemotherapy. Diffuse large B‐cell lymphoma was the leading histotype (44.4%), followed by peripheral T‐cell lymphoma (20.6%). Indolent lymphomas accounted for 30.2% of cases. Most dogs with aggressive B‐cell lymphoma had stage IV disease. Dogs with indolent and aggressive T‐cell lymphoma had more often stage V disease and were symptomatic. Liver and bone marrow were predominantly involved in B‐cell and T‐cell lymphoma, respectively. The clinical stage was significantly related to substage, sex and total lactic dehydrogenase (LDH) levels. Aggressive B‐cell lymphomas were more likely to achieve remission. Median survival was 55 days for aggressive and indolent T‐cell lymphoma, 200 and 256 days for indolent and aggressive B‐cell lymphoma, respectively. The prognosis of advanced indolent lymphoma does not appear to be appreciably different from that of aggressive disease. Familiarity with the various histotypes is critical to make the correct diagnosis and drive therapy.     

Hypercalcemia in two Amazon parrots with malignant lymphoma

Malignant lymphoma is a common malignancy in birds. Paraneoplastic syndromes, which are commonly observed in domestic animals, have not been reported in association with lymphoma in birds. Hypercalcemia and hyperglobulinemia were found on plasma chemistry in two Amazon parrots, which were presented with aspecific symptoms. In both cases radiography and ultrasound demonstrated signs of hepatomegaly, which proved to be due to malignant lymphoma on postmortem examination. The hypercalcemia was found to be most consistent with a paraneoplastic effect of the malignant lymphoma in these birds. The exact origin of the hyperglobulinemia remains unclear.     

Lipotropes (methyl nutrients) inhibit growth of feline lymphoma in vitro

Feline lymphoma is one of the most frequently diagnosed tumors in cats. Lipotropes are dietary methyl donors that may modulate DNA methylation status and the expression of genes involved in growth and apoptosis of feline lymphoma cells. The specific objective of the study was to determine if lipotropes affect the growth of feline lymphoma cells, which entailed examining a correlation between lymphoma cell proliferation and apoptosis. F1B and FeLV-3281 cells were cultured and treated with 20 times the level of lipotropes contained in the basal culture medium. Cell growth and death and caspase 3 and tumor protein p53 activity were measured. Lipotropes were found to significantly reduce cell growth; increased cell death and caspase 3 and p53 activity was seen in F1B cells after 72 h, but the effect was minimal on FeLV-3281. These results could be useful in the development of dietary strategies for treating and preventing feline lymphoma.     

Recurrent adnexal lymphoma in a horse

Lymphoma is a relatively uncommon neoplasm in the horse; however, it is considered the most common neoplasia of the equine haemolymphatic system. Limited reports of adnexal lymphoma have been documented in the literature, with no known reports of recurrence nearly a decade after mass excision. The objective is to describe a case of recurrent adnexal lymphoma in a 20-year-old Quarter Horse gelding presented to the Ophthalmology service at the University of Florida Veterinary Hospital (UFVH) for evaluation of a solitary subconjunctival mass of the right eye (OD). A focal, pink, fleshy mass associated with the dorsomedial bulbar conjunctiva was noted. An excisional biopsy was performed. Histopathology revealed lymphoma with clean margins. The client declined staging and further therapy at the initial visit. Approximately 8 years later, the horse began to exhibit intermittent mild to moderate diffuse swelling of the conjunctiva OD. Six months after onset, the swelling worsened acutely and was accompanied by severe swelling of the left conjunctiva (OS). The horse then returned to UFVH and was diagnosed with diffuse, bilateral conjunctival lymphoma. Humane euthanasia was elected. T cell lymphoma was confirmed with immunohistochemistry performed post-mortem. At necropsy, neoplastic tissue was observed throughout the adnexal and ocular tissues of both eyes and in the submandibular lymph nodes. Adnexal lymphoma is an uncommon neoplasm in the horse. To the authors’ knowledge, this is the first documentation of a nodular adnexal lymphoma that involved an 8-year period without recurrence followed by development of diffuse, bilateral disease. Typically, surgical excision of the nodular form of lymphoma involving the extraocular tissues yields an improved prognosis compared with the diffuse form of the disease. Further investigation is necessary to determine if nodular forms of adnexal lymphoma represent early stages of diffuse extraocular or systemic disease.     

Renal T-cell lymphoma with cerebral metastasis in a dog with chronic canine ehrlichiosis

A renal T-cell lymphoma with exclusive cerebral metastasis was diagnosed in a 5-year-old Staffordshire bull terrier bitch euthanased for aggression. This is the first recorded case of primary renal lymphoma in a dog. Immune suppression, due to chronic canine monocytic ehrlichiosis, may account for the unusual primary site and metastatic pattern of the tumour.     

Feline lymphoma in the post-feline leukemia virus era

Lymphoma (lymphosarcoma or malignant lymphoma) is the most common neoplasm of the hematopoietic system of cats and reportedly the cat has the highest incidence for lymphoma of any species. A 21-year retrospective survey of feline lymphoma covering the period 1983-2003 was conducted with the patient database at the Veterinary Medicine Teaching Hospital (VMTH) at the University of California, Davis, School of Veterinary Medicine. This period comprises the post-feline leukemia virus (FeLV) era. Feline lymphoma historically has been highly associated with retrovirus infection. Mass testing and elimination and quarantine programs beginning in the 1970s and vaccination programs in the 1980s dramatically reduced the subsequent FeLV infection rate among pet cats. The results of this survey confirm a significant decrease in the importance of FeLV-associated types of lymphoma in cats. In spite of this decrease in FeLV infection, the incidence of lymphoma in cats treated at the VMTH actually increased from 1982 to 2003. This increase was due largely to a rise in the incidence of intestinal lymphoma, and to a lesser degree, of atypical lymphoma. A high incidence of mediastinal lymphomas in young Siamese or Oriental breeds also was observed, supporting previous studies. Associations of intestinal lymphoma and inflammatory bowel disease and diet should be further considered.     

Lymphoma in Miniature Dachshunds: A retrospective multicenter study of 108 cases (2006‐2018) in Japan

BackgroundMiniature Dachshunds (MD) are predisposed to lymphoma with disease onset of young age and long‐term survival.ObjectivesTo compare clinical features and survival time of lymphoma in MD and non‐MD.AnimalsOne hundred and eight MDs with lymphoma and 149 non‐MD breed dogs with lymphoma were included in the study.MethodsThis was a retrospective multicenter observational study. Lymphoma was classified based on signalment, histopathology/cytology, and anatomical site of the disease. For each type of lymphoma, median survival time was analyzed by Kaplan‐Meier estimates and life table analysis. Prognostic factors for large‐cell gastrointestinal lymphoma (LGIL) were analyzed using Cox regression.ResultsGastrointestinal lymphomas were more common in MDs (53/108) compared to non‐MDs (41/149). The multicentric lymphoma was most common in non‐MD breed dogs (74/149) compared to MDs (33/108). The median age that dog developed lymphoma in MD and non‐MD were both 10 years old; however, lymphomas were more frequently observed in younger dogs (<4 years) in MDs (20/108) compared to non‐MDs (9/149; P = .002). Seventy percent were diagnosed with B‐cell with median age of diagnosis was 3 (1‐14) years. Mott cell differentiation was observed in 6 dogs. Age <4 years and B‐cell phenotype were significant factors for longer survival time in MD with LGIL.Conclusions and Clinical ImportanceLymphomas in MDs involved gastrointestinal lesions at higher frequency compared to other dog breeds examined. B‐cell lymphoma was more common in early‐onset LGIL in MD and cases that involved Mott cell differentiation were observed. Awareness of this specific presentation of lymphoma in dogs will possibly affect the treatment decision process for the owners of MD with LGIL.     

Canine indolent nodular lymphoma

Sixty-six cases of indolent canine lymphoid proliferation were reviewed. Age ranged from 1.5 to 16 years (median 9.0 years). Dogs of 26 breeds, plus 13 of mixed breeding or unknown lineage, were represented. B-Cell lymphomas (CD79a+) predominated. Marginal zone lymphoma (MZL), the largest group, involved lymph node (33 cases) and spleen (13 cases), with both tissues involved in five of these cases. Follicular lymphoma (FL) involved lymph nodes (five cases), and mantle cell lymphoma (MCL) occurred as solitary splenic masses (three cases). Nodal CD3+ T-zone lymphomas (TZL) (10 cases), were included since they resembled late-stage MZL at the architectural level. Two cases of marginal zone hyperplasia (MZH) were included to aid in differentiation of early MZL. Clonality status was determined in 54 cases by analysis of immunoglobulin heavy chain (IGH) and T-cell antigen receptor gamma (TCRG) gene rearrangement. Clonal rearrangement of IGH was detected in 28 of 35 MZL cases (80%), four of four FL cases (100%) and three of three MCL cases (100%). Concurrent cross lineage rearrangement of TCRG was detected in six MZL and two FL cases. Clonal rearrangement of TCRG was documented in five of eight TZL cases (63%). Limited survival data obtained for 18 dogs indicated that the B-cell lymphomas (MZL, MCL, and FL) and the T-cell lymphoma (TZL) were associated with indolent behavior and long survival. Although to the authors' knowledge, the true incidence of canine indolent lymphomas is unknown, the tumors are not rare and may have been underrecognized. Recognition of their architectural features, routine application of immunophenotyping, and molecular clonality assessment should alleviate this.     

Evaluation of P-glycoprotein expression in feline lymphoma and correlation with clinical outcome

P-glycoprotein (Pgp) is a transmembrane protein pump involved in drug resistance in canine and human lymphoma. There are no published clinical studies evaluating Pgp expression in feline lymphoma. The purpose of this study is to evaluate the level of Pgp expression in feline lymphoma and correlate it with clinical outcome. Two human Pgp monoclonal antibodies, C219 and C494, were used to detect Pgp expression in tissue samples from 63 cats with lymphoma. Demographic results appear comparable to recently published feline lymphoma studies. The Kaplan–Meier median remission and survival times were 164 and 571 days, respectively. Fourteen cats had positive expression of Pgp using MAb C219, and 40 were positive with C494. Variables statistically associated with survival included bone marrow involvement, stage, substage, and use of radiation therapy as a part of treatment. Pgp expression as assessed by MAb C219 and C494 is not predictive of remission or survival time in cats with lymphoma.     

Affinity of the alpha4-beta1 integrin-targeting peptide LLP2A to canine lymphoma

Lymphoma is an important disease in dogs and people, with similar biological characteristics. We tested the binding affinity of a peptidomimetic LLP2A, previously shown to bind the alpha4-beta1 integrin on human lymphoma cell lines, to lymphocytes of dogs with spontaneously occurring lymphoma. Fine needle aspirates of lymph nodes from 32 dogs with B-cell lymphoma and 7 dogs with T-cell lymphoma were evaluated using flow cytometry. For B cells, the lowest MFI levels were in unlabeled, non-neoplastic lymphocytes. The highest median fluorescent intensity (MFI) levels occurred in LLP2A-labeled lymphoma cells from dogs that had not received chemotherapy followed by labeled lymphoma cells from dogs that had received chemotherapy. The fluorescence profile of the T-cell samples was similar although many of the differences were not statistically significant, likely due to low sample number. Specifically, LLP2A-labeled T-cell lymphoma cells had a significantly higher MFI compared to unlabeled non-neoplastic lymphocytes. LLP2A affinity was not significantly different in unlabeled and labeled T-cell lymphoma cells, and labeled non-neoplastic lymphocytes. For both B and T cells, labeling with LLP2A tended to increase MFI in both normal and lymphoma cells. Lymphoma cells had higher mean MFI levels than non-neoplastic lymphocytes, and chemotherapy acted to decrease MFI. In summary, these data demonstrate that LLP2A has affinity to canine lymphoma cells and indicates expression of the alpha4-beta1 integrin on these cells. In fact, LLP2A preferentially binds neoplastic B-cells, suggesting that this small molecule may be of use in cross-species clinical trials of targeted therapeutics.     

Blunted pathogen-associated molecular pattern motif induced TNF, IL-6 and IL-10 production from whole blood in dogs with lymphoma

Lymphoma is associated with a higher risk of sepsis as compared to other forms of neoplasia in people and dogs which might be due to alterations in cytokine production. The objective of this study was to compare bacterial pathogen associated molecular pattern (PAMP) motif-induced TNF, IL-6, and IL-10 response of whole blood from dogs with na?ve lymphoma and healthy dogs. We hypothesized that whole blood from dogs with lymphoma would exhibit an impaired cytokine response to LPS, lipoteichoic acid (LTA), and peptidoglycan (PG) stimulation compared to whole blood from healthy dogs. Whole blood was collected from dogs with lymphoma (n=20) and healthy dogs (n=15) and stimulated with PAMPs or phosphate buffered saline. Whole blood production of TNF, IL-6 and IL-10 was measured. Whole blood from dogs with lymphoma had reduced TNF, IL-6 and IL-10 production capacity after LPS, LTA and PG stimulation compared to whole blood from healthy dogs. These data could partially explain why dogs with lymphoma have a higher risk for infection compared to dogs with other forms of neoplasia.     

B cell lymphoma and secondary leukaemia in a mule

A 20‐year‐old mule was evaluated for anorexia and fever. Haematological evaluation revealed a population of large, immature lymphoid cells and significant anaemia. Bone marrow aspiration was unsuccessful, and abdominal ultrasonographic evaluation was unremarkable. The mule was subjected to euthanasia due to poor prognosis, and necropsy and histological evaluation revealed multicentric B cell lymphoma. The leukaemic phase of lymphoma is rarely documented in equids, and is regarded as an indication of advanced or aggressive disease. To the authors' knowledge, lymphoma in a mule has been reported only once previously.     

Biphenotypic B‐cell lymphoma in 2 cats

The clinical and pathologic features of biphenotypic B‐cell lymphoma in 2 cats are reported. Clinical presentation varied from multiple cutaneous masses identified on the thigh in one cat to signs of lethargy from acute hemorrhage due to neoplastic infiltration of one kidney in the other. Cytology and histopathology confirmed round cell neoplasia in both cats and immunochemical staining demonstrated expression of both B‐ and T‐lymphocyte markers by the neoplastic cells in both animals. In PCR analysis of antigen receptor gene rearrangement, clonal rearrangement of B‐cell receptor genes and polyclonal T‐cell receptor gene rearrangement were demonstrated in both lymphomas. These findings were consistent with a diagnosis of B‐cell lymphoma with aberrant CD3 expression in both cases. Clinical progression of disease post diagnosis was rapid in both cats, suggesting a poor prognosis for this lymphoma type. Although bigenotypic receptor rearrangement of lymphoma cells appears relatively common, this is the first known report of actual biphenotypic lymphoma in cats.     

Primary bone marrow T‐cell lymphoma in a Golden Retriever

A 6.2‐year‐old 28‐kg (61.7 lb) intact female Golden Retriever was referred due to persistent and multiple cytopenias noted on a routine CBC prior to a mature ovariohysterectomy procedure. The patient's physical examination was unremarkable, and staging of the thorax and abdomen identified no abnormalities. At the referral hospital, moderate hypercalcemia, borderline anemia, and neutropenia were noted. Assessment of bone marrow samples by cytology, histology, immunohistochemistry, and flow cytometry indicated a T‐cell neoplasm. The patient was treated with a multi‐agent chemotherapy protocol for 6 months, which induced remission. Nine months after diagnosis, she relapsed with recurrence of hypercalcemia, cytopenias, and clinical illness. Single‐agent anthracycline (mitoxantrone) in combination with prednisone therapy was initiated for 3 months. Two months after completion, the patient relapsed again, and palliative therapy with prednisone was elected. The patient was euthanized 16 months after diagnosis due to progressive disease. Post‐mortem histopathologic evaluation showed extensive replacement of bone marrow by neoplastic cells, and infiltrates in multiple organs. The neoplasm was diagnosed as lymphoma rather than leukemia due to the lack of abnormal circulating cells throughout the course of disease. The neoplasm was detected only in marrow at the time of initial diagnosis, and the marrow was the most extensively effaced organ at the time of death. Therefore, leukemia or stage V lymphoma was considered unlikely. In patients with a cytopenia and lack of neoplastic leukocytosis or solid tissue masses, primary bone marrow lymphoma should be considered among the differential diagnoses.     

Ocular and multicentric lymphoma in a young racehorse

A 6-year-old thoroughbred gelding was presented with a history of blepharospasm and opacity in the OS of 1 weeks' duration. Ophthalmic examination findings were consistent with acute uveitis in the OS, and traditional treatment was initiated with systemic antibiotics and anti-inflammatory drugs, topical mydriatics, and corticosteroids. During the total treatment period of 4 weeks response to treatment was weak and the horse developed further problems such as cellulitis of the right hind limb with fever and eventually weight loss and dependent edema. Blood work was indicative of liver disease. Abdominal sonography revealed severe splenomegaly and slight hepatomegaly, and a liver biopsy confirmed malignant T-cell lymphoma. The horse was euthanized due to deteriorating general condition and subsequently underwent postmortem examination. Necropsy and histologic examination revealed a multicentric lymphoma with involvement of spleen, mesenteric lymph nodes, and OU.
The findings in this case demonstrate that the differential diagnosis of intraocular and systemic lymphoma should be considered in any horse presenting with anterior uveitis, especially when uveitis is unresponsive to treatment and when additional systemic signs of illness such as lethargy, fever, weight loss, or dependent edema arise.
Cytological examination of aqueous humor may provide a rapid diagnosis of intraocular lymphoma in eyes with clinical uveitis.     

Lymphoma in a rabbit: histopathological and immunohistochemical findings

Lymphoma is a very common lymphoid neoplasm in domestic animals, but few naturally occurring cases have been reported in rabbits. It presents at different sites within rabbits and, although the macroscopic pattern tends to be similar, different cell populations may be involved. This report describes a case of spontaneous lymphoma ocurring in a two-and-a-half-year-old pet Dutch dwarf rabbit. T and B lymphocyte infiltrates were observed in skin, lung, kidney, liver, intestine and lymph nodes, in each case affecting one or more tissue structures. The diagnosis, based on microscopic and immunocytochemical findings, was multicentric, T cell-rich B cell lymphoma with skin involvement.     

Nasal and nasopharyngeal lymphoma in cats: 50 cases (1989-2005)

Lymphoma is the most common nasal cavity tumor in cats, yet few reports specifically address the anatomic, immunohistologic, and cytologic features of this neoplasm. Fifty cats were diagnosed with lymphoma at necropsy, via biopsy or by cytology alone. Ten cats displayed multiorgan involvement, and in 2 of these the involvement was limited to the cerebellum and frontal cortex, respectively. Of the tumors, 41 of 50 (82%) were classified as nasal lymphoma, 5 of 50 (10%) were classified as nasopharyngeal lymphoma, and 4 of 50 (8%) involved both nasal and nasopharyngeal tissue. Histologically, all were considered diffuse lymphoid neoplasms and no cats displayed features of follicular lymphoma. Of the 44 cases available for slide review by the pathologist, 40 of 44 (91%) were classified as immunoblastic lymphoma, 2 of 44 (5%) as diffuse large cell, and 1 as diffuse mixed; 1 was unclassified. Of the 45 cats for which immunohistochemical stains were available, 32 were uniformly positive for CD79a, 7 were uniformly CD3 positive, and 6 had a mixed population of CD79a and CD3 cells. Epithelioptropism was exhibited in 4 of 5 (80%) cats in which there was sufficient epithelium present for evaluation. Of those 4, 3 were B-cell and 1 was a granulated T-cell lymphoma. In the 21 cats which nasal cytology was performed, 15 were cytologically diagnosed with lymphoma; the diagnoses in the remaining five cats were inflammatory (n = 4), normal lymphoid tissue (n = 1), or nondiagnostic (n = 1). The most common biochemical abnormalities were panhyperproteinemia in 26/46 (57%) of cats and hypocholesterolemia in 11/46 (24%) of cats.     

Large granular lymphocyte lymphoma in the skin and urinary bladder of a dog

A 10-year-old female Cavalier King Charles Spaniel presented with hematuria, pollakiuria and skin rash. Based on the histopathological and cytological examination of the skin and bladder mucosa, the dog was diagnosed with large granular lymphocytic (LGL) lymphoma of the bladder and skin. The dog responded well to the initial chemotherapy with nimustine for 3 months. Since recurrence of skin erosion and bladder wall thickening were observed, the dog was subsequently administered chemotherapy with other anticancer drugs, including chlorambucil, vincristine, doxorubicin, L-asparaginase, cytosine arabinoside, and cyclophosphamide. The dog survived for 11 months and died due to tumor-related disseminated intravascular coagulation. This is the first report of a canine case of LGL lymphoma in the skin and bladder.