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.     

Canine lymphoma

This article presents an overview of the literature regarding canine malignant lymphoma. It includes a discussion of etiology, classification, systemic manifestations of disease, therapy, and supportive care for patient management.     

Canine atypical malignant lymphoma

An instance of canine malignant lymphoma with some similarities to human Hodgkin's disease is described. Although the clinical data were all within normal limits, the histopathologic changes indicated that in many organs, the normal cell architecture was replaced by a pleomorphic cell population.     

Clonality and clinical behavior of canine indolent lymphoma

Introduction: Canine lymphomas with a follicular architecture are biologically indolent and include follicular (FL), mantle cell (MCL), marginal zone (MZL) and T‐zone (TZL) types. They are under recognized and have long survival regardless of treatment. Methods: 70 cases of canine lymphoma with fading follicular hyperplasia (FFH) received¹ over 1996 to present were reviewed. Diagnoses were determined by consensus of three pathologists^1,2 on phenotyped tissues. Clonality for B and T‐cell receptor genes was determined on DNA from paraffin blocks via PCR on 53 of 70 cases². Results: Of the total of 70 cases 52 were of B‐cell type (MZL 44, FL 4, MCL 3, MALT 1) and 9 were of T‐cell type (TZL). 9 cases of benign hyperplasia were included to assist in defining the histologic boundaries of neoplasia. Case presentation included splenic 16, and nodal 54. For 44 cases called MZL on histologic criteria, DNA was available on 33 of which 26 (78.8%) were clonal for B‐cell rearranged gene including 5 also clonal for T‐cell receptor, one clonal for T‐cell only and 6 cases negative for both and considered benign. For TZL, DNA was available on 6 of 9 cases of which 3 were clonal for T‐cell receptor, 1 for B‐cell, 1 for both and 2 polyclonal for both. Conclusions: An Ohio review of 380 cases of canine nodal lymphoma found 29% of cases to be of indolent type as described here and thus a very significant part of the patient population. Seven of 10 cases of MZL treated at Illinois with follow‐up died of other causes than lymphoma at an average of 18.8 months after diagnosis. One of the other three was lost to follow‐up, one was euthanized at owners’ choice at 9.5 m. after diagnosis still in good health and the other was terminated 3 m after diagnosis with concurrent lung carcinoma.     

Canine lymphoma: a review

Canine lymphoma (cL) is a common type of neoplasia in dogs with an estimated incidence rate of 20–100 cases per 100,000 dogs and is in many respects comparable to non-Hodgkin lymphoma in humans. Although the exact cause is unknown, environmental factors and genetic susceptibility are thought to play an important role. cL is not a single disease, and a wide variation in clinical presentations and histological subtypes is recognized. Despite this potential variation, most dogs present with generalized lymphadenopathy (multicentric form) and intermediate to high-grade lymphoma, more commonly of B-cell origin. The most common paraneoplastic sign is hypercalcemia that is associated with the T-cell immunophenotype. Chemotherapy is the treatment of choice and a doxorubicin-based multidrug protocol is currently the standard of care. A complete remission is obtained for most dogs and lasts for a median period of 7–10 months, resulting in a median survival of 10–14 months. Many prognostic factors have been reported, but stage, immunophenotype, tumor grade, and response to chemotherapy appear of particular importance. Failure to respond to chemotherapy suggests drug resistance, which can be partly attributed to the expression of drug transporters of the ABC-transporter superfamily, including P-gp and BCRP. Ultimately, most lymphomas will become drug resistant and the development of treatments aimed at reversing drug resistance or alternative treatment modalities (e.g. immunotherapy and targeted therapy) are of major importance. This review aims to summarize the relevant data on cL, as well as to provide an update of the recent literature.     

Canine nodular dermatophytosis (kerion): 23 cases

Dermatophytosis is a common zoonotic disease, and one of its clinical presentations in the dog is nodular dermatophytosis (kerion). Because the infection is located within the dermis, routine diagnostic tests such as a Wood's lamp examination, microscopic examination of hair shafts for fungal elements and fungal culture can yield negative results. In such cases, histopathological examination with routine and special stains (periodic acid-Schiff, Gomori methenamine silver) is required to confirm the diagnosis. Nodular dermatophytosis in 23 dogs of different breed, age and sex with single or multiple nodules is described. Twelve dogs had a single nodule, and 11 dogs showed multiple lesions. Wood's lamp examination was negative in all cases. Microscopic examination of plucked hairs showed arthrospores in 8 of 23 cases. Skin scrapings in mineral oil looking for arthrospores and/or hyphae were positive in 12 cases. Impression smears of exudates were diagnostic in 21 of 23 cases (91%), showing arthrospores within fragments of hair shafts or free among neutrophils and macrophages (pyogranulomatous inflammation). Histopathology was performed in two cases. Fungal culture was positive for Microsporum canis in 16 dogs and for Microsporum gypseum in one dog. In six cases, the causative agent was not identified by fungal culture. All dogs were treated with systemic antifungal therapy and in eight cases with concurrent antibiotic therapy. Nodular dermatophytosis resolved in all dogs with the prescribed treatments within 4 to 8 weeks. Transmission to people or other pets in the home was not found.     

Canine intravascular lymphoma with overt leukemia

A 6-year-old spayed Labrador Retriever Mix dog was evaluated for a 2-week history of progressive generalized weakness and reluctance to stand. Physical examination revealed severe weakness with obtunded mentation, head tilt, bilateral nystagmus, and decreased vision. CBC findings included mild nonregenerative anemia, marked thrombocytopenia, and a few atypical mononuclear cells on the blood film. The cells were 15-30 μm in diameter and had round to oval to reniform centrally placed nuclei with stippled chromatin, prominent nucleoli, and abundant basophilic cytoplasm with numerous discrete vacuoles and, occasionally, small azurophilic granules. Similar cells were found in bone marrow. On histologic examination of tissues collected at necropsy, neoplastic cells were detected in bone marrow, hepatic sinusoids, cerebral and meningeal vessels, and in capillaries of the heart, renal interstitium, small intestinal submucosa, and muscularis, and alveolar septa. A small discrete mass in the right atrium consisted of similar neoplastic cells, and the spleen was diffusely infiltrated. Tissue distribution was suggestive of intravascular lymphoma. Neoplastic cells in tissue sections were immunoreactive for vimentin, CD18, CD45, and granzyme B and lacked immunoreactivity for cytokeratin. Neoplastic cells on bone marrow aspirate smears and blood films lacked immunoreactivity for CD3, CD79a, CD1c, CD11b, CD11c, CD11d, and E-cadherin. In the absence of immunophenotypic evidence for the neoplastic cells being derived from B-cell, T-cell, or histocytic/dendritic lineages and the lack of clonal antigen receptor gene rearrangement(s), along with positive immunoreactivity for granzyme B, a tumor of NK cells was considered likely. Based on current knowledge, this is the first report of canine intravascular lymphoma, of probable NK cell origin, with peripheral blood involvement.     

Clinical,histopathological and immunohistochemical characterization of canine indolent lymphoma

Indolent lymphoma comprises up to 29% of all canine lymphoma; however, limited information exists regarding the subtypes and biological behaviour. This retrospective study describes the clinical characteristics, histopathological and immunohistochemical features, treatment, outcome and prognostic factors for 75 dogs with indolent lymphoma. WHO histopathological classification and immunohistochemistry (IHC) for CD79a, CD3, Ki67 and P‐glycoprotein (P‐gp) was performed. The most common histopathological subtype was T‐zone, 61.7%, (MST 33.5 months), followed by marginal zone, 25%, (MST 21.2 months), P = 0.542. The addition of IHC to preliminary histopathological classification resulted in a revised diagnosis in 20.4% of cases. The use of systemic treatment did not influence survival, P = 0.065. Dogs treated with chlorambucil and prednisone did not reach a MST, compared with a MST of 21.6 months with CHOP‐based chemotherapy, P = 0.057. The overall MST of 4.4 years confirms that this is indeed an indolent disease. However, the effect of systemic treatment must be determined through prospective trials.     

Canine episcleritis, nodular episclerokeratitis, scleritis, and necrotic scleritis.

This article provides a brief review of human episcleritis and scleritis, because the pathogenesis, diagnosis, and treatment of these disorders are perhaps the best understood of all species of animals. The clinical and light microscopic manifestations, therapeutic options, and prognosis for primary and secondary episcleritis and scleritis in dog are also reviewed. The focus of this article is on primary and secondary inflammatory conditions that originate in the episclera and sclera caused by idiopathic or known etiologies.     

Canine multicentric lymphoma 1: Clinico-pathological presentation of the disease

The clinicopathological features of 90 cases of canine multicentric lymphoma are described. The majority of cases occurred in middle-aged dogs (five to eight years of age) with a mean age at presentation of 6–7 years. A marked sex predisposition was noted with male dogs out numbering females by 2:1. No significant breed predispositions were found. The most common presentation was a generalised lymphadenopathy but in approximately one-third of the cases this was accompanied by other signs including polyuria and polydipsia, facial oedema and upper respiratory tract obstruction. Approximately two-thirds of all the cases showed non-specific haematological abnormalities including thrombocytopenia, anaemia and white blood cell anomalies. All the cases were clinically staged according to the anatomical extent of the disease. The majority of the dogs were classified as stage 3 or above, denoting that the disease is invariably widespread or systemic upon initial presentation.     

Canine cutaneous epitheliotropic T‐cell lymphoma: a review

Cutaneous epitheliotropic T‐cell lymphoma in the dog is a rare neoplastic condition with unknown aetiology. The dermatitis is characterized by infiltration of neoplastic T lymphocytes with a specific tropism for the epidermis and the adnexal structures. The different clinical and histological forms (mycosis fungoides, pagetoid reticulosis and Sézary syndrome) are reviewed. The disease in the dog resembles the human syndrome, but in 80% of the canine cases, neoplastic cells are CD4^?/CD8⁺ versus CD4⁺/CD8^? in 90% of the human patients. Prognosis is poor with a survival time from few months to 2 years. Treatments frequently have a low efficacy. New protocols using lomustine may improve the poor prognosis of the disease.     

Canine multicentric lymphoma 2: Comparison of response to two chemothera-peutic protocols

This paper describes the chemotherapeutic response of 90 cases of canine multicentric lymphoma. All the dogs were treated with a combination protocol using cyclophosphamide, vincristine and prednisolone. Forty-seven dogs received additional intravenous cytosine arabinoside on the first four days of treatment. Eighty-eight per cent of all cases had shown either a complete or partial response to this treatment at six weeks from the start of treatment and the overall mean survival time was 37 weeks (SD = 35.8). There was no significant difference in response or survival rates between the two treatment groups. The age and sex of the patient, the clinical stage of the disease and previous treatment with corticosteroids were all analysed to determine whether these parameters were of prognostic significance. Those dogs in clinical stages 4 and 5 carried a worse prognosis than those in stages 1 to 3. Previous treatment with corticosteroids adversely affected both tumour response and patient survival rates.     

Canine nodal marginal zone lymphoma: Descriptive insight into the biological behaviour

Canine nodal marginal zone lymphoma (nMZL) is classified as an indolent lymphoma. Such lymphomas are typified by low mitotic rate and slow clinical progression. While the clinical behaviour of canine splenic MZL has been described, characterized by an indolent course and a good prognosis following splenectomy, there are no studies specifically describing nMZL. The aim of this study was to describe the clinical features of and outcome for canine nMZL. Dogs with histologically confirmed nMZL undergoing a complete staging work‐up (including blood analysis, flow cytometry [FC] on lymph node [LN], peripheral blood and bone marrow, imaging, histology and immunohistochemistry on a surgically removed peripheral LN) were retrospectively enrolled. Treatment consisted of chemotherapy or chemo‐immunotherapy. Endpoints were response rate (RR), time to progression (TTP) and lymphoma‐specific survival (LSS). A total of 35 cases were enrolled. At diagnosis, all dogs showed generalized lymphadenopathy. One‐third was systemically unwell. All dogs had stage V disease; one‐third also had extranodal involvement. The LN population was mainly composed of medium‐sized CD21+ cells with scant resident normal lymphocytes. Histology revealed diffuse LN involvement, referring to “late‐stage” MZL. Median TTP and LSS were 149 and 259 days, respectively. Increased LDH activity and substage b were significantly associated with a shorter LSS. Dogs with nMZL may show generalized lymphadenopathy and an advanced disease stage. Overall, the outcome is poor, despite the “indolent” designation. The best treatment option still needs to be defined.     

Canine and feline retinal lymphoma: a retrospective review of 12 cases

This retrospective study identified 12 cases (6 canine and 6 feline) of ocular lymphoma with extensive retinal involvement and relative sparing of other ocular tissues. Our objectives were to describe the morphologic and immunohistochemical features of retinal lymphoma, assess the degree of correlation to the human counterpart, assign subtypes based on the veterinary‐adapted WHO classification system, and promote accurate reporting of retinal involvement in cases of intraocular lymphoma. Our findings suggest that a distinct retinal tropism is quite rare, representing approximately 1% of all cases of canine and feline ocular lymphoma. No breed or sex predispositions were identified. The mean age of the affected animal was 7 years (range 4–10) and 11 years (range 6–19) for dogs and cats, respectively. Nine cases (5 canine and 4 feline) were classified as diffuse large B‐cell lymphoma (DLBCL) subtype. The remaining cases were classified as peripheral T‐cell lymphoma (PTCL).