Chronic lymphopenia and neutropenia in a dog with large granular lymphocytic leukemia

T‐cell large granular lymphocytic leukemia (T‐cell LGLL) is the most common presentation of chronic lymphocytic leukemia (CLL) in dogs. Aleukemic or subleukemic leukemia is a particularly rare variation in both humans and dogs, where bone marrow proliferation is either not or only sparsely translated in the peripheral blood. Neutropenia is a prominent feature in cases of human T‐cell LGLL but is normally absent in canine CLL. This report describes a case of a dog presented with an almost 3‐year history of asymptomatic neutropenia, lymphopenia, and thrombocytopenia (without anemia). A bone marrow examination, the exclusion of infectious diseases, and clonality testing led to the diagnosis of subleukemic LGLL that responded well to therapy (death occurred 2.5 years later due to an unrelated cause).     

Gamma delta T‐cell large granular lymphocyte lymphoma in a dog

A 2‐year and 6‐month‐old female neutered Labrador Retriever with Horner syndrome, megaesophagus, and a mediastinal mass was referred to the Queen Mother Hospital for Animals of the Royal Veterinary College. A large granular lymphocyte (LGL) lymphoma was diagnosed on cytology; flow cytometric analysis revealed a γδ T‐cell phenotype (CD3+, CD5+, CD45+, TCRγδ+, CD4?, CD8?, CD34?, CD21?). Chemotherapy was started with a combination of lomustine, vincristine, procarbazine, and prednisolone, followed by bleyomicin. Euthanasia was elected by the owners, due to progressive deterioration and lack of quality of life, 28 days after diagnosis. This is the first cytologic and immunophenotypic characterization of a canine γδ T‐cell lymphoma with LGL morphology and probably of mediastinal origin. The role of chemotherapy in delaying the disease progression remains unknown.     

Large granular lymphocyte leukemia in a horse

Large granular lymphocytes (LGL) occur as a leukemic or aleukemic neoplasia in humans,(1) rats,(2) cats,(3,4) dogs,(5) and horses.(6) The single case of equine LGL previously reported was aleukemic.(5) In contrast to this previous report of aleukemic equine LGL neoplasia, the leukemia in the case presented here established the antemortem diagnosis of LGL.     

Transplantation of large granular lymphocyte leukemia in congenitally athymic rats.

Twenty-two congenitally athymic nude (rnu/rnu) rats were transplanted with large granular lymphocyte leukemia derived from F344 rats and then compared with ten similar rats inoculated with a suspension of normal F344 rat spleen cells. The normal spleen cells and tumor cells from a spontaneous, naturally occurring leukemia did not grow or cause clinical disease in any of the rats. All rats inoculated with a serially passaged leukemia cell inoculum had local growth at the inoculation site that spread widely and resulted in progressive tumor growth. Death occurred between 16 and 38 days after inoculation. The 22 rats that received passaged tumor cells developed leukemia and splenomegaly. Spleens were diffusely infiltrated by tumor cells and had severe depletion of lymphocytes in the white pulp. Leukemic rats were thrombocytopenic and had hemolytic anemia characterized by increased osmotic fragility, red cell width, and many nucleated erythrocytes. The disease syndrome appears similar to that of F344 rats transplanted with the same inoculum. Because the host rats lacked T cells, it is concluded that the hemolytic anemia and thrombocytopenia that develop in transplanted rats are independent of T cell function.     

Serial syngeneic transplantation of large granular lymphocyte leukemia in F344 rats

A spontaneous large granular lymphocyte (LGL) leukemia was serially transplanted in 92 male F344 rats kept under standard laboratory conditions. Serial transplantation into groups of four rats each resulted in a rapid reduction in the latent period of the disease. After 23 serial transplantations, F344 rats in groups that were injected intraperitoneally with 10(7) cells died between 12 and 16 days after transplantation. At necropsy, "transplanted" rats had enlarged mesenteric lymph nodes, thymus, and spleen. Neoplastic cells were detected in the spleen on day 3 and in peripheral blood on day 6. Extreme leukocytosis with leukemia was present on day 9. Severe hemolytic anemia coincided with a sharp increase in osmotic fragility on day 12. Splenic lymphoid depletion was observed histologically and confirmed by differential cell counts of isolated spleen cells. Analysis for surface markers of splenic lymphocytes by monoclonal antibodies and flow cytometry indicated that cells with T helper/inducer phenotypes were disproportionately decreased, while the number of T suppressor cells did not significantly change. The T helper/T suppressor lymphocyte ratio (normal = 2.09 +/- 0.35) was decreased on day 9 (0.76 +/- 0.10) and day 12 (0.25 +/- 0.04). Hemolytic anemia was not related to a decrease in the number of T suppressor cells. The passaged leukemia cell model should provide investigators with an easily maintained neoplasm of short latency with which to study pathogenesis of leukemia-related disorders.     

Effects of large granular lymphocyte leukemia on bone in F344 rats

Large granular lymphocyte (LGL) leukemia was induced in 40 F344 rats by inoculating them with neoplastic cells to evaluate the effect of acute leukemia on bone remodeling and calcium balance. The rats developed leukemia and splenomegaly by 9 days after inoculation. The rats had reduced body weight (day 12), food intake (days 4, 8, 12), urine production (day 12), and fecal output (day 12). Serum calcium and phosphorus and urinary excretion of calcium and phosphorus were decreased on days 8 and 12 in leukemic rats. Static bone histomorphometry of trabecular bone in lumbar vertebrae demonstrated reduced bone area, no change in the number of osteoclasts, and reduced osteoclast perimeter at day 12. Dynamic bone histomorphometry revealed reduced double labeled perimeter, mineralizing perimeter, trabecular mineral appositional rate, and bone formation rate in rats with LGL leukemia at days 9 and 12. There was no change in periosteal mineral appositional rate. Rats with leukemia and intramedullary neoplastic cells had a reduction in bone formation rate that resulted in a loss of trabecular bone.     

The early stage of large granular lymphocyte leukemia in the F344 rat

In the early stages of large granular lymphocyte leukemia of F344 rats, splenic congestion and lymphocytic depletion of the splenic white pulp are the most significant and consistent histologic findings. The diagnosis of early leukemia was confirmed by immunocytochemical demonstration that the cell surface of leukemic large granular lymphocytes reacted with OX-8 monoclonal antibodies and by transplantation of the disease at early stages to healthy weanling rats.     

Large granular lymphocytic leukemia in a mixed breed dog

A mixed breed dog was diagnosed with large granular lymphocytic leukemia. Immunophenotypic analysis indicated the lymphocytes were CD3+, CD8+ T cells expressing the alpha beta T cell receptor and a leukointegrin, alpha d. Chemotherapy and splenectomy resulted in an initial reduction in the lymphocyte count.     

Large granular intestinal lymphosarcoma and leukemia in a dog

A rare, large granular lymphocyte (LGL) tumor causing a protein-losing enteropathy and thrombocytopenia was diagnosed in an Irish wolfhound. The case had an aggressive clinical course, like most LGL tumors in humans. Immunophenotyping suggested that the LGL tumor in this dog was derived from a natural-killer cell.     

Malignant transformation of an aneurysmal bone cyst in a dog

OBJECTIVE: To report malignant transformation of an aneurysmal bone cyst in a dog. STUDY DESIGN: Case report. SAMPLE POPULATION: Client-owned dog. RESULTS: A 5-year-old male Labrador retriever was diagnosed with an aneurysmal bone cyst of the distal aspect of the right ulna. Surgical curettage resulted in remission of clinical signs for 33 months. Because of recurrence of clinical signs, a distal ulnar ostectomy was performed. Histopathologic examination of the excised specimen revealed a moderately differentiated chondrosarcoma at the level of the bone cyst. Limb function was normal for 17 months until a subcutaneous mass, determined to be a chondrosarcoma, occurred at the level of the shoulder. A right forequarter amputation was performed. CONCLUSIONS: Aneurysmal bone cysts are benign but may be transformed into a malignancy after surgical manipulation. Complete surgical excision should be attempted where possible. In this case, distal ulnar ostectomy was an effective means of preserving limb function and preventing local recurrence of chondrosarcoma.     

Spleen cell population changes and hemolytic anemia in F344 rats with large granular lymphocyte leukemia

A spontaneous large granular lymphocyte leukemia from a F344 rat was transplanted to 36 syngeneic recipients to study the interactions among leukemia, T lymphocytes, and the development of immunemediated hemolytic anemia. Six rats were euthanatized at biweekly intervals, and spleen weight, total spleen cellularity, and differential spleen cell counts were correlated with hemograms and osmotic fragility. Sequential changes in splenic architecture were correlated with hematologic parameters. Monoclonal antibodies defining all T lymphocytes (W3/13), T helper-inducer cells (W3/25), and T suppressor cells (OX-8) were used to identify T cells in immunocytochemical techniques on spleen sections, as well as in fluorescence activated cell sorter analysis of spleen cell suspensions. The onset of hemolytic anemic at 7 weeks after transplantation coincided with the first detection of tumor cells in the spleen and peripheral blood. Tumor cells first accumulated in the marginal zones, and then they infiltrated the red pulp sinusoids. Although the leukemia caused dispersion of the splenic lymphoid tissue, there was no significant lymphopenia, and the relative number of helper (W3/25+) and suppressor (OX-8+) lymphocytes did not change. Because the induction of anemia was a relatively early event in splenic involvement, we concluded that anemia was unrelated to disruption of lymphoid architecture; furthermore, it does not appear to be caused by changes in the numbers of regulatory T lymphocytes.     

Tumor staging in a Beagle dog with concomitant large B-cell lymphoma and T-cell acute lymphoblastic leukemia

An 8-y-old spayed female Beagle dog was presented with peripheral lymphadenomegaly. Lymph node cytology and flow cytometry led to the diagnosis of large B-cell lymphoma (LBCL). We detected minimal percentages of LBCL cells in peripheral blood and bone marrow samples. However, a monomorphic population of neoplastic cells different from those found in the lymph node was found in the bone marrow. T-cell acute lymphoblastic leukemia was suspected based on flow cytometric immunophenotyping. PCR for antigen receptor rearrangement (PARR) revealed clonal rearrangement of both B-cell and T-cell receptors, and the presence of both neoplastic clones in the lymph node, peripheral blood, and bone marrow. The dog was treated with multi-agent chemotherapy but died 46 d following diagnosis. Tumor staging and patient classification are needed to accurately establish a prognosis and select the most appropriate therapeutic protocol.     

Malignant transformation of a giant congenital pigmented nevus (hamartoma) in a dog

A male Golden Retriever was born with a large area of abnormal skin and hair on the distal pelvic limb. A tumour arose from the proximal margin of this area at 5 years of age. Histopathological examination of the abnormal area of skin revealed an area in which follicles were surrounded by nodular accumulations of densely packed round to spindle-shaped cells with fine granular intracytoplasmic melanin. Similar cells were present within the subcutaneous fat, and clusters of densely pigmented melanocytes were scattered within the basal epidermis, follicular epithelium, and dermis. A diagnosis of giant congenital pigmented nevus (hamartoma) was made. The tumour from the proximal end of this area was composed of densely packed, moderately pleomorphic, poorly differentiated and pigmented, spindle-shaped to epithelioid melanocytes, and was diagnosed as malignant melanoma. Metastasis of the malignant melanoma to the stifle and inguinal regions occurred within 6 months. To date, the authors are unaware of prior reports of a canine giant congenital pigmented nevus (hamartoma) with transformation to a malignant melanoma.     

A case of hemophagocytic syndrome progressing into large granular lymphoma in a dog

A 12‐year‐old castrated male mixed breed dog was presented with anorexia, lethargy, intermittent vomiting, diarrhea, and weight loss. Clinicopathologic and imaging abnormalities included pancytopenia, icterus, and splenomegaly with multiple minute hypoechogenic nodules. Bone marrow (BM) smears revealed 2.5% hemophagocytic macrophages. In addition, an increased number of small to intermediate lymphocytes (16.3%) and plasma cells (3.2%) were recognized in the BM smears. More than 80% of the lymphocytes contained multiple small intracytoplasmic magenta granules. Histopathologic findings of the spleen revealed hemophagocytosis. Large granular lymphocytes (LGLs) were not found on the liver cytology or splenic histopathology at this time. PCR for antigen receptor rearrangement (PARR) analysis showed a clonal reaction in the T‐cell receptor ? (TCR?) gene in the BM sample. The dog was diagnosed with hemophagocytic syndrome (HPS). The dog was maintained in good condition with immunosuppressive therapy. However, the dog developed hepatic LGL lymphoma 7 months later. At this time, PARR analysis showed a clonal TCR? gene rearrangement in the hepatic LGL lymphoma samples. The BM and liver sample clonal rearrangements showed 100% homology, indicating that the small to intermediate granular lymphocytes in the BM at the HPS stage had progressed to hepatic LGL lymphoma. To our knowledge, this is the first report of canine secondary HPS caused by the occurrence of a BM LGL lymphoma clone that progressed to hepatic LGL lymphoma.     

Development of high-grade B-cell lymphoma concurrent with T-cell chronic lymphocytic leukemia in a dog

Second malignancies are frequent complications in human patients with chronic lymphocytic leukemia (CLL). However, the clinical details and outcome of this phenomenon were unclear in their canine counterparts. Here, we report a dog with high-grade lymphoma concurrent with T-cell CLL. A 10-year-old male golden retriever presented with lymphadenopathies. The lymph nodes contained large-sized lymphocytes, raising suspicion of high-grade lymphoma. Meanwhile, small lymphocytic lymphocytosis in the peripheral blood was consistent with CLL. Interestingly, molecular biological analyses revealed that CLL cells were of the T-cell type, whereas lymphoma cells were of the B-cell type. Chemotherapy using the L-VCA short protocol was effective for 155 days, but the dog died on day 194 after diagnosis, despite rescue therapies.