Thymic lymphosarcoma of T cell lineage in a koala (Phascolarctos cinereus)

Objective To diagnose and characterise thymic lymphosarcoma in a koala.
Design A pathological case.  

Animal

Seven-year-old female koala.
Procedure The neoplastic process was investigated macroscopically, haematologically, histologically and immunohistologically.
Results The koala had difficulty swallowing because of a medial swelling in the lower neck. Biopsy of this mass and blood examination revealed lymphosarcoma with a leukaemic manifestation; necropsy and histopathological examination showed the mass to be thymus. Palatine tonsils, cervical, axillary and mesenteric lymph nodes, spleen, liver, gut, bronchi, genitalia and bone marrow were infiltrated by neoplastic cells. Immunohistological staining of the thymic mass, cervical and mesenteric lymph nodes, bone marrow, spleen and gut revealed the neoplastic cells to be of T lymphocyte origin (positive for both anti-human CD3 and CD5).  

Conclusions

It is speculated that the neoplastic process originated in the thymus and was disseminated by bloodborne neoplastic cells: This first report of thymic lymphosarcoma in a marsupial confirms that antibodies raised originally to investigate human lymphoid neoplasia can cross-react with neoplastic lymphocytes in koalas.     

Spontaneous Malignant T-cell Lymphoma in a Young Adult Crl:CD (SD) Rat

We investigated a case of spontaneous malignant T-cell lymphoma observed in a 19-week-old male Crl:CD (SD) rat. The rat showed paralysis beginning 1 week before euthanasia. Hematological examination revealed marked lymphocytosis without distinct atypia. Macroscopically, hepatosplenomegaly and partial atrophy of the thoracic spinal cord were observed. Microscopically, neoplastic cells infiltrated into the liver, splenic red pulp, bone marrow and epidural space of the thoracic spinal cord, while no neoplastic cells were observed in the thymus and lymph nodes. Moreover, the spinal cord showed focal degeneration due to compression by marked infiltration of neoplastic cells in the subdural space. The neoplastic cells were generally small-sized round cells that had a round nucleus with/without a single nucleolus and scanty cytoplasm. Immunohistochemically, the neoplastic cells were positive for CD3 and CD8 and negative for CD79α. Judging from these results, the present tumor in this young adult rat was diagnosed as malignant T-cell lymphoma.     

Diagnosis and treatment of chronic T-lymphocytic leukemia in a spotted hyena (Crocuta crocuta).

Physical examination of an asymptomatic 20-yr-old intact female spotted hyena (Crocuta crocuta) revealed a midabdominal mass. A complete blood count (CBC) revealed peripheral lymphocytosis. Abdominal ultrasonography and laparoscopy confirmed severe splenomegaly. Cytologic examination of a bone-marrow core and histologic examination of spleen and liver biopsy samples revealed neoplastic small lymphocytes. Immunohistochemical staining of liver and spleen samples with the use of leukocyte-specific monoclonal antibodies showed that the neoplastic lymphocytes were immunoreactive to T-lymphocyte CD3 receptor and immunonegative to B-lymphocyte CD79a receptor. The morphology and distribution of neoplastic T-lymphocytes within the spleen, liver, peripheral blood, and bone marrow was most consistent with chronic T-lymphocytic leukemia. Treatment with chlorambucil and prednisone effectively decreased the lymphocyte count, but was associated with thrombocytopenia, which resolved after chlorambucil treatment was temporarily discontinued. Chemotherapy was resumed with a single dose of L-asparaginase, followed by a lower dosage of chlorambucil and continued prednisone. Two years after initial diagnosis, the hyena developed a hemoabdomen and was euthanized. Neoplastic T-lymphocytes were present in spleen, liver, visceral and peripheral lymph nodes, lungs, heart, kidney, adrenal glands, mesentery, intestines, pancreas, brain, and bone marrow.     

Malignant Lymphoma with Severe Infiltrative Growth into Skeletal Muscles in WBN/Kob Rats

Although spontaneously occurring neoplasms have been reported repeatedly in F344, SD and Wistar rats, which are commonly used strains for routine toxicologic and carcinogenicity studies, there are only a few reports of malignant lymphoma or lymphatic leukemia except for large granular lymphocytic leukemia (LGL) in F344 rats. Malignant lymphoma (lymphosarcoma) is thought to be uncommon in F344 rats. The authors encountered malignant lymphomas of the non-LGL leukemia type with characteristic pathologic features in WBN/Kob rats. The mean age at onset of the disease in all 13 affected rats (8 males and 5 females) was about 60 weeks. Common and characteristic clinical signs were abnormal gait with hind limb paralysis. Macroscopically, the enlargement of the lymph nodes, spleen and liver was slight to moderate. Scattered multiple white-to-gray nodules encompassed the aorta and assumed a bead-like appearance near the thoracic and lumbar vertebrae. Histopathologically, neoplastic proliferative changes were predominant in the bone marrow tissue of the entire body, and many tumor cells infiltrated the spleen and several lymph nodes. The most striking histological features were constant and severe infiltration of tumor cells in the adipose tissue and skeletal muscle adjacent the thoracic and lumber vertebrae. Immunohistochemically, all tumor cells were positive for B-cell markers (PAX-5, CD79a and CD45) and negative for CD3. From the results of immunohistochemistry and morphological examination, these tumors were diagnosed as malignant B-cell lymphomas.     

Disseminated histiocytic sarcoma with peripheral blood involvement in a Bernese Mountain dog

Abstract: A 6‐year‐old Bernese Mountain dog was presented with a history of lethargy and weight loss of 2 weeks duration. On physical examination the dog had pale mucous membranes and tachypnea. Ultrasound examination revealed hepatomegaly, splenomegaly, and mesenteric lymphadenomegaly. Results of a CBC included marked normocytic normochromic nonregenerative anemia, marked thrombocytopenia, and moderate leukocytosis with mild neutrophilia and a large population of unclassified round cells (6.2 × 10³/μL). The unclassified cells occasionally were bi‐ or multinucleated and had variably abundant pale basophilic cytoplasm that contained multiple irregular clear vacuoles and occasionally erythrocytes. Fine needle aspirate specimens of the mesenteric lymph nodes and spleen were composed of a population of round pleomorphic cells with the same features as the circulating cells. On flow cytometric analysis of peripheral blood, the unclassified cells expressed CD18, CD45, CD11c, CD1c, and CD14; immunocytochemical analysis of blood smears also indicated the cells were positive for CD1c, CD1a, and CD11c. The dog died a few hours after referral. The histologic interpretation of samples collected from spleen, liver, and lymph nodes was malignant neoplasia of histiocytic origin. Immunohistochemical staining yielded negative results for CD11d, a marker of red‐pulp macrophages, ruling out hemophagocytic histiocytic sarcoma. Based on clinical and pathologic findings, the final diagnosis was disseminated histiocytic sarcoma (DHS) with peripheral blood involvement. To our knowledge, DHS in a dog with evidence and immunophenotyping of neoplastic cells in peripheral blood has been reported only rarely.     

Precursor B-1 B cell lymphoma in a newborn calf.

A newborn Holstein female calf had neoplastic lesions in the skin and within the thoracic and abdominal cavities but not in the bone marrow, spleen, thymus, or most lymph nodes. Because the tumor cells were positive for CD79a (B cell marker), CD5 (B-1 cell marker) and terminal deoxynucleotidyl transferase (marker for immature lymphoid precursors), a diagnosis of precursor B-1 B cell lymphoma was made. The diagnosis was strongly supported by the fact that B-1 cells can develop in the fetus, unlike B-2 cells, which are produced after birth. The lymphoma was distinct from the typical calf form of lymphoma of B-2 cell origin, which does not express CD5 and is characterized by generalized lymphadenopathy and involvement of the bone marrow, blood and spleen.     

Monitoring of large B-cell lymphoma and T-zone lymphoma in a dog via flow cytometry

A 12-y-old, castrated male Pomeranian dog was presented because of mandibular lymph node (LN) enlargement. Physical examination and a complete blood count revealed generalized lymphadenopathy and moderate lymphocytosis. Fine-needle aspirate cytology revealed expansion of medium lymphocytes in the right mandibular LN and expansion of large lymphocytes in the left popliteal LN. Flow cytometry identified 2 aberrant lymphocyte populations in both LNs, namely a CD5+CD45− T-cell population, and a large CD21+ B-cell population. Flow cytometry of the peripheral blood revealed an identical population of aberrant CD45− T cells. The patient was diagnosed with concurrent T-zone lymphoma and leukemia, and B-cell lymphoma. Multi-agent chemotherapy was instituted, and serial clinical and flow cytometric analysis revealed complete remission of the neoplastic B cells, but persistence of the neoplastic T cells and persistent lymphadenopathy. This case affirms the diagnostic value of flow cytometry and reveals a unique limitation of the RECIST criteria.     

Detection of retinoid receptors in non-neoplastic canine lymph nodes and in lymphoma

This study evaluated the difference in retinoid receptor expression between non-neoplastic lymph nodes and nodal lymphoma in dogs. Retinoid receptor expression was evaluated by immunohistochemistry in 32 canine lymph nodes. The lymph nodes had been previously diagnosed as non-neoplastic (6 normal and 7 hyperplastic lymph nodes) and B- and T-cell lymphoma (19 cases). Immunohistochemistry for retinoic acid receptors and retinoid-X receptors (and their subtypes α, β, and γ) was performed in all cases. In addition, immunohistochemistry for CD3 and CD79a was performed in all lymphoma cases. Non-neoplastic lymphocytes were negative for all retinoid receptors. Retinoic acid receptor-γ was detected in 100% of B-cell lymphoma and 78% of T-cell lymphoma, while retinoid X receptor-γ was positive in 78% of T-cell lymphoma cases. When normal lymph node architecture was still present, a contrast between retinoid-negative benign cells and retinoid-positive malignant cells was clear. Retinoid receptors were expressed in neoplastic, but not in benign lymphocytes, suggesting their value for both diagnosis and treatment of canine lymphoma.     

T-cell-rich B-cell lymphoma in a ring-tailed lemur (Lemur catta).

A 13-yr-old ring-tailed lemur (Lemur catta) was evaluated for depression, anorexia, polyuria, and polydipsia. The lemur was in poor body condition and was anemic, hypoalbuminemic, and hyponatremic. Cytologic examination of aspirates of the spleen, liver, and bone marrow and histopathologic examination of liver and bone marrow biopsies revealed a disseminated round cell tumor. After euthanasia, necropsy revealed hepatomegaly, splenomegaly, and mesenteric lymphadenomegaly. Neoplastic cells were present within the spleen, liver, kidneys, multiple lymph nodes, bone marrow, lung, small intestine, pancreas, and testicle and were composed of large anaplastic round cells in a background of small well-differentiated lymphocytes. Immunohistochemical analysis revealed that the small well-differentiated lymphocytes labeled for the anti-human T-cell marker, CD3, and the large anaplastic round cells labeled with the anti-human B-cell marker, CD79a. On the basis of the immunohistochemical staining results and morphologic appearance, a diagnosis of a T-cell-rich B-cell lymphoma was made.     

Influence of bestatin, an inhibitor of aminopeptidases, on T and B lymphocyte subsets in mice

Bestatin, a low-molecular weight dipeptide, is a potent inhibitor of aminopeptidase N which has been demonstrated to have antitumor and immunomodulatory effects. The effects of bestatin (10, 1 and 0.1 mg/kg) administered intraperitoneally once, five or ten times to mice on the total number of lymphocytes in the thymus, spleen and mesenteric lymph nodes and the percentage and the absolute number of T cell subsets (CD4+CD8+, CD4-CD8-, CD4+, CD8+) in the thymus and T (CD3+, CD4+, CD8+) and B (CD19+) lymphocytes in the spleen and mesenteric lymph nodes were studied. It has been found that bestatin administered ten times at doses of 10, 1 and 0.1 mg/kg increased the total number of thymocytes, splenocytes and lymphocytes of mesenteric lymph nodes. Bestatin also changed the percentage and the absolute number of T cell subsets in the thymus and T and B lymphocytes in the peripheral lymphatic organs. Five and ten exposures to bestatin (10, 1 and 0.1 mg/kg) increased the absolute count of both immature CD4+CD8+ and CD4-CD8- thymic cells. Moreover, both a single and multiple administration of bestatin (1 and 0.1 mg/kg) decreased the percentage and absolute count of CD3+ splenocytes and mesenteric lymph node cells with corresponding decreases in the percentage and absolute count of CD4+ and CD8+ cells. Both a single and multiple administration of bestatin at all the doses under investigation augmented the percentage and the absolute count of CD19+ (B lymphocytes) in the peripheral lymphatic organs. The results of the study show that there is a relationship between the effect induced by bestatin and the dose of the drug as well as the number of doses applied. The strongest effect on the T and B lymphocyte subsets was noted after five injections of bestatin at doses of 1 and 0.1 mg/kg.     

Feline large granular lymphocyte (LGL) lymphoma with secondary leukemia: primary intestinal origin with predominance of a CD3/CD8(alpha)(alpha) phenotype

Clinicopathologic and immunophenotypic characteristics of large granular lymphocyte (LGL) neoplasia in 21 cats were examined. All cats were domestic short (19) or long hair (2) with a mean age of 9.3 years at diagnosis. Increased peripheral blood LGL counts were present in 18/21 cats. Neutrophilia (12/21 cats) and increased serum liver enzymes (7/12), total and direct bilirubin (7/13), BUN (5/14), and creatinine (2/14) were observed. Cats usually presented with advanced disease and none survived longer than 84 days (mean 18.8 days) postdiagnosis. Cytologically, LGLs had a mature (6/21), immature (13/21), or mixed (2/21) morphology. Necropsy lesions consisted of neoplastic lymphoid infiltrates in the jejunum, ileum, and duodenum in decreasing order of frequency. In the small intestine, mucosal ulceration (9/13) and epitheliotropism of neoplastic cells (9/13) were common. Neoplastic infiltrates were also present in the mesenteric lymph nodes (13/13), liver (12/13), spleen (8/13), kidneys (5/7), and bone marrow (5/7). A T cell phenotype (CD3epsilon+) characterized LGL neoplasia in 19/21 cases. A CD8alphaalpha+ cytotoxic/suppressor phenotype was present in 12/19 T cell tumors, 2 had a CD4+CD8alphaalpha phenotype, 3 had a CD4-CD8- phenotype, and 2 were CD4+ helper T cells. CD8beta chain expression was not detected in any instance. In two cats, a B or T cell origin could not be established. CD103 was expressed by 11 of 19 (58%) of the lymphomas tested. The immunophenotypic features shared by neoplastic LGLs in the cat and feline intestinal intraepithelial lymphocytes (IELs) support a small intestinal IEL origin for feline LGL lymphoma.     

Intestinal T-cell lymphoma with severe hypereosinophilic syndrome in a cat

A Japanese domestic long-hair cat of about 8 years of age was presented with vomiting and hematochezia and was found to have significant hypereosinophilia. Bone marrow aspiration revealed moderate increases of eosinophilic lineages. Histopathological examination revealed mild eosinophilic and epitheliotropic T-lymphocytic infiltrations in the duodenum. Although the cat remained asymptomatic with only prednisolone administration, the cat presented with hematemesis, weight loss, and severe anorexia 512 days after the initial presentation. Subsequently, gastrointestinal perforation developed, and the cat died on Day 536. Histopathological examination of autopsy specimens revealed mixed cellular infiltration including eosinophils and neoplastic lymphocytes in the intestinal lymph nodes, intestine, liver, spleen, and pancreas. Immunohistochemical examination supports a diagnosis of intestinal T-cell lymphoma with severe hypereosinophilic syndrome.     

CD34+, CD41+ acute megakaryoblastic leukemia in a dog

A clinically normal, 5-year-old intact female German Shepherd dog was presented to the local veterinarian to be spayed. Results of a preoperative CBC included mild nonregenerative anemia, severe thrombocytopenia, and 17% unclassified cells. On cytologic examination of aspirates from the dog's enlarged spleen and peripheral lymph nodes, a population of primitive round cells that occasionally resembled megakaryocytes was observed. A bone marrow aspirate specimen was markedly hypercellular with approximately 65% of marrow cells comprising a homogeneous population of immature hematopoietic cells similar to those found in the spleen, lymph nodes, and peripheral blood. Using immunocytochemical stains with canine-specific antibodies, all neoplastic cells strongly expressed cytoplasmic CD41 and 20-70% of the neoplastic cells expressed CD34 weakly to moderately. Rare (<0.5%) neoplastic cells weakly expressed vWF. The cells were negative for all other markers. Based on these results and the morphology of the neoplastic cells, a diagnosis of acute megakaryoblastic leukemia (AMegL) was made. In spite of treatment, results of a CBC performed 1 week later indicated progressive anemia and thrombocytopenia, and the dog was euthanized. To our knowledge, this report documents the first case of canine AMegL diagnosed with both anti-canine CD34 and CD41 antibodies.     

Multicentric t-cell lymphoma in a dromedary camel (Camelus dromedarius).

A 7-yr-old female dromedary camel (Camelus dromedarius) was evaluated for inappetence, weight loss, polyuria, and polydipsia. The animal did not respond to antibiotic and supportive therapy, became recumbent, and died. Gross examination revealed nodules in the liver, mesenteric and perirenal lymph nodes, and both kidneys, with segmental thickening of the small intestine. Histopathologic examination revealed multifocal lymphoma with moderate mitotic activity. Immunohistochemical staining of neoplastic cells was uniformly CD3-positive, indicating a T-cell lymphoma.     

What is your diagnosis? Cervical mass in a cat

An 8-year-old female spayed domestic shorthair cat was presented for several months of weight loss, decreased appetite, and 2 bilateral, ventral cervical masses. Initial cytologic samples were interpreted as reactive lymphoid hyperplasia. Evaluation of subsequent mass aspirates revealed small numbers of large binucleated and multinucleated cells resembling Reed-Sternberg cells admixed with more numerous small and intermediate-sized lymphocytes. In histopathologic sections, the normal architecture of the lymph node was largely effaced by a slightly heterogeneous mass composed of round cells arranged in densely cellular sheets with a minor population of large (25-mum diameter) mononuclear cells and a few very large (30-40-mum diameter) binucleated or multinucleated cells interpreted as Reed-Sternberg-like cells. Immunohistochemically, the large neoplastic (Reed-Sternberg-like) cells were negative for CD18, CD3, CD20, and CD79a while the background population consisted of about 70% T cells and 30% B cells. This pattern of immunohistochemical staining along with cytologic and histopathologic findings supported a diagnosis of Hodgkin's-like lymphoma, specifically, the lymphocyte-rich subtype. Hodgkin's-like lymphoma has been reported previously in cats and should be suspected when Reed-Sternberg-like cells are observed in cytologic preparations of lymph node aspirates. Histopathology and immunohistochemistry are necessary for a definitive diagnosis.     

Hepatosplenic lymphoma in a dog

We describe a case of a dog with hepatosplenic lymphoma, a disease characterized by infiltration of the liver, spleen, and bone marrow with gammadelta T cells, absence of peripheral lymphadenopathy, and an aggressive clinical course. Physical examination findings, hematologic and biochemical abnormalities, and clinical course of the disease in this patient were similar to those in humans. Immunophenotyping of liver and spleen aspirates supported an antemortem diagnosis of T-cell lymphoma consistent with hepatosplenic lymphoma. The diagnosis was confirmed postmortem by a combination of routine histopathology, showing a consistent pattern of organ involvement, and immunohistochemistry showing the infiltrating neoplastic lymphocytes to be T cells expressing the gammadelta T-cell receptor. To our knowledge, this is the first reported case of hepatosplenic lymphoma in a dog.     

Influence of betulinic acid on lymphocyte subsets and humoral immune response in mice

Betulinic acid is a pentacyclic triterpene found in many plant species, among others, in the bark of white birch Betula alba. Betulinic acid was reported to display a wide range of biological effects, including antiviral, antiparasitic, antibacterial, anticancer and anti-inflammatory activities. The effects of betulinic acid (50, 5, 0.5 mg/kg) administered orally five times at 24 hours intervals to non-immunized and red blood cells (SRBC)-immunized mice were determined. The present study examined the total number of lymphocytes in the thymus, spleen and mesenteric lymph nodes, and the percentage of subsets of T cells (CD4+CD8+, CD4CD8, CD4+, CD8+) in thymus,T (CD3+, CD4+, CD8+) and B (CD19+) lymphocytes in the spleen and mesenteric lymph nodes, as well as white blood cell (WBC) and differential leukocyte counts in non-immunized mice, and humoral immune response in SRBC-immunized mice. SRBC was injected 24 hours after administration of the last dose of betulinic acid. It was found that betulinic acid administered orally five times at the dose of 0.5 mg/kg increased the total number of thymocytes, splenocytes, lymphocytes of mesenteric lymph node cells, and the weight ratio of the spleen and mesenteric lymph nodes in non-immunized mice. Betulinic acid also changed the percentage of T cell subsets in the thymus and T and B lymphocytes in peripheral lymphatic organs. The effects of betulinic acid on T and B cell subpopulations depended on the dose applied. The strongest stimulating effect of betulinic acid was observed when the drug was administered at the dose of 0.5 mg/kg. Five exposures to betulinic acid (0.5 mg/kg) decreased the percentage of immature CD4+CD8+ thymic cells with corresponding increases in the percentage and absolute count of mature, single-positive CD4+ thymocytes and decreased the percentage and total count of CD3+ splenocytes and mesenteric lymph node cells with corresponding decreases in the percentage and absolute count of CD4+ and CD8+ cells. Multiple administration of betulinic acid at the investigated doses augmented the percentage and absolute count of CD19+ cells in the peripheral lymphatic organs. Moreover, betulinic acid at the dose of 5 mg/kg administered prior to SRBC immunization increased the number of plaque forming cells (PFC) but decreased the production of anti-SRBC antibodies on day 4 after priming. Thus, betulinic acid is a potential biological response modifier and may strengthen the immune response of its host.     

Theileria parva infection in calves causes massive lymphocyte death in the thymus, spleen and lymph nodes without initial proliferation

In a study of trends and magnitudes of lymphocytes proliferation, destruction or apoptosis eleven 3-month-old healthy calves were experimentally infected with the protozoan parasite Theileria parva, which is reported to cause lymphocyte proliferation. Four control calves were not infected. Infected and non-infected calves were sacrificed on days 9, 12, 16, 19, 23, 24 and 25 to examine lymphoid tissue changes and lymphocyte proliferation, apoptosis or necrosis in the thymus, spleen and lymph nodes. All infected calves developed severe East Coast fever, with enlargement of lymph nodes, dyspnoea, high fever and pulmonary oedema. Lymphocyte proliferation was not observed in lymph nodes, thymus and spleen; instead there were massive deaths of lymphocytes and other cells. The terminal severe disease caused massive lymphoid parenchyma coagulation terminating with caseation, organs and cells being undeterminable histologically. Tissues surrounding the lymph nodes were oedematous. Lymph node and thymus parenchyma were caseated and cortices and medulla indistinguishable because of severe lymphocyte and accessory cell deaths. The lymph node fibrous reticular stroma was necrotic and caseated. Lymphoid follicles in lymph nodes degenerated and lacked germinal centres. Lymph nodes, spleen and thymus were grossly enlarged, hardened, potato or cheese like, but microscopically very hypocellular and in the terminal disease acellular because of massive lymphocytes destruction. In the thymus there was extensive thymocyte and epithelioid cell necrosis and loss of distinction between cortex and medulla. The spleen white and red pulps were indistinguishable because of extensive lymphoid cell necrosis. The white pulp degenerated more than the red pulp. The massive lymphocyte deaths in the lymph nodes, thymus and spleen, without lymphocyte proliferation in this T. parva infection in calves leads to a conclusion that this parasite is lympho-destructive and lympho-degenerative in vivo rather than lympho-proliferative.     

Hypereosinophilic paraneoplastic syndrome in a cat with intestinal T cell lymphosarcoma

A 10-year-old, neutered female, domestic shorthair cat was presented with a recent history of weight loss, polydipsia, diarrhoea and vomiting. On physical examination, intestinal thickening and mesenteric lymph node enlargement were apparent. Clinical investigations revealed peripheral blood eosinophilia, eosinophilic abdominal effusion and eosinophilic mesenteric lymphadenitis. There was a temporary response to treatment with glucocorticoids but signs progressed and the cat was euthanased. On histology, there was eosinophilic infiltration and fibroplasia of intestine and mesenteric lymph nodes. Large aggregates of neoplastic round cells in the intestine and lymph nodes were identified as T lymphocytes using immunohistochemistry. A diagnosis of intestinal T cell lymphosarcoma was made. This case demonstrates that hypereosinophilic paraneoplastic syndrome may occur in cats with lymphosarcoma. Eosinophil chemotaxis may be a response to the production of interleukin-5 by neoplastic lymphocytes.