Oncogenes in normal and neoplastic lymphocytes

A calf with a lymphoproliferative disease resembling human mycosis fungoides, had multiple, ulcerated skin nodules with enlarged regional lymph nodes. Tumor cells were 10–15 μm in diameter and had round to oval nuclei without indentations. Mitoses were regularly present. Pautrier's microabscesses were in the epidermis, and T-cell areas of regional lymph nodes were infiltrated by neoplastic cells. Demonstration of the T-helper/inducer origin of neoplastic lymphocytes suggested classification in analogy with human mycosis fungoides.

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Emperipolesis-like Invasion of Neoplastic Lymphocytes into Hepatocytes in Feline T-cell Lymphoma

Journal of Comparative Pathology ◽

10.1016/j.jcpa.2010.10.005 ◽

2011 ◽

Vol 144 (4) ◽

pp. 312-316 ◽

Cited By ~ 8

Author(s):

M. Suzuki ◽

Y. Kanae ◽

Y. Kagawa ◽

N. Ano ◽

K. Nomura ◽

...

Keyword(s):

T Cell ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Neoplastic Lymphocytes

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Malignant lymphoma with middle ear involvement in a Sprague-Dawley rat

Laboratory Animals ◽

10.1177/0023677218764768 ◽

2018 ◽

Vol 52 (4) ◽

pp. 418-423

Author(s):

Jean-Francois Lafond ◽

Annick Landry

Keyword(s):

Malignant Lymphoma ◽

Temporal Bone ◽

Middle Ear ◽

Chorda Tympani ◽

Sprague Dawley ◽

Sprague Dawley Rat ◽

Sprague Dawley Rats ◽

Microscopic Evaluation ◽

Neoplastic Lymphocytes ◽

Tensor Tympani Muscle

Sprague-Dawley rats are amongst the most widely used animals in biomedical research and malignant lymphoma has long been known to be a frequent neoplasm in these animals. A 9-month-old male control Sprague-Dawley rat from a toxicity study showed gelatinous material in the cranial cavity and dark, thickened cerebral meninges at necropsy. At microscopic evaluation of the temporal bone, neoplastic lymphocytes were seen invading several structures of the middle ear. The neoplastic cells appeared to extend from the marrow of the temporal bone, covered the dorsal part of the tympanic cavity wall, and surrounded and infiltrated the base of the tensor tympani muscle as well as the chorda tympani branch of the facial nerve. The lymphoma was generalized; neoplastic lymphocytes were also noted in numerous other tissues. Literature regarding neoplasms of the middle and inner ear in animals is scarce and, to our knowledge, this is the first report of a lymphoma involving the middle ear of a rat.

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Morphologic and Immunohistochemical Characterization of Spontaneous Lymphoma/Leukemia in NSG Mice

Veterinary Pathology ◽

10.1177/0300985819882631 ◽

2019 ◽

Vol 57 (1) ◽

pp. 160-171 ◽

Cited By ~ 4

Author(s):

Heather Tillman ◽

Laura J. Janke ◽

Amy Funk ◽

Peter Vogel ◽

Jerold E. Rehg

Keyword(s):

T Cell ◽

Core Protein ◽

Laboratory Mouse ◽

Interleukin 2 ◽

Low Frequency ◽

Nsg Mice ◽

Severe Immunodeficiency ◽

Neoplastic Lymphocytes ◽

Strong Immunoreactivity

The NOD.Cg- Prkdcscid Il2rgtm1Wjl/SzJ strain (NOD scid gamma, NSG) is a severely immunodeficient inbred laboratory mouse used for preclinical studies because it is amenable to engraftment with human cells. Combining scid and Il2rgnull mutations results in severe immunodeficiency by impairing the maturation, survival, and functionality of interleukin 2–dependent immune cells, including T, B, and natural killer lymphocytes. While NSG mice are reportedly resistant to developing spontaneous lymphomas/leukemias, there are reports of hematopoietic cancers developing. In this study, we characterized the immunophenotype of spontaneous lymphoma/leukemia in 12 NSG mice (20 to 38 weeks old). The mice had a combination of grossly enlarged thymus, spleen, or lymph nodes and variable histologic involvement of the bone marrow and other tissues. All 12 lymphomas were diffusely CD3, TDT, and CD4 positive, and 11 of 12 were also positive for CD8, which together was consistent with precursor T-cell lymphoblastic lymphoma/leukemia (pre-T-LBL). A subset of NSG tissues from all mice and neoplastic lymphocytes from 8 of 12 cases had strong immunoreactivity for retroviral p30 core protein, suggesting an association with a viral infection. These data highlight that NSG mice may develop T-cell lymphoma at low frequency, necessitating the recognition of this spontaneously arising disease when interpreting studies.

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Acute bilateral trigeminal neuropathy associated with nervous system lymphosarcoma in a dog

Journal of the American Animal Hospital Association ◽

10.5326/15473317-36-1-57 ◽

2000 ◽

Vol 36 (1) ◽

pp. 57-61 ◽

Cited By ~ 26

Author(s):

AM Pfaff ◽

PA March ◽

C Fishman

Keyword(s):

Nervous System ◽

Histopathological Examination ◽

Clinical Signs ◽

Neoplastic Cell ◽

Brain Parenchyma ◽

Spinal Root ◽

Trigeminal Neuropathy ◽

Neoplastic Lymphocytes ◽

Multicentric Lymphoma ◽

Masseter Muscles

A nine-year-old dog presented with clinical signs consistent with bilateral trigeminal neuropathy. Multicentric lymphoma was diagnosed, and neoplastic lymphocytes were identified in the cerebrospinal fluid. Electromyography revealed spontaneous activity in temporal and masseter muscles. Histopathological examination demonstrated neoplastic cell invasion of temporal and masseter myofibers and of multiple peripheral nerves, including the trigeminal nerve. Central nervous system pathology consisted primarily of spinal root and leptomeningeal lymphoid cell infiltration with relative sparing of spinal cord and brain parenchyma.

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Erythropoietin for the treatment of anemia of malignancy associated with neoplastic bone marrow infiltration.

Journal of Clinical Oncology ◽

10.1200/jco.1990.8.6.956 ◽

1990 ◽

Vol 8 (6) ◽

pp. 956-962 ◽

Cited By ~ 106

Author(s):

W Oster ◽

F Herrmann ◽

H Gamm ◽

G Zeile ◽

A Lindemann ◽

...

Keyword(s):

Bone Marrow ◽

Bolus Injection ◽

Bone Marrow Involvement ◽

Serum Levels ◽

Underlying Disease ◽

Bone Marrow Infiltration ◽

Low Grade ◽

History Of ◽

Neoplastic Lymphocytes ◽

Rbc Count

This clinical trial was performed to study the effects of intravenously (IV) administered recombinant human (rh) erythropoietin (EPO) at escalating doses (150, 300, and 450 U/kg, administered as an IV bolus injection, twice weekly, for 6, 4, and 4 weeks, respectively) in five patients with low-grade non-Hodgkin's lymphoma (Ig NHL) and bone marrow involvement and one patient with multiple myeloma (MM). All patients were anemic due to underlying disease. None of the patients had a history of bleeding, hemolysis, renal insufficiency, or other disorders causing anemia in addition to bone marrow infiltrating malignancy. Endogenous EPO serum levels were significantly increased in all patients (74 to 202 mU/mL). Five patients (one MM, four small-cell lymphocytic [SCLC] NHL) showed a dramatic increase of hemoglobin (Hb), hematocrit (Hk) and RBC count becoming obvious on the second EPO dose level. Initial ferritin serum values, which were high mostly due to polytransfusion, were significantly reduced in responding patients. Erythropoiesis of one patient with extensive follicular mixed (fm) NHL did not respond to EPO treatment. Platelet (PLT) count increase (greater than 75% above starting levels) during and following EPO therapy was observed in one patient with MM. Adverse events due to EPO therapy have not been recorded. These findings point out a previously unrecognized capacity of EPO given at pharmacologic doses to stimulate erythropoiesis in patients with anemia due to bone marrow infiltration by neoplastic lymphocytes in spite of enhanced endogenous EPO expression.

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Expression of Cannabinoid Receptors on the Neoplastic Lymphocytes in Patients with Chronic Lymphocytic Leukemia.

Blood ◽

10.1182/blood.v104.11.4804.4804 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4804-4804

Author(s):

Jaroslaw A. Piszcz ◽

Miroslawa Pietruczuk ◽

Janusz S. Kloczko ◽

Milena Dabrowska ◽

Marzenna Galar ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Peripheral Blood ◽

Cannabinoid Receptors ◽

Lymphocytic Leukemia ◽

Control Group ◽

Neoplastic Cells ◽

Fluorescent Intensity ◽

Cb2 Receptors ◽

Neoplastic Lymphocytes ◽

Cb1 And Cb2 Receptors

Abstract Endocannabinoids take part in the physiology of neural and immune systems. The latest data showed that these compounds and their receptors play an important role in proliferation and apoptosis of various neoplastic cells. Cannabinoids were shown to increase apoptosis in human leukemia and lymphoma cell lines and culture of neoplastic cells obtained from patients with T-cell acute lymphoblastic leukemia. The aim of the study was an assessment of cannabinoid receptors expression on lymphocytes B derived from patients with CLL. The study group contains newly diagnosed, untreated adult patients with B-cell chronic lymphocytic leukemia; 13 male and 7 female, aged from 44 to 65. All of the patients were in B or C stage according to Binet. Peripheral blood samples from 10 healthy adult donors were used as the control group. The patients were hospitalized in the Department of Haematology, Medical University in Bialystok, Poland. Diagnosis of CLL in all cases was confirmed by routine immunophenotyping study. For flow cytometric analysis 1x105 – 1x106 of peripheral blood cells were incubated with 10ul of anty CB1 and anty CB2 polyclonal antibodies (American Diagnostics). Then 10ul of monoclonal antibodies IgG1-FITC and CD19-PE (Becton Dickinson) were added and the samples were incubated for 20 min in dark in 4°C. The samples were lysed, fixed and stabilized using Immuno-Prep (Coulter procedure) and assessed by flaw cytometry (Epics XL, Coulter). Statistical analysis was performed using non parametric U Mann-Whitney and Wilcoxon Tests. The conducted study revealed high expression of CB1 and CB2 receptors on the surface of neoplastic lymphocytes. The percentage of CB1/CD19 and CB2/CD19 positive cells in CLL patients were significantly higher, compared to the control group respectively (81.2±9,8% vs 12.0±9,3% p<0,05; 94,8±11,0 % vs 9,9±4,0%, p<0,05). No difference was noticed between the percentage of lymphocytes with CB1 and CB2 receptors expression in CLL and control group. Fluorescent intensity of CB2 receptors was about ten folds higher than CB1 receptors in both groups. The study demonstrated the presence of both types of cannabinoid receptors (CB1 and CB2) on neoplastic cells derived from patients with chronic lymphocytic leukemia. The higher percentage of B-lymphocytes expressing cannabinoid receptors in CLL patient suggests that the cannabinoid system may take part in CLL development. High intensity of CB2 receptor may be another target in CLL treatment.

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Treatment of Feline Gastrointestinal Small-Cell Lymphoma With Chlorambucil and Glucocorticoids

Journal of the American Animal Hospital Association ◽

10.5326/0460413 ◽

2010 ◽

Vol 46 (6) ◽

pp. 413-417 ◽

Cited By ~ 40

Author(s):

Timothy J. Stein ◽

MacKenzie Pellin ◽

Howard Steinberg ◽

Ruthanne Chun

Keyword(s):

Response Rate ◽

Cell Lymphoma ◽

Small Cell ◽

Clinical Response Rate ◽

Minimal Amount ◽

Second Malignancy ◽

Full Thickness ◽

Neoplastic Lymphocytes ◽

Relapsed Disease

Gastrointestinal (GI) lymphoma is the most frequently diagnosed form of lymphoma in the cat and is categorized into two distinct forms based on the size of neoplastic lymphocytes. Treatments for both large- and small-cell GI lymphoma have been described previously; however, multiple chemotherapy protocols were used, a minimal amount of histopathological characterization was provided, and, in most studies, the majority of diagnoses were obtained via endoscopic pinch biopsies. Twenty-eight cats (24 with full-thickness intestinal biopsies) were diagnosed with small-cell GI lymphoma and treated with a combination of chlorambucil and glucocorticoids. The majority of cases were strongly CD3+, and many displayed epitheliotropism. The overall clinical response rate was 96%, with a median clinical remission duration of 786 days. Follow-up identified seven cats with relapsed disease—all of which were treated with a rescue protocol of cyclophosphamide and glucocorticoids; the response rate was 100%, and four of the 28 cats were diagnosed with a second malignancy.

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