Intracranial lymphomas in simian retrovirus-positive Macaca fascicularis

Two young adult Macaca fascicularis each had unilateral mydriasis and ptosis. Both animals were euthanatized, monkey No. I for progressive neurologic signs and monkey No. 2 because of a positive intradermal tuberculin test. At necropsy, each animal had a single intracranial mass on the ventral surface of the midbrain, surrounding the oculomotor nerve. Histologically, both masses were immunoblastic lymphomas. Immunohistochemical staining revealed the neoplasms to be of B-cell origin. Simian retrovirus (SRV) was isolated from both monkeys, but simian immunodeficiency virus was not found. Both animals lacked antibody to SRV. Both animals had antibodies to Epstein-Barr-like virus (EBV), but EBV antigens were not found by immunohistochemistry. Polymerase chain reaction analysis for integrated EBV DNA was unproductive. One of the animals (monkey No. 2) had a pulmonary infection with Mycobacterium avium, suggesting that immunosuppression was present. These cases represent a unique and previously undescribed type of solitary lymphoma in SRV-infected macaques.     

SIV-associated lymphomas in rhesus monkeys (Macaca mulatta) in comparison with HIV-associated lymphomas

A retrospective study was performed to characterize malignant lymphomas of 16 Simian immunodeficiency virus (SIV)-infected rhesus monkeys (Macaca mulatta), 2-9 years of age, on the basis of clinical data, histologic and immunophenotypic results, and cell death indices compiled with the TdT-mediated X-duTP nick end labeling method. We particularly focused on providing immunohistochemical evidence of expression products of EBNA2, Bc12, c-Myc, P21, P53, and Bc16. Results were compared with data from the literature on human HIV-associated lymphomas. According to the updated Kiel classification, the lymphomas were classified as 11 centroblastic lymphomas, three immunoblastic lymphomas, one Burkitt-like lymphoma, and one immunocytoma. Using antibodies to CD20, the B-cell origin of tumor cells was demonstrated. SIV antigen was not demonstrated in the tumor cells. Infection with rhesus lymphocryptovirus was present in 94% of the monkeys. Lymphomas revealed expression of Bc12 in 15/16 (94%), c-Myc in 14/16 (88%), P21 in 10/ 16 (63%), P53 in 12/16 (75%), and Bc16 in 1/16 (6%) monkeys. This study provided evidence that the expression of these gene products, which are thought to play an important role in cell proliferation and apoptosis in HIV- and non-HIV-associated lymphomas, are also involved in the pathogenesis of lymphomas in SIV-infected rhesus monkeys. A tentative relationship between the described gene products and the cell death indices was established for the expression of Bc12. The present primate model represents a suitable animal model for studying the pathogenesis of AIDS-associated lymphomas.     

Infection of a chimeric simian and human immunodeficiency virus with CCR5-specific HIV-1 envelope to Rhesus macaques

Human immunodeficiency virus (HIV) infects lymphocytes and macrophages via CD4 and chemokine receptors. In this study, the infectivity of a chimeric simian and human immunodeficiency virus (SHIV) having a CCR5-specific HIV-1 envelope gene was examined. A SHIV strain termed SHIV-JRFL could enter cells via CD4 with a chemokine receptor CCR5, not CXCR4, and the viral replication was suppressed by recombinant human RANTES, one of beta-chemokines. The intravenous inoculation of SHIV-JRFL into two rhesus macaques resulted in a systemic infection, though it was rather weak. During the early infection, the production of RANTES from Con A-stimulated PBMCs of the infected monkeys increased. These results suggested that beta-chemokine has the potential to limit the infectivity of an R5-type SHIV.     

Necropsy findings in rhesus monkeys experimentally infected with cultured simian immunodeficiency virus (SIV)/delta

Lesions induced in rhesus monkeys by different isolates of simian immunodeficiency virus (SIV)/Delta were studied at necropsy. Four groups of monkeys were inoculated with SIV/Delta isolated from other experimentally infected rhesus monkeys, while one group was inoculated with SIV/Delta from an asymptomatic mangabey monkey. Three rhesus isolates and the mangabey isolate were virulent, killing 75-100% of infected monkeys. One rhesus isolate, which had been extensively passaged in vitro, was attenuated but was restored to virulence by single animal passage. Clinically, infected monkeys had lymphadenopathy, splenomegaly, diarrhea, and a rash. Most monkeys died of enteric disease. The following lesions were seen: weight loss, thymic atrophy, lymphoid atrophy, bone marrow hyperplasia, encephalitis, colitis, amyloidosis, hepatitis, glomerulosclerosis, and the presence of syncytial cells. One Rh Epstein-Barr virus (EBV)-related lymphoma occurred. Opportunistic agents were identified: cytomegalovirus, adenovirus, Cryptosporidia, and Pneumocystis. Shigella and Campylobacter often caused colitis.     

Nodular Pneumocystis carinii pneumonia in SIV-infected macaques.

Pneumocystis carinii (PC) pneumonia is a frequent manifestation of the acquired immunodeficiency syndrome (AIDS) in humans and macaques. An unusual nodular type of PC pneumonia was observed in two simian immunodeficiency virus (SIV)-inoculated rhesus macaques (Macaca mulatta). These animals developed clinical signs of simian AIDS, including anorexia, weight loss, dyspnea, and collapse. Grossly, both animals had multifocal tan-white nodules 1-10 mm in diameter scattered throughout the lungs. One animal had similar nodules involving the diaphragm and thoracic wall. The lungs were characterized by severe PC pneumonia with numerous large nodules consisting of foamy material that compressed adjacent tissue. The nodules had central areas of necrosis and lysis of alveolar septa. Varying degrees of necrotizing vasculitis were observed in areas of nodular PC pneumonia. The presence of PC in intra-alveolar spaces and nodular lesions was confirmed by immunohistochemistry. No evidence of other agents, including viral inclusions, bacteria, fungi, and lung mites, was detected. The animal with the most severe nodular PC pneumonia had vascular involvement with extrapulmonary spread to the diaphragm, thoracic wall, and regional lymph nodes. This unusual type of nodular PC pneumonia has been rarely seen in human AIDS patients.     

New gene-based approaches for an AIDS vaccine

Vaccine approaches against AIDS have focused on inducing cellular immune responses, since many studies revealed the role of T cell responses in the control of human immunodeficiency virus or simian immunodeficiency virus (SIV) infections. The experimental infection of rhesus macaques with SIV or chimeric SHIV is routinely used as a model for AIDS. In such models, DNA immunization is a tool to elicit specific T cell responses and to study their protective efficacy. DNA immunogenicity in primates depends on parameters such as level of antigen expression, choice of the antigen among SIV proteins, use of fusion proteins, route of immunization, and addition of adjuvants. Recent results suggest that priming with DNA and boosting with attenuated recombinant viral vectors, each expressing corresponding SIV antigens, leads to improved specific immunity and, in some cases, affords protection against pathogenic challenge. After preclinical evaluations, DNA has entered clinical trials for a therapeutic or prophylactic gene-based AIDS vaccine.     

Feline nasal and paranasal sinus tumours: clinicopathological study, histomorphological description and diagnostic immunohistochemistry of 123 cases

Histological examination was performed in 123 cats with primary nasal and paranasal sinus tumours; 117 had undergone surgical biopsy and six necropsy. Special stains and immunohistochemistry were performed on poorly differentiated cases. Ninety-two percent (113/123) of the tumours were malignant. There was an increased risk for old cats (mean age of 10.9 years), and a male predilection (59% males). Clinical signs and breeds varied with the histological type of tumour. Thirty-nine percent (48/123) of the cases presented with nasal discharge, 21% (26/123) with dyspnea, 20% (24/123) with facial swelling, and 15% (19/123) with epistaxis. Forty-three percent (53/123) of the tumours were of epithelial origin. Adenocarcinomas (18/53) and squamous cell carcinomas (17/53) were the most common epithelial tumours. Fifty percent (26/53) of the epithelial tumours originated from the pseudo-stratified respiratory epithelium of the nasal cavity, 28% (15/53) from the stratified squamous epithelium of the vestibule, 9% (5/53) from olfactory epithelium, 9% (5/53) from submucosal glands and 4% (2/53) from minor salivary glands. Malignant lymphoma (35/123) was the most common tumour. Seventy-one percent (25/35) of the malignant lymphomas were B-cell tumours and 29% (10/35) were T-cell tumours. Six cases of malignant lymphomas were proved to be epitheliotropic T-cell lymphomas. This is the first report of a primary nasal epitheliotropic T-cell lymphoma in cats.     

Prevalence of feline leukaemia provirus DNA in feline lymphomas

A significant drop in the prevalence of feline leukaemia virus (FeLV) antigenaemic cats and antigen-associated lymphomas has been observed after the introduction of FeLV vaccination and antigen-testing with removal of persistently antigenaemic cats. However, recent reports have indicated that regressively infected cats may contain FeLV provirus DNA and that lymphoma development may be associated with the presence of provirus alone. In the present study, we investigated the presence of FeLV antigen and provirus DNA in 50 lymphomas by immunohistochemistry and semi-nested polymerase chain reaction, respectively. Interestingly, almost 80% of T-cell lymphomas and 60% of B-cell lymphomas contained provirus DNA while only 21% of T-cell lymphomas and 11% of B-cell lymphomas expressed FeLV antigen. In conclusion, our results support previous hypotheses that vaccination and removal of persistently antigenaemic cats have led to a drop in FeLV antigen-expressing lymphomas. However, FeLV provirus DNA is still present in a high percentage of feline lymphomas.     

T-cell lymphoproliferative disorder in an aged rhesus macaque

A CD8+ T-cell leukemia was diagnosed in an aged female rhesus macaque. Although leukemia and lymphoma in nonhuman primates are commonly associated with simian T-lymphotropic virus, gibbon ape leukemia virus, oncogenic herpesviruses, and types C, D, and E retroviruses, this monkey was not infected with any of these viruses. However, the monkey did have antibodies against herpesvirus saimiri. This likely represents cross-reactivity of the herpesvirus saimiri assay with rhesus monkey rhadinovirus (RRV) antibodies; RRV was first described in rhesus macaques that were identified as having antibodies against herpesvirus saimiri. Rhesus rhadinovirus is a gamma herpesvirus, related antigenically to herpesvirus saimiri and Kaposi's sarcoma-associated herpesvirus (KSHV), which have been linked to lymphoproliferative disorders in primates and humans, respectively. Moreover, an oncogene has been recently identified in the RRV genome that is equivalent in position to the herpesvirus saimiri and KSHV oncogenes. Presently, the association of RRV infection with disease in nonhuman primates is unknown.     

Cytomegalovirus-associated discrete gastrointestinal masses in macaques infected with the simian immunodeficiency virus

Cytomegalovirus (CMV)-associated gastrointestinal masses have been reported in human acquired immune deficiency syndrome patients. This is the first report on CMV-associated gastrointestinal masses in simian immunodeficiency virus (SIV)-infected macaques. Two SIV-infected macaques presented at necropsy with multiple nodular or umbilicated masses within the gastrointestinal tract. In one animal, the masses were located throughout the gastrointestinal tract, whereas in the other, the masses were restricted to the proximal small intestine. Grossly, the masses were indistinguishable from those caused by neoplastic conditions such as lymphoma and, histologically, were composed of hyperplastic glandular tissue, dense neutrophilic infiltrates within the lamina propria, and multifocal proprial hemorrhage. Frequent cytomegalic cells with basophilic intranuclear inclusions were found in affected regions. Immunohistochemistry for CMV demonstrated frequent immunopositive cells within affected areas. Furthermore, immunohistochemistry for the proliferation marker Ki-67 demonstrated increased proliferation in hyperplastic glands and crypts. CMV should be considered a cause of discrete mass lesions in the gastrointestinal tract of SIV-infected macaques.     

Intranasal infection of ferrets (Mustela putorius furo) with canine parainfluenza virus.

Immunocompetent and cyclophosphamide-immunosuppressed ferrets were intranasally infected with canine parainfluenza virus (CPIV) and observed for clinical signs, histopathologic lesions, the immunocytochemical demonstration of CPIV antigen in the respiratory tract and scanning electron microscopic alterations of the tracheal epithelium until 36 days post infection (p.i.). In both groups, clinical signs were minimal, restricted to the upper respiratory tract and consisted of cough elicited by tracheal compression between 3 and 7 days p.i. Microscopically, inflammatory and degenerative lesions were observed in the trachea and less frequently in the nasal cavity; bronchiolitis or interstitial pneumonia was not demonstrated. By immunocytochemistry, CPIV antigen was demonstrated in tracheal epithelial cells, whereas nasal cavity, bronchi, bronchioles and lung were devoid of viral antigen. Ferrets given CPIV alone developed a minimal lymphocytic tracheitis with minimal loss of cilia and CPIV antigen was observed only 4 days p.i. 17 days p.i., normal epithelial organization and ciliary reappearance was reestablished. Ferrets treated with cyclophosphamide and infected with CPIV exhibited mild to moderate histological lesions as above with similar scanning electron microscopic changes until 36 p.i. Tracheal lesions consisted of intraepithelial and submucosal infiltration of lymphocytes and macrophages, focal epithelial hyperplasia and multifocal loss of cilia. In addition, mild and transient neutrophilic infiltration was observed. In immunosuppressed ferrets, viral antigen expression was prominent and demonstrated 4 and 8 days p.i. These data suggest that ferrets are susceptible to aerosol CPIV infection.     

Cutaneous Lymphomas in European Pet Rabbits (Oryctolagus cuniculus)

Cutaneous lymphoma is a common skin neoplasm of pet rabbits in Europe but is rarely reported in pet rabbits in North America. These neoplasms have not been previously characterized, nor has the cause for the apparent predilection for cutaneous lymphoma in European pet rabbits compared with North American pet rabbits been investigated. In this retrospective study, the authors morphologically and immunohistochemically characterized 25 cutaneous lymphomas in European pet rabbits according to the World Health Organization classification. Tumors were classified as diffuse large B cell lymphomas, with 14 lymphomas exhibiting a centroblastic/centrocytic subtype and 11 tumors exhibiting a T cell-rich B cell subtype. To investigate a potential viral etiology of these lymphomas, 3 diffuse large B cell and 3?T cell-rich B cell lymphomas were evaluated by polymerase chain reaction for retroviral and herpesviral genes. Neither virus was detected. In contrast to other domestic animals, cutaneous lymphomas in European pet rabbits were highly pleomorphic and frequently contained multinucleated giant cells. Unexpectedly, the second most common subtype was T cell-rich B cell lymphoma, a subtype that is rare in species other than horses. Based on a limited number of samples, there was no support for a viral etiology that would explain the higher incidence of lymphoma in European pet rabbits compared with American pet rabbits. Further investigation into genetic and extrinsic factors associated with the development of these tumors is warranted.     

Pathogenesis of simian AIDS in rhesus macaques inoculated with the SRV-1 strain of type D retrovirus

Type D retrovirus was isolated from rhesus macaques with simian acquired immunodeficiency syndrome (SAIDS) and transmitted to healthy rhesus macaques with tissue culture medium containing the virus. The clinical, immunologic, and lymph node morphologic changes were observed in 9 rhesus macaques for 52 weeks after inoculation. A spectrum of clinical signs developed including early death, persistent SAIDS, and apparent remission. Animals that died or developed persistent SAIDS had characteristic lymphoid depletion, persistently depressed peripheral blood mononuclear cell (PBMC) mitogenic response, and decreased serum immunoglobulins. The SAIDS retrovirus (SRV) was recovered from PBMC of 8 of the animals after inoculation. Virus could not be recovered from PBMC of one animal in remission, but this animal developed serum-neutralizing antibodies to SRV after inoculation. Seven of the animals seroconverted to SRV after inoculation, all 9 were seronegative for human T-lymphotropic virus-III, and 5 animals tested were seronegative to human T-lymphotropic virus-I. These findings support the etiologic role of the type D retrovirus in SAIDS and further define the pathogenesis of this disease.     

SHIV-KB9病毒中国恒河猴细胞适应株的制备

试验旨在研究体外制备SHIV-KB9病毒中国恒河猴细胞适应株,在细胞水平和中国恒河猴体内评价其生物学特性。 试验将SHIV-KB9半长质粒连接后转染CEMx174细胞,转染上清与正常恒河猴PBMCs共培养。定期测定培养液中的P27抗原水平。当病毒复制达高峰期时收集培养上清,分装并冻存,测定病毒RNA载量和TCID₅₀。静脉感染中国恒河猴,研究该批次SHIV-KB9在体内的病毒学、免疫学指标变化及变异情况,分析其基本的生物学特性。结果表明,本研究共制备了95 mL SHIV- KB9病毒原液,病毒载量为2.678×10⁵ 拷贝/mL,TZM-bl细胞测定病毒的TCID₅₀为3.16×10³/mL,gp120序列分析表明病毒未发生变异。10倍稀释的3个不同浓度的SHIV-KB9均静脉成功感染中国恒河猴,引起外周血CD4⁺/CD8⁺大幅下降。因此,此次制备的SHIV-KB9细胞适应株生物学特性稳定,适合作为毒种库建立SHIV-KB9/中国恒河猴模型。     

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.     

Aberrant phenotypes and quantitative antigen expression in different subtypes of canine lymphoma by flow cytometry

Flow cytometry may be a useful tool to analyze lymphoma samples that are obtained from fine needle aspirations (FNA). This study aimed to determine if flow cytometric analysis add more objective and standardized information on the cellularity and morphology of lymphoma cells to conventional cytology. The typical immunophenotype of different lymphoma subtypes was assessed and leukocyte marker expression was evaluated to determine which antigens were more frequently over- or under-expressed in these lymphoma subtypes. Fifty FNA lymph node samples were evaluated from canine lymphomas. Thirty-one samples were identified to be of B-cell origin, sixteen were identified to be of T/NK-cell origin and three cases were classified as acute lymphoblastic leukaemia with lymph nodes involvement. The most common B-cell lymphoma subtypes were centroblastic lymphomas, whereas three cases were atypical and classified as B-large cell pleomorphic lymphomas. Among the T/NK lymphomas, small clear cells, large and small pleomorphic mixed cells, large granular lymphocytic cells and small pleomorphic cells were identified. Aberrant phenotypes and/or antigen under/over regulation was identified in thirty out of forty-seven lymphoma cases (64%; 18/31 B-cell=58% and 12/16 T-cell=75%). In B-cell lymphomas the most frequent finding was the diminished expression of CD79a (45%). CD34 expression was also observed in four cases (13%). Among T-cell lymphomas the prevalent unusual phenotype was the under-expression or absence of CD45 (25%). These findings reveal flow cytometry may be useful in confirming the diagnosis of lymphoma, as the technique allows one to add useful information about morphology of the neoplastic cells and identify antigenic markers and aberrant phenotypes.     

FIV associated neoplasms--a mini-review

Retroviral induced neoplasms have been key to understanding oncogenesis and are important etiologic agents associated with cancer formation. Cats infected with feline immunodeficiency virus (FIV), the feline analogue to human immunodeficiency virus (HIV), are reported to be at increased incidence of neoplasia. This review highlights reported risk factors and tumor cell phenotypes associated with neoplasias arising in FIV-infected animals, differences in oncogenic disease in natural versus experimental FIV infections, and similarities between FIV- and HIV-related malignancies. The most common type of FIV-associated neoplasm reported in the literature is lymphoma, specifically of B-cell origin, with experimentally infected cats developing neoplastic lesions at an earlier age than their naturally infected cohorts. The mechanism of FIV-induced lymphoma has not been completely ascertained, though the majority of published studies addressing this issue suggest oncogenesis arises via indirect mechanisms. HIV-infected individuals have increased risk of neoplasia, specifically B cell lymphoma, in comparison with uninfected individuals. Additional similarities between FIV- and HIV-associated neoplasms include the presence of extranodal lymphoma, a synergism with other oncogenic viruses, and an apparent indirect mechanism of induced oncogenesis. This literature supports study of FIV-associated neoplasms to further characterize this lentiviral-neoplasia association for the benefit of both human and animal disease, and to advance our general knowledge of mechanisms for viral-induced oncogenesis.     

Feline gastrointestinal lymphoma: mucosal architecture, immunophenotype, and molecular clonality

Gastrointestinal lymphomas were identified in 120 cats between 1995 and 2006. Lymphomas were classified according to the World Health Organization (WHO) scheme. Cats with mucosal T-cell lymphoma (n = 84) predominated and had a median survival of 29 months. Mucosal T-cell lymphoma matched WHO enteropathy-associated T-cell lymphoma (EATCL) type II. Epitheliotropic T-cell infiltrates were present in 62% of cats and occurred as clusters or diffuse infiltrates of small to intermediate-sized T cells in villous and/or crypt epithelium. Similar lymphocytes infiltrated the lamina propria in distinctive patterns. Cats with transmural T-cell lymphoma (n = 19) had a median survival of 1.5 months. Transmural T-cell lymphoma matched WHO EATCL type I. Epitheliotropic T-cell infiltrates were present in 58% of cats. Large lymphocytes (n = 11), mostly with cytoplasmic granules (LGL-granzyme B+) (n = 9) predominated. Transmural extension across the muscularis propria characterized the lesion. Both mucosal and transmural T-cell lymphomas were largely confined to the small intestine, and molecular clonality analysis revealed clonal or oligoclonal rearrangements of T-cell receptor-γ in 90% of cats. Cats with B-cell lymphoma (n = 19) had a median survival of 3.5 months. B-cell lymphomas occurred as transmural lesions in stomach, jejunum, and ileo-cecal-colic junction. The majority were diffuse, large B-cell lymphomas of centroblastic type. In conclusion, T-cell lymphomas characterized by distinctive mucosal architecture, CD3 expression, and clonal expansion predominated in the feline gastrointestinal tract.     

Immunohistochemical characterization of estrogen and progesterone receptors in lymphoma of horses

Abstract: Immunohistochemical techniques were used to examine 29 cases of equine lymphoma for estrogen receptor (ER) and progesterone receptor (PR) expression. The lymphomas examined included T-cell-rich large B-cell lymphomas, B-cell neoplasms, and T-cell lymphomas. The individual cases were also classified according to the anatomic location of the tumors. One normal equine lymph node was also examined for ER and PR expression. All of the cases of equine lymphoma and the normal lymph node were negative for ER. A total of 16/29 (55%) PR-positive lymphomas were identified. Seven of the 12 (58%) T-cell-rich large B-cell lymphomas were positive, 7/11 (64%) B-cell tumors were positive, and 2/6 (33%) T-cell neoplasms were positive. Anatomically, 6/9 (66%) subcutaneous lymphomas were PR positive, 3/5 (60%) intrathoracic lymphomas were positive, 1/4 (25%) intra-abdominal lymphomas were positive, 2/5 (40%) intra-abdominal/intrathoracic lymphomas were positive, 1/2 (50%) upper airway lymphomas were positive, and 3/3 (100%) splenic lymphomas were positive. One case involving abdominal and thoracic tumors and leukemia was negative for PR expression. The normal lymph node contained a low percentage (1.9%) of PR-positive lymphocytes. The presence of PR in neoplastic equine lymphoid tissue indicates that these tumors may be responsive to serum progesterone. Also, identification of PR-positive cells in the normal lymph node suggests that PR may be constitu-tively expressed in normal equine lymphocytes. Further studies are needed to quantify PR levels in normal and malignant equine lymphoid tissue and to determine the usefulness of either progestin or antiprogestin drugs in the management of equine lymphoma.