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Sporadic Bovine lymphosarcoma (SBL):[edit]

Sporadic Bovine lymphosarcoma (SBL) is a rare type of cancer seen in cattle, characterized by the overgrowth of lymphoid tissue[1]. It was first described in 1871 in Lithuania in a cow suffering from lymph node hypertrophy and splenomegaly [2]. The specific causative agent(s), if they exist, has not yet been discovered, as the disease appears to occur sporadically in cattle population, as the name suggests. This condition can manifest itself in three different forms: juvenile form (calf/multicentric lymphosarcoma), thymic form (thymic lymphosarcoma) and skin (cutaneous lymphoma)[3][4]. Although very similar in pathology to enzootic bovine leukosis, sporadic bovine lymphosarcoma is not related to infection from the retrovirus bovine leukemia virus (BLV)[1]. Bovine leukosis caused by bovine leukemia virus occurs frequently in adult cattle population, whereas sporadic bovine leukosis appears to affect only younger cattle. All forms of SBL are rare and are typically seen in cattle less than 2 years of age[5]. Most commonly, B-cell lymphomas are seen as a result of bovine leukemia virus infection whereas tumor cells of sporadic lymphomas are all immature lineage of T-cells and less commonly B-cells [6]. Previous findings have shown that the proto-oncogene C-Myb is expressed in most sporadic lymphomas but not in enzootic leukosis[1]. These alterations to small sets of cellular genes appear to contribute significantly to the neoplastic transformation of cells, notably leukocytes and lymphocytes in this disease[7]. All forms of sporadic bovine lymphosarcoma may have varying clinical presentation related to the affected organs[8].

Young holstein heifer within the age range of developing the juvenile form of lymphosarcoma.

Juvenile Lymphosarcoma:[edit]

Juvenile or calf lymphosarcoma is typically seen in neonatal calves and cattle up to 18 months of age. Neonates are most commonly affected by the B-cell form of calf lymphosarcoma [5] but the reasons and mechanisms around this remain unknown. Both the T-cell and B-cell form induce a diffuse lymphadenopathy causing palpable enlargement of peripheral lymph nodes in affected calves. Out of all of the dairy breeds, it appears that the milking shorthorn has the highest incidence of juvenile/calf lymphosarcoma, making researchers question the genetic implication of this disease[5].

Clinical signs:[edit]

Juvenile lymphosarcoma can be characterized by a progressive weight loss and generalized peripheral lymphadenopathy, in addition to a diffuse lymphoid hyperplasia[8]. Clinical signs will vary significantly depending on what organs have been affected. Upon examination, increased heart and respiratory rate along with bronchial sounds are often noticed[9]. Additionally, fevers, tachycardia, dyspnea, bloat, diarrhea and hind limb ataxia (or posterior paresis) were also reported[4][10][8].  Posterior ataxia was found to be caused by the formation of tumors near the spinal cord, causing a compression in the lumbar area[10].Animals with juvenile lymphosarcoma usually perish within 4 to 6 weeks following the onset of clinical signs [11].

Diagnosis:[edit]

The hematological parameters observed in cows affected with SBL are variable. Most commonly, calves will have a high incidence of circulating immature lymphocytes and roughly 50% will be leukemic[12][6]. Complete blood counts (CBC) can show both leukocytosis (>17,000/mL) and lymphocytosis (>10,800/mL), in addition to normocytic and normochromic anemia (<28% PCV)[6]. Blood serum biochemical testing often shows increased activity of gamma-glutamyltransferase (GGT > 23 U/L) secondary to neoplastic infiltration of hepatic tissue. Also hypophosphatemia (<5.9 mg/dL) and hypomagnesemia (<1.9 mg/dL) can occur as a result of anorexia[6]. Bone marrow biopsy may reveal neoplastic lymphocytes and a macrocytic anemia. In most cases, blood biochemistry will appear normal, yet some cases may show decreased globulins and increased albumin, causing an imbalanced A/G ratio[11] [13].  The presence of neoplastic cells within the medullary cavity of the bone has eroding consequences on the cortical bone and fat. This condition can lead to marrow embolism, peripheral blood cutopenias, pathologic fracture, and necrosis of medually bone and bone marrow elements[10].  Similar to enzootic bovine leukosis, enlarged lymph nodes and infiltration of neoplastic lymphocytes within the spleen, liver, bone marrow and sometimes within the body of the lumbar vertebrae and the spinal cord will be observed at post mortem[14][10].  In calves between the age of 4 and 7 months, development of visceral tumours, bone marrow lesions and peripheral leukemia have also been reported[5].

Thymic lymphosarcoma:[edit]

The thymic form of sporadic lymphosarcoma is an aggressively invasive malignant tumour which appears in cattle between the age of 6 and 24 months of age[15], although it has been reported in 30-month-old cattle [16]. Secondary to the findings of Ogawa (et al. 1986)[1] on the involvement of the proto-oncogene C-myb, it was suggested by Oliver-Espinosa et al. (1994)[4] that the thymic form may be hereditary, secondary to the transfer of these mutated genes.  The lymphosarcoma appears, or begins its rapid growth in the thymus, where it may then affect to a lesser extent lymph nodes and other organs such as the liver, spleen, kidney and lungs[17]. This form may involve the cervical and/or intrathoracic thymus[8].

Clinical signs:[edit]

The thymic form of sporadic bovine lymphosarcoma is characterised by the progressive enlargement of the thymus. This enlargement frequently remains in the thorax, although some cases may develop cervical enlargement as well[16][5]. As with the other forms of the disease, clinical signs will vary based on the location and size of the tumor(s). Most cases will develop some degree of caudal cervical swelling, which is then able to progress to the mid or cranial-ventral cervical region[5]. Thymic enlargement is the result of infiltration of neoplastic lymphocytes into the thymus organ[12]. Producers will often contact a veterinarian for other complaints such as bloat or dyspnea, which are more noticeable with this disease[18]. As thymic enlargement progresses, it leads to the compression of the esophagus which then interfered with eructation, leading to bloat[5]. In addition, tracheal compression, pulmonary displacement or compression, pleural effusion and pulmonary edema are all resulting from this compression, which leads to signs of dyspnea. This condition may also be confused with diphtheria, a bacterial infection of the larynx[5]. Upon examination, heifers may also present signs of a fever[5] [18]. Muffled heart sounds or reduced air sounds can be common in cases where extremely large thymic masses develop within the thorax or the thoracic inlet, which may distend the jugular vein, often leading to heart failure[5].

Diagnosis:[edit]

Ante mortem diagnostic testing of thymic lymphosarcoma includes analysis of synovial fluid taken from the hock joint, which may reveal high lymphocyte numbers with abnormal morphology[4]. Lymph nodes aspirate and biopsies, in addition to thoracocentesis or ultrasound-guided biopsy are also useful tools in diagnosis ante-mortem[5]. Thymic lymphosarcoma can also be confirmed at post-mortem by necropsy and histologic examination[18]. A high occurrence of immature, poorly differentiated lymphocytes would be observable[8].

Cutaneous Lymphoma:[edit]

The skin form of sporadic bovine leukosis is very rare and is only seen in cattle less than 30 months of age. This form is associated with helper/inducer T-cell origin[19] which resembles Mycosis Fungoindes and Sézary syndrome in humans[20]. Most case reports have been seronegative for BLV, showing the non-relationship between the two diseases[5]. Cutaneous lymphoma is characterized by the presence of cutaneous plaques, which are usually between 1-5cm in diameter, distributed sporadically throughout the body, with higher concentration on the neck, back, rump and thighs[8]. Some case study have described spontaneous recovery from this form of lymphoma, however, recurrence of the disease is frequent[8].

Clinical signs:[edit]

This form of SBL causes multiple skin nodules to form on the neck, trunk and rear quarters of the affected cattle. The disease progresses over the course of a few months, inducing the appearance of larger and more numerous nodules[5]. Some cases also present with pruritus (severe itching of the skin)[19]. As this form of bovine lymphosarcoma is particularly rare, knowledge on clinical signs is limited to a few case studies reported in the 1980s. Notably, a case in a 10-month old female Simmental-red Holstein crossbred was published in 1987 and described the cattle as having numerous flattered, firm cutaneous nodules of various size (3-80mm in diameter) distributed over the whole body[19]. Enlargement of inguinal lymph nodes was also noticeable upon necropsy. Further testing revealed extensive infiltration of neoplastic cells into the dermis, superficial subcutis and epidermis. Although it is often limited to regional lymph node, this lymphoma can also involve the spleen, bone marrow, liver, kidney and brain[19]. Cattle affected by this form will often appear healthy during the early stage but show progressive deterioration of health and condition over the next 6-12 months following the onset of clinical signs[5] and will then perish of diffuse neoplasia[5]. Producers should keep in mind that animals infected with this form are highly susceptible to skin infections secondary to insect bites. Superficial dermatitis and skin nodule bleeding secondary to irritation from insects may even lead to abcessation of the lymph nodes[5].

Diagnosis:[edit]

Ante-mortem diagnosis of the bovine skin lymphoma relies on biopsies and cytologies collected from effusions or target organs[5]. The presence of neoplastic cells is often a good indicator of this disease, in addition to presence of palpable target organ neoplasia and lymphadenopathy (enlargement of lymph nodes)[5]. Post-mortem diagnosis relies on necropsy findings such as enlarged neoplastic organs (liver, spleen, kidney, bone marrow or brain) and histological examinations of infected tissue to examine the presence of neoplastic cells[21]. Usually, analysis of a cell line taken from a cutaneous lymphoma case is enough to determine if the sample is from a t-cell origin[6].

References:[edit]

  1. ^ a b c d Ogawa, Y.; Sagata, N.; Tsuzuku-Kawamura, J.; Onuma, M.; Izawa, H.; Ikawa, Y. (1986). "No involvement of bovine leukemia virus in sporadic bovine lymphosarcoma". Microbiology and Immunology. 30 (7): 697–701. doi:10.1111/j.1348-0421.1986.tb02995.x. ISSN 0385-5600. PMID 3022115. S2CID 9330873.
  2. ^ Burny, A.; Bruck, C.; Chantrenne, H.; et al. (1980). Bovine leukemia virus: Molecular Biology and Epidemiology. New York: Raven Press.
  3. ^ Jacobs, R. M.; Song, Z.; Poon, H.; Heeney, J. L.; Taylor, J. A.; Jefferson, B.; Vernau, W.; Valli, V. E. (October 1992). "Proviral detection and serology in bovine leukemia virus-exposed normal cattle and cattle with lymphoma". Canadian Journal of Veterinary Research = Revue Canadienne de Recherche Veterinaire. 56 (4): 339–348. ISSN 0830-9000. PMC 1263566. PMID 1335834.
  4. ^ a b c d Oliver-Espinosa, O.; Physick-Sheard, P. W.; Wollenberg, G. K.; Taylor, J. (December 1994). "Sporadic bovine leukosis associated with ataxia and tibiotarsal joint swelling: a case report". The Canadian Veterinary Journal = la Revue Veterinaire Canadienne. 35 (12): 777–779. ISSN 0008-5286. PMC 1686812. PMID 9132289.
  5. ^ a b c d e f g h i j k l m n o p q r Divers, T. J.; Peek, S.F.; Rebhun, W.C. (2008). Rebhuns Diseases of dairy cattle. St-Louis, MO: Saunders Elsevier.
  6. ^ a b c d e Harbo, Sam J.; Barrington, George M.; Allen, Andrew J.; Sample, Gregory L.; Parish, Steve M.; Hamilton, Mary Jo; Davis, William C. (2004). "Characterization of lymphocyte populations by flow cytometry in a calf with sporadic juvenile lymphoma". Veterinary Clinical Pathology. 33 (3): 163–167. doi:10.1111/j.1939-165x.2004.tb00368.x. ISSN 0275-6382. PMID 15334353.
  7. ^ Anderson, M. W.; Reynolds, S. H.; You, M.; Maronpot, R. M. (November 1992). "Role of proto-oncogene activation in carcinogenesis". Environmental Health Perspectives. 98: 13–24. doi:10.1289/ehp.929813. ISSN 0091-6765. PMC 1519627. PMID 1486840.
  8. ^ a b c d e f g Nagy, Dusty. "Overview of Bovine Leukosis - Generalized Conditions - Merck Veterinary Manual". Merck Veterinary Manual. Retrieved 2018-04-03.
  9. ^ Theilen, G.H.; Madewell, B.R. (1987). Veterinary Cancer Medicine. Philadelphia: Lea & Febiger. pp. 408–430.
  10. ^ a b c d Doige, C. E. (March 1987). "Bone and bone marrow necrosis associated with the calf form of sporadic bovine leukosis". Veterinary Pathology. 24 (2): 186–188. doi:10.1177/030098588702400214. ISSN 0300-9858. PMID 3576914. S2CID 11422705.
  11. ^ a b Hugoson, G. (1967). Juvenile bovine leukosis: An epizootiological, clinical, pathoanatomical and experimental study. Scandinavia: Dansk Dyrlaegeforening.
  12. ^ a b Parodi, A. L.; DaCosta, B.; Djilali, S.; Michel, B.; Alogninouwa, T.; Femenia, F.; Crespeau, F.; Fontaine, J. J.; Thibier, M. (1989-09-23). "Preliminary report of familial thymic lymphosarcoma in Holstein calves". The Veterinary Record. 125 (13): 350–353. doi:10.1136/vr.125.13.350. ISSN 0042-4900. PMID 2815503. S2CID 34867361.
  13. ^ Theilen, G. H.; Dungworth, D. L. (May 1965). "Bovine Lymphosarcoma in California. 3. The Calf Form". American Journal of Veterinary Research. 26: 696–709. ISSN 0002-9645. PMID 14316787.
  14. ^ Bundza, A.; Greig, A. S.; Chander, S.; Dukes, T. W. (October 1980). "Sporadic bovine leukosis: a description of eight calves received at Animal Diseases Research Institute from 1974-1980". The Canadian Veterinary Journal = la Revue Veterinaire Canadienne. 21 (10): 280–283. ISSN 0008-5286. PMC 1789795. PMID 6254627.
  15. ^ Dubreuil, P.; Lanevschi, A.; Perrone, M. A.; Desnoyers, M. (July 1998). "Atypical sporadic lymphosarcoma in a 7-month-old Holstein heifer". The Canadian Veterinary Journal = la Revue Veterinaire Canadienne. 39 (7): 431–433. ISSN 0008-5286. PMC 1539539. PMID 9759511.
  16. ^ a b Dungworth, D.; Theilen, G.; Lengyel, J. (1964). "Bovine lymphosarcoma in California II. The thymic form". Pathological Veterinaria. 1 (4): 323–350. doi:10.1177/030098586400100403. S2CID 86807744.
  17. ^ Sandison, A. T.; Anderson, L. J. (May 1969). "Tumors of the thymus in cattle, sheep, and pigs". Cancer Research. 29 (5): 1146–1150. ISSN 0008-5472. PMID 5818671.
  18. ^ a b c Hatfield, C. E.; Rebhun, W. C.; Dill, S. G. (1986-12-15). "Thymic lymphosarcoma in three heifers". Journal of the American Veterinary Medical Association. 189 (12): 1598–1599. ISSN 0003-1488. PMID 3793601.
  19. ^ a b c d Zwahlen, R. D.; Tontis, A.; Schneider, A. (November 1987). "Cutaneous lymphosarcoma of helper/inducer T-cell origin in a calf". Veterinary Pathology. 24 (6): 504–508. doi:10.1177/030098588702400606. ISSN 0300-9858. PMID 2970712. S2CID 44291196.
  20. ^ Nasu, K.; Said, J.; Vonderheid, E.; Olerud, J.; Sako, D.; Kadin, M. (June 1985). "Immunopathology of cutaneous T-cell lymphomas". The American Journal of Pathology. 119 (3): 436–447. ISSN 0002-9440. PMC 1888020. PMID 3893149.
  21. ^ Dalgleish, R.; Callanan, J. J.; McNeil, P. E. (1991-10-05). "An atypical case of lymphosarcoma (sporadic bovine leukosis) in a heifer". The Veterinary Record. 129 (14): 308–310. doi:10.1136/vr.129.14.308. ISSN 0042-4900. PMID 1746102. S2CID 35152245.
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