• BLV;
  • Effusion;
  • Lymphosarcoma;
  • Pericardium

bovine leukosis virus

Case 1

  1. Top of page
  2. Case 1
  3. Case 2
  4. Case 3
  5. References

A 2-year-old female Holstein heifer was referred for evaluation of acute onset brisket edema and jugular venous distension. The heifer was 223 days in milk and 139 days pregnant and had been producing milk at expected levels until the day before presentation. Physical examination at admission to the University of Wisconsin Veterinary Medical Teaching Hospital revealed a bright and alert individual with a rectal temperature of 100.6 F, and pulse and respiratory rates of 76 beats and 34 breaths per minute, respectively. Muffled heart sounds were present and both jugular veins were turgid, visibly distended, and displayed retrograde fill. An echocardiogram at admission using a 2.5–3.5 MHz phased array transducer1 from a right parasternal approach identified an approximately 8-cm distension of the pericardial sac by anechoic fluid that was evident during all phases of the cardiac cycle. Some thickening of the epicardial surface was noted with strands of more hyperechoic tissue floating on the epicardial surface with the ultrasonographic appearance of fibrin. Cardiac contractility appeared subjectively poor although functional cardiac measurements were not obtained because of the depth of pericardial fluid.

A serum sample obtained at admission tested positive by both ELISA and AGID techniques for antibodies to the bovine leukosis virus (BLV). Pericardiocentesis yielded bloody fluid with a PCV of 14%, total protein concentration of 5.2 g/dL, and total nucleated cell count (TNCC) of 5.75 × 103/μL. The nucleated cells were comprised of 14% neutrophils, 64% small lymphocytes, and 22% macrophages. The lymphocytes were cytologically normal. Approximately 5.5 L of hemorrhagic pericardial fluid was removed through a 24 French chest tube placed in the left 5th intercostal space, decreasing the visible depth of pericardial fluid to approximately 2 cm. The heifer was given 0.1 mg/kg dexamethasone IV q24h for 3 days and underwent daily ultrasonographic assessment of pericardial fluid volume and subjective evaluation of cardiac function.

By day 3 of hospitalization, minimal pericardial fluid remained (<10 mm) but focal areas of epicardial fibrin still could be seen. Jugular venous distension had resolved and the heifer's heart rate was normal. It had normal appetite and milk production had improved. The heifer was returned to its farm of origin and continued to do well, producing 68 lb of milk at a subsequent test date approximately 50 days post discharge. Unfortunately, it was found dead approximately 100 days after discharge.

Necropsy showed thickening of the epicardial surface of the heart with multiple fibrous attachments connecting the epicardial surface to the pericardium. The epicardial surface was matted with extensive areas of fibrosis admixed with fibrin and hemorrhage. Multiple thoracic lymph nodes were enlarged with similar multifocal white to tan infiltrates. Histologically, the epicardium was expanded with fibrosis and highly vascular papillary projections in which there were many atypical neoplastic lymphocytes alongside a mononuclear inflammatory infiltrate of small lymphocytes and plasma cells. The myocardium had areas of fibrosis but no neoplastic infiltrate. Histologically, lymphosarcoma was confirmed in the thoracic lymph nodes.

Case 2

  1. Top of page
  2. Case 1
  3. Case 2
  4. Case 3
  5. References

A 3-year-old Holstein cow, nonpregnant and approximately 9 months in lactation, was presented to the Veterinary Medical Teaching Hospital at the University of Wisconsin for evaluation of intermittent appetite and decreased milk production over the preceding 4–6 week period. Physical examination by the referring veterinarian immediately before referral identified jugular and mammary venous distension, mild brisket edema, and muffled heart sounds. Physical examination on arrival at the teaching hospital confirmed the referring veterinarian's findings. The cow was bright and afebrile with an increased heart rate of 110 beats per minute and a respiratory rate of 24 breaths per minute. No other abnormalities were detected on physical examination.

An echocardiogram from a right parasternal approach identified an approximately 12-cm distension of the pericardial sac by anechoic fluid. Pericardiocentesis was performed and yielded a hemorrhagic fluid with a PCV of 11%, total protein concentration of 5.3 g/dL, and a TNCC of 4.98 × 103/μL comprised of 2% neutrophils, 78% small lymphocytes, and 20% macrophages. A CBC and serum biochemical profile were normal except for mild anemia (PCV 21%), increased gamma glutamyl transpeptidase activity (GGT 378 IU/L; normal reference range, 12–30 IU/L), increased alkaline phosphatase activity (AP 132 IU/L; normal reference range, 25–78 IU/L), and slight hypoalbuminemia (2.9 g/dL; normal reference range, 3.2–4.3 g/dL). A serum sample obtained at admission for antibodies to BLV tested positive by both ELISA and AGID techniques.

Pericardial drainage was performed through the left 5th intercostal space using a 24 French chest tube, yielding approximately 16 L of hemorrhagic fluid. The cow was given 0.1 mg/kg dexamethasone IV q24h for 3 days, followed by 0.05 mg/kg IV q24h for 3 more days, and 2.2 mg/kg ceftiofur IV q24h for 5 days. Daily ultrasonographic evaluation during hospitalization demonstrated resolution of the pericardial fluid to <10 mm distension by the 3rd day. The cow was discharged from the hospital after 5 days at which time her heart rate had returned to normal and venous distension also had resolved. The cow was rechecked twice as an outpatient at the VMTH over the following 24 months, and on both occasions cardiac auscultation was within normal limits. Ultrasonographic evaluation demonstrated no reaccumulation of pericardial fluid and normal cardiac function. During this time it was used first as a successful embryo transfer donor and then carried a subsequent pregnancy of her own to full term.

The cow was represented approximately 7 months into its next lactation with an acute reoccurrence of clinical signs of heart failure. Repeat ultrasound examination identified an approximate 10-cm distension of the pericardial sac by anechoic fluid. A sample of the fluid was hemorrhagic with a PCV of 10%, a total protein concentration of 5.4 g/dL and TNCC of 29 × 103/μL, comprised of 93% large, atypical, blast-like lymphocytes. The cow was euthanized at the owner's request. At postmortem examination there was diffuse epicardial fibrosis with multifocal areas of hemorrhage and highly vascular, polypoid, and papillary mesothelial proliferation, heavily infiltrated histologically by neoplastic lymphocytes (Fig 1). No endocardial or myocardial infiltration was observed. Thoracic and extrathoracic (eg, mesenteric, mammary) lymph nodes also were infiltrated by neoplastic lymphocytes. Grossly and histologically there were pathologic changes in the liver consistent with chronic cardiac disease.


Figure 1. Gross postmortem images of heart of case 2. The pericardial sac has been opened to reveal the abnormal, neoplastic epicardial surface.

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Case 3

  1. Top of page
  2. Case 1
  3. Case 2
  4. Case 3
  5. References

A 7-year-old Holstein cow was presented to the Veterinary Medical Teaching Hospital at the University of Wisconsin for evaluation of an acute onset of anorexia coincident with the development of brisket edema. It was a multiparous cow with an unremarkable medical history before the current problem. The cow was non-lactating and at approximately 7 months of gestation. Physical examination upon presentation disclosed muffled cardiac sounds with a heart rate of 88 beats per minute, but a normal respiratory rate of 20 breaths per minute and rectal temperature of 101.3 F. The jugular and mammary veins were distended and brisket edema was marked, extending to the retropharyngeal area.

Echocardiography using a 3.5 MHz phased array transducer1 from a right parasternal approach identified an approximately 8-cm distension of the pericardial sac by effusion that was present throughout all phases of the cardiac cycle. Abdominal ultrasound examination identified heptomegaly with rounded liver margins and a subjective increase in the diameter and number of visible hepatic blood vessels suggesting hepatic congestion. Fetal ultrasound demonstrated normal placentation and fetal fluids with a fetal heart rate of 110–138 beats per minute. Pericardiocentesis yielded a hemorrhagic fluid with a PCV of 10%, total protein concentration of 4.6 g/dL and TNCC of 16.37 × 103/μL, comprised of 21% nondegenerate neutrophils, 3% mononuclear cells and 76% small lymphocytes. A serum sample obtained at admission was positive for antibodies to BLV by both ELISA and AGID techniques. The hemogram and leukogram were normal but mild increases in GGT activity (159 IU/L; normal reference range, 12–30 IU/L), and CK activity (1661 IU/L; normal reference range, 50–271 IU/L) and slightly low albumin concentration (2.8 g/dL; normal reference range, 3.2–4.3 g/dL) were observed. Pericardial drainage was performed through the left 5th intercostal space using a 24 French chest tube, yielding approximately 10 L of hemorrhagic fluid.

Medical treatment with 2.2 mg/kg IV q12h ceftiofur and 0.1 mg/kg IV q24h dexamethasone was instituted after pericardial drainage. The cow improved markedly over the following 72 hours with a return to a normal appetite and a dramatic reduction in the amount of pericardial fluid to <10 mm distension by day 3. Venous distension was markedly improved. No masses or other abnormalities could be detected within the myocardium and the only detectable echocardiographic abnormality noted was the presence of small, focal areas of what appeared to be epicardial fibrin. On day 4 the dexamethasone dosage was decreased to 0.05 mg/kg IV q24h. On the 6th day of hospitalization, a blood-tinged vaginal discharge was noted that was associated with spontaneous abortion of a normal male fetus approximately 24 hours later. The dexamethasone dosage was further decreased to 0.05 mg/kg IV every other day for 3 treatments beginning on day 6, and the cow was discharged on day 10 at which time the ceftiofur was discontinued.

Over the ensuing 14 months, the cow was used successfully as an embryo transfer donor on multiple occasions before being allowed to carry a pregnancy of her own to term. After delivery of a healthy heifer calf, it was used once again as a successful embryo donor for several months before reoccurrence of clinical signs was noted by the owner.

The cow was presented to the University of Wisconsin 19 months after initial discharge with signs of congestive heart failure. Repeat ultrasound examination and pericardiocentesis demonstrated a dramatic refilling of the pericardial sac with a fluid that had a total protein concentration of 4.4 g/dL, a PCV of 2%, and TNCC of 11.65 × 103/μL, comprised of 88% large lymphoblasts and 12% nondegenerate neutrophils. Pericardial drainage of approximately 25 L of bloody fluid was performed as a salvage procedure to perform ovary harvest for postmortem oocyte aspiration 36 hours later.

At postmortem examination there was diffuse proliferative epicarditis, histologically comprised of papillary fibrovascular tissue infiltrated diffusely by large atypical lymphoblasts and a few small lymphocytes, plasma cells, and neutrophils. Histologically, the myocardium demonstrated focal areas of fibrosis, but no neoplastic infiltration was noted in the heart muscle. Thoracic and peripheral lymph nodes had no gross nor histologic evidence of lymphosarcoma, although neoplastic infiltration of the lamina propria in the abomasum and the mesenteric lymph nodes were observed. The liver had gross and histologic changes consistent with chronic passive congestion consistent with chronic heart disease.

There have been 3 previous reports in the literature of idiopathic pericardial effusion in dairy cattle.[1-3] Two of these publications represent retrospective studies documenting mature dairy cattle that were presented for evaluation at referral hospitals with clinical signs of heart failure associated with a hemorrhagic pericardial effusion and cardiac tamponade,[1, 2] the other was a single case report.[3] The outcome of these cases was much more favorable than is typically associated with other forms of cardiac disease in adult cattle such as traumatic septic reticulopericarditis, endocarditis, and cardiac neoplasia.[1] The heart is a common predilection site for lymphosarcoma in mature cattle. Identifiable cardiac tumors are present in 664[4]89%[5] of lymphosarcoma cases. The right atrium is most commonly involved.[6] As a result of cardiac involvement, clinical signs include arrhythmias, murmurs, muffled heart sounds, and potentially signs of congestive heart failure such as distended peripheral veins, edema, and exercise intolerance. The 3 cattle in this report had physical examination findings at initial presentation that were consistent with effusive pericardial disease and tamponade (muffled heart sounds, signs of congestive failure). No murmurs or arrhythmias were auscultated at any time in these cattle. These 3 cases share some similarities with the previous publications by Firshmann et al,[1] Jesty and Sweeney[2] and Buczinski and Badillo.[3] However, no mention was made of neoplasia in these reports unlike the cattle described in this study. In the study by Jesty and Sweeney,[2] after treatment, 1 of the 2 cows was healthy at 6-month follow-up and the other survived for several years before being culled for unrelated reasons. Of the 5 cattle reported by Firshmann et al,[1] 4 underwent treatment after which 2 were alive at follow-up at 12 months and 2 years, 2 died at 6 months and 1 year post discharge from unrelated reasons, and 1 was euthanized without any attempt at treatment. The euthanized cow had some similar gross postmortem findings to the cattle of this report with dark red fluid within the pericardial sac and epicardial fibrin deposits[1]. After discharge, two of the survivors in the study by Firshmann et al[1] suffered relapses that were successfully treated by pericardiocentesis or medical treatment with diuretics and corticosteroids. Although there are similarities among the 3 cases in this report and the previous reports by Jesty and Sweeney[2] and Buczinski and Badillo[3], cytologic evaluation of the pericardial effusion differed between the studies. In these cases, the predominant cell type was lymphocytes, more consistent with what had been reported by Firshmann et al[1] whereas the other 2 reports documented either a greater proportion of neutrophils[3] or a similar proportion of neutrophils and lymphocytes[2].

At the time of initial presentation, the cattle of this study had no peripheral lymphocytosis or cytologic evidence of exfoliative cardiac lymphosarcoma, despite being BLV positive. Testing and documentation of BLV status was not consistently performed in all previous reports, although several cows were documented to be BLV negative[1-3]. Thus, it is hard to draw conclusions on whether or not BLV status might influence the cytology of the pericardial fluid. The observation that hemorrhagic pericardial effusion can arise in both BLV infected and BLV uninfected cattle suggests the possibility of multiple etiologies for this syndrome in adult cattle.

Similar to some of the previous case reports, our findings support the observation that this condition is potentially treatable and that extended survival times can be achieved through combinations of pericardial drainage and corticosteroid treatment. Management of pericardial effusion associated with cardiac lymphosarcoma by drainage alone[7] or combined with pericardiotomy[8, 9] has been reported in the literature previously. However, specific survival times in these cases have been only a few weeks[8, 9] although individuals with cardiac lymphoma have been reported to survive for several months after pericardiotomy.[7] In each of these cases, dexamethasone was administered in addition to pericardial drainage at the time of diagnosis, and not surprisingly its use was associated with abortion in case 3. The decision to use dexamethasone was made in consultation with the owner of that animal.

In this case series, protracted remission was achieved in 1 cow for approximately 31 months and for 19 and 3 months, respectively, in the other 2 cows. During these periods of remission, the cows were used successfully for either reproductive or milk production purposes. Although it is impossible to rule out, it appears highly unlikely that 2 of these cattle (cases 2 and 3) had cardiac lymphosarcoma at the time they initially presented. Such protracted survival times (31 and 19 months) would be unlikely. Additional circumstantial evidence that the condition represents an atypical variant of cardiac lymphosarcoma localized to the epicardium compared to more typical right atrial myocardial lymphosarcoma[4-6, 10] can be drawn from the postmortem examinations. Each of these cattle had a predominantly epicardial location to the neoplastic infiltrate with neither myocardial nor endocardial masses and no histologic evidence of lymphosarcoma in these locations. However, all 3 cows had evidence of either local lymph node or other organ involvement. Furthermore, two of the 3 cows had biochemical evidence of hepatic injury at initial evaluation (increased GGT activity) followed by pathologic evidence of chronic, passive hepatic congestion, consistent with congestive heart disease, at necropsy. Given the relative rarity of sporadic lymphosarcoma in mature cattle and the fact that each of these cattle was seropositive for BLV infection at initial examination, it appears likely that this represents a manifestation of retrovirally induced enzootic bovine lymphosarcoma. Whether or not malignant transformation occurs against a background of chronic inflammatory epicarditis or arises de novo as a spontaneous event at a heretofore rarely described anatomic site[11] is not certain. There are precedents for chronic inflammation and cellular injury being associated with neoplasia. Both epidemiologic and pathogenetic studies have shown that chronic inflammation predisposes humans to a variety of different cancers including bladder, cervical, gastric, intestinal, prostatic, liver, and thyroid tumors.[12, 13]Although the association is less well established in large animals, a similar process may occur with squamous cell carcinoma in horses and cattle[14, 15]. Malignant transformation in association with either specific viral oncogenes or chronic viral infection, as is the case with BLV infection and lymphosarcoma, also are well documented. Establishing the fundamental mechanism and pathways by which epicardial lymphosarcoma develops in cases such as those described herein would be challenging but potentially relevant for translational medicine.

  1. 1

    Universal Systems, Bedford Hills, NY


  1. Top of page
  2. Case 1
  3. Case 2
  4. Case 3
  5. References
  • 1
    Firshman AM, Sage AM, Valberg SJ, et al. Idiopathic hemorrhagic pericardial effusion in cows. J Vet Intern Med 2006;20:14991502.
  • 2
    Jesty SA, Sweeney RW, Dolente BA, Reef VB. Idiopathic pericarditis and cardiac tamponade in two cows. J Am Vet Med Assoc 2005;226(Suppl 9):15551558.
  • 3
    Buczinski S, Badillo M. Idiopathic hemorrhagic pericarditis in a Holstein cow. Bov Pract 2009;43:5155.
  • 4
    Burton AJ, Nydam DV, Long ED, Divers TJ. Signalment and clinical complaints initiating hospital admission, methods of diagnosis, and pathological findings associated with bovine lymphosarcoma (112 cases). J Vet Intern Med 2010;24:960964.
  • 5
    Marshak RR, Coriell LL, Lawrence WC, et al. Studies on bovine lymphosarcoma. I. Clinical aspects, pathological alterations and herd studies. Cancer Res 1962;22:202217.
  • 6
    Divers TJ, Peek SF. Rebhun's Diseases of Dairy Cattle, 2nd ed. St. Louis, MO: Saunders Elsevier; 2008:627629.
  • 7
    Buczinski S, Boulay G, DesCoteaux L. Repeated pericardiocentesis as palliative treatment for tamponade associated with cardiac lymphoma in a Holstein cow. Can Vet J 2011;52:663666.
  • 8
    McGuirk SM. Treatment of cardiovascular disease in cattle. Vet Clin Nth Am Food Anim Pract 1991;7:729746.
  • 9
    Van Biervliet J, Kraus M, Woodie B, et al. Thorascopic pericardiotomy as a palliative treatment in a cow with pericardial lymphoma. J Vet Cardiol 2006;8:6973.
  • 10
    Buczinski S, Francoz D, Fecteau G, DiFruscia R. Heart disease in cattle with clinical signs of heart failure: 59 cases. Can Vet J 2010;51:11231129.
  • 11
    Ivany JM, Illanes OG. Congestive heart failure due to epicardial lymphosarcoma in a Holstein cow. Can Vet J 1999;40:819820.
  • 12
    Wai PY, Kuo P. Intersecting pathways in inflammation and cancer: Hepatocellular carcinoma as a paradigm. World J Clin Oncol 2012;3(Suppl 2):1523.
  • 13
    Chow MT, Moller A, Smyth MJ. Inflammation and immune surveillance in cancer. Semin Cancer Biol 2012;22(Suppl 1):2332.
  • 14
    Giulano EA. Equine periocular neoplasia: Current concepts in aetiopathogenesis and emerging treatment modalities. Equine Vet J Suppl. 2010;37:918.
  • 15
    Sironi G, Riccaboni P, Mertel L, et al. p53 protein expression in conjunctival squamous cell carcinomas of domestic animals. Vet Ophthalmol 1999;2:227231.