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Pathology in Practice

Pathology in Practice

Michelle Liu Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN

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Pierre-Yves Mulon Department of Large Animal Medicine, College of Veterinary Medicine, University of Tennessee, Knoxville, TN

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Mee-Ja M. Sula Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN

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DOI:
https://doi.org/10.2460/javma.20.12.0718
Volume/Issue:
Volume 260: Issue 4
Online Publication Date:
21 Jan 2022
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History

A 7-month-old 9.69-kg sexually intact female mixed-breed goat was presented to the University of Tennessee College of Veterinary Medicine farm animal medicine and surgery service because of a 2-week duration of neurologic signs. The owner also reported that the goat had tested negative for serologic detection of caprine arthritis–encephalitis virus (CAEV). Upon arrival, the goat was recumbent and unresponsive. Due to progressive clinical deterioration and a poor prognosis, the goat was euthanized and immediately submitted for necropsy. The goat’s vaccination history was unknown.

Gross Findings

Postmortem examination revealed a diffusely wet brain that oozed abundant light clear fluid (edema). Bilaterally, the lateral ventricles were moderately dilated and lined by a 1-mm-thick layer of yellow, slightly granular material (Figure 1). After fixation, cross sections through the affected regions revealed effacement of the ependyma with cavitation and loss of the white matter surrounding the right and left lateral ventricles. The cerebral cortex did not autofluoresce under UV light. Findings for the lungs were unremarkable, and all sections of lung floated in water. Findings for the carpal and tarsal joints and the mammary gland were grossly unremarkable.

Figure 1
Figure 1
Figure 1

Photographs of the cerebrum from a 7-month-old sexually intact female mixed-breed goat that was euthanized after a 2-week duration of neurologic signs. A—Lateral ventricle of the right cerebral hemisphere is mildly dilated and lined by yellow granular material (arrow), which effaces the ependyma and areas of the surrounding white matter. B—Formalin-fixed cross section of the right hemisphere of the cerebrum. The ependyma is effaced with cavitation (asterisk) and loss of the white matter surrounding the right lateral ventricle.

Citation: Journal of the American Veterinary Medical Association 260, 4; 10.2460/javma.20.12.0718

Histopathologic and Microbiological Findings

Bilaterally, the lateral ventricles were moderately dilated. Surrounding the lateral and third ventricles and extending into the internal capsule, thalamus, and cerebellum were patchy to regionally extensive regions of subependymal white matter loss with extensive cavitation and replacement with numerous foamy macrophages (gitter cells), abundant cholesterol clefts, scattered aggregates of mineral, and cellular debris (Figure 2). Surrounding these areas, the neuropil was variably rarified and vacuolated with scattered hypereosinophilic, angular neurons with pyknotic nuclei (neuronal necrosis). The remaining white and gray matter was regionally infiltrated by plump glial cells. Multiple surrounding vessels within the parenchyma and meninges were cuffed by up to 10 concentric layers of lymphocytes and fewer plasma cells.

Figure 2
Figure 2
Figure 2
Figure 2

Photomicrographs of sections of the right cerebrum (A and B) and lung (C) of the goat described in Figure 1. A—There is extensive white matter loss and cavitation (asterisk) surrounding the lateral ventricle and affecting patchy areas within the thalamus. H&E stain; bar = 5 mm. B—There is periventricular white matter loss and replacement with numerous gitter cells, cholesterol clefts (short arrows), mineral aggregates (long arrows), and necrotic debris. Vessels are cuffed by lymphocytes and fewer plasma cells. H&E stain; bar = 100 µm. C—Alveolar septa are thickened by infiltrates of lymphocytes and macrophages, which often surround vessels. H&E stain; bar = 100 µm. Inset—An alveolus is lined by type II pneumocyte hyperplasia (arrow). H&E stain; bar = 20 µm.

Citation: Journal of the American Veterinary Medical Association 260, 4; 10.2460/javma.20.12.0718

Within the lung, alveolar septa were lined by plump cuboidal cells (type II pneumocyte hyperplasia) and were thickened by fibrous tissue and perivascular infiltrates of macrophages and lymphocytes (Figure 2). Within the spleen, multiple lymphoid follicles and periarteriolar lymphoid sheaths were hyperplastic with prominent germinal centers (age-asso-ciated lymphoid hyperplasia). Sections of the kidney, liver, and heart were examined and had no important microscopic findings. Aerobic bacterial culture was performed on a swab specimen of the right lateral ventricle, which yielded mixed organisms in low numbers.

Immunohistochemical analysis for CAEV was performed on tissue sections from the cerebrum and lung at the University of Minnesota Veterinary Diagnostic Laboratory. The provided external positive and negative controls were adequate. Within the cerebrum, approximately 1% of macrophages within areas of inflammation in the cerebral white matter and thalamus had moderate intracytoplasmic punctate immunoreactivity to CAEV (Figure 3). Within the lung, approximately 5% of macrophages within areas of inflammation had strong intracytoplasmic punctate immunoreactivity to CAEV. These findings strongly supported a diagnosis of CAEV or another small ruminant lentivirus (SRLV).

Figure 3
Figure 3
Figure 3

Photomicrographs of tissue sections of brain (A) and lung (B) with immunohistochemical staining for caprine arthritis-encephalitis virus (CAEV). A—In the cerebral white matter surrounding the lateral ventricle (asterisk), scattered macrophages have moderate to strong cytoplasmic punctate immunoreactivity for CAEV. CAEV-specific immunohistochemical stain; bar = 200 µm. Inset—High-magnification view of macrophages with immunoreactivity for CAEV (arrowheads). CAEV-specific immunohistochemical stain; bar = 20 µm. B—Within the lung, scattered macrophages have strong cytoplasmic punctate immunoreactivity for CAEV. CAEV-specific immunohistochemical stain; bar = 100 µm.

Citation: Journal of the American Veterinary Medical Association 260, 4; 10.2460/javma.20.12.0718

Morphologic Diagnosis and Case Summary

Morphologic diagnosis: marked chronic periventricular necrotizing and lymphohistiocytic leukoencephalitis and mild chronic multifocal lymphocytic interstitial pneumonia.

Case summary: CAEV or another SRLV infection in a young goat.

Comments

SRLVs, which include CAEV and maedi-visna virus, are retroviruses that cause an economically important, multisystemic disease of goats and sheep.1 The SRLVs are highly diverse and generally classified into 5 genotypes (A through E), which can be further distributed into various subtypes or strains.2,3 Though some subtypes are host-specific to either goats or sheep, several subtypes are capable of cross-species infection.2,3 Lentivirus predominantly spreads through colostrum or milk, but can also be transmitted horizontally through direct contact with nasal secretions.1,4 Although infection and shedding of the lentivirus persist for life, infected goats are often sublinical.1,4 However, once clinical illness appears, the disease is often progressive and can be fatal.1

Depending on viral strain, host genetics, and concurrent infection with other pathogens, SRLV infection can manifest as 1 syndrome or a combination of syndromes, which include arthritis, encephalitis, mastitis, and pneumonia.1,4 Infection of young goats, usually 1 to 6 months of age, will typically result in fatal neurologic disease1 and concurrent pulmonary disease,4 as seen in this case. Arthritis and mastitis are more typical in adult goats4 and were not present in this case.

Grossly and microscopically, SRLV infection in sheep and goats can present similarly but vary in several ways. Typically, goats have white matter loss, and inflammation usually progresses caudally from the midbrain to the cerebellum and spinal cord. Interestingly, the goat of the present report had severe cerebral white matter loss with grossly evident cavitation, a pattern more commonly reported in sheep.5 The cerebellum and brainstem in this goat were only mildly affected, compared with the cerebrum. As the goat did not have reported clinical changes that could have been attributed to spinal cord disease, the spinal cord was not examined, but histologic findings typically involve patchy subpial white matter demyelination.5 In addition, this goat had concurrent histologic pulmonary findings of prominent type II pneumocyte hyperplasia and mononuclear perivascular cuffing, both of which are less commonly reported features in similarly affected sheep.4,5

Several diagnostic tests can be performed to confirm SRLV infection. Antemortem serologic results were negative for the detection of CAEV; however, false negative results can result from delayed antibody production following infection or periods of seronegativity.2,6 False positive results can also occur in young animals because of the consumption of infected colostrum or milk containing viral antibodies.2,7 A quantitative PCR assay was not performed in this case but is a highly sensitive test that can be useful in combination with serology to confirm the diagnosis.2,8 Additionally, PCR assay can be more advantageous over serology, given the ability of the PCR assay to detect the virus before antibody titer development.2 Furthermore, despite the genetic diversity of SRLVs, most SRLVs have conserved genes, such as gag, pol, env, and LTR, that can be specifically targeted by PCR primers for detection.2 Immunohistochemistry analysis, which was used to confirm infection in this case, can be useful in attributing the virus with the inflammatory lesions identified microscopically.

Other infectious causes for neurologic disease in young goats were also considered. Although listeriosis, or circling disease, caused by the bacterium Listeria monocytogenes, is a common differential diagnosis for neurologic deficits in goats, there were no microabscesses within the brainstem or remainder of the brain, the diagnostic histologic finding associated with L monocytogenes infection. Additionally, bacterial culture performed on a swab specimen of the right lateral ventricle revealed low numbers of mixed organisms, which were likely bacterial contaminants and not representative of clinically important microbial growth. Although rabies was not tested for in this goat, the lack of diagnostic histologic changes, such as Negri bodies within neurons, made this differential diagnosis an unlikely cause of this goat’s neurologic signs.

A common noninfectious cause of neurologic disease in young small ruminants is polioencephalomalacia, which is often associated with thiamine deficiency. In this condition, the cerebral cortex or gray matter is characteristically friable and softened to extensively lost (cerebrocortical necrosis), leaving intact white matter.5 The goat of the present report had a loss of white matter, instead of gray matter, which was inconsistent with gross findings associated with polioencephalomalacia. In addition, the cerebral cortex did not autofluoresce under UV light, as is expected with polioencephalomalacia. On the other hand, congenital swayback, associated with neonatal copper deficiency, can result in extensive bilateral cerebral white matter cavitation in goat kids; however, this condition is uncommon in eastern Tennessee, more common in lambs, and typically associated with sparse inflammation,5 unlike in this case.

There is no specific treatment or vaccination for SRLV infection.3 Serologic identification and separation of infected animals from the flock is recommended for prevention of transmission.1,9

Given the signalment, clinical signs, and postmortem findings, this was a case of concurrent SRLV pneumonia and encephalitis in a goat kid, which was striking due to the severity of cerebral white matter loss. Although forebrain cavitation is relatively common in adult sheep with SRLV infections, lesions in goats tend to be concentrated within the midbrain, cerebellum, and spinal cord and uncommonly result in grossly evident cavitation.

References

  • 1. ↑

    Wolf C. Update on small ruminant lentiviruses. Vet Clin North Am Food Anim Pract. 2021;37(1):199–208. doi:10.1016/j.cvfa.2020.12.003

  • 2. ↑

    Ramírez H, Reina R, Amorena B, de Andrés D, Martínez HA. Small ruminant lentiviruses: genetic variability, tropism and diagnosis. Viruses. 2013;5(4):1175–1207. doi:10.3390/v5041175

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3. ↑

    Center for Food Security and Public Health. Small ruminant lentiviruses: maedi-visna and caprine arthritis and encephalitis. Iowa State University. May 2015. Accessed November 22, 2020. https://www.cfsph.iastate.edu/Factsheets/pdfs/maedi_visna_and_caprine_arthritis_encephalitis.pdf

    • Search Google Scholar
    • Export Citation
  • 4. ↑

    Caswell JL, Williams KJ. Respiratory system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. Elsevier; 2016:558–560.

    • Search Google Scholar
    • Export Citation
  • 5. ↑

    Cantile C, Youssef S. Nervous system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Elsevier; 2016:309–312, 328–329, 378–379.

    • Search Google Scholar
    • Export Citation
  • 6. ↑

    de Andrés D, Klein D, Watt NJ, et al. Diagnostic tests for small ruminant lentiviruses. Vet Microbiol. 2005;107(1-2):49–62. doi:10.1016/j.vetmic.2005.01.012

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7. ↑

    Herrmann-Hoesing LM. Diagnostic assays used to control small ruminant lentiviruses. J Vet Diagn Invest. 2010;22(6):843–855. doi:10.1177/104063871002200602

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8. ↑

    Pinczowski P, Sanjosé L, Gimeno M, et al. Small ruminant lentiviruses in sheep: pathology and tropism of 2 strains using the bone marrow route. Vet Pathol. 2017;54(3):413–424. doi:10.1177/0300985816688742

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9. ↑

    Pérez M, Muñoz JA, Biescas E, et al. Successful visna/maedi control in a highly infected ovine dairy flock using serologic segregation and management strategies. Prev Vet Med. 2013;112(3-4):423–427. doi:10.1016/j.prevetmed.2013.07.019

    • Search Google Scholar
    • Export Citation

Contributor Notes

Corresponding author: Dr. Liu (mliu34@utk.edu)

In collaboration with the American College of Veterinary Pathologists

Cover Journal of the American Veterinary Medical Association
Journal of the American Veterinary Medical Association
Publication Date:
15 Feb 2022
  • Figure 1 Figure 1
    View in gallery
    Figure 1

    Photographs of the cerebrum from a 7-month-old sexually intact female mixed-breed goat that was euthanized after a 2-week duration of neurologic signs. A—Lateral ventricle of the right cerebral hemisphere is mildly dilated and lined by yellow granular material (arrow), which effaces the ependyma and areas of the surrounding white matter. B—Formalin-fixed cross section of the right hemisphere of the cerebrum. The ependyma is effaced with cavitation (asterisk) and loss of the white matter surrounding the right lateral ventricle.

  • Figure 2 Figure 2 Figure 2
    View in gallery
    Figure 2

    Photomicrographs of sections of the right cerebrum (A and B) and lung (C) of the goat described in Figure 1. A—There is extensive white matter loss and cavitation (asterisk) surrounding the lateral ventricle and affecting patchy areas within the thalamus. H&E stain; bar = 5 mm. B—There is periventricular white matter loss and replacement with numerous gitter cells, cholesterol clefts (short arrows), mineral aggregates (long arrows), and necrotic debris. Vessels are cuffed by lymphocytes and fewer plasma cells. H&E stain; bar = 100 µm. C—Alveolar septa are thickened by infiltrates of lymphocytes and macrophages, which often surround vessels. H&E stain; bar = 100 µm. Inset—An alveolus is lined by type II pneumocyte hyperplasia (arrow). H&E stain; bar = 20 µm.

  • Figure 3 Figure 3
    View in gallery
    Figure 3

    Photomicrographs of tissue sections of brain (A) and lung (B) with immunohistochemical staining for caprine arthritis-encephalitis virus (CAEV). A—In the cerebral white matter surrounding the lateral ventricle (asterisk), scattered macrophages have moderate to strong cytoplasmic punctate immunoreactivity for CAEV. CAEV-specific immunohistochemical stain; bar = 200 µm. Inset—High-magnification view of macrophages with immunoreactivity for CAEV (arrowheads). CAEV-specific immunohistochemical stain; bar = 20 µm. B—Within the lung, scattered macrophages have strong cytoplasmic punctate immunoreactivity for CAEV. CAEV-specific immunohistochemical stain; bar = 100 µm.

Figure 1

Photographs of the cerebrum from a 7-month-old sexually intact female mixed-breed goat that was euthanized after a 2-week duration of neurologic signs. A—Lateral ventricle of the right cerebral hemisphere is mildly dilated and lined by yellow granular material (arrow), which effaces the ependyma and areas of the surrounding white matter. B—Formalin-fixed cross section of the right hemisphere of the cerebrum. The ependyma is effaced with cavitation (asterisk) and loss of the white matter surrounding the right lateral ventricle.
Figure 1

Photographs of the cerebrum from a 7-month-old sexually intact female mixed-breed goat that was euthanized after a 2-week duration of neurologic signs. A—Lateral ventricle of the right cerebral hemisphere is mildly dilated and lined by yellow granular material (arrow), which effaces the ependyma and areas of the surrounding white matter. B—Formalin-fixed cross section of the right hemisphere of the cerebrum. The ependyma is effaced with cavitation (asterisk) and loss of the white matter surrounding the right lateral ventricle.
Figure 2

Photomicrographs of sections of the right cerebrum (A and B) and lung (C) of the goat described in Figure 1. A—There is extensive white matter loss and cavitation (asterisk) surrounding the lateral ventricle and affecting patchy areas within the thalamus. H&E stain; bar = 5 mm. B—There is periventricular white matter loss and replacement with numerous gitter cells, cholesterol clefts (short arrows), mineral aggregates (long arrows), and necrotic debris. Vessels are cuffed by lymphocytes and fewer plasma cells. H&E stain; bar = 100 µm. C—Alveolar septa are thickened by infiltrates of lymphocytes and macrophages, which often surround vessels. H&E stain; bar = 100 µm. Inset—An alveolus is lined by type II pneumocyte hyperplasia (arrow). H&E stain; bar = 20 µm.
Figure 2

Photomicrographs of sections of the right cerebrum (A and B) and lung (C) of the goat described in Figure 1. A—There is extensive white matter loss and cavitation (asterisk) surrounding the lateral ventricle and affecting patchy areas within the thalamus. H&E stain; bar = 5 mm. B—There is periventricular white matter loss and replacement with numerous gitter cells, cholesterol clefts (short arrows), mineral aggregates (long arrows), and necrotic debris. Vessels are cuffed by lymphocytes and fewer plasma cells. H&E stain; bar = 100 µm. C—Alveolar septa are thickened by infiltrates of lymphocytes and macrophages, which often surround vessels. H&E stain; bar = 100 µm. Inset—An alveolus is lined by type II pneumocyte hyperplasia (arrow). H&E stain; bar = 20 µm.
Figure 2

Photomicrographs of sections of the right cerebrum (A and B) and lung (C) of the goat described in Figure 1. A—There is extensive white matter loss and cavitation (asterisk) surrounding the lateral ventricle and affecting patchy areas within the thalamus. H&E stain; bar = 5 mm. B—There is periventricular white matter loss and replacement with numerous gitter cells, cholesterol clefts (short arrows), mineral aggregates (long arrows), and necrotic debris. Vessels are cuffed by lymphocytes and fewer plasma cells. H&E stain; bar = 100 µm. C—Alveolar septa are thickened by infiltrates of lymphocytes and macrophages, which often surround vessels. H&E stain; bar = 100 µm. Inset—An alveolus is lined by type II pneumocyte hyperplasia (arrow). H&E stain; bar = 20 µm.
Figure 3

Photomicrographs of tissue sections of brain (A) and lung (B) with immunohistochemical staining for caprine arthritis-encephalitis virus (CAEV). A—In the cerebral white matter surrounding the lateral ventricle (asterisk), scattered macrophages have moderate to strong cytoplasmic punctate immunoreactivity for CAEV. CAEV-specific immunohistochemical stain; bar = 200 µm. Inset—High-magnification view of macrophages with immunoreactivity for CAEV (arrowheads). CAEV-specific immunohistochemical stain; bar = 20 µm. B—Within the lung, scattered macrophages have strong cytoplasmic punctate immunoreactivity for CAEV. CAEV-specific immunohistochemical stain; bar = 100 µm.
Figure 3

Photomicrographs of tissue sections of brain (A) and lung (B) with immunohistochemical staining for caprine arthritis-encephalitis virus (CAEV). A—In the cerebral white matter surrounding the lateral ventricle (asterisk), scattered macrophages have moderate to strong cytoplasmic punctate immunoreactivity for CAEV. CAEV-specific immunohistochemical stain; bar = 200 µm. Inset—High-magnification view of macrophages with immunoreactivity for CAEV (arrowheads). CAEV-specific immunohistochemical stain; bar = 20 µm. B—Within the lung, scattered macrophages have strong cytoplasmic punctate immunoreactivity for CAEV. CAEV-specific immunohistochemical stain; bar = 100 µm.
  • 1.

    Wolf C. Update on small ruminant lentiviruses. Vet Clin North Am Food Anim Pract. 2021;37(1):199–208. doi:10.1016/j.cvfa.2020.12.003

  • 2.

    Ramírez H, Reina R, Amorena B, de Andrés D, Martínez HA. Small ruminant lentiviruses: genetic variability, tropism and diagnosis. Viruses. 2013;5(4):1175–1207. doi:10.3390/v5041175

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Center for Food Security and Public Health. Small ruminant lentiviruses: maedi-visna and caprine arthritis and encephalitis. Iowa State University. May 2015. Accessed November 22, 2020. https://www.cfsph.iastate.edu/Factsheets/pdfs/maedi_visna_and_caprine_arthritis_encephalitis.pdf

    • Search Google Scholar
    • Export Citation
  • 4.

    Caswell JL, Williams KJ. Respiratory system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. Elsevier; 2016:558–560.

    • Search Google Scholar
    • Export Citation
  • 5.

    Cantile C, Youssef S. Nervous system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Elsevier; 2016:309–312, 328–329, 378–379.

    • Search Google Scholar
    • Export Citation
  • 6.

    de Andrés D, Klein D, Watt NJ, et al. Diagnostic tests for small ruminant lentiviruses. Vet Microbiol. 2005;107(1-2):49–62. doi:10.1016/j.vetmic.2005.01.012

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Herrmann-Hoesing LM. Diagnostic assays used to control small ruminant lentiviruses. J Vet Diagn Invest. 2010;22(6):843–855. doi:10.1177/104063871002200602

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Pinczowski P, Sanjosé L, Gimeno M, et al. Small ruminant lentiviruses in sheep: pathology and tropism of 2 strains using the bone marrow route. Vet Pathol. 2017;54(3):413–424. doi:10.1177/0300985816688742

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Pérez M, Muñoz JA, Biescas E, et al. Successful visna/maedi control in a highly infected ovine dairy flock using serologic segregation and management strategies. Prev Vet Med. 2013;112(3-4):423–427. doi:10.1016/j.prevetmed.2013.07.019

    • Search Google Scholar
    • Export Citation

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