Pathology in Practice

Tamara Veiga-Parga Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.

Search for other papers by Tamara Veiga-Parga in
Current site
Google Scholar
PubMed
Close
 DVM, PhD
,
Michelle Nobrega-Lee Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.

Search for other papers by Michelle Nobrega-Lee in
Current site
Google Scholar
PubMed
Close
 DVM
, and
Shelley J. Newman Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.

Search for other papers by Shelley J. Newman in
Current site
Google Scholar
PubMed
Close
 DVM, DVSc

History

A 3.5-year-old 553-kg (1,217-lb) Holstein cow that had a 1-week history of mastitis and a 3-day history of progressive, unilateral neurologic signs was euthanized and submitted for necropsy to the University of Tennessee College of Veterinary Medicine.

Antemortem Clinical and Postmortem Gross Findings

Physical examination, performed by the referring veterinarian, revealed partial facial paralysis on the left side and left ear droop. Microscopic examination of a CSF sample (collected from the lumbosacral region) revealed mild, mononuclear pleocytosis (total nucleated cell count, 8 cells/µL; reference interval, 0.85 to 3.52 cells/µL); total protein concentration was normal (32 mL/dL; reference interval, 20 to 40 mg/dL). Overnight, the cow's condition rapidly worsened to recumbency and severe signs of depression. Following euthanasia by IV administration of pentobarbital sodium and phenytoin sodium solution, the cow was submitted for necropsy. Necropsy revealed that the major lesions were localized to the CNS. In the brainstem, there was a 3 × 3 × 3-cm dark red, soft, slightly irregular mass, most of which occupied the left side of midline (Figure 1). On horizontal cut section, the mass mainly affected the brainstem. Microbial culture of a meningeal swab specimen yielded no growth. There were no other lesions found at the root of the nerves and no evidence of middle ear infection.

Figure 1—
Figure 1—

Photographs of the cerebrum, cerebellum, and brainstem (A) and a cross-section of the formalin-fixed cerebellum and brainstem (B) of a 3.5-year-old Holstein cow that was euthanized because of progressive, unilateral neurologic signs. In panel A, notice the dark red, soft mass (3 × 3 × 3 cm) in the ventral portion of the brainstem. In panel B, the mass mainly affects the brainstem.

Citation: Journal of the American Veterinary Medical Association 248, 10; 10.2460/javma.248.10.1127

Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page →

Histologic Findings

Histologic examination of sections of the left-sided brainstem mass revealed a nonencapsulated, poorly demarcated mass composed of variably sized vascular channels that were lined by a single layer of endothelium (Figure 2). The endothelial cells were spindle shaped with indistinct cell borders, oval to flattened nuclei, and vesicular to dense chromatin. There was moderate anisokaryosis, and mitoses were not apparent. The vascular channels contained blood and were separated by neuropil. Within the intervening neuropil, multifocal to coalescing hemorrhage, gliosis, axonal swelling, and scattered activated microglia were evident.

Figure 2—
Figure 2—

Photomicrographs of sections of the brainstem mass of the cow in Figure 1. A—The mass is composed of variably sized vascular channels separated by neuropil. H&E stain; bar = 200 μm. B—The vascular channels are lined by endothelial cells. H&E stain; bar = 20 μm. C—The neuropil separating the vascular channels has evidence of gliosis (arrowhead), axonal swelling (asterisk), and scattered activated microglia (arrow). H&E stain; bar = 50 μm.

Citation: Journal of the American Veterinary Medical Association 248, 10; 10.2460/javma.248.10.1127

Morphologic Diagnosis and Case Summary

Morphologic diagnosis and case summary: vascular hamartoma in the brainstem of a cow.

Comments

Hamartomas are focal malformations that resemble neoplasms and are formed by disorderly overgrowth of tissue elements that are normally present at that site. They represent aberrant differentiation and proliferation rather than a true neoplasm; therefore, their behavior is usually benign.1 Vascular hamartomas in humans were first described by Willis2 as tumor-like, nonneoplastic malformations or inborn errors of tissue development. The same definition applies to vascular hamartomas in other animals,3 and these malformations have been identified in various tissues of both domestic and exotic species.4–9 In cattle, hamartomas have been detected in several organs10–14; however, none have previously been reported as occurring in the brain, to our knowledge. In contrast to the case described in the present report, hamartomas in animals other than humans are usually diagnosed early in life.7,11,12 Nevertheless, a delayed onset of clinical signs has been reported for some species, particularly when the CNS is affected as reported for dogs6,15,16 and more recently for a cat with a cerebral vascular hamartoma.17 Furthermore, in humans, clinical signs attributable to vascular malformations in the CNS typically become apparent at approximately 30 years of age.18 In a variety of species, this late onset of neurologic clinical signs has been correlated with hemodynamic stress and eventual hemorrhage, which can increase compression on the surrounding parenchyma and result in a secondary obstructive hydrocephalus.17

For classification of this type of lesion, terminology varies; other names include angiomatous hamartoma and telangiectatic hamartoma.4,19 Histologically, vascular hamartomas are described as disorganized or profuse variably sized capillaries that are filled with blood and separated by normal tissue parenchyma, depending on the organ of origin. Therefore, for the cow of the present report, the presence of intervening neuropil and the lack of smooth muscle were the main criteria used to differentiate this hamartoma from a cavernous hemangioma (a vascular tumor with or without smooth muscle-lined channels and very little or no intervening normal tissue).20 Gross differential diagnoses were metastatic hemangiosarcoma or, less likely, locally extensive hemorrhage. Another possible gross differential diagnosis would have been cavernous hemangioma. Moreover, a delayed onset of neurologic disease, such as in the case described in this report, would generally be more indicative of a benign proliferative growing lesion (eg, hemangioma). However, other changes secondary to the presence of the vascular hamartoma, such as compression and hemorrhage in the surrounding parenchyma, can lead to a later onset of neurologic signs, even if the hamartoma had been present for years. The lesion in the cow of the present report was large, and we were not able to perform a histologic assessment in all planes; thus, it is possible that hemorrhage did develop as well.

Hamartomas have been regarded as a continuum between neoplasia and congenital malformations because of the aforementioned compressive effects.16 In the case described in the present report, the cow's unilateral neurologic signs were consistent with damage to the left facial nerve (cranial nerve VII). Grossly, the malformation involved both sides of the brainstem, but the left side was more greatly affected. Worsening of the cow's condition to recumbency with signs of depression likely resulted from brainstem damage or compression. Other differential diagnoses associated with facial nerve paralysis in cows are listeriosis,21 bacterial meningitis, space-occupying lesions at the root of the facial nerve,22 trauma, and middle ear infections.23 In a retrospective study21 that included 94 bovids with listeriosis, more than 50% (58/94) had facial nerve paralysis, and approximately half of these animals were unilaterally affected. For the cow of the present report, listeriosis was the primary differential diagnosis; however, there were no histologic changes consistent with Listeria spp infection and results of microbial culture of a meningeal swab specimen were negative. Moreover, there were no other lesions found at the root of the nerves or any evidence of middle ear infection.

To our knowledge, there are no reports in the veterinary medical literature of treatment of intracranial vascular hamartomas. In the human medical literature, different opinions regarding this issue can be found. Although some authors maintain that not all intracranial vascular malformations should be resected because of their relatively good natural course, others advocate that all intracranial vascular hamartomas should be resected to reduce the risks of bleeding and eventual neurologic deficits,18 as in the case described in the present report and in other reported veterinary cases.6,7,17

To our knowledge, this is the first report of a vascular hamartoma in the brainstem of an adult cow. Although rare, vascular malformations should be included as possible differential diagnoses for intracranial masses in bovids with neurologic signs.

References

  • 1. Zachary JF, McGavin MD. Tumor characteristics. In: Pathologic basis of veterinary diseases. 5th ed. St Louis: Elsevier, 2012;291.

  • 2. Willis RA. Chapter 9. The borderland of embryology and pathology. 2nd ed. London: Butterworths, 1962;351.

  • 3. Summers BA, Cummings JF, de Lahunta A. Tumors of the central nervous system. In: Veterinary neuropathology. St Louis: Mosby, 1995;351401.

    • Search Google Scholar
    • Export Citation
  • 4. Fankhauser R, Luginbühl H, McGrath JT. Cerebrovascular disease in various animal species. Ann N Y Acad Sci 1965; 127: 817860.

  • 5. Cho CY, Cook JE, Leipold HW. Angiomatous vascular malformation in the spinal cord of a Hereford calf. Vet Pathol 1979; 16: 613616.

  • 6. Smith SH, Van Winkle TV. Cerebral vascular hamartomas in five dogs. Vet Pathol 2001; 38: 108112.

  • 7. Stalin CE, Granger N, Jeffery ND. Cerebellar vascular hamartoma in a British Shorthair cat. J Feline Med Surg 2008; 10: 206211.

  • 8. Saifzadeh S, Derakhshanfar A, Shokouhi F, et al. Vascular hamartoma as the cause of hind limb lameness in a horse. J Vet Med A Physiol Pathol Clin Med 2006; 53: 202204.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9. Koehler J, Cox N, Passler T, et al. Subependymal glioneuronal hamartoma in the mesencephalic aqueduct of a giraffe. J Zoo Wildl Med 2012; 43: 629631.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10. Lee CG, Ladds PW. Vascular hamartoma of the ovary in a cow. Aust Vet J 1976; 52: 236.

  • 11. Osborne JC, Troutt HF. A congenital pulmonary anomaly (hamartoma) in a seven-month-old bovine fetus. Cornell Vet 1977; 67: 222228.

    • Search Google Scholar
    • Export Citation
  • 12. Sheahan BJ, Donnelly WJ. Vascular hamartomas in the gingiva of two calves. Vet Pathol 1981; 18: 562564.

  • 13. Ladds PW. Vascular hamartomas of the liver of cattle. Vet Pathol 1983; 20: 764767.

  • 14. Tyler JW, Hassel DM, Long MT, et al. Testicular vascular hamartoma in a calf. Vet Rec 1995; 136: 420.

  • 15. Cordy DR. Vascular malformations and hemangiomas of the canine spinal cord. Vet Pathol 1979; 16: 275282.

  • 16. Sanders SG, Bagley RS, Gavin PR, et al. Surgical treatment of an intramedullary spinal cord hamartoma in a dog. J Am Vet Med Assoc 2002; 221: 659661.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17. Martin-Vaquero P, Moore SA, Wolk KE, et al. Cerebral vascular hamartoma in a geriatric cat. J Feline Med Surg 2011; 13: 286290.

  • 18. Itoyama Y, Uemura S, Ushio Y, et al. Natural course of unoperated intracranial arteriovenous malformations: study of 50 cases. J Neurosurg 1989; 71: 805809.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19. Ribas JL, Carpenter J, Mena H. Comparison of meningo-angiomatosis in a man and a dog. Vet Pathol 1990; 27: 369371.

  • 20. Burger PC, Scheithauer BW. Tumors of mesenchymal tissue. In: Burger PC, Scheithauer BW, eds. Atlas of tumor pathology: tumors of the central nervous system. Washington, DC: Armed Forces Institute for Pathology, 1994;287299.

    • Search Google Scholar
    • Export Citation
  • 21. Schweizer G, Ehrensperger F, Torgerson P, et al. Clinical findings and treatment of 94 cattle presumptively diagnosed with listeriosis. Vet Rec 2006; 158: 588592.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22. Van der Lugt JJ, Jordaan P. Facial paralysis associated with space occupying lesions of cranial nerves in calves. Vet Rec 1994; 134: 579580.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23. Jensen R, Maki LR, Lauerman LH, et al. Cause and pathogenesis of middle ear infection in young feedlot cattle. J Am Vet Med Assoc 1983; 182: 967972.

    • Search Google Scholar
    • Export Citation
  • Figure 1—

    Photographs of the cerebrum, cerebellum, and brainstem (A) and a cross-section of the formalin-fixed cerebellum and brainstem (B) of a 3.5-year-old Holstein cow that was euthanized because of progressive, unilateral neurologic signs. In panel A, notice the dark red, soft mass (3 × 3 × 3 cm) in the ventral portion of the brainstem. In panel B, the mass mainly affects the brainstem.

  • Figure 2—

    Photomicrographs of sections of the brainstem mass of the cow in Figure 1. A—The mass is composed of variably sized vascular channels separated by neuropil. H&E stain; bar = 200 μm. B—The vascular channels are lined by endothelial cells. H&E stain; bar = 20 μm. C—The neuropil separating the vascular channels has evidence of gliosis (arrowhead), axonal swelling (asterisk), and scattered activated microglia (arrow). H&E stain; bar = 50 μm.

  • 1. Zachary JF, McGavin MD. Tumor characteristics. In: Pathologic basis of veterinary diseases. 5th ed. St Louis: Elsevier, 2012;291.

  • 2. Willis RA. Chapter 9. The borderland of embryology and pathology. 2nd ed. London: Butterworths, 1962;351.

  • 3. Summers BA, Cummings JF, de Lahunta A. Tumors of the central nervous system. In: Veterinary neuropathology. St Louis: Mosby, 1995;351401.

    • Search Google Scholar
    • Export Citation
  • 4. Fankhauser R, Luginbühl H, McGrath JT. Cerebrovascular disease in various animal species. Ann N Y Acad Sci 1965; 127: 817860.

  • 5. Cho CY, Cook JE, Leipold HW. Angiomatous vascular malformation in the spinal cord of a Hereford calf. Vet Pathol 1979; 16: 613616.

  • 6. Smith SH, Van Winkle TV. Cerebral vascular hamartomas in five dogs. Vet Pathol 2001; 38: 108112.

  • 7. Stalin CE, Granger N, Jeffery ND. Cerebellar vascular hamartoma in a British Shorthair cat. J Feline Med Surg 2008; 10: 206211.

  • 8. Saifzadeh S, Derakhshanfar A, Shokouhi F, et al. Vascular hamartoma as the cause of hind limb lameness in a horse. J Vet Med A Physiol Pathol Clin Med 2006; 53: 202204.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9. Koehler J, Cox N, Passler T, et al. Subependymal glioneuronal hamartoma in the mesencephalic aqueduct of a giraffe. J Zoo Wildl Med 2012; 43: 629631.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10. Lee CG, Ladds PW. Vascular hamartoma of the ovary in a cow. Aust Vet J 1976; 52: 236.

  • 11. Osborne JC, Troutt HF. A congenital pulmonary anomaly (hamartoma) in a seven-month-old bovine fetus. Cornell Vet 1977; 67: 222228.

    • Search Google Scholar
    • Export Citation
  • 12. Sheahan BJ, Donnelly WJ. Vascular hamartomas in the gingiva of two calves. Vet Pathol 1981; 18: 562564.

  • 13. Ladds PW. Vascular hamartomas of the liver of cattle. Vet Pathol 1983; 20: 764767.

  • 14. Tyler JW, Hassel DM, Long MT, et al. Testicular vascular hamartoma in a calf. Vet Rec 1995; 136: 420.

  • 15. Cordy DR. Vascular malformations and hemangiomas of the canine spinal cord. Vet Pathol 1979; 16: 275282.

  • 16. Sanders SG, Bagley RS, Gavin PR, et al. Surgical treatment of an intramedullary spinal cord hamartoma in a dog. J Am Vet Med Assoc 2002; 221: 659661.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17. Martin-Vaquero P, Moore SA, Wolk KE, et al. Cerebral vascular hamartoma in a geriatric cat. J Feline Med Surg 2011; 13: 286290.

  • 18. Itoyama Y, Uemura S, Ushio Y, et al. Natural course of unoperated intracranial arteriovenous malformations: study of 50 cases. J Neurosurg 1989; 71: 805809.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19. Ribas JL, Carpenter J, Mena H. Comparison of meningo-angiomatosis in a man and a dog. Vet Pathol 1990; 27: 369371.

  • 20. Burger PC, Scheithauer BW. Tumors of mesenchymal tissue. In: Burger PC, Scheithauer BW, eds. Atlas of tumor pathology: tumors of the central nervous system. Washington, DC: Armed Forces Institute for Pathology, 1994;287299.

    • Search Google Scholar
    • Export Citation
  • 21. Schweizer G, Ehrensperger F, Torgerson P, et al. Clinical findings and treatment of 94 cattle presumptively diagnosed with listeriosis. Vet Rec 2006; 158: 588592.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22. Van der Lugt JJ, Jordaan P. Facial paralysis associated with space occupying lesions of cranial nerves in calves. Vet Rec 1994; 134: 579580.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23. Jensen R, Maki LR, Lauerman LH, et al. Cause and pathogenesis of middle ear infection in young feedlot cattle. J Am Vet Med Assoc 1983; 182: 967972.

    • Search Google Scholar
    • Export Citation

Advertisement