Pathology in Practice

Kristin M. Patton Department of Biomedical Sciences and the Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331

Search for other papers by Kristin M. Patton in
Current site
Google Scholar
PubMed
Close
 DVM, PhD
,
Reid Tyson Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331

Search for other papers by Reid Tyson in
Current site
Google Scholar
PubMed
Close
 DVM
,
Louise Castelanelli Pioneer Veterinary Hospital, 801 Main Ave, Tillamook, OR 97141

Search for other papers by Louise Castelanelli in
Current site
Google Scholar
PubMed
Close
 DVM
, and
Howard B. Gelberg Department of Biomedical Sciences and the Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331

Search for other papers by Howard B. Gelberg in
Current site
Google Scholar
PubMed
Close
 DVM, PhD

History

Ten days after calving, a 2-year-old registered Jersey cow was treated for endometritis with ceftiofur crystalline-free acida injected SC at the base of the left ear. A month later, a small swelling was present at the injection site. The swelling continued to grow over the next several weeks. A presumptive diagnosis of an abscess or granuloma was made, and the mass was lanced and drained. Two months after initial treatment, a second small mass near the base of the left horn and a third mass in the center of the forehead were observed. The masses did not seem to be connected. The cow continued to eat and produce milk throughout the clinical course of the disease. Approximately 3 months after identification of the initial mass, the cow was submitted for euthanasia and necropsy because of the rapidly increasing size of the latter 2 masses.

Clinical and Gross Findings

Postmortem radiographic views of the skull revealed an approximately 11.5 × 17.3 × 8.7-cm multilobular, interconnected, expansile mass that deformed the left parietal and occipital bones and contained multiple foci of bone thinning and lysis. The expansile mass was poorly mineralized with ill-defined margins and a long zone of transition, consistent with aggressive bone changes. A portion of the poorly mineralized expansile mass extended into the calvarium. Severe soft tissue swelling was associated with the mass, caudal and medial to the left ear canal.

The cow was in adequate nutritional condition with adequate body fat stores. Lesions were confined to the head. A fluctuant, multilobulated, subcutaneous, ulcerated 25- to 30-cm-diameter mass, extending from the caudal portion of the left orbit to the occiput, was centered at the site of the left horn base and extended slightly over the midline (Figure 1). The mass had eroded the calvarial bone and left orbit. At the level of the dorsolateral aspect of the mesencephalon, an approximately 5-cm-diameter, solid, botryoid portion of the mass compressed but did not invade the cerebrum. The mass remained distinctly extradural and was composed of solid tan to yellow tissue with large areas of necrosis containing thick, white fluid.

Figure 1—
Figure 1—

Photographs of the head (A) and a sagittal section (B) through the skull of a Jersey cow that developed 3 subcutaneous masses on the head over a period of several months and was euthanized. The first mass developed at the site of SC injection of ceftiofur crystalline-free acid, which was administered for treatment of endometritis. In panel A, an ulcerated, subcutaneous mass is present over the left lateral parietal region. In panel B, a variegated, yellow and red extradural mass has obliterated the parietal bone, invaded the cranial vault, and compressed the brain.

Citation: Journal of the American Veterinary Medical Association 244, 3; 10.2460/javma.244.3.287

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

Histopathologic Findings

Sections of the subcutaneous mass were stained with H&E and with immunohistochemical stains for chromogranin A, glial fibrillary acid protein, neuron-specific enolase, synaptophysin, S-100, and vimentin.b The mass consisted of broad, poorly organized, coalescing, highly cellular lobules formed by sheets of large, densely packed, anaplastic, round to polyhedral to spindloid cells punctuated by large lakes of necrotic tissue. In scattered foci, the cells formed small packets outlined by a delicate fibrovascular stroma. Occasional perivascular pseudorosettes were present. The cells had moderate amounts of poorly defined, granular to vacuolated cytoplasm and very large, pleomorphic, round, oval or indented nuclei with ruffled nuclear membranes. Chromatin was granular and dispersed, and there were single to multiple, sometimes prominent nucleoli (Figure 2). There were 0 to 2 mitoses/400× field. Results of immunohistochemical staining for chromogranin A, synaptophysin, and neuron-specific enolase were negative. The neoplastic cells were positive for vimentin (Figure 3) and S-100 (Figure 4) and were occasionally positive for glial fibrillary acid protein (Figure 5).

Figure 2—
Figure 2—

Photomicrograph of a section of the multilobular, interconnected, expansile subcutaneous cranial mass in the Jersey cow in Figure 1. Neoplastic cells have moderate amounts of poorly defined, granular to vacuolated cytoplasm and very large, pleomorphic, round, oval or indented nuclei with ruffled nuclear membranes. The cells are divided into packets by a delicate fibrovascular stroma. H&E stain; bar = 50 μm.

Citation: Journal of the American Veterinary Medical Association 244, 3; 10.2460/javma.244.3.287

Figure 3—
Figure 3—

Photomicrograph of a section of the subcutaneous cranial mass in the Jersey cow in Figure 1. Notice the strong cytoplasmic immunostaining for vimentin. Immunohistochemical stain; bar = 50 μm.

Citation: Journal of the American Veterinary Medical Association 244, 3; 10.2460/javma.244.3.287

Figure 4—
Figure 4—

Photomicrograph of a section of the subcutaneous cranial mass in the Jersey cow in Figure 1. Notice the strong nuclear and cytoplasmic immunostaining for S-100. Immunohistochemical stain; bar = 50 μm.

Citation: Journal of the American Veterinary Medical Association 244, 3; 10.2460/javma.244.3.287

Figure 5—
Figure 5—

Photomicrograph of a section of the subcutaneous cranial mass in the Jersey cow in Figure 1. Notice the strong cytoplasmic immunostaining for glial fibrillary acid protein. Immunohistochemical stain.

Citation: Journal of the American Veterinary Medical Association 244, 3; 10.2460/javma.244.3.287

Morphologic Diagnosis and Case Summary

Morphologic diagnosis and case summary: primitive neuroectodermal tumor (PNET) with ependymal differentiation in a cow.

Comments

Integumentary and subcutaneous neoplasia of cattle, including papilloma virus–associated cutaneous fibropapillomas and squamous cell carcinomas associated with solar radiation in white-faced cattle, are common.1 Less common neoplastic conditions include peripheral nerve sheath tumors (eg, Schwannomas, neurofibromas, and neurilemomas)2–5 that may develop as nodular or varicose thickenings along nerve tracks or nerve roots.5

Primitive neuroectodermal tumors are a family of neoplasms that develop in human infants and children6 but have rarely been reported in cattle.4,7,8 They are formed from primitive neuroepithelial cells with a common embryonic appearance and are thought to develop from a multipotent stem cell capable of differentiation into neuronal, glial, and possibly mesenchymal cell lines.6 Primitive neuroectodermal tumor types include a variety of embryonal neoplasms, such as medulloblastomas, ependymoblastomas, neuroblastomas, and ganglioneuroblastomas as well as tumors classified as PNET with neuronal differentiation, PNET with ependymal cell differentiation, and PNET with glial differentiation.2,9 The specific classification of these tumors is based on their location, histologic features, and immunohistochemical staining properties. Such tumors may be difficult to classify beyond the designation of PNET because of their lack of reactivity to neuronal markers. In cattle, a variety of these embryonal tumor types have been described, including ependymoblastomas, medulloblastomas, neuroblastomas, ganglioneuroblastomas, and glioblastomas.4,10–14 Undifferentiated PNETs in the spinal cord and cerebrum of young cattle have also been recently reported.6,7 Similar to cases of PNET in humans, PNET with ependymal differentiation has developed in bovids that were 6 and 18 months old.11,12 The increasing incidence of PNETs in cattle, as reported in the veterinary medical literature, is likely attributable to an increasing frequency of immunotyping of tumors in cattle.

In the cow of the present report, the relationship of the initial mass with the site of antimicrobial injection was likely incidental. Drug insert information on the safety of SC administration of ceftiofur crystalline-free acida at the base of the ear was reviewed.15 Ceftiofur crystalline-free acida was administered SC to 2,926 beef cattle for comparison of its pharmacokinetics via 2 sites of administration (either the base of the ear or the middle third of the ear). Local tolerance of the SC injection was excellent, with no postinjection problems (excessive bleeding or leak back) in 99.8% of cattle. The drug insert information reports that on days 28 and 56 after injection, 97.8% and 98.9% of the cattle had no observable swelling at the injection site.15 Similar findings following ceftiofur crystalline-free acid administration in dairy cattle have been reported.1 Results of pharmacokinetic studies16,17 provide additional evidence that SC injection of ceftiofur crystalline-free acida is well tolerated in cattle with minimal, transient inflammation.

Immunohistochemical characterization is paramount for classification of PNETs. These tumors are of stem cell linage and are unique in their clinical signs and morphology. The exact cell of origin is often difficult to establish.

a.

EXCEDE, Ceftiofur crystalline free acid sterile suspension, Pfizer Pharmacia & Upjohn Co, New York, NY.

b.

Envision, Dako, Carpinteria, Calif.

References

  • 1. Harris AM, Ginn PE. Integumentary system. In: Zachary JF, McGavin MD, eds. Pathological basis of veterinary disease. 5th ed. St Louis: Elsevier, 2012;10121015.

    • Search Google Scholar
    • Export Citation
  • 2. Koestner A, Higgins RJ. Tumors of the nervous system. In: Meuten DJ, ed. Tumors in domestic animals. 4th ed. Ames, Iowa: Iowa State Press, 2002;714716.

    • Search Google Scholar
    • Export Citation
  • 3. Omi K, Kitano Y, Agawa H, et al. An immunohistochemical study of peripheral neuroblastoma, ganglioneuroblastoma, anaplastic ganglioma, schwannoma and neurofibroma in cattle. J Comp Pathol 1994; 111: 114.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4. Uchida K, Murakami T, Tometsuka T, et al. Peripheral neuroblastoma and primitive neuroectodermal tumor in Japanese black cattle. J Vet Med Sci 1998; 60: 871875.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5. Zachary J. Nervous system. In: Zachary JF, McGavin MD, eds. Pathological basis of veterinary disease. 4th ed. St Louis: Elsevier, 2012;835839.

    • Search Google Scholar
    • Export Citation
  • 6. Wippold FJ II, Perry A. Neuropathology for the neuroradiologist: rosettes and pseudorosettes. AJNR Am J Neuroradiol 2006; 27: 488492.

    • Search Google Scholar
    • Export Citation
  • 7. Berrocal A, Montgomery DL, Mackie JT, et al. Primitive neuroectodermal tumor in the spinal cord of a Brahman crossbred calf. Vet Pathol 2005; 42: 834836.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8. Lucas M-N, Nguyen F, Abadie J, et al. Cerebral primitive neuroectodermal tumor in a heifer. J Comp Pathol 2003; 128: 195198.

  • 9. Summers BA, Cummings JF, de Lahunta A. Tumors of the central nervous system. In: Veterinary neuropathology. St Louis: Mosby Year Book Inc, 1995;378379.

    • Search Google Scholar
    • Export Citation
  • 10. Haynes JS, Leininger JR. Malignant neuroblastoma in a cow. Vet Pathol 1984; 21: 610612.

  • 11. Miyoshi N, Matsumoto M, Kawaguchi H, et al. Ependymoblastoma in a Japanese black heifer. J Vet Med Sci 2009; 71: 13931395.

  • 12. Saunders GK. Ependymoblastoma in a dairy calf. Vet Pathol 1984; 21: 528529.

  • 13. Steinberg H, Peek SF, Nelson KM. Neuroblastoma with neuronal differentiation in the spinal cord in an Aberdeen Angus heifer calf. Vet Pathol 2006; 43: 193197.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14. Ulrich R, Stan AC, Koch A, et al. Expression of brain-derived neurotrophic factor and tropomysin-related kinase-B in a bovine jejunal nodular ganglioneuroblastoma. Vet Pathol 2008; 45: 355360.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15. EXCEDE (ceftiofur crystalline free acid) sterile suspension [package insert]. New York: Pfizer Pharmacia & Upjohn Co, 2009.

  • 16. Hibbard B, Robb EJ, Apley MD, et al. Feedlot performance of steers treated concurrently with ceftiofur crystalline-free acid subcutaneously in the posterior aspect of the ear and a growth-promoting implant. Vet Ther 2002; 3: 252261.

    • Search Google Scholar
    • Export Citation
  • 17. Hibbard B, Robb EJ, Chester ST Jr, et al. Dose determination and confirmation for ceftiofur crystalline-free acid administration in the posterior aspect of the ear for control and treatment of bovine respiratory disease. Vet Ther 2002; 3: 2230.

    • Search Google Scholar
    • Export Citation
  • Figure 1—

    Photographs of the head (A) and a sagittal section (B) through the skull of a Jersey cow that developed 3 subcutaneous masses on the head over a period of several months and was euthanized. The first mass developed at the site of SC injection of ceftiofur crystalline-free acid, which was administered for treatment of endometritis. In panel A, an ulcerated, subcutaneous mass is present over the left lateral parietal region. In panel B, a variegated, yellow and red extradural mass has obliterated the parietal bone, invaded the cranial vault, and compressed the brain.

  • Figure 2—

    Photomicrograph of a section of the multilobular, interconnected, expansile subcutaneous cranial mass in the Jersey cow in Figure 1. Neoplastic cells have moderate amounts of poorly defined, granular to vacuolated cytoplasm and very large, pleomorphic, round, oval or indented nuclei with ruffled nuclear membranes. The cells are divided into packets by a delicate fibrovascular stroma. H&E stain; bar = 50 μm.

  • Figure 3—

    Photomicrograph of a section of the subcutaneous cranial mass in the Jersey cow in Figure 1. Notice the strong cytoplasmic immunostaining for vimentin. Immunohistochemical stain; bar = 50 μm.

  • Figure 4—

    Photomicrograph of a section of the subcutaneous cranial mass in the Jersey cow in Figure 1. Notice the strong nuclear and cytoplasmic immunostaining for S-100. Immunohistochemical stain; bar = 50 μm.

  • Figure 5—

    Photomicrograph of a section of the subcutaneous cranial mass in the Jersey cow in Figure 1. Notice the strong cytoplasmic immunostaining for glial fibrillary acid protein. Immunohistochemical stain.

  • 1. Harris AM, Ginn PE. Integumentary system. In: Zachary JF, McGavin MD, eds. Pathological basis of veterinary disease. 5th ed. St Louis: Elsevier, 2012;10121015.

    • Search Google Scholar
    • Export Citation
  • 2. Koestner A, Higgins RJ. Tumors of the nervous system. In: Meuten DJ, ed. Tumors in domestic animals. 4th ed. Ames, Iowa: Iowa State Press, 2002;714716.

    • Search Google Scholar
    • Export Citation
  • 3. Omi K, Kitano Y, Agawa H, et al. An immunohistochemical study of peripheral neuroblastoma, ganglioneuroblastoma, anaplastic ganglioma, schwannoma and neurofibroma in cattle. J Comp Pathol 1994; 111: 114.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4. Uchida K, Murakami T, Tometsuka T, et al. Peripheral neuroblastoma and primitive neuroectodermal tumor in Japanese black cattle. J Vet Med Sci 1998; 60: 871875.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5. Zachary J. Nervous system. In: Zachary JF, McGavin MD, eds. Pathological basis of veterinary disease. 4th ed. St Louis: Elsevier, 2012;835839.

    • Search Google Scholar
    • Export Citation
  • 6. Wippold FJ II, Perry A. Neuropathology for the neuroradiologist: rosettes and pseudorosettes. AJNR Am J Neuroradiol 2006; 27: 488492.

    • Search Google Scholar
    • Export Citation
  • 7. Berrocal A, Montgomery DL, Mackie JT, et al. Primitive neuroectodermal tumor in the spinal cord of a Brahman crossbred calf. Vet Pathol 2005; 42: 834836.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8. Lucas M-N, Nguyen F, Abadie J, et al. Cerebral primitive neuroectodermal tumor in a heifer. J Comp Pathol 2003; 128: 195198.

  • 9. Summers BA, Cummings JF, de Lahunta A. Tumors of the central nervous system. In: Veterinary neuropathology. St Louis: Mosby Year Book Inc, 1995;378379.

    • Search Google Scholar
    • Export Citation
  • 10. Haynes JS, Leininger JR. Malignant neuroblastoma in a cow. Vet Pathol 1984; 21: 610612.

  • 11. Miyoshi N, Matsumoto M, Kawaguchi H, et al. Ependymoblastoma in a Japanese black heifer. J Vet Med Sci 2009; 71: 13931395.

  • 12. Saunders GK. Ependymoblastoma in a dairy calf. Vet Pathol 1984; 21: 528529.

  • 13. Steinberg H, Peek SF, Nelson KM. Neuroblastoma with neuronal differentiation in the spinal cord in an Aberdeen Angus heifer calf. Vet Pathol 2006; 43: 193197.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14. Ulrich R, Stan AC, Koch A, et al. Expression of brain-derived neurotrophic factor and tropomysin-related kinase-B in a bovine jejunal nodular ganglioneuroblastoma. Vet Pathol 2008; 45: 355360.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15. EXCEDE (ceftiofur crystalline free acid) sterile suspension [package insert]. New York: Pfizer Pharmacia & Upjohn Co, 2009.

  • 16. Hibbard B, Robb EJ, Apley MD, et al. Feedlot performance of steers treated concurrently with ceftiofur crystalline-free acid subcutaneously in the posterior aspect of the ear and a growth-promoting implant. Vet Ther 2002; 3: 252261.

    • Search Google Scholar
    • Export Citation
  • 17. Hibbard B, Robb EJ, Chester ST Jr, et al. Dose determination and confirmation for ceftiofur crystalline-free acid administration in the posterior aspect of the ear for control and treatment of bovine respiratory disease. Vet Ther 2002; 3: 2230.

    • Search Google Scholar
    • Export Citation

Advertisement