Signalment:  

Three-year-old, female, African hedgehog (Atelerix albiventris).The animal presented for bloody vulvar discharge, right-sided facial paralysis, and multiple skin masses. Elective ovariohysterectomy was performed and multiple skin masses were removed. A firm multinodular mass was observed arising from the internal ear canal. Due to the worsening of clinical signs, the animal was humanely euthanized and submitted for postmortem examination.

Gross Description:  

On necropsy, the animal was in good body condition. Gross examination revealed a multilobulated, white and tan mass measuring 2.5 cm arising from the right parietal bone and extending toward the right occipital lobe, surrounding the external auditory meatus and protruding through the internal ear canal, as well as rostrally to the right frontal lobe involving the right turbinates. The cut surface was yellow, white, and tan, with few white areas of mineralization. In transverse sections, the mass focally compressed the cerebral hemispheres, cranial nerves and partially obliterating the ear meatus. Both lateral ventricles were moderately dilated.

Histopathologic Description:

Microscopic examination revealed that this mass arises from the skull, protrudes both internally and externally, and compresses the brain. The mass is composed of multiple welldemarcated nodules, rimmed by a thick layer of fibrous connective tissue arranged in sheets of polyhedral to spindle-shaped cells with large interspersed areas of coagulative necrosis. Numerous islands and lakes of osteoid are present throughout the tumor. The neoplastic cells have abundant eosinophilic cytoplasm and large, round to ovoid nuclei with finely stippled chromatin and often prominent nucleoli. There is marked anisocytosis and anisokaryosis. The mitotic rate is low, averaging two per ten 400x high powered fields. In some sections, cranial nerves are markedly compressed by the neoplasm, with multifocal axonal swelling and spheroid formation (Wallerian degeneration). Neurons at this level are shrunken and hypereosinophilic (necrosis).

Morphologic Diagnosis:  

Skull: Osteoblastic osteosarcoma, with cranial nerve compression, Wallerian degeneration, and neuronal necrosis.

Lab Results:  

N/A

Condition:  

Osteosarcoma

Contributor Comment:  

Neoplasms in African hedgehogs are common and represent one of the main causes of disease in this species. In retrospective studies, the prevalence of neoplasia has ranged from 29% to 51%. Of these, 85% are malignant, portending an overall poor prognosis. ³ Osteosarcomas in this species have been reported in skeletal and extraskeletal locations. Skeletal locations include: mandible, ³ ribs,^1,6 and vertebra. ⁸ Reported extraskeletal sites include the subcutis over the scapula² and flank.7 One documented case of osteosarcoma is theorized to be associated with retroviral infection.⁶ Multiple concurrent neoplasms are present in a small percentage of hedgehogs with neoplasia.³ In this case, multiple trichoepitheliomas and an endometrial stromal sarcoma were also present.

Although osteosarcoma accounts for up to 85% of malignant bone tumors in dogs and 70% in cats,² the occurrence in African hedgehogs is unusual. In dogs, osteosarcomas can be subclassified according to the predominant histologic pattern into six different categories: poorly differentiated, osteoblastic, chondroblastic, fibroblastic, teleangiectatic and giant-cell rich osteosarcoma. This classification scheme is an adaptation of a system developed for use in human medicine. Osteoblastic osteosarcoma is the most common subtype, and it can be further sub-classified into nonproductive and productive, based on the tumor bone produced. According to this classification, this osteosarcoma would be classified as a productive osteoblastic osteosarcoma. ²

Additionally, intracranial, extracranial, and skull base neoplasms often compress the facial nerve and may result in facial paralysis.⁵ In this case, cranial nerve involvement can be seen in some slides. Nerves are clearly compressed and surrounded by the neoplastic tissue, leading to Wallerian degeneration. Wallerian degeneration is a process that occurs when a nerve fiber is cut or crushed, leading to axonal separation from the neuronal cell body which degenerates distal to the injury. ⁹

JPC Diagnosis:  

Bone, cranium: Osteosarcoma, African hedgehog, Atelerix albiventris.

Conference Comment:  

Transverse histologic sections of the cranium from this case spanned from the level of the rostral diencephalon to the caudal metencephalon. As a result, conference participants noted marked slide variation based on the anatomic location of this neoplasm and its effects on the adjacent tissue. Due to extensive variation in tissue sections submitted, histologic lesions noted by participants that may not be present on every slide include: Wallerian degeneration of the cerebrum and peripheral nerves; compression of the cerebrum and peripheral nerves with adjacent neuronal necrosis; hydrocephalus of the lateral, third, and fourth ventricles; osteosarcoma (OSA) tumor emboli within adjacent vessels; skeletal muscle degeneration, regeneration, and necrosis; and hyperkeratosis of the external ear canal.

As mentioned by the contributor, neoplasia is an extremely common antemortem and postmortem finding in the African hedgehog. However, mesenchymal neoplasms, such as in this case, are relatively uncommon with an incidence of only about 4% at necropsy.^1,3,8 Epithelial neoplasms of the integument are the most common type, followed by round cell tumors. Osteosarcoma is the most common mesenchymal neoplasm reported in African hedgehogs.³

In dogs and cats, osteosarcoma is characterized by rapid progression and early metastasis to the lungs, resulting in short survival times and high mortality rate.² This aggressive biologic behavior is similar in reported cases of osteosarcoma in African hedgehogs.^1,3,8 The contributor describes six different categories of osteosarcoma in dogs based on the predominant histologic pattern. These include:

1. Poorly differentiated:

• o Variation in cell size from small primitive mesenchymal to large and pleomorphic undifferentiated cells


• o Identification depends on presence of unequivocal tumor osteoid


• o Highly aggressive and associated with pathological fractures.

2. Osteoblastic:

• o Anaplastic osteoblasts; variable amounts of basophilic cytoplasm, and hyperchromatic, eccentric nuclei


• o Further subclassified as nonproductive or productive based on presence or absence of tumor bone production


• o Productive osteoblastic OSA is the most common subtype in dogs

3. Chondroblastic:

• o Neoplastic cells produce both chondroid and osteoid matrices

4. Fibroblastic:

• o Interlacing bundles of spindle cells resembling fibrosarcoma that produce osteoid or bone

5. Telangiectatic:

• o Solid areas and large bloodfilled spaces lined by malignant osteoblasts that occasionally form spicules of osteoid


• o Resembles hemangiosarcoma, but is immunonegative for factor VIII and CD31


• o Most malignant classification with least favorable prognosis.

6. Giant cell-rich:

• o Tumor giant cells predominate with nuclear atypia and a high mitotic rate


• o Must be differentiated from the benign giant cell tumor of bone²

The conference moderator cautioned participants that histologic classification of osteosarcoma is often complicated by their heterogeneous nature, as several microscopic patterns are often evident within a single neoplasm. Regardless of classification, the prognosis for all subtypes of canine central osteosarcoma is considered poor. The conference moderator also mentioned different grading systems for osteosarcoma based on nuclear pleomorphism, mitotic index, necrosis, multinucleated cells, the amount of tumor matrix, and vascular invasion. Unfortunately, no histologic grading system has gained widespread acceptance by veterinary pathologists due to marked variation in histomorphology of the neoplastic cells within different regions of the same tumor.²

References:

1. Benoit-Biancamano M, d'Anjou M, Girard C, Langlois I. Rib Osteoblastic Osteosarcoma in an African Hedgehog (Atelerix Albiventris). J Vet Diagn Invest. 2006; 18:415–418.

2. Craig LE, Dittmer KE, Thompson KG. Bones and joints. In: Maxie MG ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:110-116.

3. Heatley J, Mauldin G, Cho D. A Review of Neoplasia in the Captive African Hedgehog (Atelerix albiventris). Semin Avian Exot Pet. 2005; 14:182–192.

4. London C, Dubilzeig R, Vail D, Ogilvie G, Hahn K, Brewer W, DVM; Hammer A, O'Keefe D, Chun R, McEntee M, McCaw D, Fox L, Norris A, Klausner J. Evaluation of dogs and cats with tumors of the ear canal: 145 cases (1978-1992). J Am Vet Med Assoc. 1996; 208: 1413-18.

5. Marzo S, Leonetti J, Petruzzelli G. Facial paralysis caused by malignant skull base neoplasms. Neurosurg Focus. 2002; 12 (5): 1-4.

6. Peauroi J, Lowenstine L, Mun R, D. Wilson. Multicentric Skeletal Sarcomas Associated with Probable Retrovirus Particles in Two African Hedgehogs (Atelerix albiventris). Vet Pathol. 1994; 31:481-484.

7. Phair K, Carpenter J, Marrow J, Andrew, G, Bawa. Management of an Extraskeletal Osteosarcoma in an African Hedgehog (Atelerix albiventris). Journal of Exotic Pet Medicine. 2011; 20 (2): 151–15.

8. Rhody J, Schiller C. Spinal Osteosarcoma in a Hedgehog with Pedal Self-Mutilation. Vet Clin Exot Anim. 2006; 9: 625–631.

9. Zachary JF. Nervous System. In: Zachary JF, McGavin MD, eds. Pathologic Basis of Veterinary 6 Disease. 5th ed. p.p. 959 St. Louis, MO: Elsevier; 2012.

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