Signalment:  

3-year-old male Labrador Retriever cross dog, (Canis familiars).The dog presented to the referring veterinarian with a one-day history of inappetance, unusual behavior, ataxia, falling over, vocalizing, incontinence, and apparent pain in the hips and back. The dog was hospitalized with rapid progression of clinical signs including rigidity of all four limbs, profuse salivation, opisthotonos, and nystagmus. Pentobarbital was administered. The dog later became unresponsive to sound and touch, and was found dead in the cage the next morning. A necropsy was performed by the referring veterinarian. Gross lesions were not observed.

Gross Description:  

Seven sections of brain were submitted in formalin for examination. There was moderate dilation of the lateral ventricles and marked dilation of the mesencephalic aqueduct and the most rostral aspects of the fourth ventricle. Occluding the lumen of the fourth ventricle there was a 0.8 cm, irregularly shaped, expansile, firm, opalescent mass. Multifocal areas of hemorrhage were noted in the adjacent cerebellum and brain stem.

Histopathologic Description:

Brain, fourth ventricle: Filling approximately 80% of the fourth ventricle and in close association with the choroid plexus, there is a multilocular (not in all sections), expansile, unencapsulated and moderately well-defined mass. The wall of the mass is composed of well-differentiated stratified squamous epithelium which exhibits gradual keratinization through a granular cell layer resulting in the formation of multiple cysts filled with lamellar keratin. The cyst wall is discontinuous and free keratin spills into the lumen of the fourth ventricle. The squamous epithelium is supported by a moderate amount of fibrovascular stroma which frequently entraps the choroid plexus. In some areas the stroma is dense and brightly eosinophilic. Within the stroma there are modest numbers of inflammatory cells which mainly include lymphocytes and plasma cells. Infrequently there are stellate shaped cells with abundant dark brown, finely granular pigment which are interpreted to be melanocytes. Occasional hemosiderin laden macrophages are noted. There is marked rarefaction neuropil and hemorrhage. This is accompanied by numerous eosinophilic, spherical structures which are interpreted to be spheroids (swollen axons). Lining the lumen of the ventricle there are multiple round cells with abundant pale, foamy to slightly granular, eosinophilic cytoplasm, and one to multiple eccentric nuclei. These are interpreted to be gitter cells.

Intercellular bridges between keratinized cells are prominent. There are approximately five mitoses per 400x field with frequent bizarre mitotic figures. There is severe anisocytosis and anisokaryosis. Multifocally within the neoplasm there are large areas of necrosis, hemorrhage and a mixed inflammatory infiltrate of lymphocytes, plasma cells, neutrophils and some macrophages. Many submucosal and subserosal vessels contain clusters of neoplastic cells (tumor emboli) as well as fibrin thrombi. Overlying the ulcerated mucosa, there is abundant fibrillar eosinophilic material (fibrin exudation) and hemorrhage, admixed with cellular and karyorrhectic debris (necrosis) and bacterial colonies. Throughout the mass, but especially along the serosa, there are multiple nodules or bands of abundant fibrous connective tissue (scirrhous response).

Morphologic Diagnosis:  

Epidermoid cyst with acquired obstructive hydrocephalus. 

Condition:  

Epidermoid cyst with malacia and hemorrhage

Contributor Comment:  

The central nervous system (CNS) develops from specialized ectoderm (neuroectoderm) which lies dorsal to the notochord throughout the axis of the embryo. Invagination of the neuroectoderm forms the neural groove and lateral processes referred to as the neural folds. Fusion of the neural folds results in the formation of the neural tube with the latter forming the ventricular system and central canal of the CNS. At the time of neural tube closure, the neuroectoderm separates from the surface ectoderm to form two distinct layers. The layer of nonneural ectoderm gives rise to structures such as the epidermis. Epidermoid cysts of the CNS are congenital lesions that are thought to be the result of inappropriate inclusion of this nonneural ectoderm at the time of closure of the neural tube.(4)

In humans, intracranial epidermoid cysts are a well-recognized entity and are thought to comprise up to 1.8% of all intracranial masses.(7) Epidermoid cysts of the CNS are uncommon in domestic animals with a handful of cases being reported in dogs, horses, mice, and rats.(2,4,9,10) In dogs, epidermoid cysts have been reported within the cranial cavity(4,6,11,12) and within the vertebral canal.(1,4) Intracranial masses are most common. 

There are too few reports of intracranial epidermoid cysts in dogs to reliably identify a breed or sex predilection. Dogs with intracranial epidermoid cysts have ranged in age from 3 months to 8 years with the majority of dogs being less than 2 years old.(4) These findings may suggest a predilection for young dogs, and could be consistent with the presence of a congenital lesion. Intracranial epidermoid cysts are slow growing masses and in people typically do not cause clinical signs until fifth decade of life.(4) The slow, linear growing pattern of these masses may explain the wide age range reported in dogs for a purportedly congenital lesion.

Intracranial epidermoid cysts exhibit an expansile growth pattern through desquamation and accumulation of keratin.(7) While these lesions may be found as incidental findings at necropsy,(4) intracranial epidermoid cysts may cause clinical signs referable to compression of adjacent structures resulting in focal neurologic dysfunction or obstruction of CSF resulting in hydrocephalus.(4,6,11,12) In both humans and dogs, epidermoid cysts have a predilection for the caudal fossa which may be a reflection of the initial closure of the neural tube in the rhombencephalon. In dogs, intracranial epidermoid cysts have been reported in the fourth ventricle and cerebellopontine angle.(4) Based on their location in the caudal fossa, canine epidermoid cysts are frequently associated with vestibular and occasionally cerebellar signs.(4,6) In addition to the space occupying nature of these lesions, other sequelae reported in people include the development of chemical meningitis, and rarely malignant transformation to squamous cell carcinoma.(7,8) Malignant transformation has not been reported in dogs, and in the current case there was no evidence of squamous cell carcinoma in the sections examined.

Pathologic features of intracranial epidermoid cysts are similar to those that are routinely encountered in the skin. Microscopic examination reveals the presence of a cyst lined by stratified squamous epithelium supported by connective tissue stroma and surrounding keratin. Portions of choroid plexus are often adhered to or are incorporated into the cyst.(4) Intracranial dermoid cysts have also been reported and also arise from the inappropriate inclusion of nonneural ectoderm in the CNS. Dermoid cysts can be differentiated from epidermoid cysts in that the former is lined by adnexal structures such as hair follicles, sebaceous glands, and sweat glands.(4) These features were not observed in the current mass favoring a diagnosis of epidermoid cyst over dermoid cyst.

JPC Diagnosis:  

Brain, 4^th ventricle: Epidermoid cyst with granulomatous rhombencephalitis, encephalomalacia, edema and hemorrhage.

Conference Comment:  

Conference participants discussed the embryologic histogenesis and clinical signs of intracranial epidermoid cysts, as reviewed by the contributor in the above comments. Clinical signs of neurologic dysfunction are generally attributed to compression of adjacent neural structures(5)- indeed one of the more striking histologic features in this case is the degree of axonal degeneration and numerous, prominent spheroids noted within the adjacent neuropil. Cyst rupture with subsequent inflammation, known in human medicine as chemical meningoencephalitis, may also contribute to the clinical signs.(6) Although intracranial epidermoid cysts are more common (and of course, extracranial epidermoid cysts are the most common), intravertebral and intramedullary spinal cord cysts with progressive ataxia and paraparesis have also been described in dogs.(1,5)

Participants also examined dermoid cysts as a related, but more frequent finding in the CNS of dogs. Like their non-congenital, dermal counterparts, both epidermoid and dermoid intracranial cysts are lined by stratified squamous epithelium. Although they have a similar embryologic origin, the dermoid cyst is derived from a more pluripotent precursor cell and often produces adnexal structures, such as sebaceous glands, apocrine glands or hair follicles.(6) Additionally, Rhodesian ridgeback dogs that carry the autosomal dominant dorsal ridge trait have been shown to be predisposed to the congenital cutaneous defect known as dermoid sinus, which is a draining sinus at the dorsal midline that occasionally communicates with the subarachnoid space.(3) Typically these dogs do not have any clinical problems. 

Intracranial epidermoid cysts occur in other veterinary species; in mice they often occur within the leptomeninges of the lumbar/sacral spinal cord or (less commonly) associated with the fourth ventricle.(2) There are generally no clinical signs in mice or rats with this lesion, which may be an indication that the cysts do not grow large enough to compress adjacent structures.(2) Intracranial epidermoid cysts in mice are thought to be strain dependent and are typically interpreted as incidental findings. Conversely, dermoid cysts in mice have rarely been associated with clinical neurologic dysfunction.(2) Epidermoid cysts have not been reported in the CNS of hamsters or cats.

References:

1. Capello R, Lamb CR, Rest JR. Vertebral epidermoid cyst causing hemiparesis in a dog. Vet Rec. 2006;158:865-867.

2. Hansmann F, Herder V, Ernst H, et al. Spinal epidermoid cyst in a SJL mouse: case report and literature review. J Comp Pathol. 2011;145:373-377.

3. Hillbertz NH, Andersson G. Autosomal dominant mutation causing the dorsal ridge predisposes for dermoid sinus in Rhodesian ridgeback dogs. J Small Anim Pract. 2006;47(4):184-188.

4. Kornegay JN, Gorgacz EJ. Intracranial epidermoid cysts in three dogs. Vet Pathol. 1982;19:646-650.

5. Lipitz L, Rylander H, Pinkerton ME. Intramedullary epidermoid cyst in the thoracic spine of a dog. J Am Anim Hosp Assoc. 2011;47:e145-e149.

6. MacKillop E, Schatzburg SJ, de Lahunta A. Intracranial epidermoid cyst and syringohydromyelia in a dog. Vet Radiol Ultrasound. 2006;47:339-344.

7. Michael II LM, Moss T, Madhu T, et al. Malignant transformation of the posterior fossa epidermoid cyst. Br J Neurosurg. 2005;19:505-510.

8. Netsky MG. Epidermoid tumors. Surg Neurol. 1988;29:477-483.

9. Nobel TA, Nyska A, Pirak M, et al. Epidermoid cysts in the central nervous system of mice. J Comp Pathol. 1987;97:357-359.

10. Peters M, Brandt K, Wohlsein. Intracranial epidermoid cyst in a horse. J Comp Pathol. 2003;12:89-92.

11. Platt SR, Chrisman CL, Adjiri-Awere A, et al. Canine intracranial epidermoid cyst. Vet Radiol Ultrasound. 1999;40:454-458.

12. Steinberg T, Matiasek K, Bruhschwein A, et al. Imaging diagnosis-intracranial epidermoid cyst in a Doberman Pinscher. Vet Radiol Ultrasound. 2007;48:250-253.

Click the slide to view.

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1-1. Cerebellum, pons, and fourth ventricle

1-2. Cerebellum, pons, and fourth ventricle

1-3. Midbrain and fourth ventricle

1-4. Fourth ventricle

1-5. Midbrain

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