Conference 23 - 2012 Case: 04 20130501

Signalment:

10-year-old castrated male Belgian, equine (Equus caballus). A 10-year-old Belgian gelding was euthanized following progressively worsening neurological signs, including severe ataxia, gait abnormalities, and sudden loss of balance with falling. The horse owner determined this was a severe safety risk for the handlers tending the horse. Originally, this horse was diagnosed positive for equine protozoal myeloencephalitis (EPM) eight months earlier. Despite appropriate medical treatment, clinical signs progressively deteriorated. This horse was insured and the insurance carrier requested a necropsy.

Gross Description:

This 10-year-old Belgian gelding appeared to be in good external condition and estimated weight was 2,500 to 2,700 pounds. An unexpected flow of cerebrospinal fluid (CSF) was observed upon separation of the atlanto-occipital junction. Similarly, a large volume of CSF poured out of the lateral ventricles upon incising the cerebral hemispheres. The CSF was yellow to light tan, and cloudy to slightly turbid. An ovoid mass was found bridging the midline and extending into both right and left lateral ventricles, with loose attachment to the floor of the left lateral ventricle. The mass was 9.5 x 5.0 x 2.75 cm, yellow/ivory to grey/tan with a smooth shiny surface, except for an area of roughened surface corresponding to a loose attachment to the floor of the left lateral ventricle. On cut surface, the mass was solid and colored similar to the surface described above. Both lateral ventricles were moderately dilated resulting in moderate internal hydrocephalus.

Histopathologic Description:

This brain mass was made up of a well-differentiated, somewhat irregularly oriented fibrous and fibrovascular supporting tissue network filled with irregular variable-sized palisading bundles or sheaves of needle-like cholesterol clefts along with variable mixed inflammation. Inflammatory cells present included histiocytes/macrophages, lymphocytes, plasma cells, neutrophils, and fewer eosinophils. Patchy edema and hemorrhage was present within the mass and many macrophages contained hemosiderin pigment. Binucleate and cytomegalic plasma cells were randomly observed within the inflammation.

Changes in cerebral cortical tissue (slides not included) surrounding the dilated lateral ventricles included rarefaction and loss of nerve cell bodies immediately peripheral to the lateral ventricle space. In a number of sections, there was complete loss of the nerve cell body layer and neuropil collapse resulting in an appearance of increased blood vessels somewhat like a line of irregular granulation tissue. Random areas of spongy degeneration were noted in cortical white matter about the dilated ventricles. Additionally, the meninges sometimes contained a few inflammatory cells, predominately histiocytes, lymphocytes, and/or neutrophils.

Morphologic Diagnosis:

Brain mass: Cholesterol granuloma, right and left lateral ventricles, cerebrum, Belgian, equine.

Condition:

Cholesterol granuloma (cholesteatoma)

Contributor Comment:

This case demonstrates the sometimes perplexing situation for clinical practitioners and veterinary pathologists alike, when a horse is presented for evaluation of what is often loosely referred to as an equine neurological case. Many of these cases may be relatively long-standing and may have been previously diagnosed, erroneously or not, with a specific neurological disease (in this case, equine protozoal encephalomyelitis [EPM]). Additionally, some cases may have been treated for a specific disease with or without improvement. At the time the veterinary pathologist receives the case, most likely some set of events or changes in the clinical state of the horse have taken place that warrant euthanasia of the horse.

Knowing the above chain of events is likely in many cases, then, the veterinary pathologist should preface the undertaking of an equine neurological case necropsy, with a set of all possible differential diagnoses, in addition to any previous clinical diagnosis. Many equine neurological cases, and particularly CNS cases, have overlap of signs. Even if a case has a diagnosis confirmed by reliable clinical testing, as in this case, that particular diagnosis may not be the cause of the recent chain of events that brought about the euthanasia of the horse. Finally, there are some equine neurological cases that may be a rule out diagnosis. Botulism is one disease that always should come to mind as an example of this. Because the levels of botulinum toxin required to affect and even kill a horse are so low that current modes of testing may be unable to detect, the pathologist should always have a conversation with the horse owner and clinical veterinarian, about any and all of the details of environment and husbandry that could possibly lead to a final rule-out diagnosis of botulism.

Clearly then, cholesterol granulomas should be considered as a differential diagnosis in any equine neurological case, especially those in older horses with predominantly CNS signs. In fact, it has been reported that 15-20% of old horses have cholesterol granulomas, although many may be present in the absence of clinical signs.

Cholesterol granulomas and cholesteatoma have been used in veterinary literature to describe the lesion diagnosed in this case.(2,3,4,6,7) There is some disagreement of sorts as to whether cholesteatoma should be used to describe this brain lesion, specifically found in old horses.(2) Cholesteatoma is a term also used to describe a nodular mass in the middle ear, although this aural cholesteatoma has not been reported in horses.(5) It may be a prudent move to restrict the use of cholesterol granulomas only to describe this specific entity of aged horses, rather than use cholesteatoma interchangeably with cholesterol granuloma.

Despite this sort of disagreement of terminology for equine cholesterol granulomas, the mechanism of development is basically agreed upon.(2,3,4,6,7) The exact underlying pathogenesis, however, seems to be uncertain.(7) Equine cholesterol granulomas are often described as an aging or degenerative phenomenon.(2,3,5,7) Repeated episodes of hemorrhage and/or chronic intermittent congestion, edema and congestive hemorrhage in the choroid plexuses are believed to be the pathological processes responsible for development of cholesterol granulomas of older horses.(2,3) Erythrocytes are likely the source of the cholesterol.(6) It is when hemorrhage results in formation of a hematoma, subsequently becoming organized, followed by breakdown of red blood cells to release cholesterol that the granuloma develops.(2) Cholesterol accumulation, both extracellular and within macrophages, is observed and the cholesterol itself stimulates a foreign body response or giant cell reaction,(6) resulting in developing and progressive granulomatous inflammation and fibrovascular organization.(2,3,4,6,7) Whether this is or can result from a single event or requires multiple episodes is speculative, but likely the larger cholesterol granulomas develop because of multiple events of this type.

Small cholesterol granulomas may remain clinically silent and are discovered incidentally. The larger cholesterol granulomas produce clinical CNS signs and signs can be variable and progressive. Most, if not all, of the effects of large cholesterol granulomas are caused by blockage of interventricular foramen resulting in development of internal hydrocephalus and progressive degeneration and compression atrophy of the cerebral hemispheres. Inflammation in the brain itself is usually minimal and represented as small infiltrates of macrophage, lymphocytes, and neutrophils in the meninges. It may be fortunate that even though the occurrence of cholesterol granulomas in old horses is reported to be 15-20%, the majority are found in the fourth ventricle; and, development of hydrocephalus, the usual cause of clinical signs, is limited to those in the lateral ventricles that can by location block the interventricular formen causing hydrocephalus.(3)

JPC Diagnosis:

Ventricle (left lateral, per contributor): Cholesterol granuloma (cholesteatoma).

Conference Comment:

Conference participants discussed the typical gross and histopathologic findings as well the pathogenesis of cholesterol granulomas, all of which are discussed in the contributors excellent summary. Conference participants also used this case as an opportunity to review the anatomy of the ventricular system of the brain. There is one lateral ventricle within each cerebral hemisphere, each of which communicates with the third ventricle through an interventricular foramen. The third ventricle is a narrow chamber that lies along the midline, between the two thalami in the diencephalon; it communicates with the fourth ventricle in the hindbrain through the mesencephalic aquaduct. The fourth ventricle communicates with the central canal of the spinal cord and the subarachnoid space via lateral recesses and apertures. This system of cavities through which cerebrospinal fluid (CSF) flows is lined by ependymal epithelial cells. Tela choroidea, (an area in which nervous tissue is absent and pia mater contacts the ependymal cells directly) forms a portion of the floor of the lateral ventricles and roof of the third and fourth ventricles. It gives rise to the choroid plexuses, which are composed of ependymal cells and microvascular proliferations. The choroid plexuses project into each ventricle, where they produce CSF via secretion and ultrafiltration.(1)

References:

1. Fletcher TF. Spinal cord and meninges. In: Evans HE, ed. Millers Anatomy of the Dog. 3rd ed. Philadelphia PA: Saunders Elsevier; 1993:824-826.
2. Jones TC, Hunt RD, King NW. The nervous system. In: Veterinary Pathology. 6th ed. Baltimore, MD: Lippincott Williams & Wilkins; 1997:1286, 1291-2.
3. Jubb KVF, Kennedy PC, Palmer N. Nervous system. In: Maxie MG, ed. Pathology of Domestic Animals. Vol. 1. Philadelphia, PA: Elsevier Saunders, 2007:345-6.
4. McGavin DM, Zachary JF. Pathologic Basis of Veterinary Disease. 4th ed. St. Louis, MO: Mosby; 2007:47, 922.
5. McGavin, Carlton & Zachary. The nervous system. In: Thomsons Special Veterinary Pathology. 3rd ed. St. Louis, MO: Mosby; 2001:448-449.
6. Moulton JE. Tumors in Domestic Animals, 3rd ed. Berekley, CA: University of California Press, 1990:647.
7. Summers B, Cummings J, de Lahunta A. Neuropathology of aging. In: Veterinary Neuropathology. St. Louis, MO: Mosby; 1995:49-53.