cns gross&histo neoplasia-1_dr kornegay

8/3/2019 CNS Gross&Histo Neoplasia-1_Dr Kornegay

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CNS NEOPLASIA

Joe N. Kornegay, DVM, PhD, ACVIM (Neurology)

University of North Carolina-Chapel Hill

School of Medicine

Departments of Pathology and Laboratory Medicine and NeurologyChapel Hill, NC 27599-7525

Primary Objectives:

1. Know the breed and age predilection, the gross morphologic features, the typicallocation, and the biologic behavior of the following CNS neoplasms of dogs:

a. Astrocytoma

b. Oligodendrogliomac. Choroid plexus papilloma

d. Meningioma

2. Know the gross morphologic features, typical location, and possible origin of equine

cholesteatomas.

Secondary Objectives:

1. Know potential secondary effects of intracranial neoplasms.

Primary intracranial neoplasms are fairly common in dogs but occur infrequently in

other domestic animal species. Most of these tumors develop as solitary masses that

grow primarily by expansion and seldom metastasize to points either within or outsidethe central nervous system. That these are biologic features of a benign neoplasm is

ironic, in that brain tumors are among the most catastrophic of all illnesses.

Nevertheless, this course of growth does account for the typically insidious onset andprogression of clinical signs resulting from most intracranial neoplasms. Occasional

variation from this clinical pattern also may be explained by the tumors biologic

behavior. Dedifferentiation (anaplasia) of cells composing the tumor generally is

associated with rapid growth, local invasiveness and an increased likelihood ofmetastasis. Tumors fulfilling these criteria are malignant and cause neurologic

dysfunction that is both acute in onset and rapidly progressive.

This table lists the intracranial neoplasms of dogs and cats. For the most part, the

data were collected from canine cases. As a general rule, the cells of the tumor will look

like the cell of origin astrocytoma cells look like astrocytes. Makes sense, doesnt it?


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Central Nervous System Neoplasms of Dogs and Cats

Tumor Type Incidence

(Dogs)

Breed

Predilection

(Dogs)

Age

Predilection

Gross Morphologic

Features

Histologic Features Location Biologic

Behavior

Astrocytoma Common Brachycephalic Old Solid, gray-white, poorly

demarcated

Variable depending on cell

origin: Protoplasmic, fibrillary,

gemistocytic, pilocytic

Cerebrum, thalamus Benign

Oligodendroglioma Common Brachycephalic Old Friable, red poorlydemarcated, hemorrhage

Small hyperchromatic nuclei,perinuclear halos

Cerebrum Ventricularinvasion

Choroid Plexus

Papilloma

Common None Middle age

to old

Papillary, gray-white to

red, well demarcated

Papilliform, resembles choroid

plexus

Cerebellopontine

angle, third and

fourth ventricles

Benign

Meningioma Common Dolichocephalic Old Solid, gray-white,

multilobulated, welldemarcated

Variable: endotheliomatous,

fibromatous

Cerebrum (dogs and

cats), cerebellumand spinal cord

(dogs)

Benign

Reticulosis Common None Middle age

to old

Poorly demarcated Variable: granulomatous,

neoplastic, microgliomatosis

Cerebrum, brain

stem

Locally

invasive

Pituitary Adenoma Common Brachycephalic Old Gray-white to red, well

demarcated, hemorrhage,

necrosis

Adenomatous Pituitary, third

ventricle, thalamus

Locally

invasive

Glioblastoma Infrequent Brachycephalic Old Solid, gray-white to red,

poorly demarcated,

hemorrhage, necrosis

Cellular pleomorphism,

hemorrhage, necrosis

Cerebrum, thalamus Locally

invasive

Ependymoma Infrequent None Middle age

to old

Soft, bulging, gray-red,

well demarcated

Small hyperchromatic nuclei,

rosettes and pseudorosettes

Lateral ventricle,

spinal cord

Locally

invasive,ventricular

invasion

Medulloblastoma Infrequent None Young to

middle age

Soft, bulging, gray-red,

well demarcated

Small hyperchromatic nuclei,

pseudorosettes

Cerebellum Ventricular

invasion,

CSFmetastasis

Epidermoid, dermoid

cyst

Infrequent None Young Soft, caseous, gray-

white, well demarcated

Cyst, squamous epithelium,

keratin

Cerebellopontine

angle, fourth

ventricle

Benign

Metastatic Common None Middle ageto old

Variable depending onprimary; usually solid,

well demarcated

Variable: sarcoma, carcinoma,melanoma

Cerebrum Variable


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Advance Slides 1 and 2

Slide 1 is a photograph of a transverse section of thalamus from a twelve-year-old Boston

Terrier dog with neurologic dysfunction referable to the right forebrain of four weeks duration.The right thalamus contains a gray-white, homogeneous mass. Do you see it? Now look at your

chart and see which of the tumors is most consistent with these features. Lets see - an olderbrachycephalic breed with a gray-white thalamic tumor. Sounds like an astrocytoma, doesnt it?Of course, youd have to have your suspicion confirmed by a pathologist, but in this case at least,

youd be right. Slide 2 is a photomicrograph of a glial fibrillary acidic protein (GFAP) stain

showing the characteristic positive yellow-brown stain seen with glial tumors. This was anastrocytoma.


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Slide 3 is a photograph of a series of transverse sections of brain from a nine-year-oldBoston Terrier dog with cervical hyperesthesia and vague neurologic dysfunction referable to the

brain-stem. We looked at a photograph of one of these sections earlier when we talked about

hydrocephalus. Recall that the mesencephalic aqueduct was partially occluded, resulting inobstructive hydrocephalus. In the other sections here, you can see a portion of the tumor. Notice

the red-black mass in the fourth ventricle. Think about this one and check the chart again. I

think youll find that its features are compatible with an oligodendroglioma with one exception.The brain stem is not a typical site for this tumor. However, on histologic evaluation, it was an

oligodendroglioma. Note in Slide 4 the characteristic fried egg appearance of

oligodendroglioma tymor cells, i. e. a central round nucleus surrounded by a clear space (thisspace has been shown to be an artifact of processing).


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Slide 5 is a photograph of a transverse section of brain at the medulla oblongata from aneight-year-old Irish Setter dog with progressive neurologic dysfunction referable to a left central

vestibular lesion of eight weeks duration. A large, pedunculated, well-demarcated mass

compresses the left medulla oblongata and cerebellum. Again, have a look at the table. What doyou think? Yes, this was a choroid plexus papilloma. In Slide 6, you see the characteristic

microscopic appearance of an epithelial tumor, fronds of tissue containing central vessels andlined peripherally by epithelial cells mirroring the appearance of normal choroid plexus.


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Advance Slide 7

This slide illustrates another characteristic site for choroids plexus papillomas. Note the tan

mass within the third ventricle. Some such tumors will cause obstructive hydrocephalus (not

well appreciated here).


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Advance Slide 8 and 9

Slide 8 is a photograph of a transverse section of brain at the medulla-oblongata from a

seven-year-old English Sheepdog with neurologic dysfunction referable to the brain stem of six

months duration. A large, well-demarcated mass compresses the medulla oblongata. This one,again, is pretty straightforward. It was a meningioma. Meningiomas have various histologic

patterns (meningothelial, fibroblastic, transitional, psammomatous, and angiomatous). One

common feature seen here in Slide 9 is a whorling pattern of mesenchymal cells. It is not clear

that pathologic definition of these types has any clinical significance.


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Advance Slide 10

This slide illustrates characteristic features of the meningothelial meningioma, clusters or

sheets of polygonal cells with prominent nuclei and nucleoli.


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Advance Slide 11

Large cysts develop in some dogs and cats withmeningiomas. An example from an

affected dog is illustrated in these T1-weighted MRI images with (bottom) and without (top)

gadolinium-DTPAenhancement. Note that portions of the tumor at the edge of the cystenhance in the lower image


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Advance Slides 12, 13, 14, and 15

Mechanisms to account for cystic lesions in meningiomas are poorly understood.

Infarction could contribute. Note apparent necrosis of tumor cells in Slide 12, with marked

congestion in Slide 13. However, others have speculated that tumor cells may become

vacuolated, with gradual merging of affected cells leading to cysts. Tumor cell vacuolation isseen in Slide 14. Cells lining the cyst are evident in Slide 15.


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Meningiomas may occur within the ventricular system. Tumors arise from the tela

choroidea of the third ventricle of cats relatively commonly. A case is illustrated in this

gadolinium-DTPA-enhanced MRI and transverse section of brain. There is associated

obstructive hydrocephalus.


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Advance Slide 18 and 19

In Slide 18, the brain from a 1-year-old mixed breed dog with signs of cerebellar diseasehas been transected at the junction of the pons and midbrain. We are looking from rostral to

caudal at the pons and cerebellum. Note that a large mass compresses the pons. The dogs

young age and involvement of the cerebellum suggest that this tumor is a medulloblastoma. Thiswas confirmed microscopically. Cells with hyperchromatic, rod (carrot) shaped nuclei that

characterize this tumor type are seen in slide 19.


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Glioblastoma multiforme (GBM) is an anaplastic, primary brain neoplasm that occurs

relatively commonly in humans but is rare in animals. Tumor cells may theoretically show

differentiation towards any of the primary glial tumor types. As an example, there is a

continuum between anaplastic astrocytomas and GBMs. Hemorrhage and necrosis arecommonly seen. A GBM that had cellular differentiation that included multinuclear cells is seen

in the ventral midbrain here.


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Advance Slide 22

Most types of extracranial neoplasms (melanomas, hemangiosarcomas, carcinomas, etc)

occasionally metastasize to the brain or spinal cord. Slide 22 is a transverse section of brain atthe level of the thalamus from a 10-year-old, mixed breed dog with acute neurologic function.

Multiple black foci typical of metastatic malignant melanoma are seen. Secondary brain tumors

usually are associated with acute, progressive neurologic dysfunction referable to the site of

metastasis. As the primary tumor often is subclinical, neurologic dysfunction may be the initialclinical sign. Nevertheless, aspiration or biopsy of unexplained dermal or abdominal masses can

provide insight regarding the underlying disease process.


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Advance Slide 25

The brain may also be affected secondarily by tumors that arise from adjacent structuressuch as the skull or pituitary gland. This is a sagittal section of brain from a dog with a pituitary

adenoma that has compressed and actually invaded the thalamus. What else do you see here?

What about the black material? That is hemorrhage. The clinical effects of intracranialneoplasms are due primarily to compression of adjacent tissue. However, secondary effects may

be equally detrimental. Brain tumors tend to disrupt the blood-brain barrier resulting in

vasogenic edema, can obstruct CSF outflow resulting in increased intracranial pressure andhydrocephalus, and also may cause vessel wall necrosis and associated hemorrhage as we see

here. Note that the caudal cerebellar vermis contains hemorrhage and has undergone necrosis

subsequent to herniation through the foramen magnum (well discuss brain herniation in the next

section).


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Slides 26 and 27 are photographs of brain from an adult horse. Notice the mass in the

lateral ventricle. Its been hemisected in Slide 27. Describe it. Well, its a solid, spherical, tanto green mass with some evidence of hemorrhage. This is a cholesteatoma. Its really not a

neoplasm but instead, on microscopic examination, consists largely of cholesterol clefts and

associated granulomatous inflammation. They are fairly common in older horses and mayrepresent a chronic reaction to hemorrhage. Choleastomas typically occur in the lateral

ventricles and may obstruct CSF outflow leading to hydrocephalus.


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Lets transition from brain to spinal cord tumors. Slide 28 is a series of transverse spinal

cord sections from a 10-year-old, mixed breed dog with progressive paraparesis On

myelography, there was an intramedullary pattern in the caudal thoracic spinal cord. Note thatthe dorsal spinal cord is effaced by a poorly defined mass with a focus of hemorrhage. A

microscopic transverse section is seen in Slide 29.


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The tumor was shown to be an ependymoma on microscopic examination. Note in Slide 30

one of the characteristic microscopic features of ependymomas - columnar cells arranged around

a central lumen to form a rosette. Slide 31 illustrates a pseudorosette - columnar cells arranged

around a vessel. Ependymoma and astrocytoma are the most common primary spinal cordtumors of dogs.


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Advance Slide 32

Another primary spinal cord tumor of dogs has features similar to those of ependymoma.

Various names have been used, with neuroepithelioma perhaps being used most commonly.

This tumor tends to occur in the intradural-extramedullary space of young dogs. Studies suggest

that the tumor may arise from embryonal nephroblasts.


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Slide 33 is a gadolinium-DTPA-enhanced T1-weighted MRI image from a dog with

neuroepithelioma. Note that much of the spinal cord has been replaced or compressed by an

enhancing lesion that is most pronounced on the right side. The lesion is seen at surgery after a

durotomy has been performed in Slide 34.


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Advance Slide 35

Nests of epithelial cells that characterize neuroepitheliomas are seen in the toluidine blue-

stained section in Slide 35. A single well-defined acinus is present towards the upper-left corner.


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Lymphosarcoma affects the spinal cord of numerous animal species, most notably dogs,

cats, and cattle. Affected cats most commonly have multicentric lymphosarcoma, suggesting

that the spinal lesion is metastatic. However, some cats have strict neurologic involvement.

Spinal tumors may develop from small islands of lymphoid tissue within the epidural orsubarachnoid spaces and compress or directly invade neural tissue. Tumors in cats and cattle are

associated with the feline leukemia virus and the bovine leucosis virus, respectively. Mosttumors in cats are located in the epidural space but some may extend to the intradural space

and/or invade the nerve roots or spinal cord. These are photomicrographs of spinal cord from a

cat with progressive tetraparesis. Note the densely cellular mass compressing the spinal cord inSlide 37. In Slide 38, you can see the cell type that composes most of the tumor. You probably

recognize these cells as immature neoplastic lymphocytes.


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Nerve roots or peripheral nerves may be involved primarily or secondarily by neoplasms.Primary tumors include neurofibroma (-fibrosarcoma) and Schwannoma. Neurofibromas

originate from connective tissue cells of the nerve sheath and Schwannomas from Schwann cells.

They are distinguished histologically because the Schwannoma is encapsulated and distinct fromthe nerve and the neurofibroma is nonencapsulated and indistinct from the nerve. For ourpurposes, they will be considered together under the term nerve sheath tumor. Most nerve sheath

tumors in the cervical area originate peripherally and only later extend intradurally, whereas

thoracolumbar tumors usually begin intradurally. In either case, tumors may eventually involveother roots or nerves. Slides 39 and 40 show characteristic myelographic and pathologic features

of an intradural-extramedullary nerve sheath tumor.


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Advance Slide 41

Slide 41 shows a resected nerve sheath tumor that arose from the ventral root and

extended subdurally. Note the dorsal root ganglion at the top of the resected mass.


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A nerve sheath tumor involving multiple nerves of the brachial plexus in a dog is seen at

surgery in Slide 42 and after partial resection in Slide 43.


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Advance Slide 44

Peripheral nerves and nerve roots also may be involved secondarily by a variety ofneoplasms. Meningiomas originating at the outfolding of meninges around the nerve roots may

compress or invade the root. Bony and soft tissue tumors also may secondarily compress nerve

roots or peripheral nerves. In cats, lymphosarcoma sometimes involves peripheral nerves ornerve roots. This is particularly true at the brachial intumescence. A characteristic tumor that

arose within the brachial plexus of a cat and extended to the subdural space (note the

discoloration) is seen here.


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Advance Slide 45

Another case in which nerve roots of a cat were directly invaded by lymphosarcoma is seen

in Slide 45.


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Advance Slide 46

Lymphosarcoma may also affect peripheral nerves. Lesions may be either primary or

secondary. A cat in which the sciatic nerve was affected by a primary dermal lesion is seen here.

Note the mass overlying the right hemipelvis.


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Characteristic immature lymphocytes were seen on evaluation of an aspirate.


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Involvement of the cavernous sinus by lymphosarcoma in a dog is illustrated in Slides 49

and 50. The pituitary and cranial nerves III, IV, V, and VI were affected (cavernous sinus

syndrome).

cns gross&histo neoplasia-1_dr kornegay

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