Update on Neoplasm of Nervous system in Livestock and their Dignosi

SEMINARON

UPDATES ON NEOPLASM OF NERVOUS SYSTEM IN LIVESTOCK,

THEIR PATHOLOGICAL DISTINCTION AND DIAGNOSIS

Presented by

Dr. Rahul G. KadamPh.D Scholar

Roll NO. P1661

“ An abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner even after cessation of the stimuli that evoked the change.”

New growth composed of cells originally derived from normal tissues, that have undergone heritable genetic changes allowing them to become relatively unresponsive to normal growth controls and to expand beyond their normal anatomical boundaries.

Cancer

Anatomy of brain

Anatomy of brain

5

Classification World Health Organization classification

– Primary tumors classified on basis of cell origin

Most primary tumors of neuroepithelial origin– From malignant transformation of astrocytes, ependymocytes,

and oligodendrocytes

Gliomas most common– Arise from astrocytes

Metastases more likely than primary CNS tumor in patient with known systemic malignant disease

Different type of nervous tissue tumors Primary Neoplasm of Neuronal cells

o Medulloblastomao Neuroblastomas

Primary Neoplasm's of Neuroglial cellso Astrocytomao Oligodendrogliomao Oligoastrocytoma (Mixed Glial Tumor)o Gliosarcomao Ependymomao Pineal tumors

Primary Neoplasm of the Choroid Plexuso Choroid Plexus Papillomao Choroid Plexus Carcinoma

Primary Neoplasm of Mesodermal Tissueo Meningioma

Epitheloid form Psammoma form Fibrous form ossified m Angiomatoid form Sacomatous form

Cont.. Primary Neoplasm of Hematopoietic system

o Lymphoma/Lymphosarcomao Plasma cell tumoro Malignant Histiocytosiso Microgliomatosis

Other primary tumors and cysto Epidermoid cysto Hemartoma or meningio-angiomatosis

Neoplasm of the peripheral nervous systemo Ganglioneromao Paragangliomao Periferal nerve sheath tumor

Secondary Neoplasm or Metastatic Tumors of Central Nervous System

Fig. Medulloblastoma between cerebellum and fourth ventricale with extention into colliculus (arrow ) in cat

Medulloblastoma, well-known in children, is rare in animals

Occurs in the young of several species, mainly calves and dogs.

This tumor of unknown parentage.

It is currently thought to arise from undifferentiated cells found in neonatal life beneath the cerebellar piamater and thought to be the precursors of the cerebellar cortex.

These tumors grow rapidly.

Cont..

Fig. Medulloblastoma in calf showing Pseudorosettes (A) and detailed in (B) as circular grouping of dark tumor cell around central pale area containing neurofibrils.

These tumors are rare and occur in any part of the CNS. They are thought to arise from primitive neuroepithelial cells with

differentiation towards postmitotic neuroblasts. The histologic appearances consisting of masses of small rounded cells

that resemble lymphocytes, with hyperchromatic nuclei and scant cytoplasm.

Fig. The histologic appearance of Spinal nephroblastoma showing glandular areas intermingling with cellular areas. The glandular areas consist of rosettes and tubules, the latter tortuous, branching and papilliferous, with infoldings reminiscent of embryonic glomerular capsules

Astrocytoma

Fig. (B) Astrocytoma in piriform lobe in dog. Note lack of definition but displacement of internal capsule (arrow) by the hemogenous tumour. (E) Hemorrhagic astrocytoma of left frontal lobe in dog

Astrocytoma is the most common primary intracranial tumor. Astrocytomas are found most commonly in dogs. More prevalent in cerebrum, thalamus, hypothalamus, and midbrain. Astrocytomas have no age predilection but are more prevalent in middle-

aged or older dogs.

Histologically, these tumors are very diverse and are classified as Low-grade astrocytoma (well differentiated) Medium-grade astrocytoma (anaplastic) High-grade astrocytoma (glioblastoma)

Low-grade astrocytoma appears as an unencapsulated expansile and subtly invasive mass that replaces pre-existing tissues and has low to moderate numbers of bland round to oval cells. It appears as an increased population of fibrous astrocytes. It include

Fibrillary astrocytoma (neoplastic cells have scant cytoplasm but abundant fibrillary processes and filaments)

Protoplasmic astrocytoma (neoplastic cells have scant cytoplasm and few short processes and filaments)

Gemistocytic astrocytoma (neoplastic cells have abundant acidophilic cytoplasm and eccentric oval to round nuclei)

Pilocytic astrocytoma (neoplastic cells are bipolar, elongated (piloid or hair-like) astrocytes and have few Rosenthal fibers)

Medium-grade astrocytoma, the population is denser; the nuclei are a little larger and darker and show slight but definite variations in size and shape but no mitoses.

High-grade astrocytoma, or glioblastoma multiforme, hemorrhage and necrosis are expected and the adventitial and endothelial cells of the vessels proliferate forming glomeruloid blood vessels. Neoplastic cells have a tendency for pseudopalisading around necrotic areas. Pleomorphism, giant nuclei, and multinucleated giant cells are common. Mitotic figures are common and atypical.

Cont..

Cont..

Fig. (A) Fibrous astrocytoma in dog (C) Gemistocytic astrocytoma in dog

Oligodendroglioma

Fig. Oligodendroglioma involving right side of brain stem and piriform lobe in dog

This is the easiest of the glial tumors to recognize even when growing rapidly.

This tumor is reported in dogs especially in brachycephalic breeds and rarely in cats.

It usually appears well demarcated, being gray, soft, and almost fluctuating some time hemorrhage and necrosis occur but are unusual.

Cont..

Fig. Oligodendroglioma showing densely cellular with no stroma and nuclei are remarkably uniform and like those of normal oligodendroglia in size and shape. The cytoplasm does not stain, but its membrane does, so that the nucleus seems to lie in a clear polyhedral or rounded halo

Oligodendroglioma

This glial neoplasm is composed of both neoplastic astrocytes and oligodendroglia.

Gliosarcoma

This rare glial tumor is composed of highly anaplastic glial cells with abundant sarcomatous components.

Ependymoma Ependymomas are neuroglial tumors derived from the lining epithelium of

the ventricles and central canal of the spinal cord. Most arise about the third ventricle. They are gray and fleshy but may be dark from hemorrhage if they

project into a ventricle. They are more prevalent in dogs and cats, but are reported in horses and

cattle.

Fig. Tpical Braching papillary structure in an ependymoma in a dog, the nuclei are small, dark and regular and cytoplasm has not distinct boundries.

Pineal tumors

The benign variant is called pineocytoma

the malignant variant is called pineoblastoma.

They are described in horses, cattle, and dogs.

The diagnosis is based on the site of the tumor and its replacement of the pineal body.

Other positive identifying characteristics are absent.

Microscopically, there is a resemblance to medulloblastoma.

The tumor may extend into midbrain and thalamus.

Teratomatous tumors with characteristics of the gonadal teratomas are not described in the pineal gland of animals.

Choroid plexus tumors

These are rare, reported in cats, horses, and cattle, and occur with higher frequency in dogs.

They may be papillomas or carcinomas.

They are vascular papillary growths that implant widely on the meninges.

The cells retain recognizable choroidal character .

According to cellular atypia and invasiveness, these tumors can be classified as papilloma or carcinoma.

Internal or communicating hydrocephalus is a complication.

Cont..

Fig. Choroid pexus papilloma in dog

Fig. Invasion into the periventricular white matter of a dog by a Choroid pexus carcinoma.

Meningioma

Meningioma is the most common type of intracranial tumor in the cat and it is one of the commonest of the intracranial and intraspinal tumors in man, and is relatively common in dogs and rare in cattle.

These tumors are otherwise known as arachnoid-fibroblastomas as they arise from the arachnoid fibroblasts of the brain and spinal chord.

Meningioma occurs singly and by expanasion causes presure on brain.

Grossly the tumor appears as white lobulated and encapsulated.

Histologically, meningioma consist of spindle shaped cells of uniform size and shape. They have elongated oval nuclei and the cells are arranged in whorls.

Histologic Varieties of Meningiomas

1. Epitheloid form:- In this type, cell resembling epithelial cells (polyhedral cells) are found in sheets or pseudo alveoli amidst vascular connective tissue.

2. Psammoma form :- In this form of growth, bluish calcified bodies, calicospherules suggestive of grains of sand are dispersed in the substance of the tumor.

3. Fibrous form :- In this variety dense fibro-collagenous tissue with or without whorl formation or sand grains is found.

4. Ossified form :- In some part of tumor , ossification with haematopoietic marrow may be seen.

5. Angiomatoid form :- In these tumors, a rich supply of blood vessels are there and these blood vessels are thin walled.

6. Sacomatous form :- It is highly cellular and anaplastic without whorl formation.

Cont..

Fig.Meningioma attached to dura and calvaria (left) and leaving an indentation in left parietal cerebral cortex of a cat.

Fig. Pasammomatous meningioma showing arrangement of cells in whorls. In the center of a whorl, lamellar hyaline tissue forms, derived possibly from cells, stroma, or a blood vessel.

Lymphoma/ Lymphosarcoma

Primary CNS lymphomas are reported mainly in dogs and cats and sporadically in ruminants.

They are mostly intraparenchymal and have an angiocentric (perivascular) pattern in contrast to lymphosarcomas metastatic from extraneural areas that are usually arranged diffusely in the meninges.

Most primary CNS lymphomas are of T-cell type.

Plasma cell tumor

A primary intracerebral intraparenchymal plasma cell tumor has been reported in a dog.

Malignant histiocytosis

Primary neural malignant histiocytosis was reported in the right parieto-occipital lobe of a miniature Schnauzer as a poorly demarcated mass composed microscopically of histiocytic cells with many binucleate and multinucleate giant cells.

Microgliomatosis The histogenic origin of the neoplastic cell in this rare neoplasm is

controversial.

The neoplasm diffusely infiltrates the cerebral white matter and brain stem with cells reminiscent of microglial cells.

The infiltration in some cases can be limited to meninges or can be perivascular.

Epidermoid cysts in the brain are confined to the fourth ventricle and environs.

They are rare, probably represent surface ectoderm misplaced at the period of closure of the neural groove, and are described only in humans, dogs, and a horse.

The cystic structure is lined by squamous epithelium, and the cavities contain keratinaceous debris.

They occur in young dogs and may develop to several centimeters in diameter.

The clinical signs are determined by the location of the tumor.

Epidermoid cysts

Hamartoma or meningio-angiomatosis is a rare benign lesion, best regarded as a malformation or hamartoma producing circumscribed plaques on the surface of the brain.

Blood vessels are in excess in the lesions and are cuffed by proliferating cells that are considered to be meningothelial.

The lesion does extend into the underlying neural substance, which shows mixed degenerative and reactive changes.

Hemartoma or meningio-angiomatosis

Ganglioneuroma

These rare tumors originate from the cranial and spinal ganglia and from sympathetic ganglia of the autonomic nervous system.

They have been reported in cats, pigs, cattle, dogs, and horses. They can be solitary or multicentric. Ganglioneuroma is composed of ganglion cells and glial cells. Ganglioneuroblastoma is composed of poorly to fairly well

differentiated ganglion cells with more atypia and high nuclear to cytoplasmic ratio.

The degree of differentiation of these tumors varies considerably, and they are a mixture of ganglion cells, Schwann cells, and nerve fibers.

The ganglion cells show different degrees of differentiation from primitive neuroblasts to some that are remarkably mature.

The adrenal medullary ganglioneuromas and ganglioblastomas are probably better regarded as hamartomatous malformations rather than as neoplasms.

Paraganglioma

This rare neuroendocrine tumor originates from extra-adrenal paraganglion chief cells associated with autonomic nervous system ganglia.

Peripheral nerve sheath tumor

These include the benign form (schwannoma, neurofibroma) or the malignant form (malignant schwannoma, neurofibrosarcoma)

Schwannoma Sehwannomas may be largely solitary infiltrating lesions at any site on a nerve

trunk. Those distant from the CNS are not encapsulated or well defined, are difficult

to dissect cleanly, and have an ordinary fibrous appearance and texture. Schwannomas of nerve roots tend to be well-defined fusiform tumors. They probably arise from a single nerve and extend proximally and distally in

conjunction with the nerve but external to it. In this way they may extend through the intervertebral foraminae and extend

also to involve other nerves that have a plexus arrangement such as the brachial plexus.

They may arise within and remain within the dura mater, and such tumors may be globose rather than fusiform and soft and discolored from hemorrhage.

Expansive intradural growth may be slow and compress the brain or cord, but some of these tumors are malignant and invasive and metastasize particularly to the lung.

Cont..

Fig. Acostic schwannoma at cerebellopontine angle and filling the fourth ventricle of a dog .

Fig. Acostic schwannoma showingclosely packed cells with oval or elongate nuclei.

Neurofibromatosis Neurofibromatosis of cattle is a well-recognized Schwannoma.

It is common in abattoir material from old animals but has been observed in very young calves.

The skin may be affected, but the lesions are usually restricted to deeper nerves of the thoracic wall and viscera.

The brachial plexus, intercostal nerves, hepatic autonomic plexus, epicardial plexus, and autonomic nerves of the mediastinum are those most frequently affected in various collective patterns.

Sympathetic ganglia, especially the stellate and others of the thorax, are also frequently involved.

Affected nerves are thickened, firm, and gray, and may bear yellow-gray nodules.

Affected ganglia may be enlarged to several centimeters and appear lobulated on section.

Secondary Neoplasm or Metastatic Tumors of Central Nervous System

Secondary tumors can metastasize from extraneural tissue to the CNS.

They are mostly observed in the cerebral hemispreres and are multiple which indicates their metastatic nature.

The majority of this metastatic tumors have their primary site in the lung.

The most common examples include canine hemangiosarcoma, malignant histiocytosis, lymphosarcoma, and malignant melanoma of dogs and rarely other species.

Early detection is the key!

Cancer diagnosis comprises of

.involves evaluation of the patient’s history,

clinical examinations

paraneoplastic disorder

review of laboratory test results

radiological data, (X-ray.CT scan ,MRI. Ultrasound imaging)

Biopsy

Cancer staging

Molecular marker.(PCR and RT PCR based technique.)

Diagnostic approaches of tumor.

IMAGING

Malignancy is based on imaging information ,later confirmed on

histology

Ultrasound (kondyo et al.,2008)

Computed topography,(Drosot et al.,1996)

Magnetic resonance imaging(MRI)(kaiser et al 1992)

Metabolic and functional ImagingMolecular imaging with magnetic resonance spectroscopy.(MRS)

Position emission topography,(PET)(Grahek D et al 2004)

• computed tomography (CT)-scans

•  magnetic resonance imaging (MRI).

• Neoplasms will often show as differently colored masses (also referred to as processes) in CT or MRI results.

IMAGING

Benign brain tumors often show up as hypodense (darker than brain tissue) mass lesions on cranial CT-scans.

On MRI, they appear either hypo- (darker than brain tissue) or isointense (same intensity as brain tissue) on T1-weighted scans, or hyperintense (brighter than brain tissue) on T2-weighted MRI, although the appearance is variable.

Cont..

Cytology and Histopathological Technique

1. Still a gold standard for diagnosis of tumour.

Recent technique ImagingIHCPCRFlow cytometary FISHMICROARRAYNANOTECHNOLOGY

The definitive diagnosis of brain tumor can only be confirmed by

Histological examination of tumor tissue samples obtained either by means of brain biopsy or open surgery.

This examination, performed by a pathologist, typically has three stages:

Interoperative examination of fresh tissue, Preliminary microscopic examination of prepared tissues, Follow up examination of prepared tissues after immuno

histochemical staining or genetic analysis.

• What is tumor marker? Tumor markers are glycoproteins produced by tumor cells or by other body cells in response to cancer or other conditions.

As tumor cells multiply, spreads & tissue is damaged TMs increase in concentration.

• How it produced?

Tumor Markers

• Where do the TMs found? These substances can be found

in the blood (plasma, serum), urine, saliva, tissue fluid, in the tumor tissue or in other tissues.

• Ag –Ab based Techniques :

i) ELISA

ii) Radio-immunoassay

iii) Flow Cytometry

iv) Immunohistochemistry

• Molecular Genetic Techniques :

i) PCR / RT PCR

ii) Fluorescence in situ Hybridization ((FISH)

iii) Comparative Genomic Hybridization (CGH)

• Other Techniques :

i) Spectophotometry

Tumor Markers detection Methods

According to the US National Cancer Institute (OTIR, 2006) “Nanotechnology willchange the very foundations of cancer diagnosis, treatment, and prevention”

NANOTECHNOLOGY IN CANCER

. Nanotechnology will make possible to run test without physically altering the cells or tissue

Cancer nanotechnology is emerging as a new field of interdisciplinary research, cutting across the disciplines of biology, chemistry, engineering, and medicine, and is expected to lead to major advances in cancer detection, diagnosis, and treatment .(Menon U, Jacobs IJ. 2000, Ferrari M. 2005.)

Schematic diagram showing nanotechnology applications in cancer through molecular tumor imaging, early detection, molecular diagnosis, targeted therapy, and cancer bioinformatics

Nanodevices Are Small Enough to Enter Cells

Cell

White blood cell

Water molecule

Nanodevices

Nanodevices

Nanodevices Can Improve Cancer Detection and Diagnosis

ImagingNanotechnology Physical Exam,Symptoms

Nanodevices Can Improve Sensitivity

and determinewhich cells arecancerous orprecancerous.

Precancerous cells

Normal cells

Nanodevices could potentiallyenter cells

Precancerous cells

Normal cells

Nanodevices Can Preserve Patients’ Samples

Cells from patientCells preserved

Active state preserved

Cells altered Active state lost

Additional tests

Cells from patient

Nanotechnology Tests

Traditional Tests

Nanodevices Can Make Cancer TestsFaster and More Efficient

Patient A Patient B

Cancer prevention

Conclusion

1.Histopathology remains the standard conventional method.

2. Recent technique such as imaging ,ICH ,PCR ,flow cytometry ,FISH, CSH ,and microarry, nanotechnalogy contribute a major break through in diagnosis prognosis of cancer.

3.In future a multimodal imaging approach will evolve, enhancing diagnostic accuracy thus minimizing loss of lives due to cancer.