Oncology

Table of Contents

General Classification of CNS Tumors

A- Cranial Tumors    

B – Cranio-vertebral Junction Tumors     

C- Spinal Tumors 

Benign Lesions of Scalp

Seborrheic Keratosis

a. Seborrheic Keratosis: It is a benign brown-colored lesion arising from the basal epithelial cells. In contrast with Actinic Keratosis, they don’t become malignant. Therapy is more for cosmetic reasons or for obtaining diagnosis.

b. Actinic keratosisDarkened or red areas with irregular borders with origin of epithelial transformation. These occur on parts of the skin exposed to radiation or extensive sunshine. It shows a tendency to malignancy.

Keratoacanthomas

These are rapid growth lesions with papillary origin and clinically confused lesions. Therefore obtaining a definitive diagnosis for performing the appropriate treatment is recommended.

Malignant Lesions of Scalp

A- Primary Malignant Lesions

Basal cell Carcinoma (BCC)

A very common form of skin lesion arising from basal cells of epidermis and maybe becomes locally destructive. BCC may metastasize and lead to death.

It accounts for about 25% of all cancers in the United States and 75% of all non-melanoma skin cancer.  Risk factors are exposure to excessive sunshine, positive HIV, and also patients that have under-gone organ transplantation.

Squamous Cell Carcinoma (SCC)

This is the second common skin cancer, but highly curable. It originates from keratinizing cell of the epidermis.

Melanoma

There are several scalp tumors, of which we will choose the melanoma, because of its increasing incidence and mortality of 40% in recent years. Cutaneous melanoma arises from epidermal melanocytes, which derives from the neural crest and produce pigment melanin.

 Skull Tumors

General Histopathological Classification of Skull Tumors

The skull tumors are not common lesions, therefore, assessing their true incidence and sequel to the health of the population is not easy. However, recent diagnostic advances have made such lesions easier to recognize, and additionally new technique of skull-base surgery have provided access to previously inoperable skull tumors.

Primary Tumor of Skull

Benign Skull Tumors

Osteomas

Osteomas are the bone forming and most common primary skull tumors (calvarias), while osteoid osteomas and osteoblastomas are rare lesions.

These account for about 20-30% of all craniofacial bone tumors. It may occur in all parts of craniofacial, such parasagittal near the suture lines, skull base and mandible. Intradural osteomas have been reported in rare cases.

Chondromas (Osteochondromas) 

These are the most common skeletal neoplasms arising from the endochondral ossification at the skull base. They may also arise from the choroids plexus, Dura or the arachnoid sheet.

Hemangiomas and Lymphangiomas

Whether they are a congenital malformation or true neoplasms still remains controversial. These are benign lesions occur mostly in vertebral column, more than lymphoma. The hemangiomas usually are unifocal, but rarely also multifocal.

These constitute about 0.7 % of all bone tumors and 10% of all skull neoplasms.

Epidermoid, Dermoid, Teratoma

These are congenital neoplasms arising from ectodermal cells (Dermoid and Epidermoid) or rarely from endodermal or neuro-ectodermal cells (Teratoma). The most favored location for epidermoid is at the cerebello-pontine angle (CPA), and paracellar region. Dermoid tumors usually occur in the midline frontal. 

Giant Cell Tumor (Osteoclastoma)

The cell origin of tumor is not well known, but tendency to malignant degeneration is about 10-15%. 

It is a rare tumor and accounts for about 5% of all body bony tumors. Most of them involve the long bones, only 2% of them may occur in head and neck. They may be found in the calvaria, or skull base involving the temporal or sphenoid bones.

Aneurysmal Bone Cyst

This is a benign lesion of unknown origin with large vascular elements, separated by bony trabeculae and fibrous elements. The ABC is a controversial subject. It is probably neither neoplasm, or aneurysm, or cyst. Trauma has been reported as a risk factor.

It accounts for approximately 1% of all aneurysmal lesions of cranial, distributed overall. 

Primary Malignant Tumors of Skull 

most common primary malignant tumors of Skull are:

Osteosarcomas

Osteomas are the bone forming and most common primary skull tumors (calvarias), while osteoid osteomas and osteoblastomas are rare lesions.

These account for about 20-30% of all craniofacial bone tumors. It may occur in all parts of craniofacial, such parasagittal near the suture lines, skull base and mandible. Intradural osteomas have been reported in rare cases.These are more common in youth than adults and female- to- male ratio is 3:1.

 different types of osteomas are:

  • Classic form (compact)
  • Fibrous form
  • Cancerous form

In the case of multiple osteomas, the Gardner’s syndrome should be considered. This is characterized by the triad of multiple osteomas, soft tissue benign neoplasm (e. g. lipomas, fibromas) and gastrointestinal polyposis with tendency to malignancy.

Fibro-sarcomas

These arise from mesenchymal cell, tissue of bone marrow and characterized by malignant fibroblasts.

Fibro-sarcoma represents only about 10% of musculoskeletal sarcomas and less than 5% of all primary tumors of bone. It occurs slightly more in men than in women.

Ewing’s Sarcomas

These are a malignant tumor arising from mesenchymal tissue of lower extremities such as femur bone or pelvic in 60%) of cases. Ewing’s sarcomas mostly occur in children and young people. They commonly arises in long bones of the below extremities such as femur, but also in pelvis in 60% of cases (1). They are either Primary- or secondary tumors. Temporal bone is most commonly affected followed by frontal and parietal bone with mostly soft tissue extension.

Primary Ewing’s sarcoma of the cranial bone is rare and contributes about 1% – 4% depend on different studies

Direct Extension Neoplasm of Skull 

Metastatic Meningioma

It is the most common intra-osseous skull tumor involving the inner table. This is very rare secondary meningioma as intra-osseous skull tumors (about 35 cases reported in the literature).  

Hyperostosis is the main character of all types of bone involvement tumors shown by initial plain x-ray of skull.

CT-scans show a homogeneous mass with partial calcification and erosion of inner table of the skull. MRI may demonstrate the invasion of the tumor intracranial and also into dural venous system. There is a typical finding called “Dural tail” or “hat brim” a sign of dural edge hyperplasia.  MRI is useful to demonstrate the spread of tumor into adjacent structures.

Lymphoma

Non-Hodgkin’s lymphoma involves the skull bone in about 25% of cases. The involvement may occur by infiltration of adjacent soft tissue lymphoma.  The secondary lymphoma of skull is more common than primary. Only a few accounts of primary lymphomas have been reported in literature.

There are a variety of signs and symptoms depending upon the character of lesion such as headache, usually due to the increased ICP, or involvement of meninges or bone destruction. However it usually doesn’t cause the bone lytic, but rather permanent change in the calvarias.

Plasmacytomas (Multiple Myeloma)  

Plasmacytoma is a solitary mass of neoplastic monoclonal plasma cells occurs either in bone or in soft tissue (extra-medullary plasmacytoma (EMP). It is usually associated with abnormal immunoglobulin. This may be present in the skull bone as a multiple lesions, but also is found in the thoracic and lumbar spine and may lead to bone fracture. The solitary plasmacytomas can be divided into two groups based on location of lesions as follow:

Skeletal bony Plasmacytoma (SBP)

Extra-medullary plasmacytoma (EMP)

shows the different type of plasmacytomas:

  • Solitary bone plasmacytoma (SBP)
  • Soft-tissue or non-osseous extra-medullary plasmacytoma (EMP)
  • Multifocal form of multiple myeloma
  • Multiple myeloma
  • Plasmablastic sarcoma

Neuroblastomas

These arise from neural crest cells. They are called a ganglio-neuroblastoma in the case of partial differentiation, and ganglio-neuroma, if it is fully differentiated. It is the most common metastasis to the skull in children.  About 50% of patients may have craniofacial metastasis.

CT- scans show the facial metastasis of tumor as an irregular texture with permanent changes, whilst the imaging appearance of tumor in the skull is plaque-like epidural or subdural enhancing mass.

These depend on the location. It may cause local swelling, visual complaints, headache and eventually cranial nerve palsies. Approximately, 1% of fibrous dysplasia tends to most common malignant osteosarcoma, but also fibrosarcoma and chondrosarcoma. 

Conditions Stimulating Skull Lesions         

 shows some different lesions that stimulating the skull tumors

  • Fibrous dysplasia
  • Paget’s disease
  • Hyperostosis frontalis interna
  • Eosinophilic granuloma
  • Lepto-meningeal
  • Osteomyelitis
  • Sinus pericranii
  • Sarcoidosis

Fibrous Dysplasia 

It is the result of a defect in the osteoblastic differentiated and maturation cells of the bone.

The etiology is still unknown. It accounts for about 2.5 % of all primary bone mass and 7% of benign masses. This affects both male and female equally.

Fibrous dysplasia is usually mon-ostotic in craniofacial region (about 80%), but there is a less frequent poly-stotic type involving the skull base associated with endocrine dysfunction and cafe au lait spots (i.e. Mc Cune-Albright-Syndrome).

These depend on the location. It may cause local swelling, visual complaints, headache and eventually cranial nerve palsies. Approximately, 1% of fibrous dysplasia tends to most common malignant osteosarcoma, but also fibrosarcoma and chondrosarcoma.  

Paget’s disease (Osteitis Deformans)

It is a multi-centric chaotic and unknown origin lesion that consists of various portions in various stages. This is most common in axial skeleton such as femur bone, vertebral body and pelvic, but the skull also is involved in 65% of cases. The favored area is frontal or occipital region of crania. Paget’s disease is usually associated with several benign and malignant neoplasms.

Pathologically it starts as a diffuse mottled thickening in the frontal or occipital area as irregular patches or lysis, which creates the appearance of a geographical skull. It develops later patchy sclerosis. 

Hyperostosis frontalis interna    

This is an idiopathic benign lesion with unknown etiology, characteristically is hypertrophy of the inner table with sparing of the midline.  It is common in middle age. This is characterized by bilateral or unilateral nodular thickening of the inner table, with progressive development of diploe in this table. It is common in elderly women and grows very slowly over years. 

There are several diseases which have been associated with Hyperostosis such as diabetes mellitus, Hypertension, headache, seizures, cranial nerve deficits and mental disturbance (30). It is also most often asymptomatic. 

Eosinophilic granuloma

This seems as an irregular lesion with no sclerosis in skull radiographic. Therapeutically is complete excision the main goal of treatment and in additional small dose radiation (10Gy) as an palliative therapy. This mostly occurs in frontal bone and spread extensively with irregular structure and margin as “map like”. The frontal- and para-nasal sinuses are also involved frequently. Therapeutically, is diagnostic biopsy and local radiation following chemotherapy is advocated

Leptomeningeal cyst

It may mimic a tumor radiologically, in particular as a lucent area with soft tissue shadow outside of the skull bone. Occasionally it grows between the tables of skull and builds an interosseous cyst or can be a complication of growing the skull bone in children. There is no an exact treatment strategy, unless intracranial involvement exist.

Osteomyelitic lesion

Chronic osteomyelitic site may appear as a multiple nodular lucent areas in the outer table or diploe. Later they condense into a large defect area with scalp edema (Pott’s puffy tumor). Sclerosis may occur at the edges of the bone with no sub-periosteal bone or sequester formation. There is no an exact treatment strategy, unless intracranial involvement exist. 

Sinus pericranii

It is a congenital skull defect consists of abnormal emissary veins, which connect an intracranial venous sinus, mostly the superior sagittal sinus. It is usually seen in the frontal region with a complex of veins or a venous angioma in the extra-cranial space.

It rarely involves the skull. It is seen as multiple punched out areas of rarefaction on the skull bone.

Tumors of Skull Base

General Histopathological Classification of the Tumors of Skull Base

 the four different groups of skull base tumors according to their origin:

  • Endo-cranial tumors with invasion to the skull-base, such as meningiomas
  • Exocranial tumors with direct extension to the skull base such as Glomus Jugular Tumors, PENT tumors
  • Osseous tumors such as chondromas, chondromsarcomas, chordomas
  • Metastatic tumors of the skull-base such as carcinomas of prostate, Lung- and breast

 

Spenoidal Wing Meningioma (Osseous Meningioma)

This type is characterized by hyperostosis, or bone destruction. Hyperstosing meningioma must be distinguished from the bone modification present in global meningiomas. Osseous changes may occur in about 50% of cases.

Hyperostosing En Plaque” meningiomas are a clear-cut type of the SB neoplasms and almost always involve the greater sphenoid wing with extension to the orbital roof and frontal bone. In the case of medial form of tumor, the lesser sphenoid wing will be involved, whereas the internal variety of meningiomas involves the anterior clinoid process, orbital medial wall and sphenoid sinus

 

 

Olfactory Groove Meningeomas

These are the clear-cut type of the SB tumors with special consideration regarding the different location, surgical approach and post-operative outcome in contrast to the central skull base tumors (CSB).

This is an anterior cranial base meningioma occasionally involving and destructing the skull base.

The exact anatomy of basal bone structure regarding the hyperstosis or bone destruction, location of olfactory nerves and also drainage veins from frontal lobes should be studied before surgical procedure.

Glomus Jugulare Tumors (Paragangliomas)

These are neural crest tumors and arise from the paravascular chemoreceptor cells known as glomus Tumors (paraganglion cells). These cells are located along neurovascular structure such as carotid bifurcation, jugular vein and cranial nerves. The tumor will carry name based on its location. The most common tumor is glomus jugular tumor arising from the jugular bulb in foramen jugular in about 90% of cases and followed by tympanic nerve in temporal bone.

Chondromas (Osteochondromas)

It is the most common skeletal neoplasm arises from the endochondral ossification at the skull base, but it may also arise from extra- cranial and extend into cranial space. Besides, there are endocranial chondromas, which arise from the embryonic cartilaginous or from choroids plexus, Dura or the arachnoidea. The favored region at the SB is posterior parasellar spheno-ethmoidal area and also clivus bone.  

It accounts for approximately 0.5% – 0.8% of intracranial tumors.

Chondrosarcoma

It is a low grade malignant tumor of SB with predilection for sphenoid or clival bone. They are usually spontaneous, but may occur in dysplastic chondroid disease such as Maffucci’s syndrome.

These also arise from the endochondral ossification at the skull base, but it may also arise from extra- cranial and extend into cranial space like chondromas. The favored region at the SB is posterior parasellar spheno-ethmoidal area and also clivus bone.  

These are low grade tumors with slow local spread, but distant metastases are very rare.

Fibrous Dysplasia

 It is characterized by an interosseous proliferative connective tissue, which may lead to the strong thickness of the involved bone. They occur almost always in young people, with unknown etiology.  

three different types of Fibrous dysplasia are:

  • Type lytic: It doesn’t destroy the bone, but involves this and changes it into a huge radiolucent area. It accounts for about 15% .
  • Type sclerotic: Compact form with thickening of bone mostly occurs in sphenoid body, but it may extend deeply into the nasal cavity. It accounts for about 50% of cases.
  • Type pseudopagetic: This is a mixed form of lytic and sclerotic.

Exophthalmos, unilateral visual impairment and cranioorbital or craniofacial deformation.  

Tumors of Intracranial Components (CNS)

The new WHO Classification of Tumors regarding the Central Nervous System defined a new comprehensive classification of neoplasms affecting the CNS. According to the (WHO 2012) classification, there are about 120 types of brain tumors, which are based on morphological pattern, and immuno-histo-chemical identification, molecular and genetic diagnosis improved the characterization of brain tumors. Molecular and genetic profiles may identify different tumor subtypes varying in biological and clinical behavior. The St. Anne/ Mayo grade has also proven to correlate better with survival than the previously common Kernohan grading system. The tumor classification dictates the choice of therapy and predicts prognosis.

In the following chapter you will get only an overview of the histo-pathological classification of CNS tumors based on (WHO 2012) and St. Anna Hospital Mayo Clinic.

Neuroepithelial Tumors

Glial Tumors (WHO I-IV)

Astrocytomas

There is a sub-classification of low grade astrocytomas Grad I-II, based on St. Anna Hospital Mayo clinic, which divided the astrocytomas in the invasive and non-invasive tumor types, however are also not recognized by the new WHO classification system, but are in common use.

There are two major groups of astrocytomas:

– Circumscribed type of astrocytomas

– Diffuse type

Grade I: These belong to the circumscribed types of astrocytomas such as Pilocytic astrocytomas, desmoplastic infantile, and subependymal giant cell astrocytomas (Non-invasive).

Grade II: Diffuse fibrillary astrocytoma, with two morphologic variations as protoplasmic astrocytomas, gemistocytic astrocytomas, which are prone to undergo malignant progression. Pleomorphic xanthoastrocytoma belongs to circumscribed type (Invasive types).

Grade III: Diffuse anaplastic astrocytomas: This is a mixture of fibrillary and gemistic cells. This is a very common type. It is a hyper cellular type with few differentiated cells, but it likely shows anaplastic progression to glioblastoma. Gliomatosis cerebry is a diffuse form mostly involving the brainstem and spinal cord. 

Grade IV: Glioblastoma (glioblastoma multiform)

Oligodendroglial Tumors (WHO II-III)

Conventional Oligodendrogliomas (WHO grade II)

These are well infiltrated and differentiated types and mostly occur in white matter of brain with „fried egg “appearance. Another histologic feature of oligodendrogliomas is “chicken-wire” with vascular pattern.

Oligodendrogliomas ultimately undergo anaplastic progression.

Anaplastic Oligodendrogliomas (WHO III):

This type shows increased cellularity, microvascular proliferation with generally focal and diffuse histologic feature of malignancy. 

Mixed Oligoastrocytomas (WHO II-III)

This type is a mixed form both types oligoastrocytoma (OA; WHO II) and anaplastic oligoastrocytoma (AOA; WHO III) and is composed of glial neoplastic cells: astrocytic and oligodendroglial cells.

Mixed Glioneural Neoplasms (WHO I)

Mixed Glio-neural Tumor, Unusual Rare Clial tumor (WHO I):

These are low grade unusual rare tumors mostly occurring in children and youth. There are 3 common types as follows:

– Dysembryoplastic neuroepithelial tumors

– Desmoplastic infantile ganglioglioma

– Ganglioglioma

 most common neuronal and mixed neuronal-glial tumors are:

  • Gangliocytoma
  • Dysplastic gangliocytoma of cerebellum (Lhermitte-Duclos)
  • Ganglioglioma
  • Anaplastic (malignant) ganglioglioma
  • Desmoplastic infantile ganglioglioma
  • desmoplastic infantile astrocytoma
  • Central neurocytoma
  • Dysembryoplastic neuroepithelial tumor
  • Olfactory neuroblastoma (esthesioneuroblastoma)
  • Ependymo-astrocytomas

Epithelial Tumors

Choroid Plexus tumors:

Choroid plexus can be involved by a variety of mass lesions such as neoplastic and metastatic mass.

Choroid Plexus Papilloma (WHO grade I):

It is a benign tumor arises from epithelium of choroids plexus mostly of the lateral ventricles, by children, rarely it occurs in third ventricle. This is curative by surgical treatment.

Choroid Plexus Carcinoma (WHO grade III)

It is also most common tumor in children. The tumors show aggressive behavior and have an unfavorable outcome.

Choroid Glioma of the third ventricle

This occurs in adults and is localized in the rostral third ventricle. Chordoid glioma is recognized as a distinct clinico-pathologic entity by WHO criteria as a neuro-epithelial tumor.  The tumor is low grade and curative by surgery, but the hypothalamic location prevents total resection. 

Primary CNS Lymphomas (PCNSL)

CNS can be involved by primary, but also by secondary lymphoma. Its incidence has increased due to acquired immunodeficiency syndrome (AIDS).

Histopathologically, PCNSLs are composed of neoplastic lymphocytes, which invade the cerebral parenchyma with a tendency to angiocentric infiltration.

The diagnosis may be performed by direct stereotactic biopsy. There is another intravascular type (angiotropic lymphoma), which may cause vascular occlusion of small intraparenchymal vessels and leads to small cerebral infarctions. This is very sensitive to the steroid therapy, which may make the histologic diagnosis more difficult.

Combination of radio- and chemotherapy provides a survival rate of 70% at 2 years and 45% at 5 years. Aids patients have a median survival of approximately 13 months after therapy.

Meningeal Tumors

Meningiomas (WHO grade I)

Meningiomas are common intracranial tumors with an incidence of approximately 13%-26% of primary intracranial neoplasms. These originate from arachnoidal cells. They can arise everywhere, where meningeal cells are present such as cerebral convexities, falx, skull base, or spinal cord.

There is a wide range of benign morphologic types, but also those characterized by more aggressive variants of meningeal tumor such as meningeal Sarcomas, hemangiopericytic Meningiomas

 Variant types of meningeal Tumors arising from meninges called (Meningiomas) are:

  • Meningothelial
  • Fibrous (fibroblastic)
  • Transitional (mixed), psammomatous, angiomatous, microcystic clear cell, chordoid, lymphoplasmacyte-rich, and metaplastic subtypes
  • Atypical meningioma
  • Anaplastic (malignant) meningioma
  • Non-menigothelial tumors of the meninges

Pineal Tumors

There is a wide range of tumors in the pineal region, most common of them are as follows:

Pineocytomas (WHO grade II)

are well-defined slow-growing tumors and composed of uniform cells arranged in lobules (Pineocytomatous rosettes), but there is another type with high cellularity and nuclear atypia called pineal parenchymal tumors, which should be treated aggressively.  

Pineoblastoma (WHO grade IV):

This is a malignant tumor, neuroectodermal tumor, with tendency to metastasize through the CSF. This usually occurs in children.

Primitive Neuroectodermal Tumors (PNET)

Supratentorial primitive Neuroectodermal Tumors (WHO grade IV)

These are highly malignant rare tumors and usually occur in the pineal region and retina.

This is classified as cerebral neuroblastoma, pineoblastoma, and retinoblastoma.    

Another very rare type is atypical teratoid rhabdoid tumor (ATRT). These usually occur 25% in the supratentorial and 75% in the inferatentorial region.

Germ Cell Tumors

Germinomas usually involve the midline structure, likely pineal region, but also occur in supracellar area, basal ganglia and thalamus. These are composed of two types of cell populations:

– Large malignant germ cell

– Small reactive inflammatory cells (composed of lymphocytes and plasma cells)

Germinomas are highly radiosensitive and are treated by radiotherapy or a combination of radio and chemotherapy.

Capillary Hemangioblastomas (WHO grade I)

CH is a benign tumor, mostly occurring in posterior fossa. These arise from stromal cells amid a capillary vasculature.

It is morphologically similar to renal cell Carcinoma, which is very often seen in von Hippel-Lindau disease (DD). It can be demonstrated by imaging studies as sharply demarcated and be treated by surgical intervention.

The Most Common Supratentorial Tumors

Clial Tumors

Low Grade Gliomas (WHO grade I-II)    

These arise from the glial cells of brain parenchyma and are mostly Grade I- II, according to the WHO classification 2012, and also Grade I and II according to the Kernohan and St. Anne hospital/ Mayo classification. This group is composed of – Astrocytomas- Oligodendrogliomas- Mixed gliomas .

different types of low grade gliomas are:

Astrocytomas:

  • Pilocytic astrocytoma non-invasive (St. Anna Mayo grade I)
  • Subependymal giant cell astrocytoma non-invasive( Mayo clinic grade I)
  • Pleomorphic xanthoastrocytoma non-invasive ( St. Anna Mayo grade I)
  • Gemistocytic Astrocytoma
  • Fibrillary Astrocytoma (WHO grade II)
  • Oligodendroglioma:
  • Conventional Oligodencroglioma (WHO II, Kernohan/ St. Anna grade II)
  • Mixed Type:
  • Mixed oligoastrocytoma (WHO II, Kernohan/ St. Anna grade II)
  • Desmoplastic infantile gangliomglioma ( St. Anna Mayo grade I)
  • Ganglioglioma (St. Anna Mayo grde I)
  • Dysembryoplastic neuroepithelial tumors (St. Anna Mayo grade I)

Incidence

Glial tumors generally account for about 50% of primary brain tumors. Definitive incidence of low-grade astrocytomas is not so clear, because of diagnostic criteria. However astrocytomas constitute about 26.6% (15% in adults, 25% in children).

 oligodendrogliomas is controversial depending on histologic criteria and account for about 2.1%, but in other reports about 18.8%-33%. The median age of patients is about 35 years. 

High-Grade Gliomas (WHO grade III-IV)

This group also arises from the glial cells of brain parenchyma and is developed according into the malignant cliomas (WHO grade III-IV).

General Classification

The first classification based on belief that these tumors arose from primitive neuroectoderm was in 1926 by Bailey and Cushing. In 1979 WHO published its classification, which was modified in 1993, 2007 and 2012.

 different Types of high grade gliomas based on a four-tier schema are:

  • Anaplastic Astrocytoma (WHO grade III), high grade glioma
  • Glioblastoma Multiform (WHO grade IV) last high grade of glioma:
  • Giant cell Glioblastoma
  • Gliosarcoma
  • Anaplstic Malignant Oligodendroglioma (WHO III)

These neoplasms make up about 2% of all adult tumors. The mean rate is about 5 cases per 199,000 population. Development and refinement of imaging studies contribute to the early diagnosis and also to increasing incidence in recent years. There is a ratio of 1.6 male to female.

Gliosarcoma is a rare subtype of GBM and is composed of glial cells and mesenchyma component and accounts for about 8% of GBM.

Malignant Oligodendrogliomas (MO) occur in adults and are approximately 10% of all intracranial gliomas. 50%-75% of recurrent oligodendrogliomas are usually anaplastic and about 15% could be frank GBM.

MO is more sensitive to chemotherapy and radiotherapy regimens.

There is no strong evidence in literature based on familial cancer syndrome, but the genetic factor plays a significant role in colonic polyps and colon cancer associated with malignant gliomas.

Genetic defect is also responsible for neurofibromatosis types I and II

TP53 tumor suppressor gene has been recognized as an important factor in the development of malignancy.   

Mechanism of Glioma spread

This is based on presence of secondary structures that are formed during the process. Spread of gliomas is related to the Extra Cellular Matrix (ECM) mulecules organized as a basement membrane. Spread of gliomas may occur perineural, perivascular, perifascicular and interfibrillary of white or gray matter or combination of these. The most common mechanisms of spread for gliomas are through the white matter or ECM.   

Multiple lesions are a result of tumor invasion from an initial monoclonal origin. There is a correlation between the motility of malignant glioma cells and increasing of malignancy grade with epidermal growth factor, because EGF is a mitogen and motogen and also plays a significant role in local recurrence. Nevertheless, anaplastic astrocytoma grows more infiltrative than GBM. Thus, multifocal gliomas are more common in anaplastic astrocytomas than GBM.

 

Choroid plexus Tumors

Coroid plexus tumors of ventricle system demonstrate a wide spectrum of histologic neoplasm. This can be involved by a variety of mass lesions such as primary benign neoplasms and also metastatic mass.

The most common primary neoplasms of choroid prexus are as follows:

Choroid plexus papilluma (WHO grade I)

This arises from epithelium of the choroid plexus of cerebral ventricles. It is a benign tumor and curative by surgical treatment.

Choroid plexus carcinoma (WHO grade III)

This is also most common in children. The tumor shows aggressive behavior and has a propensity to invade the surrounding brainstructures. It has an unfavorable outcome.

Rare and Unusual Gliomas

These tumors of CNS are rare and knowledge of their behavior, ethiopathogenesis and therapies are also confined.  These are listed as follows:

Pilocytic Astrocytomas

These are a common lesion in children and teenagers. 20% of them occur in childern younger than 15 years. It accounts for about 30% of all posterior fossa tumors of childhood. 80% of pilocytic astrocytomas are found in the posterior fossa. The first description of tumor as an independent entity was by Cushing.

These are usually related to the increased ICP such as head-ache, vomiting and pupiledema, ataxia, and dysmetria (hyper-or hypometria) can also be present in the case of involving the brainstem.

Brain stem Gliomas

These are common tumors in children and teenagers, approximately 10% -20% of all CNS tumors.

The four streotypes of brain stem gliomas according to the MRI findings:

  • Focal brain stem glioma
  • Diffuse type of BS Glioma
  • Cervicomedullary localization of tumor
  • Dorsal exophytic type of IV ventricle

Diffuse type is the most common form of BS Glioma and accounts for about 80% of all brainstem gliomas. In contrast to focal and dorsal exophitic types, it is mostly high-grade astrocytomas such as anaplastic astrocytomas. The dorsal exophytic type arises from floor of fourth ventricle sharply confined from the surrounding structures and accounts for about 20% of all brainstem tumors. Cervicomedullary type arises from cervical cord and extends superiorly to pyramidal decussations, and also dorsaly into the fourth ventricle. This is a low grade astrocytoma.

Symptoms are related to the type, location and extension of the tumors. These are almost always lower cranial nerve deficits, con-tralateral hemiparesis, ataxia, hydrocephalus and occasionally torticullis spasticus.

Subependymal Giant Cell Astrocytoma

This tumor is a slow-growth type with little risk of transformation into the malignancy. It generally occurs in patients with tuberous sclerosis and is an intraventricular lesion. This may cause symptoms in case of obstraction of ventricular outflow.

It depends on size and location of tumors causing neurological signs (ventricular obstruction) including the signs of tuberous sclerosis such as mental retardation, seizures and skin alteration.

Gangliogliomas

First description was by Perkins in 1926. It is an infrequent neoplasm found in all regions of the CNS including the spinal cord and accounts for about 0.4%-1.3% of all brain tumors. It is composed of neuroplastic neural and glial cells. These are well differenciated tumors with rare malignant features.

These are based on location of tumor, but in the case of affecting the temporal lobe in young patients seizure is the first and most common sign in about 92% of cases. Neurological deficits and increasing the ICP associated with headache are further symptoms. 

Radiological characteristics of gangliogliomas are really variable, because of different forms of tumors, cystic or solid, and propensity for harboring the calcification components. T1-weighted images show the solid tumors mostly isointense, whereas T2-weighted images demonstrate them as moderate or pronounced hyperintense. Propensity for contrast enthancement is about 50% in cystic and 80% in solid tumors.

The treatment strategy and also outcome of gangliogliomas is associated with location and involved neural tissues. These can be surgery only, surgery and radiation, surgery plus radiation and chemotherapy.

The histologic grade of the tumor is another important predictor of outcome. Lang and co-workers found no survival differences between low- and high-grade gangliogliomas, however the progression-free survival rate between both grades is different. These are about 57% in low-grade and 15% in high-grade tumors.

Desmoplastic Neuro-epithelial Tumors

Natural history of this tumor is still unknown.

It accounts for about 1% of all intracranial neoplasms. These are seen in infants as a large size mass, which is associated with enlarging the head circumference, which usually leads to surgical resection. 

These are enlarging the head circumference, cranial bulging over the tumor, bulging anterior fontanelle, sometimes increasing the ICP with vomiting or seizure and focal motor signs.

Pleomorphic Xanthoastrocytomas

The first description was by Kepes and colleagues in 1979. These have been reported in a wide range of life from infancy to the 7th decade of life. The majority of tumors are located in supratentorial and cerebral hemispheric, but also in infratentorial; cerebellum and spinal cord.

The most common neurological finding in approximately 70% – 80% of patients is seizures. This is the only complaint in 44% of patients. The other symptoms are related to increase of ICP, such as headache, local deficits, and haemorrhage occurring in the tumors.

CT- and MRI- scans both reveal a solid well- confined, but mixed intensity with cystic components in about 50%-60% of cases. Gadolinium enhancement is seen in MRI- and CT-scans.

This is total or subtotal surgical resection of tumor. In the case of progression of tumor proved by Gadolinium-enhanced MRI scans, an additional adjucent therapy should be considered.

These are quite rare tumors, therefore there are no large groups investigated. A survival rate of approximately 90% in 5 years and 82% in 10 years after surgical resection has been reported by Pahapill and colleagues. In the recent retrospective published series from the Mayo clinic the overall survival rate was 81% in 5 years and 70% in 10 years.

Astroblastomas (controversial accepted glioma)

First description was by Baily and Bucy in 1930, but the acceptance of astroblastoma as a separate entity is still controversial. The reason is that astroblastic features can be found in other types of geliomas such as anaplastic- and gemistocytic astrocytoma or glioblastoma.

There is a great variability of natural history of tumors, which has been reported. Some of them have benign clinical term with 12-20 years tumor free after surgical resection, but those cases that have a rapidly progressive nature indicative of anaplasia and progression into glioblastoma lead to fatality.

These depend on the location of tumors such as cotical, subcortical and periventricular with hemiparesis, seizures, and personality changes.

CT scans demonstrate variable features of tumors ranging from poorly confined irregularly enhanced, hypodence mass to a well-confined intensely enhanced tumor. Angiography shows a strong vascularisation tumor. There are not enough publications on MRI studies.

Surgical resection is the best modality of choice. Owing to the most cortical and subcortical localization of tumor, the total resection of tumor is possible. However, the role of radiotherapy and chemotherapy remain controversial.

It is totally different depending on the malignancy of tumor. There is evidence of long-term survival of 3-20 years in the case of benign type, but also sign of progressive degeneration into glioblastoma multiform with 1.5-2.5 years survival.

Hamartomas

Hamartomas are not really neoplasms, but they may mimic tumors, because of their size and location. These are composed of neural and glial cells. The favorable location is hypothalamus, which may cause precocious puberty (3). These have no progressive growth and don’t invade the surrounding brain tissues.

Hamartomas normally cause no major symptoms, only in thecase of compression or irritation of location tissue. When this is located in hypothalamus it may produce the precocious puberty. When these are present in the cerebral cortex they can cause epilepsy.

CT-scans demonstrate an isodense demarcated mass. These can also be hyperintense on T2-weighted MRI-scans.

in the case of precocious puberty medical treatment is the optimal choice, whereas the surgical resection is indicated in the case of tumor extension into the subarachnoid space. Radiotherapy has been used, but with unfavorable results.

Intraventricular Tumors:General Consideration

Ventricle system is a favored site for several lesions, arising from intraventricular, as well as from surrounding structures. These can be tumoral and vascular lesions or globally common infection such as Neuro-cysticercosis as intraventricular mass.

Tumors of ventricle system are primary or secondary.

The primary tumors usually arise from intraventricular structures such as ependyma, subependymal glial cells, or choroid plexus etc. Most common tumors are ependymoma, astrocytomas, meningiomas, choroid plexus papilluma, and carcinoma, colloid cysts, dermoid and epidermoid neoplsams and finally the cysticercosis larvae.

Secondary intraventricular tumors are mostly invaded and extended lesions from surrounding brain paranchyma, and priventricular white matter such as thalamus, cuadate nucleus, or internal capsule.

Several of the primary and secondary intraventricular neoplasms have been discussed in other chapters. The purpose of this chapter is to des-cribe three different types of intraventricular tumors as follows: Ependymoma, choroid plexus papilumas, colloid cyst of third ventricle.

Ependymomas

This tumor usually arises from the ependymal cells lining the ventricle system and also central canal of the spinal cord. The most favored locations are supra and infratentorial, conus medularis- filum terminale.

There are a wide range of tumors with ependymal differentiation benign to highly malignant.

different types of ependymomas are:

  • Subependymoma is an intra-ventricular tumor in adults. It may lead to obstruction of ventricle (WHO G. I)
  • Myxopapillary ependymoma almost arises from region of conus medullaris/ filum terminale (WHO G. I)
  • Mixed type is a mixed form of classic ependymoma and subependymoma (WHO G. II).
  • Classic ependymoma (WHO G. II)

Anaplastic ependymoma is common in children and arises from the ependymal lining of cerebral ventricle or from central canal of spinal cord (WHO G. III).

Choroid plexus Tumors

Coroid plexus tumors of ventricle system demonstrate a wide spectrum of histologic neoplasm. This can be involved by a variety of mass lesions such as primary benign neoplasms and also metastatic mass.

The most common primary neoplasms of choroid prexus are as follows:

Choroid plexus papilluma (WHO grade I)

This arises from epithelium of the choroid plexus of cerebral ventricles. It is a benign tumor and curative by surgical treatment.

Choroid plexus carcinoma (WHO grade III)

This is also most common in children. The tumor shows aggressive behavior and has a propensity to invade the surrounding brainstructures. It has an unfavorable outcome.

Colloid Cyst

This is a benign slow-growing tumor arising from neuroepithelial of third ventricle. It is the most common mass lesion within the third vetricle.

This usually occurs in the anterior-superior quaderant of the third ventricle and causes selective acute lateral ventricular hydrocephalus with the referable signs of IC-hypertension, which may rarely lead to sudden death.   

It accounts for about 0.5-10% of all IC-tumors. The middle age is between 2-5 decades.

It is composed of a fibrous epithelial-lined wall and contains either mucoid or hyloidsubstance. According to recent evidence, it arises probably from roof of the third ventricle or maybe from diencephalic recess of postvelar arch. It commonly occurs in the third ventricle, but sometimes elsewhere, e.g. septum pellucidum.

The symptomatic cysts are usually between1 and 2 cm in diameter and lead to intermittent obstruction of the foramen of Monro. Symptoms are usually based on the increase of ICP, with headache, vomiting, and sometimes traid signs of hydrocephalus with gait disturbance, incontinance, seizure, and sudden death.

Sudden death can occur due to the acute blockage of CSF flow resulting from herniation. Another proposed mechanism is the failure of hypothalamic mediated cardiovascular reflex control.   

Therapy of Intraventricular Tumors

A General Consideration

Therapy strategy of intraventricular tumors depends on the location and histopathological features of tumors. This can be classic surgery, endoscopic procedure, radiation and chemotherapy.  

*Surgical intervention of intraventricular tumors is very important, because of vital neurovascular structures inside and also at surrounding of the ventricles.

Surgical procedure may damage these structures. Therefore, a better understanding of the vascular anatomy may contribute to a successful surgery of the ventricular system.

The main blood input to the lateral ventricles is supplied by the anterior, lateral, posterior and medial posterior of choroidal arteries. Anterior choroidal artery arises from the ICA before its biforcation into the middle and anterior cerebral arteris. It supplies the choroid plexus of the atrium, temporal horn and also several neural structures surrounding the ventricle.

Lateral posterior choroidal artery arises from posterior cerberal artery and supplies also atrium, temporal horn and body of lateral ventricle.

Medial posterior choroidal artery arises also from posterior cerebral artery and supplies the choroid plexus in the roof of third ventricle and also all important neurostructure of diancephalon. Besides, there are some branches from pericallosal arteries and circle of Willis, which run to the floor of third ventricle.

The choroidal arteries are the main blood supplier to the lateral and third ventricle lesions. In the case of tumoral involving of intraventricular structures, these vessels are usually dilataded.

Venous drainage system of the venrtricles is also important to be preserved during surgery. These are anterior septal veins, which runs along the medial border of the foramen of Monro, and anterior caudate vein, which runs over the head of the caudate and commonly joins the thalamostriate vein at the posterior border of the formanen of Monro. These drain thalamus and the caudate nucleus and terminate in the internal cerebral vein. Inferior ventricular vein, transverse hypocampal, and amigdalar veins run in the roof of temporal horn, and along the hypocampal formation and drain into the basal vein.

The internal cerebral and basal veins join together and form the great vein of Galen. This deep vein system is very important to be preserved during surgical intervention. In particular, ligation or occlusion of the great vein of Galen should be absolutely avoided. Nevertheless a gradual occlusion of the vein of Galen with developing of the potencial collateral can be tolerated. See Micro- surgical anatomy on basic science!   

* Endoscopic procedure is an established modality for diagnosis and therapy of ventricular lesions, particularly in patients with colloid and cysticercal cysts. Nevertheless total resection of tumors in many cases, particularly in eloquent areas such as brainstem and deep location is almost not always possible, without potential postoperative morbidities.

* Radiosurgery may be sufficient in such cases in infants and adult patients, particularly in low grade tumors. Nevertheless a second operation is usually necessary in the case of residual tumors.

Radiation therapy is useful for eliminating the residual tumor in adults, whereas the chemotherapy may be needed for treating the non-operable tumors in infants and children.

A total or near total resection of tumor followed by craniospinal radiotherapy has been reported as the gold standard procedure. The maximum recommended dose to the tumor bed is 45 Gy in children.

Another report of fractionated therapy advocates 1.8 to 2.0 Gy per treatment given postoperatively once a day for a maximum total dose of about 70 Gy in adults. This may prevent the recurrance of residual tumors in subtotal resected tumors.

Lymphomas

Primary CNS Lymphoma (PCNSL)

CNS lymphoma is a malignant neoplasm and may arise from lamphocytes located perivascular in brain parenchyma such as (perivascular sarcoma). There is another intravascular type (angiotropic lymphoma), which may cause vascular occlusion of the small intraparenchymal vessels, which may lead to limited cerebral infractions. There are several terms used for CNS lymphomas such as reticulum cell sarcoma, malignant reticlusis, and microgliomatosis. The brain can be involved by primary or by secondary lymphomas.  

Primary lymphoma is a rare neoplasm of CNS and accounts for about 1% of intracranial tumors, but this has increased due to acquired immunodeficiency syndrome (AIDS) in recent years. The sixth decade is the most favored age for harboring of lymphma, but median age is fourth decade with a tendency to male rather than female. It is rare in children.

The tumor may appear solitary in 52% or as diffuse mutifocal lesions in 12% of cases. It occurs predominantly parenchymal, leptomeningeal, but also in spinal cord and in ocular structures. The most favored sites are frontal in 26%, temporal in 15% and parital lobe in 14%, and also cerebellum in 12%.

There are some risk factors playing a causative role in the developing of Primary lymphoma such as AIDS, Epstein-Barr-virus (RNA) and maybe predisposition to some cancers as second malignancy.  

PCNSLs are composed of neoplastic lymphocytes, which invade the brain parenchyma with tendency to angiocentric perivascular infiltra-tion of small blood vessels. An infiltration of T lymphocytes and also astrocytic reaction can be presented at the tumor’s margins.

The tumor’s cell structure (monoclonal B-cell) is similar to non-Hodgkin’s lymphoma, but it is never seen in CNS .

The most common symptoms are headache, vomiting, based on increasing of ICP, and also seizure and mental change depending on the location of tumor. In the case of ocular location, impairment of visual acuty will be the first sign. Approximately 80% of patients with ocular involvement may develop cerebral lymphoma and 25% of primary cerebral lymphoma may involve the ocular structures.

Secondary Lymphoma of CNS (metastatic lymphoma)

Involvement of brain paranchyma by systemic lymphoma is rare. The most common site of brain is leptomeningeal space by diffuse large cell, high grade lymphoma.

It occurs in about 10% of cases and mostly in advanced stage or in relapsing disease. Most common sites of systemic lymphoma are bone and bone marrow, testis, orbit, or paranasal sinuses.

These are mostly the signs of relapses and last stage of disease such as weight loss, sweats, fever and craniospinal neuropathies, particularly increasing the ICP with headache and vomiting. 

Meningeal Tumors

I-Supratentorial Meningiomas

II-Infratentorial Meningiomas

General Consideration of Meningiomas

They are a wide range of tumors including the benign and malignant neoplasms arising from meninges. These may originate from meningothelial cells or non-memingethelial cells, such as mesenchymal tumors. The malignacy grades are also very various and range from grade 0 to grade 3 according to the WHO 2012.

The first recognition of meningiomas was at the beginning of the 17th century. Its first operation was during 1743 and 1896 with high incidence of mortality.

The first used terminology of “meningothelioma” and later meningioma was 1922 and 1938 by Harvey Cushing.

There is different data in literature regarding the population involved at the hospital or in society at large. It may also increase with age and has a propensity for female with a ratio of about 2:1. Meningiomas account for about 1%-4% of children with average age of 11.6 years.

A large series reported by Mayo Clinic from 1935 through 1977 revealed intracranial meningiomas excluding the postmortem data in 21% of cases, and including postmortem data in 40% of cases. There are several studies from Ex-DDR and USA with the same results.    

 

Supratentorial Meningiomas

Parasagittal and falcine meningiomas

These require particular care on sagittal sinus, in the case of its involvement. Generally there are three options for choosing the appropriate strategy of handling the involved sinus.

– The first is the ligation of not occluded sinus, which can be performed only in the anterior third.

– Resection of involved portion of sinus and repair it again.

– Leave invaded part of tumor attached to the sinus, which most likely will grow and cause slow occlusion with developing of collateral venous system. This allows later easy resection.

 

Decisions about the above strategies will be individual and based on several factors such as location of tumor, symptoms and age of the patients, particularly the cortical venous collateral system.

Falcine meningiomas can be divided into anterior, middle, and posterior parts depending on their origin from the falx.

* Yasargil classified falcine meningiomas as inner and outer types. Inner type arises from conjunction with the inferior sagittal sinus and outer type arises from the main body of falx in frontal, parietal, or occipital region.

management strategies of involved sagittal sinus by mass lesions are:

  • The first act is the ligation of not occluded sinus which can be performed in the anterior third of it.
  • Resection of involved portion of sinus and repair it again.
  • Leave invaded part of lesion attached to the sinus which most likely will grow and cause slow occlusion with developing of collateral venous system. That allows later an easy resection of the involved part.

Convexity meningiomas

They account for about 15% of different types of meningiomas. Generally, they don’t invade the dura of the venous system. The surgical techniques for removal of convexity meningiomas are shown in belove table.

 

Tentorial Meningiomas

Surgical intervention and its approaches for resecting the tentorial meningiomas are really wide and very complicated based on the different locations of tumors. Besides, relationship of the tumors to different vital structures such as vascular features, cranial nerves, temporal lobe, and also brainstem makes the total removal of these tumors more critical.

There are several approaches depending on the specific location of tumors such as subtemporal, petrosal approach, zygomatic extended middle fossa approach, and supracerebellar and supra- inferatentorial approach. 

Intraventricular Meningiomas (trigonal meningiomas)

About 90% of intraventricular meningiomas are located in the trigone of the lateral ventricle.

The feeding arteries are anterior and posterior choroida arteries depending on the size of tumors.

There are also several approaches through the middle temporal lobe, posterior paramedian parietal cortex, temporoparietal and also through the corpus callosum (see intraventricular tumors).

Meningeal Sarcomas    

They are also mesenchymal neoplasms, arising from mesenchymal tissue with heterogeneous microscopic appearance. There are several types of meningeal sarcomas based on their pattern of differentiation rather than their cell origin.

Sarcomas may occur extra and intracranial at any site in the brain. They account for about 0.1% to 3% of all IC-tumors at any age of life. About 63% of tumors that arise from dura and pia- arachnoida have direct contact to dura.

Fibrosarcoma

It is the most common intracranial sarcoma, particularly in adults.These usually develop as primary IC-sarcomas or as a component of gliosarcoma after radiotherapy, particularly in the sella region. These arise from dura and may extend along the Virshow-Robin spaces. It is not easy to distinguish between a fibrosarcoma and sarcomatous degenerated meningioma. Besides, the tumors with similar components occur elsewhere, thus careful screening for primary site of tumors is recommended.      

Rhabdomyo-sarcoma

These malignant tumors mostly occur in children, and often in the posterior fossa. They are composed of rhabdomyoblasts and arise from the leptomeninges in the brain parenchyma. It is difficult to differentiate these from the medullomyoblastoma.

Mesenchymal Chondrosarcoma

It may occur in cerebrospinal in children, and usually attached to the dura. It tends to recur locally and gives distance metastasis.There are some more types of sarcomas and some of them have been described in other chapters (see on chapters of skull and skull base tumors).

The most common neurological symptoms are based on mass effect and increase the ICP, or hydrocephalus. These are headache, mental status changes, seizure and weakness.

 

The Most Common Primary Midline Tumors

Tumors of Pineal Region

Most tumors of pineal region have an infratentorial origin with extension into the third ventricle, thalamus and quadrigeminal plate; but also into supratentorial area.

 Histopathologic classification

An overview about the location of pineal gland and surrounding structures may contribute to a better understanding of the histopathology of neoplasms originating from this region. Pineal gland is an entcapsulated and extra-axial structure in center of brain. It is surrounded by Corpus Callusum superiorly, and posterior commissure ventrally and commissure habenular dorsally. Feeding arteries are branches of lateral and medial choroidal arteries, which resulted from an anastomosis of posterior cerebral- superior cerebellar- and quaderigeminal arteries. Besides, pineal parenchyma pinealocytes are surrounded by astrocytes, endothelial cells, ependymal cells of third ventricle and sympathetic nervous system.

 

Pineal Tumors

The first desription of pineal tumors was in 1717, but the first successful surgery of these tumors was in 1913 by Oppenheim and Krause. The first infratentorial approach was used in 1926 by Krause.

Histological Classification of Pineal Tumors:
– Pineocytomas (WHO grade II):

is a well-defined slow-growing tumor and is composed of uniform cells arranged in lobules (Pineocytomatous rosettes), but there is another type with high cellularity and nuclear atypia called pineal parenchymal tumors, which should be treated aggress-ively.   

Pineoblastoma (WHO grade IV):

This is a malignant neuroectodermal tumor with a tendency to metastasize through the CSF. This usually occurs in children.

There are 3 main causes presenting the symptoms:

  • Endocrine dysfunction
  • Obstractive hydrocephalus and increasing the ICP
  • Direct brainstem compression

According to the above causes, there are different symptoms present such as diabetes insipidus, precocious pseudopuberty, headache, nausea, vomiting, gait disturbance, ataxia, sylvian aqueduct syndrome, Parinaud’s syndrome and collierie sign.

Germ Cell Tumors

Germinomas usually involve the midline structure, likely pineal region, but also occur in supracellar area, basal ganglia and thalamus. These are composed of two types of cell populations:

– Large malignant germ cells

– Small reactive chronic inflammatory cells (composed of lymphocytes and plasma cells).

Germinomas are highly radiosensitive and treatment may be radiotherapy or combination with chemotherapy.

 the different types of germ cell tumors are:

  • Germ Cell Tumors:
  • Germinoma
  • Embryonal carcinoma
  • Yolk sac tumor (endodermal sinus tumor)
  • Choriocarcinoma
  • Teratoma
  • Mixed germ cell tumors

Primitive Neuroectodermal Tumors (PNET)

Supratentorial primitive Neuroectodermal Tumors (WHO Grade IV)

These are highly malignant and rare tumors usually occurring in the pineal gland and retina.

These are classified as cerebral neuroblastoma, pinaoblastoma, and retinoblastoma.    

Another very rare type is the atypical teratoid/ rhabdoid tumor (ATRT), which occurs 25% in supratentorial and 75% inferatentorial.

– Medulloepithelioma (WHO Grade IV): occurs in children and arises from brain parenchyma, periventricular or infratentorially. There are cases reported in the cauda equine.

Most common infratentorial primitive neuroectodermal tumors are medulloblastomas (PNET; WHO Grade IV). Most favored location is pineal region, but they also occur in supratentorial and posterior fossa, particularly in cerebellum.

– Medulloblastomas usually occur in vermis in children, but the desmoplastic medulloblastoma arises in cerebellar hemisphere in adults and has more favorable prognosis than the classic form. 

Most primary Infratentorial Tumors

Infratentorial Meningiomas   

Posterior Fossa Meningioma

CPA Meningiomas

The standard approach is retrosigmoid, which provides a better exposure to the tumors and surrounding neurovascular structures.

There is a constant relationship of the cranial nerves such as IV, V, VI, VII, VIII and lower cranial nerves to the meningiomas. Besides, the SCA, AICA and PICA are also close to the tumors, which should be dissected from the tumor’s capsule without damaging them. In the case of invasion of tumors into brainstem the capsule should be opened and tumor centrally debulked and devascularized.     

Petroclival Meningiomas

Thes are characterized by involving the superior 2/3 of the clivus with tumor bulk along the spheno-occipital synchondrosis. They usually involve infra- and supratentorial components.

The best microsurgical approach for resecting the petroclival tumor is the lateral skull base approach. This provides a connection between the middle and posterior fossa by drilling the petrous ridge and splitting the tentorium. Besides, it may avoid the risk of brain retraction and injuring of venous system, particularly vein of Labbe.

There are several lateral approaches demonstrated in below table such as posterior and anterior petrosal approach, middle fossa approach and combination of them.

Foramen Jugular Meningiomas

These basal posterior fossa primary meningiomas are extremley rare with few cases reported in literature. They usually obstruct the jugular bulb and compress lower cranial nerves and extend into posterior fossa. 

The best approach may be the supra or retrojugular approach maintaining the venous follow through the jugular bulb, or transjugular approach common in glomus tumors.

Foramen Magnum Meningiomas

These are two types regarding to the arising location

 the different types of foramen magnum meningiomas in related to the arising site are:

  • The ventral type arises from the lower part of clivus.
  • The craniovertebral type arises from upper cervical region (CVJ) and divides itself in two subtypes:
  • postero-lateral location to the Spinal cord
  • Dorsal location to the spinal cord.

The postero-lateral and dorsal tumors can be resected through a standard suboccipital approach, thereby the neurovacular structures such as lateral vertebral artery, and posterior located PICA should be preserved.

The ventral located meninigiomas can be resected through the transcondylar approach thereby the lower cranial nerves such as IX and X should be protected. There are several forms such as far lateral, extrem lateral, or posterolateral of the transcondylar approach.

Al-Mefty reported a satisfactory surgical outcome in 18 patients with ventral foramen magnum meningiomas using the transcondylar approach, however the most common complication is the lower cranial nerves IX and X.

Middle and Anterior Fossa Meningiomas

Tuberculum Sellae Meningioma

Tuberculum Sellae Meningiomas arise from sella region and mostly extend into one or two optic canals. These account for about 5% to10% of IC-meningiomas.

The first clinical finding is chiasmal syndrome, optic atrophy and visual symptoms. The late symptoms are frontalisation in about 10% of patients.

The best surgical approach is the supraorbital, which provides minimal brain retraction and protection of neurovascular structures. The optic nerves and feeding arteries arising from anterior circulation, in particular A1 segment are usually displaced and involved by tumors. The main goal of surgery should be careful dissection of the capsule of tumor from neurovascular structures and trying to preserve the arterial supply to the chiasm and optic nerve such as ophtalmic and central retinal arteries.

Diaphragma Sella Meningiomas

These usually arise from retrochiam and hypothalamus region and are classified in three types based on their origin shown in below table.

the different types of diaphragma sellae meningiomas in related to their origin sites are:

The surgical intervention of diafragm sellae meningiomas is more difficult than tuberculum sellae, because of the difficulty of dessecting and preserving the pituitary stalk.

Cavernous Sinus Meningiomas

Thes may arise primarily from the cavernous sinus, or C.S. can be involved by extension from tuberculum sellae, clinoidal, sphenoid wing, or sphenopetroclival meningiomas.      

Preoperative imaging such as MRA, angiography, even xenon-CT are important to dynamic and physiologic study of internal carotid artery and cerebral blood flow.      

The best surgical approach for resecting the tumor is the cranio- orbital- zygomatic approach. Proximal and distal control of ICA during the resection is crucial.

Preserving the important neurovascular components has first priority. These are ICA located between the nerves III, IV and V1 (i.e. Parkinson’s triangle), and also the cranial nerve VI, located laterally to the ICA. 

In a series reported by Al-Mefty and colleagues, the gross resection of tumor was feasible in about 76% of cases. The morbidity and moratality rates were 4.8% to 2.4%.

Optic Nerve Meningiomas

The optic nerve and orbit may be involved primarily or secondarily through the tuberculum sellae, anterior clinoidal or other surrounding meningiomas. In the case of secondary tumor spread along the optic nerve sheath, it is sometimes impossible to distinguish the origin of the tumor.

There are also multiple ectopic meningiomas of the orbit, reported in literature. The main symptoms of orbital meningioma are painless visual loss, and proptosis.

Surgical intervention for orbital meningioma is advocated in the case of involving the orbital apex or intraorbital structures. The pure optic sheath meningioma is sensitive to radiotherapy and this method is advocated in literature.

Olfactory groove Meningioas                 

These are the clear-cut type of the SB tumors with special consideration regarding the different location, surgical approach and post-operative outcome in contrast to the central skull base tumors (CSB). It is an anterior cranial base meningioma occasionally involving and destructing the skull base. The exact anatomy of basal bone structure regarding the hyperostosis or bone destruction, location of olfactory nerves and also drainage veins from frontal lobes should be studied before surgical procedure.

These will be depended upon tumor size, laterality and involvement of skull base such as right or left anosomie, visual disturbance, or frontal syndrome.

Meningeal Haemangiopericytomas

This is a malignant rare meningeal neoplasm, and probably arises from meningeal capillary pericytes with angioplastic tendency and sarcoma-like behavior.  

Its important to distinguish the hemangiopericytic meningiomas (meningothelial origin) from the hemangiopricytomas (non-meningothelial origin), which is a mesenchymal tumor. WHO has currently distinguished the Meneingeal hemangiopericytoma from meningiomas tumor.

The first term of angioblastic meningioma was used by Cushing in 1938, which was proposed in 1954 by Begg and Garrent to be a meningeal hemangiocytoma. 

It is a very rare neoplasm, and accounts for about 2% to 4% of group meningiomas. 10% of tumors occur in children. There are about 300 cases reported in literature. This may be more common than reported cases, because of misdiagnosis with meningiomas.

The tumors are very cellular with varied structural form spreading around the thin-walled vascular spaces (staghorn). The reticulin individual cells and subpopulations of cells, and also biological behavior are differential ceretarias between these neoplasms and atypical or malignant meningiomas.

These will depend on the tumor location and are usually headache, seizure and focal neurological signs.

Tumors of Posterior Fossa

Medulloblastoma

This is an embryonal small cell tumor belonging to the group of PNET, which occurs almost always in midline cerebellum in children.

First introduction of the term medulloblastoma cerebelli was in 1925 by Cushing and Bailey, but the definitive description and classification of tumor as PNET was in 1983 by Rorke, Hinton and Becker.

This accounts for about 20% of all CNS tumors in children with an age distribution peak at 3-4 years and 8-9 years. It is rare in adults, about less than 1% of all primary CNS tumors occurring before age 40. Norusi / vonovacus Ffm. 1986,- report of 38 cases in adults.

The etiology of tumor is unknown, but there is some evidence that viral infection may play a role in development of medulloblastoma such as JC virus. There is also a proposal of genetic role as a basis for medulloblastoma. It has been postulated that the tumor suppressor gene in 17p 13.3 may play a role in the tumorigenesis. The original cell of medulloblastoma is still not clear, but there are two hypotheses such as primitive multipotential cell in medullary velum, or in subependymal region may be as a basic cell for all PNETs, including the medulloblastomas.

Classic medulloblastoma is a poorly demarcated soft mass tumor, composed of the small basophilic round cells. It usually arises from medullary velum location of cerebellar hemispheres and is rare in children, but common in adults. Brainstem invasion of tumor is seen in about 15%-36% of cases.

There is an another variant of medulloblastoma, called desmoplastic medulloblastoma, which usually occurs in youths and adults.


CapillaryHaemangioblastomas (Haemangioblastoma)

(CH; WHO grade 1)

CH is a benign tumor and arises from stromal cells amid a capillary vasculature. It is morphologically similar with renal cell carcinoma, which is very often seen in “von Hippel-Lindau” (VHL) disease (DD). It occurs mostly in the posterior fossa, and supratentorial cerebral location is rare, but it has been reported in literature.

Hemangioblastomas account for about 2% of all IC tumors, 10% of all posterior fossa, and 2%-3% of all intramedullary spinal cord tumors. Approximately 25% of hemangioblastomas are associated with VHL disease. Ratio of men to women is about 1.3.

Clear Cell Renal Cell Carcinoma (CCRCC)

This is a kidney lesion mostly accompanied by cysts and may occur sporadically or associated in 25% of cases with VHL disease.

The common symptoms are flank pain, haematuria and abdominal mass founded by examination.

CT and MRI with contrast are the best modalities of screening to detect the kidney lesions. The patients with CNS hemangioblastomas should undergo routinely abdominal radiologic screening.   

The management of CCRCC in patients with VHL is beyond the scope of this chapter.

Pheochromocytoma

It is also a kidney lesion usually associated with VHL disease. The sporadically occurred pheochromocytoma is mostly unilateral, but bilateral lesion is almost always associated with VHL or one of multiple endocrine neoplasm (MEN).

Approximately, 10% of pheochromocytomas are malignant, but that is difficult to distinguish before the appearance of metastasis.

The most common symptoms are episodic headache, tachycardia, tremor and nervousness, due to the excess of catecholamine secretion from the tumor.

The best screening test is to measure the metanephrine vanillylmandelic acid in 24 hour-collected urine, which will be elevated in the case of disease.

The most common clinical test is controlling the BP in standing position, which will be lower than in lying position.

MRI is the best screening test for detecting the disease in patients with VHL and hemangioblastomas. It is strongly advocated to screen for VHL disease in following cases: In patients with CNS hemangioblastoma, patients born into a VHL disease pedigree. Screening tests should include the full CNS MRI with contrast, abdominal CT with contrast, ophtalmic examination and measuring of metanephrine assay.     

Surgical intervention is generally curable and should be performed prior to the CNS lesions. 

Tumors of Middle Fossa (Sella Region)

Trigeminus Schwannomas          

This is a benign tumor and arises from the peripheral nerve sheath and must be distinguished from traumatic neuromas, which is a proliferation of schwann cells and are not a neoplasm, as well as from neuro-fibromas that infiltrates peripheral nerve sheath. The trigeminal schwannomas can occur with other intracranial nerve schwannomas as in neurofibromatosis type II

They are rare tumors, however are the second most frequent intracranial tumor after acoustic neuromas. They present about 0.8 % – 8 % of intracranial tumors and tend to occur in middle age around 40 years and is more common in females.   

Microscopically, schwannomas are composed of antonoi-A (elongated, spindle-shaped cells) and antonoi-B (large vacuolated cells) regions. Schwannomas may arise from ganglion, root, or occasionally divisions of trigeminus nerve. It penetrates the Dura at the petrus trigeminus and superior petrosal sinus of the middle cranial fossa.

The PCA and SCA pass over the root, whereas the AICA passes under it. The nerve terminates extradural in the trigeminal ganglion (Gasserian ganglion), which lies in the groove known as Meckel’s cave. There is a classification based on the location of the schwannomas described for the first time by Jefferson as follows.

 

Pituitary Tumors

The first attempt to approach to the sella region was undertaken by the British general surgeon F.T. Paul in 1892, without success. The first successful extracranial approach to the sella region was performed by Schloffer from Vienna.

In 1909 Cushing used a variation of the Schloffer method, and Halsted used sublabial incision. The endonasal trans-sphenoidal approach was described by Oscar Hirsh in 1910.

Gerard Guiot (1912-1996) popularized the procedure later in France and passed it on to Jules Hardy, who introduced it through the microsurgical technique in North America.    

Guiot and Hardy together established the technical aspect of the microsurgical transsphenoidal procedure in the1960s, which is the basis of currently practised form.

Nowadays there are several technical adjunctions including transphenoidal endoscopy, frameless stereotaxy, but the transphenoidal microsurgery is the preferred approach to the sella region in approximately 95% of cases.

Pituitary tumors are the third most common primary brain tumors after gliomas and meningeomas. These account for approximately 10-19% of all primary brain tumors.  There are autopsy studies that show about 20-25% of general population harbor microadenomas with-out endocrine symptoms. These can be demonstrated in about 10% by routine MRI scans. Pituitary tumors are rare in children and account for about 2%, and the highest incidence peak is between the third and sixth decades of life.  A wide range of abnormalities may occur in sella region, but the pituitary adenoma is clinically and numerically the most common neoplasm affecting the pituitary gland.    

Different Types of Pituitary Adenomas

Prolactinoma

It is the most common type of pituitary adenoma, approximately 30% of all adenomas. There are two biologic profiles of prolactinonams, one microadenoma with well-defined margin and slow growth, second one with progressive growth. Although all PRL-secreting macroadenomas were once microadenomas, however not all microadenomas are destined to become macroadenomas. The risk of progression of a microprolactinoma to macroprolactinoma is about 3%-7%.

These are related to the mass effect and the endocrinologic consequences of hyperprolactinemia. Amenorrhea-galactorrhea syndrome is the well-known clinical symptom. Galactorrhea is variably present in about 30-80% of female patients, and 30% of male (it requires vigorous breast manipulation). The primary consequence of hyperprolactinemia is hypogonadism with libido, impotence and infertility. About 50% of women complain about headache, psycological and vegetative disorders. Osteoporosis occurs in men and women equally.

 

Pituitary Carcinomas

These are very rare neoplasms. According to the study of Pernicone and Co-workers, there were only 52 cases in literature plus 12 cases of theirs. Approximately 75% of the pituitary carcinomas are hormonally active with   production of PRL and ACTH.

Symptoms are caused by hormonal and mass effect of tumors.

The first choice of therapy is surgical resection and postoperative radiotherapy and also medication therapy, however the prognosis for pituitary carcinomas is very poor.

Pituitary Apoplexy

It is an acute sometimes dramatic occurrence of haemorrhagic infarction of a pituitary adenoma.

It occurs in approximately 1% – 2% of all pituitary adenomas, but subclinical form resulted from haemorrhage into pituitary gland after surgical intervention occurs in about 10% of cases. This is associated with necrosis or cystic change, but is not really a classical apoplectic event.

Craniopharyngiomas 

These are benign tumors, which have a tricky relation to the pitiutary stalk, hypothalamus, and chiasma optic. They have a potential morbidity rate through the aggressive surgical intervention damaging the vital structures.

The first description of the neoplasm was in 1857 by Zenker. The first transsphenoidal operation was in 1909 by Halstead. The initial use of the name craniopharyngioma was in 1924 by McKenzie and Sosman.  

Pathogenesis of the craniopharyngeomas is still controversial. Erdheim was the first to describe, in 1904, the origin of craniopharyngiomas based on pathway of craniopharyngeal duct and Rathke’s pouch.

There are two histopathological types:

Papillary squamous type

occurs mostly in adults, about 30% of population, and adamentinomatous craniopharyngioma occurs in 95% of children.

Adamentinomatous type

occurs mostly in the suprasellar space, and is composed of “machine-like” oily fluid and necrotic debris. It mostly adheres to the adjacent structure and vessels, whereas the papillary type is a solid tumor without adherence to the vessels. There are rarely other localisations in the nasopharynx, cerebellopontine angle, and pineal region.

Classification of Craniopharyngioma

There are several classifications based on the location and extension of tumor. The classification of Yasargil and colleagues is the most common classification as follows:

The common classification of craniopharangiomas according to Yasargil & colleagues are”

  • Type a: intrasellar, infradiagfragmatic location.
  • Type b: intra- and suprasellar, infra- and supradiagfragmatic
  • Type c: supradiafragmatic, extraventricular
  • Type d: extra- and intraventricular
  • Type e: intraventricular
  • Type f: extracranial or extradural

Most Common Tumors of Anterior Fossa

Olfactory Groove Meningiomas

Optic Nerve Gliomas

 

Olfactory groove meningiomas (OGMs) are non-cancerous tumors and arise in the midline over the cribriform plate and from frontosphenoidal structures. They may extend predominantly to one side and after reaching large sizes may present further extensions into the ethmoid sinuses reported in 15 % of patients and also in orbit and nasal cavity.

It accounts for about 10 % of intracranial meningiomas. Downward extension of large tumors into the ethmoid sinuses and nasal cavity is estimated in about 10.15 % of cases.

These are the clear-cut type of the SB tumors. The exact anatomy of basal bone structure regarding the hyperostosis or its bone destruction, but also location of olfactory nerve and other neurovascular structure on the anterior fossa should generally be considered for understanding the exact etiopathology of olfactory meningioma.

OGMs may become very large prior to producing symptoms. Common symptoms are headache and visual deficits, anosmia. Change of visual field, but true motor paresis being rare. The Foster Kennedy syndrome of unilateral optic atrophy and contralateral papilledema occurs only in a small group of patients.

Olfactory groove meningiomas often go undetected until they are found incidentally through a MRI study.

T1-weighted MRI demonstrate the OGM as an iso- or slightly hyper-intense and T1+ GD strongly hyper-intense. T2-weighted MRI also present the tumor hyper-intense. MR-Angio will define the relationship of the tumor to the neurovascular structure such as optic nerves/ chiasm as well as to the ACAs and communi-cating complex.

CT-Scans are particularly useful for defining the osseous anatomy such as hyperostosis or erosion of skull bone. Non-contrast CT scans show a homogeneously slightly hyper-dense mass comparing to the brain parenchyma.

DD: They can be differentiated from tuberculum sellae meningiomas because OGMs arise more anterior in the skull base and displace the optic nerve and chiasm more inferiorly superiorly.

 

Optic Nerve Gliomas

Optic nerve gliomas are a type of malignant brain tumor, because the optic nerve and olfactory nerve have been created through an extension process of brain tissue. So they are a part of brain with the same glial cells as brain parenchyma. Optic gliomas are low-grade tumors and are also referred to as juvenile pilocytic astrocytoma. They are found in the optic chiasm, where the optic nerves cross or /and surround. Optic nerves are often surrounded by gliomas. Optic gliomas may be associated with genetic disorder neurofibromatosis Type I, like the bilateral Acousticus Neurinomas associated with type II.

Optic nerve glioma is a rare kind of cancer and found mostly in children and youth under the age of 20. According to the Johns Hopkins Brain Tumor Center, gliomas account for approximately one-third of brain tumors (JHU, 2012), reported by Jaime Herndon.

These are vision disturbances through the tumor’s compression on chiasm, but they may also present other symptoms duo to the hormone problems, since these tumors are usually located at the base of the brain, where hormonal control is located. The common symptoms are nausea and vomiting balance problems, headaches, memory impairment.

 

Secondary Tumors of CNS (Cerebral Metastases)

Brain metastases are the most common intracranial tumors. These may cause serious morbidity and mortality in patients with systemic cancer. It is more common in adults than in children. Most common origins of the brain metastases in adults are lung, breast, skin, renal and colon, and in children are leukemia, followed by lymphoma, osteogenic sarcoma and rhabdomyo-sarcoma.

The first report of far systemic cerebral metastases was in 1898 by Bucholz.

There are several studies in literature without clear statistical data, because of some factors, which play a significant role in the epidemiology of metastases, such as histologic type of primary tumors, and age of the patients. The highest peak of age in patients with metastases is in the fifth to seventh decades.

Primary lung tumors account for about 30% to 60% of all intracranial spreads, followed by breast about 10% to 30%.

Incidence of cerebral metastases in patients with malignant melanoma accounts for about 6% to 43% in different clinical series and 12% to 90% in autopsy series.  This wide range shows the uncertainties in the estimates. 

Most common signs are based on the increased ICP such as headache, vomiting, seizure, cranial nerves palsies and also neurological deficits. The status of systemic disease and extent of primary tumor and also the neurological deficits have a strong influence on outcome and postoperative survival.

Cranio-Vertebral Tumors

In this and the next chapter we will discuss the lesions of the craniovertebral junction, vertebral axis, and the spinal cord based on anatomical classifiaction as follows:

  1. I) Extradural Neoplasms
  2. II) Intradural Extramedullary Neoplasms
  3. III) Intramedullary Neoplasms

Extradural Tumors of CVJ

CVJ comprises biomechnically and anatomically the follow-ing different components: clivus bone, foramen magnum, occipitoatlantic joint, and two upper cervical vertrebrae (atlas and dens).

The extradural space of CVJ and vertebral axis may be involved by different neoplasms, those with boney origin, those associated with bone, or those resulting from extension of the surrounding soft tissues into the region, and also metastasis resulting from distant neoplasms.

The main symptoms of all extracranial tumors with extension into the spinal canal, or reverse may have characteristics of compression of surrounding structures, and chronic neck pain. In some reports interval time between the onset of symptoms and the diagnosis of extramedulary tumors was 2.5 years.

Tumors with intracranial location may present lower cranial nerve deficits, brainstem compression and may be hydrocephalus. Patients with straddle lesions show often lower cranial nerves dysfunction and high cervical mylopathy. High cervical lesions demonstrate mostly neck pain and eventually torticollis. A suspected loss of sensory or spastic paresis of the extremities can be a strong sign of tumors in this region.

The tumors at the foramen magnum may show a mixed pattern and signs of upper and lower extremities due to the pyramidal decussation, which begins below the obex and ends near the upper cervical spinal cord. Transient symptoms may present the vascular changes or instability at the craniovertebral junction in the form of paresthesia, paralysis and drop attacks.


Osteogenic Tumors (Osseous Tumors)

True Bone Tumors

These may be derived from cells of bone such as osteogenic and osteoclastic tumors, or from cartilagenic and fibroblastic elements such as chondromas and fibromas. These are as follows

Osteoid Osteomas

It is a benign bone tumor occurring commonly in the spine 10% to 25% of all osteomas. About 59% of them occur in lumbar, followed by cervical 27%, thorasic 12% and 2% in the sacral region. It has a propensity to involve the pedicles, laminae, as well as the spinous processes.

There are 3 types of osteomas: Classic form (compact), fibrous, and cancellous form. They are usually characterized by a very vascular fibrous tissue, with surrounding osteoid. It usually is a small painful mass less than 1.5 cm and mostly occurs in young people. 

Osteoid osteomas may cause an inflammatory reaction in the surrounding tissues due to the production of prostaglandin, which may lead to a sclerosis of bone. 

Local nocturnal pain and also radiculopathy is common. A scoliosis resulting from muscle spasms with gibbus away from the lesion in middle column may be presented in 70% of the cases. Cervical osteomas often present neck pain, torticollis and limited motion of neck.


Osteoblastomas (Giant Ostoids – Osteofibromas)

This is a rare highly vascular benign bone tumor and accounts for about 1% of all primary bone tumors. The size of tumor is usually much bigger than osteoma. This occurs usually in multiple sites in the posterior structures and also in vertebral body. It tends to extend into the spinal canal and paravertebral space.

Clinical findings are the same as in osteoma. Appearance on plain X-ray and CT-scans is also the same as by osteoma only larger than osteoma and lytic. MRI may demonstrate the attachment of tumor to the dura in the case of tumor extension. But the peritumoral sclerotic reaction is less than in osteoid steoma. The isotope bone scans may show the tumor like osteoma well localized. 

The total removal of tumor should be the main goal, because it is not radiosensitive like osteoma. There is evidence of recurrence after years.

Osteoclastoma (Giant Cell Tumor)

It is a rare malignant bony vascular tumor and occurs frequently in sacral region. It involves mostly vertebral body and is characterized by hypervascularity.

There are 3 malignacy grades of tumor.

 About 5% of the tumors occur in non-sacral spine.

The radicular pain is the most common presenting symptom. 

Plain X-ray shows a non-specific lytic lesion. CT scans demonstrate a “Soap bubble” vertebral expansion. MRI shows the soft tissue and fat-containing marrow. It is not to be distinguished from a giant cell granuloma. In the case of unilocular mass a needle biopsy is indicated.

Total surgical resection is the best procedure, if possible. Otherwise the radiation therapy can be useful in the case of incomplete removing or recurrence of tumor. Recurence rate is about 40% in case of subtotal resection. Radiotherapy alone is unfortunately not effective. Follow-up of patients is an essential issue, because of local recurrence and distant lung metastasis.  

 

Osteochondromas    

It is the most common benign skeletal neoplasm arising from the endochondral ossification of the aberrant cartilage of an epiphyseal plate of long bone, but also at the skull base and may also arise intracranial from the choroids plexus, the dura or the arachnoid.

It accounts for about 0.5% of intracranial tumors. Approximately, 3% of solitary and 7% of multiple osteochondromas occur within the spine. There are only 117 cases of spinal osteochondromas reported in literature between 1843 and 1977. This tends to involve spinous process, rarely vertebral body and occurs more in the cervical or upper thoracic spine. The Peak incidence is in the third decade in males more than females.

 

Chondrosarcoma

It is a malignant tumor arising from cartilage with hyalin-secretion. It may involve spine primarily or secondarily. Approximately 7% of them occur in spine. Most of them occur at the lateral side of thoracal close to costotransverse junction.

Radicular pain, epidural compression and finally palpable mass.

X-ray shows lytic lesion with calcification. CT and MRI are the best for studying the bony and soft tissue structures. MRI shows a heterogenous structure, because of the combination of cartilage, soft tissue, and calcification.

 

Osteosarcoma

It is one of the most common malignant bone tumors, which involves the spine likely secondarily. Primary tumor accounts for about 4% of cases.

There are 3 types such as osteoplastic, fibroplastic, and chondroplastic.

These range from radiculopathy to paraplegia. Paget’s disease and osteochondroma can be predisposing factors in elderly patients.

 

Vascular Tumors

Haemangiomas

Spinal hemangioma is a benign usually asymtomatic vascular lesion. Lesions that are symtomatic mostly occur in the thoracic region with radiculo- or myelopathy.

They are mostly solitary in 66% and multiple in 34%.

These are redicular pain in the case of impingement on a nerve root, or vertebral fracture causing thecal sac compression resulting in myelopathy.

Aneurysmal Bone Cyst

It is a rare benign destructive bony lesion of unknown origin with large vascular elements, separated by bony trabeculae and fibrous tissue. Although the ABC is a controversial subject that is probably neither neoplasm, nor aneurysm nor cyst.

It accounts for approximately 1.4% to 2.3% of all primary bone neoplasms. 12% of them occur in the spine mostly in children with a predilection for female. In 60% of cases, the posterior elements and in 40% the vertebral arch is involved.  

Trauma has been reported as a risk factor. It is composed of thin-walled bone divided by bone septae, without endothelium, although it seems to be as blood-filled cavities. The solid portion of the tumor consists of osteoid structure intermixed with fibrous tissue. Approximately, 32% of lesions may be associated with fibrous dysplasia, giant cells tumor (osteoclastic).

DD: Is possible by Needle biopsy!

Pain, particularly low back pain is the most common sign, but radicular pain resulting from encroachment of tumors into the neural foramin and long-tract signs caused by thecal sac compression may be present.


Angiolipoma

It is a very rare benign tumor mostly extradural lipoma with strong vascular components and eventually compression sign on dural sac. But it may extend outside of canal. There are only 60 cases reported in literature. There are two types, more common infiltrating and rare non-infiltrating lesions.

Plain X-ray shows trabeculation and bony erosion in infiltrating type. CT and MRI demonstrate a fat density in about 70% of tumors and soft tissue density in 30% of them.

 

Malignant Tumors of CVJ & Vertebral Axis

Notochord Tumors (Chordoma)

This is a most common aggressive extradural tumor in this region with notochordal origin and locally destructive character.

It accounts for about 0.15% of all IC-tumors. About 25% of chordomas occur at the SB arise from clivus. They usually occur in adults, but 5% in children. Age peak is the fourth decade of life. They have a predilection for the spheno-occipital region.

There are three different types of chordomas shown in below table.

  • Classic Chordomas
  • Atypical Chordomas
  • Chondroid Chordomas (Chondrosarcomas)

 

Approximately,80% to 85% of all chordomas are classic type. Atypical chordomas account for 1.3% to 8% of all chordomas and occur mostly in sacral region as a solid aggressive lesion with necrotic area. Chondroid chordomas account for about 5% to 15% of all chordomas. Some authors dispute the existence of this lesion and consider it as chondrosarcoma, because of the cartilage components in tumor.

These are occipitovertebral headache, which aggravates by changing the craniovertebral position, lower cranial nerve deficites and eventually brainstem signs.   


Tumors with marrow origin

Solitary Plasmocytoma

This is a primary malignant tumor arising from plasma cells and accounts for about 3% of all plasma cell tumors. It usually is a solitary lesion, but sometimes consists of two lesions.

25% to 50% of them occur in spine and thoracic region is the most favored location. It may involve anterior and posterior components.

Local pain, radiculopathy and myelopathay caused by compression are the most common symptoms.

 

Intradural extramedullary Tumors of CVJ

The most common neoplasms of intra-dural extra-medullary tumors of CVJ are usually occurred at the foramen magnum or arising from upper cervical canal of the C1 and C2 vertebrae. They are schwannomas, neuro-fibromas, which have the same clinical and diagnostical character.

Surgery is the best therapy of choice and surgical approach will be based on two behavior factors of the tumors: Caudal extension of tumors at the foramen magnum into the upper cervical canal; in reverse order cranial extension of the upper cervical tumors into the foramen magnum.

The most common intra-dural extra-medullary tumors of CVJ

  • Meningiomas
  • Schwannomas (Neurinomas)
  • Neurofibromas
  • Neurentric Cysts

 

Surgery is the best modality of choice.

Tumors of CVJ usually occur at the forman magnum or arising from upper cervical canal of the C1 and C2 vertebrae. These are schwannomas and neurofibromas which have the same clinical and diagnostical character.

This based on two factors:

– Caudal extension of tumors to foramen magnum into the upper cervical canal

– In reverse order cranial extension of upper cevical tumors into the foramen magnum.

 

Meningiomas (Foramen Magnum Meningiomas)

Approximately 2% to 3% of all meningiomas occur at the foramen magnum. It has a propensity to the female sex about 66% to 73%, but also occasionally occurs in children.    

These are mostly increasing of ICP, brainstem and cerebellar signs, and also lower cranial nerve palsies. 

Plain X-ray shows the erosion of bone at the foramen magnum, and widening of interpedencular space at the upper cervical vertebrae. MRI demonstrates soft neurovascular structures of brainstem. T1-weighted images show the tumors isointense, and T2-images iso- to hypointense. There is an intensive enhancement after gadolinium. MRA and MRV can be useful as an alternative method to the general angiography demonstrating vascular structures, in particular evaluating the venosal and sinusal structures.

 

 

Spinal Tumors 

These are either intradural extramedullary or intramedullary tumors. But there are rarely tumors with extramedullary and intramedullary connected component. They are communicating through the nerve root entry zone, or the conus medullaris-filum terminale. The same like extra- and intradural communication of some neoplasms through the nerve root sleeve. Approximately 15% of all CNS neoplasms are spinal tumors.

Intradural Extramedullary Tumors of Spinal Collumn

They account for about 2/3 of all spinal cord tumors. Most common of the extrinsic lesions to the spinal cord are meningiomas, nerve sheath tumors, filum terminal ependymomas, but also rarely metastases mass and paragangliomas. These are usually benign tumors and curable by total surgical resection. However there are some exceptions of aggressive behavior of the tumors.

 

Meningiomas

They are usually neoplasms with arachnoid cap cell origin and may also arise from pia or dural fibroblasts with mesoderaml origin.

These occur in any age, but the peak of age is fifth to seventh decades of life dominantly in females. They account for about 25% of all intradural spinal cord tumors. The favored site is the thoracic region, followed by upper cervical spine and foramen magnum. Lumbal meningioma is very rare. Spinal meningiomas are mostly intradural, but only about 10% are entirely extradural or both extra and intradural.

They are variable such as dural attachment and calcification already described in former chapters. The spinal meningiomas usually present the symptoms of spinal cord compression, which may lead to earlier operation, so that there is no penetration in the pia, unlike the intracranial meningiomas.

These are usually suboccipital pain, parasis, atrophy and clumsiness of the distal arm and hand muscles. In the case of hydrocephalus it may lead to increased ICP.    

 

Nerve Sheath Neoplasms

There are two categorized types of (NSN) such as Schwannomas and Neurofibromas. There is some evidence of tissue culture and immunohistochemistry supporting a common schwann cell origin for both types. On the other hand, they merit consideration as separately based on their histologic, demographic and biologic behaviors.  

Schwannoma’s histologic appearance is either in the form of most common Antonio-A, with elongated bipolar cells, or less common Antonio-B with stellate-shaped cells. Neurofibroma’s histologic appearance comprised of fibrous tissue and nerve fibers within the tumor stroma. Neurofibromatosis (NF) consists of the NF1 and NF2 which are associated with nerve sheath tumors. Neurofibromas are more common in NF1, whereas schwannomas in NF2, however schannomatosis may occur in patients without presence of NF.

This is the equal frequency like in meningiomas and accounts for about 25% of all intradural spinal cord tumors. The peak incidence of occurrence is the fourth through sixth decades. Most of the tumors arise from dorsal root and are entirely intradural, but about 30% of them may extend through the dural root sleeve into the extradural space and build a dumbbell shape of tumors. Approximately, 1% of tumors are intramedullary, arising from perivascular nerve sheaths. About 2.5% of the intradural tumors are malignant and have very poor prognosis.

These are variable and based on location of tumors and may present segmental motor weakness and sensory disturbances. Asymmetrical signs, long-tract signs, and also Brown Sequard syndrom are most common. Sometimes there is a subarachnoid haemorrhage.  

 

Nerve Sheath Neoplasms

There are two categorized types of (NSN) such as Schwannomas and Neurofibromas. There is some evidence of tissue culture and immunohistochemistry supporting a common schwann cell origin for both types. On the other hand, they merit consideration as separately based on their histologic, demographic and biologic behaviors.  

Schwannoma’s histologic appearance is either in the form of most common Antonio-A, with elongated bipolar cells, or less common Antonio-B with stellate-shaped cells. Neurofibroma’s histologic appearance comprised of fibrous tissue and nerve fibers within the tumor stroma. Neurofibromatosis (NF) consists of the NF1 and NF2 which are associated with nerve sheath tumors. Neurofibromas are more common in NF1, whereas schwannomas in NF2, however schannomatosis may occur in patients without presence of NF.

This is the equal frequency like in meningiomas and accounts for about 25% of all intradural spinal cord tumors. The peak incidence of occurrence is the fourth through sixth decades. Most of the tumors arise from dorsal root and are entirely intradural, but about 30% of them may extend through the dural root sleeve into the extradural space and build a dumbbell shape of tumors. Approximately, 1% of tumors are intramedullary, arising from perivascular nerve sheaths. About 2.5% of the intradural tumors are malignant and have very poor prognosis.

These are variable and based on location of tumors and may present segmental motor weakness and sensory disturbances. Asymmetrical signs, long-tract signs, and also Brown Sequard syndrom are most common. Sometimes there is a subarachnoid haemorrhage.  

 

Intramedullary Tumors of Spinal Cord

Spinal cord can be involved by a variety of pathologic processes as primary or secondary lesions. The most common neoplasms are glial tumors situated in about 80% of intramedullary tumors. Most common of them are ependymomas, astrocytomas, hemangioblastomas and miscellaneous processes, but also non-neoplastic processes such as bacterial abscess. The most common sites of intramedullary metastasis are lung and breast.

Ependymomas

There are varieties of histologic subtypes, but the cellular ependymoma is the most common type. Almost all types are benign tumors.

About 45% of all intramedullary glial tumors are ependymomas. This is the most common intramedullary tumor in adults. They occur throughout life, particularly in middle age. Male and female are equally affected. About 65% of them are associated with syrinxes, particularly in cervical location of tumors. Besides, there is an association with NF2.

Haemangioblastomas

This is a benign vascular tumor mostly located dorsal or dorsolateral of spinal cord. There is also an association between syrings and hemangioblastomas. About 5% of all intramedullary tumors are hemangioblastomas, and about 15%-25% of them are associated with von Hippel-Lindau’s Disease.

 

Miscellaneous Processes

These are tumoral and non-tumoral lesions. The most common of them are the intramedullary lypomas with 1% of all intramedullary tumors. Metastases are also common as intramedullary lesions and most common sites are lung and breast.

Radiation necrosis may mimic as an intramedullary tumor but the history of radiation therapy can support its diagnosis. Vascular malformations are also lesions that may present intramedullary mass.  

 

Symptoms of Intramedullary Neoplasms

These depend on the locations and histological behavior of tumors. In patients with malignant or metastatic tumors the course of symptoms are much shorter than in benign tumors. This ranges between weeks and a few months, whereas in benign tumors symptoms are present 3 to 4 years before the diagnosis. Generally, local pain and weakness are the most common signs. These are also rarely radicular. The cervical located tumors may cause mostly symptoms of upper extremities. Thoracal tumors cause more spasticity and numbness, which begins distaly in the leg with proximal progression. Tumors of lumbar and conus medullaris may cause back and leg pain, and rarely bowel and bladder disfunction.       

MRI is the best imaging study of choice. The enlargement of spinal cord and contrast enhancement are the typical characteristic findings.

T1-weighted images show most of intramedullary tumors isointense or slightly hypointense, whereas on T2-weighted images the tumors appear mostly hyperintense.

Astrocytomas have a variable appearance on MRI and contrast uptake with irregular margin or patchy. In contrast to astrocytomas ependymomas demonstrate an uniform contrast enhancement exception of intratumoral cysts or necrosis. Besides a patchy contrast enhancement extending over several segments may be a sign of viral or parainfectious myelitis, whereas a ring-enhancement on T1-weighted images with lack of spinal cord enlargement can be a sign of radiation necrosis.

Spinal Metastases

Metastic neoplasms of the spine are an incurable manifestation of systemic cancer. Majority of patients with systemic cancer develop skeletal metastases, particularly spinal metastases.The role of surgery and radiation therapy or a combination of them for treatment of spinal metastase is still controversial.

Spinal metastases are the most common tumors of the vertebral axis. Thorasic region is a favored site.  Approximately, 5% to 10% of all cancer patients develop spinal metastases.The most common sites of primary tumors are lung, breast and prostate, but about 10% of all original primary tumors are unknown. The majority of spinal metastases occur extradurally. These account for about 95% of all secondary spinal tumors that spread through spinal vascular system along Batson’s plexus. Intradurall metastases are not common. These account for about 5% and usually arise as seedlings (drop metastases) from cerebral tumors through CSF. Intramedullary metastases are very rare.

Local neck and back pain and tenderness are the most manifestation in about 90% of patients with spinal metastases. Intradural extramedullary tumors usually demonstrate a burning or dysestetic pain.

Pain caused by spinal metastases may arise from anywhere, but thoracal region is the most common site. The pain tends to be constant and associated with recumbency, in particular at night.

About 30% of all patients with spinal metastases manifest neural compression. Pain, sensory motor deficits and also sphincter disfunction may be occur.


Tthe spine is the most common site of osseous metastatic disease. Imaging modalities have complimentary roles in the evaluation of spinal metastatic disease. CT is the best choice for osseous integrity while MRI is better at assessing soft tissue involvement. These can be evaluated with other imaging modalities such as FDG -PET and advanced MRI sequences. Imaging plays a fundamental role in not only diagnosis but also treatment planning of spinal metastatic disease.

The main goal of surgical management of the spinal metastases is tumor resection and stabilization of spinal column. Refinement of diagnostic modalities and improvement of surgical strategies and techniques such as minimally invasive methods has improved the outlook for patients with spinal metastases.

Therapy options such as irradiation and surgery require a multi-disceplinary team-work of neurosurgeons, radiotherapists and oncologists for applying these options to achieve the optimal results.