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.