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Selected References

Sellar Region Anatomy

Go JL et al: Imaging of the sella and parasellar region. Radiol Clin North Am. 55(1):83-101, 2017

Zamora C et al: Sellar and parasellar imaging. Neurosurgery. 80(1):17-38, 2017

Imaging Technique and Anatomy

Grajo JR et al: Multiple endocrine neoplasia syndromes: a comprehensive imaging review. Radiol Clin North Am. 54(3):44151, 2016

Normal Imaging Variants

Pituitary Hyperplasia

Syro LV et al: Pathology of GH-producing pituitary adenomas and GH cell hyperplasia of the pituitary. Pituitary. 20(1):84-92, 2017

Kocova M et al: Diagnostic approach in children with unusual symptoms of acquired hypothyroidism. When to look for pituitary hyperplasia? J Pediatr Endocrinol Metab. 29(3):297-303, 2016

Empty Sella

Saindane AM et al: Factors determining the clinical significance of an "empty" sella turcica. AJR Am J Roentgenol. 200(5):1125-31, 2013

Congenital Lesions

Pituitary Anomalies

El Sanharawi I et al: High-resolution heavily T2-weighted magnetic resonance imaging for evaluation of the pituitary stalk in children with ectopic neurohypophysis. Pediatr Radiol. 47(5):599-605, 2017

Hypothalamic Hamartoma

Kameyama S et al: MRI-guided stereotactic radiofrequency thermocoagulation for 100 hypothalamic hamartomas. J Neurosurg. 124(5):1503-12, 2016

Rathke Cleft Cyst

Park M et al: Differentiation between cystic pituitary adenomas and Rathke cleft cysts: a diagnostic model using MRI. AJNR Am J Neuroradiol. 36(10):1866-73, 2015

Neoplasms

Pituitary Adenomas

Molitch ME: Diagnosis and treatment of pituitary adenomas: a review. JAMA. 317(5):516-524, 2017

Tamrazi B et al: Apparent diffusion coefficient and pituitary macroadenomas: pre-operative assessment of tumor atypia. Pituitary. 20(2):195-200, 2017

Lilja Y et al: Visual pathway impairment by pituitary adenomas: quantitative diagnostics by diffusion tensor imaging. J Neurosurg. 1-11, 2016

Sav A et al: Invasive, atypical and aggressive pituitary adenomas and carcinomas. Endocrinol Metab Clin North Am. 44(1):99-104, 2015

Pituitary Blastoma

Scheithauer BW et al: Pituitary blastoma: a unique embryonal tumor. Pituitary. 15(3):365-73, 2012

Lymphoma

Deckert et al: Lymphomas. In: Louis DN et al (eds), WHO Classification of Tumours of the Central Nervous System. Lyon, France: International Agency for Research on Cancer, 2016, pp 272-277

Tarabay A et al: Primary pituitary lymphoma: an update of the literature. J Neurooncol. 130(3):383-395, 2016

Germinoma

Rosenblum M et al: Germ cell tumours: germinoma. In: Louis DN et al (eds), WHO Classification of Tumours of the Central Nervous System. Lyon, France: International Agency for Research on Cancer, 2016, pp 286-291

Di Iorgi N et al: Pituitary stalk thickening on MRI: when is the best time to re-scan and how long should we continue re-scanning for? Clin Endocrinol (Oxf). 83(4):449-55, 2015

Craniopharyngioma

Wijnen M et al: Very long-term sequelae of craniopharyngioma. Eur J Endocrinol. 176(6):755-767, 2017

Buslei R et al: Tumours of the sellar region: craniopharyngioma. In: Louis DN et al (eds), WHO Classification of Tumours of the Central Nervous System. Lyon, France: International Agency for Research on Cancer, 2016, pp 324-328

Nonadenomatous Pituitary Tumors

Hagel C et al: Immunoprofiling of glial tumours of the neurohypophysis suggests a common pituicytic origin of neoplastic cells. Pituitary. 20(2):211-217, 2017

Brat D et al: Pituicytoma. In: Louis DN et al (eds), WHO Classification of Tumours of the Central Nervous System. Lyon, France: International Agency for Research on Cancer, 2016, pp 332-333

Fuller G et al: Granular cell tumour of the sellar region. In: Louis DN et al (eds), WHO Classification of Tumours of the Central Nervous System. Lyon, France: International Agency for Research on Cancer, 2016, pp 329-331

Lopes M et al: Spindle cell oncocytoma. In: Louis DN et al (eds), WHO Classification of Tumours of the Central Nervous System. Lyon, France: International Agency for Research on Cancer, 2016, pp 334-335

Miscellaneous Lesions

Hypophysitis

Kyriacou A et al: Lymphocytic hypophysitis: modern day management with limited role for surgery. Pituitary. 20(2):241250, 2017

Langerhans Cell Histiocytosis

Paulus W et al: LCH. In: Louis DN et al (eds), WHO Classification of Tumours of the Central Nervous System. Lyon, France: International Agency for Research on Cancer, 2016, pp 280-281

Neurosarcoid

Anthony J et al: Hypothalamic-pituitary sarcoidosis with vision loss and hypopituitarism: case series and literature review. Pituitary. 19(1):19-29, 2016

Pituitary Apoplexy

Singh TD et al: Management and outcomes of pituitary apoplexy. J Neurosurg. 122(6):1450-7, 2015

Some important neoplasms that affect the calvaria, skull base, and cranial meninges are not included in the most recent standardized WHO classification of CNS tumors. This chapter covers several of these intriguing tumors as well as tumor-like lesions that do not easily fit into other sections of this text. Although infections, granulomatous disease, demyelinating disorders, and vascular diseases (among others) may sometimes mimic CNS neoplasms, they are treated separately in their own respective chapters.

We begin with extracranial tumors and tumor-like conditions. These lesions mostly arise within the calvaria or skull base. We then turn our attention to an interesting group of intracranial lesions that all mimic neoplasms, i.e., they are pseudotumors. These tumor-like lesions may arise within the meninges, CSF cisterns, or brain parenchyma. Some lesions may involve multiple compartments and can be intracranial, extracranial, or a combination of both.

Extracranial Tumors and Tumor-

Like Conditions

Fibrous Dysplasia

Benign fibroosseous lesions of the craniofacial complex are represented by a variety of intraosseous disease processes. These include bone dysplasias, the most common of which is fibrous dysplasia (FD).

Terminology

FD is a benign dysplastic fibroosseous lesion that is also known as fibrocartilaginous dysplasia, osteitis fibrosa, and generalized fibrocystic disease of bone.

Etiology

General Concepts. FD is a developmental lesion with local arrest of normal structural/architectural development. Abnormal differentiation of osteoblasts results in replacement of normal marrow and cancellous bone by immature "woven" bone and fibrous stroma.

Genetics. Recent studies have demonstrated that FD is a neoplastic—not dysplastic—lesion. Activating mutations of the GNAS1 gene result in

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(26-1) FD is with expansion of lateral orbital rim, sphenoid wing, temporal squamosa. Note exophthalmos, stretching of optic nerve.

(26-2) FD in a rib is a solid tan tumor that expands bone, has "ground-glass" appearance. (Courtesy A. Rosenberg, MD, G. P. Nielsen, MD.)

(26-3) FD shows "woven" bony trabeculae , fibrous stroma , reactive subperiosteal new bone . (A. Rosenberg, MD, G. P. Nielsen, MD.)

overexpression of the c-fos proto-oncogene, which contributes to the initiation and progression of FD.

Pathology

Location. Virtually any bone in the head and neck can be affected by FD. The skull and facial bones are the location of 10-25% of all monostotic FD lesions. The frontal bone is the most common calvarial site, followed by the temporal bone, sphenoid, and parietal bones. Involvement of the clivus is rare. The orbit, zygoma, maxilla, and mandible are the most frequent sites in the face (26-1).

Size and Number. FD lesions range in size from relatively small—less than 1 cm—to massive lesions that involve virtually an entire bone. Altered osteogenesis may occur within a single bone ("monostotic FD") or multiple bones ("polyostotic FD"). Monostotic FD accounts for approximately 60-80% of all lesions; polyostotic FD occurs in 20-40% of cases.

Polyostotic FD with endocrinopathy is known as McCune-Albright syndrome (MAS) and occurs in 3-5% of cases. The classic MAS triad consists of multiple FD lesions, endocrine dysfunction (typically precocious puberty), and cutaneous hyperpigmentation ("café au lait spots").

Gross Pathology. FD is tan to whitish gray (26-2). Depending on the relative amount of fibrous versus osseous content, texture varies from firm and rubbery to "gritty."

Microscopic Features. Fibrous and osseous tissues are admixed in varying proportions (26-3). In the early stages, pronounced osteogenesis with thin osteoid anastomosing trabeculae rimmed with osteoblasts is seen. A stromal fibroblastic element with variable vascularity is interspersed between trabeculae of immature "woven" bone that resembles "Chinese letters."

Almost 60% of cases demonstrate different stromal patterns admixed with the usual fibroblastic elements. These include focal fatty metamorphosis (20-25%), myxoid stroma (15%), and calcifications (12%). Cystic degeneration occurs but is uncommon.

Clinical Issues

Epidemiology. FD is rare, representing approximately 1% of all biopsied primary bone tumors. It is the second most common pediatric primary skull lesion (after dermoid cysts).

Demographics. Although FD can present at virtually any age, most patients are younger than 30 years at the time of initial diagnosis. Polyostotic FD presents earlier; the mean age is 8 years. With the exception of FD as part of MAS, which affects female patients more than male patients, there is no sex predilection.

Presentation. Symptoms of craniofacial FD depend on lesion location. Painless osseous expansion with calvarial or facial asymmetry is common. Proptosis and optic neuropathy are common in patients with orbital disease. Conductive hearing loss and facial weakness are typical in patients with temporal bone FD. Mandibular FD typically presents with "cherubism."

Polyostotic FD may cause "leontiasis ossea" (lion-like physiognomy) or complex cranial neuropathies (secondary to severe narrowing of the neural foramina).

Natural History. Disease course varies. Monostotic lesions do not regress or disappear, but they generally stabilize at puberty. In contrast, polyostotic FD generally becomes less active after puberty although long bone deformities may progress, and microfractures may develop.

Malignant transformation is very rare,occurring in less than 1% of all FD cases and has been described in both the monostotic and polyostotic forms.

Treatment options for FD are limited. Recurrence is very high following curettage and bone grafting. Radiation therapy is generally avoided, as it may induce malignant transformation. Intravenous bisphosphonate therapy has been used to ameliorate the disease course with some reported success.

FIBROUS DYSPLASIA: PATHOLOGY AND CLINICAL ISSUES

Pathology

•Location, number

○Any bone

○Craniofacial (10-25%)

○Solitary (60-80%) or polyostotic (20-40%)

•Gross pathology: "woven" bone

•Microscopic pathology

○Variable admixture of fibrous, osseous components

○Less common: fat, myxoid tissue, Ca++, cysts

Clinical Issues

•Rare (< 1% of biopsied bone tumors)

○One of the most common fibroosseous lesions

•Monostotic patients < 30 years

•Polyostotic fibrous dysplasia

○Younger (mean age = 8 years)

○McCune-Albright (3-5%)

○Craniofacial > calvarial involvement

Imaging

General Features. Most craniofacial lesions are monostotic. However, skeletal survey or whole-body MR is recommended to detect asymptomatic lesions in other bones that would indicate polyostotic disease or MAS.

Imaging findings depend on disease stage. In general, very early lesions are radiolucent and then undergo progressive calcification, resulting in a "ground-glass" appearance. Mixed patterns are common.

CT Findings. Nonaggressive osseous remodeling and thickening of the affected bone are typical. NECT shows a geographic expansile lesion centered in the medullary cavity. Abrupt transition between the lesion and adjacent normal bone is typical.

Bone CT appearance varies with the relative content of fibrous versus osseous tissue. FD can be sclerotic, cystic, or mixed (sometimes called "pagetoid"). A pattern with mixed areas of radiopacity and radiolucency is found in almost half of all cases (26-4A) (26-5). The classic relatively homogeneous "ground-glass" appearance occurs in 25%. Densely sclerotic lesions are common in the skull base. Almost one-quarter of all FD cases have some cystic changes, seen as central lucent areas with thinned but sclerotic borders.

MR Findings. FD is usually homogeneously hypointense on T1WI. Signal intensity on T2WI is variable. Moderate hypointensity is characteristic of ossified and/or fibrous portions of the lesion (26-4B). Active lesions may be heterogeneous and may have hyperintense areas on T2 or FLAIR (26-5D). Cysts appear as rounded high signal foci.

Signal intensity following contrast administration varies depending on the lesion stage and ranges from no enhancement to diffuse, avid enhancement in active lesions (26-4C).

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(26-4A) Bone CT in a 26y woman shows classic monostotic FD with "ground glass" appearance, central noncalcified fibrous stroma .

(26-4B) T2WI shows that dense, ossified bone is hypointense , but a central area of active disease is hyperintense .

(26-4C) (L) T1WI in the same case shows hypointense periphery , isointense center .

(R) T1 C+ FS shows most of mass enhances.

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Nuclear Medicine. FDG PET and 68Ga-PET/CT show increased metabolic activity in one or more sites and can mimic metastatic disease.

Differential Diagnosis

The major differential diagnoses for craniofacial FD are Paget disease and ossifying fibroma (OF).

Paget disease typically occurs in elderly patients and usually involves the calvaria and temporal bone. A "cotton wool" appearance is typical on digital skull radiographs and bone CT.

OF may mimic the cystic monostotic form of FD. OF has a thick, bony rim with a lower density center on bone CT and generally appears more mass-like and localized. Diffuse sclerosing osteomyelitis of the mandible may also resemble FD.

(26-5A) Bone CT in a 19y man with polyostotic FD and cranial nerve palsies shows multiple lesions in the facial bones and calvarium. (26-5B) More cephalad bone CT shows several lesions expanding the calvarium.

(26-5C) Sagittal reformatted bone CT shows the expansile, "ground glass" appearance of the skull base and calvarial lesions . (26-5D) Sagittal T2WI shows that the expansile skull baseand calvarial lesions are heterogeneously hyperintense. Note severe posterior fossa crowding with acquired tonsillar herniation .

Intraosseous meningioma is another differential consideration. Intraosseous meningiomas are more common in the calvaria than in the skull base and facial bones. A strongly enhancing en plaque soft tissue mass is often associated with the bony lesion. A mixed sclerotic-destructive skull base metastasis may mimic FD. In most cases, an extracranial primary site is known.

The differential diagnosis of FD includes rare fibroosseous disorders that can affect the craniofacial bones. These include osteitis deformans, florid osseous dysplasia, focal cementoosseous dysplasia, and periapical cemental dysplasia.

Facial bone changes associated with hyperparathyroidism and renal osteodystrophy may present with a classic "groundglass" appearance on both conventional radiography and CT. However, in contrast to FD, these changes are generalized and diffuse.

FIBROUS DYSPLASIA: IMAGING AND DDx

Imaging

•CT

○Bone remodeled, expanded

○"Ground-glass" appearance classic

○Sclerotic, cystic, mixed ("pagetoid") changes

•MR

○T1 hypointense, T2 variable (usually hypointense)

○Enhancement varies from none to intense

Differential Diagnosis

•Paget disease (older patients)

•Ossifying fibroma, other benign fibroosseous lesions

•Intraosseous meningioma

•Renal osteodystrophy

Paget Disease

Terminology

Paget disease (PaD) of bone, also called osteitis deformans, is the most exaggerated example of abnormal osseous remodeling. PaD is characterized by rapid bone turnover within one or more discrete skeletal lesions.

Etiology

Genetic alterations occur in both classic Paget disease of the elderly and the uncommon familial Paget-like bone dysplasias that arise during childhood. All involve defective function of the molecular pathway that regulates osteoclastogenesis (the osteoprotegerin/TNFRSF11A or B/RANKL/RANK pathway).

Mutations in the gene encoding sequestosome 1 (SQSTM1) have been identified in one-third of patients with the familial form of FD and in a smaller proportion of patients with sporadic PaD. SQSTM1 mutations affect functioning of the p62 phenotype, which increases the sensitivity of osteoclast precursors to osteoclastogenic cytokines, thus causing a predisposition to PaD. SQSTM1 mutations are also strongly associated with PaD disease severity and complications.

Mutations in the valosin-containing protein gene (VCP) cause a unique disorder characterized by classic PaD, inclusion body myopathy, and frontotemporal dementia.

Pathology

Location, Size, and Number. The skull (both calvaria and skull base) is affected in 25-65% of patients (26-6). In contrast to FD, PaD is more commonly polyostotic (65-90% of cases).

Gross Pathology. The pagetoid skull shows diffuse thickening (26-7). Patches of fibrovascular tissue initially replace fatty marrow.

Microscopic Features. In the early lytic stage, active PaD is characterized by cellular fibroosseous lesions with minimally calcified osteoid trabeculae. Increased vascularity is common. Osteoblastic rimming is present together with osteoclastic resorptive lacunae. Osteoclasts are numerous and larger than normal; they also have increased numbers of nuclei.

In the inactive stage, bone turnover and excessive vascularity decrease and the trabeculae coarsen.

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(26-6) Graphic shows diffuse Paget disease of the skull with severe diploic widening and basilar invagination .

(26-7) Autopsied Paget disease shows calvarial thickening with sclerotic bone , patches of fibrovascular tissue . (From Dorfman, 2016.)

(26-8) Bone CT in a 63y woman with Paget disease shows thick calvarium with mixed sclerotic and lucent areas .

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(26-9A) T1WI shows mixed hyper- , hypointense diploic lesions in a calvarium massively expanded by Paget disease.

(26-9B) T2WI in the same case shows the extremely "mottled" heterogeneous appearance of calvarial Paget disease.

(26-9C) Patchy enhancement is seen on T1 C+ FS, indicating that some active disease is present in this longstanding case.

Clinical Issues

Epidemiology. PaD is common, affecting up to 10% of individuals over the age of 80. It is especially prevalent in the United States, the British Isles, Canada, Australia, and some parts of Western Europe. PaD is rare in Asia and Africa.

Demographics. Classic PaD is a disease of the elderly. Most patients are 5585 years of age with less than 5% of cases occurring in patients under the age of 40. There is a moderate male predominance.

Juvenile PaD, also known as idiopathic hyperphosphatasia, is an autosomalrecessive bone dysplasia. It begins in infancy or early childhood and is characterized by long bone widening, acetabular protrusion, pathologic fractures, and skull thickening.

Presentation. Presentation varies with location, and all bones of the craniofacial complex can be affected. Patients with calvarial PaD may experience increasing hat size. Cranial neuropathy is common with skull base lesions, most commonly affecting CN VIII. Patients may present with either conductive (ossicular involvement) or sensorineural hearing loss (cochlear involvement or bony compression).

Markedly elevated serum alkaline phosphatase is a constant feature, whereas calcium and phosphate levels remain within normal range.

Natural History. In the extracranial skeleton, osseous expansion with progressive skeletal deformity is typical. Osseous weakening leads to long bone deformities and fractures. In comparison, craniofacial PaD generally has a more benign course and may remain asymptomatic for many years.

Two neoplastic processes are associated with PaD: giant cell tumor (benign) and sarcoma (malignant). Giant cell tumor is an expansile intraosseous mass that usually occurs in the epiphyses and metaphyses of long bones in patients with longstanding polyostotic PaD. Giant cell tumors that arise secondarily in pagetoid bone are rare. Just 2% occur in the skull, where the most common site is the sphenoid bone. Involvement of the calvarial vault is rare.

Malignant transformation to osteosarcoma occurs in 0.5-1.0% of cases and is generally seen in patients with widespread disease. Most osteosarcomas are high grade and have already metastasized at the time of diagnosis. Only 15% of patients survive beyond 2 or 3 years.

Treatment Options. Bisphosphonates reduce bone turnover and have been effective in many cases of PaD.

Imaging

General Features. Imaging findings in PaD vary with disease stage. In the early active stage, radiolucent lesions develop in the calvaria, a condition termed osteoporosis circumscripta. Enlarged bone with mixed lytic and sclerotic foci and confluent nodular calcifications follows (the "cotton wool" appearance) in the mixed active stage. The final inactive or quiescent stage is seen as dense bony sclerosis.

CT Findings. In early PaD, bone CT shows well-defined lytic foci (osteoporosis circumscripta). Mixed areas of bony lysis and sclerosis then develop, producing the "cotton wool" appearance (26-8). Varying degrees of dense bony sclerosis can develop.

In severe cases, the softened expanded skull base can produce basilar invagination.

MR Findings. Multifocal T1 hypointense lesions replace fatty marrow (269A). Signal intensity on T2WI is often heterogeneous (26-9B). Patchy enhancement on T1 C+ can occur in the advancing hypervascular zone of active PaD (26-9C).

Nuclear Medicine. The active stage of PaD shows markedly increased uptake on Tc-99m bone scans. 18F-NaF PET/CT can also demonstrate high uptake in PD, mimicking metastatic disease.

Differential Diagnosis

FD may appear very similar to craniofacial PaD. However, PaD occurs mostly in the elderly and does not have the typical "ground-glass" appearance that often characterizes FD.

Sclerotic metastases may resemble PaD, but no trabecular coarsening or bony enlargement is present. The early lytic phase of PaD may resemble lytic metastases or multiple myeloma; neither enlarges the affected bone.

PAGET DISEASE

Pathology

•Monostotic (65-90%)

•Calvaria, skull base affected (25-60%)

•Fibroosseous tissue replaces fatty marrow

Clinical Issues

•Affects up to 10% of patients > 80 years

•Enlarging skull, CN VIII neuropathy common

•Malignant transformation (0.5-1.0%)

○Sarcoma > giant cell tumor

Imaging

•Early: lytic ("osteoporosis circumscripta")

•Mid: mixed lytic, sclerotic ("cotton wool")

•Late: dense bony sclerosis

Differential Diagnosis

•Fibrous dysplasia (younger patients)

•Metastases, myeloma

Aneurysmal Bone Cyst

Terminology

Aneurysmal bone cysts (ABCs) are benign expansile multicystic lesions that typically develop in childhood or early adulthood. At least 70% of ABCs are primary lesions; the rest arise secondarily within a preexisting benign tumor such as giant cell tumor or osteoblastoma.

Pathology

The most common overall ABC location is the metaphysis of long bones (7080% of cases) with the vertebrae (generally the posterior elements) the site of 15% of lesions.

The craniofacial bones are a relatively uncommon location. Lesions can occur in the jaws (maxilla, mandible), petrous temporal bone, basisphenoid, and paranasal sinuses. ABCs of the skull and orbit are rare, accounting for less than 1% of all cases.

ABCs consist of blood-filled cavernous spaces with intracystic hemorrhages of variable ages. Multiple variably sized cysts are separated by septa lined by

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(26-10A) CECT shows an expansile mass with cysts and fluid-fluid levels , solid portion exhibiting relatively uniform enhancement .

(26-10B) Coronal bone CT demonstrates a thin "eggshell" rim of expanded bone around the lesion .

(26-10C) T2WI shows the lesion expands intracranially , extends into sphenoid sinus ; aneurysmal bone cyst. (Courtesy A. Illner, MD.)

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endothelium, spindle-shaped fibroblasts, and scattered multinucleated giant cells.

Clinical Issues

ABCs represent 5% of all primary bone tumors and are the second most common pathologically proven bone tumor of childhood. About 70% occur in the first two decades, with a slight male predominance. Symptoms vary with location. Many lesions are asymptomatic or present with slowly progressive swelling.

Treatments for symptomatic ABC are curettage, cryosurgery, and bone graft. Recurrence rates are high, varying from 2050%. Preoperative embolization may be helpful in selected cases.

(26-11A) Axial CECT of an aneurysmal bone cyst demonstrates multiple cysts with fluid-fluid levels and enhancing rims . (26-11B) Coronal CECT shows that the massis both intraand extracranial. The dependent blood-fluid levels in the cysts are better appreciated on the axial scan.

(26-11C) T2WI shows multiple cysts with bloodfluid levels . The thin black line draped over the mass is the displaced dura. (26-11D) T1 C+ FS shows the characteristic enhancement of the cyst walls and septations within the tumor.

Imaging

NECT scans show an eccentric lesion with expanded, remodeled, ballooned ("aneurysmally dilated") bone surrounded by a thin sclerotic rim (26-10). Multiple cystic spaces with fluid-fluid levels are present (26-11).

MR shows a multicystic lesion with a hypointense rim surrounding multiple fluid-filled spaces. Hemorrhages of varying ages with fluid-fluid levels are a prominent imaging feature, as are smaller cysts ("diverticula") that project from larger lesions. The surrounding rim and fibrous septa enhance following contrast administration (26-11).

Differential Diagnosis

Some ABCs may have a phase of relatively rapid growth and can be mistaken clinically for a more aggressive lesion. The most important imaging differential diagnosis of ABC is telangiectatic osteosarcoma (OS), which may have fluid-fluid

levels that resemble those of ABC. Incomplete margination, soft tissue mass, cortical destruction, and significant solid portions should suggest telangiectatic OS instead.

Giant cell tumor and osteoblastoma are associated with secondary ABC, and both show significant solid components.

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cancer stem-like cells have been identified in some chordomas.

Signal transducer and activation of transcription (STAT) proteins regulate key cellular fates, including proliferation and apoptosis. STAT3 is activated in chordoma.

Chordoma

Terminology

Chordomas are rare, locally aggressive primary malignant neoplasms with a phenotype that recapitulates the notochord.

Etiology

Skull base (clival) chordomas probably arise from the cranial end of primitive notochordal remnants. Subpopulations of

Pathology

Chordomas are midline tumors that may arise anywhere along the primitive notochord. The sacrum is the most common site (50% of all chordomas) followed by the sphenooccipital (clival) region (35%) and spine (15%).

Most sphenooccipital chordomas are midline lesions (26-12). Occasionally, a chordoma is predominantly extraosseous and arises off-midline, usually in the nasopharynx or cavernous sinus.

(26-12) Sagittal graphic shows an expansile, destructive, lobulated clival mass with a "thumb" of tumor indenting the pons. The pituitary gland is elevated by the tumor. Note the bone fragments"floating" in the chordoma. (26-13) (Top) Autopsy of clival chordoma shows lobulated mass invading sella. (Bottom) Microscopy shows physaliphorous cells with vacuolated cytoplasm. (From Ellison, Neuropathology, 2013).

(26-14A) Axial bone CT (top) shows a destructive lesion in the central skull base . (Bottom) The lesion is heterogeneously hyperintense on T2WI. Note posterior extension indenting the pons . (26-14B) Sagittal T1 C+ FS in the same case shows that the destructive enhancing mass displaces the pituitary gland anteriorly and indents the pons posteriorly . This is chordoma.

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Three major histologic forms of chordoma are recognized: conventional ("classic"), chondroid, and dedifferentiated. Conventional chordoma is the most common type and consists of physaliphorous cells that contain mucin and glycogen vacuoles, giving a characteristic "bubbly" appearance to its cytoplasm (26-13).

Chondroid chordomas have stromal elements that resemble hyaline cartilage with neoplastic cells nestled within lacunae. Dedifferentiated chordoma represents less than 5% of chordomas and typically occurs in the sacrococcygeal region, not the clivus.

Both conventional and chondroid chordomas are strongly immunopositive for the epithelial markers cytokeratin (especially CK8) and epithelial membrane antigen (EMA). Dedifferentiated chordomas exhibit SMARCB1/INI1 loss and are associated with dismal prognosis.

(26-15A) Axial NECT in a

39y man with multiple cranial nerve palsies shows destructive, heterogeneous-appearing central skull base mass. (26-15B) Bone CT shows near-complete destruction of the sphenoid with eroded clivus and petrous apices. Some dysmorphicappearing matrix mineralization is present within the mass.

(26-15C) Sagittal T1WI shows that the mass has destroyed almost the entire sphenoid bone with "thumb" of tumor indenting the pons. (2615D) Axial T2WI shows that the lobulated extradural mass is very hyperintense and displaces both carotid arteries laterally and the basilar artery posteriorly. Conventional chordoma was found at surgery.

Clinical Issues

Chordomas account for 2-5% of all primary bone tumors but cause almost 40% of sacral tumors. Although chordomas may occur at any age, peak prevalence is between the fourth and sixth decades. There is a moderate male predominance.

Clival chordomas typically present with headaches and diplopia secondary to CN VI compression. Large chordomas may cause multiple cranial neuropathies, including visual loss and facial pain.

Although they grow slowly, chordomas are eventually lethal unless treated with aggressive resection and proton beam irradiation. The overall 5-year survival rate of patients following radical resection is 75%. Chondroid chordomas exhibit the most favorable outcomes, whereas dedifferentiated tumors are associated with the most rapid progression and poor overall survival.

Imaging

NECT shows a relatively well-circumscribed, moderately hyperdense midline or paramedian clival mass with permeative lytic bony changes. Intratumoral calcifications generally represent sequestrations from destroyed bone.

Chordomas exhibit substantial heterogeneity on MR. Most conventional chordomas are typically intermediate to low signal intensity on T1WI. On sagittal images, a "thumb" of tumor tissue is often seen extending posteriorly through the cortex of the clivus and indenting the pons.

Conventional chordomas are very hyperintense on T2WI (2616B), reflecting high fluid content within the physaliphorous cells. Intratumoral calcifications and hemorrhage may cause foci of decreased signal within the overall hyperintense mass.

Moderate to marked but heterogeneous enhancement is typical after contrast administration. Increased tumor-to-pons

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postcontrast signal intensity is associated with more abundant blood supply and increased risk of tumor progression.

Recent studies have shown that MR grading of clival chordomas based on T2 hyperintensity and the degree of postcontrast enhancement relative to the adjacent pons may be useful in predicting more rapid tumor progression.

Differential Diagnosis

A large invasive pituitary macroadenoma can mimic CCh. CChs typically displace but do not invade the pituitary gland, whereas macroadenomas cannot be identified separate from the gland.

Signal intensity of a skull base chondrosarcoma is very similar to that of CCh. Chondrosarcomas typically arise off-midline, along the petrooccipital fissure. Ecchordosis physaliphora is a rare nonneoplastic notochordal remnant that may arise anywhere from the skull base to the sacrum. Most are small