Benign

Hemangioma/Lymphangioma

Although hemangiomas of bone are not uncommon, calvarial hemangiomas are relatively rare.^21,22 These cranial vascular lesions are found more commonly in women than men (3 : 1 ratio)^11,21–24 and have a predilection for the frontal and parietal areas.^11,21,23,25 Hemangiomas vary in size from microscopic to massive and may be classified as either capillary or cavernous, depending on their histologic appearance.²⁶ In 15% of cases, the lesions are multiple.^21,24 Skull hemangiomas are often small and asymptomatic but may evolve into a visible and palpable area of tenderness and swelling.^22,23 The scalp overlying the lesion is typically freely mobile.²² Hemangiomas in less common locations such as the base of the skull or orbit may cause cranial neuropathies or proptosis.^21,25

Histologically, cavernous hemangiomas are unencapsulated sinusoidal channels lined by flattened endothelial cells within bony trabeculae. Capillary hemangiomas are similar but contain more capillary-sized vessel loops; frequently, a mixture of both histologic forms is present. The bony trabeculae are thought to be caused by osteoclastic remodeling in response to stress from the enlarging vascular malformation.^1,21,25

Hemangiomas are always benign and may remain static for long periods.^21,23,25 When they do grow, one of two growth patterns is typically exhibited: a “sessile” pattern involving extension along the diploë or a “globular” pattern with expansion of the skull and eventual extension into the surrounding soft tissues.⁵ The sessile type is more common.¹¹ Association of skull hemangiomas with hemangiomas elsewhere in the body (including other bones), such as in the liver, kidney, spleen, and adrenal gland, has been reported, although true metastases have not.²¹

Calvarial hemangiomas tend to involve the outer table of the skull and the diploë, with relative sparing of the inner table of the skull.^11,22 The classic appearance of a hemangioma on radiographs is a “sunburst” or “honeycomb” pattern.^11,21,25 There is generally no surrounding sclerosis, and in fact, there may be a halo of decalcification.^21,25 This pattern can perhaps best be appreciated on CT bone windows.^24,25 Enhancement with contrast material is intense on both CT and MRI. Angiography may demonstrate feeding of the hemangioma by branches of the external carotid artery (ECA) and often by the superficial temporal artery or the middle meningeal artery,^11,21,24 and it may suggest a pathway for preoperative embolization.^22,25 Radionuclide bone scanning is of little use in the assessment of these lesions.⁵

En bloc surgical excision with establishment of normal bony margins (Fig. 148-1), when indicated, typically results in cure.^21,23,25 Simple curettage may increase the chance of leaving residual disease and tumor recurrence.²² Some have advocated radiation treatment for residual tumor or for skull base lesions that are difficult to access surgically.²⁰ Treatment of a symptomatic cavernous hemangioma of the occipital condyle with methacrylate embolization has also been reported.²⁷

FIGURE 148-1 Hemangioma. A 52-year-old woman had a slowly growing mass in the left frontal region that was excised completely and a cranioplasty performed. Pathologic examination showed linear infiltration of the diploë and cortex. This tumor did not recur during 5 years of follow-up. A, MRI (axial view, T1-weighted, contrast-enhanced image) showing a well-delineated, brightly enhancing mass that is atypical in that it breaches the inner table of the skull but not the outer one. B, MRI (axial, T2-weighted image) showing a variegated pattern without obvious hemosiderin deposition. C, Excised operative specimen with discoloration but no breach of the outer table of the skull. D, The inner skull table of the same specimen shows blistering and remodeling by the lesion.

Lymphangioma is a congenital soft tissue tumor most commonly found in the neck; osseous involvement is rare.^1,28,29 The first lymphangioma of bone was reported in 1947; the first solitary calvarial lesion without other visceral or skeletal involvement was noted in 1974.^28,30 Skull base involvement is even more uncommon and has been reported to cause CSF rhinorrhea and cranial neuropathy.^28,31 Lymphangioma is more common in the first 2 decades of life and is found with equal frequency in men and women.^28,29,32 The most common finding is a palpable, possibly painful mass. Spontaneous bleeding into the mass has been described.^29,32 One report described two particularly severe pediatric cases of lymphangiomatosis leading to massive osteolysis of the skull.³³

Histologically, this benign lesion is very similar to hemangioma.^28,30 Typically, the tumor is composed of large spaces lined with endothelium and filled with proteinaceous lymphocytic fluid within a fibrous connective tissue stroma. Bony trabeculae may also be present.^1,29 The proportion of lymphocytic fluid to fibrous stroma may vary considerably.³² There are three histologic subtypes: cystic (cystic hygroma), capillary, and cavernous.^28,29

As seen on plain radiographs, the lesions are lytic with a well-demarcated, nonsclerotic margin.^29,30 Multiple lesions are not uncommon.²⁹ The variable histologic makeup of lymphangioma causes the CT appearance to be similarly variable,³² and with the administration of contrast material, enhancement is weak if present at all.³² Lymphangiomas have a characteristic mixed-intensity, “bubbly” appearance on MRI sequences.³² Radionuclide bone scanning may be a useful diagnostic adjunct for these lesions.³⁰ En bloc surgical resection is the treatment of choice for symptomatic or progressive lesions.^28,29

Embryonic: Epidermoid and Dermoid

Epidermoid cysts and dermoid cysts together represent the epithelial inclusion cysts or “pearly tumors.”^34,35 Both are thought to be formed in the third to fifth week in utero as a result of faulty separation of the ectoderm and neuroectoderm.^36,37 Epidermoids are somewhat more common, are usually laterally situated, and are often found in adults.^35,38 Dermoids are more commonly found in the midline and may be associated with congenital malformations.^35,38–40

The first diploic epidermoid was described by Cushing in 1922. These cysts are usually congenital lesions caused by ectodermal rests within the skull diploë.^38,40–43 Epidermoids have also been reported to be caused by traumatic induction of epidermal rests.^40,44 Epidermoids are benign, slow-growing lesions, but they can undergo malignant change.^40,45 They are typically asymptomatic, and a palpable painless lump is frequently the first sign.^11,38,40,42 Giant intradiploic cysts can, however, cause elevated intracranial pressure and headaches.^38,44,46 Rarely, intracranial extension occurs and results in seizures or venous sinus obstruction.^{11,38,40,42,47} Intracranial rupture plus hemorrhage of diploic epidermoids has also been reported after head trauma.⁴⁰

Epidermoid cysts are usually well circumscribed, with a smooth, irregularly nodular capsule (Fig. 148-2).³⁵ The lining of epidermoids is keratin-producing squamous epithelium.^34,48 The cyst contains soft, white, waxy, grumous flaky keratin; leakage of the cyst contents into CSF may produce a severe chemical meningeal response known as Mollaret’s meningitis.^34,35 Progressive exfoliation of the cyst wall toward the interior of the cyst causes a linear growth rate and gives its contents a lamellar appearance.^11,35,38,48 The linear growth rate of the cyst is more similar to that of normal skin than to the exponential growth of most neoplasms.³⁵

FIGURE 148-2 Epidermoid cyst. A 30-year-old woman had an incidental finding of a retromastoid skull lesion when she underwent CT for paranasal sinus complaints; it was excised at her request. A, Skull radiograph (lateral) showing a well-circumscribed defect in the occipital bone. B, CT bone window showing a sharply defined lesion extending through bone to the dura. C, MRI (axial, T1-weighted, contrast-enhanced image). The lesion shows some enhancement but retains speckled areas of hypointensity. D, MRI (axial, T2-weighted image) showing inhomogeneous hyperintensity consistent with a largely fatty content. E, Operative specimen viewed from the inner aspect. The lesion eroded through to the periosteum. The material to the right of the specimen represents some of the paste-like contents of this cyst.

The radiographic appearance of epidermoids is that of a lytic lesion with sclerotic margins and diploic expansion.^{11,38,42,43,48} CT and MRI generally demonstrate a nonenhancing lesion with imaging characteristics similar to CSF, although they may be of mixed intensity on all imaging sequences and the capsule may show enhancement. Cholesterol within the cyst may give it a hypodense appearance on CT.^11,38,43 CT is particularly useful for assessment of diploic expansion and for detecting destruction of the inner and outer skull tables, as well as any intracranial extension.^38,41,44,48

Dermoid cysts are similar to epidermoids, although they are typically found in the midline, are more common in children and women, and may be associated with congenital malformations.^35,38,39 They commonly occur at the anterior fontanelle and occipital squama.^{35,36,39,49,50}

Dermoids grow by both desquamation and glandular secretion.⁵¹ As a result, the cyst typically contains thick foul-smelling yellow material in which hair may be entangled.³⁵ Unlike epidermoids, the lining of dermoids contains dermal skin appendages: hair follicles, sweat glands, and, rarely, teeth.^34,48

Similar to epidermoids, dermoids are often asymptomatic; their progressive outward expansion may lead to a palpable mass, and inward growth may compress the brain.³⁹

Dermoids have CT and MRI characteristics similar to those of fat; they generally do not show contrast enhancement with either modality.⁵¹ Plain radiographs demonstrate an osteolytic region occasionally surrounded by a sclerotic border.⁴⁹ CT shows a round, well-demarcated, hypodense lesion.⁵¹

Intracranial extension and involvement of the venous sinuses may be significant, and a preoperative magnetic resonance venogram is essential for determining this relationship.^36,49,50 Dermoid tumors in the occipital region may also be associated with a dermal sinus tract and a consequent risk for meningitis or intracranial abscess.^36,50

The treatment of choice for both types of inclusion tumor is complete surgical resection, which results in cure.^38,40,42,44 A margin of normal bone is often resected to avoid disrupting the cyst capsule.⁴¹ Ideally, the tumor should be dissected away from the dura, although in some cases the dura must be resected as well.⁴¹ The risks related to incomplete surgical resection include recurrence, progression to squamous cell carcinoma, infection, and aseptic meningitis.^{35,36,39,41,44,45,52} The prognosis in patients whose tumors undergo malignant transformation is poor.^41,44

Meningioma

Intraosseous (intradiploic) meningiomas are uncommon. True primary intraosseous meningiomas do not involve the inner or outer tables of the skull or the dura.⁸⁷ As meningiomas with no dural attachment, these tumors may be categorized as “ectopic meningiomas” or “primary extradural meningiomas.”^87,88 These are rare lesions that account for less than 2% of all meningiomas.⁸⁸ Intraosseous meningiomas constitute 14% of primary extradural meningiomas.⁸⁹

Several differences between primary extradural meningiomas and their more common intradural counterparts have been observed. The female preponderance of diploic meningiomas may not be as pronounced as it is with other meningiomas, although this finding is somewhat inconsistent.^87,88 Second, although both intradural and ectopic meningiomas affect adults, only ectopic meningiomas have a second incidence peak in the pediatric population.^88,90 Finally, extradural meningiomas may have a greater likelihood of being atypical or frankly malignant than intradural meningiomas do (11% rather than 2%).^88,91

Intradiploic meningiomas are thought to arise from rests of arachnoid cap cells trapped within sutures at birth and during molding of the head.^92,93 An alternative hypothesis is that ectopic meningiomas arise from abnormal differentiation of multipotent mesenchymal cells.^87,88 Their cause may in fact be multifactorial.⁸⁸ Awareness of a painless, slowly growing, palpable mass is the most common manifestation.^87,88,90,94 Headaches and local tenderness are also possible.^87,93 Lesions in the temporal bone may cause hearing loss or facial weakness.^95,96 A case of multiple intraosseous meningiomas has been reported.⁹⁷

Histologically, intraosseous meningiomas are not different from their intradural counterparts; they have a wide range of histopathologic findings and positive immunostaining for epithelial membrane antigen and vimentin.^88,89,94

On plain radiography and CT, most intraosseous meningiomas are hyperostotic, although some are lytic or both lytic and sclerotic.^{87,89,90,92,95} There is some speculation that as the lesion progresses, it becomes more lytic and less sclerotic.⁹² CT is often the most helpful imaging modality because it allows assessment of the extent of bone involvement.^{87,89,94,96,98} CT and plain radiographs demonstrate expansion of the diploë, with the inner and outer tables of the skull separated and thinned over the biconvex mass.^89,91,93 As seen with MRI, the tumors appear hypointense on T1-weighted and hyperintense on T2-weighted images.⁹¹ As with intradural meningiomas, intraosseous meningiomas display homogeneous contrast enhancement on both CT and MRI.^89,91,98 On basal views of the skull, the foramen spinosum may be enlarged because of hypertrophy of the middle meningeal artery.⁹² Using angiography, the intradural arteries and dural sinuses are seen to be pushed away from the inner table of the skull; this is the opposite of what is found with intradural meningiomas, wherein the vessels are displaced toward the inner table.⁹² There may be a tumor blush from its branch feeders from the ECA.⁹⁸

Intraosseous meningiomas of the skull are seldom correctly diagnosed preoperatively.^87,88 Surgical resection is the treatment of choice for these lesions (Fig. 148-3). En bloc resection with margins, when feasible, may decrease the risk for recurrence.^{87,88,90,91,93,94,96}

FIGURE 148-3 Intraosseous meningioma. A 36-year-old woman complained of a left frontal headache localized over a palpable mass. Nearly complete excision was performed, but some of the dural tail was left in situ. The MIB-1 labeling index was 3.5%. A, CT shows extrusion of tumor past the outer table of the skull and extension of involvement across the midline. B, MRI (axial, T1-weighted, contrast-enhanced image) showing a contrast-enhancing tumor in the epidural and subgaleal space, significant hyperostosis, and compression of the left frontal lobe. C, MRI (sagittal, T1-weighted, contrast-enhanced image) showing the extent of cosmetic deformity, plus the long dural tail extending posteriorly. D, MRI (axial, T2-weighted image) showing no cerebral edema. E, Operative specimen (from the inner skull table) showing multiple excrescences of tumor that appeared to be confined to bone, along with reactive dural thickening that was free of tumor in the areas sampled. F, A cranioplasty performed with a porous polyethylene implant supplemented with wire mesh produced excellent cosmetic results.

Malignant

Osteogenic Sarcoma

Osteogenic sarcoma (osteosarcoma) is the most common malignant tumor of bone, although it is relatively rare in the skull.^99–103 In the skull, the cranial vault is involved more frequently than the base.¹⁰² These tumors may arise de novo or, more commonly, as a sequela of radiation treatment or another bone disorder such as Paget’s disease or fibrous dysplasia.^{1,10,100,101,103–106} Osteogenic sarcomas that develop secondary to radiation treatment are thought to be more aggressive and have a worse prognosis than those arising de novo.¹⁰⁰ Additionally, de novo osteosarcomas tend to have a later onset.¹⁰⁰

Osteosarcomas are generally manifested as localized, painless, expansile masses.^1,100,102 Patients with tumors attaining large size or involving the skull base may complain of local tenderness, headaches, proptosis, ophthalmoplegia, facial weakness, decreased hearing ability, or tinnitus.^{100,101,103,106} Although extensive bony destruction can occur, the dura, brain, and venous sinuses are only rarely involved.¹⁰ The alkaline phosphatase level may be a useful diagnostic test; in a patient with known fibrous dysplasia, elevation of alkaline phosphatase may signify malignant transformation.^100,103,105

Histologically, osteogenic sarcomas consist of a sarcomatous spindle cell stroma with an associated osseous component.^1,101,103 The stromal cells demonstrate varying amounts of anaplasia and pleomorphism.¹ Formation of bone or osteoid by the tumor cells is required for diagnosis.^11,26 Necrosis may be present as well.^99,102 A low-grade, well-differentiated subtype of osteosarcoma has been reported.¹⁰¹

Osteosarcomas may be either osteoblastic, osteolytic, or mixed, and their radiologic appearance is contingent on the relative amounts of each subtype.^11,100,103 Osteoblastic lesions appear more sclerotic, and osteolytic lesions appear more radiolucent.¹⁰³ Mixed, predominantly osteoblastic lesions are most common.¹⁰⁰ CT is helpful in determining the amount of bony involvement.^11,100 The classic appearance on radiography and CT consists of bony destruction, cortical expansion, and a “sunburst” periosteal reaction.^101,104 CT may also demonstrate areas of irregular calcification, as well as low-attenuation areas representing necrosis.¹⁰² MRI generally demonstrates a heterogeneous signal on both T1- and T2-weighted sequences and may be helpful for determining the presence of intracranial invasion.^11,100,102 Contrast enhancement is typically heterogeneous.¹⁰¹ A radionuclide bone scan may show increased uptake of radioactive material by the tumor.^11,99 Angiography, when performed, demonstrates pathologic feeding of the lesion by branches of the ECA.^100,102,106

Gross total resection of osteosarcoma is the ideal treatment when safely attainable.^99,102,103 Local tumor recurrence is common after partial resection (Fig. 148-4).⁹⁹ Preoperative embolization may be a helpful surgical adjunct.^102,106 Osteosarcomas are relatively radioresistant, although some surgeons recommend irradiation of any residual tumor after partial resection.^99,100,105 Several groups have reported a dramatic increase in patient survival rate with the addition of chemotherapy.^{99,100,102,107} Salvati and coworkers reported an increase in the 2-year survival rate from 15% to 17% to 55% to 60% with the addition of chemotherapy.¹⁰⁰ Chennupati and associates reported that a chemotherapeutic regimen of methotrexate, doxorubicin, and cisplatin increased the 5-year survival rate from 20% to between 60% and 70%.⁹⁹ Sundaresan and colleagues advocated neoadjuvant treatment with this same regimen.¹⁰⁷ The low-grade well-differentiated subtype of osteosarcoma is relatively chemoresistant.¹⁰¹

FIGURE 148-4 Primary osteosarcoma of the skull. A 28-year-old woman had a palpable mass in the parieto-occipital area at and to the left of midline and a generalized seizure. Resection was incomplete because of proximity of the mass to the patent superior sagittal sinus, and subsequent treatment of the tumor bed with stereotactic radiosurgery was required. Lung metastasis developed and she was treated with chemotherapy, which resulted in good local control and a stable metastatic burden 16 months later. A, Lateral skull radiograph showing a subtle breach in the outer skull table at the site of the lesion. B, CT bone window showing a lesion extending from the inner to the outer skull table, with expansion of bone thickness. C, CT scan (axial, contrast enhanced) showing compression of the underlying left parietal lobe, which raises the question of sinus involvement. D, MRI (axial, T1-weighted, contrast-enhanced image) showing the presence of epidural and subgaleal tumor but no apparent invasion of the brain or scalp. The sinus is pushed in slightly. E, MRI (axial, T2-weighted image) showing findings similar to those in D and demonstrating patency of the sinus.

Although osteosarcomas of the skull tend to metastasize later than those arising in other primary sites, distant metastases will develop in 7% to 17% of patients.⁹⁹ This figure is closer to 10% with the low-grade well-differentiated subtype, and the prognosis for this subtype is better.¹⁰¹ Although systemic metastases are a common cause of death in patients with osteosarcoma arising from the long bones, local recurrence is more commonly the cause of death in those who have skull osteosarcomas.¹⁰⁶ Metastasis to extracranial sites should be regarded as a treatable rather than a terminal event.¹⁰⁰ The lungs are the most common site of distant dissemination.^{99,100,102,106} Accordingly, post-therapeutic imaging surveillance should include chest radiography or CT.⁹⁹ Spinal metastases have also been reported.¹⁰⁶ Because some cases of osteosarcoma in the skull are, indeed, metastatic to that location from an extracranial primary site, a comprehensive survey of the body is mandatory with this disease (Fig. 148-5).

FIGURE 148-5 Metastatic osteosarcoma. Swelling of the left posterior aspect of the scalp and right partial hemianopia developed in a 32-year-old woman with primary osteosarcoma in the left shoulder. Dural involvement at surgery required duraplasty, as well as cranioplasty, but brain tissue was displaced rather than invaded. A, CT (axial, bone window) showing disruption of the inner and outer tables by the tumor. B, MRI (axial, T1-weighted, contrast-enhanced image) showing the tumor indenting the temporo-occipital cortex and nestling against the sagittal sinus. C, MRI (axial, T2-weighted image) showing that the sinus is not occluded, cerebral edema is absent, and the cortical ribbon is preserved.

The extent of intracranial involvement by osteosarcoma at the time of diagnosis is thought to be the most important prognostic factor.^102,106

Carcinoma

Carcinomas of the breast, lung, and prostate are, in that order, by far the three most common primary tumors causing skull metastasis; renal and thyroid carcinoma skull metastases are not uncommon.^{142,143,145,148,150–152} The incidence of skull metastasis in patients with breast, lung, or prostate cancer may be as high as 23%.¹⁵² Metastasis of carcinoma to the cranial vault, particularly to the occipital bone, is more common than metastasis to the skull base.¹⁴⁶ Although metastases to the central skull base are uncommon, they occur more frequently than primary bone lesions in this area and are more likely to cause symptoms than metastases to the cranial vault.¹⁴⁴ Metastases to the skull base may result in one of several defined syndromes based on tumor location.^153,154 Anterior skull base lesions may cause orbital syndrome, which is manifested by orbital pain, exophthalmos (or less commonly, enophthalmos), decreased visual acuity, periorbital swelling, and external ophthalmoplegia. Middle skull base lesions may cause parasellar, middle fossa, or temporal bone syndromes. Parasellar (sphenocavernous) syndrome is manifested as ocular paresis, papilledema, and facial pain or numbness. Middle fossa (gasserian ganglion) syndrome is characterized by pain and numbness in the V2 and V3 distributions, pterygoid and masseter weakness, and possible abducens palsy. Temporal bone syndrome consists of hearing loss, otalgia, periauricular swelling, and facial weakness. Posterior skull base metastases may cause jugular foramen or occipital condyle syndromes. Jugular foramen syndrome is manifested by the involvement of various combinations of cranial nerves IX to XII and results in dysphagia, hoarseness, tongue atrophy, sternocleidomastoid/trapezius atrophy, and Horner’s syndrome. Occipital condyle syndrome affects cranial nerve XII and is characterized by tongue weakness and atrophy, occipital or nuchal pain, dysarthria, and dysphagia. In a patient with a known cancer diagnosis in whom cranial neuropathies or facial pain develops, a skull base metastasis must be suspected and investigated.^153,154

Lung, breast, renal, hepatic, and thyroid metastases are more typically associated with lytic bone destruction as seen on radiography and CT, whereas prostate cancer metastases are more commonly sclerotic.^{11,144,146,148,153,154} MRI demonstrates a hypointense lesion on T1-weighted images, with variable T2 signal characteristics and variable contrast enhancement.^147,153 The inclusion of diffusion-weighted imaging sequences improves the sensitivity for detecting nonprostatic (nonsclerotic) skull metastasis.¹⁵² Radionuclide bone scanning is a particularly sensitive method for detecting skull metastasis.^{143,144,146,153,155} Single-photon emission computed tomography is better than bone scintigraphy in helping to differentiate between malignant and inflammatory skull masses.¹⁵⁴ Examination of CSF may be particularly helpful in assessing a suspected metastasis to the skull base. If CSF is normal, metastasis is more likely than infection to be the cause of multiple cranial neuropathies.¹⁵⁴ A CSF study may also reveal the presence of meningeal carcinomatosis.¹⁵³ Typically, angiography is performed only if surgery is likely to be performed, the tumor is hypervascular, and preoperative embolization is required.¹⁵⁵

Patients with skull metastases are frequently at an advanced stage of their primary disease, and years may have elapsed since their original diagnosis.^{143,145,150,153,154} These lesions are often asymptomatic. Surgery may not be required for diagnostic or even therapeutic purposes.¹⁵⁵ Less frequently, a symptomatic or palpable skull mass may be the first sign of the underlying cancer.^144,145 In such cases, surgical resection may be helpful in establishing a tissue diagnosis, but fine-needle aspiration provides the diagnosis without surgical risk when the skull lesions are multiple or when a tumor is too small or too indolent to need resection.^144,155

Most skull metastases are asymptomatic and are often found during staging evaluation for the primary disease (Fig. 148-6).^142,143 Common symptoms that require treatment are pain, hemorrhage, skin ulceration, and intracranial growth that results in neurological deficits.^142,143,147 Hemorrhage from a skull metastasis may produce an epidural hematoma.^147,156 Involvement of a dural sinus may cause increased intracranial pressure by obstruction of venous outflow.¹⁴² Symptomatic patients may benefit from surgical resection as a palliative procedure.^145,147 Survival, although predicated on the status of the systemic disease, is usually of sufficient duration to justify surgical treatment of the skull metastasis.^143,155

FIGURE 148-6 Melanoma. Patients with melanoma metastatic to the skull often have synchronous intracerebral metastasis, and treatment varies according to the location of the disease and clinical findings, as well as with the need to treat any intracerebral tumors present. In a 28-year-old woman with both a symptomatic cerebellar tumor and a growing, tender frontal skull tumor, axial T2-weighted MRI revealed central necrosis, a purely epidural location, and disruption of both the inner and outer skull tables (A), whereas axial T1-weighted MRI revealed elevation of the dura and involvement of the overlying edge of the temporalis muscle (B). Because the cerebellar tumor required resection, it was excised at the same sitting. In a second case, a 67-year-old man with known melanoma underwent routine metastatic screening. C, Sagittal, contrast-enhanced MRI shows tumors on the caudate nucleus and in the posterior frontal lobe and a skull tumor overlying the torcular Herophili. D, MRI (axial, T2-weighted image) showing the tumor contained within the skull and adjacent to, but not compressing, the torcular. Here, stereotactic radiosurgery was used to treat all three tumors.

Resection of metastases in the cranial vault is generally straightforward. Adherence to intracranial structures, particularly to the dural sinuses, may make surgery more difficult, however. Although the overlying scalp is occasionally involved, it will usually peel away cleanly from the tumor, which typically respects the galea. This maneuver interrupts small feeding vessels crossing from the scalp to the tumor. Ideally, a circumferential trough is then drilled, through which a circumferential dural incision allows potentially involved dura to be removed as part of the specimen and eliminates the remaining vascular feeders. In this way an en bloc resection is achieved with a rim of normal bone surrounding the tumor.^142,148 The gradual, complete devascularization provided by this technique allows even the most vascular tumors (e.g., renal cell and thyroid carcinomas) to be removed with minimal blood loss and without embolization (Fig. 148-7). Such tumors should never be removed piecemeal or torrential blood loss may ensue. In addition, in keeping with basic neuro-oncologic principles, en bloc resection should theoretically decrease the rate of local recurrence.^142,148 Michael and associates described their surgical technique for resecting symptomatic calvarial metastases involving the dural sinuses (Fig. 148-8).¹⁴² Bur holes are placed on the sinus both in front of and behind the lesion. Additional bur holes are placed lateral to the lesion. As the tumor is resected from the sinus, the sinus is sutured closed. Resection of the involved sinus may be necessary and is acceptable if it is already occluded or if the tumor has invaded the anterior third of the superior sagittal sinus or a nondominant transverse sinus; preservation of the surrounding cortical veins is of paramount importance.¹⁴²

FIGURE 148-7 En bloc resection of a skull tumor with dural involvement. A metastatic tumor (see Fig. 151-8) was resected by sequential devascularization and detachment of the relevant anatomic layers to which it had attached. A, Planning the scalp incision. The elliptical area in the center of the lazy S is a scar from a previous biopsy site that was excised to eliminate any seeding by the tumor. It was positive for scattered foci of malignant cells. Most tumors metastatic to the skull do not breach the overlying galea, and peeling back the scalp results in the first phase of devascularization. B, The scalp is open, the dome of the tumor is visible, and the proposed craniectomy is marked to encompass the entire tumor plus margins. The width of the margin is least on the medial side to avoid sinus injury. C, A trough craniectomy has been drilled circumferentially around the tumor, and the dura is thereby exposed. D, The dura is cut within the circular channel shown in C, and the bone, tumor, and dura are removed as a unit. The bone edges are beveled to prepare for cranioplasty. E, A cadaveric dural allograft patch is placed. F, Cranioplasty with titanium mesh and methyl methacrylate. G, The tumor specimen with surrounding bone shows complete removal. H, Tumor specimen viewed tangentially showing an equal amount of intracranial and extracranial tumor.

FIGURE 148-8 Renal cell carcinoma. A 47-year-old woman with known renal cell carcinoma, free of disease for 4 years, noted skull swelling with a local headache. Biopsy was performed, but the operation was aborted because of profuse bleeding. A, The tumor continued to grow in the parasagittal location, and it had split the previous incision apart before being evaluated at our service. B, The scalp is reflected to show the outer surface of the intact tumor. C, Excised bone specimen (in two fragments because it straddled the superior sagittal sinus). The outer skull table is shown. D, Inner skull table showing large vascular channels honeycombing the tumor. Because a truly circumferential durotomy was not feasible here as a result of the tumor’s crossing the sagittal sinus, profuse bleeding occurred during resection. The patient lived for an additional 9 years after this operation before succumbing to diffusely metastatic disease.

Treatment of metastasis to the skull base is contingent on the location of the metastasis and the nature of the primary tumor.^153,154 Only a minority of patients with metastasis to the skull base are candidates for surgical resection.¹⁵⁴ When surgery is planned and the skull base tumor is thought to be particularly vascular (e.g., hepatic, renal, or thyroid carcinomas), some form of preoperative embolization may be useful.^151,155 However, typically, complete surgical resection is not feasible, and radiotherapy is the primary mode of treatment.^153,154 Primary radiotherapy has been used more frequently as more conformal high-dose irradiation has become available.^153,154

Solitary Plasmacytoma/Multiple Myeloma

Plasmacytoma is a solitary neoplasm of monoclonal plasma cells.^157–161 A benign lesion, plasmacytoma may progress to its disseminated form, multiple myeloma, a malignant and potentially fatal disease.^159,161 Plasmacytoma commonly affects patients in the late fifth decade, whereas multiple myeloma more frequently occurs in the late sixth decade.¹⁶² Although these lesions are more often found in the vertebral column, thoracic cage, and long bones, involvement of the cranial vault is not infrequent.¹⁶³ Less common is involvement of the skull base, which is a strong positive predictor for progression from solitary plasmacytoma to multiple myeloma. A comprehensive evaluation is indicated in this situation.^158,159,161

Plasmacytoma lesions may cause cranial nerve symptoms, orbital involvement symptoms, or symptoms of increased intracranial pressure.¹⁶¹ Lesions at the skull base may involve the cavernous sinus, petrous temporal bone, or sphenoid bone and thus are often accompanied by cranial neuropathies; abducens palsy with attendant diplopia is the most common.^{157,159,160,164,165} Additionally, cranial neuropathies may be caused by direct infiltration of the nerves with myelomatous cells.^163,166 Involvement of the orbit may result in exophthalmos or ophthalmoparesis.¹⁶¹ Intracranial extension of plasmacytoma may cause headaches or other symptoms of increased intracranial pressure.^{159,160,162,167} Intradural extension may give rise to seizures.¹⁶³

In gross appearance, plasmacytomas are typically smooth and lobulated but can cause irregular destruction of the involved bone.¹⁶⁰ Viewed histologically, plasmacytomas are made up of abnormal plasma cells that produce monoclonal immunoglobulins.¹⁶⁰ Immunologic staining typically demonstrates diffuse staining of monoclonal κ and λ light chains, which helps distinguish plasmacytoma from an inflammatory process. An excess of either type of light chain by a ratio of 16 : 1 or more strongly suggests the presence of plasmacytoma.^157,158,160

Plasmacytomas may be of low, intermediate, or high grade based on histologic findings. Low-grade tumors (plasmacytic) appear very similar to normal, mature-looking plasma cells.^158,161 High-grade tumors (plasmablastic) contain plasma cells with large vesicular nuclei, pale Golgi zones, prominent nucleoli, and a greatly elevated MIB-1 labeling index. Plasmablastic plasmacytomas may be associated with systemic multiple myeloma.^158,161

As seen on plain radiography and CT, multiple myeloma is characterized by well-defined lytic lesions involving the diploë and cortical bone, without a sclerotic border (Fig. 148-9).^{11,158,160,163,164,168} MRI is helpful for determining the presence of any associated extraosseous component, as well as for determining the presence of flow voids because these lesions can be quite vascular.^{11,160,163,168} Lesions typically appear isodense to hyperdense on CT, isointense to hyperintense on T1-weighted MRI, and markedly hypointense on T2-weighted MRI sequences.^162,163,168 Avid contrast enhancement on both CT and MRI is the norm.^{159,162,168,169} Plasmacytomas typically demonstrate restriction on diffusion-weighted images, whereas multiple myeloma will show increased diffusion.¹⁶³ It is essential to perform both CT and MRI because the former delineates the osseous involvement whereas the latter demonstrates soft tissue involvement of the meninges or brain parenchyma.¹⁶³ A “cold” lesion without tracer uptake is characteristic on radioisotope bone scanning¹⁶⁸; however, scintigraphy has a relatively high false-negative rate and is of limited clinical utility.¹¹ Angiography may demonstrate a tumor blush from ECA branch feeders.^163,168 A thorough evaluation to exclude multiple myeloma is necessary (particularly if the lesion is found at the skull base) and includes bone marrow evaluation, a skeletal survey, a bone scan, and serum and urine protein electrophoresis.^157,160

FIGURE 148-9 Plasmacytoma. An 82-year-old woman was evaluated for headache and a lytic lesion in the skull vault. Serum electrophoresis showed a monoclonal gammopathy, and a bone scan revealed multiple extracranial sites of osseous involvement. A, Skull radiograph (anteroposterior view) showing thickening of the skull on the left convexity. B, Axial contrast-enhanced CT showing a lenticular enhancing epidural mass reminiscent of epidural hematoma. C, CT (axial, bone window) showing spiculation of the inner skull table with a relatively intact outer table. D, Tangential view of a bone specimen demonstrating spiculation of the inner skull table. E, Excised specimen with a concordant radiograph exhibiting spiculation along the margins of the lytic lesion. F, Dura with tumor after separation from overlying bone showing that the tumor was entirely extradural.

Optimal treatment of solitary plasmacytomas is surgical resection followed by irradiation,^{157,159,161,163,167} although some have reported good results with surgical resection alone.¹⁷⁰ At surgery, these tumors are often found to be quite vascular, and significant blood loss should be anticipated. Preoperative embolization may be helpful.^157,168 Given that plasmacytoma is a radiosensitive lesion, patients with prohibitive medical comorbid conditions or solitary plasmacytoma lesions of the skull base may best be treated with radiotherapy alone after biopsy.^159,161,167 Bindal and coworkers found that patients who underwent resection of a solitary plasmacytoma followed by radiation therapy and in whom multiple myeloma did not develop in the postoperative period were unlikely to have multiple myeloma develop in the long term.¹⁵⁹ They did stress that skull base lesions were unlikely to represent a solitary plasmacytoma and that a thorough evaluation for multiple myeloma is therefore warranted in this setting.^159,161

Generally, skull lesions from multiple myeloma are not treated by surgical resection. Chemotherapy with C-VAD (cyclophosphamide, vincristine, Adriamycin, and dexamethasone), along with stem cell transplantation and palliative irradiation, forms the mainstay of treatment of multiple myeloma.^{157,158,160,163} Thus, skull base lesions are less likely to undergo surgical resection because a more morbid procedure is required and the patient is more likely to carry a diagnosis of systemic multiple myeloma, which has a median survival time of 3 years (range, several months to 10 years).^157,161,163

Lymphoma

Lymphoma in the cranial vault is rare.^171,172 Bone lesions occur in 7% to 25% of patients with lymphoma, but bone is the primary location in just 3% to 4% of patients.^173,174 Bone involvement often occurs late in the disease course.¹⁷⁵ When lymphoma is present in bone, the spine is the most common location. Calvarial involvement is uncommon, although somewhat less so in immunocompromised patients.^174,174 Cranial vault involvement by a true primary skull lymphoma is less common than a skull deposit from disseminated systemic lymphoma.^173,176,177 Therefore, if a solitary focus of lymphoma is found in the skull, a thorough evaluation for systemic disease is essential.¹⁷³

Typical initial symptoms of skull lymphoma include a painless palpable lump and symptoms of increased intracranial pressure from intracranial-to-extradural dissemination or bone destruction (Fig. 148-10).^171,174 Rare intradural extension may lead to seizures, focal neurological deficits, or altered mental status.^{174,175,177,178}

FIGURE 148-10 Lymphoma. A 68-year-old woman complained of generalized weakness and dizziness. A, A skull radiograph (lateral) shows multiple “punched-out” lytic lesions without a sclerotic border. B, Computed tomography (axial, bone window) shows several areas of osteolysis with relative preservation of the outer skull table. C, Magnetic resonance imaging (axial, T1-weighted, contrast-enhanced image) shows multiple contrast-enhancing lesions contained within the skull. The larger convexity tumor (arrow) was excised for diagnosis. D, The excised tumor had smooth edges, had eroded the outer skull table, and was filled with soft, pink-gray material that is easily removed by curettage. E, Bone scan showing multiple areas of activity in the spine and ribs and confirming the skull involvement.

Most lymphomas that involve the cranial vault are of the monoclonal B-cell type.^176,178 Histologic study of lymphomas shows diffuse growth of atypical lymphocytes.^171,172,176 Large immunoblastic cells with prominent central nuclei may be seen.¹⁷⁶ Tests for immune markers such as CD20 and CD79 may be positive,^171,172,175 and the MIB-1 labeling index may be elevated.¹⁷⁵

Cranial vault lymphomas usually have a significant soft tissue component with very little cortical bone destruction. Plain radiography and CT may demonstrate a lytic lesion,^173,175,179 but more typically, the tumor diffusely permeates the bone.^{171,172,174,176,178} On MRI, these tumors appear hypointense on T1-weighted and hyperintense on T2-weighted sequences and often exhibit homogeneous contrast enhancement.^171,174,179 MRI with contrast enhancement may also demonstrate meningeal involvement.¹⁷² Dural thickening may be noted beneath the calvarial lesion, but intradural invasion is rare.^{173,174,176,179} Skull lymphoma readily takes up tracer on scintigraphy studies.¹⁷⁴ The findings from angiography generally show these lesions to be relatively avascular.^171,177

Treatment involves systemic chemotherapy with an Adriamycin-containing regimen (cyclophosphamide, hydroxydaunomycin, Oncovin, prednisone [CHOP] protocol) and local radiotherapy.^{171,172,174,175,177} The 5-year survival rate is reported to be 40% to 60%.^172,174 Although some recommend surgically resecting the tumor before administering radiotherapy and chemotherapy, we do not.^171,174,176

Ewing’s Sarcoma

Ewing’s sarcoma is a highly malignant bone tumor that typically affects the pelvis and the long bones of the lower extremities in children and young adults.^180,181 It is the second most common malignant bone tumor in childhood (after osteosarcoma).¹⁸² Although primary involvement of the skull is rare,^181,182 metastases to the cranium are not infrequent.¹⁸⁰ Ewing’s sarcoma typically grows extradurally and often reaches a very large size before dural invasion or clinical detection, or both.^181,183 Symptoms tend to develop as a result of dural invasion, hydrocephalus, or raised intracranial pressure. Headaches and scalp swelling are the most common symptoms, and papilledema is the most common sign.^180,184 Males are affected more than females by a ratio of 1.8 : 1.^181,182 Approximately 90% of cases occur in the first 2 decades of life. The mean age in one series was 14.5 years, with the range being 18 months to 40 years.¹⁸¹

Ewing’s sarcoma can be considered an undifferentiated form of peripheral primitive neuroectodermal tumor (PNET).^34,183 Histologically, these tumors are characterized by sheets of small round blue cells with an increased nucleus-to-cytoplasm ratio.^{180,181,183,184} Pseudorosettes may be present, but sheets of cells are more characteristic.^181,185 Mitoses are common. Bony spicules may be present, and CD99 and vimentin may be expressed.^{180,181,183,184,186}

Plain radiographs of the skull may reveal layering of bone in an “onion peel” arrangement, with layers of bone mottling and erosion, as well as new bone formation.^34,180,181 This distinctive periosteal reaction and calcification may also be noted on CT.^182,183 In some cases, the tumor will simply be manifested as a lytic lesion on plain radiographs and CT.^181,182 MRI may show heterogeneous signal characteristics and avid contrast enhancement of any associated soft tissue component.^180,182,184 MRI is less essential than CT in the assessment of these tumors.^180,181,183 Ewing’s sarcoma exhibits increased radioisotope uptake in nuclear bone scanning images. Scintigraphy is particularly helpful in detecting the presence of any extracranial lesions.^181,182,187

Surgical resection plays an important role in the management of cranial Ewing’s sarcoma.^{181,182,184,186,188} The dura should be inspected for tumor infiltration, and if infiltration is noted, the dura should be resected as well.¹⁸¹ It is not uncommon for these patients to undergo fairly emergency surgery at the time of diagnosis because of the large size of the lesion and signs and symptoms of increased intracranial pressure.¹⁸³ Ewing’s sarcoma is often highly vascular, and the potential for excessive blood loss should be anticipated before surgery.^181,184 Local recurrence after resection has been reported.^181,184

Adjuvant therapy after resection, including radiotherapy and chemotherapy, is essential.^180,182 Adjunctive chemotherapy with a combination of vincristine, cyclophosphamide, cisplatin, etoposide, dactinomycin, and doxorubicin has raised the overall 5-year survival rate from 5% to 10% to 50% to 60%.^182,183

Although improved by treatment regimens, the prognosis for many patients with Ewing’s sarcoma continues to be poor because of early metastasis to the lungs and to other bones. This early metastasis is less common in cases of primary Ewing’s sarcoma, and thus primary Ewing’s skull tumors carry a better prognosis.^{180,182,184,188}

Neuroblastoma

Neuroblastoma is a malignant tumor that originates in the sympathetic nervous system and accounts for 10% of childhood malignancies, with 75% of them occurring in children younger than 4 years.^189,190 It is the second most common solid tumor in children and the most common in infants.¹⁹¹ At diagnosis, 65% of patients have disseminated disease, most commonly spreading to bone.¹⁹¹ Disseminated disease is typically manifested as fever and bone pain.¹⁹² Additionally, neuroblastoma is associated with a paraneoplastic syndrome of opsoclonus/myoclonus (“dancing eyes and feet syndrome”).^34,192

Neuroblastoma is the most common metastasis found in the skull in children, and detection of it there may precede diagnosis of the primary tumor.^193,194 The rate of metastasis to the skull in patients with neuroblastoma has been reported to be as high as 40%, and such tumors often diffusely involve the calvaria and skull base.¹⁹³ Skull metastases from neuroblastoma are usually multiple, with frequent involvement of the sphenoid and other bones forming the orbit.^189,195 Headache is the most common complaint, although many patients are asymptomatic.¹⁹³ These headaches frequently resolve after radiotherapy.¹⁹³ Metastases to the orbital bones and periorbital tissues may cause ecchymoses or “raccoon eyes,” which may be mistaken for a sign of traumatic skull base fracture.^190,192,195 With growth, the tumor deposit may invade the dura and cause signs and symptoms of increased intracranial pressure.¹¹

Cerebral neuroblastoma is a PNET that displays neuronal differentiation in the form of immunopositivity for synaptophysin and other neuronal markers.^34,194 Giemsa staining of histologic sections demonstrates sheets of neuroblasts (small round blue cells with large dark nuclei, small nucleoli, and little cytoplasm) and Homer Wright rosettes.^189,192,194 Molecular biology studies have demonstrated N-myc amplification in a third of these tumors.³⁴

Neuroblastoma is generally widely metastatic to the skull, with expansion of the bone, extension into the epidural space, and splaying of cranial sutures. Accordingly, the patient’s enlarging head may raise suspicion of hydrocephalus; however, subsequent imaging studies reveal normal brain and ventricle size.¹⁹⁶

Plain radiography and CT demonstrate a destructive mass growing inward from the skull along with bone spicules radiating outward in a classic “sunburst” appearance and elevation of the periosteum.^{189,194,195,197} In children, neuroblastoma often seems to metastasize directly to the cranial sutures with resultant suture diastasis. This may occur because of the increased vascularity of these sutures in children.^11,189 On MRI, neuroblastoma metastases appear as masses within the calvaria that have the intensity of soft tissue and show contrast enhancement.^194,197 Bone scintigraphy demonstrates increased uptake of radioisotope by the lesion.^190,194,195

Neuroblastomas are very radiosensitive and chemosensitive and are treated with a combination of radiotherapy and chemotherapy, with surgery generally being unwarranted.^189,193 Reports on relapse have suggested that more aggressive management is necessary in the setting of skull metastases.¹⁹¹ However, cranial irradiation is problematic in this young patient population.¹⁹³ Recently, Wolden and colleagues described encouraging results with the use of “brain-sparing radiation therapy” in such patients.¹⁹³ Because relapse remains common despite multimodality treatment, the 5-year survival rate is 10% to 30% in children older than 1 year and 55% in infants younger than 1 year.¹⁹¹

Paget’s Disease of Bone (Osteitis Deformans)

Paget’s disease of bone is a disorder characterized by the uncoupling of bone formation and resorption, with resultant bone thickening and weakening.^198–201 This excessive and abnormal bone remodeling is of unknown origin but is hypothesized to be caused by a slow virus infection.^198,202 The disease affects 3% of persons older than 40 years and 10% of persons older than 85 years.^202–204 Paget’s disease is 1.5 times more common in men than women.²⁰⁴ Alkaline phosphatase and hydroxyproline levels are elevated.^201,205,206

The skull is the second most common location after the pelvis for this disease and is involved in 65% to 70% of cases.²⁰⁴ Most commonly, patients are asymptomatic or complain of localized bone pain. As the disease progresses, the headaches that it produces can become more constant, generalized, and severe.^207,208 Involvement of the skull base by Paget’s disease can cause cranial neuropathy.^199,203,204 Mixed low-frequency conductive and high-frequency sensorineural hearing loss is a common finding when the temporal bone is included in the affected area.^198,207,209 Involvement of the sphenoid bone was thought to have caused endocrinopathy in one case.²¹⁰

With cranial vault involvement, the skull becomes quite spongiose and thickened.^{11,201,202,208} Despite its increasing size, the skull is actually weakened.^1,199,201 If the skull base is involved, it may settle and result in platybasia or basilar invagination in a third of cases (Fig. 148-11).^{199,202,203,209,211} Because the skull in patients with Paget’s disease is both more fragile and more vascular than normal bone, patients with Paget’s disease are more prone to develop an epidural hematoma should they experience head trauma. This may occur even without an associated fracture.^199,201

FIGURE 148-11 Paget’s disease. A 57-year-old man was evaluated for headaches and a markedly elevated alkaline phosphatase level. The pathologic results from a biopsy were consistent with the osteoblastic phase of Paget’s disease. He was treated initially with bisphosphonates, which partially relieved the pain. A, A lateral skull radiograph shows a mix of a “cotton wool” appearance (denoting an intermediate phase between osteolysis and sclerosis) and a markedly sclerotic skull vault overall. Basilar invagination is also evident. B, CT (axial, bone window) showing incomplete preservation of marrow, with sclerosis affecting the inner skull table in particular. C, CT (axial, contrast enhanced) showing diffuse compression of the brain because of skull thickening and reduction of intracranial volume. Hydrocephalus is present, probably from impaired venous outflow, and had led to venous hypertension. D, CT (axial, bone window) through the posterior fossa demonstrating the degree of invagination of the dens/C1 complex into the foramen magnum. This may also have contributed to the hydrocephalus.

Paget’s disease has three phases: (1) the “destructive,” “vascular,” or “osteolytic” phase, marked by resorption of bone, which is replaced by fibrous connective tissue and vascular channels; (2) the “mixed” osteoclastic/osteoblastic or “reparative” phase as the bone begins to smooth over but remains somewhat disrupted by vascular channels; and (3) the “quiescent,” “sclerotic,” or “osteoblastic” phase, wherein distinction between the cortex and the diploë is lost.^198,204,208

As seen histologically, in the early phases, large quantities of new bone form in a loose, vascular, connective marrow.^1,204 Later, simultaneous osteoblastic and osteoclastic activity may be seen.¹ A mosaic of lamellar bone of various stages is the result.²¹²

Imaging characteristics correspond to the aforementioned three phases. As seen on plain radiography and CT, lesions can appear to be lytic, sclerotic, or mixed. The initial appearance of the lesion on plain radiographs and CT is radiolucent. As the disease progresses and bone condenses, areas of sclerosis mix with the preexisting lytic areas, and a mottled “cotton wool” appearance develops.^199,206,209 With disease progression, the inner table becomes thicker than the destroyed outer table of cortical bone, and the diploë expands.^202,204 Paget’s lesions show mixed intensity on MRI. In the active phase of the disease, vascular channels are present. As the disease progresses, the distinction between cortical bone and marrow is blurred.^204,204 Paget’s disease is detected earlier by bone scintigraphy than by plain radiography or CT.²⁰⁷

Radiologic differentiation between Paget’s disease and fibrous dysplasia can be challenging. Paget’s disease is often symmetrical, whereas fibrous dysplasia tends to be unilateral, even in polyostotic cases. Paget’s disease is accompanied by thickening of the inner cortical table, whereas fibrous dysplasia may show cortical destruction. Additionally, Paget’s disease does not display the “ground glass” appearance on CT that distinguishes fibrous dysplasia. Finally, fibrous dysplasia much more commonly involves the orbit, the paranasal sinuses, and the sphenoid bone than Paget’s disease does.²⁰⁴ With respect to epidemiology, the population affected by Paget’s disease is older than that affected by fibrous dysplasia.²⁰⁴

Medical treatment with bisphosphonates or calcitonin is the first line of treatment of Paget’s disease.^207,210 Subjective symptoms of headache, tinnitus, and vertigo typically improve in response to medical management, but objective audiometric response does not.²⁰⁷ In the rare case in which surgery is indicated, the possibility of significant hemorrhage must be anticipated.^199,201

In 10% to 22% of patients, Paget’s disease of the skull will eventually undergo sarcomatous degeneration, although this figure may be much lower in asymptomatic patients with minimal disease.^{10,205,206,209,211} The most common types of sarcomatous degeneration are to osteosarcoma (50% to 60% of instances) and fibrosarcoma (20% to 25% of instances).^10,206 In other cases, Paget’s disease may progress to form a giant cell tumor. Alkaline phosphatase levels should be obtained to monitor for disease progression or recurrence.^201,205,208 Development of a soft tissue mass should raise suspicion for sarcomatous degeneration; a simple needle biopsy should then be performed.²⁰⁶ The prognosis for an osteosarcoma arising from a Paget lesion is worse than that for an osteosarcoma arising de novo.²⁰⁷

Langerhans Cell Histiocytosis (Histiocytosis X)

Langerhans cell histiocytosis (LCH) refers to a group of related disorders of abnormal uncontrolled histiocyte proliferation: eosinophilic granuloma, Hand-Schüller-Christian disease, Abt-Letterer-Siwe disease, and Hashimoto-Pritzker disease.^2,213 Although adult cases have been reported,²¹⁴ LCH predominantly occurs in children and adolescents, with the mean age at incidence being 12 years.^3,213 Manifestations of LCH are diverse, and many organs may be affected, including bone (involved in 80% to 95% of cases), lung (the most common nonosseous site), liver, skin, hypothalamus, posterior pituitary, and the lymphatic system.^3,4,215

The clinical manifestation of LCH is contingent on the location and extent of proliferation of the pathologic Langerhans cells.² The most common and simplest form of LCH is a solitary lytic lesion of bone designated eosinophilic granuloma, which accounts for 60% to 80% of cases. The skull is the most commonly involved bone.^{4–6,213,215} Patients with such solitary lesions usually exhibit localized bone pain or a palpable mass.^3,6,215 Patients with disseminated disease may have skin lesions, diabetes insipidus, or lymphadenopathy.^3,214 Lesions at the skull base have been reported to cause cranial neuropathies.^5,216

The cause of LCH is unknown.^1,213 It is unclear whether LCH is merely a reactive overproliferation of otherwise normal cells or whether the Langerhans cells are abnormal and represent either a benign or malignant neoplastic process.^3,215 One theory holds that it is a reactive proliferation of polyclonal cells, which suggests a disorder of immune regulation.^5,216 Some specimens, however, demonstrate monoclonal proliferation, which suggests that LCH may in fact be a neoplastic process.³ There is also recent speculation that LCH may be initiated by Epstein-Barr virus.²

Histologically, LCH is marked by a clonal proliferation of S-100–positive histiocytic cells in clusters mixed with inflammatory cells, which are predominantly eosinophils.^1–6 CD1a antigen staining is important for diagnosis.^3,5 Electron microscopic images reveal the presence of racquet-shaped Birbeck’s granules.^2,3,215

The skull lesions in LCH classically have a “punched-out” lytic appearance without a sclerotic border.^2,4,5,216 The bony destruction often affects the outer table more than the inner table, thus giving the skull a “beveled” appearance.^4,11 After treatment, the bony lesions may resolve completely or may maintain a sclerotic appearance.^11,214,216 LCH skull lesions often have an associated extraosseous contrast-enhancing soft tissue mass.^4,11,216 MRI may be helpful in determining the amount of intracranial extension of the soft tissue masses, which appear hyperintense on T2 sequences and are of variable intensity on T1 sequences.^5,216 Increased radioisotope uptake is noted when bone scintigraphy is performed.^5,214

Treatment of LCH may involve surgery, radiation therapy, chemotherapy, or immunotherapy (or any combination of these modalities), depending on whether systemic involvement is present.^11,214–216 Single bone lesions may best be treated by surgical resection.^4,6 Other researchers have reported success with local injection of corticosteroids followed by radiotherapy.²¹⁶

The prognosis of patients with LCH is poorly understood. Spontaneous regression, recurrence, and more aggressive disease courses have all been described.^5,214,216 Usually, the prognosis is excellent in patients with localized disease.^4,215,216 Recurrences are more likely in the systemic forms of the disease and in children.^3,215,216 These recurrences may be more likely to involve the hypothalamic-pituitary axis, with resultant diabetes insipidus.²¹⁶

Fibrous Dysplasia

Fibrous dysplasia is a fibro-osseous lesion of unclear etiology wherein normal bone is replaced by abnormal fibrous tissue and immature bone.^1,105,217 First recognized by von Recklinghausen in 1891 and further characterized and named by Lichtenstein in 1938, it is one of the most common benign skeletal disorders and can affect any bone in the body. Usually, only one side of the body is affected.^217–220 It is most common in adolescents and young adults, and progression tends to abate after puberty.^1,218,221 Sarcomatous degeneration occurs in less than 1% of patients and is more common when the patient has previously undergone radiation therapy.¹⁰⁵

There are three types of fibrous dysplasia: monostotic (the most common, accounting for 70% of cases),²¹⁷ polyostotic, and McCune-Albright syndrome.^1,104,217 McCune-Albright syndrome is characterized by polyostotic fibrous dysplasia, endocrine hyperfunction (which can lead to precocious puberty in female patients), café au lait pigmentation of the skin, and other extraskeletal abnormalities.^1,217,220 Although fibrous dysplasia alone has no sex predilection, McCune-Albright syndrome is more common in females.^104,217,220

Fibrous dysplasia has a predilection for the skull base, particularly the frontal, sphenoid, and ethmoid bones at the frontal base and orbits.^217,218,220 Consequently, patients with fibrous dysplasia may exhibit local cosmetic deformity (the most common manifestation), headaches, proptosis, impaired ocular movement, and loss of visual acuity.^{105,217,218,220,221} When the cranial vault is involved, growth tends to be outward, thereby causing cosmetic deformity.²²⁰

Histologically, the lesion is characterized by arrest of bone maturation.^11,217 The lesions consist of thin trabeculae of immature bone mixed with a fibrous stroma, which gives the appearance of “woven bone.”^{1,105,217,219,220} The degree of activity of the lesion affects its microscopic features, and in very active lesions, mitoses may be seen.²²⁰

Radiologically, the sclerotic form of fibrous dysplasia has a very distinct appearance, with bone expansion and a homogeneous radiodensity on CT; the diagnosis can often be made on the basis of this appearance alone.^{1,11,104,105,219} However, hyperostosing sphenoid wing meningiomas can have a very similar appearance. The pagetoid (mixed) subtype is more common in older patients with long-standing symptoms and exhibits bone expansion and alternating areas of radiodensity and radiolucency in a “ground glass” pattern.^{11,104,105,219} It is this “ground glass” appearance that most readily distinguishes fibrous dysplasia from Paget’s disease.²⁰⁴ The cyst-like subtype is the least common and demonstrates a lucent lesion with sclerotic borders.^{11,105,217,218} MRI tends to show mixed signal intensity on all sequences, depending on the amount of mineralization, and the addition of gadolinium contrast produces variable amounts of enhancement.^11,104,219 The sometimes avid enhancement of these lesions seen on MRI can cause them to be mistaken for neoplastic disease.^104,219

Involvement of the orbit leading to visual loss is the most feared complication, and surgical decompression may be warranted in acutely or progressively symptomatic patients (or in both).^105,217,221 Prophylactic optic nerve decompression in asymptomatic patients is not recommended because of the risk for visual compromise from unroofing the optic canal.²¹⁷ Radiotherapy and chemotherapy have no role in the treatment of fibrous dysplasia, and the former may increase the risk for malignant degeneration.^218,220

Given the tendency of these benign lesions for slow growth and eventual abatement and their common location at the skull base, the decision to proceed with surgery must be made on a case-by-case basis. In one report, the mean duration of disease progression was 9.8 years and the mean age at arrest of progression was 19.2 years, although the standard deviation in this series was quite large.²¹⁸ Progression of disease is more rapid with the polyostotic type, whereas malignant degeneration is more common with the monostotic type.²²⁰ Many patients can be managed medically with bisphosphonates, which reduce bone turnover and decrease pain.⁹⁹ When patients are acutely or progressively symptomatic and surgical resection can be performed safely, it remains the best therapeutic option.^{217,218,220,221} However, considerable hemorrhage can complicate surgery for fibrous dysplasia.¹⁰⁴

Malignant degeneration occurs in 4% of cases of fibrous dysplasia and is more common with the monostotic type.²²⁰ The interval between the diagnosis of fibrous dysplasia and evidence of sarcomatous degeneration is long, with a mean of 15 years.^104,220 Close imaging follow-up with serial CT and MRI is essential in patients with known fibrous dysplasia.¹⁰⁴ Worsening pain, development of a soft tissue mass, or elevation of alkaline phosphatase levels should raise concern for malignant degeneration.^104,105 Surgical intervention is usually necessary in this situation.¹⁰⁴

Hyperostosis Frontalis Interna

Hyperostosis frontalis interna (HFI) is a disorder characterized by progressive thickening of the inner table of frontal bone of the skull.^222–225 These enostoses are typically less than 1 cm thick, although more severe cases have been reported.²²³ Such hyperostosis is present in 5% to 12% of the elderly European and American population but is much more common in women, particularly those who are obese.^{222,223,225–227} The hyperostosis is almost always bilateral, but unilateral cases have been reported.²²⁵

HFI is usually an incidental finding, although some patients may complain of headaches (which may, of course, be coincidental); it has also been reported as a cause of cognitive impairment in patients with particularly exuberant disease that compresses the frontal lobes.^222,225,227

This condition was first described in 1765 by Morgagni, who noted an association among thickening of the frontal bone, obesity, and virility in elderly women.^224,225,227 The combination of these symptoms and mental disturbance is known as Morgagni-Stewart-Morel syndrome.²²³ Associations with a variety of other conditions have been reported, including diabetes insipidus, acromegaly, thyroid disorders, headaches, seizures, pregnancy, and hypogonadism, but clear causation has not been established.^223,225,226 The cause of HFI is unclear, but hormonal factors are suspected on the basis of these associations.^223,226,227 In particular, patients with acromegaly have diffusely thickened skulls with characteristic frontal bossing, and thickening at the skull base can narrow the foramina and cause encroachment on cranial nerves.

The fundamental process of HFI is thought to be deposition of new bone on the inner table of the frontal bone, with subsequent expansion of the diploë. Findings on histologic examination are consistent with this hypothesis. Grossly, the thickening of the skull is predominantly in the diploë.²²⁵ As viewed microscopically, the diploë consists of spongiose new bone.²²⁵ CT and MRI demonstrate bilateral smooth lobulated thickened enostoses of the inner table displacing the frontal dura.^223,224,226

Most frequently, HFI is an incidental finding and does not require treatment.²²³ Surgery to remove the thickened bone has been attempted in symptomatic patients. The effectiveness of surgical intervention for symptoms or associated conditions is unclear. The dura is not typically adherent to the skull at surgery.²²⁵

Sinus Pericranii

First reported by Percival Pott in 1760 and named by Stromeyer in 1850, sinus pericranii is an abnormal collection of veins adherent to the outer table of the skull in communication with the intracranial venous sinuses via dilated diploic and emissary veins of the skull.^228–231 The causes of this unusual venous abnormality are congenital, spontaneous (although these are sometimes thought to be congenital lesions with late diagnosis), and traumatic.^{228,229,231,232} Traumatic cases are thought to be caused by a tear in the venous sinus.²²⁸ The lesion is most commonly located in the midline, although laterally located cases have been reported.^{229,232–234} Location on the anterior midline with drainage into the superior sagittal sinus is the most common scenario.^228,231,233 Skin overlying the lesion may be hairless and tinged blue.²³¹ Thrombosis within the outer venous nodule has been reported.²³⁰ The lesion is nonpulsatile, expands with a Valsalva maneuver or while the patient is supine, and decreases with head elevation or direct compression.^{228,230,231,234} Although patients are typically asymptomatic, vertigo and local pain have been reported.^230,235

A number of associations with sinus pericranii have been described, including vascular malformations, blue rubber nevus syndrome, cavernous hemangioma, capillary telangiectasia, and aneurysm of the internal cerebral vein.^229,231,232 Sinus pericranii primarily affects children and adolescents and is rare in adults.^229,233

On microscopic tissue examination, a tangle of nonmuscular venous vessels is seen.²³² Histologically, the congenital type of sinus pericranii is lined with a single layer of flattened endothelial cells, whereas the traumatic type is lined with connective tissue.^231,232,235

Plain radiographs demonstrate a radiolucent area corresponding to the skull defect.^229,231,232 CT may demonstrate an extraosseous soft tissue mass, as well as an emissary channel through the skull, with smooth erosion of the bone’s outer table.^{11,229,230,232,233} Contrast-enhanced CT will show venous filling.^230,231 MRI characteristics are suggestive of the presence of fluid: hypointense appearance on T1, hyperintense on T2, and possible flow voids.^231,233 Ultrasonography reveals compressible, hypoechoic tubular structures beneath the scalp.²²⁸ Angiography may show a blush of ECA branch arterial feeders or late venous pooling, but frequently no abnormality is noted.^{11,230,232,236} CT venography and magnetic resonance venography are now used more commonly than angiography for diagnosis.^228,230 Direct injection of a contrast agent into the extracranial lesion followed by a plain radiograph of the skull is sometimes performed.^229,233,234

Slow lesion progression is the norm, although spontaneous regression has been reported.^230,232 When the disease is progressive or symptomatic, or both, treatment in the form of surgical resection may be indicated.²³⁰ Surgery may also be performed for cosmesis. Some recommend surgery as prophylaxis against epidural hemorrhage or air embolism, although there are no published reports of such events occurring.^231,232

There are two principal methods of surgical resection in this disease. The more conservative measure involves simple resection of the extracranial component, with bone wax used to occlude the emissary channel. Alternatively, a full craniectomy to remove the emissary channel may be performed.^231,232 Surgery may be complicated by considerable intraoperative hemorrhage, and blood products should be available before commencing the procedure.^231,233,235 Raising the head during surgery may stem the venous flow, but this must be balanced against the risk for air embolism.²³³ Slow and careful removal of adjacent bone with a diamond drill rather than craniectomy to resect the intradiploic channels has been reported to decrease intraoperative bleeding.²³⁵ Frequently, the bleeding can be controlled simply with bipolar coagulation and bone wax.²³³ Recurrence distant from the site of resection has been reported.²²⁹

Cephalohematoma

Cephalohematoma is a subperiosteal blood collection in newborns that is most commonly caused by shearing forces during traumatic delivery.^{197,237–239} Risk factors include the use of instrumentation at delivery and fetal scalp monitors and increased birth weight.^240,241 Cephalohematomas are found in 0.2% to 3% of newborns and usually resorb within 1 month.^237,239 If they do not resorb, they may calcify.^197,238,240 Cephalohematomas are generally parietal in location and do not cross suture lines.^237,242

Although most commonly associated with birth delivery, some cases of cephalohematoma are idiopathic. Additionally, Ghali and colleagues noted the late development of cephalohematomas in about 15% of patients undergoing cranial vault remodeling.²⁴² Calcification of the cephalohematoma may result in significant cosmetic deformity and asymmetry.^240,241 Additionally, the cephalohematoma may become a nidus of infection, with an accompanying risk for osteomyelitis or sepsis.^237,238

A cephalohematoma generally consists of inner and outer layers of bone.²³⁷ On plain radiographs it appears as an expansile lesion with an opaque rim.^237,238,241 CT is used most commonly for evaluation of these lesions and demonstrates a homogeneous low-density core consistent with old blood, as well as an extra outer convex band of ossification that gives the appearance of a “double skull.”^237,239 The inner rim of the cephalohematoma may be either convex or concave in orientation with respect to the skull.²³⁷ Although not often performed for evaluation of cephalohematoma, MRI demonstrates increased signal on both T1 and T2 sequences.^237,241

Cephalohematoma can be distinguished from simple caput succedaneum (which represents scalp edema) in that the latter crosses suture lines, whereas cephalohematoma does not.^197,238,239

Resorption of cephalohematomas begins after 1 week, and most will resolve within 1 month.^237,240 Thus, a period of observation is generally advocated during this interval.^238,240 As early as 1908, Cushing noted the prudence of waiting 2 weeks before operating on a cephalohematoma.²⁴¹ If the cephalohematoma persists at 1 month but has not calcified, aspiration of the collection is a treatment option.^237,238,240 Petersen and coauthors reported good results with helmet molding for two patients (3 and 4 months old) who had partially calcified cephalohematomas.²⁴⁰ Similarly, Kaufman and associates noted that simple head wrapping may have some utility.²⁴¹ However, calcification of a cephalohematoma generally requires surgical correction, particularly if it becomes evident several months after delivery.²³⁷

Historically, surgical treatment of these lesions has involved simply resecting the outer table of the ossified hematoma.²⁴⁰ However, Wong and colleagues classified two distinct entities of cephalohematoma that require different surgical management, depending on the orientation of the inner lamella.²³⁷ Type I cephalohematomas involve an extracranially bowed inner lamella. In this case, only the outer lamella needs to be resected; the inner lamella is then smoothed with a bur drill bit, and no intracranial work is performed. Type II cephalohematomas are characterized by an intracranially protruding inner lamella. In this situation, craniectomy and cranioplasty are required to restore the normal cranial contour.

Leptomeningeal Cyst

Growing skull fractures (leptomeningeal cysts) are a rare complication of head trauma marked by a skull defect with an underlying dural tear.²⁴³ Seventy-five percent of leptomeningeal cysts occur in children younger than 1 year, and 90% occur before 3 years of age.^243–246 The tear in the dura allows the leptomeningeal cyst to herniate through and progressively enlarge the skull defect.^243,247 The lesion may be associated with an underlying contusive brain injury and gliosis, which may lead to the formation of a porencephalic cavity if left untreated.^{243,244,248,249} The frontoparietal region of the vault is the most common location for these cysts, but any part of the skull, including the base, may be involved.^{243,246,248,250}

Patients are often initially seen with a palpable scalp mass.^245,248,250 Headaches, seizures, developmental delay, and hemiparesis are also reported.^{245,246,248,249} Orbital involvement may result in diplopia, proptosis, or ophthalmoparesis.^245,248 The typical duration from injury to evaluation is less than 3 years, although longer intervals have been reported.^246,247,250 Rarely, leptomeningeal cysts are detected in adults.²⁴⁹

Plain radiographs reveal the defect and usually hypertrophy and sclerosis of the bone edges.^243,248,249 CT, ultrasonography, and MRI may all be helpful in evaluation of the lesion.^{243,245,248,250} CT demonstrates an expansile lesion of the diploë with disruption of the inner table and preservation of the outer table of the skull.^249,250 MRI best demonstrates the cystic nature of the lesion.^246,250 MRI may be particularly helpful in determining the presence of any gliotic or herniated brain tissue adjacent to or within the defect, a not uncommon phenomenon.^243,245,248

Leptomeningeal cysts are often managed conservatively initially. However, spontaneous resolution is rare, progression is common, and thus surgical intervention is almost always warranted.^244,245 Duraplasty plus craniectomy with cranioplasty is typically sufficient treatment.^{243,245,248,250} The goals of surgery are to excise the cyst, resect gliotic brain tissue, and repair the dura. Meticulous dural closure is essential.^243,245,250 When planning the craniotomy, it is important to recognize that the dural tear may extend well beyond the fracture line.^243,244 The dural tear may extend until it reaches a dural sinus, involvement of which can make the operation considerably more challenging.²⁴³

Young children and infants in whom a linear skull fracture is diagnosed after trauma require close follow-up to rule out the subsequent development of a growing skull fracture.²⁴⁹