Fibrous dysplasia
Fibrous dysplasia represents 2.5% of all osseous and 7% of all benign osseous neoplasms [7]. Fibrous dysplasia results from abnormal differentiation and maturation of osteoblasts with progressive replacement of the normal bone by immature woven bone [1, 2, 5, 8, 9]. It is most commonly seen in adolescents and young adults and can be monostotic (70% of cases) or polyostotic (30% of cases) with the skull being involved in both forms of disease [1, 2, 4, 8, 9]. The monostotic form is the mildest and most common form; it involves the ribs and craniofacial bones, and is typically diagnosed between 20 and 30 years of age [1, 2, 8, 9]. The polyostotic form has an earlier onset, typically in childhood and affected patients tend to have more severe skeletal and craniofacial involvement; it may also be associated with McCune-Albright and Mazabraud syndromes [1, 2, 9]. Fibrous dysplasia preferentially affects the frontal and temporal bones and may cross sutures [2]. The diagnosis is often incidental, but may present as an enlarging mass with symptoms resulting from mass effect and narrowing of a foramen transmitting one of the cranial nerves [1,2,3,4, 8, 9]. Malignant transformation is very rare and has been reported in 0.4–1% of cases [2]. An associated aneurysmal bone cyst or pathological fracture may complicate this entity [2].
CT demonstrates an intradiploic, expansile lesion with the characteristic “ground-glass matrix” in all or part of the lesion (Fig. 2) [1,2,3,4,5,6,7,8,9]. The outer table is more prominently affected compared to the inner table [1, 2, 4]. Three patterns have been described: mixed lytic and sclerotic, homogeneously sclerotic and a predominantly cystic or lytic pattern; but the homogeneously sclerotic (ground-glass density) pattern is usually seen [1, 2, 4, 6]. Fibrous dysplasia can have varying signal and contrast enhancement on MRI depending on the ratio of fibrous tissue to mineralised matrix [1,2,3,4,5,6,7,8,9]. The lesion is typically low signal on T1- and T2-weighted images given that the homogeneously sclerotic form is most common (Fig. 2) [1,2,3,4,5,6,7,8,9]. Lesions with highly mineralised stroma tend to show lower signal intensities on T1- and T2-weighted images, whereas lesions with high fibrous tissue tend to have intermediate signal intensity on T1-weighted images and high signal on T2-weighted images [1, 2, 6, 8, 9]. It can be useful to get a CT if MRI findings are equivocal.
Treatment is based on bisphosphonates. Surgical decompression is performed when there is severe mass effect [2].
Osteoma
Osteoma is the most frequent benign tumour in adults and is most commonly seen in men between the fourth and fifth decades of life [1, 2]. It is a juxta-cortical tumour made up of well-differentiated compact or cancellous bone [1, 2, 4,5,6]. Osteomas usually arise from the outer table and rarely from the inner table and can be sessile or pedunculated [1, 2, 4,5,6]. Inner table osteomas can be misdiagnosed as ossified meningiomas; however, unlike meningioma, osteomas do not have a soft tissue component and do not enhance [4, 6].
On CT, an osteoma is a juxta-cortical, well-defined, sclerotic, homogenous lesion [1, 2, 4,5,6]. On MRI, it has homogenous low signal on T1-weighted images, but variable appearance on T2-weighted imaging, depending on the amount of compact and cancellous/trabecular bone [1, 2, 4,5,6] (Fig. 3). When multiple osteomas are seen in the skull, Gardner syndrome should be considered, a disorder characterised by multiple osteomas, colonic polyposis, sebaceous cysts and various benign tumours such as lipomas and fibromas [1, 2] (Fig. 4).
Osteomas do not require treatment unless they cause mass effect and disturb surrounding structures [1, 2].
Langerhans cell histiocytosis
Langerhans cell histiocytosis (LCH), formerly known as “histiocytosis X” is due to an idiopathic proliferation of Langerhans cells in various tissues (bone marrow, central nervous system, lung, liver, spleen, lymph nodes) causing focal or systemic disease [1, 2, 10, 11]. This disease is most common in children between 6 and 10 years of age and can occasionally be seen in young adults [1, 2, 4, 6, 10]. Langerhans cell histiocytosis comprises three clinical syndromes: (1) eosinophilic granuloma, which is limited to bone or lung; (2) Hand-Schuller-Christian disease, which presents with calvarial lesions, exophthalmos and diabetes insipidus; (3) Letterer-Siwe disease, the most aggressive form of LCH with multi-visceral organ involvement [1, 2, 10, 11]. The most frequent form of LCH is eosinophilic granuloma in which the calvarium is frequently involved [1, 2, 6]. Lesions more frequently occur in the parietal or frontal regions [2, 6]. Clinically, the lesions can be asymptomatic or present as palpable and/or tender masses [1, 2, 4, 6, 10].
On radiographs, there may be one or multiple well-defined punched-out osteolytic lesions [1, 2, 4, 6].
On CT, the early appearance of LCH is an osteolytic lesion with bevelled edges due to unequal involvement of the inner and outer tables (Fig. 5) [1, 2, 4,5,6, 10]. The centre of the lesion may contain a “button sequestrum”, a central residual intact bone [1, 2, 6, 10]. They lack a sclerotic rim or periosteal reaction [1, 2]. Multiple lytic lesions may coalesce giving the appearance of a geographic map [2]. They can also have a soft tissue component and may have extradural and extracranial extension [1, 2, 5, 6]. Later on, healing lesions, whether spontaneous or under treatment, become sclerotic with centripetal bone formation and disappearance of the osteolytic lesions [2, 6].
MRI may aid in the depiction of bone marrow or soft tissue involvement, but the signal intensity of these lesions is non-specific; however, extensive bone marrow oedema is typically present [10, 12]. Most frequently, LCH has low to intermediate signal on T1-weighted images and high signal on T2-weighted images, except in the healing phase when the signal is low on T2 imaging [6]. Eosinophilic granuloma enhances strongly with gadolinium and often has reactive dural or galeal enhancement [1, 2, 5, 6].
Treatment varies depending on the severity and bony extent. Single lesions can be treated with surveillance or systemic corticosteroids. In the more aggressive forms of disease, surgical excision, radiotherapy and chemotherapy are treatment options [2].
Osseous venous vascular malformation
The International Society for the Study of Vascular Anomalies (ISSVA) classification system divides vascular anomalies into two primary biological categories: vascular neoplasms and vascular malformations [13,14,15]. Vascular malformations include low-flow malformations (capillary, venous, and lymphatic), high-flow malformations (arterial malformation, arteriovenous malformation and arteriovenous fistula) and combined malformations (i.e. venolymphatic malformation). The previously called cavernous haemangiomas are actually venous malformations [13,14,15]. Osseous venous malformations are benign slow-growing vascular bone tumours that account for 2–10% of benign calvarial lesions and 0.2% of all bone neoplasms [1, 2, 16,17,18]. They affect the frontal and parietal bones predominantly and are more common during the 4th and 5th decades of life [1, 2, 6, 16,17,18]. Fifteen percent of skull venous malformations are multiple [18]. These lesions are more frequent in women than men with a ratio of 3:2 [2, 6, 16,17,18]. Calvarial venous malformations arise from vessels in the diploic space and are supplied by branches of the external carotid artery, with the middle meningeal and superficial temporal arteries being the main sources [14]. Most of these vascular tumours in the skull contain dilated blood vessels separated by fibrous septa [2, 16, 17]. Usually they are small and asymptomatic, but they can cause pain or present as a palpable deformity [1, 2, 6]. Calvarial venous malformations affecting the roof of the orbit can cause proptosis and even blindness; and those located in the petrous bone may present with deafness or cranial nerve palsies [2, 13,14,15]. Growth of these neoplasms occurs by expansion of the outer table. Rarely, they can have intracranial extension with few cases reported of erosion of the inner table and dura mater presenting as subdural haemorrhage [16, 17].
On plain radiographs, this vascular tumour presents as an osteolytic lesion with the characteristic “sunburst” or “honeycomb” trabecular pattern, which is due to thickened trabeculae adjacent to the angiomatous channels [1, 2, 4, 16,17,18]. CT shows a well-circumscribed intradiploic osteolytic lesion with mild expansion of the outer table and relative sparing of the inner table. A sunburst pattern of trabecular thickening radiating from a common centre is the classic finding [2, 4, 16,17,18]. On MRI, the serpentine vascular channels can be identified and the appearance depends on the fat content and vascularity of the lesions. They are characteristically isointense to hyperintense on T1-weighted images and hyperintense on T2-weighted images with a “bunch of grapes” appearance (Figs. 6 and 7). Low signal on T1 is due to decreased marrow fat or greater vascular component and has been associated with a more aggressive behaviour. Punctate or reticular low T2 signal may be present representing fibrous tissue or foci of calcification. These bony lesions enhance diffusely after contrast administration. Sometimes they can have an aggressive pattern with a soft-tissue component and may simulate a malignant neoplasm [1, 2, 6, 16,17,18].
Treatment of these lesions is mainly surgical; embolisation may be performed before surgical intervention to reduce blood loss [2].
Intraosseous meningioma
Meningiomas are the most common extra-axial dural based tumours in middle-aged and elderly patients [1, 2, 6, 19]. The characteristic finding of an intradural meningioma is reactive hyperostosis of the adjacent calvarium (Fig. 8). Occasionally, they can produce marked bone thickening with outward growth of the outer table of the skull [1, 4].
The meningiomas arising outside the dural compartment have been called ectopic, extradural or intraosseous meningiomas. Lang et al. [19] has proposed the term “primary extradural meningioma” for such lesions; this is to differentiate them from primary intradural meningiomas which may have secondary extracranial extension and/or may have metastasised into the skull and adjacent soft tissues.
Intraosseous meningioma is a rare subtype of meningioma that account for <2% of all meningiomas [19,20,21,22]. The frontoparietal and orbital regions are the most common locations [2, 19, 20]. Although primary intradural meningiomas occur twice as frequently in women compared to men and predominantly in older adults, intraosseous meningiomas occur with the same frequency in men and women and have a peak in the second decade of life [19]. It is thought that they are due to trapping of embryonic arachnoid cap cells in the developing calvaria in the cranial sutures (particularly the coronal suture) or due to trapping of arachnoid cells in a prior skull fracture or surgical osteotomy [2, 19, 20]. Calvarial intraosseous meningiomas are more prone to develop malignant changes (11%) compared with primary intradural meningiomas (2%) [19, 22].
Osteoblastic or mixed osteoblastic-osteolyic meningiomas compose most of intraosseous meningiomas, with the purely lytic form being the least common [1, 2, 4, 19]. Primary extradural meningiomas are classified as extracalvarial (type 1), purely calvarial (type 2) or calvarial with extracalvarial extension (type 3) [19].
On CT, an intraosseous meningioma typically appears as a sclerotic lesion with associated hyperostosis of the bone, and irregular and spiculated borders (Fig. 9) [2, 4]. On MRI, the tumour has low signal on T1-weighted images and variable signal intensity on T2-weighted images [2, 4, 6]. Meningeal enhancement is rare and is due to adjacent dural irritation or invasion [1, 2, 4]. Intraosseous meningiomas can rarely be osteolytic and in those cases are more commonly malignant [2, 4, 19].
In a symptomatic primary intraosseous meningioma, total tumour removal with a wide surgical resection followed by cranial reconstruction is the treatment of choice. If only subtotal resection is possible due to involvement of critical structures within the orbit, paranasal sinuses, or skull base, the residual tumour should be followed radiologically. Adjuvant radiation therapy is recommended if the residual tumour is symptomatic or if there is evidence of disease progression [2, 19].
Paget disease
Paget disease (also known as osteitis deformans) is a chronic skeletal disorder characterised by abnormal and excessive bone remodelling. Paget disease is estimated to affect approximately 3–4% of individuals older than 40 years [2, 5, 23,24,25,26]. It is a progressive disorder that evolves through various stages or phases of activity. Three major phases are recognised: the lytic phase (incipient active), in which osteoclastic resorption predominates; the mixed phase (active), in which there is both osteoblastic and osteoclastic hyperplasia with predominantly osteoblastic activity; the sclerotic or blastic phase (late inactive), in which the osteoblastic activity gradually declines. This anarchic bone behaviour produces disorganised new bone in a mosaic pattern [2, 6, 23, 24]. Paget affects the skull in 28–42% of cases, particularly the frontal and occipital bones. Other locations affected by Paget are the lumbar spine (30–75%), pelvis (30–75% of cases), sacrum (30–60%) and femur (25–65%). Polyostotic disease is more common than monostotic disease [23, 24].
Skull involvement in Paget disease can lead to increase in head size, hearing loss and entrapment of the cranial nerves in their respective foramina. When the skull base is involved, there is platybasia and basilar invagination in which the tip of the odontoid projects more than 5 mm above the Chamberlain line between the hard palate and basiocciput [23, 24].
Early in the disease, osteolytic activity predominates. In this phase, advancing osteolysis presents as large areas of radiolucency in the frontal and occipital bones, known as “osteoporosis circumscripta”. The mixed phase is notable for four cardinal features, which comprise advanced osteolysis, coarsening and thickening of bone trabecula, cortical thickening and osseous widening. In this phase, there is homogeneous enlargement of the skull vault, thickening of the tables and trabecula. The fluffy cotton-wool appearance of the skull is characteristic in this phase with diploic dense lesions in previously sclerotic areas (Fig. 10). Diploic widening is also seen in this phase [2, 5, 6, 23, 24].
As suspected, MRI features vary depending on the stage of the disease. Initially, during bone resorption, high signal intensity can be seen on T2-weighted images, as well as strong enhancement. In this stage, on T1-weighted MR images, the marrow has decreased signal intensity, generally similar to that of muscle; however, it typically contains small to extensive foci of intermixed, normal and maintained yellow marrow. This feature is important because it excludes malignant transformation. In the mixed phase, the yellow marrow signal is maintained in all pulse sequences. In the late blastic inactive phase, the marrow space has low signal intensity on both T1- and T2-weighted images representing sclerosis [2, 5, 6, 23, 24].
Sarcomatous degeneration of Paget has been described with varying frequency depending on the extent of disease. In patients with widespread skeletal involvement, sarcomatous degeneration may occur in 5–10% of cases, whereas in patients with less skeletal involvement, neoplasm can occur in less than 1% of cases [23, 27].
Treatment relies mainly on bisphosphonates [2].
Calvarial sarcoidosis
Sarcoidosis is an inflammatory disorder of unknown cause characterised by the presence of non-caseating granulomas in tissues. Sarcoidosis involves multiple organs, most commonly the lungs, skin and eyes but may be seen in any organ system, including the musculoskeletal system [28]. Skeletal involvement is an uncommon manifestation of sarcoidosis. When it occurs, bone involvement is usually limited to the vertebra and tubular bones of the hand and feet with the classic lacy lytic appearance. Skull involvement in sarcoidosis is very rare with few cases reported [28,29,30,31]. Clinically calvarial sarcoidosis may manifest with headaches and skull tenderness [28,29,30].
The lesions are osteolytic with well-demarcated margins and usually multiple. In contrast to metastasis, the calvarial tables are intact. They can also manifest as expansile lesions on CT imaging. MR can be used to assess bone marrow infiltration and associated periosseous soft tissue (Fig. 11). They have variable signal intensity and may enhance after administration of contrast [28,29,30,31]. Differential considerations include osseous venous malformation, eosinophilic granuloma, metastasis, as well as chronic infection.
Partial or complete resolution of the sarcoid lesions can occur spontaneously [30]. Treatment is usually indicated when the symptoms include uncontrolled pain, stiffness or bony destruction. Therapy generally consists of oral corticosteroids; methotrexate and hydroxychloroquine can also be used [32].
Ossifying fibroma
Ossifying fibroma is a benign fibro-osseous tumour made of highly cellular fibro-osseous connective tissue. It is more often seen in children and young adults and can affect the calvaria in approximately 12% of cases. It is a benign slow-growing tumour, but a subset of these tumours tends to be infiltrative and locally aggressive [33, 34]. Three forms of ossifying fibromas have now been distinguished: classical ossifying fibroma, psammomatoid juvenile ossifying fibroma and trabecular juvenile ossifying fibroma. The psammomatoid type of juvenile ossifying fibroma is reported more commonly than the trabecular variety, is more aggressive and has a strong tendency to recur [35].
On radiographs, ossifying fibroma appears as a monostotic, round or ovoid, well-demarcated expansile lesion. It may be predominantly cystic or sclerotic depending on the amount of non-calcified versus that of the mineralised regions. On CT, ossifying fibroma is a mass composed of enhancing soft tissue with varying amounts of internal punctate calcifications. Areas of low attenuation caused by cystic changes may be present, and can have internal haemorrhage (Fig. 12) [33,34,35].
On MRI, the solid component is usually isointense to muscle on T1-weighted images and isointense to hypointense to muscle on T2-weighted images. Post-contrast images show diffuse and heterogeneous enhancement of the solid component and thin peripheral enhancement of the cystic areas [33,34,35]. Differential considerations include fibrous dysplasia, aneurysmal bone cyst, osteoblastoma and cementum producing lesions such as cemento-osseous dysplasia and cementifying fibromas [34].
Because of its locally aggressive nature and high recurrence rate, early detection and complete surgical removal are essential [34].
Epidermoid and dermoid cysts
Epidermoid and dermoid cysts are benign slow-growing lesions that may be congenital or acquired from post-surgical or post-traumatic implantation of epidermal or dermal inclusions within the diploe. Clinically, they manifest as non-tender, slowly expanding masses enlarging over years or decades [1, 2, 4,5,6].
Epidermoid cysts are lined with squamous epithelium and contain remnants of cholesterol and keratin. Intradiploic epidermoid cysts can occur in any part of the skull, but most commonly occur laterally in the parietal and frontal bones. They are usually discovered in patients between 20 and 50 years of age [1, 2, 6].
On CT, epidermoid cysts appear as well-demarcated intradiploic osteolytic lesions with smooth sclerotic margins. These lesions often cause remodelling and expansion of the inner and outer tables. Rarely, they may have increased attenuation on CT, possibly due to haemorrhage, formation of calcium soaps or high protein content (white epidermoids) [1, 2, 4,5,6, 36].
On MRI, epidermoids have fluid-signal intensity on T1- and T2-weighted images and have characteristic restricted diffusion on diffusion-weighted imaging (DWI). They do not enhance after contrast administration (Fig. 13) [1, 2, 4,5,6, 36].
Dermoid cysts are lined by thick squamous epithelium and contain epidermal appendages such as sebaceous glands, sweat glands and hair follicles. They usually present in the first 3 decades of life. These lesions typically involve the midline of the skull near the anterior fontanelle, but may also occur along the posterior and middle cranial fossae [1, 2, 4,5,6].
On CT, dermoids appear as expansile, osteolytic midline lesions with a soft-tissue component extending into the adjacent soft tissues and intracranially. They have attenuation of lipid material because of their sebaceous secretions. Intralesional calcifications can be present.
On MRI, they have a heterogeneous appearance with fatty signal intensity on T1-weighted images, variable signal on T2-weighted images and thick peripheral enhancement after contrast administration (Fig. 14) [1, 2, 4,5,6, 37].
Treatment of both epidermoid and dermoid cysts is surgical resection; recurrence is uncommon [2].
Cleidocranial dysostosis
Cleidocranial dysostosis is a rare skeletal dysplasia with autosomal dominant inheritance due to mutation in the CBAF1 gene. It is a polyostotic disorder characterised by incomplete intramembranous ossification of midline bony structures. It affects the skull, clavicles and eruption of teeth [38, 39]. In the skull, multiple wormian bones due to islands of intrasutural bones in the sagittal and lambdoid sutures are characteristic. Premature fusion of the coronal suture or brachycephaly, as well as frontal and parietal bossing has also been described. Findings outside the skull comprise absent and/or hypoplasia of the lateral clavicle, supernumerary ribs, hemivertebrae, hypoplasia of the iliac bones and short or absent limbs (Fig. 15) [38, 39].
