Clinical manifestations

Presentation and course

Epidermoid and dermoid cysts are most commonly found in the testicles and ovaries; however, they may be found intracranially and in the spinal canal as well (119). Throughout the body, dermoids are more likely to be located along the midline, and this holds true in the intracranial space as well. Clinical manifestations of epidermoid and dermoid cysts are nonspecific and depend on their location. Although both are more likely to be found above the tentorium, epidermoids are more likely to be found off midline and in the cerebellopontine angle, whereas dermoid tumors are typically midline and sometimes associated with a dermal sinus tract (119).

Epidermoid and dermoid cysts grow slowly, envelop or displace neural and vascular structures, and are usually insidiously progressive over several years. Due to their indolent nature, many patients remain asymptomatic for decades. This leads to an average time of presentation for epidermoid tumors from the third to fifth decades. Dermoids typically present earlier in life, within the first two decades, likely due to their association with dermal sinus tracts and meningitis. However, cases with acute presentations or intermittent symptoms are well described, often related to rupture of a dermoid cyst, which can cause aseptic meningitis, seizures, or increased intracranial pressure (74; 107).

Epilepsy is the most common symptom in supratentorial epidermoids and dermoids (95; 75; 49). However, frontal and callosal masses may also lead to personality changes and headaches (110). Suprasellar tumors present with visual impairment, optic atrophy, or visual field defects similar to other mass lesions in this region. One in five cases of parasellar-suprasellar epidermoids has signs of mild hypopituitarism or diabetes insipidus (38). Spontaneous, traumatic, or iatrogenic rupture of the cysts can produce aseptic meningitis, seizures, increased intracranial pressure, vasospasm, or even stroke (53; 107; 120).

Epidermoids and dermoids of the posterior fossa can present with deafness, vertigo, facial pain, hemifacial spasm (48; 71), trigeminal neuralgia (113; 27) or bilateral gaze nystagmus (23). After cysts reach a large enough size, compression of the cerebral aqueduct can lead to obstructive hydrocephalus (62; 85; 116; 117).

Although epidermoids can occur throughout the neuraxis, they are most commonly found in the cerebellopontine angle (77; 22; 12; 65) and parasellar region (75). They are found less commonly in the intrinsic brainstem, spinal cord, spinal canal, or pineal region (60; 97). Epidermoids have also been reported to develop in the diploe of the skull (24) and the anterior fontanelle (11). Convexity masses lead to symptoms due to compression. This can include weakness, personality changes, or even idiopathic intracranial hypertension from compression of venous sinuses leading to decreased outflow (71).

Dermoids are more frequently situated in the midline (eg, fontanelles, parasellar region, fourth ventricle, spinal canal, and pineal region) (38; 76; 89) and can communicate with the skin surface. These dermal sinus tracts usually occur at the occiput or lumbar spine (42) and rarely via a nasal dermal sinus (29). Dermal sinuses have been reported in more than 50% of midline posterior fossa dermoids (76), which may lead to recurrent bacterial meningitis. Early detection of congenital dermal abnormalities along the craniospinal axis by routine examination of newborns is important before developing serious complications (59). Dermoids can be associated with other developmental abnormalities, such as Klippel-Feil syndrome and other craniocervical junction anomalies (121; 127).

Epidermoid and dermoid cysts can also develop in the spine as a developmental abnormality or may be iatrogenic in nature (64; 09; 08; 109). When presenting in the spine, they are associated with the typical findings of any mass lesion in the area. They are classically intradural, extramedullary masses, which present with myelopathic symptoms below the level of compression, including cauda equina syndrome or radiculopathy if found in the lumbar spine (105). Intramedullary spinal dermoid cysts are rare, with a predilection toward the lumbosacral spine (60%) over the thoracic (10%) or cervical spine (5%). Symptoms depend on the location and the extent of tumor and can include motor disturbances, sensory disturbance, and bowel and bladder dysfunction (88; 40). Children with a history of myelomeningocele may develop recurrent spinal cord tethering if there are dermal elements within the closure. Techniques and goals of surgical repair of open neural tube defects have been revisited to minimize inadvertent inclusion of squamous epithelial membrane, which leads to dermoid cyst and tethering of the cord that can cause further injury to the neural tissues (33).

Prognosis and complications

As mentioned above, complications from dermoid and epidermoid cysts depend on the location of the cysts and affected neurologic structures. In one study, 16 of 46 children with epidermoid or dermoid spinal cysts had neurologic impairment before surgical resection (114). Prognosis is largely dependent on the extent of surgical resection (see Management section).

Clinical vignette

A 28-year-old woman with no previous medical history woke with a severe headache and stiff neck. Notably, she had no history of meningitis, head trauma, or previous cranial surgery. She was unable to move her neck, and when she stood, she developed severe vertigo, nausea, and an increase in the headache, which led her to lie back down. She reported several episodes of lightheadedness while at work but attributed it to hypoglycemia or low blood pressure. Her primary care physician found no significant findings on examination. A CT and MRI of her brain revealed a left subfrontal lesion extending from the crista galli into the left frontal lobe just posterior to the left frontal sinus. It was avidly bright on T1 and T2, suppressed with fat-saturated images, and had no enhancement with gadolinium. There were scattered foci of T1 bright lesions around the patient's convexity. There was no evidence of hydrocephalus. She was treated with dexamethasone for her severe headaches after imaging suggested a dermoid cyst.

She was diagnosed with a ruptured dermoid cyst, and because of these findings and the previous rupture, she sought treatment from a neurosurgeon. After resolution of the aseptic meningitis, she underwent a fronto-orbitozygomatic craniotomy for resection of the frontal lesion as well as an attempt to resect the other smaller T1 hyperintense lesions. During the surgical intervention, the lesions were easily accessed and found to contain keratinaceous material as well as fat and hair, consistent with a diagnosis of a dermoid. Further exploration revealed a dermal sinus tract extending into the ethmoid sinuses. This was followed and truncated after circumferential dissection was completed for a total resection of the lesion. In the spinal fluid, there was an oily mixture seen on the surface of the lesion, which was likely from the rupture. This was irrigated copiously in an attempt to minimize her symptoms from the chemical meningitis.

Postoperatively, her recovery was uneventful, and an MRI revealed complete resection of the lesion. She was discharged, and follow-up has revealed no recurrence to date.

Biological basis

Etiology and pathogenesis

Most epidermoids and dermoids are developmental in origin and are believed to be formed by retained ectodermal tissue during the third to fifth week of development (45; 84). Rare iatrogenically induced cases of epidermoid cysts have been described following lumbar puncture (54), percutaneous cranial subdural aspiration, repair of myelomeningocele, or trauma (70). The occasional association with Klippel-Feil syndrome may suggest a disturbance of the mesoderm before the fourth week of gestation (21). The lateral location of intracranial epidermoids may be due to embryonic cell rests being carried to the cerebellopontine angle with the developing otic vesicles (37).

Epidermoids have linear growth potential similar to normal epithelial or dermal structures (07). Intracranial dermoids arise from ectopic migration of both dermal and epidermal elements. Macroscopically, epidermoid cysts are thin-walled, unilocular, lobulated, "pearly" cysts with homogenous "cheesy" contents.

Microscopically, epidermoids consist of well-differentiated squamous epithelium with layers of enucleated squames with cholesterol or keratohyaline granules, resting on a layer of connective tissue.

Dermoids lack the milky white appearance, have thicker walls, and are less homogenous than epidermoids because they are lined not only with squamous epithelium but also with dermal appendages (eg, hair follicles, adnexa, and, less commonly, bone).

There can be adjacent areas of chronic inflammation with gliosis and Rosenthal fibers in the brain parenchyma. Epidermoids and dermoids are immunoreactive for cytokeratins and epithelial membrane antigen (16; 05).

Epidemiology

It has been estimated that epidermoids account for between 0.5% and 1.5% of intracranial tumors and dermoids for 0.1% to 1% of intracranial tumors (10; 103; 69; 01). Nevertheless, dermoid cysts are one of the most common pediatric space-occupying lesions of the skull (94; 98). Most dermoid cysts are congenital, with approximately 70% of dermoids diagnosed among children 5 years of age and younger (79; 94; 50). On the other hand, the majority of epidermoid cysts occur during adulthood between 20 and 40 years of age (106). There is no significant difference in dermoid cyst diagnosis by sex (94). However, the male-to-female ratio for epidermoid cysts is 3:2 (126; 50).

Prevention

Developmental epidermoids and dermoids cannot be prevented as they form initially in utero prior to the time when most women know they are pregnant. Furthermore, there is no association with environmental toxins that lead to their development. There is a suggestion that spinal epidermoids and dermoids may develop after repair of open neural tube defects, spinal surgery, or lumbar punctures; however, this is a rare occurrence (09; 105; 33).

Differential diagnosis

Confusing conditions

Imaging of the site of clinical involvement using CT or MRI usually leads to the correct diagnosis preoperatively, but epidermoids may be difficult to distinguish from dermoids. Both generally appear on CT scan as well-circumscribed lesions with low density between CSF and brain, making differentiation from other cysts (eg, arachnoid cyst) difficult. Dermoids more commonly have lower densities than epidermoids (91). The low density of cyst contents on CT scan is due to cholesterol or keratin. The cyst wall of epidermoids may be thinly calcified, and because the contents are avascular, they do not often enhance with contrast. Dermoids also contain fat plus dermal elements, are more heterogeneous, have a thicker wall, rarely enhance, and more commonly demonstrate calcification. There is no surrounding edema in the brain. Occasionally, enhancement in the wall may be due to transformation of the cyst epithelium into a squamous cell carcinoma (80).

In the cerebellopontine angle, the differential diagnosis includes schwannoma, meningioma, hemangioblastoma, and cholesterol granuloma. When symptoms point to a slowly progressive lesion of the parasellar region, pituitary tumors, meningiomas, oligodendroglioma, and craniopharyngiomas are usually considered.

Lipomas have a similar CT density to epidermoids but usually have more calcium in them. Epidermoids in the suprasellar region may occasionally be mistaken for a Rathke cleft endodermal cyst, porencephalic cyst, or craniopharyngioma. Dermoids may be mistaken for a craniopharyngioma or well-differentiated teratoma. Rathke cleft cysts are intrasellar cysts containing CSF. Craniopharyngiomas have more complex cysts than epidermoids, thicker irregular walls, and more calcification on CT scan. Teratomas are formed from more than one germ cell layer and contain a variety of tissues including bone, cartilage, hair, and fatty tissue.

Cholesterol granulomas are most commonly found in the middle ear and mastoid cavities, but if medially situated, they can be mistaken for an epidermoid. Cholesterol granulomas are brown from hemosiderin deposits and are not lined by stratified squamous epithelium. They are isodense to brain on CT with rim enhancement and have high signal on T1- and T2-weighted MR images (06).

Diagnostic workup

The initial differential diagnosis includes arachnoid cysts and abscesses; thus, computed tomography and MRI with multiple sequences are essential to differentiate the various pathologies.

On CT scans, epidermoids and dermoids appear at the same density as CSF and look quite similar to an arachnoid cyst, especially given that they may both develop in the cerebellopontine angle.

The MRI appearances of epidermoids and dermoids are usually characteristic. On T1-weighted MRI sequences, epidermoids exhibit a variable signal (white when the lipid content is high or black if lipid content is low). Classically, epidermoids have a low signal on T1-weighted images and high signal on T2-weighted images (56).

Dermoids give high signal on T1-weighted images in areas containing fat and variable signal where there is a combination of fat, muscle, and bone.

MRI sequences, such as fluid-attenuated inversion recovery (FLAIR) and constructive interference in steady state (CISS) may be more accurate in demonstrating epidermoids (52; 51). Although epidermoids are usually hyperintense on FLAIR sequences, they may appear as low attenuation lesions. In these circumstances, echo planar diffusion scanning can be helpful in distinguishing an epidermoid from an arachnoid cyst in the cerebellopontine angle because epidermoids remain bright (31). Diffusion-weighted MRI of epidermoids shows homogenous hyperintense lesions and restricted apparent diffusion coefficient in comparison to CSF because of the squamous epithelial cells in the cyst (68; 93).

Advanced MRI techniques such as diffusion tensor imaging have been performed to try and study the microstructural anatomy of epidermoid cysts. This has demonstrated high fractional anisotropy but no restricted diffusion, and diffusion occurred along a two-dimensional plane consistent with the parallel layered arrangement of keratin filaments and flakes in the cysts (55). Magnetic resonance spectroscopy can also help differentiate epidermoid from arachnoid cysts as the former demonstrate significantly higher lactate (68). In parasellar tumors, preoperative evaluation should include assessment of the hypothalamic-pituitary axis.

In the 5% to 6% of patients with atypical MRI appearance, cysts tended to be larger and often contained hemorrhage (101). Other atypical findings are of hyperattenuation in the posterior fossa as well as enhancement of a nodule (82). Ruptured epidermoid cysts can cause a "blooming artifact" on susceptibility-weighted MRI scans that mimic the blooming artifact seen with hemorrhage (112). Spinal intramedullary cysts can provide a diagnostic challenge radiographically, in addition to a surgical challenge (90; 40). In cases where there is diagnostic doubt, further investigation depends on the site and suspected differential diagnosis (eg, possibly angiography if differential diagnosis includes cystic meningioma or tumor markers for possible pineal mixed germ cell tumor). A definitive diagnosis is made by tissue histology.

Management

Epidermoids and dermoids are potentially curable, and the best chance for cure is with a gross total microsurgical excision of the tumor and cyst wall at the first attempt (06; 38; 77; 35). Various surgical exposures can be used depending on the location of the mass; however, even with approaches that provide ample exposure, the adherent cyst wall may not be amenable to complete resection. Total resection of the cyst wall is possible only in 50% to 70% of cysts (104; 122). For example, a telovelar approach along the cerebellomedullary fissure will provide exposure of the 4th ventricular region, but the tela choroidea is often involved in the dermoid or epidermoid capsule, thus, necessitating that the surgeon intentionally leaves residual capsule (17; 34; 125). Despite this, subtotal removal is still justified because recurrence may take many years (77; 124). Large epidermoids (larger than 4 cm) of the quadrigeminal cistern can be totally resected in only about two thirds of cases, and severe morbidity or mortality will occur in 20%, which further raises the important role of subtotal resection in certain cases to preserve neurologic function and reduce surgical risk (87). During surgery, care is taken to minimize the spread of cholesterol crystals throughout the subarachnoid space to prevent aseptic meningitis or ventriculitis. Intraoperative hydrocortisone irrigation of the CSF has been demonstrated in a small, randomized controlled trial of spinal epidermoids to reduce symptoms if there is a spread of the cyst contents (58). Perioperative systemic use of corticosteroids is often used as a strategy to reduce the inflammatory response caused by the spillage of cyst material during surgery.

For patients who present with a ruptured cyst and aseptic meningitis, intravenous or oral high-dose steroids help to minimize symptoms. Clearly, care should be taken to first exclude infection or aneurysmal subarachnoid hemorrhage prior to starting this treatment (19). As dermoid tumors often have dermal sinus tracts, it is possible to have both a ruptured cyst as well as an infection due to the tract. In this instance, antibiotics and early surgical intervention have been recommended, especially if there is neurologic deterioration (18; 04).

Recurrence is common with intracranial or spinal epidermoid cysts. The use of diffusion-weighted MRI can be helpful in distinguishing epidermoid recurrence from postoperative cysts (118). Repeat resection can be attempted if the patient becomes symptomatic from the mass effect; however, surgery may be difficult given the proximity to critical neurovascular structures of the skull base and scarring from redo surgery (01). There have been reports of recurrent spinal dermoid and intracranial epidermoid cysts responding to treatment with radiotherapy (96; 14; 13; 83); however, this is not standard of care. A case series of eight patients with recurrent epidermoid cysts treated with adjuvant radiotherapy between 2000 and 2017 from a single institution shows promising results in decreasing the likelihood of recurrence without any reported malignant transformation (83).

Malignant transformation is rare with epidermoids and exceptionally rare with dermoids (Table 1) (02). Malignant transformation can occur de novo or from a remnant left after surgery (99). Acute or very rapid deterioration after years of stability should raise suspicion of malignant transformation (57). Radiotherapy has been given for epidermoid tumors with malignant transformation, and treatment with 50 Gy may extend survival by about 6 months, from 6.6 months to 12.7 months, although there are no randomized trials of radiotherapy in resected malignant epidermoids (86; 36; 123). The association of leptomeningeal spread has a particularly poor prognosis with a median survival of 9 months. Surgery followed by radiotherapy has been proposed as the best treatment (47).

Table 1. Criteria for Diagnosis of Malignant Transformation of Intracranial Epidermoid Cysts

Outcomes

Despite the advances in neurosurgical ability, the perioperative mortality rate for epidermoid and dermoid cysts remains approximately 7% but has been reported as high as 11.5% in de novo resection of large epidermoids (46; 01). These rates are much higher than what is reported with surgeries for high-grade gliomas. Repeat resections appear to have a higher morbidity (01).

Infratentorial epidermoids have a higher perioperative morbidity, mortality, and recurrence rate as well as poorer prognosis than supratentorial epidermoids (75). They present with a variety of symptoms, which can include trigeminal neuralgia, hemifacial spasm, ataxia, or cranial nerve palsy. In fourth ventricular epidermoids, about 70% of patients have gait ataxia, and 70% have raised intracranial pressure (43). A retrospective study of 50 patients with posterior fossa epidermoids that had been treated surgically showed a 9% recurrence rate where the tumor was thought to have been completely resected and a 93% recurrence rate in those partially resected (43). Transient cranial nerve deficits occur in 44% of operated cases with cerebellopontine angle epidermoids; however, only 8% are permanent (81; 03). Cerebellopontine angle epidermoids can be subtotally removed using a retro-mastoid approach, but those that extend into the cerebello-brainstem fissure are technically difficult and may require a far lateral approach or a posterior transpetrosal approach for removal (63).

Trigeminal neuralgia can develop from pressure from the epidermoid on the trigeminal nerve or by displacing vascular structures that then press on the nerve. This may require microvascular decompression of the nerve as well as removal of the tumor. Where this is achieved, the trigeminal neuralgia commonly improves (61). Trigeminal neuralgia occurs in 35% of posterior fossa epidermoid cysts, and deafness occurs in a similar percentage (29%). Hemifacial spasm associated with cerebellopontine angle tumors often also has vascular compression of the facial nerve (78%). About 90% have improvement of the hemifacial spasm postoperatively, but 20% have sequelae from the operation (48). Prepontine epidermoids provide a particular surgical challenge, including anterior transpetrosal approaches that may lead to higher rates of sixth nerve palsy (40% transient palsy postoperative) or CSF leakage (33%) (108).

Occasionally, fat from a ruptured dermoid cyst can remain intraventricularly and increase in size over the years (67). Cerebellar abscesses from posterior fossa dermoids in children have been reported (59). The infection leads to enhancement with contrast on MRI. More than 90% of patients with epidermoids live an independent, useful life after surgery, and the cumulative 20-year survival rate is 92%. Twenty-five percent of cases recur, oftentimes decades from the original surgery. Surgery for anterior tentorium-based epidermoids is associated with 8% transient postoperative neurologic deficit, 4% permanent focal deficits, and 2% postoperative mortality (41). Dermoid cysts present at a younger age, have associated malformations, and have a better prognosis (76).

Angiographically confirmed delayed ischemic deficits have been described a few days after uncomplicated removal of large intracranial dermoids (32). In a retrospective study of 428 surgically treated intracranial epidermoid cysts, Ren and colleagues described 24 cases of epidermoid cysts complicated by postoperative hemorrhage, of which 21 were “delayed” (more than 72 hours) (100). Hematoma at the surgical site was seen in 11 patients, whereas subarachnoid hemorrhage was seen in 10 patients. There was a high mortality rate among those who hemorrhaged, approaching 30%. The reasons for the high rate of delayed hemorrhage is uncertain, although there was a weak association with adhesion to neuromuscular tissues (p = 0.096). The authors of this study noted that the rate of delayed hemorrhage after surgical treatment of epidermoids was almost five times higher than that of other tumors.

Aseptic meningitis can occur following a rupture of epidermoids or dermoids, most commonly following surgery, but it occasionally occurs spontaneously or as a direct result of head injury (70). Rupture of spinal dermoids can result in aseptic meningitis, which can, in turn, cause obstructive hydrocephalus (20). Headache (57%) and seizures (42%) are the most common symptoms at the time of cyst rupture (72). However, 15.9% of patients have hemiparesis or hemisensory problems, and 6.9% have symptoms of chemical meningitis (115). Recurrent infective meningitis can occur if there is a dermal sinus tract (42). Sinuses are most commonly seen in the occiput or lumbar spine, but nasal dermal sinuses have also been recorded (15).

Special considerations

Pregnancy

There is no evidence that the hormones associated with pregnancy influence the growth of epidermoids or dermoids. Surgery can often be avoided during pregnancy, except for lesions that are causing obstructive hydrocephalus or evidence of increased intracranial pressure. If there is a need to operate during pregnancy, the risks to the fetus are the same as for any intracranial operation requiring general anesthesia. Close monitoring of the fetus is warranted in the operating room as well as in the postoperative period (44).

Anesthesia

The situation is the same as for any intracranial surgery. Care should be taken to not compress the jugular veins for posterior fossa lesions as this may lead to increased intracranial pressure.

Pediatric

Dermoids and epidermoids commonly occur intracranially in pediatric patients (17). As in adults, dermoid cysts are often associated with a dermal sinus tract, which may lead to their early detection after recurrent bouts of infectious meningitis. Calvarial dermoids and epidermoids in infants and young children can be assessed by ultrasound. Most decrease in size with time or remain static and they do not invade intracranially, but posterior fossa dermoid cysts with sinus tracts may present in children with an occipital lump (30; 102).

Case example. A 3-month-old infant presented to her pediatrician with 3 weeks of intermittent fevers and discomfort. This was initially thought to be secondary to a gastrointestinal illness; however, due to the persistent fevers, she eventually underwent a lumbar puncture. The CSF grew out methicillin-sensitive Staphylococcus aureus (MSSA). On physical examination, she was noted to have a small right scalp lesion, which was noted at birth. Her parents noted that it occasionally seemed to be larger but would then drain and become smaller. They also noted intermittent redness. Imaging revealed a small lesion in the cerebellum that was enhanced with contrast. The patient underwent a suboccipital craniotomy and total excision of the cerebellar dermoid.