Endodermal cysts are benign developmental lesions that contain epithelia resembling those derived from the endodermal germ layer, specifically respiratory and gastrointestinal. They occur outside of the central nervous system (CNS) paraspinally as bronchogenic and enteric cysts, respectively. In the CNS, those with respiratory epithelium may go by different names depending on the site; in the sellar and suprasellar spaces, they are Rathke cleft cysts; those in the third ventricle are colloid cysts. Those with gastrointestinal epithelium are often referred to as enterogenous or neurenteric cysts. In any location, any of the above may be more generically termed endodermal or neurenteric cysts.

Endodermal cysts are common surgical neuropathology specimens, most often presenting as Rathke cleft or colloid cysts. They rarely present congenitally, although most are resected in early and middle adulthood. The signs and symptoms with which endodermal cysts present depend on location: Rathke cleft cyst with hypopituitarism and/or visual problems; colloid cyst with headache and hydrocephalus (and occasionally sudden death (1)); and spinal cord lesions with weakness. Rathke cleft cysts have also been described to present with “Rathke cleft cyst apoplexy,” in which sudden hemorrhage into the cyst cavity produces acute enlargement and rapid onset of severe headache, visual disturbance, and pituitary insufficiency (2). Colloid cysts have been noted in familial clusters, typically in females, but it is not clear whether this represents a specific genetic defect or coincidence (3,4).

Neuroimaging of endodermal cysts shows a sharply circumscribed round to ovoid mass that is usually intradural and extra-axial, or, for colloid cysts, intraventricular. Less commonly, some examples are
intraparenchymal (5). Again, endodermal cysts occur throughout the length of the neuraxis, yet are most common around the base of the brain and in the posterior fossa. Although variable, the cyst contents are most often hyperintense on T1-weighted magnetic resonance sequences and hyperintense on T2-FLAIR, sometimes with a partial rim of contrast enhancement, reflecting reactive changes in surrounding tissue (6). Computed tomography (CT) images infrequently show calcification of the cyst wall.

Grossly, the cyst lining is an inconspicuous membrane that holds variable contents from thin, clear, or cloudy liquid to inspissated, translucent, thyroid-like colloid.

Simple surgical excision is the preferred treatment for endodermal cysts, resulting in generally favorable outcomes. The overwhelming majority of endodermal cysts are benign, yet several cases with malignant progression and/or dissemination have been described (7,8,9).

The linings of endodermal cysts reflect the variety of endodermally derived surface epithelia seen in the digestive and respiratory tracts, in most cases (Figure 1-1). Cells range from cuboidal to tall columnar and may be pseudostratified. Cilia often project from the apical surface. Mucin-bearing goblet cells may be interspersed between columnar cells and less commonly can form the vast majority, creating a gastric foveolar-type surface. Squamous metaplasia is uncommon but can be extensive and overwhelm the other elements (Figure 1-2). By metaplastic production and accumulation of keratinaceous debris, what originated as an endodermal cyst can metamorphose into a lesion similar to an epidermoid cyst over time.

Rathke cleft cysts occasionally contain such squamous metaplasia, and this feature can be misleading in the sellar–suprasellar area because craniopharyngiomas may also sometimes incorporate ciliated respiratory epithelium. Metaplasia in Rathke cleft cysts should therefore be interpreted with caution and invoked only when clear maturation to dry keratin flakes is observed. This topic is discussed further in Chapter 8 with craniopharyngiomas.

Another source of confusion regarding Rathke cleft cysts is that long-term degeneration of hemorrhage into the cavity can produce contents similar to those of adamantinomatous craniopharyngiomas: “machine oil” fluid containing xanthogranulomatous debris and cholesterol crystals. In such cases, this material may mislead the radiologist, neurosurgeon and, potentially, the pathologist. Such cyst contents are more common in craniopharyngiomas, but cannot necessarily be taken as evidence for that diagnosis.

Nondescript, loose fibrous tissue typically underlies the epithelium of endodermal cysts; smooth muscle, or possibly other mucosa-associated tissues, may be present (10).

These common CNS lesions occur in patients of all ages with no clear predominance in either sex. The anatomic distribution for epidermoid
cysts is diffuse, with examples from every location along the neuraxis. They are most frequent in the posterior fossa, especially near the cerebellopontine angles (11). Patients often present with headache and/or cranial nerve dysfunction (12). In contrast, dermoid cysts tend to occur as midline lesions in younger patients. These cysts may have a sinus tract to the skin surface that allows for cyst infection (13). Either may occur as cystic, intraosseous skull lesions.

Magnetic resonance imaging (MRI) of most epidermoids and dermoids shows a T1-hypointense, T2-hyperintense mass that does not enhance with contrast material (11,12). Like abscesses, the contents of epidermoid cysts impede the free motion of water molecules, causing “restricted diffusion” on diffusion-weighted MR sequences and providing an important diagnostic cue for radiologists (14). The cyst contents are hypodense on CT scan.

Because the surrounding tissues may be densely adherent to the cyst wall, total resection may be difficult. Nevertheless, even with subtotal resection, the outcome after surgery is generally favorable, with little difference in recurrence rates from totally resected cases in one review of the literature (12). Rarely, epidermoid or dermoid cysts undergo malignant transformation (15,16,17). Rupture of cyst contents into the cerebrospinal fluid (CSF) precipitates chemical meningitis.

The epidermoid/dermoid cyst lining, by definition, consists of keratinizing squamous epithelium, with dermal adnexa in the case of dermoid. The squamous cells mature normally toward the center and accumulate as sheets of anucleate keratin, which constitute the majority of the tumor mass. In contrast to craniopharyngioma and metaplastic endodermal cysts, the other squamous primary lesions of the CNS, epidermoid, and dermoid cysts have a granular layer (Figure 1-3).

Papillary craniopharyngiomas are also squamous lesions, but they are readily distinguished from dermoid/epidermoid cysts because they lack the keratohyalin granular layer and accumulation of mature flakes of “dry” keratin seen in the latter. The calcified and inflamed cellular debris of adamantinomatous craniopharyngiomas is also not a feature of epidermoid cysts.

Mature teratomas histologically and clinically overlap with dermoid cysts, but contain additional tissues derived from other germ layers, whereas dermoid cysts only contain ectodermally derived tissue.

A keratin-filled cyst can arise from metaplasia in an endodermal lesion but cannot be diagnosed as such, unless corresponding epithelium is identified. Lack of a granular layer in a keratinaceous cyst epithelium suggests a metaplastic process.