Keywords
epidermoid cyst - sellar region - pathology - central nervous system cysts - brain
neoplasms
Palavras-chave
cisto epidermoide - região sellar - patologia - cistos do sistema nervoso central
- neoplasias cerebrais
Introduction
Epidermoid cyst (EC) is a benign cystic lesion covered by mature keratinized squamous
epithelium and occupied by keratin lamellae, without adnexal structures in its wall.
The process corresponds to ∼ 0.2 to 1.8% of all primary intracranial tumors and are
4 to 9 times as common as dermoid cysts.[1]
[2]
[3]
[4] Most ECs compromising the central nervous system (CNS) are extraaxial, leptomeningeal
lesions, with the cerebellopontine angle (40–50% of patients) being the most common
location. Epidermoid cysts can also be found in the 4th ventricle (17%), in the sellar/parasellar region (10–15%), in the cerebral hemispheres,
in the brainstem, in the skull, and in the spine.[1]
[2]
[3]
[4]
[5]
[6]
Most tumoral and non-tumoral sellar lesions are solid process, and pituitary adenoma
is the most common tumor in this topography. Cystic sellar lesions are not as frequent
as pituitary adenoma, and Rathke cysts and craniopharyngioma are usually the final
diagnosis. Epidermoid cysts of the CNS present slowly progressive symptoms, such as
headache and cranial nerve dysfunction.[2]
[3]
[6]
[7]
[8]
[9]
[10]
[11] Epidermoid cysts arise from ectodermal inclusion during the neural tube closure
in the third to the fifth week of embryogenesis. They have an excellent long-term
survival, and gross total resection is usually curative.[1]
[2]
[8]
[9]
[10]
[11]
The authors describe a case of sellar EC presenting endocrine alterations and progressive
visual disturbance in a 35 years female patient, and discuss the most common physiopathological
findings of this lesion, and its differential diagnosis.
Case History
A female patient, 35 years old, presenting clinical complaint of amenorrhea in the
previous 20 months was referred to the neurosurgical service due to a sellar cystic
mass. The patient had been accompanied by an endocrinologist during this period, with
regular use of prednisone (5 mg/day) and levothyroxine (100 ucp/day). In the last
4 months, the patient complained of visual disturbances. Magnetic resonance imaging
showed an increase in the dimensions of the process, which also exhibited hemorrhagic
areas, and measured 2.7 × 2.0 × 1.7 cm ([Fig. 1]). The campimetry showed peripheral visual loss. On physical examination, no signs
of neurological deficits were found. Chest and abdominal computed tomography (CT)
did not identify significant alterations. A clinical hypothesis of pituitary adenoma
with degenerative changes was established, and resection of the lesion was proposed.
The transsphenoidal approach identified an expansive lesion compromising the sellar
region ([Fig. 2]), with significant compression of the optic chiasm. A gross total resection was
performed. The pathological specimen was composed of some elastic, pale gray, irregular
fragments of tissue, the largest one measuring 1.1 × 1.0 × 0.8 cm. At microscopy,
a benign cystic lesion covered by keratinized stratified squamous epithelium and a
fibrous wall was found ([Fig. 3]). The process was filled with keratin lamellae and dystrophic tissue, and was contiguous
to normal hypophyseal tissue. The diagnosis of sellar EC was then established. In
the immediate postoperative period, the patient developed diabetes insipidus, which
was controlled with the use of desmopressin. After a follow-up of 8 months, no signs
of recurrence were identified on radiological evaluation, and the patient was asymptomatic.
During this period of clinical follow-up, the patient presented normal serum levels
for pituitary hormones and estrogen. The use of prednisone, levothyroxine, and desmopressin
was then discontinued.
Fig. 1 Epidermoid cyst: preoperative magnetic resonance imaging showing an expansive sellar
process.
Fig. 2 Sellar epidermoid cyst: a pale gray expansive lesion.
Fig. 3 Sellar epidermoid cyst: A benign cystic lesion covered by keratinized stratified
squamous epithelium, hematoxylin-eosin, 200x.
Discussion
Epidermoid cysts are rare processes that probably represent developmental lesions
resulting from embryologic displacement of ectoderm into the CNS tissue.[6] The pattern of embryological formation of the hypothalamic-pituitary-axis plays
a major role in its propensity in the development of sellar ECs.[3]
[4]
[12]
[13]
[14]
[15]
[16] Neurulation can be divided broadly into primary and secondary phases. In primary
neurulation, which occurs throughout the future brain, the neural tube is formed by
neural folding. The formation and closure of the neural tube occur between 18 and
26 days postconception. Closure of the neuropores occurs at the end of this developmental
process around day 26.[12]
[13]
[14] The current hypothesis is that there are multiple local (possibly five) neural tube
closure sites. Primary neurulation begins with neural induction, leading to the appearance
of the neural plate, a thickened dorsal midline ectodermal structure. The neural folds
converge toward the midline and fuse, forming the neural tube on day 22 in the future
cervical/occipital boundary. Initially, the wall of the neural tube is composed by
a columnar pseudostratified neuroepithelium. The skull base and facial skeleton are
derived from the neural crest.[12]
[13]
[14] The pituitary diverticulum of the stomodeum roof (oral ectoderm) will give rise
to the adenohypophysis. The neurohypophyseal diverticulum of the diencephalon floor
(neuroectoderm) will give rise to the neurohypophysis. Adenohypophyseal tissue can
be trapped anywhere along the path followed by Rathke's pouch during fetal development.[12]
[13]
[14] Two general patterns of neural tube malformation are encountered. In the first,
there is a failure of the developing neural tube to close properly, with secondary
disruption of the axial mesoderm, which determines abnormal neuroectodermal tissue
protruding through a secondary defect in mesenchymal structures.[12]
[13]
[14] In the second pattern, the primary embryonic defect is related to the development
of the axial mesoderm, and the neural tube is closed. During these development cellular
events, including migration, proliferation and differentiation, abnormal ectoderm
tissue can be associated with the future development of midline ECs. Neural tube defects
include meroencephaly, craniorachischisis, occult spina bifida, meningomyelocele,
encephalocele, and myeloschisis.[12]
[13]
[14] Unfrequently, CNS ECs arise from implants of epithelium carried into the meninges
during percutaneous aspiration of the subdural or subarachnoid space. A proportion
of spinal ECs, especially those in the lumbosacral region, occur in conjunction with
spina bifida or diastematomyelia. Unlike dermoid cysts, ECs often occur laterally,
without a preference for midline sites.[3]
[4]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
Intracranial ECs account for only 1% of all intracranial tumors, if suprasellar examples
are excluded. The cerebellopontine angle and parapontine regions are the most common
intracranial site for ECs.[2]
[3]
[8]
[11]
[15]
[16]
[17] Epithelial rests may be transplanted to regions such cerebellopontine angle by the
lateral migrating otic capsule or developing neurovasculature. Intraspinal lesions
are less common. Rarely, ECs are located in the cranial diploe of the middle ear region
or frontal bone, where they present as a lytic defect.[2]
[3]
[7]
[8]
[11]
[15]
[16]
[17]
[18]
The authors reported a female patient with clinical complaint of amenorrhea due to
a sellar EC. Symptoms associated to sellar EC can be related to a slow growing mass
effect, and include focal neurologic deficits or non-localizing signs such as headache,
visual alterations, and pituitary dysfunction.[15]
[18]
[19]
[20]
[21]
[22] Epidermoid cysts tend to surround adjacent structures, and its rupture can produces
chronic inflammation of the leptomeninges or ependyma.[15]
[18]
[19]
[20]
[21] Sellar/suprasellar ECs can determine disturbances in the release and/or production
of hormones, because the compressive effect of the process may affect the physiology
of the pituitary gland or even determine hypothalamic disorders. Since any hypothalamic
hormone can be synthesized in more than one hypothalamic nucleus, and a single nucleus
may express several hormones, different clinical signs can be identified.[19] Alterations in the suprachiasmatic nucleus of the hypothalamus can be associated
with decrease in gonadotropin release.[19] Lesions of the supraoptic nuclei can decrease the synthesis of oxytocin and vasopressin.
Damage of the ventromedial nucleus results in obesity; conversely, destruction of
the ventrolateral nucleus causes anorexia and cachexia. The arcuate (infundibular)
nucleus plays a major role in the modulation of anterior pituitary function. The paired
medial and lateral nuclei are associated with autonomic function, in special temperature
control and olfaction.[19] The posterior nucleus has been implicated in temperature regulation, and its large
neurons are thought to be the source of hypothalamic efferents, which descend to the
reticular formation of the brainstem. Increase of prolactin serum levels can be attributed
to injury of the arcuate nucleus, which controls the secretion of dopamine (an inhibitor
of prolactin secretion).[19] Hyperprolactinemia exerts an inhibitory activity on the positive feedback effect
of estradiol on gonadotropin-releasing hormone (GnRH) secretion. Increase of prolactin
seems to depend on decrease of factors that inhibit prolactin secretion, such as dopamine
produced by the arcuate nucleus of the hypothalamus (probably compressed by EC). In
females, hyperprolactinemia can determine galactorrhea, oligomenorrhea/amenorrhea
and infertility.[19]
Sellar ECs determining hypothalamic hyperfunction syndromes can be related to early
puberty, ectopic production of hypothalamic hormones, and inappropriate secretion
of antidiuretic hormone. Hypofunction syndromes can be associated to different endocrine
disorders like hypothalamic dwarfism, diencephalic syndrome, obesity, hypothalamic
hypogonadism, amenorrhea, diabetes insipidus, and hypopituitarism.[19] Other alterations include changes in appetite and thirst, hypothermia, hyperthermia,
disorders in the pattern of sleep and wakefulness, behavioral disorders, visual disturbances,
spasticity, hyperreflexia, ataxia, and uncoordinated movements.[19]
On CT, most sellar ECs are circumscribed, nonenhancing, extraaxial lesions, which
can exhibit calcification areas around 10% of cases. Magnetic resonance imaging findings
include variable intensity on T1-weighted images, and hyperintensity on fluid-attenuated
inversion recovery (FLAIR) and T2-weighted images.[1]
[4]
[6]
[10]
[15]
[17]
[19]
[20] On gross, sellar ECs are a pale-gray, uniloculated, translucent lesion, which can
measure from a few millimeters to over 4 cm in diameter.[1]
[4]
[6]
[9]
[15]
[16]
[21]
[22] At microscopy, ECs are covered by a mature keratinizing squamous epithelium, and
the lumen is occupied by lamellae of keratin. No evidence of atypias can be found
and the wall is constituted by connective tissue. Mitotic figures are very rare and
foreign body giant cell reaction is present in cases of a ruptured cyst. Sellar EC
shows positive immunoexpression for keratins and negative pattern for glial fibrillary
acidic protein (GFAP) and synaptophysin.[1]
[4]
[6]
[9]
[15]
[20]
[22]
In the sellar/suprasellar region, the differential diagnosis of EC includes dermoid
cysts, craniopharyngioma, enterogenous cyst, neuroglial cyst, arachnoid cysts, endodermal
cyst, Rathke cleft cyst with extensive squamous metaplasia, eventually metastatic
well differentiated squamous cell carcinoma, and mature teratoma.[4]
[5]
[6]
[9]
[11]
[15]
[20]
[23]
[24] Dermoid cysts (DCs) arise more commonly in the midline of infants, being related
to fontanel, the fourth ventricle, or the spinal canal. Dermoid Cyst (DM) exhibit
a thick wall and contain adnexal structures, such as hair follicles and sebaceous
glands.[4]
[5]
[6]
[10]
[13]
[20]
[21]
[22] Adamantinomatous craniopharyngioma exhibits a thick, complex, palisaded epithelium,
while papillary craniopharyngioma shows a thick epithelium disposed in irregular papillae
with fibrovascular core. Papillary craniopharyngioma lacks keratohyalin granules and
anucleate squames. Mature teratoma are more frequently solid masses constituted by
cartilaginous tissue, sebaceous gland, and mature dermis and epidermis.[4]
[5]
[6]
[10]
[15]
[21]
[24]
[25]
The curative treatment for sellar ECs is gross total surgical removal by transsphenoidal
approach, but the presence of dense adherence of the lesion to the adjacent structures
can limit the complete resection of the cyst.[2]
[3]
[4]
[8]
[16]
[25] The most common postoperative complications are diabetes insipidus, endocrine disturbances,
and chemical meningitis, due to leakage of keratin into the cerebral spinal fluid
(CSF) pathways.[2]
[3]
[4]
[6]
[8]
[16] After a follow-up of 9 months, no signs of recurrence or endocrine disturbances
were noted.
