Keywords
brain cyst - glioblastoma - central nervous system - pathology - prognosis
Palavras-chave
cisto cerebral - glioblastoma - sistema nervoso central - patologia - prognóstico
Introduction
Cystic lesions of the central nervous system (CNS) parenchyma comprise distinct pathological
entities.[1]
[2]
[3] Benign cystic process arising in CNS include arachnoid cyst, epidermoid and dermoid
cysts, colloid cyst, ependymal cyst, pineal cyst, Rathke cleft cyst, or even infectious
diseases such as cysticercosis and abscesses.[1]
[2]
[3]
[4] Slow-growing CNS neoplasms such as ganglioglioma, hemangioblastoma, and pilocytic
astrocytoma may exhibit cystic areas. Cysts differ from cystic neoplasms in that they
lack a solid nodular area.[1]
[2]
[4] This typical finding is fundamental to distinguish glial cysts from cystic gliomas
with mural nodules, and cystic craniopharyngiomas from epithelial cysts. In adults,
glioblastomas and metastatic carcinomas can develop into cystic variations.[1]
[4]
[5] Mural nodule biopsy is recommended to obtain an accurate diagnosis. However, in
some cases, the mural nodule may be difficult to detect.[2]
[4]
[5]
[6] In this case report, the authors describe two distinct cystic lesions, a developmental
disorder and a high-grade glial neoplasm, to discuss characteristic histological findings
and differential diagnosis.
Case 1
A 60-year-old female patient presented with an incidental finding of an expansive
brain lesion during hospitalization for coronavirus disease 2019 (COVID-19). The patient
reported frequent episodes of chronic headache, systemic arterial hypertension, dyslipidemia,
patent foramen ovale, and myocardial revascularization. Neurological examination showed
no abnormality. Magnetic resonance imaging (MRI) revealed a cystic lesion near the
suprasellar cistern ([Fig. 1]), extending toward the interpeduncular cistern and defining a bulging area of the
inferior wall of the third ventricle, with obliteration of the infundibular recess.
The signal intensity of the lesion was similar to that of the cerebral spinal fluid,
and the lesion measured 4.6 × 3.6 × 3.5 cm ([Fig. 2]).
Fig. 1 Enterogenous cyst: MRI exhibiting a cystic lesion near the suprasellar cistern.
Fig. 2 Enterogenous cyst: MRI showing a cystic lesion measuring 4.6 × 3.6 × 3.5 cm and arising
in inferior wall of the third ventricle.
The patient underwent left pterional craniotomy, dissection of the Sylvian fissure,
and visualization and resection of the lesion close to the interpeduncular fossa.
The specimen was sent for anatomopathological examination with a clinical–surgical
hypothesis of a parasitic lesion. Microscopic examination of the process revealed
a benign cystic lesion with walls consisting of connective tissue and internally covered
by cuboidal and/or cylindrical epithelium, sometimes simple, sometimes pseudostratified,
with ciliated or muciparous cells ([Fig. 3]), compatible with an enterogenous cyst.
Fig. 3 Enterogenous cyst: benign cystic lesion covered by cuboidal and/or cylindrical epithelium,
hematoxylin-eosin, 100x.
Case 2
An 18-year-old, previously healthy, male patient was referred to the hospital with
complaints of severe headache and hypertensive peaks associated with temporary deviation
of the rima oris for the past 7 days. He also reported episodes of fever, tremors,
and sweating. On physical examination, the patient was somnolent and disoriented,
with dysarthria, left hemiparesis, and a score of 13 on the Glasgow scale. Computed
tomography and MRI revealed a solid cystic lesion in the topography of the third ventricle,
measuring 5.4 × 5.0 × 4.7 cm ([Fig. 4]) and causing hydrocephalus, compression of the interpeduncular region of the midbrain,
a significant reduction in the amplitude of perimesencephalic cisterns, and cerebral
edema, ([Fig. 5]) suggestive of craniopharyngioma. The patient developed nausea, vomiting, intracranial
hypertension, and Parinaud syndrome.
Fig. 4 Glioblastoma: MRI revealed a solid cystic lesion in the topography of the third ventricle.
Fig. 5 Glioblastoma: MRI exhibiting a solid-cystic lesion, which determined hydrocephalus,
compression of the interpeduncular region of the midbrain, a reduction of perimesencephalic
cisterns, and edema.
External ventricular drainage was performed, leading to partial improvement of symptoms.
The patient progressed to spasticity, anisocoria without light reflexes, tachycardia,
tachypnea, and decorticate and decerebrate posturing, with no eye opening. Orotracheal
intubation was then performed. The electroencephalogram showed slow and dysfunctional
background activities, dominated by diffuse delta waves and a small amount of superimposed
theta activity, compatible with diffuse dysfunction of brain activity without epileptiform
paroxysms. The patient underwent resection of the lesion. Pathological examination
revealed a poorly differentiated, pleomorphic, malignant neoplasm characterized by
epithelioid/polygonal cells with high mitotic index and areas of necrosis ([Fig. 6]).
Fig. 6 Glioblastoma: A high-grade glioma with high mitotic index and necrosis, hematoxylin-eosin,
200x.
The lesion exhibited strong and diffuse positive immunoexpression for GFAP, OLIG2,
synaptophysin, CD99, INI-1, and ATRX, and was negative for IDH, p53, H3K27M, PHOX2B,
SALL4, and HCG. The Ki-67 expression was observed in 95% of neoplastic cells ([Fig. 7]). These histopathological findings were compatible with glioblastoma associated
with an area of primitive neuroectodermal characteristics and some giant tumor cells,
grade 4 according to the World Health Organization (WHO) 2021 system.
Fig. 7 Glioblastoma: High proliferative index estimated by Ki-67 imunoexpression, Ventana Systems, 400x.
The patient evolved with diabetes insipidus, central hypothyroidism, secondary adrenal
insufficiency, fever, leukocytosis with deviation, thrombosis in the left upper limb,
progressive worsening of the neurological condition, and nonreactive mydriasis associated
with septic shock. Death occurred 9 weeks after the surgical procedure.
Discussion
Intracranial cystic lesions are a heterogeneous group of processes, including parasitic
infections, abscesses, developmental cysts, and primary and metastatic neoplasms.[1]
[2]
[4] In the case of primary and metastatic neoplasms, analysis of medical history often
leads to the correct diagnosis.[1]
[2]
[4] Recently, imaging, especially new MRI techniques, has proven to be particularly
useful for the diagnosis of these challenging lesions. However, it is only after histological
analysis that a definite diagnosis can be made.[2]
[4]
[5]
[6]
Infectious diseases, such as neurocysticercosis, echinococcosis, cryptococcosis, tuberculosis,
amebiasis, and toxoplasmosis, are often suspected in patients with a cyst, as revealed
by imaging, and presenting with severe headache, convulsion, fever, or delirium. By
contrast, incidentally found intracranial cysts are commonly congenital.[2]
[4]
[5]
[7] Arachnoid, pineal, epidermoid, dermoid, ependymal, Rathke cleft, and enterogenous
cysts are some of the nonneoplastic diagnostic possibilities.[2]
[5]
[7]
[8]
[9] Benign neoplastic intracranial diseases include craniopharyngiomas, usually suspected
when located at the suprasellar region, having excellent survival rates. Intratumoral
necrosis or hemorrhage is responsible for cystic presentation of both intracranial
metastases and higher-grade primary tumors. The former usually presents as a multifocal
lesion.[1]
[5]
[7]
[8]
[9]
[10]
In our first report, we described a rare case of an intracranial enterogenous cyst,
also called endodermal cyst. This entity is a benign developmental lesion of endodermal
origin.[2]
[3]
[11]
[12]
[13] Its pathogenesis is not fully understood, but probably arises after failure of obliteration
of the neurenteric canal, with displacement of endodermal cells. It is more commonly
found in the spine, rarely as an encephalic lesion.[2]
[11]
[12]
[13] Histologically, the cyst is lined by gastrointestinal or respiratory-type epithelium,
with or without cilia, cuboidal to columnar, and simple to pseudostratified. It is
sometimes impossible to histologically distinguish a Rathke cleft cyst from an enterogenous
cyst; the former is often diagnosed when the lesion is intra- or suprasellar.[1]
[5]
[7]
[8]
[13]
[14] Given the nonneoplastic nature of enterogenous cysts, symptoms depend on lesion
size and location, ranging from headaches (in almost 50% of patients) to seizures
and deficits. Treatment in most cases is by surgical resection. Follow-up is recommended,
as recurrence is common.[1]
[5]
[7]
[8]
[14]
[15]
In our second report, we described the case of an H3-/IDH-wildtype glioblastoma, with
giant cells and primitive neuroectodermal component, presenting as an acute, aggressive,
solid cystic lesion of the third ventricle. Glioblastoma is a high-grade glioma featuring
nuclear atypia, pleomorphism, mitotic activity, diffuse growth pattern, microvascular
proliferation, and necrosis.[1]
[4]
[7]
[11]
[15]
[16] It is the most frequent malignant brain tumor in adults, very rarely occurring in
the pediatric population. In the latter case, the malignancy is defined as pediatric-type
high-grade diffuse glioma, according to the 2021 WHO CNS classification.[10] Glioblastomas develop rapidly, primarily manifesting as focal neurological deficits,
as in our case. Imaging reveals irregularly shaped and ring-shaped zones of contrast
enhancement around a dark central area of necrosis, sometimes interpreted as a cystic
area in the lesion.[2]
[3]
[10]
[14]
[16]
[17] Surgical excision is the primary treatment, although the disease is almost invariably
fatal. An abrupt change in morphology may reflect new clone proliferation through
new genetic alterations.[1]
[2]
[5]
[9]
[10] The primitive neuronal component represents a variation in glioblastoma, with one
or more solid-looking nodules showing primitive neuronal morphology sharply demarcated
from adjacent glioma, markedly increased cellularity, higher N/C ratio, mitotic activity,
karyorrhexis, and anaplastic cytology similar to that of other CNS embryonal neoplasms.[2]
[3]
[5]
[7]
[8]
[11]
[13]
[17] It usually shows synaptophysin positivity, loss of GFAP expression, and a high Ki-67 index. This subtype has a high frequency of MYC gene amplification and p53 immunoreactivity.
Although the survival time is similar to that of other glioblastomas,[9] our case presented as a very aggressive acute disease, with 2 months from first
symptoms to death.[1]
[5]
[9]
[10]
[18] We add this unfortunate case to the very few literature reports of this aggressive
high-grade glioma variant in the pediatric population.
