Keywords
astrocytoma - primary brain neoplasm - hypothalamus - neurosurgery
Palavras-chave
astrocitoma - neoplasias encefálicas - hipotálamo - neurocirurgia
Introduction
The pilomyxoid astrocytoma (PMA) is a rare tumor of the central nervous system with
higher prevalence among young children and generally located on the hypothalamic area.
It was first described as a separate entity in 1999.[1] Previously, the PMA was classified as a pilocytic astrocytoma (PA) due to several
features that they share. The histological differentiation between PMA and PA provided
a further analysis of the PMA's behavior and, consequently, a better development of
its management, though neurosurgeons and neurologists still have not reached a consensus.
Though considered different entities, many authors describe the PMA as a variant of
PA, in which it is believed that the PMA is part of the natural process of maturation
of the PA.[2]
[3]
[4] This study presents a case of a 16-year-old female patient with the diagnosis of
PMA.
Case Report
A 16-year-old female patient, previously healthy, presented to the medical service
complaining of nausea and vomiting for a period of over 2 weeks. Patient had a history
of headaches, which started 6 months prior to her current presentation and were progressively
worsening. She denied having focal neurological deficits or any other symptoms. The
neurological examination revealed only bilateral papilledema.
Magnetic Resonance imaging (MRI) of the head displayed a well-circumscribed lesion
of solid and cystic components at the intraventricular and thalamic regions. There
was also a peritumoral edema associated with mass effect and hydrocephalus ([Fig. 1]).
Fig. 1 (a) Coronal T1-weighted magnetic resonance imaging (MRI) demonstrating a well-circumscribed
periventricular lesion, mildly enhanced. (b and c). Axial T1-weighted MRI revealing
periventricular and hypothalamic lesion, mildly enhanced. On all scans, peritumoral
edema, mass effect and signs of hydrocephalus can be seen.
The patient underwent ventriculoperitoneal shunt to treat the hydrocephalus and intracranial
hypertension. After 2 weeks, she underwent another surgical procedure through frontal
craniotomy with transcallosal approach, which resulted in subtotal resection of the
lesion.
The histological examination identified a glial neoplasm composed of a monomorphic
population of cells with oval nuclei and elongated cytoplasmic processes in a myxoid
background. No mitotic figures or atypical cells were found. There was no evidence
of Rosenthal fibers or eosinophilic granular bodies— which is typical in cases of
PMA. The immunohistochemical analysis was positive for S100 protein, glial fibrillary
acidic protein (GFAP), P53, integrase interactor 1 (INI-1) and was strongly positive
for ki67, ranging from 80–90%. The synaptophysin stain was inconclusive and the epithelial
membrane antigen (EMA) study was negative.
After the surgery, the patient started chemotherapy with temozolomide as adjuvant
therapy associated with radiosurgery. The patient has been in follow-up for 9 months
until the present date, and she has been asymptomatic so far. The MRI scan has shown
no signs of progressions of the remaining lesion.
Discussion
The PMA is a rare tumor of the central nervous system first described in 1999.[1] Previously, due to some of its characteristics, the PMA was classified as pilocytic
astrocytoma (PA). However, recent studies differentiated them, setting PMA and PA
as two distinct entities. Still, some authors consider PMA a variant of PA, accounting
PMA as part of a natural process of maturation of PA.[2]
[3]
[4]
The PMA represents 10% of tumors previously diagnosed as PA; PMA is more prevalent
in the hypothalamus, while PA is the most common fossa posterior tumor during infancy.[3] On average, PMA is diagnosed by the age of 18 months, and PA by the age of 58 months,
both being considered childhood tumors.[5]
Typical PMA histological characteristics consist of piloid monomorphous cells in a
myxoid background, often without Rosenthal fibers and eosinophilic granular bodies.[1]
[2]
[4]
[5]
[6] The tumor cells are generally arranged around vessels making a pattern that resembles
pseudorosettes.[1]
[2]
[4]
[5]
[6] By contrast, PA often presents eosinophilic granular bodies and Rosenthal fibers
associates with dense cellular areas alternating loose and cystic regions.[1]
[4]
The clinical manifestations of PMA and PA can also distinguish these two tumors. When
compared with PA, PMA has shown a more aggressive behavior, being responsible for
higher rates of cerebrospinal fluid dissemination, shorter progression-free survival
and shorter overall survival.[1]
[2]
[5]
[7]
Imaging findings describe PMA as a well-circumscribed lesion, with solid and cystic
components, often located on the hypothalamus.[2]
[3]
[8] The lesions are generally isointense on T1-weighted MRI images and hyperintense
on T2-weighted ones.[2]
[8] Evidence of necrosis is rare and occasionally signs of hydrocephalus, mass effect
and peritumoral edema may be seen.[2]
[3]
[8] Several of these characteristics are shared with PA findings and therefore, there
are no radiographic features that can reliably distinguish these two entities.[2]
[8]
Though recently PMA has been further studied, its behavior is still a matter of debate.
The previous World Health Organization (WHO) classification for tumors of the central
nervous system classified the PMA as a grade II tumor, while PA is reported as grade
I.[9] The latest classification, released in 2016, suppressed the grade of PMA due to
the lack of elucidation of PMA's behavior and of its relation to PA. In this last
classification, PA remained classified as grade I, owing it to its indolent course.[9]
This lack of consensus regarding PMA's clinical course is reflected in the controversy
in its management. Surgical resection is the mainstay treatment for low-grade astrocytomas.[2]
[5] Depending on the location of the lesion, gross total resection (GTR) is indicated,
as it is the best predictor of favorable outcomes.[2] Surgery is not an option when it cannot be performed without aggravating or creating
neurological deficit.[10] Granted that PMA is mainly located on the hypothalamus, GTR is often not possible,
leading to partial or subtotal resection of the tumor.[5]
[7] Ventriculoperitoneal shunt is often performed, given the findings of mass effect
and symptoms of intracranial hypertension.[10]
Adjuvant therapy is administered in the cases in which surgery is not an option of
treatment, GTR is not possible or in cases of recurrence of the tumor.[2] The main types of adjuvant therapy are chemotherapy, radiotherapy and radiosurgery.
Chemotherapy is the usual choice of treatment, once PMA is more frequent during infancy
and radiosurgery and radiotherapy are not indicated in early ages.[7]
[10]
Surgery is considered the choice of treatment for recently diagnosed circumscribed
gliomas in which the rates of progression of disease are lower; however, PMA shows
a higher rate of recurrence after surgery when compared with PA.[5]
[6]
[10] Regarding relapsed tumors, a combined therapy consisting of surgery, chemotherapy
and radiotherapy displayed more favorable outcomes.[5]
This case report shows a 16-year-old female patient with the diagnosis of PMA who
underwent subtotal resection of the tumor associated with adjuvant therapy with temozolomide
and radiosurgery, as the patient is old enough to accept radiation. Nine months after
the treatment, no progression of the disease was seen on MRI and the patient is asymptomatic.
Conclusion
Pilomyxoid astrocytoma is a rare central nervous system tumor recently described and
with few reports thus far, which leads neurosurgeons and neurologists to a lack of
understanding of the behavior of the tumor and, consequently, its management. The
authors report a case of a 16-year-old female patient with PMA who underwent subtotal
resection of the tumor associated with chemotherapy and radiosurgery and has shown
no signs of progression of the disease on a 9-month follow-up.
Pilomyxoid astrocytoma has been described as a more aggressive tumor of the infancy
when compared with PA, and its treatment remains controversial. Further studies are
necessary for a better understanding of this tumor's clinical course and hence, for
an improvement on the types of treatment.
