Keywords atypical rhabdoid teratoid tumor - embryonic tumors - malignancies in childhood -
neuroectodermal tumors
Palavras-chave tumores teratoides rabdoides atípicos - tumores embrionários - malignidades em crianças
- tumores neuroectodérmicos
Introduction
The atypical rhabdoid teratoid tumor (ARTT) is a rare embryonic tumor, defined as
a distinct entity in 1996 and included in the World Health Organization (WHO) classification
of central nervous system (CNS) tumors in 2000.[1 ]
[2 ]
[3 ] In 2016, the WHO ranked the ARTT as a CNS embryonal tumor with rhabdoid features.[4 ] The ARTT is a highly malignant tumor whose survival period is around 1 year. This
tumor is usually diagnosed in children under 3 years of age and is related with a
genetic mutation that causes an inactivation of the SMARCB1 gene, losing the expression
of the INI1 protein,[2 ] a tumor suppressor.[5 ] The authors present the case of a child patient, who showed an ARTT in the left
frontal lobe, with history of 1 day of symptoms.
Clinical Summary
We present the case of a 3-year-old Caucasian male patient, with a history of headache
and vomiting, followed sometimes by absence seizures, temporal automatism and syncope,
accompanied by sialorrhea, sphincteric loss and postictal period. The computed tomography
(CT) scan of the patient's brain revealed an expansive lesion in the left frontal
lobe, hypodense, heterogeneous, with calcifications. The mass was irregular and had
poorly defined borders, measuring ∼ 2.4 × 4.8 cm with deviation of the midline. The
magnetic resonance imaging (MRI) confirmed the left frontal lesion, with local mass
effect, invasion of the corpus callosum, and irregular gadolinium enhancement and
restriction to diffusion, suggesting a high cellular tumor ([Fig. 1a ]–[f ]). A surgical subtotal resection was performed, and the postoperative CT scan confirmed
a residual lesion ([Fig. 2a ]–[c ]).
Fig. 1 MRI (a) Axial T1-Weighted with gadolinium enhancement: large intra-axial mass, with
irregular contrast enhancement in the left frontal lobe extending to the frontal horn
of the ipsilateral ventricle. (b) Coronal T1-Weighted with gadolinium enhancement:
irregular enhancement. (c) Sagittal T1-Weighted with gadolinium enhancement: invasion
of the rostrum of the corpus callosum. (d) Axial T2-Weighted: hyperintense lesion
invading the corpus callosum. (e) Axial FLAIR: mild edema, besides the great diameter
of the lesion. (f) Axial Diffusion Tensor: intense restriction to diffusion inside
the tumor.
Fig. 2 (a) Immediate postoperative CT scan: subtotal resection of the tumor due to the invasion
of the corpus callosum. (b) Axial T1-Weighted MRI with gadolinium enhancement: internal
CSF leak, as well as intense ventricular enlargement, and gadolinium enhancement inside
the ventricle and in the operative site. (c) Axial T1-Weighted MRI with gadolinium
enhancement: performed 2 months after the latter, evidencing recrudesce of the lesion.
Shortly after the initial surgery (less than 2 months), the symptoms recurred, and
the new neuroimaging study confirmed tumor recrudescence. The patient was submitted
to a new surgical procedure and developed meningitis due to a cerebral spinal fluid
(CSF) leak, which was treated with antibiotics and intervention to the fistula. In
the following months, three cycles of chemotherapy were performed, and the patient
developed severe pancytopenia, acute hydrocephalus, intracranial hemorrhagic events
and tumor recurrence. Due to the aggressive behavior of the tumor, as well as the
poor clinical status of the patient, palliative care was undertaken.
Pathological Findings
The pathological examination evidenced a tumor with atypical elongated and polygonal
cells, eosinophilic and bright cytoplasm, vesicular nuclei with not very evident nucleolus.
The immunohistochemical study demonstrated inactivity of INI1 and presence of S-100
protein and Ki -67 (a cellular proliferation antigen). These results confirmed the diagnosis of ARTT
([Fig. 3a ]–[d ]).
Fig. 3 (a) HE(200x). Atypical rhabdoid cells exhibiting vesicular nuclei. (b) HE(200x).
Neoplastic cells sketching mucosaccharides. (c) HE (100x). Neoplastic cells with fusiform
aspect. (d) Immunohistochemical study (400x) evidencing negative INI1 stain.
Discussion
The ARTT definition originates because, histologically, tumor cells show diversity,
in a combination of rhabdoid cells and neuroectodermal, epithelial, and mesenchymal
elements, but lack divergent tissue development pathognomonic of teratoma.[1 ]
The ARTT can be localized everywhere inside the CNS, including the cerebellopontine
(CP) angle cisterns, meninges, cranial nerves, spinal canal and extradural sites.
It can also be found outside the CNS.[2 ] Supratentorial tumors are usually located in the cerebral hemispheres, while infratentorial
lesions are more common in cerebellar hemispheres, CP angle and brainstem, being more
prevalent in children younger than 2 years.[4 ] The frontal lobe is commonly involved in supratentorial ARTTs, with a thick irregular
heterogeneously enhancing wall encircling the central cystic or necrotic lesion.[1 ] Tumors wider than 4 cm are commonly found in Caucasian male children younger than
3 years, and they normally involve the cerebellum, ventricles, or frontal lobe.[6 ]
The clinical features depend on the age of the patient, as well as on the location
of the tumor. The most common symptoms include headache, vomiting, lethargy, failure
to thrive, regression of developmental milestones, irritability and macrocephaly,
in very young children. If the tumor involves the cerebellar hemispheres, the patient
can present ataxia, head tilt and nystagmus, and if the CP angle is involved, the
patient can also present with cranial nerve palsies.[1 ]
Brain CT scan usually demonstrates hyperdense lesion and heterogeneous contrast enhancement.
Calcifications may be seen in up to 40% of tumors. Magnetic resonance imaging usually
shows heterogeneous isointense signal on both T1 and T2-weighted images and variable
enhancement with gadolinium— heterogeneous, peripheral nodular, intense, or mild.[1 ] Embryonic tumors have similar images features. They can be iso- or hyperdense, intensifying
in a homogeneous manner in the CT scan; cysts, calcifications and hemorrhage can also
be found, and hydrocephalus is usually present in these patients. The MRI defines
more accurately the dimension of the tumor and possible dissemination.[7 ]
Medulloblastoma is the main radiological differential diagnosis of ARTT. It may also
include other embryonic tumors, such as supratentorial primitive neuroectodermal tumor,
and ependymoma, teratoma, choroid plexus tumors, pilocytic astrocytoma, and desmoplastic
infantile ganglioglioma.[1 ]
The main treatment for ARTTs is a combined approach, with maximal excisional surgery,
radio and chemotherapy. Surgery is always performed when indicated, but, depending
on the clinical status, only radiotherapy, chemotherapy or both, are performed.[6 ]
[7 ]
Histopathologic studies can evidence a tumor composed by rhabdoid cells, with cytoplasmic
vacuolation and arranged in nests or sheets, frequently with a jumbled appearance.
However, these typical cells are found in the minority of cases. The majority of cases
are formed by variable components, as primitive neuroectodermal, mesenchymal, and
epithelial features. The most common components found are small-cells, mitotic figures,
necrosis and hemorrhage. Mesenchymal and epithelial differentiation and myxoid matrix
are less commonly found.[4 ] Immunohistochemical stain showed that these lesions lose the nuclear expression
of INI1 (a tumor suppressor gene, usually mutated in malignant rhabdoid tumors), and
are positive for Vimentin, S-100 protein and epithelial membrane antigen (EMA).[2 ] In our case, both INI1 ([Fig. 3d ]) and neu-N (a neuronal marker) were negative in the immunohistochemical stain, while
it was positive for S-100 protein (present in cells derived from the neural crest),
glial fibrillary acid protein (GFAP), typical of glial lesions, and Synaptophysin
(representing neural/neuroendocrine tissues). Also, the Ki -67 was positive, in the order of 70%. This combination was compatible with ARTT.
The diagnosis of ARTT is increasing, mainly because before immunohistochemical studies,
this tumor was commonly misdiagnosed, worsening the dismal prognosis of the disease.[2 ]
This report shows the case of a young patient diagnosed with ARTT, whose clinical
condition dramatically worsened within a couple of months. This demonstrates the malignant
and lethal behavior of ARTT in children, despite all the efforts that can be made.
