Key-words: Atypical teratoid rhabdoid tumor - diabetes insipidus - suprasellar
Introduction
Atypical teratoid rhabdoid tumor (ATRT) is a rare primary malignant tumor of the central
nervous system. It occurs mainly in children below 3 years old in posterior fossa.[[1 ]] To our knowledge, about fifty cases are reported in adult population, mainly in
females. The cases reported in sellar/suprasellar region have a sellar component with
suprasellar extension.[[2 ]] According to the World Health Organization classification of central nervous system
tumors 2016, ATRT is Grade 4. Diagnosis is mainly pathological through immunohistochemistry
either by alterations or loss of integrase interactor 1 (INI1) protein or BRG1 protein.[[3 ]] Due to limited number of reported cases, little knowledge is available about natural
history, behavior, prognosis, and best management guidelines of such tumor. Hence,
we present a unique case of purely suprasellar ATRT without sellar component. We are
reporting a case of purely suprasellar ATRT of a middle aged male who presented initially
with diabetes insipidus (DI).
Case Report
A 46-year-old male presented with sudden-onset anorexia, nausea, fatigue, dry mouth,
thirst, polyuria, polydipsia, and dizziness on standing for 10 days. There was no
other complaint. On examination, the patient was confused Glasgow Coma Scale 14, dry
mouth, dry tongue, bitemporal hemianopia, moving all limbs. Workup found increased
urine output (more than 3 L/day), high serum sodium (159 mmol/L), high serum osmolarity
(356 mosm/kg) with relatively low urine osmolarity (125 mosm/kg), and high creatinine
(160 μmol/L) (acute kidney injury due to dehydration) which improved after few days
of proper hydration. Hormonal profile revealed panhypopituitarism. Radiological images
revealed [[Figure 2 ]]a and [[Figure 2 ]]b suprasellar mass lesion. The patient was diagnosed as a case of central diabetes
insipidus with panhypopituitarism. He was started on desmopressin, hydrocortisone,
and thyroxine which resulted in improvement of his symptoms, signs, and sodium levels.
Ophthalmology examination preoperative revealed visual acuity 6/9 aided (glasses)
in both eyes [[Figure 1 ]]a and [[Figure 1 ]]b.
Figure 1: 1:(a,b) visual field examination of left eye on the left side and right eye on the
right side
Figure 2: (a) Axial DWI, T1 pre and post IV contrast, CISS, T2 and FLAIR WI MR images of the
brain showing midline intracranial extra-axial mass lesion centered on the supra-sellar
cistern of intermediate signal intensity in T1 and T2 WI and relatively high signal
intensity in FLAIR WI that shows intense non-homogenous post contrast enhancement
pattern as well as evidence of restricted diffusion pattern that indicates high cellularity
of the lesion. The differential diagnosis includes germ cell tumor, hypothalamic glioma,
meningioma and atypical teratoma. (b) Sagittal and Coronal thin sellar section T2
and T1 WI before and after IV contrast administration clearly showing the lesion in
the supra-sellar region indenting the floor of the third ventricle and being separable
from the pituitary gland and optic chiasm. (c) 1st day Post-operative MR imaging in
Axial T2, FLAIR and T1 pre and post IV contrast, Sagittal and Coronal Thin sellar
sections in T1 WI pre and post IV contrast showing almost total resection of the mass
lesion with expected post-operative changes; histopathological diagnosis of Atypical
Teratoid Rhabdoid tumor (ATRT) was given and the patient was referred to medical oncology
care.
After stabilization of patient medical conditions, he underwent right supraorbital
craniotomy and resection of suprasellar lesion [[Figure 5 ]]a and [[Figure 5 ]]b. Frozen section intraoperative was suggestive of high-grade malignant lesion.
Final pathology revealed ATRT [[Figure 3 ]] and [[Figure 4 ]]a,[[Figure 4 ]]b,[[Figure 4 ]]c,[[Figure 4 ]]d. Postoperative day 1, magnetic resonance imaging showed almost total resection
of the tumor [[Figure 2 ]]c.
Figure 3: Microscopic view showing sheets of rhabdoid cells with dense eosinophilic inclusion-like
cytoplasm (H&E ˟400)
Figure 4: (a)Tumor cells are diffusely positive with epithelial membrane antigen (EMA), (immunohistochemistry
˟200) (b) Tumor cells are significantly positive with cytokeratin AE1/AE3) (immunohistochemistry
˟200) (c) Tumor cells are focally expressing glial fibrillary acidic protein (GFAP)
(immunohistochemistry ˟400) (d) Loss of nuclear staining by INI-1 while blood vessels
show retained nuclear staining (immunohistochemistry ˟400)
Figure 5: (a) Microscopic images showing right supraorbital craniotomy approach and resection
of suprasellar lesion (atypical teratoid/rhabdoid tumor) yellow star: Dura, green
star: Right optic nerve, red star: Internal carotid artery black arrow atypical teratoid
rhabdoid tumor. (b) Endoscopic images showing right supraorbital craniotomy approach
and resection of suprasellar lesion (atypical teratoid/ rhabdoid tumor)
The case was discussed in a multidisciplinary meeting and planned for adjuvant chemoradiotherapy.
Pathological description of atypical teratoid/rhabdoid tumor
Sections show highly cellular tumor consisting of sheets, nests, and papillary structures.
The tumor cells have heterogeneous morphology, in some areas they appear small primitive,
while in others, they appear large polygonal with abundant dense eosinophilic cytoplasm,
and in most of the areas, they have rhabdoid appearance with eccentrically placed
vesicular nuclei, prominent nucleoli, and abundant eosinophilic inclusion-like cytoplasm
[[Figure 3 ]]. By immunohistochemistry, tumor cells show immunophenotypic heterogeneity characterized
by positivity with epithelial membrane antigen [[Figure 4 ]]a, cytokeratin AE1/AE3 [[Figure 4 ]]b, glial fibrillary acidic protein [[Figure 4 ]]c, S100, smooth muscle actin, Olig2, synaptophysin, and vimentin, but most importantly,
they show loss of nuclear staining by INI1 [[Figure 4 ]]d.
Discussion
ATRT is embryonal tumors containing rhabdoid component (eccentric round nuclei, large
cell body, small-to-medium size nucleoli, and open chromatin) in addition to primitive
neuroectodermal, mesenchymal, epithelial features. It was first described 1978 in
the kidneys. Brain tumors similar to primitive neuroectodermal tumor with rhabdoid
component were first described 1987 and named “atypical teratoid tumors of infancy."[[1 ]] Diagnosis is mainly pathological through immunohistochemistry either by alterations
or loss of INI1 protein or BRG1 protein in addition to rhabdoid components.[[1 ]],[[3 ]]
Based on our literature review, only fifty cases are reported in adults, with more
than two-third of cases in females.[[3 ]] The average age of diagnosis is 36.7.[[3 ]] The most common locations include cerebral hemispheres and sellar/suprasellar regions.
To our knowledge, all reported cases in sellar/suprasellar regions occurred in females
and all of them have sellar component with suprasellar extension.[[2 ]],[[4 ]],[[5 ]],[[6 ]],[[7 ]],[[8 ]],[[9 ]],[[10 ]],[[11 ]],[[12 ]],[[13 ]],[[14 ]],[[15 ]],[[16 ]] Our case is the first reported case to occur in middle-aged males with purely suprasellar
location without any sellar components. Intraoperative lesion appeared to be arising
from hypothalamus. Hence, it can direct research toward pathogenesis and origins of
such tumors.
Clinical presentation varies based on patient age, location, and tumor size. All cases
reported in sellar/suprasellar region presented mainly with headache and diplopia.[[2 ]],[[4 ]],[[5 ]],[[6 ]],[[7 ]],[[8 ]],[[9 ]],[[10 ]],[[11 ]],[[12 ]],[[13 ]],[[14 ]],[[15 ]],[[16 ]] Two of the reported cases presented with subarachnoid hemorrhage associated with
intraventricular extension.[[2 ]],[[11 ]] As our case is purely suprasellar (hypothalamic) with compression of pituitary
stalk, so presentation was a little bit different as diabetes insipidus and panhypopituitarism.
We preferred right supraorbital craniotomy approach based on many reasons. First,
it is a minimally invasive approach. Second, exposure is almost similar to other approaches
(pterional and interhemispheric). Third, you can work in different windows including
interoptic window, carotico-optic window, translamina terminalis, and lateral to carotid
window. In addition, our surgery included both microscopic and endoscopic techniques.
Putting in mind, you do not have to manipulate the optic nerve in supraorbital approach.
Right supraorbital approach is preferred as it is nondominant hemisphere, and we can
decompress optic nerve as there is more deficit on right side. On the other hand,
interhemispheric approach not superior to supraorbital approaches, it gives you access
only to midline windows including interoptic window and translamina terminalis but
not lateral to carotid window.[[17 ]],[[18 ]]
Based on genetic studies, ATRT arises as a result of chromosome 22 deletion including
area INI1/hSNF5 tumor suppressor gene required to suppress rhabdoid tumor.[[1 ]],[[19 ]] There is still no agreement about the best management guidelines. However, like
our case, treatment started with surgical resection followed by chemoradiotherapy.[[2 ]]
Prognosis is poor, and majority of sellar/suprasellar cases die within 2 years of
diagnosis.[[2 ]] There is no previous case as purely suprasellar (hypothalamic). Thus, we have no
data about the prognosis of purely suprasellar lesions.
ATRT is rarely considered in the differential diagnosis either radiologically, intraoperative.
Preoperative radiological differential diagnoses were germ cell tumor, hypothalamic
glioma, meningioma, and atypical teratoma. Our impression intraoperative was high-grade
glioma arising either from optic chiasm or hypothalamus. Fresh frozen sample sent
for pathology intraoperative and impression was highly malignant lesion either glioma
or metastasis. On the contrast, final pathology report was ATRT.
Therefore, we should to start consider ATRT in our differential diagnosis for suprasellar
lesions as it will affect our management either early surgical intervention for resection
and pathological diagnosis or follow-up with serial imaging. More basic and clinical
research is needed on multicenter level as a number of cases are limited to address
issues of natural history, behavior, radiological distinguishing specific features,
prognosis, and management strategy.
Conclusion
Our case is the first reported purely suprasellar (hypothalamic) ATRT without sellar
component in an adult male. We should consider ATRT in our differential diagnosis
of suprasellar lesions. We recommend gross total resection of such malignant lesion
followed by chemoradiotherapy. Reevaluation of our understanding of pathogenesis and
molecular genetics should be done to broaden our knowledge about actual origin of
these tumors. More research is needed to address natural history, behavior, radiological
distinguishing specific features, prognosis, and management strategy.
