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CASE REPORT |
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| Ahead of print
publication |
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Desmoplastic infantile ganglioglioma: A rare entity
Batuk D Diyora, Rahul M Chhajed, Gagan Dhall, Mehul Patel
Department of Neurosurgery, Lokmanya Tilak Municipal General (L.T.M.G.) Hospital and Medical College (Sion Hospital), Mumbai, Maharashtra, India
| Date of Submission | 28-Mar-2021 |
| Date of Decision | 03-Nov-2021 |
| Date of Acceptance | 13-Oct-2021 |
| Date of Web Publication | 30-Jan-2023 |
Correspondence Address:
Batuk D Diyora,
Department of Neurosurgery, Lokmanya Tilak Municipal General (L.T.M.G.) Hospital and Medical College (Sion Hospital), Sion West, Mumbai 400022, Maharashtra
India
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/jpn.JPN_71_21
 Abstract | | |
Desmoplastic infantile ganglioglioma (DIG) is a very uncommon intracranial tumor with an incidence of 0.1%–1.25%. It is most often seen in the first 2 years of life. We describe two cases of this unusual entity in a 5-month-old boy and a 15-month-old child, both of whom had a history of convulsions and were diagnosed as DIG on histopathology after surgery. Gross total excision resulted in a successful treatment outcome without the requirement of any additional treatment.
Keywords: Desmoplastic infantile astrocytoma, desmoplastic infantile ganglioglioma, ganglioglioma, infantile brain tumor, supratentorial tumor
| Introduction | |  |
Vanderberg et al.[1] coined the term desmoplastic infantile ganglioglioma (DIG) in 1987. The clinical, imaging, and prognostic characteristics of DIG are close to those of desmoplastic infantile astrocytoma (DIA), with the exception that DIA lacks ganglion cells.[2] This tumor is categorized as neural and mixed glio-neuronal tumors and categorized as grade I by the World Health Organization (WHO).[2] Approximately 110 cases of DIG have been reported in the literature so far.[1] This neuroepithelial tumor has dense desmoplastic tissues with divergent astrocytic and ganglionic differentiation on histopathology.[2],[3] Male children under 2 years are the most commonly affected.[2],[3] The supratentorial position is frequently observed, with the temporal and frontal lobe being the common locations.[1],[3] Increased head circumference with stressed bulging fontanel, headache, seizures, and motor delay are the symptoms of DIG.[3] We report two such unusual cases of DIG accompanied by convulsions.
| Case 1 | | |
A 5-month-old male child was taken to the clinic with a complaint of seizure. He was the first baby of the couple, delivered vaginally at full term. The family history was non-contributory. Physical and neurological examinations did not identify any aberration. Magnetic resonance imaging (MRI) of the brain showed mixed intensity lesion in the right temporal lobe. On T1-weighted images, cystic component was hypointense and solid component was isointense [Figure 1A]. On T2-weighted images, cystic component was hyperintense and solid component was isointense [Figure 1B]. Solid component was enhancing on contrast administration, whereas cystic was not [Figure 1C]. The patient underwent right frontotemporal craniotomy with gross total excision of the lesion. The postoperative course was phase was uneventful. Histopathological examination showed a desmoplastic reaction with ganglion cells [Figure 2A] and [B]. Immunohistochemistry (IHC) showed positivity for S-100, glial fibrillary acidic protein (GFAP), and synaptosin proteins [Figure 2C] and [D]. The follow-up of the patient after 24 months of surgery was unremarkable, and there was no evidence of seizure or disease recurrence. | Figure 1: Magnetic resonance imaging of the brain (axial view) showing mixed intensity lesion in the right temporal lobe. On T1-weighted images, cystic component was hypointense and solid component was isointense (A). On T2-weighted images, cystic component was hyperintense and solid component was isointense (B). Solid component was enhancing on contrast administration while cystic was not (C)
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,  | Figure 2: Photomicrograph showing the presence of: (A) desmoplasia, (B) ganglion cells on H & E stain, (C) GFAP positivity, and (D) synaptosin positivity on immunohistochemistry stain
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| Case 2 | | |
A 15-month-old female child was admitted with a complaint of seizure. Physical and neurological examination did not identify any problem. MRI of the brain revealed mixed intensity lesion in the left frontoparietal region. On T1-weighted images, cystic component was hypointense and solid component was isointense [Figure 3A]. On T2-weighted images, cystic component was hyperintense and solid component was isointense [Figure 3B]. Solid component was enhancing on contrast administration, whereas cystic was not [Figure 3C]. Postoperative T1-weighted image [Figure 3D], T2-weighted image [Figure 3E], and postcontrast image [Figure 3F] showed no evidence of recurrence. The child underwent left frontoparietal craniotomy with total excision of the lesion. The postoperative course was uneventful. Histopathological examination showed dense fibrotic stroma [Figure 4A] with scattered ganglion cells [Figure 4B]. IHC showed positivity for GFAP [Figure 4C]. After 24 months of the surgery, the follow-up is unremarkable, with no seizure or disease recurrence evidence. | Figure 3: Magnetic resonance imaging of the brain (axial view) showing mixed intensity lesion in the left frontoparietal region. On T1-weighted images, cystic component was hypointense and solid component was isointense (A). On T2-weighted images, cystic component was hyperintense and solid component was isointense (B). Solid component was enhancing on contrast administration while cystic was not (C). Postoperative T1-weighted image (D), T2-weighted image (E), and postcontrast image (F) showing no evidence of recurrence
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,  | Figure 4: Photomicrograph showing the presence of: (A) desmoplasia, (B) ganglion cells on H & E stain, and (C) glial fibrillary acidic protein positivity on immunohistochemistry stain
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| Discussion | | |
DIGs are uncommon intracranial tumors that may resemble DIA, and both belong to a category of desmoplastic infantile glioneuronal tumors (DIGNT).[4] The ages of two cases described here are 5 months and 15 months, respectively. Although most DIG cases are diagnosed in the first 2 years of life, non-infantile ganglioglioma cases have also been identified in the literature.[3],[4] DIG is more common in males than in females, with an M:F ratio of 1.7:1.0.[3] However, we had one male child and one female child.
The supratentorial area is involved exclusively, with the temporal or frontal lobes being the most common sites.[3] They increase in size over time and have a mixed solid and cystic component. Similar findings were observed in both of our cases. These large tumors are firmly attached to the dura, with wide infiltration of the subarachnoid space but do not enter the ventricular system.[4],[5] The DIG histologically shows the most prominent feature of desmoplasia and spindle cells with a storiform pattern.[3] They also show ganglion cells in clusters or as a single cell.[3] The DIGs are known to show the presence of a substantial number of mitoses, associated with increased MIB-1 indices and the presence of necrotic foci.[5] On IHC, they are GFAP and synaptophysin positive.[5] The DIG needs to be differentiated from the pleomorphic xanthoastrocytoma, gliofibroma, ganglioglioma, and other small blue cell tumors of the central nervous system such as medulloblastoma, primitive neuroectodermal tumors, and pineoblastomas.[3],[6] These patients usually present with symptoms of intracranial hypertension, sunset eye, enlarging head circumference, bulging fontanels, variable localizing signs, including seizures or paresis.[3] Similarly, both of our patients presented with seizures.
DIGs do not show the genetic alterations commonly encountered in diffuse astrocytes. Given the fact that tumor cells express both glial and neuronal proteins along with basal lamina formation, the origin is postulated from the subpial astrocytes.[6] Recent literatures have entitled DIG as a low-grade MAPK pathway-driven neuroepithelial tumor, despite the varied opinion of it being the driver mutation or a subclonal event. Although the BRAFV600E mutation frequency is in the low range even in the high tumor percent, it is attributed to the reactive macrophage population in the desmoplastic region which is immune-negative for these mutations. In addition, further studies documenting TPM3-NTRK1 fusions in DIG have opened up new avenues for NTRK targeted therapies.[7]
Some cases of bone abnormalities adjacent to a tumor have been reported in the past.[1] However, few atypical presentations of DIG are also documented, including primary vermian localization, primary spinal localization, occurrence in patients older than 6 years.[3],[8] Rare cases have shown CSF dissemination, malignant transformation, metastatic spread, and multiple cerebral lesions.[8] Computerized tomography (CT) scan and MRI show infiltrating and aggressive features, despite being superficial cerebral lesions with a solid and cystic component.[4] The solid element of the tumor commonly shows contrast enhancement.[3],[4]
Gross total excision is the treatment of choice, which shows an excellent prognosis.[3] However, in the case of partially resected tumors, follow-up with neuroimaging is recommended, as these tumors are observed at a very young age.[3] Tamburrini et al.[9] reported an operated case of DIG of a 9-month-old baby, in which a nodule, firmly adherent to the internal cerebral veins and vein of Galen, was left behind. Follow-up MRI brain, 9 months’ postsurgery, showed disappearance of the nodule with no recurrence even after 11 years of surgery. The literature documents up to 19 years of recurrence-free period.[3]
Controversy exists with the use of adjuvant therapy, especially in cases of incompletely resected tumors. The role of adjuvant treatment is minimal, and chemotherapy is provided to those patients with high-grade tumors displaying brisk mitosis, aneuploidy, and raised MIB, involving eloquent part of the brain, unsafe for operation.[10] The latest finding of mitogen-activated protein kinase (MAPK) pathway activation in DIG chiefly in the form of BRAF alterations (V600E/D mutations, FXR1-BRAF fusion) shows that DIG may denote another MAPK pathway-driven neuroepithelial tumor, like pilocytic astrocytoma, thus increasing treatment options for patients that require adjuvant therapy.[7] Hoving et al.[11] reported favorable outcome in an operated DIG patient associated with the presence of a primitive cell component and an elevated MIB-1/Ki 67 LI, with repetitive cycles of high-dose chemotherapy consistent with cyclophosphamide, cisplatin, etoposide, vincristine, and thiotepa, along with peripheral blood stem cell rescue.
In these two patients after 24 months of the surgery, there was no evidence of disease recurrence or spread and did not require additional therapy. Therapeutic analysis of 84 DIG cases shows that only surgery was done in 60.7%, 23.8% of patients required surgery plus chemotherapy, 10.7% required surgery plus radiotherapy, and 15.5% needed second surgery. Leptomeningeal spread was seen in 8.3% of the patients and death was the outcome in 8.3% of DIG cases.[1]
| Conclusion | | |
DIG is a rare intracranial tumor. Gross total excision is the treatment of choice, which shows an excellent prognosis. Controversy exists with the use of adjuvant therapy, especially in cases of incompletely resected tumors. The importance of adjuvant radiotherapy has not been established.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
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