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Year : 2019  |  Volume : 62  |  Issue : 3  |  Page : 495-497
Extracranial metastasis in a IDH- wild type glioblastoma

1 Department of Pathology, Oncquest Lab Ltd, Mohandai Oswal Hospital, GT Road, Ludhiana, Punjab, India
2 Department of Medical Oncology, Mohandai Oswal Hospital, GT Road, Ludhiana, Punjab, India

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Date of Web Publication26-Jul-2019

How to cite this article:
Goyal R, John PJ, Bhatoa S, Arora R. Extracranial metastasis in a IDH- wild type glioblastoma. Indian J Pathol Microbiol 2019;62:495-7

How to cite this URL:
Goyal R, John PJ, Bhatoa S, Arora R. Extracranial metastasis in a IDH- wild type glioblastoma. Indian J Pathol Microbiol [serial online] 2019 [cited 2020 Nov 25];62:495-7. Available from: https://www.ijpmonline.org/text.asp?2019/62/3/495/263484


Glioblastoma is the most common and most aggressive primary brain tumor. It usually spreads by direct extension and infiltration into the adjacent brain tissue and along with white matter tract rather than by metastasis. Extraneural metastasis from glioblastoma is rare despite the highly invasive nature with reported incidence of less than 2%. The rarity of this phenomenon has been attributed to various aspects of pathophysiology that prevent glioblastoma cells from infiltrating and surviving beyond the intra-cranial environment. We report a case of IDH-wild type glioblastoma with extracranial metastasis in submandibular region.

A 33-year-old male presented with headache, dizziness, and visual disturbance. The MRI brain showed irregular heterogenous mass in left temporal lobe. It measured 50 × 50 × 47 mm with necrotic and hemorrhagic areas and perifocal vasogenic edema [Figure 1]. There was mass effect with left uncal herniation and rightward mild midline shift of 5 mm and ependymal enhancement of left lateral ventricle. Left temporal craniotomy and microsurgical total excision of left temporal tumor was done. Peroperatively, the tumor was non-encapsulated, heterogenous in color and texture, with areas of necrosis and hemorrhage. It was infiltrating into the left sylvian fissure and extending inferiorly up to left inferior cerebral artery. The microscopic examination revealed it to be pleomorphic astrocytic tumor with frequent mitosis, microvascular proliferation, and palisading necrosis [Figure 2]a. IHC showed GFAP [Figure 2]b and S-100 positivity [Figure 2]c, whereas IDH-1 [R132H mutant] [Figure 2]d, ATRX, synaptophysin were negative. The Ki-67 index was 30%. From histomorphology and IHC findings, the diagnosis made was glioblastoma, NOS, WHO grade IV. A subsequent IDH 1 and 2 gene mutation analysis by PCR-sequencing [tested for IDH1 - R132H, R132C, R132S, R132G, R132L, R132V and IDH2 – R140G, R140W, R140L, R140Q, R172K, R172G, R172M, R172W] did not show any mutation. He was further treated with chemotherapy (temozolomide) and radiotherapy. Two months post-radio therapy, he developed palpable mass in the left submandibular region. Fine-needle aspiration cytology (FNAC) was performed, and it showed sheets of partly degenerated tumor cells with abundant necrosis. Subsequently, trucut biopsy from submandibular mass showed mainly round to epithelioid cells with hyperchromatic nuclei along with foci of necrosis. On re-examination, the primary tumor also showed few foci with similar round to epithelioid cells [Figure 3]a and [Figure 3]b. It was interpreted as metastatic deposit of the glioblastoma, which was confirmed with IHC (GFAP positive, vimentin positive; cytokeratin, IDH-1, and ATRX negative). The MRI brain revealed recurrence/residual lesion in the temporal lobe. The patient was then treated with bevacizumab, irinotecan, and carboplatinum. Patient did not show any response and progressed further. He has been put on carmustine and etoposide.
Figure 1: MRI brain showed irregular heterogenous mass measuring 50 × 50 × 47 mm in left temporal lobe

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Figure 2: (a) Microphotograph of pleomorphic astrocytic tumor with frequent mitosis, microvascular proliferation, and palisading necrosis [×400]. (b) Microphotograph showing GFAP positivity in tumor cells [×400]. (c) Microphotograph showing S-100 positivity in tumor cells [×400]. (d) Microphotograph showing IDH negativity in tumor cells [×400]

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Figure 3: (a) Microphotograph of brain tumor showing round to epithelioid cell rich area [×400]. (b) Microphotograph of metastatic site biopsy showing round to epithelioid cells [×400]

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IDH-wild type glioblastoma is the most common and most malignant astrocytic glioma, accounting for 90% of all glioblastoma.[1] IDH-wild type glioblastoma carry a significantly worse prognosis than IDH-mutant type glioblastoma. Glioblastoma has low potential to metastasize outside the confines of the central nervous system (CNS). The first documented metastatic glial tumor was described by Davis in 1928.[2] The extracranial metastases of glioblastoma are rare with a reported incidence of less than 2%.[2] Metastasis occurs most often in lung and pleura (found in 60% of patients with metastatic glioblastoma), regional lymph nodes (51%), bones (31%), and liver (22%).[3] Other targets for metastasis less commonly reported include operative flap, dural veins, meninges, scalp, kidney, spleen, adrenal gland, parotid gland, orbit, spleen, heart, and skin.[2] Among the lymph node metastasis, 62% were situated in cervical area and almost always occurs ipsilateral to the craniotomy but sometimes occur bilateral.[4]

The various protective factors against the metastasis in glioblastoma include the absence of lymphatic vessels, action of blood brain barrier, the extremely shortened survival of patients, the dense connective tissue barrier of dura mater, the virtual absence of collagen, and fibronectin within the CNS parenchyma that would facilitate dissemination, lack of permissive stroma in other organs, poor affinity of glioma cells for arterial blood vessels, and lack of direct connection between subarachnoid space and the hematogenous or lymphatic system.[5]

Despite the various protective factors, the extraneural metastasis is known. Lymph node metastases are commonly seen following surgery, especially craniotomies. This has lead to assumption that tumor cells gain access to the scalp lymphatics and vascular pathways during surgery. However, there are reports of metastasis in the absence of surgery.

Metastatic glioblastoma has been reported commonly in adult patients [with median age around 40 years], younger than in the typical elderly population of glioblastoma. Secondary glioblastoma also are more common in this younger population, and it is thought that the higher risk of metastasis may correspond to the longer duration of the tumor existence in these patients.[4] However, the index case is IDH-wild type glioblastoma, which typically arise de novo, with no recognizable lower grade precursor lesion.[1]

The presence of extraneural metastasis of glioblastoma should be suspected if clinical history of primary CNS tumor is present. FNAC is a simple and reliable diagnostic method if such lesion is suspected from the history.[4] However, histomorphologic confirmation is mandatory in indeterminate cases. In general, histomorphology is similar to that observed in primary glioblastoma.[5] In the index case, there were foci of similar morphology in the primary and metastatic site. The neoplastic cells were negative for cytokeratin on IHC which helped in excluding a separate primary of salivary gland origin, which may also show Glial fibrillary acidic protein (GFAP) positivity.

The treatment of glioblastoma includes surgical excision of the primary tumor, followed by radiation therapy. Solitary and localized metastasis may be treated with surgical excision. Chemotherapy is frequently given in combination with radiation as an adjuvant treatment either before or after surgery.[5] Although several treatment approaches have been in clinical use, glioblastoma is still an aggressive tumor with unfavorable prognosis. Despite several theories to explain the mechanism of distant metastasis of GBM, the issue has not yet clarified. The diagnosis of extraneural metastasis has increased because of the improved survival from more radical surgery, better imaging studies, a higher index of suspicion, and improvement in adjuvant treatment.[5]

To summarize, we report a case of IDH-wild type glioblastoma with extracranial metastasis in submandibular region. None of the previous reports or studies in metastatic glioblastoma mention about IDH mutation studies. Whether, the presence or absence of IDH mutation has any association on extracranial metastasis needs to be studied further.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Louis DN, Suva ML, Burger PC, Perry A, Kleihues P, Aldape KD, et al. Glioblastoma IDH-wildtype. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Editors. WHO Classification of Tumours of the Central Nervous System. 4th ed. France: IARC; 2016. p. 28.  Back to cited text no. 1
Piccirilli M, Brunetto GMF, Rochi G, Giangaspero F, Salvati M. Extra central nervous system metastases from cerebral glioblastomamultiforme in elderly paients. Clinico-pathological rmarks on our series of seven cases and critical review of the literature. Tumori J 2008;94:40-51.  Back to cited text no. 2
Cervico A, Piediomonte F, Salaberry J, Alcorta CS, Salvat J, Diez B, et al. Bone metastases from secondary glioblastomamultiforme: A case report. J Neurooncol 2001;52:141-8.  Back to cited text no. 3
Rashid A, Ilyas MA, Rehman K, Hussain M, Haider I, Mehmood T, et al. Glioblastomamultiforma with cervical lymph node and skeletal metastases: A case report and review of literature. World J Surg Med Radiat Oncol 2015;4:10-7.  Back to cited text no. 4
Romero-Rojas AE, Diaz-Perez JA, Amaro D, Lozano-Castillo A, Chinchilla-Olaya SI. Glioblastoma metastasis to parotid gland and neck lymph nodes: Fine needle aspiration cytology with Histopathologic correlation. Head Neck Pathol 2013;7:409-15.  Back to cited text no. 5

Correspondence Address:
Richa Goyal
Oncquest Lab Ltd, Mohandai Oswal Hospital, GT Road, Ludhiana - 141 009, Punjab
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_432_18

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  [Figure 1], [Figure 2], [Figure 3]


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