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Table of Contents
Year : 2020  |  Volume : 3  |  Issue : 2  |  Page : 76-81

Extraneural metastatic gliosarcoma: A case report and review of the literature

1 Department of Surgery, Division of Neurosurgery, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
2 Department of Surgery, Division of Plastic Surgery, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
3 Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand

Date of Submission20-Apr-2020
Date of Acceptance28-May-2020
Date of Web Publication27-Jun-2020

Correspondence Address:
Dr. Thara Tunthanathip
Department of Surgery, Division of Neurosurgery, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/glioma.glioma_7_20

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Extraneural metastasis of gliosarcoma (GS) is a rare event. In this report, we describe a 15-year-old girl with a frontal GS who underwent complete resection, but developed tumor recurrence requiring a second operation after 3 years. Eight months after the second operation, she presented with a left postauricular mass. The clinical, neuroimaging, and histopathological findings were described. We also conducted a literature review and identified 26 cases of GS with extraneural metastasis, including the current report. The prognosis of GS with extracranial metastasis was poor, with a median survival of approximately 8.0 months. The common metastatic organs were the lungs (65.4%), liver (34.6%), and skeleton (23.1%). We also discuss the pathogenesis of GS with extraneural metastasis. We report an unusual case of a pediatric patient with GS with extraneural metastasis, with a long survival. GS with extraneural metastasis should be considered as a differential diagnosis in patients with soft-tissue masses. This work was approved by the Ethics Committee of the Faculty of Medicine, Prince of Songkla University, Thailand (REC 62-259-10-1) on September 9, 2019.

Keywords: Extracranial metastasis, extraneural metastasis, gliosarcoma, high-grade glioma, malignant glioma

How to cite this article:
Tunthanathip T, Tawaranurak N, Kanjanapradit K. Extraneural metastatic gliosarcoma: A case report and review of the literature. Glioma 2020;3:76-81

How to cite this URL:
Tunthanathip T, Tawaranurak N, Kanjanapradit K. Extraneural metastatic gliosarcoma: A case report and review of the literature. Glioma [serial online] 2020 [cited 2023 Feb 5];3:76-81. Available from: http://www.jglioma.com/text.asp?2020/3/2/76/288181

  Introduction Top

Gliosarcoma (GS) is a variant of glioblastoma (GBM) comprising mixed gliomatous and sarcomatous components. GS accounts for 2% of all GBMs and most commonly occurs in the fourth to sixth decades of life.[1] The prognosis of patients with GS is poor and comparable to GBM.[2] Tumor recurrence associated with a poor prognosis has been reported with distant metastasis.[3] However, extracranial metastases are uncommon, and lung, liver, and lymph node metastases of GS have been reported in the literature.[4],[5],[6] We describe a sporadic case of pediatric GS with postauricular metastasis and discuss this case in light of the literature.

  Case Report Top

A 15-year-old girl presented with a progressive headache and was admitted to Suratthani Hospital in 2015. Neuroimaging demonstrated a left frontal mass, and she underwent a craniectomy with total tumor removal. The tumor was diagnosed with GS based on histology. She denied receiving postoperative radiotherapy and did not follow-up.

Three years after the first operation, the patient developed a generalized tonic–clonic seizure and was admitted to the same provincial hospital. She was diagnosed with recurrent GS and referred to our hospital for reoperation [Figure 1]A and B]. The following day, she underwent a second operation with total resection. The histological results from the second operation are shown in [Figure 2]. One month postoperatively, she received radiotherapy (60 Gy) following ifosfamide, carboplatin, and etoposide chemotherapy.
Figure 1: Neuroimaging of gliosarcoma. Coronal (A) and axial (B) enhanced T1-weighted images of before the second operation showing a heterogeneously enhanced mass in the left frontal lobe (arrows). (C and D) Coronal-enhanced T1-weighted images before third operation showing no intracranial recurrence in the left frontal lobe but a left postauricular mass (arrows). (E and F) Axial-enhanced T1-weighted images before the third operation showing extracranial mass in the left postauricular area and multiple rim-enhancing lesions, about 0.9–1.4 cm diameter, in the left posterior cervical nodes (arrows)

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Figure 2: Histological examination of left frontal mass after the second operation showing pleomorphic astrocytic cells (black arrow) with endothelial proliferation (white arrow). Scale bar: 100 μm (×400)

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Eight months after the second operation, the patient developed a left postauricular mass. Brain magnetic resonance imaging demonstrated an extracranial rim-enhancing mass measuring 3.6 cm × 2.1 cm × 3.8 cm in the left postauricular area, with multiple cervical lymphadenopathies and no intracranial recurrence [Figure 1]C–F]. During the investigation, the left postauricular mass grew rapidly from 3 to 4.5 cm diameter in 1 month [Figure 3]A, [Figure 3]B, [Figure 3]C.
Figure 3: Extraneural metastatic gliosarcoma before the third operation (A) Lateral view; (B) oblique view; (C) posterior view

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She, therefore, underwent a third operation with wide excision and a supraclavicular flap. The postoperative period was unremarkable. Histological examination of the left postauricular mass revealed a biphasic configuration consisting of gliomatous and sarcomatous patterns. The gliomatous part included pleomorphic neoplastic cells with necrosis, immunopositive for glial fibrillary acidic protein, whereas the sarcomatous part was a vascular spindle cell tumor, immunopositive for reticulin [Figure 4]A, [Figure 4]B, [Figure 4]C,[Figure 4]D, [Figure 4]E. Therefore, she denied further treatments and died in 29 months after the second operation (65 months after the first operation).
Figure 4: Histological examination of left postauricular mass after third operation. (A) Hematoxylin and eosin stain showing nests of astrocytic cells (white arrow) with necrosis (black arrow). Scale bar: 20 μm (×20). (B) Hematoxylin and eosin stain showing sarcomatous component of spindle cells (arrow). Scale bar: 20 μm (×20). (C) Hematoxylin and eosin stain showing glial component of pleomorphic astrocytic cells (arrow). Scale bar: 10 μm (×400). (D) Glial fibrillary acidic protein immunostaining highlighting astrocytic tumor cells (arrow). Scale bar: 100 μm (×400). (E) Reticulin stain showing numerous black reticulin fibers surrounding tumor cells. Scale bar: 50 μm (×200). (F) DNA sequencing showed no alteration of the coding DNA sequence at codon R132 (blue highlight)

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Potential mutations in the isocitrate dehydrogenase 1 gene (IDH1) at the hotspot codon R132 were evaluated by the polymerase chain reaction and direct nucleotide sequencing. However, no nucleotide alterations were detected and the GS was wild-type IDH1 [Figure 4]F.

The patient gave informed consent for her images and other clinical information to be reported in a journal before a loss to follow-up. The study was performed with the permission of the Ethics Committee of the Faculty of Medicine, Prince of Songkla University, Thailand (REC 62-259-10-1) on September 9, 2019.

  Discussion Top

GS is a sporadic variation of GBM comprising both gliomatous and sarcomatous features. Extraneural metastasis of GS is an uncommon presentation. GS was slightly predominant in males (approximately two-thirds). The median age was 57 years (interquartile range, 14.75). The temporal lobe was the most common location of GS. Most patients underwent surgical resection, except for one who was diagnosed with GS at necropsy. Six patients (23.1%) were treated with temozolomide. The most common metastatic organs were the lungs (65.4%), liver (34.6%), and skeleton (23.1%).[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21]

We reviewed cases of GS with extraneural metastasis in the relevant literature using MEDLINE, Embase, Web of Science, and Scopus from 1948 to 2019, using the keywords “gliosarcoma” OR “metas*” OR “extracranial metas*” OR “extraneural metas*.” The exclusion criteria were non-English language papers, and papers from which it was not possible to extract individual data, such as systematic reviews or meta-analyses. Twenty-five previous cases are identified in [Table 1],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21] and the clinical characteristics with survival time are summarized in [Table 2]. In addition, survival curves were created using the Kaplan–Meier method from pooled data. Statistical analysis was performed using the R version 3.5.3 software (R Foundation, Vienna, Austria). Based on the literature review, the preferred treatment for GS was maximal safe resection followed by adjuvant radiotherapy or concurrent chemoradiotherapy.[22],[23] Adjuvant therapy was not associated with an improved prognosis, because of a lack of large-scale studies evaluating adjuvant treatment. Patients with GS generally have poor overall survival outcomes, with a median survival of 8.3–16.7 months,[24],[25],[26],[27] whereas the median overall survival of patients with GS with extracranial metastasis was only 8.0 months (95% confidence interval [CI] 6.7–9.2) [Figure 5]A.
Table 1: Summary of previous studies and present study of patients with gliosarcoma with extraneural metastasis

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Table 2: Clinical characteristics of patients with gliosarcoma with extraneural metastasis (n=26)

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Figure 5: Kaplan–Meier survival curves for patients with gliosarcoma with extraneural metastasis. (A) Overall survival time. (B) Intraabdominal metastasis significantly increased the risk of death (log-rank test, P = 0.001)

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Although the pathogenesis of extraneural metastasis of GS or GBM is unknown, lymphatic drainage and hematogenous dissemination are possible mechanisms. Hematogenic dissemination of tumor cells requires contact with the systemic circulation.[28] Metastasis may also occur as a result of direct implantation of tumor cells from the contaminated surgical wound. Bekar et al.[4] reported distal metastasis of GS to the tensor fascia lata donor site, which is used for repairing a dural defect. They discussed the possible role of intraoperative rupture of the tumor and contaminated surgical instruments in the etiology of distant metastasis of GS.[4] However, this theory was based on a single case, and more evidence is needed to support this hypothesis.

The embedding ability of malignant tumor cells involves the C-X-C chemokine receptor type 4/C-X-C motif chemokine ligand 12 (CXCR4/CXCL12) axis. CXCR4 is a chemokine receptor for stromal cell-derived factor-1 alpha, also known as CXCL12.[1],[29],[30] and Zagzag et al.[31] demonstrated the critical role played by hypoxia and the CXCR4/CXCL12 axis in glioma cell migration and metastasis.

Intraabdominal metastasis was associated with a poor prognosis in terms of survival in the current review [hazard ratio 7.66, 95% CI 1.84–31.81; [Figure 5]B. The prognosis of GS is similar to that of GBMs. Winkler et al.[32] reported the cases with long survival when the extent of resection was a key factor. Moreover, a high proportion of sarcomatous feature was also associated with a better prognosis and longer progression-free survival,[33] whereas distant metastases were frequently associated with a poor prognosis.[34] Intraabdominal metastasis was significantly associated with a poor prognosis [Table 3].
Table 3: Cox-regression analysis of factors associated with death

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  Conclusion Top

We report an uncommon case of a pediatric patient with GS extraneural metastasis. GS with extraneural metastasis should be considered as a differential diagnosis in patients with a soft-tissue mass.

Financial support and sponsorship


Institutional review board statement

This work was approved by the Ethics Committee of the Faculty of Medicine, Prince of Songkla University, Thailand (REC 62-259-10-1) on September 9, 2019, and conducted in concordance with the principles of the Declaration of Helsinki.

Declaration of patient consent

The authors certify that they have obtained the appropriate patient consent form. In the form, the patient has given her consent for her images, and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and efforts will be made to conceal her identity.

Conflicts of interest

There are no conflicts of interest.

  References Top

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

  [Table 1], [Table 2], [Table 3]


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