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Year : 2020  |  Volume : 3  |  Issue : 1  |  Page : 48-51

Reporting two cases of second primary brain tumors and how to differentiate from metastasis preoperatively with magnetic resonance imaging

1 Department of Neurosurgery, Yashoda Hospitals, Secunderabad, Telangana, India
2 Department of Medical Oncology, Yashoda Hospitals, Secunderabad, Telangana, India

Date of Submission07-May-2020
Date of Acceptance04-Jun-2020
Date of Web Publication2-Jul-2020

Correspondence Address:
Dr. Anandh Balasubramaniam
Department of Neurosurgery, Yashoda Hospitals, Alexander Road, Shivaji Nagar, Secunderabad - 500 003, Telangana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJNO.IJNO_10_20

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The incidence of second primary tumors in adults is increasing due to betterment in the diagnosis and management of first primary tumors. In literature so far, second primary brain tumors are not reported. Glioblastoma has a poor prognosis despite all recent advances in its molecular genetics and treatment. We report two cases of glioblastoma presenting as second primary tumor of the brain. The first patient was a 70-year-old female with seizures who was treated for carcinoma cervix 6 years back. The second patient was a 75-year-old male patient, a known case of colonic carcinoma treated a year back, and he presented with seizure. Both the patients were operated, and biopsy turned out glioblastoma. A solitary brain lesion in the known first primary patient may be a glial tumor which needs proper evaluation since its management differs from metastasis.

Keywords: Brain primary, metachronous tumors, second primary

How to cite this article:
Kumar G K, Singh SS, Kumar A, Balasubramaniam A, Rajesh B J, Vaswani BA. Reporting two cases of second primary brain tumors and how to differentiate from metastasis preoperatively with magnetic resonance imaging. Int J Neurooncol 2020;3:48-51

How to cite this URL:
Kumar G K, Singh SS, Kumar A, Balasubramaniam A, Rajesh B J, Vaswani BA. Reporting two cases of second primary brain tumors and how to differentiate from metastasis preoperatively with magnetic resonance imaging. Int J Neurooncol [serial online] 2020 [cited 2022 Jun 27];3:48-51. Available from: https://www.Internationaljneurooncology.com/text.asp?2020/3/1/48/288785

  Introduction Top

In adults, cerebral metastasis is by far the most common intracranial tumors. It is estimated that 20%–25% of patients with systemic malignancy found to have cerebral metastases on autopsy.[1] Due to improvement in diagnosis, management, and surveillance, the overall survival among cancer patients has increased significantly. This led to an increase in the incidence of second primary malignancy. Incidence is about 2%–17% among cancer survival patients.[2] In literature so far, there are no reports of second primary in the brain. We report two such cases with second brain primary malignancies without any family history or syndromic association.

  Case Description Top

Case 1

A 70-year-old female presented in May 2019 with seizure. The patient was a known case of squamous cell carcinoma of cervix Stage 3B treated 6 years back. Magnetic resonance imaging (MRI) brain showed multiple enhancing lesions in the brain [Figure 1], and positron emission tomography–computed tomography (PET-CT) scan showed a metabolically active right temporal lesion. No other metabolically active lesion was seen. Hence, provisional diagnosis of metastasis was made, for which whole-brain radiotherapy and boost to the right temporal lesion were given. The patient clinically improved and was on regular follow-up. After 9 months, the patient again presented to casualty in altered sensorium. MRI brain was done which was suggestive of irregular heterogeneous lesion in the right temporal lobe, which was T1 hypointense and T2 hyperintense with multiple foci of blooming noted within lesion suggestive of hemorrhage. The lesion showed irregular peripheral enhancement on contrast. Magnetic resonance (MR) spectroscopy showed elevated lipid lactate peak and mildly elevated choline peak. MR perfusion showed no obvious area of high perfusion. Findings were suggestive of radiation necrosis [Figure 2]. Due to mass effect and midline shift, the patient was taken for surgical decompression of mass. Histopathology was suggestive of glioblastoma Isocitrate dehydrogenase (IDH) wild type, with radiation-induced changes in adjacent parenchyma [Figure 3].
Figure 1: Magnetic resonance imaging of case 1 – (a and b) T1 postcontrast axial images showing multiple contrast-enhancing lesions largest being in the right temporoparietal region

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Figure 2: Magnetic resonance imaging of case 1 – Postirradiation showing a peripheral enhancing lesion with mass effect and midline shift in the right temporoparietal region

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Figure 3: Histopathology of case 1 – (a) Hematoxylin and eosin stain showing high-grade glial neoplasm composed of anaplastic ovoid fibrillary and gemistocytic astrocytes, (b) IDH negative, (c) ATRX retained

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Case 2

A 75-year-old male presented with seizure in March 2020. The patient was a known case of carcinoma rectum (moderate differentiated adenocarcinoma) Stage IIB. The patient has undergone surgical resection, followed by 5-fluorouracil-based chemotherapy in 2017. MRI brain showed a heterogeneous mass in the left frontal lobe, which was hyperintense on T2, hypointense on T1, and diffusion restriction present suggestive of central necrotic area. Postcontrast, it revealed peripheral rim enhancement. MR spectroscopy revealed reduced N-Acetylaspartate (NAA) and increased choline levels. MR perfusion revealed high perfusion both in peripheral and central [Figure 4]. PET-CT scan revealed metabolically active lesion in the left frontal lobe, and no other metabolically active sight was noted in the rest of the body. A diagnosis of high-grade glioma was made and other differential being metastasis. The patient underwent left frontal craniotomy and excision of tumor. Histopathology was suggestive of glioblastoma IDH wild type with ependymoma-like areas [Figure 5].
Figure 4: Magnetic resonance imaging of case 2 – (a-c) Postcontrast images showing infiltrative irregular-shaped peripheral enhancing lesion in left basifrontal region, (d) T2 axial image heterogeneously hyperintense with perilesional edema in the left basifrontal region with mass effect and subfalcine herniation

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Figure 5: Histopathology of case 2 – (a) Hematoxylin and eosin stain showing infiltrative high-grade neoplasm composed of anaplastic ovoid and fibrillary astrocytes along with sheets of cells with rosettes and perivascular anucleate zones resembling ependymoma, (b) IDH-negative, (c) ATRX-retained, (d) GFAP diffusely positive with focal perivascular accentuation

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  Discussion Top

Childhood cancer survivors have increased the risk of developing a second primary malignancy, followed by syndromic association. The 5-year relative survival rate among all cancer patients is now 66%, and the incidence in adults is also increasing. Second primary tumors can be synchronous or metachronous depending on the time duration of diagnosis from the first primary; if <6 months, then it is synchronous. The second primary grouped into three categories based on their factors such as treatment-related, syndromic, and shared etiology.[2],[3] Nearly 45% of the cancer survivors develop brain metastasis within 6 years of their primary diagnosis. Around 80% of metastatic lesions are multiple in the brain.[1]

In Indian literature so far, there were two published articles on second primary malignancy [Table 1]. In both series, there were no cases of second primary involving the brain. The most common second primary site is breast, followed by gastrointestinal and genitourinary tracts.[4],[5] In our study, both the patients were elderly adults, presenting as metachronous second primary. The first patient developed in previously irradiated site in the right temporal region. Both the patients had no family history and syndromic association.
Table 1: Indian literature on second primary tumors

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In adults, cancer survivors with solitary lesion of the brain may be a metastatic or glioma. In such cases, MRI can be helpful to distinguish between these two preoperatively [Flowchart 1]. Unlike metastasis, glioblastoma presents as solitary tumor, but there are exceptions to this rule. The aggressive proliferation and invasiveness of glioblastoma can influence the tumor morphology. In highly proliferating gliomas, clusters of cells may separate from tumor surface presenting as multiple lesions. The shape of glioblastoma is complex as its growth pattern follows white matter tract. Metastatic lesions expand more homogenously and appear spherical in shape.[6] Glioblastoma normally appears as an irregular hypointense lesion on T1- and iso-hyperintense in T2 with various degrees of edema. With contrast, it is present as ring-like enhancement surrounding the irregular-shaped areas of presumed necrosis. Cerebral metastasis occurs at gray-white matter junction or in the arterial watershed area. Cerebral metastasis on T1-weighted images was seen as a regular hypointense lesion with uniformly ring enhancement on contrast and spherical in shape. In MR spectroscopy, the glioblastoma shows an increased choline peak with reversal of NAA-choline ratio.[7] Diffusion tensor imaging shows that white matter tracts are infiltrated but not deformed in glioblastoma, whereas metastasis deforms these tracts.[8] MRI perfusion best differentiates metastasis from glioblastoma. In both the cases, the central part has increased mean Relative cerebral blood volume (rCBV), but in glioblastoma, it is very high about 3–10 compared to metastasis (around 2–3). In the peritumoral region, maximum rCBV is calculated if the value is high (>0.98), suggestive of glioblastoma with 94% accuracy.[9]

The survival of these patients depends on the second primary malignancy.[3] Early diagnosis and treatment may increase the survival. The management of metastasis differs from glioblastoma; hence, imaging and histopathology play a definitive role. Even with optimal treatment, the median survival is 2 years for glioblastoma.[10]

  Conclusion Top

Solitary brain lesion in elderly patients and with known systemic primary tumor should be subjected for detailed imaging preoperatively. The outcome of these patients depends on the nature of the lesion and its management.

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

Takakura K, Sano K. Clinical features of intracranial metastatic tumors. In: Takakura K, Sano K, Hojo S, Hirano A, editors. Metastatic Tumors of the Central Nervous System. Tokyo-New York: Igaku-Shoin; 1982. p. 112-37.  Back to cited text no. 1
Vogt A, Schmid S, Heinimann K, Frick H, Herrmann C, Cerny T, et al. Multiple primary tumours: Challenges and approaches, a review. ESMO Open 2017;2:e000172.  Back to cited text no. 2
Travis LB, Rabkin CS, Brown LM, Allan JM, Alter BP, Ambrosone CB, et al. Cancer survivorship--genetic susceptibility and second primary cancers: Research strategies and recommendations. J Natl Cancer Inst 2006;98:15-25.  Back to cited text no. 3
Bagri PS, Singhal D, Singh M, Guman M, Gaurav J, Shankar B, et al. Double primary malignancies: A clinical & pathological analysis report from a regional cancer institute in India. Iran J Cancer Prevent 2014;7:66-72.  Back to cited text no. 4
Sharma D, Singh G, Kakkar N, Raj S. Second primary malignancy: A retrospective analysis report from a tertiary cancer center of North India. Indian J Cancer 2016;53:595-9.  Back to cited text no. 5
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Stein AM, Demuth T, Mobley D, Berens M, Sander LM. A mathematical model of glioblastoma tumor spheroid invasion in a three-dimensionalin vitro experiment. Biophys J 2007;92:356-65.  Back to cited text no. 6
Chen W, Silverman DH. Advances in evaluation of primary brain tumors. Semin Nucl Med 2008;38:240-50.  Back to cited text no. 7
Tsuchiya K, Fujikawa A, Nakajima M, Honya K. Differentiation between solitary brain metastasis and high-grade glioma by diffusion tensor imaging. Br J Radiol 2005;78:533-7.  Back to cited text no. 8
Malgorzata NM, Joanna B, Marek S, Anna Z. Differentiation of glioblastoma multiforme, metastases and primary central nervous system lymphomas using multiparametric perfusion and diffusion MRI of a tumor core and peritumoral zone- Searching for a practical approach. PLoS One 2018;13:e0191341.  Back to cited text no. 9
Wen PY, Kesari S. Malignant gliomas in adults. N Engl J Med 2008;359:492-507.  Back to cited text no. 10


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

  [Table 1]


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