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Year : 2017  |  Volume : 13  |  Issue : 6  |  Page : 1065-1067

To B(iopsy) or not to B(iopsy)

1 Department of Radiation Oncology, Baylor Scott & White Health, Texas A&M University Health Science Center College of Medicine, Temple, Texas 76502, USA
2 Department of Pathology, Baylor Scott & White Health, Texas A&M University Health Science Center College of Medicine, Temple, Texas 76502, USA

Date of Web Publication13-Dec-2017

Correspondence Address:
Dr. Matthew M Gestaut
Department of Radiation Oncology, Baylor Scott & White Health, Texas A&M University Health Science Center College of Medicine, Temple, Texas 76502
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.220417

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 > Abstract 

Often in metastatic disease, biopsy confirmation of suspicious central nervous system (CNS) lesions is not mandated according to the American College of Radiology, International Radiosurgery Association, and the National Comprehensive Cancer Network. We present a case of an individual who was thought to have metastatic nonsmall cell lung cancer (NSCLC) T2aN0M1b with motor deficits and CNS metastasis to the left postcentral gyrus. The patient underwent biopsy of the primary lung mass confirming NSCLC. He subsequently underwent treatment with stereotactic radiosurgery (SRS) for presumed CNS oligometastatic disease and palliative chemotherapy. Two months after SRS, the patient had progression of CNS disease with new motor deficits. A magnetic resonance imaging revealed and enlarging mass in the previously radiated area. The patient underwent craniotomy with tumor resection and a second primary CNS tumor was discovered. That patient was downstaged from a Stage IV to a Stage IIB lung cancer with concomitant CNS primary.

Keywords: Glioblastoma, oligometastatic, radiosurgery

How to cite this article:
Gestaut MM, Strober ED, Jhavar SG, Patel MK. To B(iopsy) or not to B(iopsy). J Can Res Ther 2017;13:1065-7

How to cite this URL:
Gestaut MM, Strober ED, Jhavar SG, Patel MK. To B(iopsy) or not to B(iopsy). J Can Res Ther [serial online] 2017 [cited 2020 Oct 21];13:1065-7. Available from: https://www.cancerjournal.net/text.asp?2017/13/6/1065/220417

 > Introduction Top

Often in metastatic disease, biopsy confirmation of suspicious central nervous system (CNS) lesions is not mandated. Clinically, especially when metastatic disease is presumed, physicians have to balance the risk and benefits of further diagnostic procedures. It is often the case a patient will present with oligometastatic disease to the brain and a known primary that carries cerebral affinity. These cases can often present challenging management decisions concerning whether or not to complete pathological confirmation of metastatic disease. We present a case of presumed oligometastatic nonsmall cell lung cancer (NSCLC) which was drastically downstaged after progression secondary to lack of definitive metastatic biopsy upfront.

 > Case Report Top

In July 2014, a 75-year-old otherwise apparently healthy man with a 20 pack-year smoking history and an Eastern Cooperative Oncology Group performance status of 1, presented with a 4-day history suggestive of pneumonia. His medical history included a malignant melanoma Stage IIB (T3bN0M0, nodular type, with ulceration, Breslow thickness 3–4 mm, Clark level IV) of the arm from 2007.

Further workup with computed tomography (CT) with contrast of the chest (completed on July 23, 2014) revealed a 4.3 cm lobulated mass within the inferior aspect of the right lower lobe [Figure 1]. A transbronchial biopsy of the R4 and R11 lymph nodes tested negative for malignancy. Magnetic resonance imaging (MRI) with and without contrast of the brain on August 23, 2014, revealed a 2.4 cm heterogeneously enhancing lesion within the left postcentral gyrus. There was extensive T2 fluid-attenuated inversion recovery abnormality surrounding the lesion [Figure 2]. Neurosurgery recommended against a biopsy of the brain lesion. Instead, a CT-guided core biopsy of the lung mass was performed on August 27, 2014 showing high-grade carcinoma with sarcomatoid features [Figure 3]. Tumor cells were negative for melanocytic markers HMB-45, S100, and SOX10 and also negative for TTF-1, napsin A, cytokeratin-5, weakly positive for p63, and strongly positive for pankeratin. Staining for epidermal growth factor receptor and ALK-EML4 was also negative. Positron emission tomography was completed on September 9, 2014, which showed a hypermetabolic right lower lobe mass without nodal involvement or distant metastases [Figure 4]. Stereotactic MRI of the brain with and without contrast was completed on September 9, 2014, which showed solitary left posterior frontoparietal mass with interval enlargement and central necrosis.
Figure 1: Initial computed tomography scan showing lung mass

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Figure 2: Initial magnetic resonance image of the brain showing mass

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Figure 3: Micrograph of lung sarcomatoid features

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Figure 4: Positron emission tomography showing uptake in the mass

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With a working diagnosis of Stage IV T2aN0M1b NSCLC and after multidisciplinary tumor board review, he received stereotactic radiation surgery (SRS) to the left frontoparietal brain lesion to a dose of 2000 cGy in one fraction on September 18, 2014, followed by chemotherapy with carboplatin (area under the curve-5) on day 1, and gemcitabine (1000 mg/m 2) on days 1 and 8 delivered at 3 weekly intervals. Follow-up CT of the chest with contrast on November 19, 2014 showed stable disease. In mid-November 2014 after completing his third cycle of chemotherapy, he developed worsening dysarthria, a left-sided facial palsy and right upper extremity loss of fine motor skills and light touch sensation. MRI of brain with and without contrast on November 17, 2014 showed an increasing rim-enhancing lesion in the left posterior frontoparietal lobe measuring 3.4 cm. Radiological differential diagnosis included [Figure 5] radiation necrosis versus progression of treated oligometastatic lesion status post-SRS.
Figure 5: Magnetic resonance scan of growing brain lesion

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He underwent left frontal craniotomy on November 26, 2014 and gross total resection of the mass. On pathological examination, brain parenchyma with vast areas of necrosis and viable brain infiltrated by a high-grade glioma was identified. A glial fibrillary acid protein stain was diffusely positive demonstrating the astrocytic nature of the glioma. This in addition to the presence of microvascular hyperplasia and necrosis rendered a diagnosis of a glioblastoma multiforme (GBM), World Health Organization Grade IV [Figure 6].
Figure 6: Glioblastoma path slide

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He was subsequently planned for definitive concurrent chemoradiation for the GBM with intent to begin definitive lung treatment with stereotactic body radiation therapy following completion. Given his decline in performance status, he wished not to pursue any further treatment and entered hospice.

 > Discussion Top

There are several important points of discussion that arise from this case report. Whether the lesion in the brain seen in March was a GBM synchronously occurring with NSCLC or did it occur after treatment of the presumed metastatic lesion? There is no way to definitively answer this question. Upon our review, there are no published reports of similar situations. Assuming the mass was a GBM to begin with, GBMs have been treated with salvage SRS in several small retrospective series with poor clinical outcomes, but little data exist on definitive treatment utilizing this modality.[1],[2] Given the poor response rate, high recurrence rate of GBM, and the short duration of time from SRS treatment to tumor site progression, it is likely that this was a synchronous primary.

Second, should we biopsy a solitary lesion in the brain occurring synchronously with a diagnosis of NSCLC or medical history of aggressive cancer such as melanoma? Obtaining a biopsy in the case of a solitary brain metastasis is not addressed in the American Association of Neurosurgeons Brain metastases guidelines.[3] The National Comprehensive Cancer Network currently recommends a biopsy if a primary malignancy has yet to be identified. Therefore, biopsy confirmation is dependent on the clinical situation with a known malignancy.[4] The American College of Radiology recommends biopsy if no additional lesions are seen on contrast-enhanced MRI,[5] whereas the International Radiosurgery Association recommends biopsy only if an extracranial primary has not been identified.[6] Given that approximately 40% of brain metastases present with a solitary brain lesion and two primary malignancies that routinely metastasize to the brain were already confirmed, we still could have pushed neurosurgery without significant risk to obtain a biopsy with such a peripheral brain lesion in a patient with excellent performance status.[7] Interestingly, the landmark Patchell et al. study revealed that 11% of patients with solitary brain lesions were found to have a second CNS primary or an infection.[8] Other more contemporary investigations have quoted MRI misdiagnosis rates of cerebral metastases as low as 2%.[9] This raises the question, should we be pursuing biopsies on more patients with solitary brain metastases? Clear guidelines do not exist on the matter.

Finally, what are the implications of tissue diagnosis in such circumstances on management? Both primaries could have been treated with definitive management upfront rather than delaying treatment for the GBM and putting the patient through unnecessary toxicity associated with palliative chemotherapy and a delay in care.

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Conflicts of interest

There are no conflicts of interest.

 > References Top

Combs SE, Widmer V, Thilmann C, Hof H, Debus J, Schulz-Ertner D. Stereotactic radiosurgery (SRS): Treatment option for recurrent glioblastoma multiforme (GBM). Cancer 2005;104:2168-73.  Back to cited text no. 1
Pouratian N, Crowley RW, Sherman JH, Jagannathan J, Sheehan JP. Gamma Knife radiosurgery after radiation therapy as an adjunctive treatment for glioblastoma. J Neurooncol 2009;94:409-18.  Back to cited text no. 2
Bhangoo SS, Linskey ME, Kalkanis SN; American Association of Neurologic Surgeons (AANS); Congress of Neurologic Surgeons (CNS). Evidence-based guidelines for the management of brain metastases. Neurosurg Clin N Am 2011;22:97-104, viii.  Back to cited text no. 3
Nabors LB, Ammirati M, Bierman PJ, Brem H, Butowski N, Chamberlain MC, et al. Central nervous system cancers. J Natl Compr Canc Netw 2013;11:1114-51.  Back to cited text no. 4
Gaspar LE, Gutin PH, Rogers L, Schneider JF, Larson D, Bloomer WD, et al. Pre-irradiation evaluation and management of brain metastases. American College of Radiology. ACR appropriateness criteria. Radiology 2000;215:1105-10.  Back to cited text no. 5
Radiosurgery Practice Guideline Initiative Stereotactic Radiosurgery for Patients with Metastatic Brain Tumors; 08 May, 2008. Available from: http://www.irsa.org/metastatic%20guideline.pdf. [Last retrieved on 2015 Sep 25].  Back to cited text no. 6
Gavrilovic IT, Posner JB. Brain metastases: Epidemiology and pathophysiology. J Neurooncol 2005;75:5-14.  Back to cited text no. 7
Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 1990;322:494-500.  Back to cited text no. 8
Mintz AH, Kestle J, Rathbone MP, Gaspar L, Hugenholtz H, Fisher B, et al. A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis. Cancer 1996;78:1470-6.  Back to cited text no. 9


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]


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