Metachronous brain and intramedullary spinal cord ... · copy, and the biopsy demonstrated bronchogenic adeno-carcinoma. Left pneumonectomy was performed after WBRT. Pathology revealeda

Kaohsiung Journal of Medical Sciences (2012) 28, 289e293

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CASE REPORT

Metachronous brain and intramedullary spinal cordmetastases from nonsmall-cell lung cancer: A case report

Wen-Chih Liu a, Chia-Li Chung b,c, Chee-Yin Chai d,e, Lia-Beng Tan f,Chih-Jen Wang g, Aij-Lie Kwan g,h,*

a School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanbDepartment of Surgery, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University,Kaohsiung, TaiwancGraduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University,Kaohsiung, TaiwandDepartment of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University,Kaohsiung, TaiwaneDepartment of Pathology, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanfDepartment of Urology, St. Joseph Hospital, Huwei, Yunlin, TaiwangDepartment of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University,Kaohsiung, TaiwanhDepartment of Neurosurgery, University of Virginia, Charlottesville, VA, USA

Received 1 December 2010; accepted 24 March 2011Available online 22 February 2012

KEYWORDSMetastatic braintumor;Intramedullarytumor;Lung tumor

* Corresponding author. DepartmentE-mail address: [email protected]

1607-551X/$36 Copyright ª 2012, Elsedoi:10.1016/j.kjms.2011.11.008

Abstract A 44-year-old man had a brain tumor secondary to lung adenocarcinoma and under-went craniectomy to remove the brain tumor. After postoperative whole-brain radiationtherapy, he underwent pneumonectomy followed by chemotherapy, mediastinal radiotherapy,and target therapy for lung cancer. Thirty-six months after the initial brain surgery, he sufferedfrom neck pain and right upper limb numbness that rapidly progressed to upper extremityweakness and paralysis in 2 months. Magnetic resonance imaging demonstrated an intramedul-lary spinal cord lesion at the C4 level. Laminectomy and gross intramedullary tumor removalwere performed. The patient’s neurological function improved after the operation. Neverthe-less, 4 months after the intramedullary tumor removal, he began to show multiple metastases.Unfortunately, the patient died from respiratory failure 8 months after diagnosis with intrame-dullary spinal cord metastasis. In this case, early diagnosis and aggressive surgical treatmentcombined with postoperative radiotherapy and chemotherapy might have provided this patientwith a prolonged survival and better quality of life.Copyright ª 2012, Elsevier Taiwan LLC. All rights reserved.

of Neurosurgery, Kaohsiung Medical University Hospital, 100 Tzyou 1st Road, Kaohsiung 807, Taiwan.om (A.-L. Kwan).

vier Taiwan LLC. All rights reserved.

290 W.-C. Liu et al.

Introduction

Lung cancer is a common and fatal malignancy [1]. Metas-tases to the central nervous system such as the brain andmeninges are often seen in patients with primary lungcancer [2]. However, intramedullary spinal cord metastasis(ISCM) from lung cancer is relatively rare compared withother system malignancies. Among cases of metastasis tothe central nervous system (CNS), the frequency of ISCM is4.2e8.5% in published autopsy reports [3e5].

The clinical features of ISCM have been described asa rapidly progressive neurological deficit [6]. Therefore,prognosis of ISCM is poor [7]. In a cohort study, individualswith brain metastases show a median survival time of 2.7months after first admission with brain metastases. For lungcancer patients with brain metastasis, the survival time iseven shorter. On average, these patients survive 2.5 monthsafter their first admission with brain metastases [8].

Involvement of other sites within the CNS has beenshown to be common in patients with ISCM. In Schiff andO’Neill’s report, 32.5% of patients with ISCM had a historyof brain metastasis preceding the diagnosis of ISCM [9].The published medical literature rarely shows a goodlong-term survival in patients with primary lung cancer andbrain metastasis. Moreover, the prognosis of patients withprimary lung cancer and brain metastasis deteriorating toISCM is worse.

In this report, we present a patient with metachronousbrain and ISCM from lung cancer.

Case report

A 44-year-old man was transferred to the neurosurgerydepartment due to a 2-week history of headache, dizziness,and left leg numbness. He had a one-pack-a-day history ofsmoking lasting more than 20 years. His Karnofsky Perfor-mance Status (KPS) was 90%, without any adverse prognosticfactors such as weight loss or laboratory abnormalities.

Figure 1. (A) Chest plain film showing no definite diagnostic anodisease in the middle mediastinum (white arrow) with partial atel

His preoperative chest X-ray film showed no definite

imaging (MRI) found a heterogeneous nodule in the rightpostcentral gyrus (Fig. 2A). The cerebral lesion wascompletely surgically removed (Fig. 2B). Pathologyrevealed a metastatic adenocarcinoma, and immunohisto-chemical studies showed positivity for both TTF-1 and CK 7(Fig. 3AeC), suggesting a pulmonary origin. Whole-brainradiation therapy (WBRT), consisting of a total dose of3400 cGy in 200-cGy daily fractions, was administeredpostoperatively.

Chest computed tomography (CT) was performed andrevealed metastatic disease in the middle mediastinum (seeFig. 1B). An endobronchial lesion was found on bronchos-copy, and the biopsy demonstrated bronchogenic adeno-carcinoma. Left pneumonectomy was performed afterWBRT. Pathology revealed a moderately differentiated, lungadenocarcinoma (pT2N1M1) (Fig. 3D).

After lung surgery, the patient’s KPS remained at 90%.He underwent five courses of chemotherapy with paclitaxeland cisplatin. Subsequently, positron emission tomographyfound multiple intense foci of fludeoxyglucose-avid lesionsin the mediastinal lymph nodes and left posterior cervicallymph nodes. As a metastatic lesion was highly suspected,radiotherapy with a total dose of 5220 cGy for a medias-tinal metastasis was performed. In addition, the patientcontinued chemotherapy with two courses of paclitaxelalone, one course of intravenous vinorelbine, and sixcourses of pemetrexed. In addition, he had target therapywith gefitnib for 2 months.

Three years after the initial brain surgery, the patientbegan to suffer from neck soreness followed by right upperlimb numbness. Two months later, these neurologicalsymptoms rapidly progressed to upper extremity weaknessand paralysis. At that time, his KPS was 60%. The cervicalspine MRI showed an intramedullary tumor at C4 level(Fig. 4A). Therefore, he underwent C3eC5 laminectomywith gross removal of the C4 intramedullary tumor. Thesurgical pathology revealed a metastatic adenocarcinoma

maly. (B) A chest computed tomography scan shows metastaticectasis of the left lingular lobe (black arrows).

Figure 2. (A) Contrast-enhanced T1-weighted imaging shows a heterogeneous nodule with mild gadolinium enhancement in theright postcentral gyrus (arrow). Perinodular hyperintensity can be noted. (B) Two years after brain surgery, contrast-enhanced fastfluid-attenuated inversion-recovery (FLAIR) imaging shows that the tumor has been completely removed without recurrence.

Figure 3. (A) The brain shows metastatic adenocarcinoma composed of hyperchromatic nuclei and pleomorphic tumor cellsarranged in a papillary glandular or cribriform pattern. H&E, 200�. (B) The tumor cells of the metastatic lesion (brain) areimmunopositive for TTF-1. TTF-1 immunohistochemical stain, 200�. (C) The tumor cells of the metastatic lesion (brain) areimmunopositive for CK7. CK-7 immunohistochemical stain, �200. (D) Histologically, the left lung shows features of adenocarci-noma. H&E, 200�. (E) The cervical cord shows metastatic adenocarcinoma composed of cancerous cells with moderate pleo-morphism arranged in a glandular or villoglandular pattern. H&E, 200�.

Brain and intramedullary metastases 291

Figure 4. (A) Contrast-enhanced T1-weighted imaging showing an intramedullary tumor with marked ring enhancement (arrow).(B) Four months after cervical spine surgery, a -enhanced T1-weighted image shows a small part of the residual intramedullarytumor at the level of the C4 spinal cord and edema. A metastatic brain tumor is in the cerebellum (circle).

292 W.-C. Liu et al.

(Fig. 3E). The patient was then transferred to rehabilitationdepartment. His neurological symptoms and signs subsided,and his KPS returned to 80%.

Four months later, the patient’s follow-up chest CTfound several osteoblastic metastatic lesions in the spineand ribs bilaterally. A bone scan revealed multiple bonemetastases from lung cancer. Brain MRI revealed multiplemetastatic brain tumors in the cerebrum, cerebellum, andsubependymal area. Hence, chemotherapy with two cour-ses of gemcitabine was given concurrently with radio-therapy consisting of a total dose of 3000 cGy in 300-cGydaily fractions, for lumbar spine and sacroiliac jointmetastases. In addition, he underwent radiotherapy, con-sisting of a total dose of 3060 cGy in 340-cGy daily fractions,for brain metastases.

The patient became weaker and developed shortness ofbreath. He was admitted to the hospice ward for palliativetreatment and unfortunately died from respiratory failure 8months after the diagnosis of ISCM.

Discussion

Patients with lung cancer and brain metastasis have a poorprognosis. Surgery plus postoperative WBRT providesa favorable prognosis for patient with a single metastaticbrain tumor [10,11]. Many studies have recommendedsurgery for the primary lung tumor, suggesting a longerfunctional survival than without surgical intervention[12,13]. Nevertheless, Billing et al. [14] suggested thatsurgical resection provides benefit only in patients withoutlymph nodes metastases. They reported that no patientwith mediastinal lymph node involvement survived longerthan 3 years. In our report, this 4-year survivor underwentdual resection of both the lung primary and brain

metastases followed by radiotherapy, chemotherapy, andtarget therapy. We deem that aggressive treatment for lungcancer with brain metastasis is an optimal approach thatwould lead to a favorable prognosis.

ISCM represents a rare evolution of cancer from systemiccancer, and it is a challenge in terms of diagnosis andtreatment. Prior to the advent of MRI, many diagnoses wereestablished post mortem [3e5]. Gadolinium-enhanced MRIshows a high sensitivity and has become the gold standardin diagnosis of this disease [9,15,16]. Nowadays, otherdiagnostic tests, such as plain radiographs of spine andcerebrospinal fluid analysis, have comparatively less valuein the diagnosis of ISCM [9].

Lung cancer and breast cancer represent the mostcommon primary sources of extra-CNS ISCM, with lungcancer accounting for almost half of the cases [7,9,17].ISCM may occur at any level of the spinal cord. In a reviewarticle [7], 147 patients with ISCM were analyzed. Metas-tasis to the cervical cord was most common (42%), whichmight relate to the greater bulk and richer vascular supplyin the cervical cord [18].

Previous studies illustrated three pathways of ISCM,including hematogenous spread [7,19], direct intra-medullary invasion by meningeal carcinomatosis [20], anddirect invasion from a contiguous structure [3,20]. With theevidence of multiple CNS metastases from lung cancer, wepostulate that the most likely pathway is via the arterialroute, as well as direct extension via cerebrospinal fluiddistribution from the central canal into the intramedullaryspace.

From a treatment perspective, we consider surgicalresection to be the optimal treatment for patient withISCM. In the medical literature [16,20], radiotherapy isoften indicated for patients with ISCM; even so, surgicalresection for intramedullary spinal cord tumor can also be

Brain and intramedullary metastases 293

performed in selected cases and has been associated witha favorable prognosis [21e24]. In the present case, thepatient’s neurological function improved after surgery. Webelieve that surgery would provide a favorable internaldecompression, which is helpful to relieve the rapidneurological deterioration.

The duration between a patient’s initially diagnosedtumor and ISCM has been shown to be 25 months onaverage, the mean period between the occurrence of thepatient’s symptom and the diagnosis with ISCM being 52days [7]. In our case, this patient was diagnosed with ISCM38 months after the diagnosis of his primary lung cancer.We believe that the prolonged survival of this patient isthe result of increased awareness of the condition andan improvement in investigative techniques, as well asaggressive surgical treatment with postoperative adjuvantchemotherapy and radiotherapy.

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