Unusual magnetic resonance imaging findings of brain and leptomeningeal metastasis in lung adenocarcinoma:A case report

AbstractMetastatic tumors are the most common malignancies of central nervous system in adults,and the frequent primary lesion is lung cancer.Brain and leptomeningeal metastases are more common in patients with non-small-cell lung cancer harboring epidermal growth factor receptor mutations.However,the coexist of brain metastasis with leptomeningeal metastasis(LM)in isolated gyriform appearance is rare.We herein presented a case of a 76-year-old male with an established diagnosis as lung adenocarcinoma with gyriform-appeared cerebral parenchymal and leptomeningeal metastases,accompanied by mild peripheral edema and avid contrast enhancement on magnetic resonance imaging.Surgical and pathological examinations confirmed the brain and leptomeningeal metastatic lesions in the left frontal cortex,subcortical white matter and local leptomeninges.This case was unique with respect to the imaging findings of focal gyriform appearance,which might be caused by secondary parenchymal brain metastatic tumors invading into the leptomeninges or coexistence with LM.Radiologists should be aware of this uncommon imaging presentation of tumor metastases to the central nervous system.

Brain metastasis;Leptomeningeal metastasis;Magnetic resonance imaging;Lung cancer;Epidermal growth factor receptor;Case report

Published by Baishideng Publishing Group Inc.All rights reserved.

Patients with non-small-cell lung cancer harboring epidermal growth factor receptor(EGFR)mutations were more susceptible to develop into brain or leptomeningeal metastases when compared to those with wild-type EGFR.However,parenchymal brain metastasis combined with leptomeningeal metastasis(LM)in isolated gyriform appearance is rare.We herein presented a case of a 76-year-old male with EGFR-mutated lung adenocarcinoma metastases of the brain with isolated gyriform appearance in imaging findings.We speculated that the focal gyriform lesions were likely to be caused by secondary leptomeningeal invasion from parenchymal brain metastatic tumors or coexisting of parenchymal brain metastasis with LM.

Li N,Wang YJ,Zhu FM,Deng ST.Unusual magnetic resonance imaging findings of brain and leptomeningeal metastasis in lung adenocarcinoma:A case report.2022;10(5):1723-1728

https://www.wjgnet.com/2307-8960/full/v10/i5/1723.htm

Neurological examination was conducted,which revealed no obvious pathological signs of tumor metastasis.

Moreover,the patient’s MR imaging showed only mild white matter edema below the lesions,which was different from the extensive edema surrounding the typical metastatic tumors.The extracellular space of white matter was wider than that of the gray matter,so white matter was prone to edema.It was speculated that the mild peritumoral edema was related to tumors mainly located in the cortex.

本文所提方法最大的特點在于滿足中軸線提取結果可視化的基本要求下，實現了全自動化提取。對提取結果完成拓撲檢查后，直接進行網絡空間分析。比如對于河網中軸可進行連通性分析。由于本文所選數據為河網數據，以下將對中軸提取結果建立網絡拓撲并進行連通性分析。

lNTRODUCTlON

Due to ambiguity in imaging findings,craniotomy was performed to establish the diagnosis.During operation,the mass was shown to be located in the left frontal lobe and adjacent leptomeninges,with a local gray-white tumor tissue,wherein a small part of it appeared pink fish-like,and had abundant blood supply.Resection of tumor tissue was performed in the frontal lobe,and then along the cerebral gyrus and sulcus to remove the invasive residual tumors and leptomeningeal lesions.The pathological examination results revealed abnormal epithelioid cell nests in the brain tissue(Figure 1).Immunohistochemical stains were positive for cytokeratin 7,thyroid transcription factor-1,Napsin-A,and epithelial membrane antigen and negative for glial fibrillary acidic protein,P53,S-100,Vim and ALK,which was consistent with that of primary lung metastasis.Also 40% proliferative activity was reported with Ki-67.

CASE PRESENTATlON

Chief complaints

A 76-year-old male patient with nausea and vomiting without obvious inducement,and dizziness,headache and fatigue was admitted to our hospital for further evaluation.

History of present illness

Similar to the pathophysiology of brain metastases,LM was likely to be a multistep biological process[11].The spread of cancer cells to leptomeninges might occurmultiple routes,including direct metastatic brain tumors infiltration,hematogenous dissemination of tumors,orendoneurial/perineural and perivascular pathways[12].The imaging and intraoperative findings of this case confirmed the seeding of tumors into the brain parenchyma and leptomeninges.Therefore,we speculated that the isolated gyriform lesions were likely metastatic brain parenchymal tumors with secondary leptomeningeal infiltration or a coexistence of brain metastasis with LM.

History of past illness

The patient underwent cerebrospinal fluid(CSF)tests 2 mo after craniotomy.The CSF results were as follows:Glucose:0.7 mmol/L;Chloride:117.4 mmol/L;β-trace protein:2283 mg/L;White cell:220 × 10/L;Neutrophils:20%;and Lymphocytes:80%.The Pandy’s test was positive,and CSF cytology showed malignant epithelial cells in the CSF(Figure 1).

Personal and family history

The patient had no particular individual or family history.

Physical examination

https://dx.doi.org/10.12998/wjcc.v10.i5.1723

Laboratory examinations

In 2014,the patient underwent radical resection of the right middle lobe lung cancer for the first time.The postoperative diagnosis showed lung adenocarcinoma(T1aN0M0,stage Ia),without adjuvant radiotherapy and chemotherapy.In January 2019,the patient underwent a puncture biopsy because of the newly discovered ground-glass nodule in the right lower lung,and postoperative pathology confirmed lung adenocarcinoma.Polymerase chain reaction of tumor specimens showed EGFR mutations at exon 21.Radiofrequency ablation of right lung cancer was performed after the surgery.At this time,MRI of brain showed no metastatic tumors in the central nervous system.

津巴布韋似乎已意識到多年來農業生產中所犯的錯誤，Chinamasa說：“新政府領導下的未來是光明的。目前國家正在采取新的努力，穩定土地所有權管理，支持有效利用。”

Imaging examinations

In October 2019,MRI of the brain(Figure 2)revealed a cortical and subcortical isolated gyriform mass in the left frontal lobe,with T/FLAIR hyperintensities,obvious contrast enhancement,subtle perilesional edema,and restricted diffusion,which was unusual for metastatic tumors.Therefore,it was misdiagnosed as glioma or subacute cerebral infarction.In addition,TWI enhancement also revealed local leptomeningeal lesions(Figure 2E),which were missed in the process of imaging diagnosis.Magnetic resonance angiography(MRA)showed no obvious abnormalities in the intracranial blood vessels.

殘月如鉤，月色似霧，月色輕輕地蓋住了破碎的山河。入夜后，四周的青蛙開始唱歌，這些不知人間疾苦的東西，整夜整夜唱著歌，蟋蟀也在田野的四處調情，幾根手指粗的蚯蚓落在壕溝里，扭來扭去，漫無目的地爬行著。

Further diagnostic work-up

Metastatic tumors account for the majority of central nervous system(CNS)neoplasms,which outnumber the primary brain tumors,and the most common source for these is lung cancer[1].CNS metastasis involves brain parenchyma,dura or leptomeninges.Neuroimaging findings often indicate metastatic diseases.In particular,the gadolinium-enhanced magnetic resonance imaging(MRI)of the brain is regarded beneficial for the detection of leptomeningeal metastasis(LM)[2].Herein,we presented a case of a 76-year-old male with epidermal growth factor receptor(EGFR)mutated lung adenocarcinoma metastases of the brain with unique appearance in imaging findings.

FlNAL DlAGNOSlS

The final diagnosis of the presented case was brain and leptomeningeal metastases in EGFR-mutated lung adenocarcinoma.

TREATMENT

After surgery,the patient's condition was stabilized,but his consciousness was still clouded.

OUTCOME AND FOLLOW-UP

The patient did not receive chemotherapy after surgery and died due to acute brain failure two months later.

DlSCUSSlON

Lung cancer is the most common primary tumor associated with CNS metastases,and it eventually develops into CNS metastases in 23%-36% of lung cancer patients[3].LM is rare and occurs in 3%-5% of patients with advanced non-small-cell lung cancer[4].Patients with non-small-cell lung cancer harboring EGFR mutations were more susceptible to develop brain or leptomeningeal metastases when compared with those bearing wild-type EGFR[5,6].Patterns of brain metastasis might vary in non-small cell lung cancer patients,as it depends on the tumor nodules and is more or less related to cystic and necrotic lesions[7,8].However,parenchymal brain metastasis combined with LM in the appearance of isolated gyriform are rare.After all,LM usually presents as more diffused tumor involvement,and isolated one is not frequently seen.A case of EGFR-mutated lung adenocarcinoma with brain parenchymal and leptomeningeal metastases in a focal gyriform appearance was herein presented.

The lesions of left frontal cortex,subcortex and local leptomeninges,forming an isolated gyriform,were shown with avid contrast enhancement in our case,which was considered to be rare in tumor metastasis into the CNS.Making a diagnosis of LM is difficult,which is relied on cerebrospinal fluid(CSF)analysis result,and clinical and radiographic findings.CSF cytology remains the gold standard for diagnosing LM,but it is invasive and associated with relatively low sensitivity[9].Gadolinium-enhanced MRI of the brain is considered to be the best imaging technique for evaluating LM,and the images of LM appear as nodular,linear,arched,focal or diffuse intensification[2,10].The clinical manifestations of the patient in this case were non-specific,and cytological examination of CSF was not performed before operation.LM was also neglected during preoperative MRI diagnosis.Compared with TWI enhancement sequence,the contrast-enhanced T-weighted FLAIR sequence is more sensitive to detect leptomeningeal tumoral or infective-inflammatory involvement.A limitation of this study was that other smaller areas of metastasis on the leptomeningeal surface may be ignored because contrast-enhanced T-weighted FLAIR was not taken.LM was eventually discovered during the surgery.CSF cytology examination also showed malignant tumor cells 2 months later.In fact,preoperative TWI enhancement in the present case had significantly revealed LM(Figure 2E).

Patient’s symptoms started 3 d ago.

該次研究工作中，經分析可知，患者年齡、患者文化程度、患者健康狀況以及患者的肺炎疫苗認識情況均為接種肺炎疫苗的影響因素。見表1。

根據構建的指標體系，搜集原始指標數據，整理計算得出的指標數據并以此作為指標數據樣本，得到指標數據矩陣:

The prognosis of non-small cell lung carcinoma with LM remained poor,and the median overall survival was only 3 mo[5].Systemic chemotherapy is the preferred treatment choice for lung cancer patients with LM[13].In this case,the patient had brain and leptomeningeal metastases,and underwent surgical resection without postoperative adjuvant chemotherapy.His condition worsened after surgery and died due to brain failure 2 mo after the diagnosis of CNS metastasis.

適宜的音樂刺激聽覺中樞，使人體交感神經系統活動減弱，副交感神經活動增強，從而能讓患者在應激下保持平穩狀態［17］。音樂療法可顯著降低患者的激素水平［18-19］、心率、呼吸頻率和舒張壓。研究發現，音樂干預對心率影響較小［20-21］，可降低舒張壓約 2 mm Hg，但對收縮壓沒有作用［13］。Ni等［22］觀察發現音樂干預對生命體征的影響非常輕微，還有報道指出音樂干預對收縮壓和心率沒有影響，但音樂有益于安撫待手術患者的情緒，能改善患者的手術體驗和提高療效。

鑒于高職院校韓國語傳統教學方法存在的諸多問題，有必要將多媒體引入韓國語課堂，這將有效彌補傳統教學的不足，同時，高職院校韓國語教師要多加學習，熟練掌握多媒體技術，制作高質量的教學課件，提高多媒體教學能力，為高職院校韓國語教學質量的提高做出應有的貢獻。

Intracranial focal gyriform lesions should be distinguished from cerebral infarction in elderly patients.In subacute infarction,cortical edema and necrosis may lead to enhanced gyral lesions,and may even lead to leptomeningeal enhancement lesions due to meningeal inflammation and early fibrosis[14].But the enhanced lesions of subacute cerebral infarction demonstrated no obvious mass effect,and the cerebral parenchyma around the enhanced lesions also showed varying degrees of ischemia.However,the mass effect of intracranial enhancement lesions in the present case was obvious,and no adjacent brain parenchyma was involved.Moreover,the clinical manifestations of this patient included only nausea and vomiting,and no symptoms of stroke.

Besides,the diagnosis of this case should be differentiated from high-grade gliomas on imaging.High-grade gliomas tend to occur in the subcortical white matter,and large tumors can cause white matter necrosis,showing circular enhancement images.Furthermore,metastatic peritumoral edema is purely vasogenic,and no infiltrating tumor cells are present outside the perivascular space,which leads to hypoperfusion,with relatively normal magnetic resonance spectrum(MRS)in the peritumoral edema area.The peritumoral edema of high grade gliomas,on the other hand,is a mixture of vasogenic edema,infiltrating neoplastic cells and feeding blood vessels,which is expected to have an increased blood perfusion and higher Cho/NAA and Cho/Cr ratios on MRS,compared to solitary brain metastases[15,16].Therefore,perfusionweighted imaging and MRS of peritumoral edema could assist in differential diagnosis of high-grade gliomas versus brain metastases,but the patient didn't receive these tests.

In addition,this case should also be differentiated from cases of leptomeningeal involvement diseases,such as primary central nervous system vasculitis(PCNSV)and tuberculous meningitis(TBM).Unlike the isolated cortical mass in this case,the common MRI features of PCNSV are multiple bilateral supratentorial lesions,involving the gray and white matter,predominantly in the subcortex,deep white matter and corpus callosum,accompanied with focal cerebral infarction[17].Although PCNSV images could manifest as irregular linear enhancement on subcortical white matter and leptomeninges,there was no obvious mass effect.TBM tended to occur at basal areas,with multiple bilateral foci and obstructive hydrocephalus,which could be differentiated from CNS metastases.

同時，在變頻器輸出側安裝共模電壓濾波器，可以從源頭上減小共模電壓，對變頻器供電的電機軸電流有非常好的抑制作用。

CONCLUSlON

A rare case of EGFR-mutated lung adenocarcinoma with cerebral parenchymal and leptomeningeal metastases characterized by isolated gyriform appearance was reported.We speculated that this unique appearance is likely to be due to the induction of secondary leptomeningeal invasion from parenchymal brain metastasis or coexisted with LM.Therefore,when patients with a history of lung adenocarcinoma were dealt,radiologists should be aware of this uncommon imaging presentation of CNS metastases and carefully observe for the existence of leptomeningeal lesions on Tenhancement to avoid missed diagnosis.