A 77-year-old woman with no history of malignancy presented with anorexia and bilateral lower extremity weakness. Her consciousness level worsened daily, so we performed a lumbar puncture. Cerebrospinal fluid (CSF) analysis indicated meningitis, but three rounds of CSF cytology showed no malignant cells. The patient’s carcinoembryonic antigen (CEA) level was highly elevated in CSF, but normal in serum. Through gadolinium-enhanced brain/spinal magnetic resonance imaging and gastrointestinal endoscopy, she was diagnosed with leptomeningeal carcinomatosis (LC) from gastric cancer. CEA level in CSF facilitated the diagnosis of LC from gastric cancer because there were no malignant cells on CSF cytology

Hashimoto, Daisuke

Ino, Riku

Kawamura, Masafumi

Miyauchi, Atsushi

Nojima, Shigeru

Sada, Ken-ei

Yamanaka, Shingo

English

Okayama University Scientific Achievement Repository

L eptomeningeal carcinomatosis (LC) is the multi-focal spreading of malignant tumour cells along the meninges.  LC occurs in 5% of all patients diag-nosed with cancer,  but rarely in patients with gastric cancer [1 , 2].  Almost all patients with LC have already been diagnosed with advanced cancers with distant metastases and present neurological symptoms,  such as cranial nerve palsies,  headache,  psychiatric symptoms,  quadriplegia,  nausea,  and vomiting [3].  Although the cytologic examination of cerebral spinal fluid (CSF) is the gold standard for the diagnosis of LC,  its sensitivity reaches only 90%,  even after repeated tests [4].  Several reports have shown the utility of tumour marker levels in CSF to diagnose LC in patients with cancer,  com-pared with the cytologic examination of CSF [5-7].  Here,  we report a patient with LC as an initial symptom of gastric cancer.  Her carcinoembryonic anti-gen (CEA) level in CSF facilitated the LC diagnosis because no malignant cells were found in a total of three rounds of CSF cytologic examination.Case DescriptionA 77-year-old woman who had suffered from anorexia for 3 weeks and bilateral lower extremity weakness for a few days was admitted to our hospital.  She presented with general malaise,  mild posterior neck pain,  and gait disturbance,  but had no headache or digestive symptoms.  Her consciousness was clear,  and her vital signs included a body temperature of 36.7°C,  blood pressure of 189/95 mmHg,  pulse rate of 73/min,  Acta Med.  Okayama,  2021Vol.  75,  No.  5,  pp.  659-661CopyrightⒸ 2021 by Okayama University Medical School.http ://escholarship.lib.okayama-u.ac.jp/amo/Case ReportAdded Diagnostic Value of Cerebrospinal Fluid Carcinoembryonic Antigen in a Patient with Leptomeningeal Carcinomatosis as the Initial Manifestation of Gastric CancerRiku Inoa,  Ken-ei Sadaa,b,c＊,  Atsushi Miyauchia,  Daisuke Hashimotoa,  Shigeru Nojimaa,  Shingo Yamanakaa,  and Masafumi KawamuraaaDepartment of Internal Medicine,  Kochi Prefectural Hata-Kenmin Hospital,  Sukumo,  Kochi 788-0785,  Japan bDepartment of Clinical Epidemiology,  Kochi Medical School,  Kochi University,  Nankoku,  Kochi 783-8505,  Japan,  cDepartment of Nephrology,  Rheumatology,  Endocrinology and Metabolism,  Okayama University Graduate School of Medicine,  Dentistry and Pharmaceutical Sciences,  Okayama 700-8558,  JapanA 77-year-old woman with no history of malignancy presented with anorexia and bilateral lower extremity weakness.  Her consciousness level worsened daily,  so we performed a lumbar puncture.  Cerebrospinal fluid (CSF) analysis indicated meningitis,  but three rounds of CSF cytology showed no malignant cells.  The patient’s carcinoembryonic antigen (CEA) level was highly elevated in CSF,  but normal in serum.  Through gadolini-um-enhanced brain/spinal magnetic resonance imaging and gastrointestinal endoscopy,  she was diagnosed with leptomeningeal carcinomatosis (LC) from gastric cancer.  CEA level in CSF facilitated the diagnosis of LC from gastric cancer because there were no malignant cells on CSF cytology.Keywords:  leptomeningeal carcinomatosis,  gastric cancer,  carcinoembryonic antigen,  cerebrospinal fluid cytologyReceived January 26,  2021 ; accepted April 16,  2021.＊Corresponding author. Phone : +81-880-66-2222; Fax : +81-880-66-2111E-mail : sadak@kochi-u.ac.jp (K.Sada)Conflict of Interest Disclosures: No potential conflict of interest relevant to this article was reported.and respiratory rate of 16/min.  She had no neck stiff-ness or sensory neurologic deficits.  Manual muscle testing showed mild quadriceps and iliopsoas weakness.  Her abdomen was flat and soft,  and no tenderness was found.  Her serum CEA level was 2.9 ng/mL.  Whole-body computed tomography and brain spinal magnetic resonance imaging (MRI) without contrast showed no specific findings,  including hydrocephalus.  Her level of consciousness worsened daily and we therefore per-formed a lumbar puncture.  Her CSF opening pressure was 17 cm H2O.  CSF analysis revealed nine mononu-clear and four polynuclear cells/μL,  a glucose level of 27 mg/dL (CSF-blood glucose ratio: 0.18),  and a total protein value of 261 mg/dL,  inidicating meningitis.  CSF gram staining was negative,  a total of three rounds of CSF cytology showed no malignant cells,  and her CSF CEA level was highly elevated at 117.1 ng/mL.  Gadolinium-enhanced TI-weighted MRI showed dif-fuse leptomeningeal contrast enhancement following the cortical surface of the cerebrum,  the cerebellar folia,  and the ventral surface of the brainstem,  as well as lin-ear and nodular enhancement along the surface of the spinal cord and cauda equina,  indicating LC (Fig. 1).  The patient’s bilateral lower extremity muscle weakness was considered to be due to a lesion in the spinal pyra-midal tract.  When exploring the primary site,  a gastric tumor was found by gastrointestinal endoscopy and histologically diagnosed as human epidermal growth factor receptor 2 (HER2)-negative poorly differentiated adenocarcinoma (Fig. 2).  The patient’s level of con-sciousness deteriorated rapidly,  and she died 25 days after admission.DiscussionWe experienced a patient with LC as an initial symptom of gastric cancer,  and her CEA levels in CSF facilitated the diagnosis of gastric LC.  To the best of our knowledge,  this is the first report on the utility of CEA levels in CSF for the diagnosis of gastric LC in a patient with no malignant cells on cytologic examination of CSF and normal serum CEA levels.LC rarely develops as an initial symptom of gastric cancer.  It occurs in approximately 8% of patients with solid cancers [1],  but in only 0.17-0.69% of patients with gastric cancer [2],  and the majority of patients 660 Ino et al. Acta Med.  Okayama　Vol.  75,  No.  5A BDCFig.  1　 Gadolinium-enhanced T1-weighted MRI showing diffuse leptomeningeal contrast enhancement following the cortical surface of the cerebrum (A),  the cerebellar folia (B),  the ventral surface of the brain-stem (C),  and linear or nodular enhancement along the surface of the spinal cord and cauda equina (D).with LC have already been diagnosed with advanced cancers with distant metastases [3].  The most frequent symptoms of LC include cranial nerve palsies (75%),  headache (66%),  psychiatric symptoms (45%),  quadri-plegia (44%),  and nausea and vomiting (20%) [2].  Although there have been previous case reports in which LC was an initial symptom of gastric cancer,  the patients in these reports had certain neurological symp-toms [8 , 9].  Because our patient presented with only mild symptoms and had no history of malignancy,  we did not initially consider the possibility of LC.  A previ-ous report found that brain metastasis is frequent in breast cancer patients with HER2-positive or tri-ple-negative disease,  and the patients with triple-nega-tive disease had the worst prognosis [10].  Therefore,  HER2-negative status in this case might also be associ-ated with a poor prognosis in gastric cancer patients with metastasis to the central nervous system,  as tri-ple-negative disease in breast cancer.  CEA levels in CSF may contribute to the diagnosis of LC,  even if no malignant cells are found on cytologic examination.  Although the cytologic examination of CSF is the gold standard for the diagnosis of meningeal carcinomatosis,  its sensitivity reaches only 90%,  even after repeated tests [4].  A previous study reported the utility of CEA levels in CSF to diagnose meningeal carcinomatosis in patients with cancer,  compared with cytologic exam-ination as the gold standard [5].  Our patients showed no malignant cells in a total of 3 rounds of CSF cyto-logic examination but showed elevated CEA levels in CSF and normal serum CEA levels.  Therefore,  the measurement of CEA levels in CSF,  in addition to a cytologic examination,  may improve sensitivity for diagnosing LC.In conclusion,  it is uncommon to consider the pos-sibility of LC in patients who present mild symptoms and have no history of malignancy.  However,  CEA levels in CSF with cytologic examination may be helpful in diagnosing gastric LC,  despite a lack of malignant cells on cytologic examination of CSF and normal serum CEA levels.References 1.  Beauchesne P: Intrathecal chemotherapy for treatment of leptome-ningeal dissemination of metastatic tumours.  The Lancet Oncology (2010) 11: 871-879. 2.  Lee JL,  Kang YK,  Kim TW,  Chang HM,  Lee GW,  Ryu MH,  Kim E,  Oh SJ,  Lee JH,  Kim SB,  Kim SW,  Suh C,  Lee KH,  Lee JS,  Kim WK and Kim SH: Leptomeningeal carcinomatosis in gastric can-cer.  Journal of neuro-oncology (2004) 66: 167-174. 3.  Oh SY,  Lee SJ,  Lee J,  Lee S,  Kim SH,  Kwon HC,  Lee GW,  Kang JH,  Hwang IG,  Jang JS,  Lim HY,  Park YS,  Kang WK and Kim HJ: Gastric leptomeningeal carcinomatosis: multi-center ret-rospective analysis of 54 cases.  World journal of gastroenterology:  WJG (2009) 15: 5086-5090. 4.  Thomas JE,  Falls E,  Velasco ME and Zaher A: Diagnostic value of immunocytochemistry in leptomeningeal tumor dissemination.  Archives of pathology & laboratory medicine (2000) 124: 759-761. 5.  Kang SJ,  Kim KS,  Ha YS,  Huh SY,  Lee JH,  Kim JK and Kim MJ: Diagnostic value of cerebrospinal fluid level of carcinoembry-onic antigen in patients with leptomeningeal carcinomatous metas-tasis.  Journal of clinical neurology (2010) 6: 33-37. 6.  Kosmas C,  Tsavaris NB,  Soukouli G,  Gouveris P,  Tsakonas G,  Katselis J,  Alexopoulos H,  Mylonakis N and Karabelis A: Changes of cerebrospinal fluid tumor marker levels may predict response to treatment and survival of carcinomatous meningitis in patients with advanced breast cancer.  Medical oncology (2005) 22: 123-128. 7.  Zhang Z,  Tian C,  Shi Q,  Hao J,  Zhao N and Liu Z: Diagnostic Value of CYFRA 21-1 in the Cerebrospinal Fluid for Leptomeningeal Metastasis.  Disease markers (2017) 2017: 2467870. 8.  Yamada T,  Furukawa K,  Yokoi K,  Ohaki Y,  Okada S and Tajiri T: Case of meningeal carcinomatosis with gastric cancer which manifested meningeal signs as the initial symptom; the palliative benefit of radiotherapy.  J Nippon Med Sch (2008) 75: 216-220. 9.  Kawasaki A,  Suzuki K,  Takekawa H,  Nakamura T,  Yamamoto M,  Asakawa Y,  Okamura M and Hirata K: Co-occurrence of multiple cerebral infarctions due to hypercoagulability associated with malignancy and meningeal carcinomatosis as the initial manifesta-tion of gastric cancer.  BMC neurology (2014) 14: 160.10.  Martin AM,  Cagney DN,  Catalano PJ,  Warren LE,  Bellon JR,  Punglia RS,  Claus EB,  Lee EQ,  Wen PY,  Haas-Kogan DA,  Alexander BM,  Lin NU and Aizer AA: Brain Metastases in Newly Diagnosed Breast Cancer: A Population-Based Study.  JAMA oncology (2017) 3: 1069-1077.October 2021 CSF CEA in Leptomeningeal Carcinomatosis 661Fig.  2　 Gastrointestinal endoscopy showing advanced gastric cancer.

Added Diagnostic Value of Cerebrospinal Fluid Carcinoembryonic Antigen in a Patient with Leptomeningeal Carcinomatosis as the Initial Manifestation of Gastric Cancer

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Added Diagnostic Value of Cerebrospinal Fluid Carcinoembryonic Antigen in a Patient with Leptomeningeal Carcinomatosis as the Initial Manifestation of Gastric Cancer

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