Diagnosis Of Meningeal Carcinomatosis Research Articles

The diagnostic significance of cerebrospinal fluid cytology and circulating tumor DNA in meningeal carcinomatosis.

The objective of this research is to investigate the clinical application value of cerebrospinal fluid (CSF) cytology and circulating tumor DNA (ctDNA) in lung adenocarcinoma (LUAD) meningeal metastasis-meningeal carcinomatosis (MC), and to further explore the possible molecular mechanisms and drug treatment targets of LUAD meningeal metastasis by next-generation sequencing (NGS). We retrospectively analyzed LUAD with MC in 52 patients. CSF cytology was carried out using the slide centrifugation precipitation method and May-Grüwald-Giemsa (MGG) staining. Tumor tissue, plasma and CSF ctDNA of some MC patients were detected by NGS. Of the 52 MC patients, 46 (88.46%) were positive for CSF cytology and 34 (65.38%) were positive for imaging, with statistically significant differences in diagnostic positivity (P < 0.05). In 32 of these patients, CSF cytology, cerebrospinal fluid ctDNA, plasma ctDNA and MRI examination were performed simultaneously, and the positive rates were 84.38, 100, 56.25, and 62.50% respectively, the difference was statistically significant (P < 0.001). Analysis of the NGS profiles of tumor tissues, plasma and CSF of 12 MC patients: the mutated gene with the highest detection rate was epidermal growth factor receptor (EGFR) and the detection rate were 100, 58.33, and 100% respectively in tumor tissues, plasma and CSF, and there were 6 cases of concordance between plasma and tissue EGFR mutation sites, with a concordance rate of 50.00%, and 12 cases of concordance between CSF and tissue EGFR mutation sites, with a concordance rate of 100%. In addition, mutations not found in tissue or plasma were detected in CSF: FH mutation, SETD2 mutation, WT1 mutation, CDKN2A mutation, CDKN2B mutation, and multiple copy number variants (CNV), with the most detected being CDKN2A mutation and MET amplification. CSF cytology is more sensitive than traditional imaging in the diagnosis of meningeal carcinomatosis and has significant advantages in the early screening and diagnosis of MC patients. CSF ctDNA can be used as a complementary diagnostic method to negative results of CSF cytology and MRI, and CSF ctDNA can be used as an important method for liquid biopsy of patients with MC, which has important clinical significance in revealing the possible molecular mechanisms and drug treatment targets of meningeal metastasis of LUAD.

Characteristics of Patients with Meningeal Carcinomatosis Combined with Myelopathy.

ObjectiveTo explore the disease manifestations and radiological characteristics of patients with meningeal carcinomatosis (MC) combined with myelopathy.Patients and MethodsThe detailed medical information of patients who suffered from MC with myelopathy in record system were collected and reviewed.ResultsIn these patients, five cases were male and two cases were female. The age was from fifteen to fifty-seven years. In the course of disease, tumor cells were discovered in cerebrospinal fluid of three patients and in biopsy samples of four patients. Cerebrospinal fluid (CSF) test results showed white blood cell counts increased in seven patients, protein increased in six patients and glucose reduced in five patients. In addition, MRI revealed that the white matter abnormalities showed in all cases and pia mater was enhanced in four patients, meningeal enhanced was observed in three patients. All patients were given appropriate therapy during hospitalization. Follow-up result showed that all patients passed away two to five months after diagnosis.ConclusionMC causes spinal membrane, spinal nerve root to be involved besides, also can produce the matter of myelopathy. Early detection of intramedullary lesion is conducive to strengthening the awareness of the diagnosis of MC.

Detection and significance of exosomal mRNA expression profiles in the cerebrospinal fluid of patients with meningeal carcinomatosis.

Exosomes are cell-derived membrane vesicles with cargo that can be transported into receiver cells to exert their biological roles. Exosomal RNA signature profiles and exosome-derived proteomics are often used to explore the molecular regulation of diseases, and can mirror the conditional state of their tissue of origin, thus serving as biomarkers. The onset of meningeal carcinomatosis (MC) is concealed, and early diagnosis is difficult. To enable early diagnosis of MC, it is essential to identify new biomarkers. Few studies have investigated the function of exosomes in MC. In this study, high-throughput sequencing was used to examine the mRNA profiles of exosomes in the cerebrospinal fluid (CSF) of patients with MC. We further analyzed the functions and signaling pathways associated with the differentially expressed genes in exosomes to reveal the putative mechanisms by which the exosomal mRNAs function in MC. In summary, this study identified biomarker candidates for MC, and provided new insights into the significant role of exosomal mRNA regulation in MC.

Evaluating the cerebrospinal fluid ctDNA detection by next-generation sequencing in the diagnosis of meningeal Carcinomatosis

BackgroundMeningeal carcinomatosis (MC) is the most severe form of brain metastasis and causes significant morbidity and mortality. Currently, the diagnosis of MC is routinely confirmed on the basis of clinical manifestation, positive cerebrospinal fluid (CSF) cytology, and/or neuroimaging features. However, negative rate of CSF cytology and neuroimaging findings often result in a failure to diagnose MC from the patients who actually have the disease. Here we evaluate the CSF circulating tumor DNA (ctDNA) in the diagnosis of MC.MethodsA total of 35 CSF samples were collected from 35 patients with MC for CSF cytology examination, CSF ctDNA extraction and cancer-associated gene mutations detection by next-generation sequencing (NGS) at the same time.ResultsThe most frequent primary tumor in this study was lung cancer (26/35, 74%), followed by gastric cancer (2/35, 6%), breast cancer (2/35, 6%), prostatic cancer (1/35, 3%), parotid gland carcinoma (1/35, 3%) and lymphoma (1/35, 3%) while no primary tumor could be found in the remaining 2 patients in spite of using various inspection methods. Twenty-five CSF samples (25/35; 71%) were found neoplastic cells in CSF cytology examination while all of the 35 CSF samples (35/35; 100%) were revealed having detectable ctDNA in which cancer-associated gene mutations were detected. All of 35 patients with MC in the study underwent contrast-enhanced brain MRI and/or CT and 22 neuroimaging features (22/35; 63%) were consistent with MC. The sensitivity of the neuroimaging was 88% (95% confidence intervals [95% CI], 75 to 100) (p = 22/25) and 63% (95% CI, 47 to 79) (p = 22/35) compared to those of CSF cytology and CSF ctDNA, respectively. The sensitivity of the CSF cytology was 71% (95% CI, 56 to 86) (n = 25/35) compared to that of CSF ctDNA.ConclusionsThis study suggests a higher sensitivity of CSF ctDNA than those of CSF cytology and neuroimaging findings. We find cancer-associated gene mutations in ctDNA from CSF of patients with MC at 100% of our cohort, and utilizing CSF ctDNA as liquid biopsy technology based on the detection of cancer-associated gene mutations may give additional information to diagnose MC with negative CSF cytology and/or negative neuroimaging findings.

Application of cerebrospinal fluid cytological slides repeated destaining and redying in diagnosis of meningeal carcinomatosis

目的： 探讨脑脊液细胞片行褪色再染在脑膜癌病诊断中的运用。 方法： 回顾性的收集经组织学证实肿瘤原发灶伴发影像学脑转移的脑脊液细胞片7例（肺腺癌脑转移5例，胃腺癌脑转移2例），选取每例中的HE片入95%乙醇+0.5%盐酸乙醇褪色再巴氏染色，巴氏片入80%乙醇+0.5%盐酸乙醇褪色再免疫细胞化学双重染色。 结果： 巴氏重染细胞透亮度佳，核质分明，核染色质及核仁结构清晰，胞核蓝色，胞质灰蓝色；免疫细胞化学双染效果：甲状腺转录因子1（TTF1）/Napsin A：核/质呈棕褐色/红色表达；CDX2和过碘酸雪夫双染：核/质呈浅褐色/粉红色表达。巴氏和免疫细胞化学重染均未见细胞脱落，细胞形态完整、无交叉反应，核质分明，背景干净。 结论： 褪色再染可在同一张脑脊液细胞片上实现，对于细胞学中脑转移癌的肿瘤类型及追溯原发灶提供诊断的依据。.

Meningeal carcinomatosis from bladder cancer: A case report and review of the literature.

A 66-year-old Japanese male patient was referred to Saitama Medical University International Medical Center for treatment of bladder cancer (clinical stage T2 or higher without metastasis), and underwent radical cystectomy with pelvic lymphadenectomy. The histopathological diagnosis was high-grade urothelial carcinoma (pathological stage T2bN2, ly1, v0) and 2 cycles of adjuvant systemic chemotherapy (gemcitabine plus cisplatin) were administered. At 15 months after the operation, mediastinal and lung hilar lymph nodes and multiple bone metastases were identified on computed tomography imaging. After 3 cycles of the previous regimen as salvage systemic chemotherapy, the lymph node metastases had shrunk and the bone metastases were stable; therefore, further chemotherapy was planned. At 26 days after the initiation of the 4th cycle, the patient felt nausea and lower limb weakness. Spinal and brain magnetic resonance imaging with contrast medium revealed diffuse enhancement at the surface of the spinal cord and brain. In addition, abnormal signal intensity in the subarachnoid space was observed on fluid-attenuated inversion recovery imaging; therefore, the patient was diagnosed with meningeal carcinomatosis (MC). Treatment, including whole-brain radiotherapy, was planned for MC; however, the patient's condition rapidly worsened and he succumbed to the disease 14 days after the diagnosis of MC. The definitive diagnosis of MC was confirmed at autopsy.

Prognostic Markers and Histologic Subtypes in Patients with Meningeal Carcinomatosis in Breast Cancer

Objective: Meningeal carcinomatosis (MC) is a rare complication in breast cancer patients. It is defined as a diffuse or multifocal leptomeningeal metastasis. Study Design: From our institution database, we retrospectively studied 19 patients diagnosed with MC in the cerebrospinal fluid (CSF) in 1997-2015, in order to evaluate tumor prognostic markers, histologic subtypes, and clinical outcome. Results: All patients were female, with a mean age of 53 years (range 36-75 years). The mean interval between diagnosis of breast carcinoma and MC was 28 months (range 6-62 months). The median survival from the time of diagnosis was 2 months (1-51 months). Sixteen cases (84%) were the ductal phenotype, 62% of which were of a high grade (grade 3), and 3 cases (16%) were lobular. Estrogen and progesterone receptors were positive on immunohistochemistry (IHC) in 53 and 33% of patients, respectively. HER2 IHC was positive (3+) in 20% of the cases; all were amplified by fluorescence in situ hybridization. The incidence of MC in triple-negative tumors was 40%. Twelve patients (63%) already had known metastasis at the time of diagnosis. Conclusions: Most cases of MC are high-grade ductal. MC is more common in triple-negative breast cancers. The outcome of these breast cancer patients with MC was poor. There was no survival difference according to age, histologic subtype, grade, or hormonal or HER2 status.

Gadobutrol-enhanced magnetic resonance imaging of meningeal carcinomatosis: case report with emphasis on early diagnosis

BackgroundTimely diagnosis of meningeal carcinomatosis is often difficult even with the assistant of magnetic resonance imaging examination, cerebrospinal fluid analysis, or both. To the best of our knowledge, gadobutrol-enhanced MRI has not been reported in the diagnosis of meningeal carcinomatosis. Here we present two cases where meningeal carcinomatosis was identified on gadobutrol-enhanced magnetic resonance imaging.Case presentationWe identified two cases of meningeal carcinomatosis who had been diagnosed with malignant tumors several years ago. Both patients presented with progressive headache and seizures. Gadopentetate dimeglumine-enhanced magnetic resonance imaging of the brain was performed and did not detect any abnormality of meninges. Lumbar puncture was performed repeatedly, but cerebrospinal fluid cytology showed no evidence of malignant cells. Finally the gadobutrol-enhanced magnetic resonance imaging detected the meningeal metastasis, and supported the diagnosis of meningeal carcinomatosis.ConclusionGadobutrol provides higher lesion conspicuity and enhances lesion detection in meningeal metastasis compared with gadopentetate dimeglumine. Our observation is a cue to analyze the accuracy in the diagnosis of meningeal carcinomatosis, and presents a choice that may facilitate early diagnosis.

The concentration of CYFRA 21-1, NSE and CEA in cerebro-spinal fluid can be useful indicators for diagnosis of meningeal carcinomatosis of lung cancer

We aimed to investigate the concentration of CYFRA 21-1, NSE and CEA in cerebro-spinal fluid (CSF) and to explore their clinical value in the meningeal carcinomatosis (MC) of lung cancer. So that, sensitive and specificity of CSF examination can be improved in the initial diagnosis of MC. A total of 35 lung cancer patients and 35 patients with benign brain tumor in the same period enrolled in this study. The concentrations of tumor markers CEA, CYFRA 21-1 and NSE in CSF and peripheral blood were examined. The concentrations of three tumor markers of CYFRA 21-1, NSE and CEA in blood serum and CSF were obviously higher than that of benign disease group. In MC patients, the concentrations of three tumor markers of CYFRA 21-1, NSE and CEA in blood serum were significant lower than that in CSF. The maximum of Youden's index was identified as the cutoff value of indicator of MC in three tumor markers in CSF which were CEA > 4.7 μg/L, NSE > 14.6 μg/L and CYFRA21-1 > 5.5 μg/L respectively. Based on the cutoff values, the CEA had the highest sensitivity while the CYFRA21-1 had the highest specificitiy. Three tumor markers in the CSF had higher positive rate than those in blood serum. We combined the levels of CEA, NSE and CYFRA21-1 in CSF to diagnosis of MC. Positive of CEA or CYFRA21-1 had the greatest sensitivity of 100% while the specificity of 91.4%; the positive of both CEA and CYFRA21-1 had the highest specificity of 100% while the sensitivity of 74.3%. Both positive predictive value and negative predictive value were 100% when combination positive were confirmed when the all three markers were positive. The combination of CEA and CYFRA21-1 can be recommended in early screening of meningeal carcinoma. Especially, for the patient who was difficult to be diagnosed by CSF histology and MRI, it will be a useful auxiliary marker in diagnosis of MC. The combination of CEA, NSE and CYFRA21-1 can be an effective clinically confirmation and exclusively diagnose indictor of MC.

A Survey of Non-Small Cell Lung Cancer Patients with Meningeal Carcinomatosis in Japan: Incidence and Medical Resource Consumption

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) may be effective for patients for non-small cell lung cancer (NSCLC) with meningeal carcinomatosis (MC), but evidence is limited particularly for the economics aspects. This study aimed to estimate the incidence of MC and resource consumption for NSCLC patients with MC as an exploratory study for further pharmacoeconomic evaluation of EGFR-TKI treatment in these patients. Methods: Patients diagnosed with NSCLC in Kyoto University Hospital between January 1, 2005 and December 31, 2008 was identified using medical record data in the hospital. The cumulative incidence of MC was calculated taking into account the competing risk of death. The economic analysis adopted the payer perspective and included direct medical costs (2010 costs) from the date of diagnosis of MC until the time of death. The resource utilization data are expressed as costs per patient per month. Results: Of 376 patients diagnosed with NSCLC in the study period, 28 were diagnosed with MC up to December 31, 2009 and the cumulative incidences at 1 and 2 years after NSCLC diagnosis were 2.4% and 6.0% respectively. The drug costs per patient per month in MC patients treated with an EGFR-TKI were more than twice that in the non-EGFR-TKI group, but the total costs per patient per month were lower in the EGFR-TKI group. A comparison of sub-categories of costs showed that hospitalization accounted for the highest percentage of medical resource consumption. Conclusions: These estimates constitute a basis for cost-effectiveness analysis of EGFR-TKI treatment for NSCLC patients.

402 - Risk of Meningeal Involvement in Metastatic Breast Cancer Patients

ABSTRACT Background Meningeal Carcinomatosis (MC) occurs in 4-15% of patients with solid tumors, usually as a late event in the natural history of disease. Improvement in cancer treatments and patient survival and advances in neuro-imaging techniques have recently led to an increased incidence of MC, mostly in metastatic breast cancer. About 2-5% of breast cancer patients develop MC: median overall survival is 4-6 weeks without treatment and about 2-6 months when specific therapies are used. Objective: The aim of our study is to determine clinical, histological and immunological patterns of primary breast cancer which increase risk of MC. Patients and methods We performed a retrospective analysis of a cohort of 1037 consecutive patients treated for breast cancer from April 1994 to May 2010 at San Giovanni Battista Hospital in Turin. Diagnosis of MC was carried out in presence of neoplastic cells at cerebrospinal fluid citology. In case of negative or inconclusive citology, despite the presence of a characteristic clinical picture of MC, diagnosis was made using neuro-radiological findings, obtained by magnetic resonance imaging. Results We found 29 of 1037 breast cancer patients (2,8%) who developed MC. Among continuous variables associated with increased risk of MC (p Conclusions We identified breast cancer patients at high risk to develop MC. These patients may benefit from an early diagnosis of MC to obtain better results with current treatments and to improve quality of life. Disclosure All authors have declared no conflicts of interest.

Value of MRI enhanced scanning in diagnosis of meningeal carcinomatosis

The clinical data and findings in MRI enhanced scanning of 16 patients with meningeal carcinomatosis were analyzed retrospectively.Meningeal carcinomatosis with subacute- or chronic-onset deteriorated progressively presenting the characteristics of intracranial hypertension and meningeal irritation.Fourteen out of 16 patients showed abnormal linear and strip signal enhancement of meninges by enhancement scanning.Meningeal carcinomatosis presented in diversified patterns and contrast-enhanced MRI is of referential value for the diagnosis of the disease. Key words: Meningeal neoplasm; Magnetic resonance imaging

Ocular manifestations of meningeal carcinomatosis: A case report and literature review

Background Meningeal carcinomatosis (MC) is a devastating and frequently fatal complication of cancer, affecting approximately 5% of patients with systemic malignancies. The disease is characterized by diffuse infiltration of the meninges and cerebrospinal fluid by metastatic tumor cells. The disease affects all levels of the central nervous system, with the most common symptoms of the disease being headache, change in mental status, diplopia, hearing loss, facial numbness, and vision loss. Ocular or visual symptoms have been reported in 91% of patients with MC and may progress to total blindness. Case report This report presents a case of MC with multiple ocular manifestations and a review of the literature regarding diagnosis and treatment of the disease. Conclusion Eye care professionals can play a critical role in directing care and achieving an early diagnosis of MC and should be educated about this rare condition.

Meningeal carcinomatosis in breast cancer: prognostic factors and outcome

Meningeal carcinomatosis (MC) occurs in up to 5% of breast cancer patients. Few studies have evaluated prognostic markers in breast cancer patients with MC. Our aim was to describe the treatment of breast cancer patients with MC, and identify prognostic factors related to survival. Sixty breast cancer patients that had a diagnosis of MC between January 2003 and December 2009 were included. The median age was 46years (range 27-76). Most patients had invasive ductal carcinoma (78.3%) and high histological/nuclear grade (61.7/53.3%). Estrogen and progesterone receptors were positive in 51.7 and 43.3% of patients, respectively, and 15% were HER-2-positive. Symptoms at presentation were headache, cranial nerve dysfunction, seizures, and intracranial hypertension signals. Diagnosis was made by CSF cytology in 66.7% of cases and by MRI in 71.7%. Intrathecal (IT) chemotherapy was used in 68.3% of patients, and 21.6% received a new systemic treatment (chemo- or hormone therapy). Median survival was 3.3months (range 0.03-90.4). There was no survival difference according to age, nuclear grade, hormonal and HER-2 status, CSF features, sites of metastasis, systemic and IT chemotherapy, or radiotherapy. However, histological grade and performance status had a significant impact on survival in the multivariate analysis. Only four papers have addressed prognostic factors in breast cancer patients with MC in the last two decades. The results of those reports are discussed here. High histological grade and poor performance status seem to impact survival of breast cancer patients with MC. Prospective studies are necessary to clarify the role of IT and systemic treatment in the treatment of those patients.

A case of primary uterine cervical neuroendocrine tumor with meningeal carcinomatosis confirmed by diagnostic imaging and autopsy

Primary uterine cervical neuroendocrine tumors are rare, but affect relatively young women and the prognosis is poor despite multidisciplinary treatment. The incidence of meningeal carcinomatosis arising from malignant tumors of the uterine cervix is extremely low, only two patients with meningeal carcinomatosis arising from a uterine cervical neuroendocrine tumor have been reported in the English literature. Moreover, there have been no reports in which this was confirmed at autopsy. We encountered a pregnant woman aged 33years who was diagnosed as having atypical carcinoid of the uterine cervix after radical surgery. Despite multidrug chemotherapy (paclitaxel+etoposide+cisplatin and irinotecan+carboplatin), the patient developed multiple organ metastases. Although there was no metastasis to the brain parenchyma or the spinal cord parenchyma, the patient also developed meningeal carcinomatosis. Whole-brain radiation therapy was performed, but was ineffective. The patient died at 19months after her initial operation and 10days after diagnosis of meningeal carcinomatosis. The presence of meningeal carcinomatosis was confirmed at autopsy.

Meningeal carcinomatosis in patients with breast cancer: clinical features and prognostic factors in 91 patients from a single institution.

Abstract Abstract #1090 Background&amp;#x2028; Breast cancer is the leading solid tumor responsible for meningeal carcinomatosis (MC) and the incidence is rising. To date, there is no standard of care and few prospective trials. Intrathecal treatment is provided but the modalities remain controversial.&amp;#x2028; Methods&amp;#x2028; From our data base we recorded 91 patients with breast MC admitted to Institut Curie between 2000-2007. Lumbar punction was performed in all patients for cerebrospinal fluid (CSF) cytology, protein level and dosage of CYFRA 21. Intra-thecal treatment: methotrexate 15 mg day1 to 5 and hydrocortisone acetate day 1 with oral folinic acid rescue day 1 to 5 every two weeks.&amp;#x2028; Results&amp;#x2028; Median age was 53 years (range 30-78). Tumor type was ductal carcinoma (63%), lobular (28%), ER positive 74%, HER2 overexpressed 10% and triple negative 31%. All patients presented other metastatic site: bone (67%), liver (42%) lung (29%), brain (38%). The median interval between primary tumor and diagnosis of MC was 60 months.&amp;#x2028; Amongst the 80 patients treated (87%) with intra-thecal MTX, clinical response was observed in 88% of cases. There was a strong correlation between clinical response and survival (p&amp;lt;0.001). Normalization of cerebrospinal fluid cytology (CSFC) was observed in 13 % of patients and was associated with better survival: 13 months versus 2 months (p=0.003). Improvement of other biologic parameters as CSF protein and CYFRA 21 was observed in 17% and 80% of patients respectively. The median survival was 4.5 months (0-53). In multivariate analysis, prognostic factors were: performance status 3-4 (p&amp;lt;0.0001), more than 3 chemotherapy regimens before MC diagnosis (p=0.04), lack of ER (p=0.04) and high CYFRA 21 at diagnosis (p=0.01). With these factors a prognostic score may select patients with a true benefit to IT MTX (20% survival &amp;gt; 1 year) or patients for whom treatment will have no impact on survival (&amp;lt; 3 months).&amp;#x2028; Conclusion: This score has to be confirmed in prospective study and new modalities of treatments need to be evaluated according to the biology of disease. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1090.

Cytologically Proven Meningeal Carcinomatosis in Patients with Lung Cancer: Clinical Observation of 34 Cases

Meningeal carcinomatosis (MC) is a rare neurologic complication of lung cancer. Occasionally, it is the initial presentation of lung cancer. The clinical features of MC exclusively in lung cancer patients have not been well identified and characterized. The purpose of this report is to disclose the clinical features, laboratory findings, treatment and survival of patients with MC from lung cancer. We reviewed the medical records of 34 lung cancer patients with cytologically diagnosed MC at National Taiwan University Hospital from 1992 to 2002. Clinical symptoms and signs, cerebrospinal fluid parameters and lung cancer staging at the time of presentation were summarized. Previous treatment modalities for lung cancer, various treatments and response of MC, complications and survival times were also analyzed. Cerebrospinal fluid cytology revealed adenocarcinoma in 32 patients, and small cell carcinoma and squamous cell carcinoma in one each. MC occurred in approximately 0.7% of lung cancer patients. Nine patients had MC as the initial presentation of lung cancer. Symptom improvement was found in six patients who had whole brain irradiation for MC and one patient who had a ventriculoperitoneal shunt. Two of the patients with whole brain irradiation survived for longer than 1 year. Survival from cytologic diagnosis of MC ranged from 1 day to 82 weeks (median, 5.1 weeks). There was no difference in survival between patients treated by whole brain irradiation and other treatment modalities. The prognosis of MC from lung cancer is poor. A prospective study is needed to establish the effectiveness of combined modality therapy for patients with MC from lung cancer.

Pathological examination of spinal lesions in meningeal carcinomatosis

For elucidation of the mechanism of spinal cord disorders associated with meningeal carcinomatosis, we investigated meningeal infiltration and parenchymal, vascular, and radicular damage in spinal cords subjected to pathological autopsy. Spinal cords were collected from 24 patients with a histopathological diagnosis of meningeal carcinomatosis. Infiltration from the subarachnoid space into the spinal cord occurred primarily along the perivascular tissue, and infiltration from the anterior median fissure to the anterior horn was found along the central artery in cases of marked meningeal dissemination. Meningeal dissemination was particularly evident with small cell carcinoma of lung, breast cancer and melanoma, and direct infiltration from the meninges into the spinal cord was found. Direct infiltration into the nerve roots was frequently observed, and infiltration was more evident in the dorsal roots than in the ventral roots, with loss of nerve fibers. Circular necrosis of the white matter in the periphery of the spinal cord was noted in cases of marked meningeal dissemination, which probably resulted from circulatory disturbance secondary to tumor infiltration. In cases of marked dorsal radiculopathy, there was secondary ascending degeneration of the posterior funiculus in cases of marked dorsal radiculopathy. These pathological changes associated with spinal cord disorders are important findings in reviewing spinal cord symptoms and radiographic findings in meningeal carcinomatosis.

感音難聴で発症した髄膜癌腫症例

We report the case of a 45-year-old man with meningeal carcinomatosis who presented with bilateral progressive sensorineural hearing loss. The patient had been operated on for sigmoid colon cancer and lung cancer in 2006. He had experienced left hearing loss and left susurrus aurium since April 2007. Magnetic resonance imaging (MRI) revealed an enhanced mass in the left internal acoustic meatus, so we first suspected vestibular schwannoma. One month later, sudden sensorineural hearing loss developed on the other side. We examined the cerebrospinal fluid (CSF), and adenocarcinoma was detected. A diagnosis of meningeal carcinomatosis was made. With a history of malignant tumor, meningeal carcinomatosis should be considered as a cause of sensorineural hearing loss.

Application of intrathecal trastuzumab (Herceptin™) for treatment of meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer

Leptomeningeal carcinomatosis represents a rare manifestation of metastatic breast cancer (MBC). A 39-year-old female presenting with HER2-overexpressing MBC and suffering from meningeal carcinomatosis was treated with the humanized antibody trastuzumab directed to HER2 by intrathecal administration. The patient was diagnosed with HER2-overexpressing stage III breast cancer in December 2003. In August 2004, the patient developed a singular intracerebral metastasis which was resected by neurosurgery followed by whole-brain radiotherapy. Since MRI and cerebrospinal fluid (CSF) analyses indicated meningeal carcinomatosis, the patient was commenced on trastuzumab (6 mg/kg q3w) and capecitabine (2.500 mg/m2 d1-14, q3w). Prompted by clinical deterioration, 5 repeated doses of intrathecal methotrexate (15 mg/dose) were administered, yet without clinical improvement. There is initial evidence that trastuzumab does not reach an adequate concentration in CSF after intravenous application. Nevertheless, infiltration of trastuzumab into CSF is facilitated under conditions of an impaired blood-brain barrier, as it is known for meningeal carcinomatosis. For patients with leptomeningeal disease, intrathecal application of trastuzumab may provide an interesting therapeutical approach for patients with HER2 overexpressing metastatic breast cancer. Therefore, an Ommaya reservoir for intrathecal treatment with trastuzumab was placed surgically and intrathecal therapy was begun with escalating doses of trastuzumab (5-20 mg), which proved to be effective and well tolerated by the patient. Within 2 weeks after treatment, the patients' condition improved significantly and cell counts in CSF obtained from the Ommaya reservoir remained low for 11 months after first diagnosis of meningeal carcinomatosis when clinical symptoms and MRI indicated progression of meningeal and cerebral disease.