Cytological Examination Of Cerebrospinal Fluid Research Articles

Cerebrospinal fluid cytology in nonmalignant aseptic meningeal disorders.

Cerebrospinal fluid cytology examination is a common and reliable primary and/or complementary procedure for the diagnosis of central nervous system (CNS) disorders. This review provides an update of aseptic meningeal disorders that may be encountered in cytopathology practice. The article covers the cytological findings and helpful ancillary studies needed of nonmalignant aseptic CNS disorders such as viral, bacterial, fungal and parasitic infections, and other noninfectious diseases, such as Mollaret's meningitis (recurrent benign lymphocytic meningitis), Guillain-Barré syndrome, multiple Sclerosis, subarachnoid haemorrhage, and drug-induced disorders.

Detection value of tumor cells in cerebrospinal fluid in the diagnosis of meningeal metastasis from lung cancer by immuno-FISH technology.

To investigate the detection value of tumor cells in cerebrospinal fluid (CSF) in the adjuvant diagnosis of meningeal metastasis from lung cancer by immunofluorescence in situ hybridization (immuno-FISH) technology. The circulating tumor cells (CTCs) in the CSF of 16 patients with meningeal metastasis from lung cancer and 8 with non-tumor diseases in the brain were detected using immuno-FISH technology. The diagnosis of meningeal metastasis from lung cancer was based on neurological symptoms, enhanced magnetic resonance imaging (MRI) scans and CSF cytological examination. The number of CTCs in the patients with meningeal metastasis from lung cancer was significantly higher than those with non-tumor diseases in the brain (P<0.01). The critical point of the maximum correct diagnostic index (Youden index) was regarded as the judging criterion for positive tumor cells in CSF according to the receiver operating characteristic curve. When there was one tumor cell in 7.5 ml CSF, the area under curve was 0.875 (95% confidence interval, 0.705~1.000). The diagnostic sensitivity, specificity, effectiveness, positive and negative predictive values were 75.0, 100.0, 83.3, 100.0 and 66.7%, respectively. There may be great clinical value in the detection of CTCs in CSF for the diagnosis of meningeal metastasis from lung cancer by immuno-FISH technology.

Osimertinib activity in patients (pts) with leptomeningeal (LM) disease from non-small cell lung cancer (NSCLC): Updated results from BLOOM, a phase I study.

9002Background: LM disease is a severe type of NSCLC disease progression, associated with poor prognosis. Osimertinib (AZD9291) is an oral, potent, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) selective for activating (EGFRm) and T790M resistance mutations. We present updated data from a phase I study, BLOOM (NCT02228369), of osimertinib in pts with LM disease from EGFRm NSCLC. Methods: Pts with EGFRm advanced NSCLC who had progressed on prior EGFR-TKI therapy and LM disease confirmed by positive cerebrospinal fluid (CSF) cytology were enrolled. Pts were treated with osimertinib 160 mg, once daily. Response was assessed based on CSF cytology, intracranial (IC) imaging, and neurological examination. EGFRm DNA in CSF was determined by Droplet Digital PCR. Results: As of December 30, 2015, 20 pts were dosed, of whom 7 were dosed for ≤ 3 weeks. Maximum treatment duration was 37 weeks. Of 12 pts reaching a 12-week IC image assessment, 7 had radiological improvement, 2 had ...

P2-21-3 - Two Cases of Primary B Cell Lymphoma of Cauda Equina

Introduction: The spinal cord is an extremely rare site for primary central nervous system lymphoma. Here, we present two cases of B cell lymphoma of cauda equina.Case1: A 80 year-old woman was admitted to our hospital with progressive pain and muscle weakness of both lower extremities. Magnetic resonance imaging (MRI) uncovered a tumor in cauda equina. A diagnosis of B cell lymphoma was made with cytological examination of cerebrospinal fluid. The patient received one cycle of high-dose methotrexate therapy, but it was not effective.Case2: A 62 year-old man was referred to our hospital because of a progressive pain and paralysis of lower extremities. MRI revealed a significant large tumor in the cauda equina. Diagnosis of diffuse large B cell lymphoma was made with biopsy of the tumor. The patient received three cycles of chemotherapy with high-dose methotrexate and high-dose cytarabine with 40 Gy of irradiation, leading to partial remission.Conclusion: We presented two cases of B cell lymphoma of cauda equina. Neither of the two cases achieved complete remission with high-dose methotrexate chemotherapy. Treatment of primary B cell lymphoma of spinal cord is very difficult because most cases are refractory to standard chemotherapy, including high-dose methotrexate. More effective therapeutic regimens with novel agents are urgently needed for treating primary B cell lymphoma of spinal cord.

Hemorrhagic stroke and cerebral paragonimiasis.

We retrospectively analyzed the clinical and imaging characteristics, diagnosis, and treatment outcomes of 10 patients with hemorrhagic cerebral paragonimiasis (CP), and we evaluated the influence of Paragonimus infection on cerebrovascular damage. Ten patients (7 male and 3 female; median age 15.7 years, range 4-46 years) with hemorrhagic CP were diagnosed between April 2009 and January 2013. All patients underwent the head computed tomography scans and 9 patients underwent MRI examinations. Four patients underwent computed tomographic angiography, magnetic resonance angiography, and digital subtraction angiography. Liquid-based cytological examination of cerebrospinal fluid was performed in 7 patients. Follow-up examinations were performed for 9 cases for a period of 12 to 62 months. Hemorrhagic CP accounted for 37% of CP cases (10/27). No patients were initially diagnosed with CP. The major symptoms of hemorrhagic CP included acute headache, vomiting, hemiparalysis, epilepsy, blurred vision, sensory impairment, and tinnitus. Four cases were surgically treated. Most symptoms markedly improved, but fine motor dysfunction and mental dysfunction remained in 3 surgical patients. Hemorrhagic stroke typically occurred during the acute stage and in the early stages of further Paragonimus migration. Delay of treatment increased the risk of initial and recurrent stroke.

Hepatic myelopathy with spastic paraparesis: report of two cases and review of the literature

The present report illustrates two men aged for 59 and 43 years, respectively, who presented with slowly progressive spastic paraparesis. Two case reports and review of literature. The patent's history, clinical examination, biology, magnetic resonance imaging (MRI) findings and treatment are reported. We also discuss the pathogenesis and various treatment options. Neurologic examination showed spastic paraparesis without other neurological disorders. MRI of the spinal cord and brain were normal. Cytologic examination of cerebrospinal fluid from each patient was normal. Hemogram disclosed a pancytopenia. Partial thromboplastin time was prolonged. Liver function tests revealed raised serum bilirubin, normal alanine aminotransferase and aspartate aminotransferase, reduced total protein and albumin. Plasma ammonia was elevated. Blood vitamin B12 and folate values were in normal ranges. Serum antibodies to human T cell lymphotropic virus, human immunodeficiency virus, syphilis and hepatitis C virus were absent. Hepatitis B virus antibody assay was positive. The electromyographic evaluation for second motor neuron involvement was also normal. Endoscopy revealed esophageal varices and a spleno-renal shunt. Hepatic myelopathy remains a default diagnosis assigned only after the exclusion of other causes of spastic paraparesis and partial transverse myelopathy. An accurate history, along with appropriate imaging and laboratory findings, is crucial.

The application values of cerebrospinal fluid cytological examination by slide centrifugation for diagnosis of central nervous system infectious diseases

According to the analysis of cerebrospnial fluid (CSF) cytological examination (by slide centrifugation) results of 15 940 central nervous system infectious cases, this cytologic examination method shows definite diagnostic values as follows: 1) better etiological diagnostic value for central nervous system infectious diseases, such as purulent, viral, tuberculous, fungus and parasitic encephalitis meningitis and meningoencephalitis; 2) better differential diagnostic value for acute infectious toxic encephalopathy, meningeal carcinomatosis and central nervous system non infectious diseases such as tumorous, leukemic and hemorrhagic meningoencephalitis and encephalopathy; 3) better clinical value for severity monitoring and prognostic judgement of central nervous system infectious diseases.

Primary anaplastic large T cell lymphoma of central nervous system

Background Primary anaplastic large T cell lymphoma (ALCL) of central nervous system (CNS) can occur in people of all ages, and is usually unrelated with immunodeficiency. It is often misdiagnosed as meningitis, especially tuberculous meningitis, on clinical practice and imaging examination. In pathological diagnosis, the morphological changes of primary ALCL of CNS are similar to the systemic ALCL and the anaplastic lymphoma kinase⁃1 (ALK⁃1) can be positive or negative. Being misdiagnosed as meningitis, hormone therapy with glucocorticoid before biopsy is always used, and massive necrosis and a lot of histocyte proliferation and phagocytosis can be found under histological findings. Therefore, when the material is not enough, primary ALCL of CNS is often misdiagnosed as cerebral infarction or malignant histocytosis and so on. This paper reports a case of primary ALCL of CNS and makes a review of relevant literature, so as to summarize the clinical manifestations and elevate the recognition of clinicians and pathologists on this disease. Methods and Results A 12⁃year⁃old boy was admitted because of fever, worsening headache, numbness and weakness of right limbs. MRI showed local gyri swelling and abnormal enhancement of pia mater in the right parietal lobe, expanding to the right temporal lobe, and pia mater enhancement in the left parietal lobe. The right temporo⁃parietal lobe lesion biopsy revealed irregularly shaped tumor cells of large size, rich and eosinophilic cytoplasm and horseshoe⁃shaped or kidney⁃shaped nuclei. Immunohistochemical examination showed tumor cells positive for CD3, CD45RO, CD30, ALK⁃1 and epithelial membrane antigen (EMA), and negative for CD20 and CD79a. Conclusion Primary ALCL of CNS is an extremely rare tumor which is usually misdiagnosed as meningitis according to clinical and imaging examinations. Therefore, for those patients who are considered as meningitis but with poor treatment effect and replase of illness, brain tissue biopsy, which is an important means for diagnosis, or cerebrospinal fluid cytologic examination, should be carried out as soon as possible.

Guidelines for the investigation and management of mantle cell lymphoma.

The guideline group was selected to be representative of UK-based medical experts and patients representatives. Ovid MEDLINE, EMBASE and NCBI Pubmed were searched systematically for publications in English from 1980 to 2011 using the MeSH subheading 'lymphoma, mantle cell' and 'lymphoma, mantle cell' as a keyword, as well as all subheadings. In addition, all references to mantle cell lymphoma in the World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissue (Swerdlow et al, 2008) and the British Committee for Standards in Haematology (BCSH) Guideline: Best Practice in Lymphoma Diagnosis and Reporting (Parker et al, 2010) have been included. The writing group produced the draft guideline, which was subsequently revised by consensus by members of the Haemato-oncology Task Force of the BCSH. The guideline was then reviewed by a sounding board of approximately 50 UK haematologists, the BCSH and the British Society for Haematology Committee and comments incorporated where appropriate. The 'GRADE' system was used to quote levels and grades of evidence, details of which can be found in Appendix I. The objective of this guideline is to provide healthcare professionals with clear guidance on the investigation and management of patients with mantle cell lymphoma. The guidance may not be appropriate to patients with other lymphoma sub-types and in all cases individual patient circumstances may dictate an alternative approach.

Contribution of CSF cytology in the diagnostic work-up of breast cancer patients with neurological symptoms: a retrospective analysis over two decades

The aim of this study was to evaluate the contribution of cytological analysis of cerebrospinal fluid (CSF) in the diagnostic work-up of breast cancer patients who present with neurological symptoms suspected for central nervous system (CNS) metastases. In the period 1989-2009, a total of 81 patients with breast cancer underwent CSF cytological examination. Relevant tumour characteristics, clinical presentation and radiological findings were scored. The CSF cytological diagnosis was classified according to the 1996 NCI-sponsored conference approach as malignant, suspicious for malignancy, atypical, benign or inadequate. During the course of 20 years, 145 CSF cytological examinations were performed. Relatively common neurological symptoms resulting in cytological CSF examination were headache (n = 25), nausea and vomiting (n = 19), sensory disturbances (n = 16), and cranial nerve dysfunction (n = 16). Of these, headache and nausea/vomiting were most often associated with malignant cells in the CSF (CSF(+)) (in 48 and 53% of the cases, respectively). The 4 patients with both headache and confusion/altered mental status all had CSF(+). In 10 patients, CSF(+) was found despite the absence of radiological evidence for metastasis in/around the CNS. In our series, repeated CSF analysis appeared to have limited additional value, and CSF(+) was strongly correlated with shorter survival. A substantial number of patients with neurological symptoms but without radiological abnormalities can have CSF(+). In our series, the additional value of repeated cytological examination of CSF was limited. Our study underscores the value of CSF cytology as a tool for the unequivocal diagnosis of metastatic spread of breast cancer to the CNS, and confirms that CSF(+) is a strong predictor of poor survival.

The influencing factors in further development of domestic centrifugated slide cerebrospinal fluid cytological examination

The influencing factors in further development of domestic centrifugated slide cerebrospinal fluid cytological examination

Follow‐up evaluation of radiation‐induced DNA damage in CSF disseminated high‐grade glioma using phospho‐histone H2AX antibody

Cytological examination of cerebrospinal fluid (CSF) is used not only for the diagnosis of spinal disease, but also to assess the postoperative effect of treatment. We experienced a case of high-grade glioma in disseminated CSF, and retrospectively examined the clinical, pathological and cytological features. We further investigated radiation-induced DNA damage in glioma cells using phospho-Histone H2AX antibody. A five-year-old boy received a clinical diagnosis of optic nerve glioma, and was followed-up for three months after chemotherapy. Magnetic resonance imaging was repeated, revealing abnormalities in other brain areas. The pathological diagnosis was anaplastic astrocytoma. CSF dissemination was detected, and increases in the number and mitosis of tumor cells were observed in CSF cytology. After radiotherapy the tumor cells in CSF decreased markedly. On cytomorphologic and immunocytochemical evaluation post-irradiation, tumor cells showed vacuolation of both the nucleus and cytoplasm, degeneration of nuclear chromatin, and alteration of the phospho-Histone H2AX expression, compared with tumor cells before the irradiation. CSF cytology is an effective means of evaluating DNA damage in tumor cells after irradiation, and may be useful in assessing the therapeutic response.

Fatal Human Case of West Nile Disease, Mexico, 2009

Fatal Human Case of West Nile Disease, Mexico, 2009

Meningeal carcinomatosis in patients with small cell lung cancer

Six patients (2.7%) developed meningeal carcinomatosis among 207 patients with small cell lung cancer (SCLC) receiving intensive combination chemotherapy. The cumulative probability of developing meningeal carcinomatosis was 2.7% at 3 years and 7.8% at 5 years after diagnosis of SCLC. Pain in legs, gait disturbance, headache, nausea and vomiting were the characteristic symptoms at the onset of meningeal carcinomatosis. Although cytological examination of cerebro-spinal fluid (CSF) was essential for the diagnosis of meningeal carcinomatosis, elevated protein, LDH, CEA and/or NSE concentration and decreased glucose concentration in CSF were also helpful for the diagnosis. For treatment of meningeal carcinomatosis, all patients received intrathecal administration of methotrexate, cytosine arabinoside and/or prednisolone. Additionally, 3 patients received spinal irradiation, and one received cerebro-spinal irradiation. However, only 2 patients responded, and survival was brief ranging from 2 to 38 weeks. Development of meningeal carcinomatosis seems to be a rare event; however, it may be an obstacle to the prolongation of patient survival in the treatment of SCLC.

An Unusual Case of Pancreatic Cancer with Leptomeningeal Infiltration

Pancreatic cancer is a common malignancy and often presents at an advanced stage. Metastases are common but neurological involvement is rare. We aim to describe an unusual case of leptomeningeal involvement from pancreatic cancer. A 59-year-old man presented with a several-year history of abdominal pain, weight loss and anaemia, which had been extensively investigated. Four years after initial presentation, he presented with left leg weakness and sensory disturbance. He was observed to suffer intermittent complex seizures. CT scan of the abdomen showed subtle narrowing of the common bile duct and pancreatic ducts. Endoscopic ultrasound showed a 5-cm lesion in the head of the pancreas with adenocarcinoma cells on fine needle aspiration. Serum CA19.9 was 2,293 U/ml. MRI study of the brain and spinal cord showed widespread leptomeningeal enhancement. Cytological examination of cerebrospinal fluid revealed epithelial cells staining positive for MNF116 and EMA. He started on a weekly regimen of intrathecal combination chemotherapy of hydrocortisone 50 mg, methotrexate 12.5 mg and cytarabine 50 mg. He was also treated synchronously with palliative systemic gemcitabine. His clinical condition continued to deteriorate, cytotoxic therapy was withdrawn after 2 weeks and he died the following month. This case represents the unusual presentation of advanced leptomeningeal carcinomatosis in a locally early stage pancreatic adenocarcinoma. Other reported cases have been in patients with advanced metastatic disease. In the case of significant neurological symptoms and signs, clinicians should have a low threshold for performing investigations to exclude neurological involvement.

“Primary” leptomeningeal medulloblastoma

We report the case of an 8-year-old boy who presented with a 2-month history of headaches and mild visual impairment and was found to have a medulloblastoma with primary leptomeningeal involvement. No mass lesion was found on imaging studies, during subsequent intraoperative surgical inspection or at autopsy. The pathologic findings were first documented on cerebrospinal fluid cytologic examination and biopsy of the cerebellum and were later confirmed at necropsy. To our knowledge, this is the third reported case of medulloblastoma identified with primary leptomeningeal involvement without a cerebellar mass and the first such case with documented autopsy findings.

Epithelioid cell cluster in cerebrospinal fluid: An unusual finding in tubercular meningitis

Tubercular meningitis is one of the serious manifestations of tuberculosis. It remains a significant contributor to the morbidity and mortality in children. Meningeal involvement in tuberculosis is detected by physical, chemical and cytological examination of cerebrospinal fluid (CSF). The cytological picture of CSF in tubercular meningitis is quite similar to that of viral meningitis showing a mixed population of lymphoid series cells. The presence of epithelioid cell cluster is very rare finding. We present here such a case of 2(1/2) yr old boy who presented with fever off and on for 2 months and altered sensorium along with vomiting for 2-3 days.

Posterior fossa lymphoma with initial vertigo presentation

This study retrospectively reviewed our experience in the diagnosis of six patients with posterior fossa lymphoma during the past decade. Initial manifestation included vertigo in all patients (100%) and ataxia in 4 (67%), with a mean duration of 40 days. Audiometry revealed sensorineural hearing loss in five patients (83%). Gaze-evoked nystagmus was also noted in five patients (83%). Electronystagmography (ENG) showed multiple central signs, e.g., abnormal eye tracking test, abnormal optokinetic nystagmus test, abnormal caloric and/or visual suppression tests. MR imaging demonstrated single or multiple or diffuse enhanced mass lesions in the cerebellum and/or brainstem. Two patients received lumbar puncture for cytological examination of cerebrospinal fluid (CSF) which disclosed lymphoma cells, while the other four patients underwent craniotomy for tissue proof, and the histopathological study confirmed as lymphoma. Then, all patients underwent irradiation coupled with chemotherapy. At the close of this study, three patients died, two were lost and one was alive. Although rare, aggressive posterior fossa lymphoma should be kept in mind when seeing a patient with persistent vertigo and ataxia accompanied by multiple central signs in ENG examination. An MRI scan followed by CSF cytological examination or histopathological study may help to confirm the diagnosis.

A Case of Meningeal Carcinomatosis with Gastric Cancer Which Manifested Meningeal Signs as the Initial Symptom; the Palliative Benefit of Radiotherapy

A 53-year-old male presenting with anorexia, intermittent diplopia, general fatigue, headache and vertigo was admitted to our hospital. He was diagnosed as having gastric cancer by endoscopy of his upper gastrointestinal tract. Brain computed tomography (CT) showed no abnormalities, but magnetic resonance imaging (MRI) showed slight enhancement in the cerebellar sulcus. Cytological examination of cerebrospinal fluid revealed malignant cells. He became blind one week after hospitalization. We diagnosed his condition as meningeal carcinomatosis (MC) and started radiotherapy. His vision improved after four weeks of treatment, and then he became totally blind again. Since his general condition remained poor, we did not perform chemotherapy. He died on the 127th day of hospitalization. MC is a rare pathosis of gastric cancer in comparison with leukemia and malignant lymphoma. This disease does not often show characteristic pictorial images, and early diagnosis is difficult. Moreover, it usually manifests itself in its late stages after several months or more of treatment, and it is rare for MC to be present at the time of initial diagnosis. We present a case of gastric cancer with meningeal signs present when the primary tumors were diagnosed. Radiotherapy alleviated some of the symptoms, and the patient survived for as long as patients undergoing enforced chemotherapy.

Feasibility and Toxicity of Intrathecal Liposomal Cytarabine in 5 Children and Young Adults With Refractory Neoplastic Meningitis

Intrathecal (IT) treatment of neoplastic meningitis secondary to relapsed or refractory malignancies is a major challenge for clinicians. We studied feasibility and toxicity of IT administered liposomal cytarabine on a compassionate basis in 5 patients (male, n=4; female, n=1; age at diagnosis 5 to 18 y) with recurrent acute lymphoblastic leukemia (n=3), primary refractory acute myeloid leukemia (n=1), or relapsed medulloblastoma (n=1). All of them had evidence of meningeal involvement as shown by presence of leukemic blasts or solid tumor cells on cytologic examination of cerebrospinal fluid and were refractory to standard central nervous system (CNS) therapy. A total of 33 doses were given. Leukemic blasts or solid tumor cells were cleared from cerebrospinal fluid in all patients. IT liposomal cytarabine was well tolerated in 2 patients, but may have contributed to neurologic side effects in 2 other patients with 1 patient who received high-dose methotrexate 96 hours before IT liposomal cytarabine developing transient encephalopathy. Another patient experienced seizures after 6 well-tolerated doses of IT liposomal cytarabine. In the fifth patient, treatment with IT liposomal cytarabine was not continued after a single dose because of toxic cauda equina syndrome, resulting from previous intensive CNS therapy. If administered simultaneously to other neurotoxic drugs, IT liposomal cytarabine may contribute to neurologic side effects in patients who had received prior intensive CNS-directed therapy. IT liposomal cytarabine should, therefore, be used cautiously, if a patient receives other potentially neurotoxic drugs simultaneously.