Cerebrospinal fluid cytology diagnosis of meningeal carcinomatosis in patients with small-cell carcinoma of the lung. A study of interobserver and intraobserver variability

The interobserver and intraobserver variation in the cytologic diagnosis of malignancy was determined in 62 cerebrospinal fluid (CSF) specimens from 46 patients with small-cell carcinoma of the lung. In all patients, lumbar puncture was carried out because of suspected central nervous system metastases. Forty CSF specimens from 26 patients with meningeal carcinomatosis and thus with a high probability of a positive CSF cytology were mixed with 22 specimens from 20 patients without meningeal carcinomatosis. The slides were evaluated blindly by two observers, one of whom evaluated all specimens on two separate occasions; only positive, negative and suspicious conclusions were permitted. The consistency of the intraobserver and interobserver conclusions on the initial CSF specimen in each case was 87%. In 13% of the initial CSF specimens in each case, a suspicious conclusion was reached in one of the three evaluations. For all 62 CSFs, the intraobserver and interobserver disagreement was 2% and 3%, respectively. In the first and second evaluations by the one observer and the single evaluation by the other, 17 (65%), 15 (58%) and 12 (46%), respectively, of the 26 "high probability" patients were found to have malignant cells in the CSF. CSF cytology was negative in all 20 patients without meningeal carcinomatosis. Of 10 patients with autopsy-proven meningeal carcinomatosis, 40% were not diagnosed while alive. Multiple CSFs from repeated lumbar punctures increased the number of positive evaluations by 30%. At least 60% of those patients with a suspicious CSF cytology did in fact have meningeal carcinomatosis. On the other hand, 30% of the patients with a positive lumbar puncture had a subsequent negative one.     

The cytopathology of cerebrospinal fluid. II. Metastatic cancer, meningeal carcinomatosis and primary central nervous system neoplasms

The evaluation of cerebrospinal fluid (CSF) requires adaption of basic cytopathologic principles to the specific neoplasms that involve the central nervous system (CNS). In this review, general criteria for detecting malignant cells in CSF are presented. The incidence and cytologic characteristics of specific metastatic tumors that involve CSF are reviewed, and the incidence, pathogenesis and natural history of meningeal carcinomatosis are discussed. The role of cytopathology in the detection and management of primary CNS tumors is presented. Emphasis is placed on the cytologic characteristics of individual types of primary brain tumors and the application of fine needle aspiration biopsy to intracranial lesions.     

Leptomeningeal carcinomatosis presenting as eosinophilic meningitis

The case of a 67-year-old man with underlying carcinomatous meningitis who presented with meningismus and cerebrospinal fluid (CSF) eosinophilia is reported. CSF eosinophilia can reflect a number of underlying conditions; however, carcinomatous meningitis is not generally considered. In this case, studies for bacterial, fungal and parasitic agents were negative. Cytologic examination of a lumbar puncture specimen revealed malignant epithelial cells in an inflammatory background. When unexplained eosinophilia is found in the CSF, a thorough search for coincident meningeal carcinomatosis should be undertaken.     

Mumps meningoencephalitis; a clinical review of 119 cases with one death

Mumps is one of the most common viruses to affect the central nervous system and should be given primary consideration in the differential diagnosis of aseptic meningitis. Many cases of numps infection do not involve the salivary glands. The course of numps meningoencephalitis is usually benign, with fever and signs of meningeal irritation lasting less than five days. The findings in the cerebrospinal fluid are usually distinctive, with leukocyte content greater than 200 per milliliter, of which 80 per cent or more are lymphocytes. Sequelae, even of a minor nature, are rare. Death is extremely rare in recorded literature. A fatal case of numps meningoencephalitis is described herein.     

3例婴儿脑膜炎败血伊丽莎白菌脑膜炎临床分析

总结脑膜炎败血伊丽莎白菌感染患儿的临床特点,以期提高临床诊治水平。收集中山市博爱医院2010年1月至2020年12月收治的3例脑膜炎败血伊丽莎白菌引起的脑膜炎患儿临床资料,结合相关文献进行总结分析。结果显示,3例患儿脑脊液中培养出脑膜炎败血伊丽莎白菌,其中2例血培养为同种细菌。3例患儿均为足月顺产,2例为新生儿期发病,1例为出生后35天发病,起病前均未发现致病高危因素。患儿以发热为主要起病表现,无抽搐及脑膜刺激征表现。3例患儿外周血常规白细胞总数、C反应蛋白、降钙素原均升高;脑脊液潘氏试验均为阳性,伴脑脊液白细胞数增高,脑脊液蛋白明显增高,脑脊液葡萄糖降低。头颅磁共振成像(magnetic resonance imaging,MRI)或电子计算机断层扫描术(computer tomography,CT)可见脑膜强化、软脑膜增厚、脑外间隙增宽,均无脑实质受累。3例检出菌株的药敏结果表现出高度一致性,均提示对环丙沙星、哌拉西林/他唑巴坦、左氧氟沙星、复方新诺明敏感。2例患儿以环丙沙星治疗,1例患儿以美罗培南联合万古霉素治疗。其中1例治愈,2例临床症状好转后出院。经电话随访,3例患儿一般情况尚可,无生长发育异常。本病例报道提示,脑膜炎败血伊丽莎白菌脑膜炎主要见于新生儿期,以发热起病为主要表现,该菌对儿科常用抗菌药物多显示体外耐药,对喹诺酮类药物敏感。     

Primary malignant melanoblastosis of the meninges. Clinical, cytologic and neuropathologic findings in a case

A 66-year-old man presented with a six-month history of neurologic symptoms suggestive of a craniospinal tumor or a diffuse inflammatory process in the subarachnoid space. Cytologic examination of cerebrospinal fluid (CSF) revealed inflammatory changes and malignant melanin-containing cells, leading to a diagnosis of meningeal spread of a melanoma. There was no history of skin excisions and no clinical evidence of primary melanoma of the eye. Neuroradiologic investigations, including CT and myelography, to confirm the diagnosis were negative. Despite intrathecal cytostatic therapy, the patient died eight months after the onset of symptoms. Autopsy disclosed diffuse meningeal melanoblastosis of the spinal cord and the base of the brain, confirming the cytologic diagnosis. In addition, two micrometastases in the liver were found as only extraneural manifestation. This case emphasizes the importance of CSF cytology in the diagnosis of diffuse infiltrating processes in the subarachnoid space.     

Etude d'infections à virus ECHO 9

At Ste. Justine Hospital, Montreal, during the period 1957-61, ECHO 9 virus was isolated in 27 cases, in 20 of these during the summer of 1961. All had evidence of meningeal irritation, accompanied by fever and headache. Four of the 20 patients diagnosed during the summer of 1961 had convulsions; 12 presented with a rash; and two simulated meningococcemia. Of the 27 patients, two were paralyzed and one case was diagnosed as transverse myelitis. ECHO 9 virus was isolated from stools and from throat specimens in equal proportion; it was isolated from cerebrospinal fluid in only two instances. Pathogenicity for suckling mice was observed in two of 22 inoculated directly with the specimen material and in 10 of 11 inoculated with the cultured material.     

SPONTANEOUS SUBARACHNOID HEMORRHAGE

Sudden development of pain in the head followed by evidences of meningeal irritation, with or without motor or sensory symptoms or signs, is almost pathognomonic of subarachnoid hemorrhage. The final diagnosis rests upon the demonstration of blood in the cerebrospinal fluid. If the hemorrhage is massive, or from an aneurysm of an unprotected arterial trunk, the patient may die in a comparatively short time. If the bleeding is less abundant and from an aneurysm which is protected by adjacent structures the patient may survive. Angiography should probably be done early in most cases. If neurological signs or the results of angiography indicate that the aneurysm is in such a location that surgical treatment is feasible it should probably be undertaken. If medical treatment is to be carried out the patient should have protracted rest, frequent spinal drainage so long as the cerebrospinal fluid contains blood or is under materially increased pressure, sedatives and analgesics, and passive movements of the neck and limbs to forestall limitation of motion of joints.     

Gallbladder carcinoma cells in cerebrospinal fluid as the first manifestation of a tumor. A case report

BACKGROUND: Meningeal carcinomatosis (MC) rarely occurs as the first evidence of a tumor. In such cases cytology of the cerebrospinal fluid is crucial to the diagnosis. The most frequent primary MCs are lung and breast cancers. MC from a gallbladder carcinoma is uncommon. CASE: A 58-year-old woman presented with paroxysmal headaches, seizures and coma. Analysis of the cerebrospinal fluid revealed carcinoma cells and a low protein concentration. Only postmortem examination discovered gallbladder adenocarcinoma to be the source of the tumor cells. CONCLUSION: A case with the onset of MC secondary to rare mucinous adenocarcinoma of the gallbladder is presented. Cytology of the cerebrospinal fluid was the only examination that uncovered malignancy. Nine similar cases were found in the literature. Low cerebrospinal fluid protein seems to be of diagnostic value.     

Is CSF cytology a useful diagnostic procedure in staging paediatric CNS tumours?

Objectives:  To evaluate whether there are any factors that predict malignant cells being found in paediatric cerebrospinal fluid (CSF) samples. To determine whether CSF provides useful staging information not provided by magnetic resonance imaging (MRI) in paediatric patients with primary central nervous system (CNS) malignancy.
Methods:  We compared the CSF cytology and spinal MRI staging results in paediatric patients with primary CNS malignancy at a UK tertiary referral centre, over a decade.
Results:  Of 159 CSF samples, 72 samples were from 72 patients with primary CNS malignancy with spinal MRI available for comparison. Eight of these 72 had positive cytology (seven malignant and one suspicious). All had a high clinical suspicion of tumour at the time of sampling. Of the 72 patients, only two had evidence of CSF spread on MRI spinal staging and CSF cytology; ten had MRI without cytological evidence and six had cytological without MRI evidence.
Conclusions:  In paediatric patients with primary CNS tumours, CSF cytology provides useful staging information. Spinal MRI alone may miss some patients with CSF spread who would be identified with CSF cytology.     

Primary intracranial epidermoid carcinoma

The cytologic findings in the cerebrospinal fluid in a case of primary intracranial epidermoid carcinoma are presented. The presence of a few squamous cells showing hyaline cytoplasm compatible with keratinization suggested the possible nature of the tomographically observed lesion. These tumors may arise in congenital epidermoid cysts at the base of the brain. Because of their location and meningeal spread, such tumors may cause severe symptoms and death despite a minute size, as illustrated by this case.     

Stereotactic biopsy and cytological diagnosis of solid and cystic intracranial lesions

Cytological smears from 115 consecutive cases of stereotactic biopsies of intracranial lesions were reviewed. Ninety-five lesions were solid and 20 cystic. Material from 90 solid and 13 cystic lesions was sent both for cytological and histological examination. In 66 of the solid lesions, the cytological diagnosis was confirmed by histology (five were benign lesions and 61 malignant tumours: 56 primary brain tumours, three metastases and two lymphomas). In 24 cases with discrepant cytology and histology, the histology was inconclusive or insufficient in 14 cases, while cytology established the diagnosis of astrocytoma grade II (seven cases), metastases (two cases), gliosis (one case) and benign (four cases). Necrosis of tumour type was observed cytologically in six patients representing glioblastoma (two cases), anaplastic astrocytoma (one case), lymphoma (one case) and normal brain (two cases) histologically. Three cases reported cytologically as benign were primary brain tumour (two cases) and gliosis (one case). One smear of a glioblastoma was insufficient for cytological diagnosis. Cystic lesions were cytologically benign in 17 cases and malignant in three cases. Histology from the cyst wall confirmed the malignant diagnosis in three cases and showed tumour in six more cases, a benign process (two cases), changes induced by radiotherapy for arteriovenous malformation (one case) and insufficient material (one case). In conclusion, cytology from solid brain lesion allows an accurate diagnosis and subtyping of tumours in a majority of cases, and can thus be used to choose type of therapy. In cystic brain tumours, however, examination of the cystic fluid, is often inconclusive and a biopsy from the cyst wall should be performed if there is clinical or radiological suspicion of tumour.     

Carcinomatosis of the Meninges

Some clinical and pathological features of carcinomatosis of the meninges are reviewed along with a report of four cases. This condition usually presents in middle age as a subacute meningitis with cranial nerve involvement, but the diagnostic importance of the various mental disturbances which may be encountered early in its course are noted. The acute or subacute course may reflect a widespread mechanical interference with normal cerebral metabolism, a notion which is supported by recent clinical measurements in these patients of the rate of glucose transport across the blood-brain barrier. It is probable that the route taken by tumour cells to reach the meningeal spaces is a relatively unimportant factor in determining this pattern of growth and that the intrinsic growth characteristics of the primary tumour, its nutritional needs, and gravity probably play the major roles in production of this unusual type of secondary invasion. Greater therapeutic use of irradiation for these patients is encouraged.     

Intrathecal administration of Y-27632, a specific rho-associated kinase inhibitor, for rat neoplastic meningitis

The small GTP-binding protein Rho and its target Rho-associated kinase trigger an intracellular signaling cascade that controls actin cytoskeleton and plays an essential role in cell motility and adhesion. A specific Rho-associated kinase inhibitor, Y-27632, has been reported to inhibit cancer invasion. Clinically, disseminated tumor cells in the cerebrospinal fluid invade the intraparenchymal region, damaging the brain and nerves, resulting in fatal brain stem dysfunction, despite intrathecal chemotherapy. To expand therapeutic options for this devastating neoplastic meningitis, we evaluated the potential use of intrathecal Y-27632 administration by employing Walker 256 cells, a rat mammary cancer cell line. Y-27632 dose-dependently inhibited chemotactic and invasive activity of Walker 256 cells. Y-27632 also inhibited the phosphorylation level of regulatory myosin light chain in vitro, but the effect was temporary and was considerably diminished within 16 hours. Y-27632 induced striking morphologic changes in Walker 256 cells, as evidenced by decreased cell-matrix adhesion in culture dishes and three-dimensional collagen I gels, and slightly inhibited colony formation in soft agar. Nevertheless, this drug treatment did not affect Walker 256 cell growth rate. We were able to administer continuous delivery of this inhibitor using an osmotic pump and maintaining drug concentration of 10 mumol/L within the brain. Importantly, this concentration of Y-27632 showed minimal neurotoxicity both in vitro and in vivo. We found that an intrathecal therapy, combining 5-fluoro-2'-deoxyuridine with Y-27632, significantly increased the survival time of rats bearing meningeal carcinomatosis in comparison with animals treated with 5-fluoro-2'-deoxyuridine alone. Taken together, our findings indicate that continuous intrathecal administration of Y-27632 could be a promising therapeutic method when combined with chemotherapy for treating human neoplastic meningitis.     

The saccus dorsalis of the rainbow trout,Salmo gairdneri Richardson

The saccus dorsalis of the brain of the rainbow trout, Salmo gairdneri Richardson, has been investigated by means of histological, cytochemical, enzyme-cytochemical, electron microscopical autoradiographical techniques. The saccus dorsalis is a rostro-dorsal evagination of the diencephalic roof, and consists of a partly folded epithelial wall separating the cerebrospinal fluid from the meningeal matrix fluid. The well-developed vascular system around the epithelial wall, consisting of capillaries with different diameters, seems to be part of the pineal vascular system. No structures were found that may be involved in a possible mechanical or nervous blood flow control. The single-layered epithelium consists of highly specialized cells of one specific type. These cells are mainly characterized by infolded basal membranes, long microvilli of a peculiar shape, non-folded lateral membranes bordering intercellular spaces, apical concentrations of elongate and cup-shaped macromitochondria, a basally located rough endoplasmic reticulum, an apically situated smooth endoplasmic reticulum and apical concentrations of micropinocytotic vesicles. Morphological evidence is presented of a multiple function of these cells: (1) fluid secretion, (2) extrusion of low molecular weight organic substances into the ventricular system, (3) uptake of high molecular weight substances, and (4) uptake of low molecular weight organic substances (aminergic neurotransmitters [GABA]) from the cerebrospinal fluid. The significance of light and dark cells is discussed. Indications of a possible innervation of the saccus dorsalis epithelial cells were not observed. The functional significance of the saccus dorsalis (possible analogue of the choroid plexus?) is discussed.     

Exfoliative cytology of nonlymphoreticular neoplasms in children

During the last 11 years, 144 nonlymphoreticular neoplasms were diagnosed in exfoliative cytology specimens obtained from patients younger than 17 years of age. Neuroblastoma was the single most common neoplasm (30 cases). Other categories of malignant neoplasms were primary bone tumors (30 cases), soft-tissue sarcomas (25 cases), brain tumors (25 cases) and epithelial neoplasms (7 cases). Of the 780 cytologic specimens, 335 were positive for malignant cells. Serous effusions provided most of the positive specimens from patients with neuroblastoma, germ-cell tumors and bone sarcomas. Exfoliated cells of metastatic embryonal rhabdomyosarcoma and primary brain tumors were detected most often in cerebrospinal fluid specimens. A most unusual presentation of an immature teratoma of the ovary is described in some detail. Despite the rarity of pediatric neoplasms, certain specific or suggestive cytologic features were recognized, including rosette formation of neuroblasts, nuclear notching of myoblasts, pleomorphism of osteoblasts and fibrillar processes of glial elements.     

Rapid Diagnosis of Infection by Gas-Liquid Chromatography: Analysis of Sugars in Normal and Infected Cerebrospinal Fluid

A highly reproducible procedure was developed for gas-liquid chromatographic analysis of trimethylsilyl derivatives of normal human cerebrospinal fluid. Fourteen normal human cerebrospinal fluid samples tested with this procedure contained alpha- and beta-glucose as well as isomers of two unidentified sugars. Chromatographic changes in three cases of meningeal inflammation (two cryptococcosis and one thalamic astrocytoma) were limited to decreased concentrations of all sugars. In one case of early meningitis, the concentrations of the unknown sugars decreased before glucose. Now that a reproducible chromatogram of the trimethylsilyl derivatives of normal human cerebrospinal fluid has been established, more samples of abnormal cerebrospinal fluid should be prepared by these methods and examined by gas-liquid chromatography. It may be possible to identify unique products of infectious agents which will permit rapid diagnosis of central nervous system infection.     

An ultrastructural study of the melanophages in the cerebrospinal fluid of the tadpoles of Xenopus

Melanin deposits in the brain ventricles of Xenopus tadpoles were studied with light and electron microscopy (TEM and SEM). They appeared to be aggregations of melanophages which accumulated free pigment granules excreted by ependymal cells into the cerebrospinal fluid. Whereas the meningeal melanophores contained oval melanosomes of various sizes, the melanosomes in the scavenger cells were all spherical, large (0.6–1.1 μm) and fairly uniform in size. Moreover, they were arranged in spherical groups which were never seen in the cytoplasm of the melanophores. The melanosomes within the cells were identical to the free melanosomes found in the cerebrospinal fluid and those which occurred within the ependymal cells in the young larva, suggesting a common origin from the egg cytoplasm. The number of the melanosomes in the melanophages increased with age. Fine cytoplasmic projections were involved in catching and engulfing the melanosomes. Some other features of the cytoplasm, e.g., large deposits of cell detritus, also indicated that the cells were macrophages. In the later stages, (48, 49) no projections were observed, but the cells were totally filled with melanosomes.     

Choroid plexus carcinoma. Cytologic identification of malignant cells in ascitic fluid

Abdominal deposits of a choroid plexus carcinoma in a patient with a ventriculoperitoneal shunt were cytologically diagnosed by examination of ascitic fluid after regression of the primary tumor. The morphology of the malignant cells in ascitic fluid was more similar to that of mesothelial cells than to the appearance of cells from this lesion in cerebrospinal fluid.     

脑脊液中转移性腺癌细胞免疫表型的变化

目的探讨脑脊液中转移腺癌细胞在没有血供的条件下的生长特征,是否有血管内皮标记物CD34,CD105,FⅧ,淋巴管内皮标记物D2_40及碱性成纤维生长因子(b-FGF)的表达,并促进肺癌的脑转移及肿瘤细胞自我生存的调控。方法采集109例腺癌脑转移患者的脑脊液为研究对象,其中肺癌脑转移107例(包括49例肺癌术后5年内脑转移,58例无肺癌病史直接经脑脊液穿刺发现肺癌脑转移),乳腺癌2例。以40例主要成分为炎性细胞的脑脊液及40例原发性肺腺癌组织标本为对照,采用免疫化学染色方法检测脑转移腺癌细胞及腺癌组织中CD34,CD105,FⅧ,D2_40,b-FGF,VEGF及vimentin的表达。结果 109例脑脊液标本中,CD34,CD105,FⅧ,D2_40,b-FGF及VEGF在转移癌细胞中的阳性率分别为64.2%,67.9%,66.9%,63.8%,56.8%,70.6%明显高于脑脊液对照组(阳性率均为0)且差异具有统计学意义(P0.05)。vimentin在脑脊液转移腺癌细胞中阳性表达,表达率为88.1%。在原发肺癌标本中,CD34,CD105,FⅧ和VEGF表达较弱或不表达。D2-40在癌中不表达。B-FGF与Vimentin在原发肺腺癌中的表达率分别为50.1%和29.3%。结论在肺癌脑转移过程中,肿瘤细胞能够表达不同的血管生长因子,提示可能具备内皮细胞的生物学特性,可能有助于增强肿瘤细胞的转移能力和对环境的耐受能力。