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

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.

Analysis of intrapatient heterogeneity of circulating tumor cells at the single-cell level in the cerebrospinal fluid of a patient with metastatic gastric cancer.

BACKGROUND: The aims of this study were to detect circulating tumor cells (CTCs) at the single-cell level in cerebrospinal fluid (CSF) and to identify intrapatient heterogeneity of CTCs in a patient with gastric cancer (GC) with leptomeningeal metastasis (LM) using Di-Electro-Phoretic Array technology. MATERIALS AND METHODS: The CSF samples were drawn from a patient who was diagnosed with GC with LM. The CSF samples were centrifuged and stained with antibody cocktail to recognize 4',6-diamidino-2-phenylindole, cytokeratin, and epithelial cell adhesion molecule (EpCAM). Gene sequencing was also conducted to evaluate the status of the gene alteration profile of CSFCTCs as compared with those of the CSF non-CTCs and the primary tumor tissue. RESULTS: Among total 38 cells from the samples, 25 cells represented CK+ (EpCAM+), which boiled down to 0.53 CTCs in 1 mL of CSF. Each CTC was heterogeneous in terms of morphology and degree of marker expression. Some CTCs have a spindle-like shape, whereas others have a round shape. Based on molecular profiling between the 25 CK+ (EpCAM+) CTCs and 13 CK-/EpCAM- cells (i.e., the non-CTCs), CSFCTCs harbored mutations such as MDM2, TP53, KRAS, STK11, and ALK, whereas mutation of these genes was not observed in the CSF non-CTCs. Four genes of nine mutational genes totally observed in the CSFCTCs were also noted in the primary tumor tissue. CONCLUSIONS: We enriched CTCs through a single-cell sorting process in CSF samples of a GC patient with LM. We also demonstrated the intrapatient heterogeneity of the CTCs at the single-cell level.

Combined application of cytodiagnostic technics to the cerebrospinal fluid.

The major purpose of the examination of the cells in the cerebrospinal fluid (CSF) is the diagnosis of malignant growths. However, unequivocal tumor cell diagnosis is often problematical, since cells of local origin can also demonstrate considerable proliferative activity and great morphological variety. In these circumstances, it is advisable to evaluate cells from several points of view. One can demonstrate morphological characteristics with panoptic staining and can gain an impression of the RNA content of a cell with acridine orange (AO) fluorescent stain. Quantitative measurements of DNA synthesis in vitro can be made by labelling with tritiated thymidine. Multidimensional cytodiagnosis gives a comprehensive impression of the quality of the cells in question and provides the clinician with information which can be valuable for subsequent diagnostic and therapeutic efforts.

Immunocytochemical localization of carcinoembryonic antigen in cerebrospinal fluid with metastatic carcinoma of the stomach: report of four cases.

A study was undertaken to evaluate the cellular findings of gastric carcinoma in cerebrospinal fluid (CSF). Immunocytochemical localization of carcinoembryonic antigen (CEA) was performed on four cases of metastatic gastric carcinoma cells in CSF samples. A positive peroxidase-antiperoxidase (PAP) reaction was obtained in all cases, with intense staining for CEA in the CSF samples as well as in the paraffin-embedded tissue sections from the primary gastric tumors. Cellular morphology and the results of immunoperoxidase staining can be studied simultaneously. We believe that the PAP method for CEA increases diagnostic accuracy of cytology in the CSF.

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.

[Treatment of meningeal carcinomatosis--neocarzinostatin perfusion therapy in the CSF pathway].

The authors presented the results of perfusion chemotherapy in the CSF pathway with neocarzinostatin (NCS) for the treatment of meningeal carcinomatosis. In three cases of stomach cancer and one case of malignant lymphoma, cranial polyneuropathy, progressive hydrocephalus and positive cytology of the CSF were found during treatment of malignant tumors. NCS therapy was performed by means of perfusion from the spinal subarachnoid space to the ventricle utilizing Ommaya's reservoir, or simply by repeated lumbar punctures. In all of four cases the number of malignant cells in the CSF was significantly diminished, and temporary neurological improvement was observed until the patient's death due to advanced primary lesions. These results indicated that in cases of meningeal carcinomatosis, NCS perfusion therapy using the CSF pathway was a much more favorable method than treatment with other chemotherapeutic agents with less noticeable side effects.

Mucus-secreting 'signet-ring' cells in CSF revealing the site of primary cancer.

A case is reported of leptomeningeal carcinomatosis in which identification of mucus-secreting 'signet-ring' carcinoma cells in the CSF allowed diagnosis of an otherwise asymptomatic gastric cancer. When lumbar puncture is performed, careful cytological examination of the CSF should be carried out in any undiagnosed patient with neurological symptoms and signs.

[Carcinomatous meningitis. Usefulness of spinal fluid cell morphology in the diagnosis of 2 cases]. / La meningite carcinomatosa. Utilità dell'indagine citomorfologica liquorale nella diagnosi di due casi.

This paper deals with two cases of carcinomatous meningitis as metastatic reproduction respectively of a bronchial and a stomach carcinoma. In both patients (37 and 62 years) the clinical picture consisted in combined neurologic symptoms and signs of brain and spinal roots damage, while in the first one there was also a deficit of some cranial nerves. In the past history of the subjects there had been no evidence of tumours. The diagnosis remained uncertain for a long period, although several laboratory and neuroradiologic investigations had been carried out. The C.S.F. cytomorphologic study, performed with the filtration method, gave a rapid and exact identification of carcinomatous cells and, therefore, a correct diagnosis. Such C.S.F. diagnostic test should be carried out in all cases of suspected carcinomatous meningitis. If biochemical markers are used as well, this combination of tests gives additional information.