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Cui et al. Diagnosis and treatment of meningeal carcinomatosis

signs and symptoms include lower motor weakness, carbohydrate antigen, carbohydrate antigen 125,
dermatomal sensory loss, pain in the neck or back and carbohydrate antigen, neuron specific enolase, alfa-
radiculopathy. Nuchal rigidity is less common which fetoprotein, CYFRA 21-1, and epidermal growth factor
present in less than 15% of cases. [16,17] receptor (EGFR) can be relatively specific for MC when
increased in CSF compared to serum. [25-27] Combined
CSF examination assay of different markers may enhance the sensitivity
Routine CSF examination of MC diagnosis. Occasionally, the biomarkers
[26]
Intracranial hypertension (> 200 mmH O) is observed in provide diagnostic support for MC in cases suspected
2
46% cases with MC. More than 90% of patients with MC as MC with negative CSF cytology. However,
[28]
have abnormal routine test and biochemistry indicators detection of tumor cells in the CSF by CSF cytology
in CSF with increased leukocytes (> 4/mm ) in 57%, remains the golden criteria for diagnosis of MC.
3
elevated protein (> 50 mg/dL) in 76%, and decreased
glucose (< 60 mg/dL) in 54%. The nonspecific routine Genetic testing
[18]
CSF examination should not dissuade consideration of When tumors diffuse into the central nervous
this diagnosis. system (CNS), the patients are usually already in
an advanced disease stage and is unresponsive
CSF cytology to therapy. Mechanisms of cancer dissemination
Cytological examination of CSF is still the golden and development within the CNS are unknown due
criteria. The literatures reported that the sensibility to limited access to tumor tissue. Sasaki et al.
[19]
[29]
of May-Grunwald Giemsa stain method for diagnosing analyzed the EGFR mutation status of CSF straightly
MC was 75-90%, with the specificity 100%. Prior using real-time polymerase chain reaction that was
related foreign researchers suggest that the positive more sensitive than cytology to diagnose MC in
[20]
rate of CSF cytology with the first lumbar puncture is seven patients with non-small cell lung carcinoma
45%, which increased to 80-90% with a second CSF (NSCLC) harboring an EGFR mutation (sensitivity
exam. Little benefit is obtained from a third lumbar of 100% vs. 28.6%). A separate study used next-
puncture. Of the 42 patients with MC accepted into generation sequencing by Pentsova et al. to reveal
[30]
the trial reported by He et al., the sensitivity of a somatic alterations in tumor-derived DNA from CSF
[21]
first lumbar puncture is 85.7%, while the tumor cells in patients with CNS metastases of solid tumors and
were found in remaining 14.3% of cases from repeat primary brain tumors. These studies demonstrated
lumbar punctures. There are still some false positive
rates of CSF cytology check. Sometimes it is hard to that identification of genomic mutations in tumor-
distinguish the normal cells from the lymphoma cells. derived cell-free DNA from CSF using a sufficiently
sensitive platform in patients with CNS involvement.
Some simple measures can improve the sensitivity These techniques may be useful in complementing
for the diagnosis including CSF sample disposal. the diagnosis of MC, monitoring response to therapy
The CSF specimen should be processed within an and identifying resistance mutations. Therefore, in
hour after collection which will improve the sensitivity recent years, CSF has attracted the greatest attention
of CSF cytology. Large CSF sampling volumes (> and may be considered as a “liquid biopsy” for
10.5 mL) is also critical to improve the yield of CSF patients with MC. Currently, the technology of high-
sensitivity. May-Grünwald-Giemsa staining is better throughput sequencing of CSF may recognize cancer-
[22]
than Papanicolou stain for delineation of nuclear related DNA in cases with known or suspected CNS
morphological characteristics and cytoplasmic limits. involvement, which will provide significant aid for the
Nonetheless, there remains 25-30% of patients with MC diagnosis and treatment response.
diagnosed based on clinical picture, and radiographic
findings, and persistently negative CSF cytology. [14,18] Neurological imaging
Computed tomography (CT) is not sensitive in
Tumor markers diagnosing MC with an estimated 23-38% of sensitivity
The evaluation of serial biochemical markers in the CSF of scan reported. [31,32] Magnetic resonance imaging
may be of value in the adjunctive diagnosis of MC and (MRI) is considered the standard for the cancer patients
[33]
assessment in therapeutic efficacy. Some biomarkers with clinical suggestive of MC. The sensitivity of
may be nonspecific, such as β-glucuronidase, CK-BB, MRI in the diagnoses of MC varied from 20% to
lactate dehydrogenase, tissue polypeptide antigen, 91%. [11,14,34] Subarachnoid or ventricular enhancing
beta2-microglobulin, carcinoembryonic antigen, nodules, diffuse or focal leptomeningeal enhancement,
vascular endothelial growth factor (VEGF), which ependymal, sulcal, and nerve root enhancement are
can be helpful as indirect indices of MC. [23,24] Other common MRI findings in MC. Brain parenchymal
tumor markers such as carbohydrate antigen 15-3, metastases can be observed in 21-82% of MC. [34-37]
Neuroimmunology and Neuroinflammation ¦ Volume 4 ¦ September 18, 2017 169