Thinprep plus Papanicolaou stain method is more sensitive than cytospin-coupled Wright Giems stain method in cerebrospinal fluid cytology for diagnosis of leptomeningeal metastasis from solid tumors

Abstract

Background: The present study was designed to determine whether the Thinprep plus Papanicolaou stain (Thinprep) method is more sensitive than the Cytospin-coupled Wright-Giemsa (WG) stain (Cytospin) method in diagnosis of leptomeningeal metastasis (LM) from malignant solid tumors in cerebrospinal fluid (CSF). We also explored if the Thinprep method could be used in the differential diagnosis of the type of primary tumor cells based on the morphology of tumor cells in CSF samples.

Methods: The morphological features of tumor cells in fresh CSF samples were analyzed using both methods. The tumor cell detection rates were compared between the two methods.

Results: Using the Thinprep method, we found that each type of tumor cells in the CSF samples had specific identifiable morphological features linked to their primary cancer origins, such as adenocarcinomas originated from the lungs, breast, and stomach, and lung squamous cell carcinomas, small cell lung cancer, large-cell neuroendocrine lung cancer, hepatocellular carcinoma, and malignant melanoma. In a retrospective study with 88 LM patients, cancer cells were detected in 80 out of the 88 CSF samples. In the comparative study with 45 LM patients, the initial detection rate of the Thinprep method was significantly higher than that of the Cytospin method (73.3% vs. 57.8%, P<0.01). The cell morphology was better preserved and subcellular structures were clearer using the Thinprep method, compared to the Cytospin method.

Conclusions: The Thinprep method is more sensitive and suitable for LM diagnosis in CSF in patients with malignant solid tumors than the Cytospin method. The Thinprep method may facilitate primary tumor detection and help design early treatment regimens for LM patients with tumors of unknown primary origin.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Different pathological types of tumor cells detected in CSF specimens.

a-n, adenocarcinoma cells; o-q, cancerous squamous cells; r-s, small-cell lung cancer cells; t-u, hepatocellular carcinoma cells; v-x, large-cell lung cancer cells; y-z, malignant melanoma cells. (Thinprep, Pap staining, ×400)

Fig 2. Side-by-side comparisons of CSF cytology results between the Thinprep plus Papanicolaou stain method (a, c, e, g, i and k) and the Cytospin-WG method (b, d, f, h, j and l) in patients with LM from various solid tumors.

Representative slides from identical CSF samples are shown for the same samples using the two methods in paired photos: a and b, gastric adenocarcinoma origin; c-h, lung adenocarcinoma origin; i and j breast adenocarcinoma origin; k and l, small-cell lung cancer origin. m-p, the typical features of malignancy of tumor cells seen by the Cytospin- WG stain method.