Toward a multimodal cell analysis of brush biopsies for the early detection of oral cancer.
BACKGROUND
This report describes what to the authors' knowledge is the first clinical application of semiautomated multimodal cell analysis (MMCA), a novel technique for the early detection of cancer for cases with a limited number of suspicious cells. In this clinical study, MMCA was applied to oral cancer diagnostics on brush biopsies. The MMCA approach was based on the sequential application of multiple stainings of identical, slide-based cells and repeated relocalizations and measurements of their diagnostic features, resulting in multiparametric features of individual cells. Data integration of the variously stained cells increased diagnostic accuracy. The implementation of MMCA also enabled fully automatic, adaptive image preprocessing, including registration of multimodal images and segmentation of cell nuclei.


METHODS
In a preliminary clinical trial, 47 slides from brush biopsies of suspicious oral lesions were analyzed. The final histologic diagnoses included 20 squamous cell carcinomas, 7 hyperkeratotic leukoplakias, and 20 lichen planus mucosae.


RESULTS
The stepwise application of 2 additional approaches (morphology, DNA content, argyrophilic nucleolar organizer region counts) increased the specificity of conventional cytologic diagnosis from 92.6% to 100%. This feasibility study provided a proof of concept, demonstrating efficiency, robustness, and diagnostic accuracy on slide-based cytologic specimens.


CONCLUSIONS
The authors concluded that MMCA may become a sensitive and highly specific, objective, and reproducible adjuvant diagnostic tool for the identification of neoplastic changes in oral smears that contain only a few abnormal cells.
Remmerbach
Torsten W
TW
Department of Oral, Maxillofacial, and Plastic Surgery, University of Leipzig, Leipzig, Germany.
Meyer-Ebrecht
Dietrich
D
Aach
Til
T
Würflinger
Thomas
T
Bell
Andre A
AA
Schneider
Timna E
TE
Nietzke
Nadja
N
Frerich
Bernhard
B
Böcking
Alfred
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D034961:Antigens, Nuclear / Q000032:analysis; D001706:Biopsy / Q000379:methods*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D042241:Early Diagnosis; D006801:Humans; D019044:Image Cytometry / Q000379:methods; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism / Q000473:pathology; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009697:Nucleolus Organizer Region / Q000737:chemistry; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016622:Silver Staining
D034961:Antigens, Nuclear; D004273:DNA, Neoplasm; C051963:nucleolar organizer region associated proteins