The Role of Exfoliative Cytology in the Diagnosis and Treatment of Malignant Disease

THE study of cells derived from the various lining and covering surfaces of the body dates back to the days of the first microscope, for surely, cells scraped from the lining of the mouth and from other areas were among the first wonders to be observed with the new contrivance. Detailed observation of exfoliated cells was first undertaken by Pouchet, however, who in i847, reported the changes occurring in unstained vaginal smears during the female sex cycle. This kind of material was but little used thereafter, until I917, when Stockard and Papanicolaou published the first of a series of articles on cyclic changes in vaginal smears. These studies contributed materially to our present understanding of the mammalian sex cycle. The indentification of malignant cells in various body fluids began with the report of Beale in i86o, that he had found particles from a malignant pharyngeal tumour in sputum, and in i 64, Sanders recorded the discovery of malignant tumour particles in the sediment of urine. 'Increasing interest in the diagnostic possibilities of this method followed, particularly with reference to fluids from the pleural and peritoneal cavities. 'A Handbook of Clinical Microscopy ' by Bizzozero, appearing in its second German Edition in I887, mentions the cellular elements to be found in sputum, urine, serous fluids and feces with occasional reference to the possible identification of tumour cells. The development of tissue sectioning technique and improved staining methods in the early I900S obscured the potential value of these observations, however, and the field of tissue pathology evolved. Papanicolaou's announcement in 1928 that abnormal cells could be identified in vaginal smears from.women with cancer of the genital tract fell on deaf ears generally until the classic monograph describing his methods, criteria and results was published in I943. In the ensuing i8 years great efforts have been extended throughout the world to put this technique to the widest possible use in the detection of malignancy of the female genital tract and also to adapt it to the solution of diagnostic problems'in other areas. The publication of Papanicolaou's 'Atlas of Exfoliative Cytology' in 1954 marked the firm establishment of the method as an accepted diagnostic adjunct and an important branch of anatomic pathology. Success in utilizing the criteria of malignancy so developed depends upon obtaining suitable cells in the fresh state, dispersing them properly on the slides and fixing immediately in the solution of ether and alcohol. If the cells are permitted to degenerate or to dry on the slide, the important intranuclear features (Fig. i) differentiating benign from malignant cells cannot be visualized and cell types are difficult to distinguish. The rather delicate, but not difficult, staining procedure results in very pleasant clear pastel cytoplasmic coloration, which quite reliably differentiates squamous cells from histiocytic and other types. In vaginal smears of good quality the colour of the cytoplasm of the squamous cells assists in the evaluation of hormonal states as well, since estrogenic effect generally causes a high proportion of them to take the eosin stain. The nuclear stain is hlmatoxylin and in well fixed smears the chromatin material has a very distinct network or granular pattern. Histopathologists are familar with many of the nuclear criteria for malignancy which can be applied' to exfoliated cells, such as large nuclear size, hyperchromatism, irregular shape, duplication of nuclei and an increased ratio of nuclear to cytoplasmic area. Derangements of chromatin structure, however, are rarely of value in formalinfixed and imbedded material. In cytologic smears, the normal. interphase nucleus is a smooth oval with a sharp regular wall of chromatic material and an internal structure resembling a transparent cocoon. As the stain is relatively transparent one can focus through the fine by coright.