Cytomorphologic Evaluation of the Neoplastic Potential of 28 Cell Culture Lines by a Panel of Diagnostic Cytopathologists

A panel of 7 diagnostic cytopathologists, i.e., physicians trained to diagnose the malignant potential of human cells in Papanicolaou-stained smears, was asked to evaluate two sets of microscope slides of stained coverslip preparations of 28 cell culture lines, 15 of which were neoplastic. Slide Set I consisted of 13 pairs of cell lines, one member of each pair being nontumorigenic and the other tumorigenic; the lines were of mouse (9 pairs), rat (3 pairs), and human (1 pair) origin. Slide Set II contained 4 human lines: one lung cancer, one melanoma, and two fibroblast lines. Of a total of 114 diagnostic decisions by the panel, 88 were correct (66/86, 77%) in choosing which member of a pair was neoplastic and 22 were correct (22/28, 79%) in choosing whether a given individual human line was or was not neoplastic. Two members of the panel were correct more frequently, with 16/17 (94%) correct diagnoses, each. Five nuclear morphologic criteria of malignancy used by cytopathologists were prominent in the tumorigenic lines: altered chromatin pattern characterized by increasing size of chromatin granules and chromatin clumping, sharp angularity of large nucleolar and/or chromocenter borders with spicule formation (pointed projection), irregular parachromatin clearing (increase in the clarity of the clear spaces between chromatin threads, granules and clumps), uneven thickness of chromatin at the nuclear border, and variability in nuclear size and shape from cell to cell. These markers of neoplastic transformation, when added to those previously reported, should increase overall accuracy in the diagnosis of neoplastic transformation of mammalian cells in culture.