Extent, origin, and implications of observer variation in the histopathological diagnosis of suspected leprosy

Identical slides from 100 biopsies obtained from individuals suspected of having leprosy, ascertained in a total population survey in Malawi, were examined twice, independently, by three histopathologists. Results were reported in a standard protocol, and were compared among themselves and with a standardized clinical assessment of each "suspect." The proportion of biopsies considered to show definite evidence of leprosy ranged from 29 to 55 among the six evaluations (twice by each of three histopathologists). Comparisons of variations within and between histopathologists revealed three different patterns. Two of the pathologists were very consistent as individuals, but differed markedly between themselves in that one was the least inclined and the other the most inclined to report definite evidence of leprosy. The third pathologist was less consistent, reporting appreciably more definite leprosy on the first than on the second examination of the same biopsies. Although acid-fast bacilli (AFB) were reported on at least 1 examination in 40 of the biopsies, they were observed in all six examinations of only six of the biopsies. There was greater agreement regarding classification than regarding diagnosis, except with reference to the indeterminate category which was employed more frequently by one histopathologist than by the other two. A workshop of participants at the end of the investigation highlighted several reasons for the variations observed. The fact that AFB were reported in only nine biopsies by one histopathologist but in 33 by another reveals the importance of the examination method and time in arriving at a diagnosis of leprosy. The differences in the interpretation of cellular evidence of inflammation revealed the need for further studies of nerve-related pathology in nonleprosy conditions to serve as a reference against which to judge possible evidence of leprosy per se.