(abstract). Berman JJ, Moore GW.  Dysplasia in Atypical Liver
  Nodules.  Letter to the Editor.
  Human Pathology 27(2):211-213, 1996

To the editor:- The article by Le Bail et al.(1) the authors make the startling and seemingly impossible observation that dysplasia is not present in atypical liver nodules. In their study, dysplasia was observed only in liver nodules that lacked atypia (so-called ordinary adenomatous hyperplasia). Atypical adenomatous nodules contained no dysplastic cells.

How is it possible that non-atypical liver nodules contain dysplastic cells and atypical liver nodules contain no dysplastic cells? The authors use criteria for dysplasia established by Anthony et al., in 1973 (2). Anthony described cells with nuclear pleomorphism, hyperchromasia and cellular enlargement and referred to the morphologic condition as "liver cell dysplasia". Le Bail and coworkers used the same criteria as Anthony and refer to the lesion described by Anthony et al as "large liver cell dysplasia." Since Anthony and coworkers described the dysplastic cells as "large," a generation of liver researchers have been hunting for "large" cells, thus basing their observations on nonstandard cytologic criteria requiring cell enlargement.

Modern cytologists base their assessment of dysplasia (regardless of tissue of origin) on accepted criteria relating to alterations in nuclear size and shape, nuclear rim morphology, and chromatin distribution. Dysplasia may be present in large or small cells depending on nuclear morphology. This is particularly important in liver, as hepatocellular carcinomas tend to be populated by cells that are smaller than non-neoplastic hepatocytes.

Using current cytologic criteria for dysplasia, we have previously shown that liver foci containing dysplastic cells are often aneuploid, as are hepatocellular carcinomas. Based on this observation, we suggested that dysplastic foci may be precursor lesions for hepatocellular carcinomas.(3) A large body of evidence supports the hypothesis that the neoplastic process progresses from dysplasia to carcinoma in situ to invasive cancer. This conceptual framework is the basis for the clinical success of cervical cytology and is used for virtually every epithelial tissue except liver.

Some liver researchers believe that "liver dysplasia is often a chance discovery associated with a developed malignant tumor and is described only incidentally in the conclusions of the anatomopathologists's report." (4). Contrary to this assessment, there is every reason to assume that liver carcinogenesis proceeds in a manner identical to that of all other epithelial tissues. In a recent letter, we suggested that current attempts to establish a nomenclature for liver nodules be abandoned in favor of cytologic criteria for dysplasia like those in current use for every other epithelial tissue (5). In our opinion, the basic paradigms and terminology used by Le Bail et al. and many others in the field of human liver carcinogenesis are arbitrary and unnecessarily specialized, and lead to observations that defy sensible interpretation by all but a small cadre of liver specialists.

Jules J. Berman, Ph.D., M.D.
G. William Moore, M.D., Ph.D.

1. Le Bail B, Belleannee G, Bernard P, Saric J, Balabaud C, Bioulc-Sage P. Adenomatous hyperplasia in cirrhotic livers: histological evaluation of 35 macronodular lesions in the cirrhotic explants of 10 adult French patients. Hum Pathol 26:897-906, 1995

2. Anthony PP, Vogel CL, Barker LF. Liver cell dysplasia: a premalignant condition. J Clin Pathol 26:217-223, 1973.

3. Thomas RM, Berman JJ, Yetter, RA, Moore GW, Hutchins GM. Liver cell dysplasia: a DNA aneuploid lesion with distinct morphologic features. Hum Pathol 23:496-503, 1992.

4. DePrez C, Kiss R. To the Editor. Am J Clin Pathol 706-708, 1993.

5. Berman JJ. Liver Nodule Criteria (Letter to the Editor). Am J Surg Pathol 18:960-961, 1994.