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(American Journal of Pathology. 2000;156:311-319.)
© 2000 American Society for Investigative Pathology

Regular Articles

Clonality as Expression of Distinctive Cell Kinetics Patterns in Nodular Hyperplasias and Adenomas of the Adrenal Cortex

Salvador J. Díaz-Cano^*, Manuel de Miguel, Alfredo Blanes^§, Robert Tashjian^*, Hugo Galera and Hubert J. Wolfe^*

From the Department of Pathology,^*
Tufts University-New England Medical Center, Boston, Massachusetts; the Department of Pathology,
St Bartholomew’s and the Royal London School of Medicine and Dentistry, London, United Kingdom; the Department of Pathology,
University Hospital of Seville, Seville, Spain; and the Department of Pathology,^§
University Hospital of Malaga, Malaga, Spain

Although histopathologic criteria for adrenal cortical nodular hyperplasias (ACNHs) and adenomas (ACAs) have been developed, their kinetics and clonality are virtually unknown. We studied 20 ACNHs and 25 ACAs (based on World Health Organization criteria) from 45 females. Representative samples were histologically evaluated, and the methylation pattern of the androgen receptor alleles was analyzed on microdissected samples. Consecutive sections were selected for slide cytometry, flow cytometry, and in situ end labeling (ISEL). Apoptosis was studied by flow cytometry (nuclear area/DNA content plotter analysis) and by ISEL. Appropriate tissue controls were run in every case. Polyclonal gel patterns were revealed in 14/18 informative ACNHs and in 3/22 informative ACAs, whereas monoclonal gel patterns were observed in 4/18 ACNHs and 19/22 ACAs. Overlapping proliferation rates (PRs) were observed in both clonal groups, and apoptosis was detected only in G₀/G₁ cells, especially in monoclonal ACNHs (3/4; 75%) and in polyclonal ACAs (2/3; 67%). Significantly higher PRs were observed in ACNHs with polyclonal patterns and G₀/G₁ apoptosis and in ACAs regardless of clonality pattern and presence of G₀/G₁ apoptosis. All except one ACNH (19/20; 95%) and 15/25 ACAs (60%) showed diploid DNA content, whereas the remaining cases were hyperdiploid. A direct correlation between PR and ISEL was observed in polyclonal lesions (PR = 29.32 ISEL - 1.93), whereas the correlation was inverse for monoclonal lesions (PR = -9.13 ISEL + 21.57). We concluded that only simultaneous down-regulated apoptosis and high proliferation result in selective kinetic advantage, dominant clone expansion, and unbalanced methylation patterns of androgen receptor alleles in ACNHs and ACAs.

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