Skip to main content
PMC home page
Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1987 Apr;40(4):418–423. doi: 10.1136/jcp.40.4.418

Granular cells as a marker of early amiodarone hepatotoxicity: a pathological and analytical study.

N A Shepherd, A M Dawson, P R Crocker, D A Levison
PMCID: PMC1140975  PMID: 3584485

Abstract

Two contrasting cases of amiodarone hepatotoxicity are described. In one, perivenular collections of swollen cells, probably macrophages, with granular cytoplasm in an otherwise nearly normal liver were observed. Transmission electron microscopy showed that the cytoplasmic granularity was due to lysosomal bodies of various sizes. X-ray energy and wavelength spectroscopic analysis showed a high iodine content in these lysosomal bodies, good presumptive evidence of the presence of amiodarone or one of its metabolites. In the second case there was a micronodular cirrhosis, and similar granular cells also containing iodine were seen in the fibrous connective tissue. These cases seem to represent the very early and late stages of amiodarone hepatotoxicity. In a patient taking this drug aggregates of swollen granular cells may be a sensitive and histopathologically useful marker of early amiodarone toxicity.

Full text

PDF
418

Images in this article

420Fig 1
on p.420
421Fig 2
on p.421
421Fig 3
on p.421

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bretschneider A., Burns W., Morrison A. "Pop-off" technic. The ultrastructure of paraffin-embedded sections. Am J Clin Pathol. 1981 Oct;76(4):450–453. doi: 10.1093/ajcp/76.4.450. [DOI] [PubMed] [Google Scholar]
  2. Capron-Chivrac D., Reix N., Quénum C., Capron J. P. Hépatopathie aiguä due à l'amiodarone. Etude d'un cas et revue de la littérature. Gastroenterol Clin Biol. 1985 Jun-Jul;9(6-7):535–539. [PubMed] [Google Scholar]
  3. Costa-Jussà F. R., Corrin B., Jacobs J. M. Amiodarone lung toxicity: a human and experimental study. J Pathol. 1984 Oct;144(2):73–79. doi: 10.1002/path.1711440202. [DOI] [PubMed] [Google Scholar]
  4. Dake M. D., Madison J. M., Montgomery C. K., Shellito J. E., Hinchcliffe W. A., Winkler M. L., Bainton D. F. Electron microscopic demonstration of lysosomal inclusion bodies in lung, liver, lymph nodes, and blood leukocytes of patients with amiodarone pulmonary toxicity. Am J Med. 1985 Mar;78(3):506–512. doi: 10.1016/0002-9343(85)90346-8. [DOI] [PubMed] [Google Scholar]
  5. Goldman I. S., Winkler M. L., Raper S. E., Barker M. E., Keung E., Goldberg H. I., Boyer T. D. Increased hepatic density and phospholipidosis due to amiodarone. AJR Am J Roentgenol. 1985 Mar;144(3):541–546. doi: 10.2214/ajr.144.3.541. [DOI] [PubMed] [Google Scholar]
  6. Harris L., McKenna W. J., Rowland E., Holt D. W., Storey G. C., Krikler D. M. Side effects of long-term amiodarone therapy. Circulation. 1983 Jan;67(1):45–51. doi: 10.1161/01.cir.67.1.45. [DOI] [PubMed] [Google Scholar]
  7. Lim P. K., Trewby P. N., Storey G. C., Hole D. W. Neuropathy and fatal hepatitis in a patient receiving amiodarone. Br Med J (Clin Res Ed) 1984 Jun 2;288(6431):1638–1639. doi: 10.1136/bmj.288.6431.1638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Poucell S., Ireton J., Valencia-Mayoral P., Downar E., Larratt L., Patterson J., Blendis L., Phillips M. J. Amiodarone-associated phospholipidosis and fibrosis of the liver. Light, immunohistochemical, and electron microscopic studies. Gastroenterology. 1984 May;86(5 Pt 1):926–936. [PubMed] [Google Scholar]
  9. Rigas B., Rosenfeld L. E., Barwick K. W., Enriquez R., Helzberg J., Batsford W. P., Josephson M. E., Riely C. A. Amiodarone hepatotoxicity. A clinicopathologic study of five patients. Ann Intern Med. 1986 Mar;104(3):348–351. doi: 10.7326/0003-4819-104-3-348. [DOI] [PubMed] [Google Scholar]
  10. Sherlock S. The spectrum of hepatotoxicity due to drugs. Lancet. 1986 Aug 23;2(8504):440–444. doi: 10.1016/s0140-6736(86)92144-6. [DOI] [PubMed] [Google Scholar]
  11. Simon J. B., Manley P. N., Brien J. F., Armstrong P. W. Amiodarone hepatotoxicity simulating alcoholic liver disease. N Engl J Med. 1984 Jul 19;311(3):167–172. doi: 10.1056/NEJM198407193110308. [DOI] [PubMed] [Google Scholar]
  12. Varma R. R., Troup P. J., Komorowski R. A., Sarna T. Clinical and morphologic effects of amiodarone on the liver. Gastroenterology. 1985 Apr;88(4):1091–1093. doi: 10.1016/s0016-5085(85)80057-3. [DOI] [PubMed] [Google Scholar]
  13. Yagupsky P., Gazala E., Sofer S., Maor E., Abarbanel J. Fatal hepatic failure and encephalopathy associated with amiodarone therapy. J Pediatr. 1985 Dec;107(6):967–970. doi: 10.1016/s0022-3476(85)80206-7. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Pathology are provided here courtesy of BMJ Publishing Group

RESOURCES