Histopathologic and immunohistochemical features in human skin after exposure to nitrogen and sulfur mustard

Kathleen J. Smith, William J. Smith, Tracey Hamilton, Henry G. Skelton, John S. Graham, Carlin Okerberg, Robert Moeller, Brennie E. Hackley

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

N-methyl-2,2'-dichlorodiethylamine (HN2)is a topical chemotherapeutic agent used as therapy for cutaneous T-cell lymphomas (CTCL). Di(2- chloroethyl)sulfide (SM), and less often HN2, have been used as chemical weapons, with the skin being a principle target. The mechanisms by which these chemicals produce their therapeutic and toxic effects in skin, however, are not clearly defined. We exposed human skin explants to two doses of HN2 and SM. At 18 hours after exposure, histopathologic features were compared. In addition, immunohistochemical markers to basement membrane proteins were used to evaluate the effects of both chemicals on the basement membrane zone. Gross vesication was not seen. Pyknotic nuclei with or without dyskeratotic changes within epidermal keratinocytes were present at both doses. These changes varied more between skin specimens than they did between doses. Ballooning degeneration was more marked after SM exposures. Diffuse dermal- epidermal separation was present only at high-dose exposures and did not appear to correlate with the degree of changes locally in the overlying epidermis. Antibodies to laminin-5 showed decreased immunoreactivity after exposure to HN2 and SM. Immunoreactivity for laminin- was decreased to a lesser extent, and immunoreactivity for collagen IV and VII was unchanged. HN2 and SM produce similar histopathologic and immunohistochemical features after cutaneous exposure. These features suggest that part of mechanism of action of HN2 and SM is a direct effect on the basement membrane zone. Understanding the effects of HN2 and SM separate from their effect on DNA may be important in designing therapies and in advancing our understanding of the pathophysiologic changes induced by these chemicals when delivered topically.

Original languageEnglish (US)
Pages (from-to)22-28
Number of pages7
JournalAmerican Journal of Dermatopathology
Volume20
Issue number1
DOIs
StatePublished - 1998
Externally publishedYes

Keywords

  • Chemical agents
  • Cutaneous histopathology
  • Nitrogen mustard
  • Sulfur mustard

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Dermatology

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    Smith, K. J., Smith, W. J., Hamilton, T., Skelton, H. G., Graham, J. S., Okerberg, C., Moeller, R., & Hackley, B. E. (1998). Histopathologic and immunohistochemical features in human skin after exposure to nitrogen and sulfur mustard. American Journal of Dermatopathology, 20(1), 22-28. https://doi.org/10.1097/00000372-199802000-00005