Correspondence

Development of Kaposi's Sarcoma at the Site of a Biopsy

N Engl J Med 2002; 347:763-764September 5, 2002

Article

To the Editor:

Dr. Webster-Cyriaque (April 18 issue)1 reports the development of Kaposi's sarcoma at the site of a recent biopsy of minor salivary glands in a patient with human immunodeficiency virus infection. Although the development of Kaposi's sarcoma at the sites of surgical wounds and other skin trauma (Koebner's phenomenon) has been described before,2,3 this case is remarkable in that the original biopsy specimen showed no pathological abnormalities or expression of Kaposi's sarcoma–associated herpesvirus, also called human herpesvirus 8 (HHV-8). Immunoperoxidase staining of a specimen from a subsequent biopsy of the Kaposi's sarcoma lesion showed the expression of HHV-8 antigen by macrophages, endothelial cells, and epithelial cells.

Dr. Webster-Cyriaque proposes that the trauma may have precipitated inflammatory changes that recruited HHV-8–infected macrophages to the damaged tissue and induced them to release growth and angiogenic factors. We offer an additional important mechanism for the development of Kaposi's sarcoma in this patient — namely, that hypoxia occurring around the edges of the wound (as a result of the severing of blood vessels) may have activated latent HHV-8 in the infiltrating cells and helped spread the virus to adjacent endothelial or epithelial cells. Our group of investigators has recently found that hypoxia can activate HHV-8 in latently infected B cells,4 and this may be an important stimulus for the reactivation of HHV-8 in a variety of cells in vivo. Hypoxia-induced activation of HHV-8 may help explain the proclivity for Kaposi's sarcoma to develop at the sites of wounds as well as in the lower extremities, which are often hypoperfused.

Robert Yarchoan, M.D.
David A. Davis, Ph.D.
National Cancer Institute, Bethesda, MD 20892

Andrea Rinderknecht, B.A.
Brown Medical School, Providence, RI 02912

4 References

1. 1

   Webster-Cyriaque J. Development of Kaposi's sarcoma in a surgical wound. N Engl J Med 2002;346:1207-1210
   Full Text | Web of Science | Medline

2. 2

   Maral T. The Koebner phenomenon in immunosuppression-related Kaposi's sarcoma. Ann Plast Surg 2000;44:646-648
   CrossRef | Web of Science | Medline

3. 3

   Paparizos VA, Kyriakis KP, Polydorou-Pfandl D, Hadjivassilou M, Stavrianeas NG. Epidemiologic characteristics of Koebner's phenomenon in AIDS-related Kaposi's sarcoma. J Acquir Immune Defic Syndr 2000;25:283-284
   CrossRef | Web of Science | Medline

4. 4

   Davis DA, Rinderknecht AS, Zoeteweij JP, et al. Hypoxia induces lytic replication of Kaposi sarcoma-associated herpesvirus. Blood 2001;97:3244-3250
   CrossRef | Web of Science | Medline

Author/Editor Response

Dr. Webster-Cyriaque replies:

To the Editor: Virus was not present at the site of the Kaposi's sarcoma lesion, but there was shedding of HHV-8 into the patient's saliva before the lesion appeared. In this instance, the disease occurred in oral mucosa damaged by a surgical procedure. It is possible that the inflammatory changes associated with wound healing contributed to the recruitment of HHV-8 to the site and the subsequent rapid, aggressive development of the lesion. Since acute exposure of latently infected cells to hypoxia has been found to induce lytic HHV-8 replication, transient hypoxia induced by a surgical incision could have provided a stimulus for HHV-8 reactivation.

It is my opinion that trauma and secondary wound healing, even in the absence of a surgical wound, are key factors in the development of Kaposi's sarcoma. For example, the development of Kaposi's sarcoma in the hallux secondary to trauma has been reported in an immunosuppressed person.1 In addition, in oral Kaposi's sarcoma, the palate is the most common site of primary involvement, with a particularly high incidence in men who have sex with men.2 It is possible that palatal trauma occurs in the oral cavity secondary to sexual practices, and it may be the precipitating event, drawing inflammatory cytokines and virus-infected cells to the site. It is also possible that bruising precipitates the lesions detected on the limbs of elderly Mediterranean men who have the classic form of the disease.

Jennifer Webster-Cyriaque, D.D.S., Ph.D.
University of North Carolina Schools of Dentistry and Medicine, Chapel Hill, NC 27599-7455
jennifer@med.unc.edu

2 References

1. 1

   Gorsky M, Epstein JB. A case series of acquired immunodeficiency syndrome patients with initial neoplastic diagnoses of intraoral Kaposi's sarcoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:612-617
   CrossRef | Web of Science | Medline

2. 2

   Berkowitz KD, Bonner AC, Makimaa B, Flash JP, Sasken H, Blaise JF. Trauma-induced Kaposi's sarcoma of the hallux: an unusual case. J Am Podiatr Med Assoc 1998;88:500-505
   Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Liron Pantanowitz, Ashlee V. Moses, Bruce J. Dezube. (2009) The inflammatory component of Kaposi sarcoma. Experimental and Molecular Pathology 87:2, 163-165
   CrossRef