Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that causes the differentiation and proliferation of granulocytes and macrophages [1]. It may be involved in the functional activity of dendritic cells, antigen-presenting cells that are important in host defense mechanisms [2]. Alone or with other cytokines (interleukin-2, interleukin-4), GM-CSF induced antitumor responses in murine models [3] and in humans [4]. We report the regression of metastatic adnexal skin cancer achieved by use of intralesional GM-CSF.

A 76-year-old man presented in December 1990 with a 1-cm x 1.5-cm indurated nodule underneath the skin of the right infraorbital area. A biopsy of the nodule and subsequent wide surgical excision revealed a poorly differentiated apocrine (sweat gland) adenocarcinoma. The patient received postoperative radiation therapy (6500 cGy) and did well for 46 months. In October 1994, he developed a biopsy-proven recurrence in the right lower eyelid that extended into the right orbit. He underwent right orbital exenteration followed by radiation therapy (4000 cGy). Response was satisfactory until June 1996, when multiple skin metastases developed on the left cheek and left subdigastric lymph nodes. The patient received chemoradiation therapy (6600 cGy of radiation plus carboplatin and taxol) and did well for 7 months. In February 1997, disease progressed on the submental area; additional radiation therapy (4000 cGy) had no effect, and progressive skin nodules developed. Aspiration cytology of the nodules revealed an apocrine adenocarcinoma.

After informed consent was obtained, weekly courses of GM-CSF, 500 µg, were given intralesionally. After 4 weeks of GM-CSF treatment, the ulcerated nodule regressed. Repeated biopsy of this nodule revealed only inflammatory cells (Figure 1), and immunohistochemical staining of the infiltrate revealed the population to be CD4⁺, CD8⁺, CD28⁺, CD86⁺, and CD35⁺ cells. Both the injected skin lesion and metastatic lesions distant from the injection site regressed. The patient continues to receive weekly GM-CSF therapy; the only side effects are myalgia and arthralgia.

View larger version (124K): [in this window] [in a new window]   Figure 1. Punch skin biopsy specimen showing inflammatory infiltrate in dermis (original magnification, x100).