Non-surgical management of primary invasive melanoma

Abstract

Surgical excision is standard-of-care for primary invasive melanoma, but best care can be unclear for patients who are surgically high-risk or for whom resection may be excessively morbid. Alternatives to surgical excision have emerged for treatment of metastatic melanoma but have not yet been explored for primary invasive melanoma. Two elderly patients with primary invasive melanoma with many medical co-morbidities who were not surgical candidates were determined to be appropriate candidates for an intralesional IL-2 based regimen. Herein we report their clinical and histological outcome. An intralesional-based regimen (intralesional IL-2, topical imiquimod cream 5%, and tretinoin cream 0.1% under occlusion to the treatment site) was administered over the course of six to seven weeks, followed by two weeks of topical-only therapy. A complete response was seen after eight to nine weeks of treating invasive melanomas that were ≥1.85 mm and 5.5 mm thick. For patients with primary invasive melanoma on high morbidity sites and patients who are poor surgical candidates, a neoadjuvant intralesional IL-2-based approach may be a reasonable alternative. The two cases presented here suggest that alternative intralesional-based treatment modalities may minimize the size of the excision site and can be associated with complete histological clearance of invasive melanoma.

Keywords: Intralesional IL-2; TVEC; imiquimod; interleukin-2; non-surgical alternatives; primary invasive melanoma; tretinoin.

Figure 1.. Acral melanoma (stage pT4a Nx Mx) with macroscopic satellite lesions in an elderly patient before and after therapy.

Patient had a recently discovered enlarging pigmented nodule with surrounding scattered pink papules on the plantar aspect of her left foot (A), found on biopsy to be a 5.5 mm thick acral melanoma with ulceration and a mitotic index of 12 (10x magnification) (B). Histopathology demonstrated a large cellular ulcerated tumor of atypical melanocytes with irregular nests of melanocytes found in the epidermis, numerous mitotic figures in the dermis. The atypical cells (40x magnification) (C) stained positive for S100 (D), Melan-a, and HMB45, negative for AE1/AE3, CD45, and CK5/6, supporting the diagnosis of melanoma. Acral site status post completion of therapy (E). Patient had no clinically apparent residual disease or on histopathology, as shown at 4x magnification (F) and at 20x magnification (G). The biopsy showed spongiosis, fibrosis and mild to moderate lymphocytes and was negative for occult melanoma staining positive for SOX-10 (H).

Figure 2.. Amelanotic melanoma (at least stage pT2a Nx Mx) in an elderly patient, before and after therapy.

Prior to commencing an intralesional IL-2-based regimen, the patient presented to our team with a pearly papule that recurred after the initial diagnostic biopsy (A). Initially, the patient presented to an outside dermatologist with a 0.6 × 0.7 cm pearly papule that was found on biopsy to be at least a 1.85 mm thick amelanotic melanoma without ulceration (B and C, 4x and 40x magnification) and a mitotic index of 18. On histopathology, the tumor was transected at the base at a depth of 1.85 mm thus preventing accurate pathologic staging (stage ≥ pT2a). Histopathology showed nodular collections of cells with large nuclei and scattered necrotic cells and mitoses. The atypical cells stained positive for SOX-10 and negative for neurofilament and CK-Pan. Treatment site 3 weeks status post completion of therapy had presence of an atrophic scar (D). No tumor or residual disease was found on histopathology, as shown at 4x magnification (E) and at 40x magnification (F). The biopsy showed fibrosis with granulomatous inflammation and was negative for tumor and for occult melanoma staining positive for SOX-10.