Bruce R. Nelson

Merkel cell carcinoma

Merkel cell carcinoma is a malignant neuroendocrine tumor with features of epithelial differentiation. Biologically aggressive, it may be difficult to diagnose and, particularly in its late stages, even more difficult to treat effectively. This article addresses what is known and what is still controversial about the histogenesis, diagnosis, and management of Merkel cell carcinoma and the structure and function of the Merkel cell from which it is believed to be derived. The incidence, clinical presentation and diagnosis, ultrastructure, immunocytochemistry, treatment, and prognosis of this tumor will be discussed.

Squamous cell carcinoma of the skin (excluding lip and oral mucosa)

The striking impression obtained from reviewing the cancer literature is how difficult it is to analyze the data for answers to many important biologic, behavioral, prognostic, and therapeutic questions about squamous cell carcinoma of the skin. This article addresses current concepts, controversies, and management of cutaneous squamous cell carcinoma (excluding the lip and oral mucosa).

Mohs micrographic surgery for the treatment of dermatofibrosarcoma protuberans. Results of a multiinstitutional series with an analysis of the extent of microscopic spread.

BACKGROUND Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft-tissue tumor of the skin; its microscopic extent of invasion beyond the grossly visible tumor is frequently difficult to appreciate. Although wide local excision has been the standard treatment of DFSP, recurrence rates range from 11% to 53%. Because Mohs micrographic surgery allows the extent of excision to be tailored to the microscopic extent of tumor, we evaluated this technique for the treatment of primary and recurrent DFSP. OBJECTIVE Our purpose was to determine the local recurrence rate and microscopic extent of spread of primary and recurrent DFSP after treatment with Mohs micrographic surgery. METHODS The records of 58 patients with primary and recurrent DFSP treated with Mohs micrographic surgery at three institutions were reviewed and the macroscopic and microscopic extents of tumor were recorded. RESULTS One patient with a twice-recurrent DFSP had another recurrence after Mohs micrographic surgery, for an overall local recurrence rate of 2% (zero for primary tumors and 4.8% for recurrent tumors). There were no cases of regional or distant metastases. Macroscopic tumor size ranged from 0.3 x 0.6 cm to 30 x 20 cm, whereas microscopic (postoperative) size ranged from 1.8 x 1.0 cm to 35 x 40 cm. We calculated the likelihood that a given width of excision around the macroscopic tumor would clear the entire microscopic extent of tumor. Standard wide excision with a width of 1 cm around the primary tumor would have left microscopic residual tumor in 70.7%; a width of 2 cm, 39.7%; 3 cm, 15.5%; and 5 cm, 5.2%. Even an excision width of 10 cm would not have cleared the microscopic extent of some tumors, despite taking a huge excess of normal tissue. CONCLUSION Treatment of primary and recurrent DFSP by Mohs micrographic surgery results in a low recurrence rate because of the ability of the technique to permit the detection and excision of microscopic tumor elements in even the most asymmetric tumors. Whatever type of surgery is chosen to treat DFSP, it is necessary to assess the entire perimeter of the tumor for microscopic extension and to achieve tumor-free margins in all directions.

Current therapy for cutaneous melanoma

We review the current therapy for melanoma. The diagnosis, prognostic variables, staging, treatment, and follow-up guidelines for cutaneous melanoma are reviewed from the earliest to the most advanced stages. New guidelines for margins are discussed. A new, evolving, innovative radiographic technique, positron emission tomography using 2-fluorine-18-fluoro-2-deoxy-D-glucose, may be useful to identify subclinical nodal and visceral disease. Recent advances with respect to tumor vaccines, gene therapy, immunotherapy, and interleukin 2 as well as current concepts regarding lymph node dissection are discussed.

Soft tissue reconstruction with skin grafting

Free skin grafts for soft tissue reconstruction can be classified into three types: full-thickness skin grafts, split-thickness skin grafts, and composite grafts. The indications, techniques, donor site considerations, and postoperative complications of each type of skin graft are reviewed.

Microcystic adnexal carcinoma

Microcystic adnexal carcinoma is a rare cutaneous neoplasm characterized by invasive, relentless, and destructive local growth. The incidence of perineural invasion and tumor recurrence is high. We report two cases of microcystic adnexal carcinoma with typical clinical features. The use of formalin-fixed, paraffin-embedded horizontal Mohs sections is described in one case. We also review the current concepts and management of microcystic adnexal carcinoma.

Treatment of extramammary Paget disease with topical imiquimod cream: case report and literature review.

Extramammary Paget disease is an uncommon cutaneous neoplasm that presents as erythematous plaques most frequently located in the anogenital region. Management of patients with extramammary Paget disease involves evaluation of the individual for: (1) a disease-associated, unsuspected, visceral malignancy and (2) secondary adenocarcinoma in the underlying dermis or regional lymph nodes. Several modalities, each with variable effectiveness, are available to treat the cutaneous component of the disease: electrodesiccation and curettage, laser surgery, aminolevulinic acid photodynamic therapy, radiotherapy, topical chemotherapy, and wide surgical excision. However, surgical excision using the Mohs micrographic technique is currently the modality of choice for treating the cutaneous lesions of extramammary Paget disease. Recently, a topical imidazoquinoline immunomodulator that induces cytokine production and stimulates the innate and cellular immune responses—imiquimod cream—has been used for the management of primary or relapsing extramammary Paget disease. Complete healing, without recurrence, of extramammary Paget disease in patients whose cutaneous lesions were treated topically with imiquimod 5% cream was observed. We describe a man with suprapubic extramammary Paget disease whose condition was primary and limited to his skin. Biopsy-confirmed complete resolution of his disease was observed after the topical application of imiquimod 5% cream 3 times per week (on alternate days) for 16 weeks. After reviewing the published reports of other patients with extramammary Paget disease whose disease was successfully treated with imiquimod cream, we suggest that topical imiquimod 5% cream–at least 3 times per week (with 1–2 d of nontreatment in between) for a minimum of 8 to 16 weeks—be considered as an initial treatment for primary cutaneous extramammary Paget disease. Surgical excision or an alternative therapeutic modality is recommended for patients whose extramammary Paget disease persists or recurs after treatment with topical imiquimod.

Pilot histologic and ultrastructural study of the effects of medium-depth chemical facial peels on dermal collagen in patients with actinically damaged skin

BACKGROUND Chemical peels are employed for a variety of benign and premalignant skin disorders. OBJECTIVE We compared clinical and histologic features with ultrastructural changes that occur after medium-depth chemical facial peel. METHODS Three men with actinically damaged facial skin underwent a single 35% trichloroacetic acid peel. Biopsy specimens were taken before the peel, and 2 weeks and 3 months after the peel, for histologic examination, electron microscopy, and gel electrophoresis to assess total collagen type I content. RESULTS Clinical resolution of actinic damage corresponded with restoration of epidermal polarity. Collagen type I was markedly increased after the peel. Characteristic ultrastructural features of skin after peeling include markedly decreased epidermal intracytoplasmic vacuoles, decreased elastic fibers, and increased activated fibroblasts. CONCLUSION Electron microscopic studies after a medium-depth chemical peel of photodamaged skin reveal more profound changes than those seen histologically.

Carbon dioxide laser treatment of actinic cheilitis: Clinicohistopathologic correlation to determine the optimal depth of destruction

BACKGROUND The carbon dioxide laser is an effective modality for the treatment of actinic cheilitis, but the number of passes required is unknown. After each pass different visual tissue qualities are observed. OBJECTIVE Our purpose was to identify and characterize histologically the tissue zones seen after laser impact and thereby to determine the optimal depth of destruction of diseased tissue. METHODS Twenty-three biopsy specimens from 14 patients were obtained from zones of different tissue qualities after one and three passes with the laser. Specimens were histologically examined for the presence or absence of diseased epithelium and degree of thermal necrosis. RESULTS Complete destruction of the epithelial layer was observed in all specimens irrespective of the number of laser passes. The amount of dermal homogenization increased with multiple passes. CONCLUSION Treatment to the first or second surgical zone is effective for actinic cheilitis.

Treatment of keratoacanthomas with intralesional methotrexate

Multiple modalities exist for the treatment of keratoacanthoma. Excisional surgery is currently the treatment of choice for the majority of keratoacanthomas. This can result in functional and cosmetic defects when large or strategically located lesions are treated. An effective nonsurgical treatment would be desirable in such cases. Intralesional therapy, particularly with 5-fluorouracil, has been shown to be effective in the treatment of keratoacanthomas. Systemic methotrexate has been tried, with variable success. We report an open, noncontrolled study of nine consecutive patients with unusually large or strategically located solitary keratoacanthomas treated successfully with intralesional methotrexate. All lesions responded promptly, with complete resolution after a mean of 3.0 weeks and a mean of 1.7 injections. No side effects occurred, and scarring was minimal. We concluded that intralesional methotrexate is a simple and effective modality for the treatment of select keratoacanthomas and may offer greater efficacy, a more rapid response, decreased pain, and lower cost compared with intralesional 5-fluorouracil.