Multiple myeloma diagnosed secondary to analysis of a lytic bone lesion encountered during Mohs micrographic surgery.

An 89-year-old man underwent Mohs micrographic surgery for treatment of a squamous cell carcinoma of the scalp. A lytic bone lesion was found that led to the diagnosis of multiple myeloma.

The role of observation in the management of atypical nevi.

OBJECTIVE: The definition and management of the atypical nevus remains a controversial issue. Some believe that atypical nevi are common variants of benign melanocytic nevi while others believe they are lesions intermediate between benign melanocytic nevi and melanoma. Therefore, the question of whether or not partially removed atypical nevi should be re-excised with clear margins in order to prevent their evolution into melanoma remains unanswered. Although studies have shown that most atypical nevi will never progress into melanoma, re-excision, when biopsy margins are positive, is commonly practiced. We argue that re-excision in such cases is not necessary. METHODS: Our cohort study includes 55 previously biopsied atypical nevi that were not re-excised and which were followed for at least 5 years with a mean follow up time of 6.12 years. RESULTS: The experimental group included 26 atypical nevi whose biopsy revealed at least one involved margin. The control group included 29 atypical nevi whose biopsy revealed clear margins. No melanomas were observed to arise in association with a pre-existing atypical nevus in either the experimental or control group during the follow-up period. CONCLUSIONS: The results of our study support observation as a safe alternative to re-excision for incompletely removed atypical nevi. A large prospective study with longer follow up would be necessary to better answer the question of how often atypical nevi evolve into melanoma and over what time period this occurs.

Conditional expression of K-ras in an epithelial compartment that includes the stem cells is sufficient to promote squamous cell carcinogenesis.

Ras genes are the most frequently mutated oncogenes in human cancer. However, the contribution of ras to tumor initiation still is unclear because ras expression in primary cells can cause cell cycle arrest and even cell death by apoptosis. Furthermore, when expressed in the epidermis of mice, mutant ras promotes the formation of benign papillomas, only few of which will progress into carcinomas. However, in these cases, ras-transgene expression often is restricted to suprabasal or follicular epithelial cells that may lack self-renewal capacity. Thus, it still is conceivable that expression of active ras in other epithelial compartments may exert a distinct ability to promote malignant progression. To address this possibility, transgenic mice carrying the tetracycline-inducible system (tet-on receptor) targeted to the basal layer of stratified epithelium, which includes the epithelial stem cells, were engineered and crossed with mice expressing the K-ras(G12D) oncogene under the control of tet-regulated responsive elements. On doxycycline administration, proliferative lesions ranging from hyperplasias, papillomas, and dysplasias to metastatic carcinomas developed in squamous epithelia of the skin, oral mucosa, salivary glands, tongue, esophagus, forestomach, and uterine cervix within just 10 to 20 days. The most noticeable lesions were invasive squamous carcinomas of the skin and oral mucosa. These findings suggest that the expression of oncogenes in an epithelial compartment that includes the stem cells may be sufficient to promote squamous carcinogenesis. They also provide a molecularly defined conditional animal model system in which the mechanisms responsible for cancer initiation, maintenance, and metastatic spread can be readily investigated.

Mutations in the CYLD gene in Brooke-Spiegler syndrome, familial cylindromatosis, and multiple familial trichoepithelioma: lack of genotype-phenotype correlation.

Brooke-Spiegler syndrome (BSS), familial cylindromatosis (FC), and multiple familial trichoepithelioma (MFT), originally described as distinct entities, share overlapping clinical findings. Patients with BSS are predisposed to multiple skin appendage tumors such as cylindroma, trichoepithelioma, and spiradenoma. FC, however, is characterized by cylindromas and MFT by trichoepitheliomas as the only tumor type. These disorders have recently been associated with mutations in the CYLD gene. In this report, we describe three families with BSS, one with FC, and two with MFT phenotypes associated with novel and recurrent mutations in CYLD. We provide evidence that these disorders represent phenotypic variation of a single entity and lack genotype-phenotype correlation.

Phase diagram of molecular oxygen adsorption on the (111) platinum surface.

Molecular oxygen adsorption on the Pt(111) surface is studied based on ab initio computations and thermodynamics. An O2 adsorption phase diagram is determined. There are two possible chemisorbed molecular states: one at a bridge site and another one at an fcc hollow site. While some population in the bridge sites persists at all coverages, the states coexist through the intermediate coverage phases. The relative coverage of the two species on the surface is determined by the competition between the Pt lattice distortion energy (that results from O2 adsorption) and the O2 repulsion energy. Our results give a reasonable explanation for the seemingly contradictory findings in previous experimental and theoretical work.

Defect involving both the cutaneous and the vermilion lip.

An 89-year-old white male presented for Mohs micrographic surgical extirpation of an invasive squamous cell carcinoma on his right lower lip. Extirpation required two stages of Mohs surgery and produced a 1.5 x 3.7 cm partial-thickness defect involving both the cutaneous and the vermilion lip, with little loss to the underlying orbicularis oris muscles (Figure 1). How would you repair the defect?

Short-term side effects of fractional photothermolysis.

OBJECTIVE: To ascertain the immediate and short-term side effects of fractional photothermolysis for the treatment of a variety of skin disorders involving the face, neck, chest, and hands. METHODS: Physician-administered questionnaires were given during 60 follow-up visits for fractional photothermolysis treatment for a variety of facial skin disorders in patients with skin types ranging from I to IV. The questionnaire addressed 14 possible side effects, pain, and limitation of social activities. In addition, all patients were asked about any additional side effects not mentioned in the survey. An analysis of the data was performed once 60 surveys had been collected. RESULTS: All patients (100%) undergoing fractional photothermolysis had transient post-treatment erythema. Other frequently reported post-treatment side effects were transient and included facial edema (82%), dry skin (86.6%), flaking (60%), a few (one to three) small, superficial scratches (46.6%), pruritus (37%), and bronzing (26.6%). Other more rarely reported effects included transient increased sensitivity (10%) and acneiform eruption (10%). Most patients reported that the pain level was easily tolerated, with an average pain score of 4.6 on a scale of 10. Most patients (72%) reported limiting social engagements for an average of 2 days after treatment. There were no long-lasting adverse events noted in our survey. CONCLUSION: Fractional photothermolysis to treat dermatologic conditions on the face, neck, chest, and hands is a well-tolerated and safe procedure with several immediate, and slightly delayed, post-treatment side effects. In our experience, these side effects were transient and limited to erythema, edema, dry skin, flaking skin, superficial scratches, pruritus, increased sensitivity, and acneiform eruption. Importantly, we did not see the development of post-treatment scarring, herpetic activation, hypopigmentation, hyperpigmentation, persistent erythema, persistent edema, or infection.

Nonablative radiofrequency treatment of facial laxity.

OBJECTIVE: To share our current experience and review the current literature concerning the use of radiofrequency for the treatment of facial laxity. METHODS: We discuss our experience and review the current literature. RESULTS: Radiofrequency can impart mild tightening of mid- and lower facial laxity as well as periorbital laxity. In addition, it may help acne scars and acne. CONCLUSIONS: Radiofrequency appears to impart mild improvement to facial laxity and is a viable nonsurgical option for patients with mild facial laxity. There is, however, a need for blinded, randomized controlled studies to further validate these claims.

Concurrent use of a handheld forced cold air device minimizes patient discomfort during fractional photothermolysis.

OBJECTIVE: To assess the analgesic effect of a handheld forced cold air device during fractional photothermolysis. METHODS: Twenty patients who were being treated with full-face fractional photothermolysis were asked to rate their pain level with and without the handheld air-cooling device. Pain was rated on a scale of 1 to 10, with 10 being the worst. RESULTS: Nineteen of 20 patients noted decreased pain with the addition of handheld cooling. The mean level of pain without air-cooling was 6.95 +/- 2.0. The mean level of discomfort with air cooling was 4.0 +/- 1.8. The mean decrease in pain with the addition of air-cooling was 2.9 +/- 1.8. CONCLUSION: The addition of a handheld forced cold air device to cool the skin before and after fractional photothermolysis treatment is an effective adjunctive analgesic modality.

Mohs surgical extirpation of a basal cell carcinoma in a patient with familial multiple trichoepitheliomas.

BACKGROUND: The success of Mohs surgery relies on the ability to histologically differentiate tumor from the normal background tissue of the patient. In most cases of basal cell carcinoma and nonmelanoma skin cancer, this is a relatively straightforward process. However, in distinction, when only subtle histopathologic features differentiate the background tissue from the tumor of interest, the determination of a tumor-free margin becomes more challenging. OBJECTIVE: Our objective is to highlight the histopathologic features that we used to differentiate our patient's near-confluent background of trichoepitheliomas from the basal cell carcinoma that we were extirpating. METHODS: Case report. RESULTS: A 41-year-old white female with a history of familial multiple facial trichoepitheliomas presented for removal of a basal cell carcinoma on her right lower cutaneous lip. Mohs surgery was used to remove the tumor. The characteristic features of basal cell carcinoma and trichoepithelioma were used to differentiate the basal cell carcinoma that we were removing from the surrounding trichoepitheliomatous neoplasia. CONCLUSION: Mohs surgical extirpation of a basal cell carcinoma in a patient with multiple familial trichoepitheliomas requires a clear understanding of the histopathologic features that differentiate a trichoepithelioma from a basal cell carcinoma.

Use of avian retroviral vectors to introduce transcriptional regulators into mammalian cells for analyses of tumor maintenance.

A key issue in cancer biology is whether genetic lesions involved in tumor initiation or progression are required for tumor maintenance. This question can be addressed with mouse models that conditionally express oncogenic transgenes, i.e., under the control of tetracycline (tet)-dependent transcriptional regulators. We have developed a system for studying tumor maintenance by using avian retroviral [i.e., replication-competent avian leukosis virus long terminal repeat with splice acceptor (RCAS)] vectors to deliver the reverse tet transcriptional transactivator (rtTA) gene to somatic mammalian cells. rtTA can regulate any transgene in which the protein coding sequence is preceded by a tet-operator (tet-o); RCAS viruses infect only cells engineered to express ectopically the avian retroviral receptor, TVA. One vector, RCAS-rtTA-IRES-GFP, also encodes GFP to identify infected cells. Infection of cells from beta-actin TVA transgenic mice with this vector permits efficient regulation of tet-responsive transgenes. Sarcomas arise when p53-deficient murine embryonic fibroblasts carrying beta-actin TVA and tet-o-K-ras4bG12D transgenes are infected with RCAS-rtTA-IRES-GFP and introduced into nude mice treated with the tet analog, doxycycline (dox); when dox is withdrawn, K-ras4bG12D levels fall, cells undergo apoptosis, and tumors regress. Regression can be prevented by means of a genetic complementation assay in which tumors are superinfected before dox withdrawal with other RCAS viruses, such as those carrying an active allele of K-ras. Many TVA and tet-regulated transgenic mice have been generated; thus, this method for somatic cell-specific and temporally controlled gene expression may have broad applications for the study of oncogenesis and tumor maintenance, as well as other cell functions and development.