[Show abstract][Hide abstract] ABSTRACT: Skin infections are not uncommon after cosmetic laser procedures. Infection rates following ablative laser resurfacing procedures are reported to be as high as 7.6%, compared to 1.9% for fractional ablation. (1,2) An infrequent yet important infectious complication of ablative laser treatment is that caused by non-tuberculous mycobacteria (NTM).
No preview · Article · Jan 2015 · Journal of drugs in dermatology: JDD
[Show abstract][Hide abstract] ABSTRACT: Background: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin. Immunosuppression is associated with increased incidence of MCC. Objective: We sought to determine whether solid organ transplant recipients (SOTR) with MCC had decreased progression-free, disease-specific, and overall survival compared with immunocompetent patients. Methods: We conducted a retrospective cohort study examining 8 SOTR with MCC and 89 immunocompetent control subjects. Cox regression models were generated for outcomes of progression, disease-specific death, and death from any cause, adjusted for patient sex, age at diagnosis, and stage at presentation. Results: SOTR had a 4.1-fold increased hazard for progression (95% confidence interval 1.57-10.95, P = .004), a 10.5-fold increased hazard for all-cause mortality (95% confidence interval 3.06-35.98, P < .0001), and an 11.9-fold increased hazard for MCC-specific death (95% confidence interval 2.67-53.08, P = .001), adjusted for sex, age, and stage at presentation. SOTR had decreased 1-year overall survival, 46.8% versus 88.6%, and decreased 1-year MCC-specific survival, 56.3% versus 95.2%. Limitations: This is a single-center study from a tertiary academic care center, and may not be generalizable to all patient populations. Conclusions: SOTR have a significant reduction in overall, MCC-specific, and progression-free survival compared with immunocompetent patients. Further studies will determine whether aggressive treatment may improve outcomes in this high-risk population.
No preview · Article · Jun 2014 · Journal of the American Academy of Dermatology
[Show abstract][Hide abstract] ABSTRACT: Merkel cell carcinoma is an aggressive neuroendocrine tumor with a high incidence of local recurrence, regional nodal and distant metastasis, and a high mortality rate. It has been linked to a polyomavirus in addition to immune suppression. Traditionally, treatment options have been limited to surgery and radiation therapy. Better understanding of the molecular pathways of infection and carcinogenesis has provided potential molecular targets and potential immunotherapies which are discussed in this review.
No preview · Article · Jun 2014 · Seminars in Cutaneous Medicine and Surgery
[Show abstract][Hide abstract] ABSTRACT: Background
The effects of primary tumor size on nodal involvement and of number of involved nodes on survival have not, to our knowledge, been examined in a national database of Merkel cell carcinoma (MCC).
We sought to analyze a retrospective cohort of patients with MCC from the largest US national database to assess the relationships between these clinical parameters and survival.
A total of 8044 MCC cases in the National Cancer Data Base were analyzed.
There was a 14% risk of regional nodal involvement for 0.5-cm tumors that increased to 25% for 1.7-cm (median-sized) tumors and to more than 36% for tumors 6 cm or larger. The number of involved nodes was strongly predictive of survival (0 nodes, 76% 5-year relative survival; 1 node, 50%; 2 nodes, 47%; 3-5 nodes, 42%; and ≥6 nodes, 24%; P < .0001 for trend). Younger and/or male patients were more likely to undergo pathological nodal evaluation.
The National Cancer Data Base does not capture disease-specific survival. Hence, relative survival was calculated by comparing overall survival with age- and sex-matched US population data.
Pathologic nodal evaluation should be considered even for patients with small primary MCC tumors. The number of involved nodes is strongly predictive of survival and may help improve prognostic accuracy and management.
Preview · Article · Apr 2014 · Journal of the American Academy of Dermatology
[Show abstract][Hide abstract] ABSTRACT: Regulatory T cells (Tregs), which are characterized by expression of the transcription factor Foxp3, are a dynamic and heterogeneous population of cells that control immune responses and prevent autoimmunity. We recently identified a subset of Tregs in murine skin with properties typical of memory cells and defined this population as memory Tregs (mTregs). Due to the importance of these cells in regulating tissue inflammation in mice, we analyzed this cell population in humans and found that almost all Tregs in normal skin had an activated memory phenotype. Compared with mTregs in peripheral blood, cutaneous mTregs had unique cell surface marker expression and cytokine production. In normal human skin, mTregs preferentially localized to hair follicles and were more abundant in skin with high hair density. Sequence comparison of TCRs from conventional memory T helper cells and mTregs isolated from skin revealed little homology between the two cell populations, suggesting that they recognize different antigens. Under steady-state conditions, mTregs were nonmigratory and relatively unresponsive; however, in inflamed skin from psoriasis patients, mTregs expanded, were highly proliferative, and produced low levels of IL-17. Taken together, these results identify a subset of Tregs that stably resides in human skin and suggest that these cells are qualitatively defective in inflammatory skin disease.
Full-text · Article · Feb 2014 · The Journal of clinical investigation
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Merkel cell carcinoma (MCC) is among the deadliest of cutaneous malignancies. A lack of consensus evaluation and treatment guidelines has hindered management of this disease. The utility of simultaneous positron emission tomography and computed tomography (PET/CT) has been demonstrated for a variety of tumors yet remains underinvestigated for MCC. OBJECTIVES: To report the value of fluorodeoxyglucose PET/CT imaging in the initial staging and ongoing management of individuals with MCC and to determine whether any patient or tumor characteristics may predict when PET/CT is more likely to have greater influence on medical decision-making. MATERIALS AND METHODS: A single-institution retrospective chart review was conducted of all patients diagnosed with MCC who underwent FDG-PET/CT scanning from 2007 to 2010. The outcome of each of these studies was evaluated as to the influence on patient staging and management. Patient clinical information and information on gross and microscopic tumor characteristics were collected and analyzed. RESULTS: Twenty patients underwent 39 PET/CT scans. Results of PET/CT imaging revealed previously unknown information related to MCC in four (20%) patients, leading to changes in management in three of these four cases. Three previously unknown neoplasms were detected. CONCLUSION: Fluorodeoxyglucose-positron emission tomography and computed tomography is a valuable tool for initial staging and to assess response to therapy of patients diagnosed with MCC. Larger prospective studies would be required to establish the optimal timing for this imaging modality.
No preview · Article · Jun 2013 · Dermatologic Surgery
[Show abstract][Hide abstract] ABSTRACT: Presentation: A 93-year-old male presented to the dermatologist with multiple firm, deeply erythematous nodules covering the majority of the parietal scalp (Fig. 13.1). He stated that the nodules appeared rapidly, never bled, and were not painful. Punch biopsies were performed at two locations and both were shown to be consistent with Merkel cell carcinoma (MCC). His past medical history was notable for hypertension, hyperlipidemia, and coronary artery disease.
[Show abstract][Hide abstract] ABSTRACT: Merkel cell carcinoma presents a diagnostic challenge, as it is a relatively asymptomatic tumor with no pathognomonic features. Given the propensity for locoregional and distant metastasis, and the associated morbidity and mortality, early detection is important for survival. Features that should alert clinicians to the possibility of MCC include rapid growth of an asymptomatic red to violaceous lesion in a sun-exposed area of an elderly Caucasian patient over the age of 65. Immune suppressed patients are particularly vulnerable and may be affected at younger ages. Oftentimes, MCC patients will develop or have a history of other cancers, including skin cancers.
[Show abstract][Hide abstract] ABSTRACT: A 69-year-old otherwise healthy Caucasian woman was evaluated for a small, asymptomatic, erythematous papule on her right infraorbital cheek. After 4 months, she developed a second red plaque on her left distal medial calf. Her past medical history included a left arm squamous cell carcinoma excised 5 years prior hypertension and dyslipidemia. She had no history of immunosuppression. Medications included lisinopril, hydrochlorothiazide, and lovastatin. She had a family history of a grandmother with melanoma and a grandfather with bladder carcinoma.
[Show abstract][Hide abstract] ABSTRACT: Accurate staging of human malignancy is often the best predictor of outcome and aids practitioners in decision making with regard to treatment and patient counseling. Uniform staging also provides a language by which to describe a given type of cancer to facilitate communication with other providers and patients, and for more robust research endeavors. Merkel cell carcinoma (MCC) is an aggressive cancer of the skin with a high propensity to spread to local and distant sites. To date, six MCC staging systems have been published between 1991 and 2010. As the incidence of MCC continues to rise, better efforts have been made to study the disease in consistent fashion. This is reflected in the evolution of staging systems, as they have increasingly included valuable information to better predict the behavior of the disease based upon more accurate classification of cases.
[Show abstract][Hide abstract] ABSTRACT: Merkel cell carcinoma (MCC) is a rare but aggressive carcinoma of the skin, arising most commonly in sun-exposed sites of elderly patients. The diagnosis is based on characteristic histopathologic features. In 2008, the discovery of the Merkel cell polyomavirus led to intensified research into the viral pathogenesisis of MCC. MCC staging guidelines were established in 2010, and it demonstrated the importance of distinguishing clinical vs. pathologic evaluation of lymph nodes in MCC. Surgery and/or radiation is of the mainstay of therapy for early disease, while chemotherapy is reserved for more advanced disease. Treatments based on immunologic mechanisms are currently in development.
No preview · Article · Dec 2012 · Hematology/oncology clinics of North America
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Cigarette smoking is the leading cause of preventable death and a major public health concern. Numerous clinical and experimental studies have examined the effect of nicotine on wound healing and surgical procedures, but there are limited published reports in the dermatologic surgery literature. OBJECTIVE: This article seeks to develop evidence-based recommendations regarding the effect of tobacco use in patients undergoing dermatologic surgery procedures. METHODS: This article reviews the existing published English-language literature pertaining to the effects of tobacco on wound healing and surgical complications. RESULTS: Tobacco use is associated with a higher incidence of postoperative complications including wound dehiscence, flap or graft necrosis, prolonged healing time, and infections. LIMITATIONS: This review article only summarizes past reports and studies. CONCLUSION: Recommendations for smoking cessation before dermatologic surgery are provided based on the available data.
No preview · Article · Oct 2012 · Journal of the American Academy of Dermatology
[Show abstract][Hide abstract] ABSTRACT: Merkel cell carcinoma (MCC) represents a cutaneous malignancy with high associated mortality. Numerous studies have attempted to define characteristics to more accurately predict outcome. Two recent studies have demonstrated that Merkel cell polyomavirus (MCPyV) seropositivity correlated with a better prognosis, while a third study revealed no difference. Expression of p63 by tumor cell nuclei has been shown to be associated with a worse prognosis in a European cohort. To better understand the relationship between prognosis and MCPyV or p63 status, we used immunohistochemistry to evaluate both attributes in 36 US patients with MCC. Our results show that when considered as a binary variable, p63 expression represents a strong risk factor (p < 0.0001, hazards ratio (HR) = ∞) for shortened survival. In addition, our results show that MCPyV status does not correlate with survival (p = 0.6067, HR = 1.27). Our study corroborates the European observation that p63 immunoexpression is useful as a prognostic tool. Larger studies will need to be performed in order to determine whether p63 status should be included in MCC staging, since our study is limited by its relative small size.
No preview · Article · Jul 2012 · Journal of Cutaneous Pathology
[Show abstract][Hide abstract] ABSTRACT: In general, the rate of complications in dermatologic surgery is extremely low. A single-center prospective analysis of 1,343 cases of Mohs micrographic surgery reported an overall complication rate of 1.6% (22/1,343), including wound infection, postoperative hemorrhage, hematoma, wound dehiscence, and flap or graft necrosis  (IV/B). This chapter reviews the available evidence regarding the prevention and management of bleeding complications of cutaneous surgery. Although much of the data will be generated from the collective dermatologic experience with Mohs micrographic surgery, the conclusions drawn will be applicable to standard excisional surgery, as well other common procedures of the dermatologist and dermatologic surgeon. Not only is peri-operative bleeding the most common complication associated with cutaneous surgery, but it is also the subject for which the most robust evidence exists. It is additionally important to note that complications involving dehiscence, necrosis, poor wound healing, and infection often occur after difficulties with hemostasis.
[Show abstract][Hide abstract] ABSTRACT: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin. Disease progression usually occurs via lymphatic spread to regional lymphatic draining basins, followed by distant metastasis. We report the clinical course, histopathology and genetic analysis of a 69-year-old woman with likely hematogenous spread of cutaneous neuroendocrine carcinoma manifesting as a single metastatic lesion to a distant cutaneous site. Although the possibility of two cutaneous primary MCCs was considered, array comparative genomic hybridization (aCGH) identified identical distal amplification of a region of chromosome 12p, and synchronous loss of chromosomes 8p and 17p, effectively ruling out the possibility of independent primaries. We propose that this represents a primary cheek MCC with rapid, isolated cutaneous metastasis to the contralateral ankle via hematogenous spread. The distinction between a second primary MCC and a distant cutaneous metastasis clearly has important implications with regard to staging, treatment and prognosis. To our knowledge, this represents the first report of the use of aCGH to clarify the relationship of multiple synchronous cutaneous MCCs and the first report of a single distant cutaneous focus of hematogenous spread. Our data calls into question prior reports alleging multiple cutaneous primaries of this very rare tumor.
Ahronowitz IZ, Daud AI, Leong SP, Shue EH, Bastian BC, McCalmont TH, Yu SS. An isolated Merkel cell carcinoma metastasis at a distant cutaneous site presenting as a second ‘primary’ tumor.
No preview · Article · Oct 2011 · Journal of Cutaneous Pathology
[Show abstract][Hide abstract] ABSTRACT: Timely intervention for cancer requires knowledge of its earliest genetic aberrations. Sequencing of tumors and their metastases reveals numerous abnormalities occurring late in progression. A means to temporally order aberrations in a single cancer, rather than inferring them from serially acquired samples, would define changes preceding even clinically evident disease. We integrate DNA sequence and copy number information to reconstruct the order of abnormalities as individual tumors evolve for 2 separate cancer types. We detect vast, unreported expansion of simple mutations sharply demarcated by recombinative loss of the second copy of TP53 in cutaneous squamous cell carcinomas (cSCC) and serous ovarian adenocarcinomas, in the former surpassing 50 mutations per megabase. In cSCCs, we also report diverse secondary mutations in known and novel oncogenic pathways, illustrating how such expanded mutagenesis directly promotes malignant progression. These results reframe paradigms in which TP53 mutation is required later, to bypass senescence induced by driver oncogenes.
[Show abstract][Hide abstract] ABSTRACT: The incidence of cutaneous squamous cell carcinoma (cSCC) is increasing. Although most patients achieve complete remission with surgical treatment, those with advanced disease have a poor prognosis. The American Joint Committee on Cancer (AJCC) is responsible for the staging criteria for all cancers. For the past 20 years, the AJCC cancer staging manual has grouped all nonmelanoma skin cancers, including cSCC, together for the purposes of staging. However, based on new evidence, the AJCC has determined that cSCC should have a separate staging system in the 7th edition AJCC staging manual.
We sought to present the rationale for and characteristics of the new AJCC staging system specific to cSCC tumor characteristics (T).
The Nonmelanoma Skin Cancer Task Force of AJCC reviewed relevant data and reached expert consensus in creating the 7th edition AJCC staging system for cSCC. Emphasis was placed on prospectively accumulated data and multivariate analyses. Concordance with head and neck cancer staging system was also achieved.
A new AJCC cSCC T classification is presented. The T classification is determined by tumor diameter, invasion into cranial bone, and high-risk features, including anatomic location, tumor thickness and level, differentiation, and perineural invasion.
The data available for analysis are still suboptimal, with limited prospective outcomes trials and few multivariate analyses.
The new AJCC staging system for cSCC incorporates tumor-specific (T) staging features and will encourage coordinated, consistent collection of data that will be the basis of improved prognostic systems in the future.
No preview · Article · Jun 2011 · Journal of the American Academy of Dermatology