Jennifer L. Hand

Malignant Melanoma in the 21st Century, Part 1: Epidemiology, Risk Factors, Screening, Prevention, and Diagnosis

Malignant melanoma is an aggressive, therapy-resistant malignancy of melanocytes. The incidence of melanoma has been steadily increasing worldwide, resulting in an increasing public health problem. Exposure to solar UV radiation, fair skin, dysplastic nevi syndrome, and a family history of melanoma are major risk factors for melanoma development. The interactions between genetic and environmental risk factors that promote melanomagenesis are currently the subject of ongoing research. Avoidance of UV radiation and surveillance of high-risk patients have the potential to reduce the population burden of melanoma. Biopsies of the primary tumor and sampling of draining lymph nodes are required for optimal diagnosis and staging. Several clinically relevant pathologic subtypes have been identified and need to be recognized. Therapy for early disease is predominantly surgical, with a minor benefit noted with the use of adjuvant therapy. Management of systemic melanoma is a challenge because of a paucity of active treatment modalities. In the first part of this 2-part review, we discuss epidemiology, risk factors, screening, prevention, and diagnosis of malignant melanoma. Part 2 (which will appear in the April 2007 issue) will review melanoma staging, prognosis, and treatment.

Malignant Melanoma in the 21st Century, Part 2: Staging, Prognosis, and Treatment

Critical to the clinical management of a patient with malignant melanoma is an understanding of its natural history. As with most malignant disorders, prognosis is highly dependent on the clinical stage (extent of tumor burden) at the time of diagnosis. The patients clinical stage at diagnosis dictates selection of therapy. We review the state of the art in melanoma staging, prognosis, and therapy. Substantial progress has been made in this regard during the past 2 decades. This progress is primarily reflected in the development of sentinel lymph node biopsies as a means of reducing the morbidity associated with regional lymph node dissection, increased understanding of the role of neoangiogenesis in the natural history of melanoma and its potential as a treatment target, and emergence of innovative multimodal therapeutic strategies, resulting in significant objective response rates in a disease commonly believed to be drug resistant. Although much work remains to be done to improve the survival of patients with melanoma, clinically meaningful results seem within reach.

Outcome of Whole Exome Sequencing for Diagnostic Odyssey Cases of an Individualized Medicine Clinic: The Mayo Clinic Experience

OBJECTIVE To describe the experience and outcome of performing whole-exome sequencing (WES) for resolution of patients on a diagnostic odyssey in the first 18 months of an individualized medicine clinic (IMC). PATIENTS AND METHODS The IMC offered WES to physicians of Mayo Clinic practice for patients with suspected genetic disease. DNA specimens of the proband and relatives were submitted to WES laboratories. We developed the Genomic Odyssey Board with multidisciplinary expertise to determine the appropriateness for IMC services, review WES reports, and make the final decision about whether the exome findings explain the disease. This study took place from September 30, 2012, to March 30, 2014. RESULTS In the first 18 consecutive months, the IMC received 82 consultation requests for patients on a diagnostic odyssey. The Genomic Odyssey Board deferred 7 cases and approved 75 cases to proceed with WES. Seventy-one patients met with an IMC genomic counselor. Fifty-one patients submitted specimens for WES testing, and the results have been received for all. There were 15 cases in which a diagnosis was made on the basis of WES findings; thus, the positive diagnostic yield of this practice was 29%. The mean cost per patient for this service was approximately

Cutaneous porphyrias part I: epidemiology, pathogenesis, presentation, diagnosis, and histopathology

8000. Medicaid supported 27% of the patients, and 38% of patients received complete or partial insurance coverage. CONCLUSION The significant diagnostic yield, moderate cost, and notable health marketplace acceptance for WES compared with conventional genetic testing make the former method a rational diagnostic approach for patients on a diagnostic odyssey.

Oral manifestations of genodermatoses.

The porphyrias are a group of disorders characterized by defects in the heme biosynthesis pathway. Many present with skin findings including photosensitivity, bullae, hypertrichosis, and scarring. Systemic symptoms may include abdominal pain, neuropsychiatric changes, anemia, and liver disease. With advances in DNA analysis, researchers are discovering the underlying genetic causes of the porphyrias, enabling family members to be tested for genetic mutations. Here we present a comprehensive review of porphyria focusing on those with cutaneous manifestations. In Part I, we have included the epidemiology, pathogenesis, presentation, diagnosis, and histopathology. Treatment and management options will be discussed in Part II.

Pediatric hospital dermatology: Experience with inpatient and consult services at the mayo clinic

Many genodermatoses have distinct oral features that may help identify or confirm a genetic diagnosis. Oral features of the disorders described here are summarized in Table 1. These conditions provide clear examples of rapid progress in the field of genetic technology relevant to patient care. Less than a decade ago, the exact genetic locus of most of these disorders was unknown. Today, for many of these disorders, the exact location of the disease-causing mutation is known and clinical genetic testing is available for patients. This information has impact not only for genetic counseling and anticipatory medical care, but also provides insight into the mechanisms of disease. How this rapid progress will impact care, and ultimately treatment of patients, remains to be seen.

Rare Presentations of Primary Melanoma and Special Populations: A Systematic Review

Data describing the management of pediatric patients admitted to a hospital under the care of a dermatologist and dermatology hospital consults for pediatric inpatients are limited. We aim to describe the role of an inpatient hospital service jointly run by dermatology and pediatrics and the activities of a pediatric dermatology hospital consult service. We retrospectively identified pediatric (age < 18 yrs) dermatology inpatients and hospital consult patients from January 1, 2009, through December 31, 2010. We examined patient demographics, indications for admission, length of stay, treatment provided, consult‐requesting service, and consult diagnosis. One hundred eight admissions were by a dermatologist. The mean age was 5.8 years; the median length of stay was 3 days. Indications for admission included atopic dermatitis (86.1%), psoriasis (3.7%), and eczema herpeticum (2.8%). The main treatment provided was wet dressings (97.2%). Eighty‐three dermatology hospital consults were requested. The mean age was 7.4 years. The main indications for dermatology consultation included drug rash (12.1%), cutaneous infections (12.1%), contact dermatitis (9.6%), psoriasis (8.4%), atopic dermatitis (6.0%), and hemangiomas (6.0%). This study describes the utility of the hospital pediatric dermatology inpatient and consult services in treating patients with severe skin disease.

Psoriasis and Psoriasiform Eruptions in Pediatric Patients with Inflammatory Bowel Disease Treated with Anti-Tumor Necrosis Factor Alpha Agents.

A subset of patients with melanoma present in rare and unique clinical circumstances requiring specific considerations with respect to diagnostic and therapeutic interventions. Herein, we present our review of patients with: (1) primary mucosal melanoma of the head and neck, gastrointestinal, and genitourinary tracts; (2) primary melanoma of the eye; (3) desmoplastic melanoma; (4) subungual melanoma; (5) melanoma in special populations: children, nonwhites, as well as a discussion of familial melanoma.

Cutaneous porphyrias part II: treatment strategies.

Anti–tumor necrosis factor alpha (TNF‐α) agents are used to treat a variety of autoimmune and inflammatory conditions, including psoriasis. Paradoxically, numerous reports have documented new‐onset or exacerbation of psoriasis or psoriasiform skin lesions (PSO) in patients treated with these agents for conditions other than PSO—particularly in adults with inflammatory bowel disease (IBD). Not much is known regarding similar cases in children.

Acute paralysis in a 17-year-old man with subtle cutaneous vascular malformations: an unusual case of Cobb syndrome.

The porphyrias are diverse in pathophysiology, clinical presentation, severity, and prognosis, presenting a diagnostic and therapeutic challenge. Although not easily curable, the dermatological manifestations of these diseases, photosensitivity and associated cutaneous pathology, can be effectively prevented and managed. Sun avoidance is essential, and patient education regarding the irreversibility of photocutaneous damage is a necessary corollary. Beyond preventative measures, the care of fragile, vulnerable skin, and pain management, each of the porphyrias has a limited number of unique additional therapeutic options. Many of the treatments have been published only in small case series or anecdotal reports and do not have well‐understood nor proven mechanisms of action. This article presents a comprehensive review of available therapeutic options and long‐term management recommendations for the cutaneous porphyrias.