Philip Kerr

Melanoma in the elderly patient: relevance of the aging immune system

The rapidly expanding segment of the aging population with its rising incidence of cutaneous melanoma will present major challenges in therapeutic management. Immune strategies will be important in designing effective treatment of melanoma because it is a highly immunogenic tumor. Aging, however, is associated with dysregulation of the immune system and is likely to affect the success of melanoma treatment in the elderly population. This population represents an ideal in vivo model to study the effects of the aging immune system on the natural history of melanoma in the elderly. We review the epidemiology, histopathologic features, and treatment outcomes of elderly melanoma patients with reference to their immune function. Various components of the normal immune system are described, and the immune response to melanoma is recapitulated. Particular emphasis is placed on the growing understanding of the innate, adaptive, and regulatory arms of the aging immune system.

Vitamin D and the skin

Vitamin D is a fat-soluble nutrient that humans obtain through the diet and by synthesis in the skin upon exposure to ultraviolet B. Vitamin D is then converted by the liver to 25-hydroxyvitamin D, its major circulating form. This form is the best indicator of vitamin D nutritional status and is easily measured. Under the influence of parathyroid hormone, the kidney then converts 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D, the biologically active, hormonal form of the nutrient that is important in the metabolism of calcium and phosphorus and is critical in building and maintaining healthy bones. Many cell types outside of the skeletal system, including various cells in the skin, also express the vitamin D receptor. In addition, many cell types convert circulating 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D for local use. This metabolite has been shown to exert potent effects on cellular differentiation, cellular proliferation, and immune regulation. It is theorized that by these mechanisms vitamin D and its analogues are effective treatment options for psoriasis and other skin diseases. Insufficient vitamin D nutritional status has been associated with a host of other diseases, most notably cancer. There is evidence that supplementation with vitamin D reduces the overall incidence of cancer, although current evidence is insufficient to prove a causative effect. Sunscreen use blocks the ability of the skin to photosynthesize vitamin D, although the effect this has on the vitamin D status of the general population is unclear.

Melanoma on the move: The progression of melanoma: Novel concepts with histologic correlates

Careful observation and pattern recognition is the realm of the dermatopathologist. Although specific criteria have been described that define the histologic diagnosis of melanoma, morphologic and architectural variations have been observed for this tumor. And while the immunohistochemical profile of melanoma is well characterized, some melanomas exhibit immunophenotypic aberrations not typical of melanocytic differentiation. These findings can make the microscopic diagnosis of melanoma difficult. In this review article, we have assembled some of the recent advances in melanoma research that challenge the traditional models of melanoma pathogenesis and progression. We describe concepts that are associated with changes identifiable under light microscopy, which may explain some of the variable histologic and aberrant immunohistochemical profiles of melanoma. These advances are still the subject of active investigation and are best viewed as ‘‘works in progress’’ rather than widely accepted principles.

Prominent papillary dermal edema in dermatophytosis (tinea corporis).

Background: Commonly described histologic ‘clues’ to the diagnosis of dermatophytosis include neutrophils in the stratum corneum and/or epidermis, compact orthokeratosis and identification of fungal hyphae between two zones of cornified cells. Prominent (striking) papillary dermal edema (PPDE) is not commonly reported with dermatophytosis (tinea corporis).

Melanoma: Kids are not just little people

Malignant melanoma can affect patients of any age. It has been well documented that the overall incidence of melanoma has increased in the past several decades, and this increase extends to the pediatric population (both preadolescent and, to a greater extent, adolescent children). Melanoma in adolescents, commonly defined as patients 11 to 19 years of age, behaves similarly to melanoma in adults; however, there are a number of distinct differences in the presentation and prognosis of melanoma in the preadolescent population. Though our treatment options for melanoma are increasing with the advent of novel drugs and clinical trials, the rarity of pediatric melanomas often excludes this population from clinical studies. The treatment options for the pediatric patient are predominantly based on adult clinical trials. Awareness of the differences in clinical presentation, as well as management of melanoma in younger patients compared with their adult counterparts, is crucial to guarantee prompt and appropriate care.

Cutaneous metastasis of renal cell carcinoma with Zellballen-like inflammatory reaction pattern on immunohistochemical studies.

Skin tumors show variable infiltration by subtypes of inflammatory cells. The composition of these cellular infiltrates, particularly tumor-associated macrophages and dendritic cell numbers, may be responsible for skin tumor progression or regression. In addition, these cells may give rise to diagnostic dilemmas on immunohistochemical studies. The authors report on the local inflammatory reaction to a metastatic renal cell carcinoma to the skin. Histologic examination and immunohistochemical studies demonstrated zellballen-like changes with S-100-positive spindled cells identified around and within tumor cell nests. The role of tumorassociated macrophages and dendritic cells in the skin is discussed.

Ecthyma gangrenosum secondary to methicillin-sensitive Staphylococcus aureus

Ecthyma gangrenosum (EG) is a well-described skin manifestation of Pseudomonas aeruginosa septicemia in immunocompromised patients. However, it can be seen in association with other bacteria, viruses, and fungi. We report a case of a 54-year-old African American female with metastatic gastric adenocarcinoma and recent chemotherapy and neutropenia who developed EG-like lesions due to methicillin-susceptible Staphylococcus aureus. We also review the literature to evaluate all reported cases of S aureus-associated EG and their clinical presentation, diagnosis, and treatment.

A deep look into thin melanomas: What’s new for the clinician and the impact on the patient

Melanoma incidence and mortality are on the rise and although most new cases of melanoma are thin, a significant percentage of these patients still experience disease progression. The American Joint Committee on Cancer publishes staging criteria for melanoma, which were recently updated to the 8th edition. The most significant revision from the 7th edition affects the T1b classification, which now includes melanomas with a Breslow depth of 0.8 mm to 1.0 mm. The second major revision eliminates mitoses as a criterion to upstage a thin melanoma to T1b. Although mitotic figures have been established as an independent prognostic factor, they do not have a significant correlation with sentinel lymph node (SLN) biopsy positivity. SLN status remains the most important independent prognostic factor in thin melanomas. Nonetheless, the identification of patients who are at the highest risk for having a positive SLN test result remains difficult. Importantly, a positive SLN test result has high positive predictive value, but a negative one has very low negative predictive value. Since there is no proven survival benefit in performing an SLN biopsy in T1 disease, dermatologists need to have a personalized discussion with patients with thin melanomas to review expected risks and benefits before undertaking this procedure.

Warty (follicular) dyskeratoma on the mons pubis

Warty (follicular) dyskeratoma (WD) is a discrete nodular lesion that demonstrates the characteristic histopathologic findings of acantholysis and dyskeratosis. WDs most commonly occur on the head and neck of adults. We present a case of WD that occurred on the mons pubis of a 53-year-old woman. Only a few other cases of WDs occurring on the vulva have been reported. WD most likely represents a tumor of the follicular infundibulum. Despite its name, there is no evidence that WD is caused by a human papillomavirus (HPV) infection. Although occurrences on the vulva are rare, they must be distinguished from HPV-induced squamous tumors when found in this area.

Staging of Melanoma

The Melanoma Staging Committee of the American Joint Committee on Cancer (AJCC) was formed in 1998 and is comprised of experts from all relevant medical specialties, including many of the major melanoma centers in North America, Europe, and Australia. This committee set up the AJCC Melanoma Staging Database for the collection of prospective outcome data on melanoma patients from 13 cancer centers and cooperative groups in order to establish and subsequently revise a melanoma staging system. The staging system for melanoma has undergone multiple revisions in the last decade, reflecting the rapid and continuous acquisition of new information and advances in this field.