Stanley J. Miller

Biology of basal cell carcinoma (Part II)

Host-tumor relationships involve several factors that can enhance or suppress neoplastic growth. This second part of a review of basal cell carcinoma biology examines the role that hormones, cytokines, local and systemic immunity, congenital and genetic syndromes, and environmental factors play in the development of this neoplasm. Theories of etiology and pathogenesis are discussed, and transplantation and cell culture techniques used to study this cancer are explored. Valuable second-line therapies for treatment of multiple tumors are reviewed, and important areas of present and future research are emphasized.

Adverse Events Associated With Mohs Micrographic Surgery Multicenter Prospective Cohort Study of 20 821 Cases at 23 Centers

IMPORTANCE Detailed information regarding perioperative risk and adverse events associated with Mohs micrographic surgery (MMS) can guide clinical management. Much of the data regarding complications of MMS are anecdotal or report findings from single centers or single events. OBJECTIVES To quantify adverse events associated with MMS and detect differences relevant to safety. DESIGN, SETTING, AND PARTICIPANTS Multicenter prospective inception cohort study of 21 private and 2 institutional US ambulatory referral centers for MMS. Participants were a consecutive sample of patients presenting with MMS for 35 weeks at each center, with staggered start times. EXPOSURE Mohs micrographic surgery. MAIN OUTCOMES AND MEASURES Intraoperative and postoperative minor and serious adverse events. RESULTS Among 20 821 MMS procedures, 149 adverse events (0.72%), including 4 serious events (0.02%), and no deaths were reported. Common adverse events reported were infections (61.1%), dehiscence and partial or full necrosis (20.1%), and bleeding and hematoma (15.4%). Most bleeding and wound-healing complications occurred in patients receiving anticoagulation therapy. Use of some antiseptics and antibiotics and sterile gloves during MMS were associated with modest reduction of risk for adverse events. CONCLUSIONS AND RELEVANCE Mohs micrographic surgery is safe, with a very low rate of adverse events, an exceedingly low rate of serious adverse events, and an undetectable mortality rate. Common complications include infections, followed by impaired wound healing and bleeding. Bleeding and wound-healing issues are often associated with preexisting anticoagulation therapy, which is nonetheless managed safely during MMS. We are not certain whether the small effects seen with the use of sterile gloves and antiseptics and antibiotics are clinically significant and whether wide-scale practice changes would be cost-effective given the small risk reductions.

11 – Keratinocyte stem cells of cornea, skin and hair follicles

This chapter reviews present knowledge of keratinocyte stem cells of the cornea, epidermis, and hair follicle. All external surfaces of the body, including the skin and cornea, are covered by a stratified squamous epithelia composed of keratinocytes. These cells synthesize tissue-restricted keratin intermediate filament proteins, and form a specialized submembrane structure known as the comified envelop in the final stages of differentiation that is composed of covalently crosslinked proteins, including involucrin and loricrin. Stem cells exist in specific locations within a given tissue, and comprise a small percentage of the total cell population. They are ultrastructurally unspecialized, with a large nuclear-to-cytoplasmic ratio and few organelles. Stem cells have a proliferative potential that exceeds an individuals lifetime. Because stem cells cycle slowly, and represent only a small percentage of a cellular population, an intermediate group of more rapidly proliferating cells exists, that form clonal expansions resulting in the final, differentiated cell population. The stem cells of the corneal epithelium are located in a narrow section of the peripheral cornea, bordering the bulbar conjunctiva, termed the limbus. In this chapter, nine characteristics of stem cells derived initially from studies of the hematopoietic system are used as a framework to discuss keratinocyte populations.

Nonmelanoma Skin Cancer

This article provides readers with a comprehensive review of the evaluation and management of nonmelanoma skin cancers. Treatment recommendations are heavily based on the most recent guidelines from the National Comprehensive Cancer Network. Merkel cell carcinoma and dermatofibrosarcoma protuberans are also discussed. After reviewing this article, readers should be equipped with a better understanding of these entities and the current recommendations for their management.

Eccrine syringofibroadenoma (Mascaro): an ultrastructural study

To confirm the eccrine acrosyringeal differentiation of eccrine syringofibroadenoma (ESFA) and to elucidate the histogenesis of its angiofibrotic stroma, a case of ESFA from a 45‐year‐old man was examined by light and electron microscopy. Histologically, the parenchyma featured anastomosing, slender epithelial cords containing small cuboidal cells and occasional duct‐like structures. The stroma had increased numbers of mast cells, increased capillaries with swollen endothelial cells, and prominent fibrosis. Ultrastructurally, the following findings were characteristic of ESFA: a) abundant glycogen particles in epithelial cells, b) numerous intracytoplasmic and extracellular spaces lined with microvilli, c) intraepithelial duct formation, consisting of microvilli, vesicles, rod‐shaped dense bodies, multivesicular dense bodies, and peripheral network of tonofilaments, and d) large numbers of mast cells, closely associated with fibroblasts, surrounding increased numbers of capillaries containing swollen endothelial cells. These ultrastructural features support the acrosyringeal differentiation of ESFA. We hypothesize that mast cell hyperplasia and degranulation may play an important role in the formation of the angiofibrolic stroma.

Skin biopsy: Biopsy issues in specific diseases

Misdiagnosis may result from biopsy site selection, technique, or choice of transport media. Important potential sources of error include false-negative direct immunofluorescence results based on poor site selection, uninformative biopsy specimens based on both site selection and technique, and spurious interpretations of pigmented lesions and nonmelanoma skin cancer based on biopsy technique. Part I of this 2-part continuing medical education article addresses common pitfalls involving site selection and biopsy technique in the diagnosis of bullous diseases, vasculitis, panniculitis, connective tissue diseases, drug eruptions, graft-versus-host disease, staphylococcal scalded skin syndrome, hair disorders, and neoplastic disorders. Understanding these potential pitfalls can result in improved diagnostic yield and patient outcomes.

Therapeutic options to decrease actinic keratosis and squamous cell carcinoma incidence and progression in solid organ transplant recipients: A practical approach

BACKGROUND Solid organ transplant recipients (SOTRs) have a 50 to 250 times greater risk of squamous cell carcinoma (SCC) than the general population and experience higher rates of invasive and metastatic disease. These greater risks are a product of the tumorigenic effects of their immunosuppressive medications. As the number of transplantations and the life expectancy of SOTRs increase, SCCs are becoming a major source of morbidity and mortality. OBJECTIVE To present a practical approach for busy practicing clinicians to the care of SOTRs who are developing SCCs. Topics include assessment and treatment of new and neglected SOTRs; the dermatologists role with the transplantation team; and practical considerations in the choice of topical agents, systemic agents, and immunosuppressive therapy manipulation. METHODS AND MATERIALS An extensive literature search of the understanding of SCC pathophysiology and treatment in SOTRs was conducted. RESULTS Presented here is a logical, concise guide to the care of SOTRs who are developing actinic keratoses and SCCs. CONCLUSION Proper assessment of patients, understanding therapeutic alternatives and their application, and early institution of preventative and adjuvant therapies can help to decrease skin cancer–related morbidity and mortality in SOTRs.

Epithelial Stem Cells, Hair Follicles, and Tumor Formation

The hair follicle is a remarkable structure that undergoes a phase of sustained growth (anagen), followed by a period of cellular degeneration and rearrangement (catagen), and succeeded by an interval of rest (telogen) (Dry 1926; Chase et al. 1951; Chase 1954; Kligman 1959). This cycle can be repeated many times during the life of a hair follicle. In humans, individual hair follicles cycle independently. However, in many mammals, especially those used in experimental carcinogenesis (e.g., mouse, rat, and rabbit), hair follicles cycle in synchrony (Johnson 1958). The equilibrium that exists between new cell formation and epithelial cell loss due to terminal differentiation are prime examples of a self-renewing or “steady-state” tissue. By definition, the growth and regeneration of all self-renewing tissues (e.g., epidermis, hair follicle, intestinal epithelium, and hematopoietic system) are governed by stem cells. These cells are believed to be long-lived; they have great potential for cell division; and they are ultimately responsible for homeostasis of continuously renewing tissues (Potten et al. 1979; Wright and Alison 1984; Potten and Morris 1988). It is also generally accepted that a subpopulation of cells having stem cell characteristics are the target cells that interact with carcinogens and eventually become transformed (Boutwell 1964; Stenbach et al. 1981; Van Duuren et al. 1975; Argyris 1985; Morris et al. 1986).

Mohs Surgery for Melanoma in Situ

Mohs micrographic surgery is a valuable option for the treatment of melanoma in situ, especially lesions of the lentigo maligna subtype that are clinically ill defined. Complete peripheral margin assessment of a tumors borders by means of frozen or permanent sections can help reduce the surgical defect size and maximize cure rate as compared with standard excision with preset 5-mm margins. This article reviews the different variations of Mohs micrographic surgery that are currently used for melanoma in situ.

Staging Cutaneous Squamous Cell Carcinoma

C REATING A STAGING SYSTEM FOR CANCER is not easy. The goal is to stratify patients based on the likelihood of developing an adverse event, most commonly metastasis or death. Groupings should be distinctive (the likelihood of developing the adverse event differs between groups), monotonous (the likelihood increases with increasing stage), and homogeneous (the likelihood is similar within each group). It has also been suggested that staging systems should be clinically relevant (no one grouping is too rarely or too frequently utilized) and parsimonious (all other things being equal, simpler is better). Finally, as suggested by Jambusaria-Pahlajani et al in this issue of the journal, in cancers like cutaneous squamous cell carcinoma (CSCC), in which the likelihood of metastasis and death is low, it is helpful if a staging system can “concentrate” those patients who are most likely to develop adverse events. This will allow testing and use of adjuvant interventions in those individuals for whom it is most appropriate.