Melanoma trials that defined surgical management: Overview of trials that established NCCN margin guidelines.

Since the observation that clearance of all visible and microscopic tumors from cutaneous melanoma is critical to prevent a recurrence, wide surgical margins have been central to surgical dogma. In the last several decades, more conservative margin widths have been vigorously studied by surgical investigators to lessen wound complications, the need for reconstruction, and healthcare costs. This review summarizes surgeon-led clinical trials that define current guidelines and highlights the challenges to initiate and perform trials today.

State of Melanoma: An Historic Overview of a Field in Transition.

The management of melanoma significantly improved within the last 25 years. Chemotherapy was the first approved systemic therapeutic approach and resulted in a median overall of survival less than 1 year, without survival improvement in phase III trials. High-dose interferon α2b and IL-2 were introduced for resectable high-risk and advanced disease, respectively, resulting in improved survival and response rates. The anti-CTLA4 and anti-programmed death 1 monoclonal antibodies along with BRAF/MEK targeted therapies are the dominant therapeutic classes of agent for melanoma. This article provides an historic overview of the evolution of melanoma management.

Gene Discovery Using Twins.

One of Nick's key early achievements at QIMR was to establish a twin study on melanoma risk factors. The Brisbane Twin Nevus Study (BTNS) had an initial focus on nevus (mole) count in adolescents but, reflecting Nick's broad interests, expanded in scope enormously over the decades. In the skin cancer arena, BTNS was essential to genetic discoveries in melanoma, eye color and pigmentation. Later studies amassed data on thousands of phenotypes, ranging from molecular phenotypes such as gene expression to studies where gene mapping findings in adolescents turned out to have translational potential in late-onset diseases. Nick's twin data have formed the basis for an enormous range of discoveries, with Nick and his colleagues continuing to capitalize on these data.

From δ-aminolevulinic acid to chlorophylls and every step in between: in memory of Constantin (Tino) A. Rebeiz, 1936-2019.

Constantin A. (Tino) Rebeiz, a pioneer in the field of chlorophyll biosynthesis, and a longtime member of the University of Illinois community of plant biologists, passed away on July 25, 2019. He came to the USA at a time that was difficult for members of minority groups to be in academia. However, his passion for the complexity of the biochemical origin of chlorophylls drove a career in basic sciences which extended into applied areas of environmentally friendly pesticides and treatment for skin cancer. He was a philanthropist; in retirement, he founded the Rebeiz Foundation for Basic Research which recognized excellence and lifetime achievements of selected top scientists in the general area of photosynthesis research. His life history, scientific breakthroughs, and community service hold important lessons for the field.

Basal Cell Carcinoma among Cutaneous Tumours in "Caricature," Painted by Bartolomeo Passerotti (1529-1592).

A fine and fair depiction of basal cell carcinoma is documented with great fidelity in "Caricature" by Bartolomeo Passerotti (1529-1592). The cancer is pearly white and contains an elevated centre with a sharp and somewhat depressed outline due to ulceration of the lesion. The painting is of essential didactic worth for practicing medical doctors. In addition, the masterpiece contains images of the brown elevated lesions that could turn out to be verrucous melanocytic nevi or pigmented seborrheic keratoses, but it cannot be excluded that these nodules are also basal cell carcinomas covered by a brownish crust. It is standard that microscopic verification is required for all these tumours. However, a pearly white irregular tumour is the most characteristic macroscopic presentation of basal cell carcinoma.

From Breslow to BRAF and immunotherapy: evolving concepts in melanoma pathogenesis and disease progression and their implications for changing management over the last 50 years.

Since it was first recognized as a disease entity more than two centuries ago, advanced melanoma has, until recently, followed a very aggressive and almost universally fatal clinical course. However, over the past 50 years crucial ground breaking research has greatly enhanced our understanding of the etiology, risk factors, genomic pathogenesis, immunological interactions, prognostic features and management of melanoma. It is this combined body of work which has culminated in the exciting improvements in patient outcomes for those with advanced melanoma over the last ten years. In this the 50th anniversary of Human Pathology, we highlight the key developments in melanoma over this period.

Revisiting the history of the "Mongolian spot": The background and implications of a medical term used today.

"Mongolian spot" is a term still commonly used today and found in many dermatology textbooks. This article examines historic literature to understand the social and political climate at the time of its coining. By doing so, this article critically examines the choice of words in pediatric dermatology and how we can use medical terminology to gain the trust and respect of our patients.

Frederic E. Mohs, MD, and the history of zinc chloride.

The history of zinc chloride therapy before and including Frederic E. Mohs' (1910-2002) early contributions to dermatologic oncology is presented. In 1932, Mohs devised a method of cutaneous surgery that employed zinc-chloride paste to devitalize basal or squamous cell carcinoma. Because zinc chloride coagulates malignant tissue without destroying cellular architecture, he described the surgery and its preservative effect as the fixed-tissue method. This method involved the serial removal of devitalized malignant tissue and the freezing and histologic examination of each layer; the process was continued until a cancer-free plane was reached. In 1953, a modified version of the micrographic system, the fresh-tissue method, was introduced. For improved efficiency, Mohs retained the systematic mapping of a neoplasm but eliminated the chemical escharotic. Although the fresh-tissue method has become the preferred treatment mode, zinc-chloride paste therapy remains in use today. Although the history of Mohs micrographic surgery is well documented, its background has not received sufficient attention. This paper surveys the chemical synthesis of zinc chloride, the formulation of zinc-chloride paste as a cutaneous escharotic, and the extent to which Mohs' method compares with those of 19th and early 20th century predecessors.

Survival of cutaneous melanoma based on sex, age, and stage in the United States, 1992-2011.

Women diagnosed with cutaneous melanoma have a survival advantage compared to men, which has been hypothesized to be due to difference in behavior and/or biology (sex hormones). It remains controversial whether this advantage is dependent on age or stage of disease. We sought to compare melanoma-specific survival between females in pre, peri, and postmenopausal age groups to males in the same age group, adjusting for stage of disease. This is a retrospective population-based cohort study using the Surveillance, Epidemiology, and End Results (SEER) database. Patients diagnosed from 1 January 1992 through 31 January 2011 with primary invasive cutaneous melanoma were included in our cohort. Melanoma-specific survival was the main outcome studied. Of the 106,511 subjects that were included, 45% were female. Females in all age groups (18-45, 46-54, and ≥55) with localized and regional disease, were less likely to die from melanoma compared to males in the same age group. Among patients with localized and regional disease, the relative risk of death due to melanoma increased with advancing age at diagnosis; this increase was more pronounced among females than males. In contrast, we observed no female survival advantage among patients with distant disease and no effect of age on relative risk of death from melanoma. Females with localized and regional melanoma have a decreased risk of death compared to males within all age groups. Our data show no differences in survival between men and women with metastatic melanoma, indicating that the influence of sex on survival is limited to early stage disease but not confined to pre or perimenopausal age groups.