In order to successfully prepare slides of skin specimens, the histologist must understand basic skin histology. Two major reasons for this are:
- The pathologist must be able to see the dermal-epidermal junction. The vast majority of skin pathology takes place in this area.
- Skin specimens are composed of three major tissue areas: epidermis, dermis and sub-cutaneous (adipose). This has ramifications for processing and cutting.
Dermis / Epidermis
Skin may be thought of as being comprised of two layers: an outer epidermis and lower dermis. Adipose tissue may or may not be present below the dermis.
The two layers interlock by folds in the epidermis (rete ridges) and dermis projections (dermal papillae). The epidermis sits on the basement membrane, whereon rests the basal layer of the epidermis (Figure 1).
Cells of the Epidermis
The basal cells that sit on the basement membrane divide and move up toward the surface of the epidermis as they differentiate into stratified squamous epithelium in a controlled fashion, replacing the epidermis as it is worn away, damaged, etc. If they grow out of control, they become a basal cell carcinoma (BCC). Similarly, if any of the squamous cells begin to grow out of control, a squamous cell carcinoma (SCC) may result. Usually, these cancerous cells remain in place, and are removed surgically to cure the patient. Very rarely, these cancers may metastasize and spread throughout the patient’s body.
Within the epidermis are many specialized cells, including melanocytes that contain the pigment melanin. Each melanocyte is associated with several basal keratinocytes via dendritic processes. The melanocyte transfers melanin into these cells. The melanin provides protection from ultraviolet (UV) light to the underlying cells. The more UV exposure, the more melanin is produced, and results in a darkening of the skin, or “tan”. Excessive exposure to the sun, and UV light, can damage the DNA of all epidermal cells, causing them to grow and divide out of control. This can result in a basal cell carcinoma, squamous cell carcinoma or malignant melanoma, depending upon the original cell type affected. While BCC and SCC rarely metastasize (i.e. spread) in a patient, malignant melanoma has a very high rate of metastasis. Thus, it is important to diagnose these cancers early and cure them by surgical removal. As a histologist, we will see that you play a critical role in helping to cure patients of skin cancer.
Malignant melanoma is, historically, a treatment resistant cancer. However, recently, there has been a breakthrough in treatment with the use of targeted therapies and immunotherapies. Currently, metastatic melanoma can be treated with potentially curative treatment.
Melanoma is an aggressive and treatment resistant cancer, accounting for 75% of all skin cancer deaths. The cancer arises from normal melanocytes, which produce melanin in the skin, meninges and mucosal epithelia. Two main types of pigment are produced by melanocytes: melanin (brown/black) and pheomelanin (red) (Figure 2). Melanoma risk factors include family history, immunosuppression, and ultraviolet light exposure.
A substance called “vemurafenib” was the first targeted therapy to show promise as a treatment for melanoma. The treatment shows rapid stabilization of the disease in patients with the proper BRAF gene mutations, with limited survival (i.e. 5 – 7 months).
Immune response is important in patients with melanoma. In fact, it has been noticed for years that patients undergoing immune therapy for a disease, may develop melanoma as a secondary complication. Experiments using melanoma vaccines and treatments with nonspecific immune stimulants have proved to be not highly beneficial. However, work with T cell treatments and blocking monoclonal antibodies have shown more promise.
There are certainly more successful treatments on the horizon as researchers work toward a therapy for patients with malignant melanoma.
- Lo and Fisher. The melanoma revolution: From UV carcinogenesis to a new era in therapeutics. Science. Vol 346, Issue 6212, pp. 945-949. 21 November 2014.
- Chapman CM. Dermatopathology: A Guide for the Histologist. Copyright 2003.