Advancing the Understanding of Seborrheic Keratosis

May 2017 | Volume 16 | Issue 5 | Original Article | 419 | Copyright © May 2017

Susan C. Taylor MD

Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

skin types. A prospective study by Niang from Dakar, Senegal, of 30 African patients with an average age of onset of DPNs of 22 years, revealed that the lesions initially appeared on the face and then encompassed all photoexposed areas.13 DNPs numbered 50-100 (ranging in size from 1-5 mm) in 66.6% of the cases and coalesced to form plaques in 26.6% (reaching a size of 8 mm). There was a family predisposition in 93.3% of the cases of DPNs. The second variant of SKs, the stucco keratoses present as white or white-grey 1-4 mm warty papules on the extremities. The lesions appear to be stuck onto the skin and can be scraped off without bleeding.14 SKs may be a feature of paraneoplastic syndrome. The sign of Leser-Trelat has been described as the explosive onset of multiple SKs associated with an underlying malignancy. The three most common malignancies associated with the sign of Leser- Trelat were gastric, colorectal, and breast cancer. 15 A case of hypoinsulinemic hypoglycemia and the sign of Leser-Trelat associated with a malignant fibrous tumor with insulin-like growth factor-2 (IGF-2), demonstrated improvement in both conditions after tumor excision.16 This suggests that IGF- 2 may play a causative role in SKs. Growth hormone exerts its effects through insulin growth factors. Cells must have receptors for growth factors to act upon. Both growth hormone and insulin like growth factor receptors have been detected in normal keratinocytes. In fact, growth hormone receptors have been reported in benign cutaneous proliferations.17 Ginarte evaluated the growth hormone receptor (GHR) expression on SKs and found no differences between keratinocytes from normal epidermis and keratinocytes from SKs. This has implications in regard to the etiology of SKs. The differential diagnosis of SKs includes the benign lesions, common warts, lentigines, melanocytic nevi, as well as the premalignant and malignant lesion, actinic keratosis, Bowen disease, basal cell and squamous cell carcinomas, and melanoma.13,18 Quality of Life (QOL) An observational study by Del Rosso from 10 United States dermatology practices captured how the diagnosis of asymptomatic SKs affected QOL as well as treatment concerns.10 These authors found that the primary concern for 22% of patients enrolled was related to the appearance of the SKs, 34% were concerned about the health implications, and 45% were equally concerned about appearance and health. 61% of patients, primarily women, attempted to disguise or cover their SKs by avoiding particular types of clothing (12%), wearing clothing designed to hide the SKS (16%), using makeup (28%), or hairstyles (7%) to cover SKs. In subjects in the Del Rosso study who had previously had SKs removed, the most common reasons included concernsthat they represented something serious (57%), not liking the appearance (53%), and not liking how SKs felt when touched (44%). When shown photographs of treatment results, 83% of subjects were at least somewhat interested in having their SKs treated. Del Rosso also evaluated the reasons that the study patients did not remove their SKs. Cosmetic concerns impacted 35% of the subjects who “did not want to risk having a scar” (14%), “didn’t want to risk having a white spot” (10%), and “I have too many spots to treat” (10%). As asymptomatic and non-irritated SKs are considered cosmetic in nature, the cost of removal could play a role in the decision not to have a lesion treated. Del Rosso reported that 17% of subjects in their study decided not to have SKs treated because “out of pocket cost of treatment was too high”. Thus, the benign asymptomatic SK impacts the QOL of patients in a variety of ways and financial concerns may impact their ability to have SKs treated. Etiology and Pathogenesis Genetics Studies in the past decade have identified genomic alterations in benign lesions including SKs. Genomic alterations identified in SKs have included mutations of the FGFR3 and the gene encoding for PIK3CA.1 Logie first suggested a causative role of somatic FGFR3 mutations after demonstrating a similar mutation in transgenic mice.8 The mice developed benign epidermal tumors with features of SKs. These investigators went on to find the FGFR3 mutation in 39% of the human SKs that they studied. Hafner then analyzed 65 acanthotic SKs for FGFR3 mutations.19 FGFR3 mutations were found in 57% of SKs including flat (or newer) and thick (older) SKs. The mutation was significantly higher in SKs than in normal epidermis and increased age was felt to be a risk factor for the mutation. It was hypothesized that activation of the FGFR3 mutation provided proliferative signals for keratinocytes as well as induction of anti-apoptotic pathways that results in prolonged survival of these keratinocytes. FGFR3 mutations in the Hafner study occurred preferentially in SKs of the head and neck for which the authors suggested a causative role of cumulative ultraviolet exposure. Finally, not all SKs were found to have the FGFR3 mutation, suggesting the involvement of additional genes. In another investigation by Hafner of the stucco and DPN variants of SKs, it was determined that mutations in FGFR3 and PIK3CA also existed.14 This supports the concept that stucco SKs and DPNs are indeed variants of SK and share a common genetic background with SKs. Hafner went on to investigate FGFR3 mutations in a German family with 7 affected members in 2 generations with large numbers of SKs at a young age.1 FGFR3 mutations were present in 3 of 5 SKs analyzed from the family and 1 SK with a FGFR3 mutation was further analyzed and showed a hotspot PIK3CA mutation. However, none of these mutations was