ABSTRACT
Skin cancer risk varies substantially across the body, yet how this relates to the mutations found in normal skin is unknown. Here we mapped mutant clones in skin from high- and low-risk sites. The density of mutations varied by location. The prevalence of NOTCH1 and FAT1 mutations in forearm, trunk, and leg skin was similar to that in keratinocyte cancers. Most mutations were caused by ultraviolet light, but mutational signature analysis suggested differences in DNA-repair processes between sites. Eleven mutant genes were under positive selection, with TP53 preferentially selected in the head and FAT1 in the leg. Fine-scale mapping revealed 10% of clones had copy-number alterations. Analysis of hair follicles showed mutations in the upper follicle resembled adjacent skin, but the lower follicle was sparsely mutated. Normal skin is a dense patchwork of mutant clones arising from competitive selection that varies by location. SIGNIFICANCE: Mapping mutant clones across the body reveals normal skin is a dense patchwork of mutant cells. The variation in cancer risk between sites substantially exceeds that in mutant clone density. More generally, mutant genes cannot be assigned as cancer drivers until their prevalence in normal tissue is known.See related commentary by De Dominici and DeGregori, p. 227.This article is highlighted in the In This Issue feature, p. 211.
Subject(s)
Carcinoma, Basal Cell/genetics , Carcinoma, Squamous Cell/genetics , Skin Neoplasms/genetics , Adult , Aged , Cadherins/genetics , Carcinoma, Basal Cell/pathology , Carcinoma, Squamous Cell/pathology , Clone Cells , Female , Forearm , Humans , Leg , Male , Middle Aged , Mutation , Receptor, Notch1/genetics , Skin Neoplasms/pathology , ThoraxABSTRACT
Primary adenocarcinomas of the parotid gland are rare, accounting for < 5% of all head and neck malignant neoplasms. The biological behaviour of these tumours varies considerably. Low-grade tumours are minimally invasive, whereas high-grade tumours show a high incidence of local recurrence and distant metastases. We report a case of metastatic parotid adenocarcinoma which presented with cutaneous features. This case illustrates that such salivary gland malignancies can very rarely present to the dermatologist. These potentially aggressive tumours require prompt diagnosis and management with multidisciplinary team input to ensure that the appropriate treatment is instigated.
Subject(s)
Adenocarcinoma/secondary , Lung Neoplasms/secondary , Parotid Neoplasms/pathology , Skin Neoplasms/secondary , Thyroid Neoplasms/secondary , Adenocarcinoma/pathology , Aged, 80 and over , Fatal Outcome , Female , Humans , Lymphatic Metastasis , Skin Neoplasms/pathologyABSTRACT
We report a 9-year-old boy with a gradual onset of multilobulated cysts on his nose and cheeks and histology in keeping with milia. His presentation was compatible with a diagnosis of multiple eruptive milia. As far as we are aware, this is only the second patient reported. Patterns whereby milia may present in children are discussed.
