ing the study period. The subjects with BA x-rays re- mens, what role BA radiographs play during rou- ceived more GH injections and had more frequent tine clinical practice has been questioned. These visits documented in the NCGS database than did the data from the NCGS support the notion that not cohort with no BA measurements. This would suggest only do pediatric endocrinologists find it of value that NCGS investigators find it of value to obtain BA to obtain BA determinations at enrollment, but that measurements in most subjects. Although the slightly they also find it beneficial to assess serially skeletal improved height SDS and height age outcomes during development. BA assessment should be considered treatment of the subjects with BA readings might be an important component of the follow-up of pa- attributed to their older age and pubertal status, there tients treated with GH. still remains the suggestion that somehow radiographs are used by the NCGS investigators to maximize GH ACKNOWLEDGMENTS therapy. Because final height data were not yet avail- Supported by an educational grant from Genentech, Inc, South able, it is possible that by assessing skeletal maturation San Francisco. at frequent intervals, GH treatment might be extended We thank Kevin Connelly for analysis and programming sup- longer, other agents (such as sex steroids or luteinizing port, and Sandra Blethen, MD, PhD, and Jim Frane, PhD, for releasing hormone analogues) might be added more helpful suggestions. often and in a more efficacious manner, or, because of more frequent visits, subjects might be more compliant REFERENCES with treatment regimens, all which would ultimately 1. Gruelich WW, Pyle SI. Radiographic Atlas of Skeletal Development of the improve the outcome of the cohort followed with BA Hand and Wrist. Stanford, CA: Stanford University Press; 1993 2. Buchlis JG, Irizarry L, Crotzer BC, Shine BJ, Allen L, Macgillivray MH. radiographs. Comparison of final heights of growth hormone-treated vs untreated The conclusion of this study, that it is important to children with idiopathic growth failure. J Clin Endocrinol Metab. 1998; follow BA x-rays for the pediatric endocrinologist, is 83:1075–1079 supported by the survey of GH treatment practices that 3. Coutant R, Carel J-C, Letrait M. Short stature associated with intrauter- was conducted by Wyatt et al6 in 1993 and reported in ine growth retardation: final height of untreated and growth hormone- treated children. J Clin Endocrinol Metab. 1998;83:1070–1074 1995. Of the 251 pediatric endocrinologists surveyed, 4. Balducci R, Toscano V, Mangiantini A, et al. Adult height in short BA determinations were used by 60% of them to de- normal adolescent girls treated with gonadotropin-releasing hormone termine who should start GH treatment, and BA delay analog and growth hormone. J Clin Endocrinol Metab. 1995;80:3596–3600 was ranked 5 of 14 on the scale of auxologic and labo- 5. Rosenfeld RO, Frane J, Affie KM, et al. Six-year results of a randomized, prospective trial of human growth hormone and oxandrolone in Turner ratory criteria used to initiate GH. These findings were syndrome. J Pediatr. 1992;121:49–55 similar to the percentages of those who ranked obtain- 6. Wyatt DT, Mark D, Slyper A. Survey of growth hormone treatment ing a BA determination as an important criterion to practices by 251 pediatric endocrinologists. J Clin Endocrinol Metab. discontinue GH. Again, 61% of those surveyed stated 1995;80:3292–3297 that BA was important, and they ranked it 5 of 14 in 7. Hopwood NJ, Hintz RL, Oertner JM, et al. Growth response of children with non-growth-hormone deficiency and marked short stature during criteria used to stop GH therapy. three years of growth hormone therapy. J Pediatr. 1993;123:215–222 There is no doubt that assessment of skeletal 8. Plotnick L, Attie KM, Blethen SL, Sy JP. Growth hormone treatment of maturation is at the foundation of research per- girls with Turner syndrome: the National Cooperative Growth Study formed evaluating GH treatment.7–9 Although BA experience. Pediatrics. 1998;102:479–481 9. August GP, Julius JR, Blethen SL. Adult height in children with growth radiographs are used to distinguish benefit from hormone deficiency who are treated with biosynthetic growth hormone: harm during studies of GH efficacy in novel clin- the National Cooperative Growth Study experience. Pediatrics. 1998;102: ical situations and in innovative therapeutic regi- 512–516 The Physiology of Pigmented Nevi Jay Kincannon, MD, and Christine Boutzale, BS ABSTRACT. Melanocytes are pigment-producing cells nosomes. Within the melanocyte, tyrosine is converted to derived from the neural crest. These specialized exocrine dopa, and then dopaquinone via the bifunctional enzyme cells produce melanin, which is packaged and dispersed tyrosinase. Dopaquinone is oxidized further to form the to neighboring keratinocytes in organelles called mela- pigment melanin. Each epidermal melanocyte secretes melanosomes to approximately 36 adjacent keratino- From the Department of Pediatric Dermatology, University of Arkansas for cytes, forming an epidermal melanin unit. Genetically Medical Sciences, Little Rock, Arkansas. programmed constitutive skin color is determined by the Presented in part at the National Cooperative Growth Study Twelfth An- amount of cutaneous melanin pigmentation. nual Investigator’s Meeting; October 8–11, 1998; New Orleans, LA. The common mole or acquired melanocytic nevus Received for publication May 13, 1999; accepted Jun 22, 1999. (AMN) is a collection of nevomelanocytes grouped into Reprint requests to (J.K.) Arkansas Children’s Hospital, 800 Marshall St, Little Rock, AR 72202-3591. E-mail: [email protected] nests located in the epidermis (junctional nevus), dermis PEDIATRICS (ISSN 0031 4005). Copyright © 1999 by the American Acad- (dermal nevus), or both (compound nevus). It is hypoth- emy of Pediatrics. esized that nevomelanocytes are derived from either epi- 1042 SUPPLEMENT Downloaded from www.aappublications.org/news by guest on September 30, 2021 dermal melanoblasts or dermal Schwann cells. AMN first pathway. What is known as a premelanosome is appear at ;1 year of age, peaking in number during the formed in the smooth endoplasmic reticulum, second or third decades of life, and disappearing by the whereas the rough endoplasmic reticulum is pro- seventh to ninth decades. AMN may appear suddenly or ducing the copper-containing oxidase known as become more prominent in response to sun exposure, tyrosinase. Final maturation occurs in the Golgi cortisone and corticotropin, blistering diseases, chemo- apparatus as tyrosinase is transported by coated therapy, immunosuppression, and other factors that are not well-defined. Reports of AMN increasing in size and vesicles to the premelanosome. There it catalyzes darkening in color during puberty and pregnancy have the conversion of tyrosine to dopa and then dopa- been reported but not quantitated systematically. quinone, which is oxidized further to form the Pediatrics 1999;104:1042–1045; melanocytes, keratino- pigment melanin. cytes, acquired melanocytic nevi. Eumelanin is a black–brown pigment, whereas pheomelanins are pigments that contribute primarily ABBREVIATIONS. AMN, acquired melanocytic nevus; CMN, to hair color. The biochemical pathway for the pro- congenital melanocytic nevus. duction of pheomelanin varies somewhat to yield a more yellow–red color. he incidence of malignant melanoma is in- BIOLOGY OF PIGMENTED NEVI creasing within the population. Risk factors for Melanotic nevi, or moles, are quite common. Usu- Tthe development of cutaneous melanoma in- ally brown, they vary in shape and size, and can be clude: 1) a new or changing mole; 2) adulthood (15 found anywhere on the skin. A pigmented nevus is a years or older); 3) family history of melanoma; 4) benign proliferation of cells with melanocytic differ- dysplastic nevus syndrome; 5) large congenital ne- entiation. These cells can be formed from either pre- . vus ( 20 cm); 6) several nevi; 7) white race; 8) severe existing melanocytes or cells called nevomelano- childhood sunburns; and 9) immunosuppression. cytes. The origin of the nevomelanocyte is the nevomelanoblast. Embryologically, nevomelano- BIOLOGY OF MELANOCYTES blasts are melanocytes within the neural crest.1 The Melanin, the skin pigment that is the primary de- cells migrate to the epidermis and dermis, where terminant of skin color, is produced by melanocytes, they differentiate into nevomelanocytes. One hy- which make up ;15% of the basal layer of sun- pothesis is that the nevomelanoblasts in the upper exposed skin and 6% of unexposed skin. In its pri- dermis and epidermis are derived from epidermal mary role of absorbing ultraviolet light, melanin is melanocytes, whereas those in the lower dermis are deposited in keratinocytes of the interfollicular epi- from Schwann cells of nerves. For a melanocyte to dermis, thus protecting the genome of the dividing express a normal morphology, it must be located in basal keratinocytes and melanocytes. The melano- the basement membrane zone. Recent studies show somes are located supranuclearly in the melanocytes that when melanocytes migrate to other locations, before being distributed throughout the cell to pro- they lose dendrite expression, decrease production of vide maximal protection from damaging ultraviolet melanin and enzymes such as tyrosinase, and mor- light. Melanin also has been shown to be a free phologically begin to resemble Schwann cells.4 These