Table Of ContentNevogenesis
Ashfaq A. Marghoob
Editor
Nevogenesis
Mechanisms and Clinical
Implications of Nevus Development
Editor
Ashfaq A. Marghoob
Memorial Sloan-Kettering
Skin Cancer Center
Hauppauge
New York
USA
Coordinator
Mark E. Burnett
Dermatology Service
Memorial Sloan-Kettering Cancer Center
New York
USA
ISBN 978-3-642-28396-3 ISBN 978-3-642-28397-0 (eBook)
DOI 10.1007/978-3-642-28397-0
Springer Heidelberg New York Dordrecht London
Library of Congress Control Number: 2012950464
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Preface
The theories of how nevi develop including hypotheses regarding mecha-
nisms of inception, growth, and ultimate senescence have received surpris-
ingly little attention since Paul Gerson Unna originally proposed the
“Abtropfung” theory of nevogenesis over 100 years ago. For almost a century
this theory of nevogenesis was accepted as truth and remained uncontested.
Over the past few decades some researchers, based on newly acquired obser-
vations from histopathology and embryogenesis, have questioned the validity
of the “abtropfung” theory in favor of the “hochsteigerung” theory. In essence
the “hochsteigerung” theory is the reverse of the “abtropfung” theory with the
former stating that nevus cells migrate from the dermis to the epidermis and
the latter stating that nevus cells migrate from the epidermis to the dermis.
However, new insights grained from the epidemiology of nevi, cross-sectional
and longitudinal study of nevi, dermoscopy and confocal microscopy investi-
gation of nevi, as well as the cellular and molecular study of nevi bring into
question the aforementioned theories. The focus of this book is to help eluci-
date what is currently known about nevogenesis, help stimulate thought in
this field by bringing into question some of the established nevogenesis theo-
ries while at the same time providing possible alternative pathways explain-
ing the life cycle of nevi, and encourage further research in the field of
nevogenesis. Since nevi are associated with an increased risk of melanoma,
understanding nevogenesis may help to unravel some of the mysteries of
melanomagenesis.
v
Contents
1 Nevogenesis: Changing Theories ................................................ 1
Mark E. Burnett, Alon Scope, and Ashfaq A. Marghoob
2 Classifying Melanocytic Nevi ...................................................... 25
Iris Zalaudek, Caterina Longo, Cinzia Ricci, Giuseppe Albertini,
and Giuseppe Argenziano
3 Evolution of Nevi .......................................................................... 43
Harald Kittler
4 The Dual Pathway of Nevogenesis .............................................. 49
Iris Zalaudek, Alon Scope, Giuseppe Argenziano,
Caterina Longo, Simonetta Piana, Caterina Carticalà,
and Ashfaq A. Marghoob
5 Confocal Microscopy: Improving Our
Understanding of Nevogenesis .................................................... 59
Barbara De Pace, Barbara Ferrari, Barbara Predieri,
Lorenzo Iughetti, Leonardo Veneziano, Iris Zalaudek,
Giuseppe Argenziano, Caterina Longo, and Giovanni Pellacani
6 Nevi in Children and Adults: Dermoscopic Patterns
and the Development of New Nevi .............................................. 69
Tracey Liebman, Natalia Jaimes Lopez, and Stephen W. Dusza
7 Etiology of Congenital Melanocytic Nevi
and Related Conditions ............................................................... 73
Miguel Reyes-Múgica, Mark Beckwith, and Heather C. Etchevers
8 Molecular Nevogenesis: An Update............................................ 99
Andrew L. Ross, Margaret I. Sanchez, and James M. Grichnik
9 Nevogenesis: A Benign Metastatic Process?: An Update ......... 111
Andrew L. Ross, Margaret I. Sanchez, and James M. Grichnik
10 Nevus Senescence: An Update .................................................... 117
Andrew L. Ross, Margaret I. Sanchez, and James M. Grichnik
11 Genes and Nevogenesis ................................................................ 127
Stephen W. Dusza and Mark E. Burnett
vii
viii Contents
12 Malignant Transformation of Melanocytic Nevi ....................... 137
Alexander Marzuka-Alcalá and Hensin Tsao
13 Disappearance of Melanocytic Nevi ........................................... 145
Vitaly Terushkin, Alon Scope, Rainer Hofmann-Wellenhof,
and Ashfaq A. Marghoob
Index ...................................................................................................... 155
N evogenesis: Changing Theories
1
M ark E . B urnett, A lon S cope,
and A shfaq A . M arghoob
I ntroduction event in youth; in fact, 75 % of children between
ages 11 and 14 (5th to 8th grade) develop new nevi
T he life cycle of most individual melanocytic [ 9 ] . Moreover, approximately 30 % of adults over
nevi is shorter than the lifetime of the individual the age of 20 and 16 % of individuals over the age
harboring them [ 1 –3 ] . We are born with few or no of 45 develop new nevi over a follow-up period of
nevi and enter old age with few or no nevi, while 49 months ( unpublished data). Because cross-
nevi development occurs between these two time sectional studies have shown that nevus counts
periods (Fig. 1 .1) [ 2 –8 ] . This conception of nevo- decrease with older age, nevus involution was
genesis appears relatively straightforward from a thought to occur late in life. Yet, longitudinal der-
cross-sectional perspective, when only total moscopic follow-up of individual nevi shows that,
nevus counts are considered. in fact, 28 % of children between the ages of 11 and
H owever, longitudinal follow-up of individual 14 also have nevi that disappear [ 9 ] . Thus, younger
nevi has elucidated important details about the age groups exhibit higher rates of new nevi form-
inception and growth, as well as the disappearance ing than nevi regressing, resulting in a net increase
of nevi. The development of new nevi is a common in nevus counts [ 9 ] . The opposite appears to be the
case in adult life with more nevi regressing than
M .E . B urnett, M .D., BS new nevi forming, resulting in a net decrease of
D ermatology Service, total nevus counts. As a corollary, events in the life
M emorial Sloan-Kettering Cancer Center, cycle of a single melanocytic nevus, namely, incep-
1 60 East 53rd St., N ew York, N Y 1 0022, U SA tion and growth, followed by senescence and,
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