Natural History Study of Moles and Suspicious Melanoma

The objective of this study is to understand early transformation and malignant progression
events of cutaneous melanoma by obtaining detailed clinical information and lesional tissue
for analysis, cell culture, and immortalization from patients with melanocytic nevi, which
frequently are precursor lesions of melanoma, and primary melanoma. An important goal of
this study is the acquisition of melanocytes from lager congential melanocytic nevi (LCMN)
and acquired melanocytic nevi (AMN) for analysis, culture and experimental manipulation. We
do not propose to acquire melanocytes from pigmented lesions suspected to represent primary
melanoma because of the importance of preserving all lesional tissue required to render
accurate histopathological diagnosis. However, another aim of the study is the development
of enhanced clinical criteria for the diagnosis of primary cutaneous melanoma, particularly
using digital epiluminescent skin microscopy, or dermoscopy, for pigmented lesion image
acquisition and analysis. The close comparison of dermoscopic images of pigmented skin
lesions suspicious for melanoma with lesional histopathology should be useful for expanding
the knowledge base about how dermoscopy , a relatively new technique used to evaluate
pigmented skin lesions, can be used to diagnose a pigmented skin lesion as benign or
malignant. These detailed comparisons may also provide information about how specific visual
features within the dermoscopic image field correlate with histologic features of the
lesion. This information may be useful for future possible studies designed to predict
accurately which portions of a primary malignant melanoma can be removed for esperimental
study while retaining sufficient lesional information to guide further treatment and render
an accurate prognosis.

The study population will consist of three categories of patients: (1) infants and children
with large congenital melanocytic nevi, (2) adults with numerous (less than 100) melanocytic
nevi, and (3) patients with primary malignant melanoma. Establishment of the Pigmented
Lesion Clinic required for the execution of this protocol will provide a mechanism for the
evaluation of patients with numerous or unusual pigmented lesions, and for the entry of
eligible patients into ongoing therapeutic trials for malignant melanoma. As the study
progresses, it is anticipated that a substantial amount of formalin-fixed nevus and primary
melanoma tissue with a high-degree of clinical annotation will be collected. As a secondary
objective , the availability of this collection will be useful to support studies designed
to evaluate new markers and techniques for the diagnosis of melanoma and atypical nevi, and
for incorporation into a tissue microarray that will be available to the melanoma research
community for target foundation validation.

Background:

The molecular events resulting in melanocyte transformation and the development of early
melanoma are incompletely understood. Risk factors for the development of melanoma include
genetic, phenotypic and environmental risk factors and can overlap. Also, persons with large
numbers of nevi face a higher risk of melanoma. These risk associations, combined with
knowledge obtained from basic studies on the survival, differentiation, and proliferation of
the melanocyte, can provide hints about the molecular mechanisms that underlie the
development of nevi and melanoma.

In this study we plan to acquire lesional tissue from pigmented lesions and develop enhanced
clinical criteria for the diagnosis of primary cutaneous melanoma, particularly using
digital epiluminescent skin microscopy, or dermoscopy, for pigmented lesion image
acquisition and analysis. This information may be useful for future possible studies
designed to predict accurately which portions of a primary malignant melanoma can be removed
for experimental study while retaining sufficient lesional information to guide further
treatment and render an accurate prognosis.

Objectives:

To obtain tissue from benign melanocytic nevi and from large congenital melanocytic nevi
(LCMN) for experimental study.

To refine culture and immortalization methods for melanocytes derived from melanocytic nevi,
permitting in vitro expansion of these cells for functional study.

To correlate clinical and dermoscopic observations of primary melanomas with histopathology
to establish standards for sampling primary melanomas in a possible future study.

Eligibility:

Infants/Children less than 5 years of age with large congenital melanocytic nevus (LCMN,
diagnosed clinically or by biopsy) that is greater than 20 cm in any one dimension or that
is greater than 8 cm in any one dimension involving the scalp.

Adults greater than 18 years of age with greater than 100 melanocytic nevi greater than 2 mm
in diameter with at least one melanocytic nevus greater than 4 mm in longest dimension or
with a current pigmented lesion clinically suspicious for primary melanoma.

Design:

This is a natural history protocol designed to enroll 110 subjects who will be evaluated and
followed over the course of their disease.

- INCLUSION CRITERIA:

Infants/Children

Must be less than or equal to 5 years.

Must have large congenital melanocytic nevus (LCMN, diagnosed clinically or by biopsy)
that is greater than 20 cm in any one dimension or that is greater than 8 cm in any one
dimension involving the scalp.

Must have outside referring physician.

OR

Adults

Must be greater than 18 years.

Must have greater than or equal to 100 melanocytic nevi greater than 2 mm in diameter.

Must have at least one melanocytic nevus greater than or equal to 4 mm in longest
dimension.

Can have prior history of cutaneous or ocular malignant melanoma.

Must have outside primary physician.

OR

Adults

Must be greater than 18 years.

Must have a current pigmented lesion clinically suspicious for primary melanoma.

Must have outside primary physician.

AND

All patients, or in the case of infants and children their parents or legal guardians,
must be able to understand and sign an informed consent.

EXCLUSION CRITERIA:

The patient does not meet the inclusion criteria.

Diagnosis of genetic syndrome associated with multiple lentigines or nevi (Peutz-Jeghers
syndrome, Carney complex, turner syndrome, Noonan's syndrome).

Two or more first-degree relatives with history of cutaneous melanoma and familial
atypical mole-melanoma syndrome phenotype.

Diagnosis of cancer-associated syndrome (xeroderma pigmentosum, type I neurofibromatosis,
Li-Fraumeni syndrome).

Inability to tolerate surgical procedure due to bleeding diathesis or disorder or other
cause as determined by principal investigator.

Patient is unwilling to consider elective biopsy of a melanocytic nevus.