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(American Journal of Pathology. 2002;161:1163-1169.)
© 2002 American Society for Investigative Pathology

Regular Articles

Genetic Changes in Neoplasms Arising in Congenital Melanocytic Nevi

Differences Between Nodular Proliferations and Melanomas

Boris C. Bastian^*, Jessie Xiong, Ilona J. Frieden^*, Mary L. Williams^*, Pauline Chou, Klaus Busam^¶, Dan Pinkel and Philip E. LeBoit^*

From the Departments of Dermatology^* and Pathology, and the University of California at San Francisco Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California; the Department of Pathology, Children’s Memorial Hospital, Northwestern University, Chicago, Illinois; and the Department of Pathology,^¶ Memorial Sloan Kettering Cancer Center, New York, New York

Large congenital melanocytic nevi (CMN) are at an increased risk of developing melanoma. Several forms of secondary proliferations can arise in congenital nevi on rare occasions. Although some of these closely resemble melanoma both clinically and histologically, metastasis is rare. We used comparative genomic hybridization to analyze chromosomal aberrations in different types of proliferations arising in CMN and compared them to typical congenital nevi, clear-cut melanomas arising in congenital nevi, as well as primary cutaneous melanomas that were not associated with a CMN. Cases of CMN and CMN with secondary proliferations were assigned to six groups according to the predominant histological pattern: group I, bland congenital nevi (n = 6); group II, congenital nevi with foci of increased cellularity (n = 4); group III, CMN with a proliferation simulating superficial spreading melanoma in situ (n = 3); group IV, CMN with a proliferation simulating nodular melanoma (n = 9); group V, proliferating neurocristic hamartoma (n = 1); and group VI, melanoma arising in congenital nevus (n = 6). No aberrations were found in groups I to III, whereas seven of nine cases of group IV, and one of one case of group V, showed aberrations. In group IV six of seven cases with aberrations (86%) showed numerical aberrations of whole chromosomes exclusively. This pattern differed significantly from the findings in melanoma that arose within CMN (n = 6), group VI, or independent of CMN (n = 122) in which only 5% showed numerical changes only. The single case in group V showed aberrations similar to melanoma. The finding of frequent numerical chromosomal aberrations in atypical nodular proliferations arising in CMN identifies these as clonal neoplasms with a genomic instability consistent with a mitotic spindle checkpoint defect. This difference compared to the aberration pattern found in melanoma might explain their more benign clinical behavior and may be of diagnostic value in ambiguous cases.

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