9p21 gene locus in Spitz nevi of older individuals: absence of cytogenetic and immunohistochemical findings associated with malignancy

• Published in: Human pathology Vol. 44; no. 12; pp. 2822 - 2828
• Main Authors: Horst, Basil A., MD, Dr.med, Terrano, David, MD, PhD, Fang, Yuqiang, MD, Silvers, David N., MD, Busam, Klaus J., MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2013; Elsevier Limited
• Subjects: 9p21 FISH; Age; Aged; Aged, 80 and over; Aggressiveness; CDKN2A; Child; Chromosome Aberrations; Cyclin-Dependent Kinase Inhibitor p16; Diagnosis, Differential; Female; Genes, p16; Histology; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Melanoma; Melanoma - diagnosis; Melanoma - genetics; Melanoma - metabolism; Middle Aged; Neoplasm Proteins - metabolism; Nevus, Epithelioid and Spindle Cell - diagnosis; Nevus, Epithelioid and Spindle Cell - genetics; Nevus, Epithelioid and Spindle Cell - metabolism; p16 IHC; Pathology; Patients; Skin Neoplasms - diagnosis; Skin Neoplasms - genetics; Skin Neoplasms - metabolism; Spitz nevus; Spitzoid melanoma; Tumors; Spitzoid melanoma; 9p21 FISH; CDKN2A; Spitz nevus; p16 IHC
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2013.07.034

Summary The diagnosis of Spitz nevus in an elderly individual is often met with skepticism because the lesion can be difficult to distinguish from melanoma and because the probability of a malignant melanoma is higher in older patients. Recently, increased sensitivity for detection of malignant spitzoid neoplasms using 9p21 fluorescence in situ hybridization (FISH) has been described. In this study, we address the question of whether histopathologically typical Spitz nevi occurring in patients 50 years and older show any abnormalities regarding the 9p21 CDKN2A tumor suppressor gene locus. p16 immunohistochemistry (IHC), as well as dual-color FISH for assessment of diploid or hypodiploid status at 9p21, was performed in 25 classic Spitz nevi from patients 50 years and older and was compared with findings in a younger control population. All cases of typical Spitz nevi occurring in older patients retained p16 expression by immunohistochemistry and showed normal, diploid 9p21 FISH signals. Heterozygous loss of 9p21 by FISH was noted in a control case of a 9-year-old girl and is of unknown significance. These findings indicate that p16 expression by immunohistochemistry in classic Spitz nevi correlates well with absence of malignancy-associated cytogenetic abnormalities at 9p21 by FISH independent of the patient's age. Assessment of p16 expression by standard immunohistochemistry may therefore be reassuring in routine clinical practice when the patient is of advanced age, and can be helpful as a screening tool to select IHC-negative cases for extended FISH analysis targeting the 9p21 gene locus.