A woman in her late 60s presents with a pigmented lesion that is clinically suspected to represent either a benign or atypical nevus.

Because the lesion warrants further evaluation, a shave biopsy is performed. Initial examination appears relatively reassuring; however, the biopsy transects the lesion, limiting evaluation of its deeper portions.

The incomplete sample creates an important diagnostic question: When the initial findings appear relatively benign but the entire lesion has not been adequately evaluated, how should clinicians approach the possibility of a more concerning diagnosis?

Further examination of the deeper, transected portion of the lesion reveals atypical melanocytes, raising concern that the lesion may not be as benign as initially suspected.

Additional immunohistochemical evaluation is performed. The deeper areas demonstrate reduced p16 expression and an atypical HMB-45 staining pattern, adding to concern for malignancy.

The new findings raise another question: When histopathologic and immunohistochemical findings remain concerning but the diagnosis is not yet definitive, what can help clarify the nature of the lesion?

Although the lesion initially appeared relatively benign, examination of the deeper portion of the transected biopsy revealed atypical melanocytes that prompted further investigation.

Immunohistochemical staining demonstrated reduced p16 expression in deeper areas and an atypical HMB-45 pattern. Comparative genomic hybridization subsequently identified significant chromosomal abnormalities associated with melanoma, supporting a malignant diagnosis.

The case illustrates how an initially reassuring assessment may not tell the full story when a melanocytic lesion is incompletely sampled. In diagnostically challenging cases, integrating histopathology, immunostaining, molecular testing, and clinical information can help clarify the diagnosis.