Anatomic Distribution of Melanocytes in Normal Nail Unit

Abstract

Very few histologic reports describe normal melanocytes of the nail unit. Previous studies predominantly address the distal nail matrix melanocytes; we found no review of nail-bed melanocytes in the literature. The proximal nail matrix melanocytes are difficult to identify; the cells cannot be identified by L-DOPA staining. More recently, their scarcity was confirmed by immunohistochemistry with a large panel of antibodies directed against melanocytes. We wished to detect the proximal nail matrix dormant melanocytes and compare their density and distribution with that of the other melanocytes in the distal matrix and nail bed and to establish criteria of normality that may help clarify the pathologic features of benign nevoid melanonychia in the nails of whites. A panel of five monoclonal antibodies (MoAbs), including HMB45 and TRP1 directed against antigens localized in early melanosomal vesicles, was investigated in frozen sections of six nail specimens from whites. Both vertical and horizontal sections were assessed to determine the presence of dormant melanocytes. Results showed that the proximal nail matrix melanocytes were clearly identified with MoAbs HMB45 and tyrosinase-related protein-1 (TRP-1). By contrast, melanocytes stained by MoAb against tyrosinase and L-DOPA reaction were evident, especially in the distal matrix. With MoAb TRP-1, the epithelial sheets showed counts of approximately 217+/-84/mm2 in the proximal matrix and of 132+/-34/mm2 in the distal matrix; the nail bed counts were only 45+/-25/mm2. The split epithelial sheets had 103+/-17/mm2 L-DOPA-positive melanocytes in the distal third of the matrix, but only a few of them were detected in the proximal matrix and none were noted in the nail bed. We clearly identified proximal nail melanocytes using MoAb HMB45 and TRP1. The total number of matrix melanocytes can be estimated as approximately 217/mm2. In proximal matrix, the dormant melanocytes compartment was predominant. In the distal matrix, two compartments were identified: a functionally differentiated and a dormant compartment. Contrary to classical opinion, longitudinal melanonychia originates more frequently in the distal matrix, not secondary to the larger melanocyte density but because only the distal matrix contains an active melanin synthesis compartment. Furthermore, the superficial distribution of proximal nail melanocytes in vertical sections showed a histologic feature that may simulate the pagetoid pattern of melanoma in situ.

Histopathological analysis of the progression pattern of subungual melanoma: late tendency of dermal invasion in the nail matrix area

“…The melanocytes in the nail matrix were distributed throughout the basal layer and suprabasally in solitary units and small clusters. 16 Because there are many more active melanocytes (DOPA-positive) in the distal matrix than the proximal matrix, 17 longitudinal melanonychia and subungual melanoma are believed to originate more frequently in the distal matrix. The relative large number of active melanocytes in the distal matrix may account for the more prominent stacking of atypical melanocytes and the late tendency of dermal invasion of subungual melanoma in the nail matrix.…”

Diagnosis and management of nail pigmentations

“…18 Lack of melanin inclusions suggests that the condition is caused by a nonmelanocytic lesion that has resulted in nail hyperchromia. It is also common in subungual hemorrhage to see multiple reddish globules at the lateral and proximal edge of the pigmented area.…”

Nail Anatomy and Physiology for the Clinician

“…Beside keratinocytes, the matrix contains other cell lines, particularly melanocytes [ 2 ]. They are less numerous than in the skin and located often suprabasally and in small clusters of 3-5 cells.…”