To the Editor: The “onychodermis hypothesis” remains a concept widely disseminated in the literature.1–4 The major virtue of this hypothesis is its simplicity with the possibility to suggest that polydactyly nail unit shares major characteristic with the normal nail unit and overall represents a very similar structure, useful for the investigation of nail diseases and nail biology.4 However, based on a comparative anatomy of polydactyly and adult nail units,5 it has been demonstrated that the connective tissue of the adult nail and the onychodermis of polydactyly are 2 completely different structures (Fig. 1). Furthermore, as recently reported,3 the misnomer term “onychofibroblasts” refers to mesenchymal stem cells of the polydactyly onychodermis that have the potential to differentiate into adipogenic, osteogenic, and chondrogenic lines. Unlike the numerous studies on adult nails,5,6 no study has yet been conducted on the microscopic anatomy of the nail unit in children. The aim of this letter is to analyze the structure of the pediatric nail unit and to determine its degree of homology with the developing nail in cases of polydactyly.FIGURE 1.: Schematic representations of the onychodermis of polydactyly and the dermis and hypodermis of the adult nail. A, Polydactyly type 1a: The onychodermis is closely linked to the thick perichondrial/periosteal layer of the developing distal phalanx. MD, CD10-/CD34- matrical dermis, the papillary elastic network in an arborescent pattern is indicated by a deep green color; NM, nail mesenchyme characterized by a loose connective tissue and a dense population of CD10+/CD34- nail mesenchymal stem cells, the so-called onychofibroblasts, the thin papillary elastic network in a serrated pattern is indicated by a deep green color; FV, feeder vessel surrounded by an adventitial CD34-positive stroma; PP, perichondrial/periosteal mesenchyme; CF, felting of fine collagen fibers emanating from the periosteal mesenchyme; P, periosteal mesenchyme; arrow-head indicates the dermis of the proximal nail fold. B, Polydactyly type 2a: The onychodermis is closely linked to a thick area of periosteal/fascial mesenchyme. The latter surrounds an ossification center. DE, digitiform extension of CD10+/CD34- nail mesenchyme; CF, felting of fine collagen fibers emanating from the periosteal mesenchyme; OC, ossification center; PM, periosteal mesenchyme. C, Adult nail unit of the thumb and hallux. The thumb and hallux differ from the other fingers and toes in 2 ways: (1) the distal hypodermis is characterized by a prominent myxoid area associated with numerous multivacuolated telocytes (2) the density of CD10+/CD34- telocytes is relatively high in the proximal superficial dermis of the nail bed and, to a lesser extent, in the distal hypodermis. In the rest of the connective tissue, the density of telocytes is low (see Fig. 4). FPNF, fascia of the proximal nail fold; AT, adipose tissue; PMH, proximal matrical hypodermis characterized by adipose tissue intermingled with a loose connective tissue or fibrous trabeculae; MD, matrical dermis, the papillary elastic network in an arborescent pattern is indicated by a deep green color; DMH, distal matrical hypodermis; NBD, nail bed dermis; BCB, broad collagen bundles connected to periosteum; A, aponeurosis of the extensor tendon; ET, extensor tendon; PO, periosteum; VP, volar plate; FT, flexor tendon.In previous studies5,6 on the normal anatomy of the nail using cadavers, the author had the opportunity to observe a child's nail. Toe 1 of a child because of accidental amputation was analyzed. The digit had been donated by the child's guardian to the department of anatomy. Pediatric specimen showed a growing bone with a thick periosteum/perichondrium. However, the ligamentous and mesenchymal relationships between the nail unit and the distal phalanx of the adult and children were similar.5 The extensor tendon had no connection with the nail unit (Figs. 2A, B). The fibers of the extensor tendon fused with the most proximal part of the perichondrium. The distance from the extensor hallucis longus tendon insertion to the matrix was 2.52 mm versus 3.76 mm (range 3.10–4.57) in adult.5 The complex fascial and adipose connective tissue of the proximal nail fold surrounded the proximal nail unit with a well visible fascia of the fibrous nail root (Figs. 2B, C). The nail connective tissue was composed of 3 microanatomical distinct regions (Figs. 2B, C and 3A, B) as in adult (Fig. 1C): the matrical dermis, the matrical hypodermis, and the nail bed dermis. The adipose tissue of the matrical hypodermis was limited to collections of adipocytes intermingled with a loose connective tissue. The proximal part of the matrical hypodermis was thin (Fig. 2C), whereas the distal part was prominent (Fig. 3A) with mucin deposition. The hypodermal compartment was loosely attached to the thick periosteum (Figs. 2C and 3A). The nail bed dermis consisted of thick collagen bundles associated with a dense elastic network (Fig. 3B). In the deep portion of the nail bed, broad collagen bundles blended with the thick periosteum. Immunohistochemistry was performed with a fully automated system (Dako, EnVision Detection System). The expression profiles of CD34 (clone Q bend, prediluted, Dako) and CD10 (clone 56C6, prediluted, Dako) markers in child's nail were like that observed in adults' nail.6,7 The matrical dermis and the proximal matrical hypodermis showed a sparse population of CD34+/CD10-telocytes (Fig. 4A). The proximal superficial dermis of the nail bed and, to a lesser extent, the distal hypodermis were characterized by a dense network of CD 10+/CD34- telocytes (Fig. 4B). The deep part of the proximal nail bed dermis and the entire distal nail bed dermis were devoid of telocytes (Fig. 4C). At high magnification, the moniliform appearance of the telopodes with dilated (podoms) and thin (podomeres) segments characteristic of telocytes was observed (Figs. 4A, D). In the distal fibromyxoid hypodermis, as in the adult nail,5,6 the telocytes acquired an oval to round morphology with multiple intracytoplasmic vacuoles (Fig. 4D).FIGURE 2.: The relationships between the distal interphalangeal joint and the nail unit. Longitudinal sections of the pediatric nail unit. A, Section at the level of the distal interphalangeal joint with insertion of the extensor tendon on the perichondrium (original magnification ×20). ET, extensor tendon; PC, perichondrium. B, Sections at the level of proximal matrix (original magnification ×20). PO, periosteum. C, High magnification of (B) (original magnification ×40). FFR, fascia of fibrous nail root; MD, matrical dermis; arrows indicate the thin proximal matrical hypodermis.FIGURE 3.: The connective tissue of the pediatric nail. A, View of matrix including the lunular matrix (original magnification ×40). PMD, proximal matrical dermis; DMD, distal matrical dermis (lunular matrix); DMH, distal matrical hypodermis; the arrows indicate the boundary between the matrix dermis and the matrix hypodermis. B, View of the matrix and nail bed (original magnification ×20). NBD, nail bed dermis.FIGURE 4.: The telocytes population in pediatric nail. A, Matrical dermis, the dermal telocytes have bipolar, long, and thin cytoplasmic processes; the dilated portions (podoms) of their telopodes are indicated by an arrow (CD34, original magnification ×200). B, The distal hypodermis and proximal superficial dermis of the nail bed have a relatively dense population of CD10-positive telocytes. Note the partial detachment of a part of the bone (original magnification ×20). C, The deep part of the proximal nail bed dermis and the entire distal nail bed dermis are devoid of telocytes. The empty space is an artifact of cutting corresponding to the bone (original magnification ×20). D, Fibromyxoid hypodermis. Note the piriform multivacuolated telocyte that retains a thin dendrite. The numerous plump telocytes are intermingled with fusiform telocytes. The dilated portions (podoms) of their telopodes are indicated by an arrow. (CD10, original magnification ×400).The interest of this case lies in the possibility of verifying the validity of the onychodermis/onychofibroblast hypothesis in the context of a pediatric nail with its distal phalanx still developing. The connective tissue of the child's nail specimen was completely different from the mesenchyme of polydactyly onychodermis. First, the nail bed dermis had a ligamentous structure, and, as in adults, the fatty component varied in importance in the matrix hypodermis. In contrast, the mesenchyme of the onychodermis is characterized by loose connective tissue with a homogeneous structure from the matrix to the nail bed (see Figs. 7 and 8 in reference 5). Second, the mesenchyme of onychodermis is characterized by a dense population of CD10+/CD34-nail mesenchymal stem cells, the so-called onychofibroblasts (see Fig. 10 in reference 5). In this pediatric specimen as in adult nails (see Figs. 5 and 6 in reference 5), only the area at the junction of the distal hypodermis and the superficial part of the proximal bed had a relatively dense population of CD10+/CD34- telocytes. In the rest of the connective tissue of the nail, the density of telocytes remained low. Based on their dendritic morphology and the moniliform appearance of telopodes, the telocytes were clearly differentiated from nail fibroblasts. Third, the mesenchyme of onychodermis is closely linked to the perichondral/periosteal mesenchyme of the distal phalanx (see Figs. 7 and 9 in reference 5). In contrast, the matrical connective tissue of the pediatric nail was independent of the synovio–entheseal complex of the distal interphalangeal joint and the proximal periosteum. The hypothesis that the polydactyl nail unit constitutes a substitute model for analyzing normal nail biology has recently been called into question.3,5–7 This observation extends previous comparative work5 and suggests that pediatric nails, like adult nails, do not possess the mesenchymal substructure characteristic of polydactyly onychodermis. However, this conclusion is based on a single pediatric sample. Further studies are needed to confirm these results in a larger cohort of normal pediatric nails. Analysis of the perilesional tissue from nail biopsies in children could provide a complementary and indirect means of confirming the provisional conclusion proposed here. In the author's experience, the compartmentalization of connective tissue is clearly visible on an optimal deep nail biopsy. In some cases, the author has performed detailed immunohistochemical analysis. The density of telocytes in these pediatric biopsy samples varies considerably depending on the pathologic process involved. If the analysis focuses on the most peripheral part of the perilesional tissue, only the distal hypodermis and the superficial part of the proximal bed may show a larger population of CD10+/CD34- telocytes compared with a normal nail. For the rest of the connective tissue of the nail, the density of telocytes generally remains relatively close to that observed in the normal state.
Christophe Perrin (Thu,) studied this question.
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