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Figure 1.  Histology of Nail Units From Cadaveric Human Tissue
Histology of Nail Units From Cadaveric Human Tissue

Hematoxylin-eosin staining of human cadaveric nail unit, sliced longitudinally. The box in A indicates the enlarged area shown in B, and the box in B indicates the enlarged area shown in C. Proximal is on the left-hand side of the images, and distal is on the right-hand side.

Figure 2.  Positive Melanocyte Staining in the Nail Matrix
Positive Melanocyte Staining in the Nail Matrix

Anti-tyrosinase staining of nail matrix (A and B) and nail bed (C and D). The boxes (A and C) show the areas enlarged in the corresponding images (B and D, respectively). Positively stained cells have magenta coloring.

1.
Banfield  CC, Dawber  RP.  Nail melanoma: a review of the literature with recommendations to improve patient management.  Br J Dermatol. 1999;141(4):628-632.PubMedGoogle ScholarCrossref
2.
Izumi  M, Ohara  K, Hoashi  T,  et al.  Subungual melanoma: histological examination of 50 cases from early stage to bone invasion.  J Dermatol. 2008;35(11):695-703.PubMedGoogle ScholarCrossref
3.
Perrin  C, Michiels  JF, Pisani  A, Ortonne  JP.  Anatomic distribution of melanocytes in normal nail unit: an immunohistochemical investigation.  Am J Dermatopathol. 1997;19(5):462-467.PubMedGoogle ScholarCrossref
4.
Martin  B. Nail histopathology.  Actas Dermosifiliogr. 2013;104(7):564-578. PubMedGoogle ScholarCrossref
5.
Luzar  B, Bastian  BC, Calonje  E. Diseases of the nails. In: McKee  PH, Calonje  E, Granter  SR, eds.  Pathology of the Skin: With Clinical Correlations. 3rd ed. Philadelphia, PA: Mosby; 2005:1051-1075.
6.
Tosti  A, Cameli  N, Piraccini  BM, Fanti  PA, Ortonne  JP.  Characterization of nail matrix melanocytes with anti-PEP1, anti-PEP8, TMH-1, and HMB-45 antibodies.  J Am Acad Dermatol. 1994;31(2 Pt 1):193-196.PubMedGoogle ScholarCrossref
Research Letter
May 2016

Histologic Evidence of Melanocytes Isolated to the Nail Matrix

Author Affiliations
  • 1Medical Scientist Training Program, Stony Brook University, Stony Brook, New York
  • 2Department of Dermatology, Atlantic General Hospital, Berlin, Maryland
  • 3Division of Dermatology, Albert Einstein College of Medicine, New York, New York
  • 4Dermatology Service, Memorial Sloan Kettering Cancer Center, Hauppauge, New York
JAMA Dermatol. 2016;152(5):573-575. doi:10.1001/jamadermatol.2015.5869

Acquired pigmented lesions of the nail have a variety of clinical presentations and etiologies, including subungual melanoma. Previous work has suggested that melanocytes in the distal nail matrix most often develop into subungual melanoma, although there have been reports of it originating from the proximal nail matrix, hyponychium, or paronychium.1-3 Many argue that pigmented melanomas, which excludes amelanotic melanoma, can originate directly from melanocytes in the nail bed.1,2 However, a search of the literature does not reveal any evidence of a pigmented melanoma being diagnosed while isolated to the nail bed. We therefore hypothesized that if pigmented melanomas arise from the nail matrix and not the nail bed, then melanocytes are probably isolated to the nail matrix and absent from the nail bed. We performed a qualitative histologic analysis of nail units from cadaveric human tissue to detect the location of melanocytes within the nail unit. Using 4 different melanocyte-specific stains, we show that melanocytes are present in the nail matrix and largely absent in the nail bed.

Methods

Two longitudinal nail biopsies were taken from the median portion of a normal finger and an accessory digit from 2 white male cadavers with no history of dermatologic disease. Cadavers were maintained in accordance with postmortem preservation protocols at Stony Brook University. Staining with hematoxylin-eosin was done as previously described.3 Antibodies used were anti-tyrosinase (Cell Marque, 1:400 dilution), anti-MelanA (Dako, 1:800 dilution), anti-MTIF (microphthalmia-associated transcription factor) (Cell Marque, 1:2000 dilution), and anti-Sox-10 (Sry-related HMG-BOX gene-10) (Cell Marque, 1:50 dilution).

All antibody staining was done according to manufacturer guidelines. All histologic specimens were prepared, maintained, and assessed by a board-certified dermatopathologist (P.C.).

Approval was not required for this study according to the institutional review board of Stony Brook University, and all cadavers were deidentified before use.

Results

We began with hematoxylin-eosin characterization of cadaveric nail units to determine if any difference existed between them and nail units of noncadaveric specimens. Sagitally sliced cadaveric nail units were histologically identical to sagitally sliced noncadaveric units, as previously shown,3,4 although superficial nail layers displayed less adherent cornified tissue, possibly because of postmortem degradation (Figure 1).

To detect the presence of melanocytes, we used 4 melanocyte-specific stains based on the antibodies described in the Methods section. Within the nail matrix, the anti-tyrosinase stain revealed multiple melanocytes within the basal-cell layer, although no suprabasilar melanocytes were observed (Figure 2, A). At higher resolution (Figure 2, B), the stained cells reflected the classic melanocyte morphology of large cell bodies with superficially oriented projections.4,5 Interestingly, the anti-tyrosinase staining was more prominent proximally, approximating the nail matrix. Distally, in regions approximating the nail bed, there was a complete absence of anti-tyrosinase staining at both low and high magnification (Figure 2, C and D). This finding was consistent across multiple specimens as well as in a nail unit from an accessory digit. Comparable results were found for MelanA–, MITF–, and Sox-10–stained tissue.

Discussion

Using an array of melanocyte specific stains on cadaveric nail units, we provide evidence that the nail matrix and not the nail bed is the primary location of melanocytes in the nail. Specifically, all 4 stains that we used identified melanocytes within the distal nail matrix, which is consistent with previous work.3,6 Contrasting with our findings, previous studies show a low density of melanocytes in the nail bed. We attribute this to differences in antibodies used in those studies and in the present study.3 The clinical implications of our findings are that isolated pigmented lesions of the nail bed warrant preliminary consideration of causes other than subungual melanoma for their occurrence, such as hemorrhage and infection. However, persistent pigmented lesions must be further scrutinized because they may mask underlying malignant diseases, such as amelanotic melanoma or squamous cell carcinoma.

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Article Information

Accepted for Publication: November 30, 2015.

Corresponding Author: Rashek Kazi, PhD, Medical Scientist Training Program, Stony Brook University, Basic Sciences Tower, Eighth Floor, Room 101, Stony Brook, NY 11794 (rashek.kazi@stonybrookmedicine.edu).

Published Online: February 10, 2016. doi:10.1001/jamadermatol.2015.5869.

Author Contributions: Dr Chu had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Chu, Marghoob.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Kazi.

Critical revision of the manuscript for important intellectual content: All authors.

Administrative, technical, or material support: Chu.

Study supervision: Chu, Marghoob.

Conflict of Interest Disclosures: None reported.

References
1.
Banfield  CC, Dawber  RP.  Nail melanoma: a review of the literature with recommendations to improve patient management.  Br J Dermatol. 1999;141(4):628-632.PubMedGoogle ScholarCrossref
2.
Izumi  M, Ohara  K, Hoashi  T,  et al.  Subungual melanoma: histological examination of 50 cases from early stage to bone invasion.  J Dermatol. 2008;35(11):695-703.PubMedGoogle ScholarCrossref
3.
Perrin  C, Michiels  JF, Pisani  A, Ortonne  JP.  Anatomic distribution of melanocytes in normal nail unit: an immunohistochemical investigation.  Am J Dermatopathol. 1997;19(5):462-467.PubMedGoogle ScholarCrossref
4.
Martin  B. Nail histopathology.  Actas Dermosifiliogr. 2013;104(7):564-578. PubMedGoogle ScholarCrossref
5.
Luzar  B, Bastian  BC, Calonje  E. Diseases of the nails. In: McKee  PH, Calonje  E, Granter  SR, eds.  Pathology of the Skin: With Clinical Correlations. 3rd ed. Philadelphia, PA: Mosby; 2005:1051-1075.
6.
Tosti  A, Cameli  N, Piraccini  BM, Fanti  PA, Ortonne  JP.  Characterization of nail matrix melanocytes with anti-PEP1, anti-PEP8, TMH-1, and HMB-45 antibodies.  J Am Acad Dermatol. 1994;31(2 Pt 1):193-196.PubMedGoogle ScholarCrossref
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