Histopathology of the Nail

Onychopathology

Eckart Haneke

• Publisher: CRC Press
• Year: 2017
• Print ISBN: 9781482212327
• eBook ISBN: 9781351729833
• Edition: 1
• Topic: Medicine
• Subtopic: Dermatology

This comprehensive review of the histopathology of the human nail will act as a masterclass for all dermatologists, dermatopathologists, and nail-interested pathologists who have to interpret histological sections of nail tissue, which can be challenging for many reasons. In addition to a wealth of illustrated examples, the text guides the reader through the specialized terminology of nail science and supplies clinical data to help reach a reliable histopathological diagnosis.

1

Development, structure, and function of the nail

The nail is a plate of hard keratin that overlies the distal dorsal tip of the digits.1,2 Apart from mechanical protection and an ever-growing aesthetic importance, it has a variety of other functions such as being a most versatile tool, aiding in manual dexterity, being a defense tool, and enhancing the digital tips’ extremely elaborate sensory functions. Particularly on the big toe, it provides counterpressure when, during gait, the whole body weight, which is enhanced 2.5 times by the forward thrust, is concentrated on the pulp of the toe, which would otherwise be gradually dislocated dorsally to form a false distal nail wall; in fact, some developmental biologists believe that without our great toe’s specific properties human beings would not have evolved. The nail is made up of α-keratin intermediate filaments of approximately 40–70 kDa molecular weight plus a sulfur-rich amorphous interfilament matrix. The keratins of the nail plate belong both to the soft epithelial and the hard hair-nail keratins. The latter were sequenced from their genes and classified into two groups according to their sequence homology: 11 type I or acidic and 9 type II or basic keratins3–5; however, apparently not all of these hair and nail keratins are actually expressed in the human nail. The potential different mechanical roles of these hard keratins in the nail are not yet known. The amorphous matrix or interfibrillar component consists of keratin-associated proteins of a molecular weight of 8–30 kDa.6–8 Over 100 keratin-associated proteins have been identified. Disulfide bonds link them to the 7–10 nm thick intermediate keratin filaments.9

Keratin contains about 3% sulfur, 7% hydrogen, 14% oxygen, 15% nitrogen, 45% carbon,10 and 8%–10% inorganic components, which are mostly polyphosphates with carbonate. Sulfur and nitrogen occur predominantly in amino acids of the nail plate.11,12 The water content is between 10% and 30% depending on ambient humidity.13

1.1 Embryology

Under the influence of transforming growth factor-β (TGF-β), digit formation starts. Activin β A initiates chondrogenesis and activin β B is necessary for the formation of the distal phalanx (Figure 1.1a). Fingers and toes are discernible at week 8 of gestation.14–16 The development of the human nail starts at around the ninth gestational week17,18 as a condensation of epithelial cells on the dorsal aspect of the distal phalanx, the so-called apical ectodermal ridge, which develops into the nail anlage; both are dependent on the bone anlage. The anterior-posterior polarity requires sonic hedgehog signaled protein. Probably the number of progenitor cells of the nail plate at each digit is only about 3 as estimated from lyonization studies of female nails.19 The cell condensation develops into the placode, a plaque of cells that grow proximally and finally form an invagination (Figure 1.1b).20 At 10 weeks, the nail field is seen as a continuous shallow groove that is first ovoidal in shape and extends beyond the tip of the finger.21 Later it becomes flat as in the adult nail with well developed proximal, lateral, and distal nail grooves, the latter being very prominent due to the distal ridge. The nail field grows into a proximal direction with a continuously enlarging area of germinative matrix cells. By week 13, the proximal nail fold overlies part of the matrix and by week 14, a nail plate is seen emerging from under the proximal nail fold. It covers most of the nail field by week 17. The distal ridge has flattened to become the hyponychium. The nail bed stops producing keratohyalin granules and appears parakeratotic. The distal groove gradually disappears and at birth, the nail plate has usually overgrown the tip of the digit.22 The nail continues to grow for the rest of the life.

Figure 1.1 Development of the nail. (a) Time of evolution of the nail and factors necessary to form the nail unit. (b) The nail develops from a cellular densification called placode to an epithelial peg until this develops into a proximally directed invagination to finally form the nail.

In the late embryogenesis when the nail organ resembles that of an adult, the transcription factor B lymphocyte induced maturation protein 1 (Blimp-1), which is expressed in terminally differentiated keratinocytes, appears in the keratogenous cells of the matrix and superficial cells.23

The nail plate is the terminally differentiated structure formed by the germinative matrix. It is composed of keratin, which is physico-chemically identical to hair keratin.24 Its production starts with the embryonal nail anlage, and both soft epithelial as well as hard hair and nail keratins are produced. Keratin 2e is observed in the nail bed as early as from the 10th to the 13th gestational week and then shifts to the nail fold;25 its exact function is not understood. For correct nail formation, the transcription factor FOXN1 is necessary.26

The matrix is the sole structure to form the nail plate14,16,27–29 although this was disputed based on nail plate thickness measurements.30,31 Magnetic resonance imaging has shown that the length of the matrix is correlated with the nail plate thickness. Using an antibody to the proliferation marker Ki-67, the matrix was found to have a proliferation index of 20% compared to 1% in the nail bed.32 However, in nail bed diseases like psoriasis and onychomycosis, 29% nail bed labeling was found. The proliferation index, measured with antibodies to the proliferating cell nuclear antigen and the AgNOR technique, proportionally decreases with age.33 In adults, no hard ker...

Table of contents

• Cover
• Half Title
• Title Page
• Copyright Page
• Contents
• Foreword
• Acknowledgments
• Introduction
• 1. Development, structure, and function of the nail
• 2. Technical aspects: Nail biopsies, handling, processing, sectioning, staining, and reading the slides
• 3. Inflammatory dermatoses affecting the nail
• 4. Infections and infestations affecting the nail
• 5. Nail changes in systemic diseases and drug reactions
• 6. Genodermatoses affecting the nail
• 7. Nail specific conditions
• 8. Epithelial and fibroepithelial tumors
• 9. Fibrous tumors
• 10. Vascular tumors
• 11. Tumors with adipocyte, myxoid, muscular, osseous, and cartilaginous features
• 12. Neurogenic tumors
• 13. Histiocytic lesions
• 14. Hematogenous tumors
• 15. Melanocytic lesions
• 16. Metastases of the digital tip
• Index