Phenotypic Diversity as a Feature of Follicular Cyclic Phenomena:
Hair Cycles and Histopathology: The morphology of hair follicles is multifaceted; hair cycles, in periods of active growth, are expressed in varied and complicated, structural and cellular patterns. Basically, a follicle has a constant component (above the isthmus) and an inconstant component (below the isthmus). The constant component maintains a relatively uniform structure, irrespective of the developmental stage of the inconstant component. In a resting stage, follicular epithelium is composed of relatively nondescript squamous cells; there are few distinguishing cytologic features. The infundibulum (that portion of the excretory duct of a follicle that is lined by epithelium whose keratinized product is mediated at the level of cells containing keratohyaline granules) is certainly constant throughout the cycles of hair follicles. As an appendage just above the isthmus, sebaceous glands may persist as a constant feature, and sebaceous cells are cytologically distinctive. In the sebaceous excretory portions, the squamous epithelium, bordering the ostia of sebaceous glands, finds distinctiveness in the character of the keratinizing product; the viable surface cells are overlaid by a band of condensed, brightly eosinophilic keratinized debris. This property finds expression in steatocystomas; for examples of steatocystomas in which sebaceous gland lobules are not represented in the plane of the histologic section, an identification of this pattern of keratinization provides a significant aid in diagnosis. Beyond the thin condensed band of keratinized debris, keratin in the lumen of the excretory duct of the sebaceous glands is loosely laminated. This quality also finds expression in the character of the keratinized debris in the lumen of a steatocystoma.
Follicular epithelium, at a depth beyond that of both the infundibulum and the sebaceous duct epithelium, must be considered to be of a different order than that of the constant portion of a hair follicle. This is certainly true of a population of non-descript cells of the resting portion of a hair follicle; cells within this component, although cytologically most non-descript, are said to retain the genetic potentials that are required to repeat the exposition of distinctive cell types as manifested in anagen phases, including trichogenic cells of the hair bulb, non-trichogenic cells of the hair bulb (i.e., progenitors of the inner root sheath with its three layers), the inner root sheath, and the outer root sheath (a population that probably is independent of the germinative cells of the hair bulb). It is a common feature of catagen patterns for a bulge of squamous cells, manifesting the cythopathic features of catagen phenomena, to be caught in an upward migration toward the domain of the constant portion. In addition, a tail of squamous cells marks the trail of the upward migration. At its extremity, the epithelial stub usually manifests a prominent row of basal cells; it seems more likely that the genetic capability for a resumption of anagen phenomena would reside in this layer of basal cells.
Most of the pictorials for Chapters 8-12 are representative of changes in follicles of the scalp adjacent to - not part of - a nevus sebaceus. They are representative of a variety of follicular changes within the confines of a single surgical specimen. In the descriptions accompanying the Pictorials of tier 3 (Ch 9-13a), a pattern (F3Ch12P3) has been characterized as having the contour of an invasive wedge; the wedge consists of the inner root sheath (as defined herein, a tri-laminar epithelial sleeve, including Henle’s layer, Huxley’s layer, and the “cuticle” of the inner root sheath), and the poorly developed hair shaft with the cellular precursor of its cuticle.
Herein, as a basic premise, the cuticle of the inner root sheath, and Henle’s layer, are depicted as expressions of terminal differentiation of cells of Huxley’s layer (a layer of cells rich in trichohyalin). The terminally differentiating cells form a file on both sides of the tube-shaped collection of cells of Huxley’s layer. Maturation of the inner root sheath at its superficial extremity finds expression in the formation of angulated, keratinized, dead cells; they retain the basic shape of their viable progenitors; in the process of keratinization -as an intermediate stage - the keratinizing cells contain pyknotic nuclei (a variation of parakeratosis). The cells of Henle’s layer, on the outer surface of Huxley’s layer, are cytologically different from the row of cells on the inner surface of Huxley’s layer. On the other hand, the destiny of the two cell layers seem to be basically the same. At a level that is variable, even for individual cells in each row, cells show pyknosis and then loss of nuclei; the dying cells keratinize but do not contract to form flattened lamellae; they cling to the viable cells of Huxley’s layer. They lose their identity by merging with the cone of keratinizing cells at the superficial extremity of Huxley’s layer. It seems to me that the inner root sheath, above the level of the progenitor cells of the bulb, is composed of 3 layers, and that its outer and inner layers are distinctive keratinizing cells.
At an early stage (F3Ch12P3), before a hair shaft is well-formed, the walls of the inner root sheath converge, from the deep to the superficial level, as the developing bulb moves away from its site of origin. In the non-trichogenic portions of the hair bulb (the peripheral expanse in the pattern of an inverted cup)), two lamina are recognizable; one lamina is composed of dark cells (closest to the trichogenic portion), and the other is composed of pale cells (the most peripheral layer). The dark progenitors give rise to the file of precursor-cells along the surface of the developing hair shaft. The pale progenitors give rise both to the file of cells along the inner surface of Huxley’s layer (these cells eventually keratinize to form the cuticle along the inner surface of the inner root sheath), and Huxley’s layer (as presented herein, they also give rise to the cells of Henle’s layer). At the superficial level, where the outer sheath loses its distinctive cytologic features, distinctive, keratinized, dead cells (a product of the keratinization of the “cell layers” of the inner root sheath) remain attached to the tip of the inner root sheath to form a cap. The cap represents a contribution from Henle’s layer, the “cuticle” of the inner sheath, and a direct contribution of Huxley’s layer. At this extremity, near the junction with the isthmus, the aggregated, distinctive, dead cells are clustered to form the cap. In Ch12P3, at the superficial extremity of the complex of Henle’s layer, Huxley’s layer, and the “cuticle of the inner root sheath,” the converging walls come together to form the conical cap (in longitudinal section). The apex of the conical cap is contributed by the terminally differentiating cells of Huxley’s layer, and by the confluence of Henle’s layer and the “cuticle” of the inner root sheath (F1-5Ch10). A layer of keratin in which the contours of each terminally differentiated keratinocyte is preserved, forms the superior extremity of what essentially is an epithelial tube. In cross section, this keratinized product remains attached to the outer root sheath; it forms a multi-layered lining of terminally differentiated (dead) cells that is separate and distinct from the hair shaft.
As one proposal, the interface between the outer root sheath and the inner root sheath is fluid. The upward movement of the inner root sheath (epithelial tube), in its longitudinal growth, ceases at about the level where the population of glycogenated cells of the outer root sheath ends. Once the shaft has separated from the inner root sheath, the outer root sheath, with the layer of dead keratinized cells from the inner root sheath, forms the walls of a channel (the isthmus?); the separation of the hair from the inner root sheath results in the formation of a lumen. This lumen, being a portion of the inconstant portion of the follicle soon encounters, and then becomes, continuous with the lumen of the constant portion of a hair follicle. At this point, the hair and its cuticle leave the inconstant portion of the follicle behind; they independently traverse the lumen of the constant portion of the follicle; they exit to the surface at the follicular ostium.
The observation that the confluent “cuticles” remain attached to the outer root sheath beyond the level at which the cuticle of the hair shaft separates from the inner root sheath would appear to be against the interpretation that the interface between in inner, and the outer root sheaths is fluid. As an explanation for the patterns in Ch12P3, the trichogenic cells of the hair bulb might grow at a rate that is independent of the cells of the inner root sheath; in this proposal, a potential, but fluid, interface would be between the precursors of the hair cuticle and the cuticle, on the one hand, and the “cuticle” of the inner root sheath, on the other. Dependency with synchronous growth, then might be required between “Henle’s layer” and the outer root sheath. I would favor the notion that on both surfaces of the inner root sheath (to include all three of its layers) the interface is fluid.
The outer root sheath is composed of glycogen-rich, vacuolated cells. Perhaps these cells have sustentacular functions in support of cells of the inner root sheath, and in some manner delay keratinization of the granular cells of Huxley’s layer. Perhaps, the availability of an energy source, or a fluid-rich environment provides an explanation for the long life of the cells of Huxley’s layer. In addition, the vacuolated cells may exert pressure on the developing inner layers and, in the act, help to maintain contact between the layers.
It appears that an epithelial wedge, of hair bulb origin, is formed, early on, in the development of the follicle (F3Ch13). The apex of the wedge thus becomes the anchoring point as the bulb develops, and moves, along its fibrous tract, deeper into the dermis, and even into the fat; the outer root sheath follows along the surface of the inner root sheath.
The bulb over the papilla is composed of germinative cells, and pigmented melanocytes; this portion represents the trichogenic core of the bulb. Prominent dendrites extend from the melanocytes of the basal layer of this core into the epithelial interstitium to percolate among the germinative cells. This is surely evidence of a function other than the mere pigmentation of hair. In this arrangement, the epithelial interstitial spaces are widened. Nutrients would be readily accessible. Perhaps this arrangement facilitates the ability of the germinative cells to independently grow at a rate that is disparate to that of cells in the root sheaths. The hair papilla is a protrusion of distinctive connective tissue; it has myxoid qualities. In an actively growing follicle, the interface between the papilla and the neighboring hair matrix often is ill-defined. Perhaps, the papilla is neuromesenchyme; as such, it could be a direct contribution from a special nerve. The condensation of fibrous tissue that separates the papilla from common mesenchyme somewhat resembles a portion of a perineurium. In this approach, the melanocytes of the bulb would interact with what might be characterized as genetically related mesenchyme.
In chapter 9, images of the lower portion of an anagen follicle are presented. The images include those of a hair bulb, and those of the lower portion of an anagen follicle (above the level of the bulb).
In chapter 10, the images include those of the inconstant portion of an anagen follicle, excluding those of a hair bulb.
In chapter 11, the images include anagen and catagen patterns with some emphasis on the influence of a catagen phase on the histologic character of the keratinized material that is produced by the involuting bulb. A pattern of perifollicular fibrosis that is associated with atrophy of the inconstant portion of a follicle is illustrated.(F6Ch11).
In chapter 12, the follicular patterns, of interest, include those of catagen and resting phases.
In chapter 13, follicular components are illustrated and discussed.
In chapter 13a, catagen patterns are illustrated and discussed. In addition, the form and function of the epithelial units of squamous epithelium are discussed (F4-6Ch13a).
In chapter 14a, additional structural components of follicles are discussed, along with additional illustrations of the manner in which catagen phenomena influence structure.