Hair Follicle Bulb Region: A Potential Nidus for the Formation of Osteoma Cutis
Osteoma cutis (OC) is an extraneous ossification of the skin. Heterotopic ossification can be either primary or secondary, depending on the presence of a preexisting lesion. Little is known about the morphogenesis of OC. During routine dermatopathologic examinations for unrelated conditions, small osteocalcific micronodules were noted in close approximation of the lower aspect of hair follicles. In most instances, osteocalcific lesions were found near a hair bulb and exceptionally within the hair bulb. Small osteocalcific nodules incidentally noted in close proximity to the lower aspect of the hair bulb may be a precursor to OC. They may form near or within the hair bulb, possibly under the influence of bone morphogenetic proteins (BMPs).
Practice Points
- Understanding the pathogenesis of osteoma cutis (OC) can help physicians devise management of these disfiguring lesions.
- Small osteocalcific nodules in close proximity to the lower aspect of the hair bulb may be an important precursor to OC.
Some disturbance or imbalance in hair bulb homeostasis leads to overactivity of BMP signaling, causing osteoinduction in the hair bulb region and formation of PONs. The cause of the disturbance could be a traumatic or inflammatory injury to the hair follicle, as in the case of the secondary form of MMOC in association with chronic acne. In the primary form of osteoma cutis, the trigger could be more subtle or subclinical.
Trauma and inflammation are the main initiating factors involved in ossification in patients with fibrodysplasia ossificans progressiva due to ectopic activity of BMPs.9 The primary form of ossification appears to be similar to the mechanism by which intramembranous ossification is laid down (ie, by differentiation of mesenchymal cells into osteoblasts). In the proposed scenario, the cells of FDP, under the influence of BMPs, differentiate into osteoblasts and lay down osteoid, forming a limited-capacity “ossification center” or pilar osteocalcific nodule.
It is difficult to know the exact relationship of PONs or OC to the hair bulb due to the 2-dimensional nature of histologic sections. However, considering the finding of a rare case of osteoid forming within the bulb and in another the presence of melanin within the osteocalcific nodule, it is likely that these lesions are formed within the hair bulb or in situations in which the conditions replicate the biochemical characteristics of the hair bulb (eg, pilomatricoma).
,The formation of PONs might act as a terminal phase in the hair cycle that is rarely induced to provide an exit for damaged hair follicles from cyclical perpetuity. An unspecified event or injury might render a hair follicle unable to continue its cyclical growth and cause BMPs to induce premature calcification in or around the hair bulb, which would probably be the only known quasiphysiological mechanism for a damaged hair follicle to exit the hair cycle.
Another interesting aspect of osteoma formation in human skin is the similarity to osteoderms or the integumentary skeleton of vertebrates.14 Early in evolution, the dermal skeleton was the predominant skeletal system in some lineages. Phylogenetically, osteoderms are not uniformly distributed, and show a latent ability to manifest in some groups or lay dormant or disappear in others. The occurrence of primary osteomas in the human integument might be a vestigial manifestation of deep homology,15 a latent ability to form structures that have been lost. The embryologic formation of osteoderms in the dermis of vertebrates is thought to depend on the interaction or cross-talk between ectomesenchymal cells of neural crest origin and cells of the stratum basalis of epidermis, which is somewhat similar to the formation of the hair follicles.
Conclusion
Under certain conditions, the bulb region of a hair follicle might provide a nidus for the formation of OC. The hair bulb region contains both the precursor cellular element (mesenchymal cells of FDP) and the trigger cytokine (BMP) for the induction of osteogenic metaplasia.
