Multiple miliary osteoma cutis is a distinct disease entity: four case reports and review of the literature.
Myllyla, R. M. 1; Haapasaari, K. M. 2; Palatsi, R. 3; Germain-Lee, E. L. 4,5; Hagg, P. M. 3; Ignatius, J. 6,7; Tuukkanen, J. 1
[Article]
British Journal of Dermatology.
164(3):544-552, March 2011.
(Format: HTML, PDF)
Background: Multiple miliary osteoma cutis (MMOC) is a rare nodular skin disease characterized by tiny bone nodules which usually form on the facial skin, typically in middle age. The aetiology of this phenomenon is poorly understood.
Objectives: To search for possible bone formation progenitors and to look for a possible association with mutations in the GNAS gene (encoding the G-protein [alpha]-stimulatory subunit) and related hormonal parameters in patients with MMOC. We also reviewed the literature and discuss the aetiology and pathogenesis of adult-onset primary osteomas.
Methods: We report four cases of MMOC. Histological samples were analysed for bone morphogenetic protein (BMP)-2, BMP-4 and oestrogen receptor-[alpha] known to be involved in bone formation. Endocrinological laboratory investigations and hand X-rays were performed to exclude a systemic disease. The GNAS gene was sequenced from DNA extracted from peripheral blood in all four patients and from a skin sample in one patient to exclude somatic mutations.
Results: Histological analyses revealed intramembranous cutaneous bone formation resembling the findings seen in GNAS gene-based osteoma cutis disorders. However, we did not find any germline or somatic GNAS gene mutations in our patients and all laboratory investigations gave normal results. BMP-2 and -4 were expressed normally in MMOC samples, but oestrogen receptor-[alpha] was not expressed. Altogether 47 MMOC cases, 41 female and six male, have been published between 1928 and 2009. Of these cases, 55% had a history of pre-existing acne and only 15% had extrafacial osteomas.
Conclusions: MMOC is a rare but distinct disease entity of unknown aetiology. Histologically, the tiny nodular osteomas show intramembranous superficial ossification but the aetiology appears to be different from GNAS-related disorders. The osteomas seem to increase slowly in number after appearing in middle age.
(C) 2011 British Association of Dermatologists