The correct diagnosis of the JAMA Dermatology Clinicopathological Correlation of a glomus tumor presenting as longitudinal erythronychia was straightforward – I was fascinated by this comment in the discussion: “The presence of multiple glomus tumors in the digits should raise suspicion for neurofibromatosis type I” (1).
I was unaware of that!
Securing the diagnosis of neurofibromatosis type I (NF1) may be difficult in very young children. The diagnostic criteria for NF1 according to the NIH consensus conference 1988 includes: 1) 6 or more café au lait macules > 0.5 cm in greatest diameter in prepubertal individuals and > 1.5 cm in postpubertal patients; 2) 2 or more neurofibromas of any type or 1 plexiform neurofibroma; 3) Axillary and inguinal freckling; 4) Optic pathway glioma; 5) 2 or more Lisch nodules; 6) A distinctive osseous lesion such as sphenoid wing dysplasia or thinning of the long bone cortex with or without pseudoarthrosis; and 7) A first-degree relative (parent, sibling, or offspring) with NF1 by the above criteria. Recently, attention has been paid to nevi anemici (singular – nevus anemicus, NA) being a possible criterion as such lesions may be observed with increased frequency in NF1. In a study of 100 NF1 patients, 28 had NA, which is above the 5% prevalence of NA in the general population (2). Another clue to the diagnosis of NF1 includes juvenile xanthogranulomas in the context of a child with café au lait macules.
According to Hernádez-Martin and Duat-Rodriguez: “The association of NF1 with glomus tumors was suspected since 1938, but it was not until 2009 when this association was definitively confirmed when NF1 mutations on both alleles was demonstrated in glomus cells. Glomus tumors are benign vascular lesions that originate in the glomus body, a neuro-myo-arterial structure specialized in the regulation of vascular flow. The lesions are usually located in acral regions, particularly below the nails, and they are characterized by paroxysmal pain on applying pressure and with temperature changes. In patients with NF1, these lesions are usually multiple and recurring. They are rare in children, with an estimated prevalence of 5% in adult patients with NF1. Although they can appear in healthy individuals, around 30% of patients with glomus tumors have NF1. From the histological point of view, they are characterized by the presence of fine-walled vessels surrounded by uniform cells with rounded and dark nuclei. Unlike in sporadic cases, these cells do not express neurofibromin in individuals with NF1.” (3)
In a review of 36 patients with glomus tumors and neurofibromatosis in the literature, 79% were female. Tumors were multifocal in 32%, and arose in nonsubungual locations in 38% (4).
In conclusion, glomus tumors, digital or otherwise, point a finger at the diagnosis of NF1. As these lesions are painful, I do not think it is necessary to advise NF1 patients to be on the lookout for them – they’ll let us know. The real importance of this association is to quickly screen for the possibility of NF1 based on the aforementioned criteria. I am amazed at how patients, especially those without a family history of the disorder, may have their NF1 undiagnosed for years.
- Lipner SR, Scher RK. Longitudinal erythronychia of the fingernail. JAMA Dermatology 2016; 152: 1271-2.
- Vaassen P, Rosenbaum T. Nevus anemicus as an additional diagnostic marker of neurofibromatosis type I in childhood. Neuropediatrics 2016; 47: 190-3.
- Hernádez-Martin A, Duat-Rodriguez A. An update on neurofibromatosis type I: Not just café au lait spots and freckling. Part II. Other skin manifestations characteristic of NF1. NF and cancer. Actas Dermosifilogr 2016 Jul-Aug; 107(6):465-73.
- Harrison B, Sammer D. Glomus tumors and neurofibromatosis: A newly recognized association. Plast Reconstr Surg Glob Open 2014; 2e214.