An Atlas of Lumps and Bumps, Part 30: Neurofibroma

Neurofibroma

Neurofibromas are benign peripheral nerve sheath tumors composed of an extracellular matrix and a heterogeneous mixture of Schwann cells, perineural cells, fibroblasts, and mast cells.^1-3 Cutaneous neurofibromas (the most common type of neurofibroma) are the most common tumor of the peripheral nerve sheath.⁴ They can develop as a solitary tumor or part of neurofibromatosis type 1 (NF1).⁵ Approximately 90% of neurofibromas occur sporadically while the rest are associated with NF1.^1,5 The sex ratio is approximately equal.⁴ There is no ethnic or racial predilection.⁴ Cutaneous neurofibromas are rarely seen in young children.¹ They often appear during puberty or pregnancy, increase in size and number with age and are found in almost all adults with NF1.¹ Clinically, cutaneous neurofibromas present as asymptomatic, soft (Fig. 1) or elastic, violaceous or skin-colored (Fig. 2), papules, nodules or pedunculated lesions (Fig. 3).¹

Fig. 1. A neurofibroma is shown.

Fig. 2. Cutaneous neurofibromas present as asymptomatic, soft, or elastic.

Fig. 3. Neurofibromas can appear as violaceous or skin-colored papules, nodules, or pedunculated lesions.

The size of individual lesion is usually less than 2 cm in diameter.¹ Cutaneous neurofibromas often invaginate into the skin and exhibit the "button-hole" sign (Fig. 4) when gentle digital pressure is applied to the surface and reappear on the release of pressure (Fig 5).^1,3,4

Fig. 4. Cutaneous neurofibromas can exhibit the "button-hole" sign.

Fig. 5. The size of individual lesion is usually less than 2 cm in diameter.

In contrast, subcutaneous neurofibromas, which are usually firm and painful, are deeply seated in the dermis and, therefore, less circumscribed.¹ Plexiform neurofibromas result from diffuse thickening of nerve trunks and/or roots. They are found in 30 to 50% of individuals with NF1.^2,6-8 Although plexiform neurofibromas are usually congenital, only approximately 44% of these tumors are detected by 5 years of age.^6.9 Plexiform neurofibromas may become highly irregular, thick, and tortuous and feel like "a bag of worms".^2,4,10 Lesions can be skin-colored or, more commonly, hyperpigmented (Fig. 6).⁴

Fig. 6 Lesions can be skin-colored or, more commonly, hyperpigmented.

There may be overlying café-a-lait macules, hypertrichosis and, rarely, leukotrichia.⁷ Plexiform neurofibromas are slow-growing and usually asymptomatic.^6,10 They may be locally invasive and may present with pain, paresthesia, and numbness with involvement of adjacent structures.⁴ Plexiform neurofibromas are associated with an increased risk of bone erosion, spinal cord compression, carpal tunnel syndrome, overgrowth of an extremity, and malignant transformation.^4,11 A diffuse neurofibroma, a rare variant of neurofibroma, most commonly involves the head and neck regions and has an onset mainly in adolescents and young adults.¹²

One of the diagnostic criteria for NF1 is two or more neurofibromas of any type or one plexiform neurofibroma.¹³ To make the diagnosis of NF1, two or more of the seven National Institutes of Health (NIH) diagnostic criteria must be present.¹³ In most children, the diagnosis of NF1 can be confidently made using the NIH diagnostic criteria by 8 years of age.¹⁴ Other diagnostic criteria include six or more café-au-lait spots, 1.5 cm or larger in postpubertal persons and 0.5 cm or larger in prepubertal persons; freckling in the axillary or inguinal regions; optic pathway glioma; two or more Lisch nodules; a distinctive osseous lesion, such as dysplasia of the sphenoid bone or dysplasia or thinning of the long bone cortex (with or without pseudoarthrosis); and a first-degree relative with NF1, according to the preceding criteria.¹³

AFFILIATIONS:
¹Clinical Professor of Pediatrics, the University of Calgary, Calgary, Alberta, Canada
²Pediatric Consultant, the Alberta Children’s Hospital, Calgary, Alberta, Canada
³Dermatologist, Medical Director and Founder, the Toronto Dermatology Centre, Toronto, Ontario, Canada
⁴Associate Clinical Professor of Pediatrics, Dermatology and Skin Sciences, the University of British Columbia, Vancouver, British Columbia, Canada.
⁵Pediatric Dermatologist, the Pediatric Institute, Kuala Lumpur General Hospital, Kuala Lumpur, Malaysia

CITATION:
Leung AKC, Barankin B, Lam JM, Leong KF. An atlas of lumps and bumps, part 30: Neurofibromas. Consultant. 2023;63(8):e8. doi:10.25270/con.2023.08.000005.

CORRESPONDENCE:
Alexander K. C. Leung, MD, #200, 233 16th Ave NW, Calgary, AB T2M 0H5, Canada (aleung@ucalgary.ca)

EDITOR’S NOTE:
This article is part of a series describing and differentiating dermatologic lumps and bumps. To access previously published articles in the series, visit: https://www.consultant360.com/resource-center/atlas-lumps-and-bumps.