Derm Dx: Cafe au lait macules, soft fleshy nodules and skin-colored, bag-like protrusions - Clinical Advisor

Derm Dx: Cafe au lait macules, soft fleshy nodules and skin-colored, bag-like protrusions

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  • Neurofibromatosis Type 1_1211_Derm Dx_1

  • Neurofibromatosis Type 1_1211_DermDx_B

  • Neurofibromatosis Type 1_1211DermDxC

A 37-year-old pregnant Hispanic woman presents for her 34-week obstetric exam. She states she has had skin problems her whole life. She had multiple café au lait macules (CALMs) when she was born and has subsequently developed multiple skin findings since she was a teenager.

On exam, the patient is well nourished, well developed and in no distress. Her skin exam is significant for scattered, tan CALMs; multiple soft, skin-colored polyps on her trunk and areolae; and several fleshy, bag-like protrusions on her trunk. Additional pertinent findings include freckles in her axillae bilaterally.

Neither of her parents had any skin abnormalities; however one of her two sons was born with six CALMs. The patient complains that during her pregnancy she has developed increased numbers of the polyps. What’s your diagnosis?

Submit your answer, and then read the full explanation below. If you like this activity or have a suggestion, tell us about it in the comment box at the bottom of the page.

Neurofibromatosis (NF) type 1 is an autosomal dominant disorder that affects approximately one in 3,000 individuals. NF1 is due to a gene mutation in the NF1 gene located on the long-arm of chromosome 17, which encodes neurofibromin, a tumor suppressor...

Submit your diagnosis to see full explanation.

Neurofibromatosis (NF) type 1 is an autosomal dominant disorder that affects approximately one in 3,000 individuals. NF1 is due to a gene mutation in the NF1 gene located on the long-arm of chromosome 17, which encodes neurofibromin, a tumor suppressor protein. 

Penetrance is approximately 100%, meaning that if a patient inherits the defective gene, he or she has a 100% chance of developing NF1 manifestations. New germ-line mutations occur in 50% of cases; therefore, patients may not have a prior family history of the disease.

Cutaneous manifestations of NF1 include multiple café au lait macules (CALMs), neurofibromas and freckles in the axillae and groin. CALMs are well-demarcated tan or dark brown patches and macules that range from several millimeters to several centimeters. CALMs are present in greater than 90% of affected individuals and are the only cutaneous manifestation that can be present at birth; however, sometimes CALMs only appear during the first year of life. 

The diagnostic criteria for NF1 require six or more CALMs larger than 0.5 cm prior to puberty and larger than 1.5 cm after. 

There are several variants of neurofibromas. These are:

Cutaneous neurofibromas (CNFs) are the most common and are polypoid, soft to rubbery, flesh-colored nodules with a wide range of sizes that invaginate easily into the skin when pressed (the “buttonhole” sign).  CNFs are present in 60 to 90% of affected individuals. CNFs can develop by age 4 years, but most typically appear after puberty and can proliferate during pregnancy. 

Plexiform neurofibromas (PNFs) are present in 25% of affected individuals, occur deeper in the skin and are less well circumscribed than CNFs. PNFs can track along nerves and cause large and disfiguring subcutaneous masses. PNFs are congenital, but do not become apparent until age 4 to 5 years. PNFs have a 3% to 15% chance of progressing to aggressive malignant peripheral nerve sheath tumor.  In this patient, the soft, bag-like mass on the trunk is likely a PNF.

Axillary and/or groin freckling, also called Crowe’s Sign, usually appears around age 4 to 6 years and is present in approximately 80% of affected individuals. 

    In addition to cutaneous manifestations, ocular, neurologic, skeletal and cardiovascular symptoms can also occur with NF1. Ocular manifestations include benign hamartomas of the iris, called “Lisch nodules,” which are present in 90% of patients older than 20 years. Optic gliomas account for about 15% of neurologic manifestations, whereas 5% are non-optic CNS tumors. Among patient with neurologic involvement, 30% to 50% have learning disabilities and 5% have seizures. 

    Macrocephaly (20%-50%) and scoliosis (5%-10%) are the most common skeletal abnormalities; less common skeletal deformities include pseudarthrosis of the long bones and sphenoid wing dysplasia. 

    The most common cardiovascular abnormality is hypertension, which is present in approximately 30% of NF1 patients. NF1 patients have an increased risk for renal artery stenosis (2%) and pheochromocytoma (1%).                                 

    Diagnosis

    NF1 diagnosis requires patients have two or more of the following criteria:

    • Six or more café-au-lait macules
    • Two or more cutaneous neurofibromas or one plexiform neurofibroma
    • Axillary or inguinal freckles
    • Optic nerve gliomas
    • Two or more Lisch nodules
    • Sphenoid wing dysplasia
    • Long bone cortex thinning
    • First-degree relative with NF1

    Treatment

    There is no cure for NF1, so treatment focuses on establishing a diagnosis and managing complications. This frequently involves a multidisciplinary or team approach involving dermatologists; neurologists; ophthalmologists; cardiologists; learning disability specialist; physical therapists; plastic and orthopedic surgeons; physical and occupational therapists; and other specialists as required. Genetic counseling is crucial since children born to an NF1 parent have a 50% chance of acquiring the disorder.    

    Adam Rees, MD, is a graduate of the University of California Los Angeles School of Medicine and a resident in the Department of Dermatology at Baylor College of Medicine in Houston.

    References

    1. Bolognia J, Jorizzo JL, Rapini RP. Dermatology. 2nd Ed. Elsevier; 2008: Chapter 60.

     

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