eMedicine Specialties > Dermatology > Pediatric Diseases

Neurofibromatosis: Differential Diagnoses & Workup

Author: Jennifer R Kam, MD, Staff Physician, Southtowns Radiology Associates
Coauthor(s): Thomas N Helm, MD, Clinical Associate Professor, Departments of Dermatology and Pathology, State University of New York at Buffalo; Director, Buffalo Medical Group Dermatopathology Laboratory
Contributor Information and Disclosures

Updated: Oct 23, 2009

Differential Diagnoses

Multiple Endocrine Neoplasia Type 1

Other Problems to Be Considered

Abdominal neurofibromatosis 
Neurofibromatosis type 1
Neurofibromatosis type 1 with Noonan syndrome 
Neurofibromatosis type 2
Segmental neurofibromatosis

Workup

Laboratory Studies

  • Currently, mutation analysis using sophisticated genetic techniques, which are 60-70% accurate in detecting these mutations, is available for type 1 neurofibromatosis and type 2 neurofibromatosis. However, this type of testing is not readily available. Perhaps in coming years, linkage analysis or mutation analysis will be available for the prenatal diagnosis of infants at risk.

Imaging Studies

  • Plain radiography may show growth disturbance (ie, hyperplastic bones, "streaky" appearance to the medullary cavity, skull asymmetry, or sphenoid dysplasia), bowing deformities, or pseudoarthrosis of long bones.6
  • MRI of the brain and the cervical spine may be helpful in patients with type 1 neurofibromatosis, especially if signs or symptoms suggest lesions. MRI is used to assess the soft-tissue extent of disease and to determine involvement of the adjacent bone and spinal canal. Neurofibromas demonstrate low or intermediate signal on T1-weighted pulse sequences and homogeneously bright signal on T2-weighted sequences. Heterogeneity on T2-weighted sequences raises suspicion for malignant transformation.7
  • In patients suspected of having type 2 neurofibromatosis, MRI of the head is recommended in early adolescence. Dedicated MRI of the internal auditory canals is the most sensitive study for the detection of acoustic neuromas, especially small intracanalicular lesions.
  • Optic glioma, a criterion for the diagnosis of type 1 neurofibromatosis, requires imaging for detection. MRI of the orbits is the study of choice. Using MRI to detect optic gliomas in asymptomatic children with type 1 neurofibromatosis is controversial because of the risks associated with the sedation required for an optimal diagnostic MRI. Large optic nerves likely indicate low-grade gliomas in these patients. MRI of the brain may demonstrate scattered foci of high T2 signal in the basal ganglia, thalamus, brain stem, and white matter of up to 50% of children with neurofibromatosis.
  • 18-Fluorodeoxyglucose positron emission tomography (18-FDG PET) may be helpful in determining malignant changes in plexiform neurofibromas in persons with type 1 neurofibromatosis.8
  • Typical CT findings in persons with type 1 neurofibromatosis with chest involvement include small well-defined surface neurofibromas, focal thoracic scoliosis, vertebral scalloping, enlarged neural foramina, and characteristic rib notching from adjacent neurofibromas. Dural ectasia, meningoceles, and dumbbell-shaped masses are related to the presence of neurofibromas or abnormal pressure in and around the spinal canal. Dural ectasia is circumferential dilatation of the dural sac with fluid attenuation. The expanding dura can erode the surrounding osseous structures, widening the spinal canal, thinning the lamina, and disrupting the vertebral elements.

Other Tests

  • A Wood lamp examination may be useful in patients with very pale skin in an effort to better view café au lait macules.
  • Slit-lamp examination is recommended for children older than 6 years to confirm the presence of Lisch nodules.

Histologic Findings

Histologic evaluation of axillary or inguinal freckling reveals increased pigmentation along the basal layer of the epidermis and the presence of macromelanosomes. These macromelanosomes are not usually noted in Albright syndrome. Neurofibromas are characterized by wavy, spindle-shaped nuclei and a loose mucinous stroma.

A low-power view of a neurofibroma reveals spindl...

A low-power view of a neurofibroma reveals spindled cells in the dermis (hematoxylin and eosin).

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A low-power view of a neurofibroma reveals spindl...

A low-power view of a neurofibroma reveals spindled cells in the dermis (hematoxylin and eosin).


Higher-power view of a neurofibroma reveals spind...

Higher-power view of a neurofibroma reveals spindled cells with wavy nuclei embedded in an acidophilic stroma. The mast cells are increased in number.

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Higher-power view of a neurofibroma reveals spind...

Higher-power view of a neurofibroma reveals spindled cells with wavy nuclei embedded in an acidophilic stroma. The mast cells are increased in number.


Sheets of spindled cells are depicted in this mal...

Sheets of spindled cells are depicted in this malignant schwannoma. Malignant degeneration should be expected in a painful or rapidly enlarging tumor in any patient with neurofibromatosis.

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Sheets of spindled cells are depicted in this mal...

Sheets of spindled cells are depicted in this malignant schwannoma. Malignant degeneration should be expected in a painful or rapidly enlarging tumor in any patient with neurofibromatosis.


High-power view of a malignant schwannoma reveals...

High-power view of a malignant schwannoma reveals sheets of hyperchromatic spindle cells with pleomorphic nuclei.

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High-power view of a malignant schwannoma reveals...

High-power view of a malignant schwannoma reveals sheets of hyperchromatic spindle cells with pleomorphic nuclei.


More on Neurofibromatosis

Overview: Neurofibromatosis
Differential Diagnoses & Workup: Neurofibromatosis
Treatment & Medication: Neurofibromatosis
Follow-up: Neurofibromatosis
Multimedia: Neurofibromatosis
References
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References

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  2. National Institutes of Health Consensus Development Conference. Neurofibromatosis. Conference statement. National Institutes of Health Consensus Development Conference. Arch Neurol. May 1988;45(5):575-8. [Medline].

  3. Crawford AH, Schorry EK. Neurofibromatosis update. J Pediatr Orthop. May-Jun 2006;26(3):413-23. [Medline].

  4. Barker D, Wright E, Nguyen K, et al. Gene for von Recklinghausen neurofibromatosis is in the pericentromeric region of chromosome 17. Science. May 29 1987;236(4805):1100-2. [Medline].

  5. Rouleau GA, Wertelecki W, Haines JL, et al. Genetic linkage of bilateral acoustic neurofibromatosis to a DNA marker on chromosome 22. Nature. Sep 17-23 1987;329(6136):246-8. [Medline].

  6. Kormano M. Tumors of Fatty, Muscular, Neural and Osseous Tissue. In: Radiologic Findings in Skin Diseases and Related Conditions. Paris, France: Thieme; 1999:167.

  7. Stoller DW. Bone and Soft Tissue Tumors. In: Magnetic Resonance Imaging in Orthopaedics & Sports Medicine. 2nd ed. Philadelphia, Pa: Lipponcott-Raven; 1997:1327.

  8. Ferner RE, Lucas JD, O'Doherty MJ, et al. Evaluation of (18)fluorodeoxyglucose positron emission tomography ((18)FDG PET) in the detection of malignant peripheral nerve sheath tumours arising from within plexiform neurofibromas in neurofibromatosis 1. J Neurol Neurosurg Psychiatry. Mar 2000;68(3):353-7. [Medline].

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Further Reading

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Keywords

neurofibromatosis, von Recklinghausen's disease, von Recklinghausen disease, neurofibromatosis type 1, peripheral NF, neurofibromatosis type 2, central NF, NF-1, NF-2, segmental NF, café au lait macules, Lisch nodules

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Contributor Information and Disclosures

Author

Jennifer R Kam, MD, Staff Physician, Southtowns Radiology Associates
Disclosure: Nothing to disclose.

Coauthor(s)

Thomas N Helm, MD, Clinical Associate Professor, Departments of Dermatology and Pathology, State University of New York at Buffalo; Director, Buffalo Medical Group Dermatopathology Laboratory
Thomas N Helm, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Society for Dermatologic Surgery, and American Society of Dermatopathology
Disclosure: Nothing to disclose.

Medical Editor

Ponciano D Cruz Jr, MD, Vice-Chair, JB Shelmire Professor, Department of Dermatology, University of Texas Southwestern Medical Center
Ponciano D Cruz Jr, MD is a member of the following medical societies: Texas Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Edward F Chan, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine
Edward F Chan, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

CME Editor

Catherine M Quirk, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania
Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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