neurofibromatosis type 1 - mcgovern medical school...• neurofibromatosis type 1 is an autosomal...

Neurofibromatosis Type 1

Megan Mont

9/18/2019

Diagnostic Radiology: RAD 4001

Nicholas M. Beckmann, MD

McGovern Medical School

Clinical History

15-year-old male initially seeing PCP for left leg pain while playing soccer. Patient has long standing history of a skin nodule along the posterior left thigh. No other pertinent medical history. Mother has history of neurofibromatosis type 1.


femur femur

tibia tibiafibula fibula

patella

Lytic lesion with surrounding

sclerosis


T2 T2

femur femur

tibia tibia

Quadriceps tendon

Patellar tendon

patella

PCL

meniscus

Biceps femoris

Popliteus

Soleus

Gastrocnemius

Vastus intermedius

Vastus medialis

Vastus lateralis

Sartorius

Extensor digitorum longus

Mixed high and low T2

signal


PD T1 post-contrast

Biceps femoris (long head)

Vastus medialis

Vastus lateralis

Semimembranosus

Gracilis

Sartorius

Femur (with lesion)

Popliteal artery and vein

Tibial nerve(with lesion)

Common peroneal nerve(with lesion)

Enhancing skin nodule


PD T1 post-contrast

Biceps femoris (long head)

Semitendinosus

Semimembranosus

Sartorius

Gracilis

Adductor longus

Adductor magnus

Biceps femoris (short head)

Rectus femoris

Vastus lateralis

Vastus intermedius

Vastus medialisFemoral artery and vein

Sciatic nerve

Femur

Enhancing intermuscular

nodule


PD

Tibialis anterior

Fibula

Tibia

Extensor hallucis longus

Extensor digitorum longus

Tibialis anterior artery and vein

Tibialis posterior

Peroneal artery and veinFlexor hallucis longus

Peroneus longus et brevis

Tibial nerve(with lesion)

Sural nerve(with lesion)


Key Imaging Findings

• Lytic lesion in the distal femur metadiaphysis• X-ray: septations, sclerotic rim

• MRI: Lobulated margins and mixed high and very low T2 signal

• Skin nodule in the posterior distal thigh • MRI: high signal on proton density images with diffuse avid enhancement

• Hamstring, tibial nerve, and peroneal nerve nodules • MRI: increased PD signal and avid enhancement


Differential Diagnosis

• Lytic lesion with surrounding sclerosis:• Non-ossifying fibroma (a.k.a. fibroxanthoma)

• Osteoid Osteoma / Osteoblastoma

• Brodie abscess (subacute pyogenic osteomyelitis)

• Enhancing lesions:• Plexiform neurofibroma

• Diffuse cutaneous neurofibroma

• Schwannoma


Discussion• Most likely diagnosis: Neurofibromatosis Type 1 with non-ossifying

fibroma and plexiform neurofibroma (1)• “Von Recklinghousen disease”• Mutation in or deletion of NF1 gene• Autosomal dominant

• NF1 encodes neurofibromin and negatively regulates RAS-MAPK signaling, responsible for cell cycle regulation (2)

• Mutations in NF1 can lead to a variety of tumors

• NIH diagnostic criteria, must include at least 2 of the following: (1)• café-au-lait macules, axillary/inguinal freckling, optic glioma, Lisch nodules,

neurofibromas, distinctive osseous lesion, first degree relative with NF1


Discussion

• Jaffe-Campanacci Syndrome (3)• Characterized by features of NF1 and multiple non-ossifying fibromas

• Rare syndrome: 0.4 -0.5% of patients with multiple NOFs

• Genetic profile not yet determined, could be a subtype of NF1

• Over 50% risk of pathologic fracture

• Treatment (3)• Curettage and bone grafting of NOFs to prevent fracture

• Consider osseous screening for all newly diagnosed NF1 patients


Final Diagnosis: NF1

• Curettage of the femur lesion was performed with a pathologic diagnosis of non-ossifying fibroma

• The large nodule at the skin surface was also resected with pathologic diagnosis of plexiform neurofibroma.

• The nodules throughout the tibial and peroneal nerves are consistent with additional neurofibromas, as is the nodule in the hamstring muscles.

• Given mother’s history of NF1 and plexiform neurofibroma, the diagnosis of NF1 can be made in this patient.


Treatment

• Curettage and bone grafting of the femur lesion was performed

• After curettage, the resultant defect usually fills and heals, even without grafting (4)

• Lesions > 70 cm are more likely to suffer complications including postoperative fracture and insufficient healing

• Surgical intervention can be considered to prevent both fracture and deformity (4)


ACR appropriateness Criteria• Chronic knee pain (5)


ACR appropriateness Criteria• Primary Bone Tumors (5)

• Within guidelines!


Imaging Cost Calculation

• Average study cost in Houston, TX without insurance (6):• X-ray knee: $73 ($60-$140)

• MRI Lower Extremity: $543 ($420 - $1100)

• TOTAL: $616• Low estimate: $480

• High estimate: $1240


Take Home Points

• Neurofibromatosis Type 1 is an autosomal dominant disorder that is rarely associated with non-ossifying fibromas.

• NOFs appear as lytic lesions with surrounding sclerosis that have a mix of high and very low T2 signal.

• Consider osseous screening for patients with newly diagnosed Neurofibromatosis Type 1 to avoid pathologic fractures secondary to non-ossifying fibromas.


References1. Ferner RE, Huson SM, Thomas N, et al. Guidelines for the diagnosis and management

of individuals with neurofibromatosis 1. J Med Genet. 2007;44(2):81–88. doi:10.1136/jmg.2006.045906

2. Bovée JV, Hogendoorn PC. Non-ossifying fibroma: A RAS-MAPK driven benign bone neoplasm. J Pathol. 2019;248(2):127–130. doi:10.1002/path.5259

3. Cherix, S., Bildé, Y., Becce, F., Letovanec, I., Rüdiger, H., & Cherix, S. (2014). Multiple non-ossifying fibromas as a cause of pathological femoral fracture in Jaffe-Campanaccisyndrome. BMC Musculoskeletal Disorders, 15(1), 218–218. https://doi.org/10.1186/1471-2474-15-218

4. Kundu ZS, Gupta V, Sangwan SS, Rana P. Curettage of benign bone tumors and tumor like lesions: A retrospective analysis. Indian J Orthop. 2013;47(3):295–301. doi:10.4103/0019-5413.111507

5. https://acsearch.acr.org/list

6. Newchoicehealth.com

https://doi.org/10.1186/1471-2474-15-218

https://acsearch.acr.org/list

Questions?

neurofibromatosis type 1 - mcgovern medical school...• neurofibromatosis type 1 is an autosomal...

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