106 Lower Extremity Peripheral Nerve Sheath Tumor

Case 106 Lower Extremity Peripheral Nerve Sheath Tumor

Robert L. Tiel

Clinical Presentation

A 15-year-old right-handed boy presented with a lump on the posterior lateral aspect of his right leg, just above the popliteal crease.

Although the lump is usually painless, if knocked or manipulated he experiences a shooting sensation down his leg into the side and top of his foot.

The frequent pains thus generated have forced him to abandon playing soccer.

His neurologic examination is normal.

When the lump is palpated it seems to have the dimensions of a large olive-sized (2 × 2 × 2-cm) mass. It moves from right to left, but not vertically. When lightly percussed, a sharp sensation is elicited, which goes into the dorsum of the right foot.

Other physicians had previously seen the patient. After a magnetic resonance imaging (MRI) scan had been obtained (Fig. 106.1), they advised him to have the lump monitored, to limit his activities, and to “live with” the condition.

Questions

What is your working diagnosis?

Provide a detailed differential diagnosis.

What are the ancillary diagnoses for which he should be evaluated?

What are the clinical findings associated with these diagnoses?

The mother has a friend in whom neurofibromatosis was suspected; she states that this friend was sent to an ophthalmologist for diagnosis. Why?

She asks you if this tumor could be malignant. What is your answer?

The other physicians recommended “living with” the condition. What are this patient’s options? What are the risks to the patient?

Should surgical excision be advised?

Should a needle biopsy be performed first?

Which incision should be used for general exposure?

Describe the steps in removing the tumor.

Should a frozen section be requested?

The tumor is removed; final sections are available for review 3 days later. Representative samples are shown in Figs. 106.2, 106.3, 106.4, and 106.5. What is your diagnosis?
Which immunohistochemical stains are useful in diagnosing peripheral nerve sheath tumors?

Fig. 106.1 T1-weighted contrast-enhanced magnetic resonance image of a schwannoma. Note widening of the nerve.

Fig. 106.2 Low magnification (40×) of tumor with two areas of interest (hematox ylin and eosin [H&E] stained).

Fig. 106.3 High magnification (200×) of area 1 (H&E) stained).

Fig. 106.4 High magnification (200×) of area 2 (H&E stained).

Fig. 106.5 High magnification (200×) of tumor pathology (H&E stained).

Answers

What is your working diagnosis?

The working diagnosis is that of peripheral nerve sheath tumor.

The lump suggests tumor pathology. The MRI (Fig. 106.1) shows a contrast-enhancing intraneural mass widening the nerve.

The lateral mobility is evident, but vertical mobility strongly suggests a lesion within a movable peripheral nerve.

Finally, the paresthesias associated with manipulation point toward primary neural involvement in a specific peripheral nerve distribution (in this case the common peroneal nerve).
Provide a detailed differential diagnosis.
- The differential diagnosis of nerve sheath tumor includes the following¹:
- Benign tumors
  - Schwannoma
    - Cellular schwannoma
    - Plexiform schwannoma
    - Melanotic schwannoma
  - Neurofibroma
    - Diffuse (cutaneous)
    - Localized
    - Plexiform
  - Perineurioma
  - Nerve sheath myxoma
  - Granular cell tumor
  - Ganglioneuroma
- Malignant tumors
  - Malignant peripheral nerve sheath tumors (MPNST)
  - Variants of above
  - Secondary neoplasms
- Tumor-like lesions
  - Reactive lesions
    - Traumatic neuroma
    - Inflammatory pseudotumor
  - Inflammatory and infectious lesions
  - Intraneural ganglion cysts
  - Hyperplastic lesions
    - Localized hypertrophic neuropathy
  - Hamartomas
    - Fibrolipomatous hamartoma
What are the ancillary diagnoses for which he should be evaluated?
- The presence of a peripheral nerve sheath tumor warrants evaluation for neurofibromatosis types 1 (NF-1) and 2 (NF-2) and for schwannomatosis.
What are the clinical findings associated with these diagnoses?
- Diagnostic criteria for NF-12 (two or more of the following):
  - Six or more café-au-lait spots
    - Greater than 1.5 cm or larger in postpubertal individuals
    - Greater than 0.5 cm or larger in prepubertal individuals
  - Two or more neurofibromas of any type
  - One or more plexiform neurofibromas
  - Axillary or groin freckling, an optic pathway glioma, two or more Lisch nodules
  - A first-degree relative with NF-1 (as defined by the preceding criteria)
  - Characteristic osseous lesions, such as sphenoid dysplasia
- Diagnostic criteria for NF-2³
  - The main characteristic of NF-2 is the presence of bilateral vestibular schwannomas – tumors arising from the vestibular branch of the eighth cranial nerve (CN VIII).
  - Other diagnostic features consistent with NF-2
    - A first-degree relative with NF-2
    - A unilateral vestibular schwannoma in a patient younger than age 30 years
  - Or any two of the following:
    - Meningioma
    - Glioma
    - Schwannoma
    - Juvenile posterior subcapsular lenticular opacities
    - Juvenile cortical cataracts
- Diagnostic criteria for schwannomatosis^3,4
  - Individuals should not fulfill the diagnostic criteria for NF-2 or have any of the following:
    - A vestibular schwannomas of CN VIII
    - Constitutional NF-2 mutation
    - First-degree relative with NF-2
  - Definite schwannomatosis
    - Older than 30 years and two or more nonintradermal schwannomas (at least one confirmed by histology)
    - One schwannoma confirmed with histology and a first-degree relative who meets the above requirements.
    - Lack of radiographic evidence of CN VIII tumor on an imaging study performed after age 18 years.
  - Possible schwannomatosis
    - Older than 30 and two or more nonintradermal schwannomas (at least one confirmed by histology)
    - Older than 45 years and no symptoms of CN VIII dysfunction and two or more nonintradermal schwannomas (at least one confirmed by histology)
    - Radiographic evidence of a schwannoma and a first-degree relative who meets the criteria for definite schwannomatosis
The mother has a friend in whom neurofibromatosis was suspected; she states that this friend was sent to an ophthalmologist for diagnosis. Why?
- The ophthalmologists would be conducting a slit-lamp evaluation to identify Lisch nodules or posterior subcapsular lenticular opacities.
- A Lisch nodule is a melanocytic hamartoma of the iris.
  - They appear after age 3.
  - They are present in 90% of NF-1 patients.
  - They are specific for NF-1.
  - They are usually clear yellow to brown.
  - A slit-lamp examination may be necessary to differentiate them from nevi on the iris, where they present as flat or minimally elevated, densely pigmented lesions with blurred margins.
- Juvenile posterior subcapsular lenticular opacities
  - Usually asymptomatic
  - Occur in NF-2
She asks you whether this tumor could be malignant. What is your answer?
- The possibility of malignancy is always present until the permanent histologic sections are evaluated.
- Incidence in the general population is 0.0001%.⁵
- Although the likelihood of malignant transformation is higher in NF-1 patients, only half of malignant nerve sheath tumors arise from NF-1 patients; the other half arise de novo from people without neurofibromatosis.
- From the clinical perspective the tumor size and the presence of a more constant pain suggest the diagnosis of malignancy.
  - Loss of function in the distribution of the nerve suggests malignancy. Although benign nerve sheath tumors may attain a large size, they usually displace the fascicles aside and involve the fascicles minimally.
  - A Tinel sign or mechanical irritability should not be confused with the pain of malignancy, which is more constant and often throbs “at night”.
The other physicians recommended living with the condition. What are this patient’s options? What are the risks to the patient?
- Have the tumor resected
  
  Resection of the tumor causes little morbidity.
  
  The risk of schwannoma together with a normal examination
  
  Will lead to no postoperative motor deficit in 90% of operated cases
  
  Resolves nerve irritability and pain in 75% of operated cases
  
  The risk of solitary neurofibroma without motor deficit
  
  Allows 78% to have no postoperative motor deficit
  
  Allows pain to be resolved or improved in 88% of cases⁶
Should surgical excision be advised?
- Given the relatively low risks of resection combined with the uncertainty of diagnosis, resection represents the single best option unless age or associated medical morbidity precludes surgery.
- The lifetime focal cure rate for schwannomas is 95%.
- The histologic diagnosis is determined and the tumor definitively treated.
Should a needle biopsy be performed first?
- No, needle biopsy should not be advised for most nerve sheath tumors.6
- In contradistinction to other soft tissue tumors, biopsy of nerve sheath tumors increases the morbidity of management.
- The biopsy needle must first blindly traverse the nerve sheath tumor, piercing the outside capsule and displaced fascicles, risking nerve damage to a functioning nerve.
- Intraneural tissue planes that aid in tumor removal might be lost by biopsy-related hemorrhage or scarring.
- An exception may be large painful tumors that show increased activity on positron emission tomography scanning because a targeted biopsy might allow determination of malignancy prior to operation.
Which incision should be used for general exposure?
- An extensile incision should be located over the tumor and along the course of the nerve.
- For the peroneal nerve above the popliteal fossa a “Lazy S” incision would be appropriate (Fig. 106.6).
Describe the steps in removing the tumor.
- The steps in tumor removal proximal to an entrapment site (for the peroneal nerve, the fibular head) include the following⁷:
  - The skin incision is made and the peroneal nerve and tumor are freed from all surrounding tissue.
  - In the location where the peroneal nerve can be entrapped by the fascial tissue at the head of the fibula, the nerve is “released” past the fibular head, well into the peroneus longus muscle.
  - Nerve action potential (NAP) recording (if available) is performed along the entire nerve. A NAP should be easily recordable (Fig. 106.7).
  - Attention is turned to the tumor once the nerve and its branches have been completely neurolysed.
  - A fascicle-free area of the is tumor is determined
    - By inspection (Fig. 106.8)
    - By cautious nerve stimulation (Fig. 106.9)
  - Attempting to discover the dissection plane of the tumor, the surgeon makes an incision into the tumor and its primary fascicle and gentle dissection is used to develop this plane between tumor and fascicles (Fig. 106.10).
  - The tumor and its primary entry and exit fascicle are dissected out (Fig. 106.11).
  - A NAP recording is done of the entering fascicle (Fig. 106.12). A flat trace is elicited, thereby insuring that the fascicle from which the tumor arose is nonfunctioning or solely sensory.
  - The tumor is removed well into the originating and exiting fascicle to ensure complete tumor excision (Fig. 106.13).
  - A whole nerve NAP is recorded after resection to insure a functioning nerve.
  - The meticulous hemostasis of the tumor bed is achieved prior to closure.
  - The incision is closed.
Should a frozen section be requested?
- A frozen section is usually unnecessary if the tumor dissection proceeds easily.
- If dissection planes are not found:
  - The nerve adheres to soft tissue structures, and a frozen section may be warranted to evaluate the suspected tissue for malignancy or alternative diagnosis.
- If the nerve seems unusually hard or fibrotic:
  - The diagnosis of peripheral nerve pseudotumor is now being considered, and a representative sample is usually warranted to determine whether dissection should proceed.
The tumor is removed; final sections are available for review 3 days later. Representative samples are shown in Figs. 106.2, 106.3, 106.4, and 106.5. What is your diagnosis?
- The diagnosis is benign schwannoma.⁸
- Antoni A pattern (Fig. 106.4)
  - Compact elongated cells with tapered spindle-shaped nuclei
  - Variable chromasia
  - Ample pink cytoplasm
- Antoni B pat tern (Fig. 106.3)
  - Loose texture “cobweb like meshwork”
  - Multipolar processes
  - Round and oval nuclei
  - Occasional microcysts
- Verocay bodies (Fig. 106.5)
  - Nuclear clusters in a palisading arrangement
  - Double rows of nuclei separated by aligned eosinophilic cell processes (Fig. 106.14)
Which immunohistochemical stains are useful in diagnosing peripheral nerve sheath tumors?
- The immunohistologic stains useful in identifying peripheral nerve tumors are summarized in Table 106.1.^9–14
- They include
  - S-100 (so called because of its solubility in 100% saturated ammonium sulfate)
  - CD-34 (cluster of differentiation molecule)
  - EMA (epithelial membrane antigen)
  - Nestin