Malignant peripheral nerve sheath tumours M E Elsebaey.pdf

detailed micro-anatomy and pathology and surgical options and approaches for management of the peripheral nerve sheath tumors especially the malignant types.

1. Malignant Peripheral Nerve Sheath Tumours,
MPNST assessment and management
Mohamed Elsayed Elsebaey, MD
Lecturer of Neurosurgery
General organization of Teaching Hospitals and Institutes
GOTHI
Benha Teaching Hospital
2023
1

2. 2

3. Clinical
•Pain: dull aching, annoying or electrical like
sensation.
•Palpable swelling.
•Tenderness in certain region.
•Marked swelling (seen by patient and others).
•Limitation of movement.
•Motor deficit
•Vascular manifestations like, popliteal tumours
•Accidental
3

4. •Double basement membrane is the
characteristic of schwann cells.
•This basement membrane differs schwann cell
from fibroblast.

4

5. PNS tumours
•DD:
Shwannomas
Lipofibromatous
hamartomas
Granular cell tumours
Intraneural hemangiomas
Perineuromas
Intraneural ganglion cysts
Lipomas
Desmoid tumours
•Malignant transformation
oRecurrence
oMorbidity
oMortality

5

6. 6

7. •Nerve fibers are not found within the
schwannoma itself.
•The schwannoma itself tends to discplace the
fascicles of the nerve outwardly, causing the
nerves appear stretched over the tumour.
•Gross examination,
Encapsulated (solid or cystic)
•Histological:
Antoni A (much cellular) , Antoni B (less cellular)
7

8. •Both may present within the same tumoural
mass.
•Secondary changes includes:
1.hyalinization
2.cysts
3.Micro-hemorrhage
4.mineralization
8

9. Schwannoma
Cellular schwannoma
•Rare variant of benign
schwannoma
•Showing hypercellularity and
nuclear atypia
•No more than 6 mitotic figures
per 40 high-powered fields are
noted
•No areas of frank necrosis
•Characterized by central cystic
formation
•Prognosis is equal to other
benign schanommas
Malignant schwannoma
•Malignant varient
•Necrosis, hemorrhage,
mineralization
•Many mitotic figures

9

10. Radiologic assessment
Magnetic Resonance Neurography (MRN)
relation to surrounding structures
Extent of involvement


10

11. Radiology DD
neurofibromas
•Centrally located within the nerve sheath
•Fascicles are runnig through the tumour
•Expanding the tumour in fusiform fashion
•Commonly show a target sign, peripheral
hyperintense rimand a central hypointense
regionin T2 MRI
•Hypoechoic on ultrasound
•Their appearance mimic the ganglion cyst.
•Several fascicles involved in the tumoural
mass and they are functioning fascicles so,
intra-fascicular dissection is a must with
preservation of the fascicles.
•If fasciles can not be idnetified except the
entry and exit fascile stumps, nerve graft
cables are used for interpositional grafts or
conduits.
•Permanent neurologic dysfunction is more
common following tumours in proximal arm,
immobile, painful and > 4 cm in size
schwannomas
•Eccentric located
•More encapsulated
•Fascicles run at periphery
•show diffuse contrast
enhansed on T1 MRI
•Single fascicle enters and
exits the tumoural mass and
it is non-functioning so, you
can resect mass and cut it.
11

12. Benign PNST
•Target sign

Malignant PNST
•Gallium uptake
•Infiltrated margins
12

13. Surgical intervention
•Microscopic resection
•Successed in preserving nerve function as follows
•90% of schwannomas
•80% of neurofibromas
•66% of neurofibromas in those with NF1
•Intracapsular enucleation
•Patients whose previous biopsy or surgery have poorer
outcomes
•Recurrence are rare with complete resection
•Neural elements should be identified and protected and
mobilized proximally and distally to the tumour itself

13

14. •Longitudinal epineurotomy should be done in
bare area of the tumour to be devoided of
fascicular structures.
•Intraop. Electrophysiology or nerve
stimulation can help identify safe zones to
determine functioning and non-functioning
fascicles and help in resection
14

15. Malignant Peripheral Nerve Sheath
tumours (MPNST)
•Constitute heterogenous of malignant tumours that
arise from peripheral nerve branches or their sheaths
and derived from schwann cells or pluripotent cells of
neural crest origin.
•MPNST represents 5 to 10% of soft tissue sarcomas
•Malignant neoplasms that generally arise in presence
of neurofibroma or schwannoma.
•In the past, other terms were used like neurosarcoma,
neurofibrosarcoma, malignant neuroma
•Gene aberrations in chromose 17, 22

15

16. MPNST
•Aggressive
•Poor prognosis
•Limited ttt options.
•Significant higher incidence of local recurrence
•Malignancy can occur de novo or from previously
benign nerve cells
•Suspected when
1.Irregular shape
2.high intensity areas in T1 MRI
3.heterogenous contrast enhancement
16

17. MPNST
•History of NF1 NF2 or schwannomatosis
•Rapid increase in size
•Progressive neurologic symptoms
•Increasing pain
•Motor sensory reflexes
•Numbness ‘pins and needles’ or ‘electric shock’
17

18. MPNST
•Equal in men and women
•Potentially affect the affected organs of NF
•MPNST has strong association with NF1 than
NF2
•If isolated it is common in 7
th
decade, while if
associated with NF1, it is common with 3
rd

and 4
th
decade
•Malignant transformation is common if NF
involves the major nerve trunks.
18

19. Radiation
•10% of MPNST occur in patients who have
undergone radiation ttt for other diseases.
•Also malignancy can occur about 12 to 15 years
after radiation exposure.
•Metastases to lung, liver, brain, soft tissue,
bone, regional LN, skin or retro-peritoneum
are common.
19

20. Radiation
•Tumour biopsy is the most conclusive test.
•MRI, CT, radioscan help in aiding in localizing
tumour and mets. If present.
•Needle biopsy is recommended as low risk of
pain and less neurogenic deficit but it is non
conclusive (as not all area of mass included)
•Generally, complete excisional biopsy is
advocated to minimize sample error and
decrease nerve damage.
20

21. Radiation
•PET with FDG scan is a
technique that allows the visualization and
quantification of glucose metabolism in cells and
reflects the greater metabolism of malignant
tumours.
•PET CT scan is sensitive and specific diagnostic
tool.
21

22. Classification
•Classification used for soft tissue sarcoma
•Based on the number of the mitotic figures.
•Mitotic figures
•Nuclear and cellular atypia
•Macroscopic (gross) size
•Mitotic figures are evaluated using the high power field
(HPF) microscopic analysis
•> than 5 mitotic per 10 HPF is classified high-grade
MPNST
•Tumour size > 5 cm grading it as high
•Tumour size correlates with pathologic grade
22

23. Grading
Enneking system
Classifies sarcomas and nerve tumours of
extremities by histologic appearance

Criteria Grade
Low grade sarcoma
< 25% chance of metastasis
Stage 1
High grade sarcoma
>25% chance of metastasis
Stage 2
Any grade
Already metastasized
Stage 3
Type B Type A
Extra-compartmental
Irregular invasion
Intra-compartmental
Tumours are contained within
fascial planes
More likely to be controlled
with surgical resection 23

24. Histopathology
Using hematoxylin & eosin stained (H&E)
sections, MPNST are graded based on
1.Cellularity
2.Nuclear pleomorphism
3.Anaplasia
4.Mitotic rate per 10 HPF
5.Microvascular proliferation
6.Degree of necrosis/ invasion

24

25. So, definition
•MPNST are;
Non-encapsulated infiltrating tumour composed
of spindle cells arranged in whorling pattern
with irregular nuclei, cyst formation and nuclear
palisading.
•50 to 90% of the cases are immunoreactive
with S-100 protein staining.

25

26. •Diagnosis of MPNST can not be augmented by using
H&E stain alone as sarcomas arising from fibroblasts or
smooth muscle cells may have similar appearance.
•Stains for
1.Desmin
2.Myogenin
3.Vimentin
4.S-100
5.Marker MIB-1
6.Expression of p53, p27 & p16
26

27. Treatment
•In gross inspection,
MPNST commonly be like fusiform, fleshy, tan-
white mass with areas of degeneration and
secondary hemorhage.
•Proximal and distal ends may be thickened as
spread of tumour along the epineurium.
•Only complete excision before occurance of
metastses is the way for survival.
•Reported local recurrence rate of MPNST after
complete resection is about 65%.

27

28. Treatment
•Ultimate aim of surgery is complete removal of
the lesion with tumour free margins.
•Complete excision with limb preservation can not
be always done.
•Surface of the tumour is mapped using nerve
stimulator to find safe inter-fascicular entry zone.
•Non functioning fascicles can be sacrified.
•Functioning fascicles are traced through the mass
to preserve them if possible.
28

29. Treatment
•If functioning fascicles must be sacrificed, nerve
grafting can be used for bridging them.
•Nerve continuity after removal of malignant
brachial and lumbosacral plexus lesions is not
advocated as adjuvant radiation and
chemotherapy will compromise the ability of
axons to grow again to the target organ.
•Amputation may be indicated for extensive
MPNST
& for mass that recur after adequate excision.
29

30. Radiotherapy
•Operative resection is the cornerstone for adjuvant
therapy.
•External beam or catheter-directed brachytherapy
radiation improves local control and delays onset of
recurrence but
has little effect of long term survival.
•Usual dose is 6000 to 7000 cGy
•Pre-operative irradiation is recommended if
1.Dissection along critical organ is expected
2.Leaving microscopic part is a must
•Post- op radiotherapy is recommended as a policy

30

31. Radiotherapy
Adjuvant
•Given whenever possible
for intermediate to high
grade lesions.
•For low grade tumours after
complete excision
•irradiation of the entire
operative field with 5 cm
field margin.
Neoadjuvant
•Irradiation of the tumour
alone with 5-cm margin
31

32. Chemotherapy
•Used for ttt of metastases
•Neoadjuvant chemotherapy used for reduce
the need for amputation and allow wide
excision with -ve margins at the time of the
surgery.
•Useful to achieve tumour resection in patients
with unresectable primary tumours.
•Can aid in 10 years for progression free
survival for local and distant relapse
32

33. Prognosis
•Poor
•Worse in NF1 patients
•Metastases to lung, liver, brain, soft tissue, bone, regional LN, skin
or retroperitoneum get MPNST poor in prognosis.
•Hematogenous spread common to lungs
•Paraspinal MPNST more aggressive behaviour
•poorer prognosis is with :
1.Tumour size >5 cm
2.High tumour grade
3.Advanced histology
4.Positive surgical margins
5.Associated NF1
6.Recurrent
33

34. 34

35. 35

36. 36

37. 37

38. 38

39. 39

40. 40

41. 41

42. •Then after 3 months, the patients entered in
deep coma after liver metastases then died.
42

43. 43

44. 44

45. 45

46. 46

47. 47

48. 48

49. So,
How to manage ??
49

50. Welcome
Benha Teaching Hospital

50