Difference between revisions of "Malignant peripheral nerve sheath tumour"

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#redirect [[Peripheral nerve sheath tumours#Malignant peripheral nerve sheath tumour]]
{{ Infobox diagnosis
| Name      = {{PAGENAME}}
| Image      = Malignant_peripheral_nerve_sheath_tumour_-_high_mag.jpg
| Width      =
| Caption    = MPNST. [[H&E stain]].
| Micro      = spindle cell lesion (or very rarely epithelioid lesion) with nuclear atypia, mitotic activity, +/-[[herring bone pattern]]
| Subtypes  = [[malignant triton tumour]]
| LMDDx      = [[synovial sarcoma]], [[fibrosarcoma]], cellular [[schwannoma]], plexiform schwannoma
| Stains    =
| IHC        =
| EM        =
| Molecular  =
| IF        =
| Gross      =
| Grossing  =
| Site      = [[soft tissue lesions|soft tissue]]
| Assdx      = [[neurofibroma]], [[plexiform neurofibroma]]
| Syndromes  = [[neurofibromatosis type 1]]
| Clinicalhx =
| Signs      = mass
| Symptoms  =
| Prevalence =
| Bloodwork  =
| Rads      =
| Endoscopy  =
| Prognosis  = poor
| Other      =
| ClinDDx    =
}}
'''Malignant peripheral nerve sheath tumour''', abbreviated '''MPNST''', is an uncommon malignant tumour of the nerve sheath.
 
It is also known '''neurofibrosarcoma'''<ref name=pmid21317712>{{Cite journal  | last1 = Mills | first1 = AM. | last2 = Karamchandani | first2 = JR. | last3 = Vogel | first3 = H. | last4 = Longacre | first4 = TA. | title = Endocervical fibroblastic malignant peripheral nerve sheath tumor (neurofibrosarcoma): report of a novel entity possibly related to endocervical CD34 fibrocytes. | journal = Am J Surg Pathol | volume = 35 | issue = 3 | pages = 404-12 | month = Mar | year = 2011 | doi = 10.1097/PAS.0b013e318208f72e | PMID = 21317712 }}</ref>, '''neurogenic sarcoma'''.<ref name=pmid23139572>{{Cite journal  | last1 = Sham | first1 = ME. | last2 = Ghorpade | first2 = A. | last3 = Shetty | first3 = S. | last4 = Hari | first4 = . | last5 = Vinay | first5 = . | title = Malignant peripheral nerve cell tumour. | journal = J Maxillofac Oral Surg | volume = 9 | issue = 1 | pages = 68-71 | month = Mar | year = 2010 | doi = 10.1007/s12663-010-0019-6 | PMID = 23139572 }}</ref> and '''malignant schwannoma''' - these terms are however depreceated.<ref>{WHOCNS2007}</ref>
 
==General==
*Malignant - as the name implies.
*Usually assoc. with a peripheral nerve.<ref>{WHOCNS2007}</ref>
*May be seen in the context of [[neurofibromatosis type 1]] or radiation induced.<ref>{{Cite journal  | last1 = Ducatman | first1 = BS. | last2 = Scheithauer | first2 = BW. | last3 = Piepgras | first3 = DG. | last4 = Reiman | first4 = HM. | last5 = Ilstrup | first5 = DM. | title = Malignant peripheral nerve sheath tumors. A clinicopathologic study of 120 cases. | journal = Cancer | volume = 57 | issue = 10 | pages = 2006-21 | month = May | year = 1986 | doi =  | PMID = 3082508 }}</ref>
*Approx 50-70% arise from  (mostly plexiform) [[neurofibroma]]s.
*Usu. adults
*Approx. 5% of all malignant soft tissue lesions.
 
<gallery>
File:MPNST.PNG | MPNST in a NF1 case (WC/Filip em).
File:MPNST Pathology gross.jpg | MPNST gross pathology (Flickr/drbloodmoney).
</gallery>
 
==Microscopic==
Features:<ref>{{Cite journal  | last1 = Pekmezci | first1 = M. | last2 = Reuss | first2 = DE. | last3 = Hirbe | first3 = AC. | last4 = Dahiya | first4 = S. | last5 = Gutmann | first5 = DH. | last6 = von Deimling | first6 = A. | last7 = Horvai | first7 = AE. | last8 = Perry | first8 = A. | title = Morphologic and immunohistochemical features of malignant peripheral nerve sheath tumors and cellular schwannomas. | journal = Mod Pathol | volume = 28 | issue = 2 | pages = 187-200 | month = Feb | year = 2015 | doi = 10.1038/modpathol.2014.109 | PMID = 25189642 }}</ref>
*Cellular - usu. spindle cells.
**Very rarely epithelioid.<ref name=pmid22082606>{{Cite journal  | last1 = Carter | first1 = JM. | last2 = O'Hara | first2 = C. | last3 = Dundas | first3 = G. | last4 = Gilchrist | first4 = D. | last5 = Collins | first5 = MS. | last6 = Eaton | first6 = K. | last7 = Judkins | first7 = AR. | last8 = Biegel | first8 = JA. | last9 = Folpe | first9 = AL. | title = Epithelioid malignant peripheral nerve sheath tumor arising in a schwannoma, in a patient with neuroblastoma-like schwannomatosis and a novel germline SMARCB1 mutation. | journal = Am J Surg Pathol | volume = 36 | issue = 1 | pages = 154-60 | month = Jan | year = 2012 | doi = 10.1097/PAS.0b013e3182380802 | PMID = 22082606 }}</ref>
*Nuclear atypia.
*Mitoses.
*+/-Herring bone pattern.
*Perivascular hypercellularity.
*Tumor herniation into vascular lumens.
*"Pseudocapsule" with tumour invasion of adjacent tissue.
 
Notes:
*May be diagnosed in a poorly diff. tumour if patient has [[NF1]].
 
DDx:
*Cellular [[schwannoma]].
*Plexiform schwannoma.
*[[Malignant triton tumour]].
**aka. MPNST with mesenchymal differentiation.
 
DDx of herring bone:
*MPNST.
*[[Synovial sarcoma]].
*[[Fibrosarcoma]].
 
===Images===
<gallery>
Image:Malignant_peripheral_nerve_sheath_tumour_-_intermed_mag.jpg | MPNST - intermed. mag. (WC)
Image:Malignant_peripheral_nerve_sheath_tumour_-_high_mag.jpg | MPNST - high mag. (WC)
Image:Malignant_peripheral_nerve_sheath_tumour_-_very_high_mag.jpg | MPNST - very high mag. (WC)
File:MPNST chondroid differentiation.jpg | MPNST with chondroid dedifferentiation (Triton tumor). (WC)
</gallery>
www:
*[http://path.upmc.edu/cases/case112/micro.html MPNST - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case406.html MPNST - case 2 - several images (upmc.edu)].
 
===Grading===
*Can be graded histologically, according WHO<ref name=pmid14508395>{{cite journal |author=Zhou H, Coffin CM, Perkins SL, Tripp SR, Liew M, Viskochil DH |title=Malignant peripheral nerve sheath tumor: a comparison of grade, immunophenotype, and cell cycle/growth activation marker expression in sporadic and neurofibromatosis 1-related lesions |journal=Am. J. Surg. Pathol. |volume=27 |issue=10 |pages=1337–45 |year=2003 |month=October |pmid=14508395 |doi= |url=}}</ref> and this is prognostic.<ref name=pmid16923196>{{cite journal |author=Kar M, Deo SV, Shukla NK, ''et al.'' |title=Malignant peripheral nerve sheath tumors (MPNST)--clinicopathological study and treatment outcome of twenty-four cases |journal=World J Surg Oncol |volume=4 |issue= |pages=55 |year=2006 |pmid=16923196 |pmc=1560134 |doi=10.1186/1477-7819-4-55 |url=}}</ref>
*grade IV: Presence of necrosis (3/4 of all MPNST).
*grade III: Mitotic count exceeds 4/1 HPF.
*grade II: nuclear size (<3x of neurofibroma cell), hyperchromatic nuclei.
**overlap with cellular ("atypical") neurofibroma (DDx).
 
 
Sarcoma grading system<ref name=pmid6693192>{{cite journal |author=Trojani M, Contesso G, Coindre JM, ''et al.'' |title=Soft-tissue sarcomas of adults; study of pathological prognostic variables and definition of a histopathological grading system |journal=Int. J. Cancer |volume=33 |issue=1 |pages=37–42 |year=1984 |month=January |pmid=6693192 |doi= |url=}}</ref> - based on:
*Tumour differentiation.
*Mitotic rate.
*[[Necrosis]].
 
==IHC==
Features:<ref name=pmid18636017>{{cite journal |author=Nonaka D, Chiriboga L, Rubin BP |title=Sox10: a pan-schwannian and melanocytic marker |journal=Am. J. Surg. Pathol. |volume=32 |issue=9 |pages=1291–8 |year=2008 |month=September |pmid=18636017 |doi=10.1097/PAS.0b013e3181658c14 |url=}}</ref>
*S-100 +ve ~ 30% of tumours.
*SOX10 +ve ~ 50% of tumours.
*Neurofibromin (NFC) -ve (88% in NF1, 43% sporadic MPNST)<ref>{{Cite journal  | last1 = Reuss | first1 = DE. | last2 = Habel | first2 = A. | last3 = Hagenlocher | first3 = C. | last4 = Mucha | first4 = J. | last5 = Ackermann | first5 = U. | last6 = Tessmer | first6 = C. | last7 = Meyer | first7 = J. | last8 = Capper | first8 = D. | last9 = Moldenhauer | first9 = G. | title = Neurofibromin specific antibody differentiates malignant peripheral nerve sheath tumors (MPNST) from other spindle cell neoplasms. | journal = Acta Neuropathol | volume = 127 | issue = 4 | pages = 565-72 | month = Apr | year = 2014 | doi = 10.1007/s00401-014-1246-6 | PMID = 24464231 }}</ref>
*H3K27me -ve<ref>{{Cite journal  | last1 = Schaefer | first1 = IM. | last2 = Fletcher | first2 = CD. | last3 = Hornick | first3 = JL. | title = Loss of H3K27 trimethylation distinguishes malignant peripheral nerve sheath tumors from histologic mimics. | journal = Mod Pathol | volume = 29 | issue = 1 | pages = 4-13 | month = Jan | year = 2016 | doi = 10.1038/modpathol.2015.134 | PMID = 26585554 }}</ref>
*MIB-1 ≥20% is highly predictive of malignant peripheral nerve sheath tumor (87% sensitivity and 96% specificity).<ref>{{Cite journal  | last1 = Pekmezci | first1 = M. | last2 = Reuss | first2 = DE. | last3 = Hirbe | first3 = AC. | last4 = Dahiya | first4 = S. | last5 = Gutmann | first5 = DH. | last6 = von Deimling | first6 = A. | last7 = Horvai | first7 = AE. | last8 = Perry | first8 = A. | title = Morphologic and immunohistochemical features of malignant peripheral nerve sheath tumors and cellular schwannomas. | journal = Mod Pathol | volume = 28 | issue = 2 | pages = 187-200 | month = Feb | year = 2015 | doi = 10.1038/modpathol.2014.109 | PMID = 25189642 }}</ref>
 
 
Others:<ref name=pmid14508395>{{cite journal |author=Zhou H, Coffin CM, Perkins SL, Tripp SR, Liew M, Viskochil DH |title=Malignant peripheral nerve sheath tumor: a comparison of grade, immunophenotype, and cell cycle/growth activation marker expression in sporadic and neurofibromatosis 1-related lesions |journal=Am. J. Surg. Pathol. |volume=27 |issue=10 |pages=1337–45 |year=2003 |month=October |pmid=14508395 |doi= |url=}}</ref>
*p53.
*p16 -ve.<ref>{{Cite journal  | last1 = Pekmezci | first1 = M. | last2 = Reuss | first2 = DE. | last3 = Hirbe | first3 = AC. | last4 = Dahiya | first4 = S. | last5 = Gutmann | first5 = DH. | last6 = von Deimling | first6 = A. | last7 = Horvai | first7 = AE. | last8 = Perry | first8 = A. | title = Morphologic and immunohistochemical features of malignant peripheral nerve sheath tumors and cellular schwannomas. | journal = Mod Pathol | volume = 28 | issue = 2 | pages = 187-200 | month = Feb | year = 2015 | doi = 10.1038/modpathol.2014.109 | PMID = 25189642 }}</ref>
*p27.
*p75NTR +ve (80%).
*EGFR +ve <ref> {{Cite journal  | last1 = Pekmezci | first1 = M. | last2 = Reuss | first2 = DE. | last3 = Hirbe | first3 = AC. | last4 = Dahiya | first4 = S. | last5 = Gutmann | first5 = DH. | last6 = von Deimling | first6 = A. | last7 = Horvai | first7 = AE. | last8 = Perry | first8 = A. | title = Morphologic and immunohistochemical features of malignant peripheral nerve sheath tumors and cellular schwannomas. | journal = Mod Pathol | volume = 28 | issue = 2 | pages = 187-200 | month = Feb | year = 2015 | doi = 10.1038/modpathol.2014.109 | PMID = 25189642 }}</ref>
 
==Molecular==
Features:<ref>{{Cite journal  | last1 = Röhrich | first1 = M. | last2 = Koelsche | first2 = C. | last3 = Schrimpf | first3 = D. | last4 = Capper | first4 = D. | last5 = Sahm | first5 = F. | last6 = Kratz | first6 = A. | last7 = Reuss | first7 = J. | last8 = Hovestadt | first8 = V. | last9 = Jones | first9 = DT. | title = Methylation-based classification of benign and malignant peripheral nerve sheath tumors. | journal = Acta Neuropathol | volume =  | issue =  | pages =  | month = Feb | year = 2016 | doi = 10.1007/s00401-016-1540-6 | PMID = 26857854 }}</ref><ref>{{Cite journal  | last1 = Hirbe | first1 = AC. | last2 = Dahiya | first2 = S. | last3 = Miller | first3 = CA. | last4 = Li | first4 = T. | last5 = Fulton | first5 = RS. | last6 = Zhang | first6 = X. | last7 = McDonald | first7 = S. | last8 = DeSchryver | first8 = K. | last9 = Duncavage | first9 = EJ. | title = Whole Exome Sequencing Reveals the Order of Genetic Changes during Malignant Transformation and Metastasis in a Single Patient with NF1-plexiform Neurofibroma. | journal = Clin Cancer Res | volume = 21 | issue = 18 | pages = 4201-11 | month = Sep | year = 2015 | doi = 10.1158/1078-0432.CCR-14-3049 | PMID = 25925892 }}</ref>
* Atypical neurofibromas and low-grade MPNST have a common methylation profile and frequent losses of CDKN2A.
* A subset of MPNST show loss of trimethylation of histone H3 at lysine 27 (H3K27me3).
* P53 and beta-spectrin mutations during progression reported.
==See also==
*[[Peripheral nerve sheath tumours]].
 
==References==
{{Reflist|2}}
 
[[Category:Diagnosis]]
[[Category:Peripheral nerve sheath tumours]]

Latest revision as of 09:28, 27 April 2017

Malignant peripheral nerve sheath tumour
Diagnosis in short

MPNST. H&E stain.
LM spindle cell lesion (or very rarely epithelioid lesion) with nuclear atypia, mitotic activity, +/-herring bone pattern
Subtypes malignant triton tumour
LM DDx synovial sarcoma, fibrosarcoma, cellular schwannoma, plexiform schwannoma
Site soft tissue
Associated Dx neurofibroma, plexiform neurofibroma
Syndromes neurofibromatosis type 1
Signs mass
Prognosis poor

Malignant peripheral nerve sheath tumour, abbreviated MPNST, is an uncommon malignant tumour of the nerve sheath.

It is also known neurofibrosarcoma[1], neurogenic sarcoma.[2] and malignant schwannoma - these terms are however depreceated.[3]

General

  • Malignant - as the name implies.
  • Usually assoc. with a peripheral nerve.[4]
  • May be seen in the context of neurofibromatosis type 1 or radiation induced.[5]
  • Approx 50-70% arise from (mostly plexiform) neurofibromas.
  • Usu. adults
  • Approx. 5% of all malignant soft tissue lesions.

  • MPNST in a NF1 case (WC/Filip em).

  • MPNST gross pathology (Flickr/drbloodmoney).

Microscopic

Features:[6]

  • Cellular - usu. spindle cells.
    • Very rarely epithelioid.[7]
  • Nuclear atypia.
  • Mitoses.
  • +/-Herring bone pattern.
  • Perivascular hypercellularity.
  • Tumor herniation into vascular lumens.
  • "Pseudocapsule" with tumour invasion of adjacent tissue.

Notes:

  • May be diagnosed in a poorly diff. tumour if patient has NF1.

DDx:

DDx of herring bone:

Images

  • MPNST - intermed. mag. (WC)

  • MPNST - high mag. (WC)

  • MPNST - very high mag. (WC)

  • MPNST with chondroid dedifferentiation (Triton tumor). (WC)

www:

Grading

  • Can be graded histologically, according WHO[8] and this is prognostic.[9]
  • grade IV: Presence of necrosis (3/4 of all MPNST).
  • grade III: Mitotic count exceeds 4/1 HPF.
  • grade II: nuclear size (<3x of neurofibroma cell), hyperchromatic nuclei.
    • overlap with cellular ("atypical") neurofibroma (DDx).


Sarcoma grading system[10] - based on:

  • Tumour differentiation.
  • Mitotic rate.
  • Necrosis.

IHC

Features:[11]

  • S-100 +ve ~ 30% of tumours.
  • SOX10 +ve ~ 50% of tumours.
  • Neurofibromin (NFC) -ve (88% in NF1, 43% sporadic MPNST)[12]
  • H3K27me -ve[13]
  • MIB-1 ≥20% is highly predictive of malignant peripheral nerve sheath tumor (87% sensitivity and 96% specificity).[14]


Others:[8]

  • p53.
  • p16 -ve.[15]
  • p27.
  • p75NTR +ve (80%).
  • EGFR +ve [16]

Molecular

Features:[17][18]

  • Atypical neurofibromas and low-grade MPNST have a common methylation profile and frequent losses of CDKN2A.
  • A subset of MPNST show loss of trimethylation of histone H3 at lysine 27 (H3K27me3).
  • P53 and beta-spectrin mutations during progression reported.

See also

References

  1. ↑ Mills, AM.; Karamchandani, JR.; Vogel, H.; Longacre, TA. (Mar 2011). "Endocervical fibroblastic malignant peripheral nerve sheath tumor (neurofibrosarcoma): report of a novel entity possibly related to endocervical CD34 fibrocytes.". Am J Surg Pathol 35 (3): 404-12. doi:10.1097/PAS.0b013e318208f72e. PMID 21317712.
  2. ↑ Sham, ME.; Ghorpade, A.; Shetty, S.; Hari, .; Vinay, . (Mar 2010). "Malignant peripheral nerve cell tumour.". J Maxillofac Oral Surg 9 (1): 68-71. doi:10.1007/s12663-010-0019-6. PMID 23139572.
  3. ↑ {WHOCNS2007}
  4. ↑ {WHOCNS2007}
  5. ↑ Ducatman, BS.; Scheithauer, BW.; Piepgras, DG.; Reiman, HM.; Ilstrup, DM. (May 1986). "Malignant peripheral nerve sheath tumors. A clinicopathologic study of 120 cases.". Cancer 57 (10): 2006-21. PMID 3082508.
  6. ↑ Pekmezci, M.; Reuss, DE.; Hirbe, AC.; Dahiya, S.; Gutmann, DH.; von Deimling, A.; Horvai, AE.; Perry, A. (Feb 2015). "Morphologic and immunohistochemical features of malignant peripheral nerve sheath tumors and cellular schwannomas.". Mod Pathol 28 (2): 187-200. doi:10.1038/modpathol.2014.109. PMID 25189642.
  7. ↑ Carter, JM.; O'Hara, C.; Dundas, G.; Gilchrist, D.; Collins, MS.; Eaton, K.; Judkins, AR.; Biegel, JA. et al. (Jan 2012). "Epithelioid malignant peripheral nerve sheath tumor arising in a schwannoma, in a patient with neuroblastoma-like schwannomatosis and a novel germline SMARCB1 mutation.". Am J Surg Pathol 36 (1): 154-60. doi:10.1097/PAS.0b013e3182380802. PMID 22082606.
  8. ↑ 8.0 8.1 Zhou H, Coffin CM, Perkins SL, Tripp SR, Liew M, Viskochil DH (October 2003). "Malignant peripheral nerve sheath tumor: a comparison of grade, immunophenotype, and cell cycle/growth activation marker expression in sporadic and neurofibromatosis 1-related lesions". Am. J. Surg. Pathol. 27 (10): 1337–45. PMID 14508395.
  9. ↑ Kar M, Deo SV, Shukla NK, et al. (2006). "Malignant peripheral nerve sheath tumors (MPNST)--clinicopathological study and treatment outcome of twenty-four cases". World J Surg Oncol 4: 55. doi:10.1186/1477-7819-4-55. PMC 1560134. PMID 16923196. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1560134/.
  10. ↑ Trojani M, Contesso G, Coindre JM, et al. (January 1984). "Soft-tissue sarcomas of adults; study of pathological prognostic variables and definition of a histopathological grading system". Int. J. Cancer 33 (1): 37–42. PMID 6693192.
  11. ↑ Nonaka D, Chiriboga L, Rubin BP (September 2008). "Sox10: a pan-schwannian and melanocytic marker". Am. J. Surg. Pathol. 32 (9): 1291–8. doi:10.1097/PAS.0b013e3181658c14. PMID 18636017.
  12. ↑ Reuss, DE.; Habel, A.; Hagenlocher, C.; Mucha, J.; Ackermann, U.; Tessmer, C.; Meyer, J.; Capper, D. et al. (Apr 2014). "Neurofibromin specific antibody differentiates malignant peripheral nerve sheath tumors (MPNST) from other spindle cell neoplasms.". Acta Neuropathol 127 (4): 565-72. doi:10.1007/s00401-014-1246-6. PMID 24464231.
  13. ↑ Schaefer, IM.; Fletcher, CD.; Hornick, JL. (Jan 2016). "Loss of H3K27 trimethylation distinguishes malignant peripheral nerve sheath tumors from histologic mimics.". Mod Pathol 29 (1): 4-13. doi:10.1038/modpathol.2015.134. PMID 26585554.
  14. ↑ Pekmezci, M.; Reuss, DE.; Hirbe, AC.; Dahiya, S.; Gutmann, DH.; von Deimling, A.; Horvai, AE.; Perry, A. (Feb 2015). "Morphologic and immunohistochemical features of malignant peripheral nerve sheath tumors and cellular schwannomas.". Mod Pathol 28 (2): 187-200. doi:10.1038/modpathol.2014.109. PMID 25189642.
  15. ↑ Pekmezci, M.; Reuss, DE.; Hirbe, AC.; Dahiya, S.; Gutmann, DH.; von Deimling, A.; Horvai, AE.; Perry, A. (Feb 2015). "Morphologic and immunohistochemical features of malignant peripheral nerve sheath tumors and cellular schwannomas.". Mod Pathol 28 (2): 187-200. doi:10.1038/modpathol.2014.109. PMID 25189642.
  16. ↑ Pekmezci, M.; Reuss, DE.; Hirbe, AC.; Dahiya, S.; Gutmann, DH.; von Deimling, A.; Horvai, AE.; Perry, A. (Feb 2015). "Morphologic and immunohistochemical features of malignant peripheral nerve sheath tumors and cellular schwannomas.". Mod Pathol 28 (2): 187-200. doi:10.1038/modpathol.2014.109. PMID 25189642.
  17. ↑ Röhrich, M.; Koelsche, C.; Schrimpf, D.; Capper, D.; Sahm, F.; Kratz, A.; Reuss, J.; Hovestadt, V. et al. (Feb 2016). "Methylation-based classification of benign and malignant peripheral nerve sheath tumors.". Acta Neuropathol. doi:10.1007/s00401-016-1540-6. PMID 26857854.
  18. ↑ Hirbe, AC.; Dahiya, S.; Miller, CA.; Li, T.; Fulton, RS.; Zhang, X.; McDonald, S.; DeSchryver, K. et al. (Sep 2015). "Whole Exome Sequencing Reveals the Order of Genetic Changes during Malignant Transformation and Metastasis in a Single Patient with NF1-plexiform Neurofibroma.". Clin Cancer Res 21 (18): 4201-11. doi:10.1158/1078-0432.CCR-14-3049. PMID 25925892.
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