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IntroductionMalignant peripheral nerve sheath tumors (MPNSTs) are
sarcomas which originate fromperipheral nervesor from cells
associated with the nerve sheath, such as Schwann cells,perineural cells, or fibroblasts. Because MPNSTs can arise from
multiple cell types, the overall appearance can vary greatly from
one case to the next. This can make diagnosis and classification
somewhat difficult. In general, a sarcoma arising from a
peripheral nerve or aneurofibromais considered to be a
MPNST. The term MPNST replaces a number of previously
used names including malignant schwannoma,
neurofibrosarcoma, and neurogenic sarcoma (Ref. 38).
A sarcoma is defined as a MPNST when at least one of the
following criteria is met:
1. It arises from a peripheral nerve
2. It arises from a preexisting benign nerve sheath tumor(neurofibroma)
3. It demonstratesSchwann celldifferentiation on histologic
examination
EpidemiologyMPNSTs comprise approximately 5-10% of all soft tissue
sarcomas. They can occur either spontaneously or in association
with neurofibromatosis-1 (NF1).
The etiologyis unknown but there is a higher incidence in
patients with a history of radiation exposure (Refs. 1, 2, 11, and
26). Up to 50% of MPNSTs occur in patients with NF1 (Refs. 9and 22), demonstrating the tendency for this tumor to arise from
a preexisting neurofibroma. Cross sectional studies have
previously demonstrated a 1-2% prevalence of MPNST among
NF1 patients (Ref. 20) although a recent study showed these
patients have a 10% lifetime risk of ultimately developing an
MPNST (Ref. 13).
The development of plexiform neurofibromas has been linked
to the loss of NF1 gene expression in a mouse model, whilethe development of MPNST has been related to other genetic
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insults, such as those involving p53 and p16 (Refs. 8, 32, and
34). While NF1 gene activity does not independently causeMPNSTs, it may in fact predispose these patients to such an
event.
MPNSTs generally occur in adulthood, typically between the
ages of 20 and 50 years of age. Approximately 10-20% of cases
have been reported to occur in the first 2 decade of life (Ref.
10), with occasional cases involving infants as young as 11
months of age (Ref. 12).
Figure 1: A clinical photograph of a large mass of the distal femur...
Clinical Features of MPNSTMPNSTs usually present as an enlarging palpable mass. Pain isa variable complaint. Rapid enlargement occurs more often in
the setting of NF1 and should raise concern for malignant
degeneration of a neurofibroma. MPNSTs arising from
peripheral nerves may result in a variety of clinical patterns,
includingradicular pain,paresthesias,and motor weakness.
Most MPNSTs occur in conjunction with large peripheral
nerves such as thesciatic nerve,thebrachial plexusand
thesacral plexus(see Figures 1 and 2).
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Figure 2: AP and Lateral X-Rays of the mass seen in Figure 1...
They are usually deep-seated and often involve the proximal
upper and lower extremities as well as the trunk. Dermal or flat
plexiform neurofibromas, commonly encountered in cases of
NF-1, have not been shown to undergo malignanttransformation and do not usually require close monitoring. On
the other hand, larger nodular tumors associated with large
peripheral nerves and deep extensive plexiform neurofibromas
do have the potential to undergo malignant transformation and
should be observed more diligently (Ref. 14). In rare instances,
multiple MPNSTs can arise in the setting of NF1. Most of these
tumors are considered high-grade sarcomas with the potential to
recur as well as to metastasize.
Referring to a Sarcoma Team
The importance of referring a patient to a tertiary care center
with a formalmultidisciplinary sarcoma servicecannot be
emphasized enough. A multidisciplinary sarcoma service willtypically review patient information and formulate a treatment
plan within the setting of a formal sarcoma conference.
Representatives from all involved disciplines will typicallyattend and participate actively. This allows for optimal
dialogue and efficient coordination of care.
Imaging
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Figure 3-5: MRI image of a large soft tissue mass...
Magnetic resonance imaging (MRI) is the imaging modality of
choice. To some extent, MPNSTs share basic imaging
characteristics with their benign counterparts such as
neurofibromas and schwannomas. These include
a fusiformshape and a longitudinal orientation in the directionof the nerve. However, some distinctions are noteworthy. Large
tumors (> 5 cm), invasion of fat planes, heterogeneity, ill-
defined margins, andedemasurrounding the lesion are more
suggestive of MPNSTs (Refs. 16 and 30); see Figures 3, 4, and
5.
Figure 6: Axial images from a PET scan and the corresponding CT scan...
Imaging studies of the chest are an important part of any initial
sarcoma evaluation. MPNSTs are most likely to metastasize to
the lungs, followed by the bone and finally thepleura. For this
reason, aComputed Tomographyof the chest is the preferredimaging study to screen for distant disease. Abone scanshould
also be obtained to help identify metastatic bone disease.
FDG PET is a dynamic imaging modality which evaluates
metabolic activity by quantitatively assessing intracellular
glucose use (Ref. 18). It has been shown to reliably identify
areas of increased metabolic activity such as those seen in
malignancies; see Figure 6.
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While FDG PET has proven useful in detecting metastatic or
recurrent disease (Ref. 18), its value in differentiatingmalignant nerve sheath tumors from benign ones remains
unclear (Refs. 15, 19, and 29). More recently, it has been
suggested that 18FDG PET technology has prognosticrelevance. In a review of 16 NF1 patients with MPNSTs, SUV
(standardized uptake values) values were found to predict
long-term survival with an accuracy of 94%. Kaplan-Meiersurvival analysis demonstrated a mean survival time of 13
months in patients with SUV values above 3, in contrast to a
mean survival time of 52 months in patients with SUV valuesbelow 3 (Ref. 4). As experience with FDG PET technology
grows (Ref 18), clarification of its diagnostic and prognostic
implication is expected.
MPNST StagingStaging describes the most pertinent tumor characteristics and in
turn permits for adequate planning and appropriate treatment. In
addition, staging offers prognostic information and allows for
comparison in the context of a clinical trial. In general, staging
systems are designed to describe either existing metastases or
the likelihood of developing metastases. With regard to soft
tissue sarcomas, staging is dependent upon histologic grade,
tumor size, tumor depth, and the presence or absence of
metastases. In the absence of detectable metastases, histologic
grade, tumor size, and tumor depth are the strongest predictors
of eventual metastases. The stage is based upon imaging studies,
which demonstrate the local and distant extent of the disease,
and upon the histologic grade, which describes the histological
characteristics of individual tumor cells.
A number of staging systems have been described. The mostcommonly employed staging system is the American Joint
Committee on Cancer Staging System for Soft Tissue
Sarcomas (see Table 1). Stage I essentially describes any low-grade small soft tissue sarcoma without evidence of
metastasis. Stage II describes small high-grade tumors and
large but superficial high-grade tumors without evidence ofmetastasis. Stage III describes high-grade large tumors which
are deep. Stage IV includes any tumors with evidence ofmetastasis. One limitation of this staging system is that it does
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not reflect the tumors anatomic location. This has been
demonstrated to be relevant, especially in the setting of localrecurrence (Ref. 33).
Table 1: The American Joint Committee onCancer (AJCC) Staging System for Soft Tissue
Sarcoma, 6th EditionStage Size Depth Grade Metastases
I Any Any Low No
II< 5cm, anydepth OR >
5cm
Superficial
High No
III > 5cm Deep High No
IV Any Any Any Yes*Depth is termed superficial (above the deep fascia) or deep (deep to the deepfascia). Retroperitoneal tumors are considered deep.
A biopsy is an integral part of the staging system. It offers both
ahistologictissue diagnosis and the ability to determine the
grade of the lesion. This information, in turn, permits adequate
planning andadjuvant treatmentsuch
as radiation or chemotherapy. In addition, this information is
incorporated into the tumor staging process which providesprognostic information with regard to the disease and treatment
generalizations.
Fine needle aspirationsor FNAs is a biopsy method employed
to obtain individual cells forcytologicreview. It can be done
with a very small needle which is more easily tolerated by the
patient and is often useful to establish the presence of malignant
cells. However, it is not large enough to demonstrate thearchitectural pattern within a tumor and for this reason is not
often used to make an initial diagnosis. In cases of established
diagnoses, such as after surgical resection of a tumor, FNA can
often be successfully used to sample tissue which is suspected to
be recurrent disease.
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Figure 7: Axial image from a CT-guided biopsy demonstrating proper...
A second type of biopsy is a core needle or tru-cut needle
biopsy, which uses a larger hollow-bored needle gauge to obtain
a more substantial tissue sample. This type of sample offers
inspection of both individual cells as well as the architectural
arrangement of those cells within a given part of the tumor
mass. This information is often important in establishing a
histopathologic diagnosis. In many tertiary care cancer centers,
core needle biopsies are often performed with either CT or
ultrasound image guidance; see Figure 7. This is an outpatient
procedure and it allows for adequate tissue sampling while
minimizing bleeding and minimizing contamination or seeding
of surround tissue with tumor cells. In addition, it often avoids
the need for general anesthesia. In some cases a formal open
biopsy is required. This can either be an incisional biopsy,
where a small piece of tissue is removed from the larger tumor
mass, or an excisional biopsy, in which case the entire tumor is
removed. In general, an incisional biopsy is recommended when
a sarcoma is suspected.
Who Should Perform the Biopsy
Errors, complications, and changes in outcome were
demonstrated to greatly increase when the biopsy is
performed in a referring institution as opposed to asarcoma
treatment center(Ref. 27). This again underscores the
importance of referral to a tertiary care center with amultidisciplinary sarcoma team.
Needle Biopsy
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A needle biopsy is typically an outpatient procedure, which
means the patient does not have to stay in the hospitalovernight. It is usually done by an interventional radiologist
and it is usually guided by either an ultrasound or a CT scan to
ensure proper placement of the needle. Usually localanesthetic or mild sedation is provided to minimize the
patients discomfort. Once the sample is obtained the
pathologists can review the specimen under the microscope. Acomplete review of the biopsy may take a few days or even a
few weeks, depending upon the technical limitation such as
the use of special stains.
Histology
Figures 8-9: Under the microscope...The general appearance of MPNSTs is one of dense cellular
fascicles which alternate with myxoid regions. This swirling
arrangement of intermixed dense and myxoid areas has been
described as a marbleized pattern (see Figure 8). The cells may
be spindle shaped with very irregular contours. Alternatively,
cells may be rounded or fusiform in shape (see Figure 9).
Nuclear palisading has also been shown but in less than 10% of
cases and even then, only focally. Malignancy is suggested byfeatures such as invasion of surrounding tissues, invasion of
vascular structures, nuclear pleomorphism, necrosis, and mitotic
activity.
Histologic Features of MPNST
Approximately 80-85% of MPNSTs are spindle cell tumors withfasciculating patterns that contain histologic features similar to
those of a fibrosarcoma. They are often high-grade,demonstrating 4 or more mitotic figures per high powered
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field. The remaining 15% of MPNSTs is composed of tumors
that exhibit variable differentiation, allowing them to be sub-classified as distinct entities. A MPNST with rhabdomyoblastic
differentiation is characterized by both neural and skeletal
muscle differentiation. Within this category is the malignanttriton tumor, which refers specifically to a MPNST occurring in
association with rhabdomyosarcoma. Other examples of
MPNSTs with differentiation include glandular malignantschwannoma, epithelioid malignant schwannoma, and
superficial epithelioid MPNST (Ref. 38).
S-100 has been identified in approximately 5090% of
MPNSTs, however the staining pattern has been noted to be
both focal and limited to few cells. Leu-7 and myelin basicprotein are noted in 50% and 40% of cases respectively. In
general, a combination of antigens is used to help exclude other
spindle cell lesions and to confirm the diagnosis of MPNST.
Surgical Treatment for MPNSTThe mainstay of treatment is surgical resection. The goal of the
operation is to achieve complete surgical excision of the tumor
with negative (wide) margins. This offers the best outcome withrespect to both local recurrence and distant metastases.
Radiation TherapyRadiation therapy has become an integral part of local disease
control in most soft tissue sarcomas and likewise can be
employed in pre-operative, intraoperative, and post-operative
settings for MPNST. Together with wide surgical excision,
radiation therapy offers local and overall survival rates whichare similar to those following amputation, and the combined
modality treatment often allows patients the option to undergo
successful limb-salvage surgery. Treatment of soft-tissue
sarcomas with adjuvant radiation therapy has yielded a
statistically significant reduction in the rates of local disease
recurrence. It has not, however, had a meaningful reduction in
either rates of distant metastases or overall survival (Ref 35 and
40).
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Preoperative external beam radiation therapy is administered
before surgical resection. This approach offers a number of
potential benefits including accurate radiation planning and
tumor localization, smaller treatment volumes, and smaller dose
requirements. Pre-operative treatment also offers the theoretical
advantages of the "oxygen-enhancement effect" which argues
that radiation treatment is more effective in the setting of well-
oxygenated tissue. Finally, radiation therapy may result in
substantial tumor necrosis, making tumor spill less likely and in
some instances making successful limb salvage technically
easier. These benefits come at a cost of delayed wound healing,
surgical delay following radiation treatments, and less tissue
from which to obtain a diagnosis. In such cases a postoperativeboost dose of irradiation is administered for positive margins.
Post-operative radiation therapy is administered following
surgical resection. Post-operative radiation therapy offers the
patient immediate surgical excision, fewer wound healing
complications, and a larger specimen from which to make a
tissue diagnosis. Its disadvantages, however, are larger treatment
volumes, higher dose requirements, and the risk of seeding thesurgical scar and bed with viable tumor.
When it is anticipated that a close or microscopically positive
margin will occur at the time of resection, intraoperative
radiation therapy may be administered in the operating room
immediately following surgical resection. Similarly, radiation
administered via catheters (plastic tubes) which, are implanted
in the surgical bed at the time of resection and loaded withradioactive material in the peri-operative period is another
option that may be considered to help with a close or positive
margin. This type of radiation is referred to as brachytherapy.
Both methods offer focal concentrated treatment, limited
collateral damage to surrounding tissue, smaller overall doses,
and minimal to no delay in treatment following resection.
However, these treatment methods are employed without
knowing final pathology margin results. They may also result inwound healing problems.
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ChemotherapyChemotherapy is intended for systemic disease which is either
too small to detect or too diffuse, rendering local treatment
techniques ineffective. The use of chemotherapy is onlyemployed in high-grade disease, in which metastatic disease is
likely. The benefits of chemotherapy must be weighed against
its side-effects, some of which are irreversible. For this reason,
the decision to treat with chemotherapy is somewhat tailored to
an individual patient and his or her individual disease.
Chemotherapy can be administered in the pre-operative and
post-operative settings. Benefits of pre-operative chemotherapy
include immediate treatment of micrometastatic disease and the
potential for tumor shrinkage in certain chemotherapy-sensitive
tumor types. It has also been shown to radiosensitize some
tumors, making a combined protocol of radiation therapy and
chemotherapy synergistic. In these ways, it may aid in limb-
salvage surgery by making the surgical resection technically
easier. Finally, tumor response to chemotherapy may be
quantified following tumor resection, which in theory allows for
adjustment of adjuvant treatment protocols.
Chemotherapy is typically not administered in the case of
smaller lesions, defined as less than 5 to 8 cm in maximum
dimension. It is often avoided in cases which are confined to
local cutaneous or subcutaneous locations. Significant medical
comorbidities or significant cardiac disease often precludes
chemotherapy treatment. Lastly, the decision to forgo
chemotherapy is sometimes made in the case of extensiveterminal disease, in order to avoid a worsened quality of life.
In general, chemotherapy candidates are patients under the age
of 65 with good cardiac function and limited medical
comorbidities. Large, deep, high grade tumors and tumors which
demonstrate metastases or metastatic potential are typical
indications for chemotherapy treatment.
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MPNST PrognosisRecurrence can be discussed in terms of local disease and
distant or metastatic disease. The local recurrence rate for
MPNSTs has historically been reported to range from 40-65%and the distant recurrence rate has similarly been reported to
range from 40-68% (Refs. 18, 23, and 39). Five-year survival
has been reported to range from 16-52%. Longer survival has
been correlated with complete surgical excision, small tumor
size (
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often vary depending upon institutional experience, physician
preference, and patient or case restrictions. In the past, studies of
treatment of metastatic MPNSTs with chemotherapy did not
show significantly improved survival rates (Refs. 3, 6, and 36).
More recently, limited success using adjuvant chemotherapy has
been demonstrated. The Italian and German soft-tissue sarcoma
cooperative group reported an overall pediatric response rate of
45%, which included complete, partial, and minimal responders.
The highest response rate (65%) was notably within the
ifosfamide group (Ref. 5). In addition, isolated case reports have
demonstrated limited success as well (Refs. 21, 24, and 28).
Future IssuesMalignant peripheral nerve sheath tumors have historically been
difficult tumors to treat. This in large part resulted from their
inherently aggressive nature; however, limitations in both
diagnostic and therapeutic methods played an important role as
well.
To date, advances in imaging methods, such as MRI and PET
have realized earlier disease detection and characterization.Advances in immunohistochemistry have in turn, allowed for
more accurate disease identification and classification.
Experience with both chemotherapy and radiation therapy has
broadened considerably and the multi-disciplinary team
approach to sarcoma patient care has become well established.
Future gains will likely stem from a better understanding of the
genetics and the molecular biology of soft tissue sarcomas. Forexample, genetic profiling of MPNST has recently suggested
that NF1 related MPNSTs and sporadic MPNSTs are in fact
distinct unique entities (Refs. 37). Defining characteristics on a
molecular level might allow for more precise screening tests,
earlier disease detection, and perhaps more reliable prognostic
information. Clinical relevance may also be realized through a
molecularly engineered medication, specifically targeted to
promote or interfere with a particular receptor or pathway.Glivec, for example, is a receptor tyrosine kinase inhibitor
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which was developed to specifically target KIT receptors and
has shown marked improvement in patients with gastrointestinal
stromal tumors previously unresponsive to treatment. Similar
therapies will hopefully be designed and developed for
malignant peripheral nerve sheath tumors in the future.
References
1. Adamson DC, C. T., Friedman AH: Malignant peripheral nerve sheathtumor of the spine after radiation therapy for Hodgkin's lymphoma. ClinNeuropathol, 23((5)): 245-55, 2004.
2. Amin A, S. A., Flanagan A, Patterson D, Lehovsky J: Radiotherapy-induced malignant peripheral nerve sheath tumor of the cauda equina.Spine, 29((21)): E506-9, 2004.
3. Angelov L, D. A., O'Sullivan B, Bell R, Guha A: Neurogenic sarcoma:experience at the University of Toronto. Neurosurgery, 43((1)): 56-64,1998.
4. Brenner W, F. R., Gawad Ka, hagel C, von Deimling A, de Wit M,Buchert R, Clausen M, Mautner VF: Prognostic relevance of FDG PET inpatients with neurofibromatosis type-1 and malignant peripheral nervesheath tumours. Eur J Nucl Med Mol Imaging, 11: 1-5, 2006.
5. Carli M, F. A., Mattke A, Zanetti I, Casanova M, Bisogno G, CecchettoG, Alaggio R, De Sio L, Koscielniak E, Sotti G, Treuner J: Pediatric
malignant peripheral nerve sheath tumor: the Italian and German softtissue sarcoma cooperative group. J Clin Oncol, 23((33)): 8422-30, 2005.
6. Casanova M, F. A., Speafico F, Luksch R, Cefalo, massimino M,Gandola L, Lombardi F, Fossati-Bellani F: Malignant peripheral nervesheath tumors in children: a single institution twenty-year experience. JPediatr Hematol Oncol, 21((6)): 509-13, 1999.
7. Cashen DV, P. R., Raskin K, Hornicek FJ, Gebhardt MC, Mankin HJ.:Survival data for patients with malignant schwannoma. Clin Orthop RelatRes, 426: 69-73, 2004.
8. Cichowski K, S. T., Schmitt E, Santiago S, Reilly K, McLaughlin ME,Bronson RT, Jacks T: Mouse model of tumor development inneurofibromatosis type I. Science, 286: 2172-6, 1999.
9. D'Agostino AN, S. E., Miller RH: Sarcomas of the peripheral nerves andsomatic soft tissues associated with multiple neurofibromatosis (VonRecklinghausen's disease). Cancer, 16: 1015-27, 1963.
10. Ducatman BS, S. B., Piepgras DG, Reiman HM: Malignant peripheralnerve sheath tumors in childhood. J Neurooncol, 2((3)): 241-8, 1984.
11. Ducatman BS, S. B., Piepgras DG, Reiman HM, Ilstrup DM: Malignantperipheral nerve sheath tumors. A clinicopathologic study of 120 cases.
Cancer, 57((10)): 2006-21, 1986.
8/10/2019 MPNST
15/27
12. Ellison DA, C.-B. J., Parham DM, Jackson RJ: Malignant triton tumorpresenting as a rectal mass in an 11-month-old. Pediatr Dev Pathol,8((2)): 235-9, 2005.
13. Evans DG, B. M., McGaughran J, Sharif S, Howard E, Moran A:Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J MedGenet, 39((5)): 311-4, 2002.
14. Ferner, R. E., and Gutmann, D. H.: International consensus statementon malignant peripheral nerve sheath tumors in neurofibromatosis. Cancerresearch, 62(5): 1573-7, 2002.
15. Ferner RE, L. J., O'Doherty MJ, Hughes RAc, Smith MA, Cronin BF andBingham JB: Evaluation of 18 fluorodeoxyglucose positron emissiontomography in the detection of malignant peripheral nerve sheath tumors
in neurofibromatosis 1. J Neurol Neurosurg Psychiatry, 68: 353-7, 2000.
16. Friedrich RE, K. L., Funsterer C, Mautner VF: Malignant peripheral
nerve sheath tumors (MPNST) in neurofibromatosis type 1 (NF1):diagnostic findings on magnetic resonance images and mutation analysisof the NF1 gene. 25, (3A)(May-Jun): 1699-702, 2005.
17. Heslin ML, C.-C. C., Lewis JJ, Woodruff JM, Brennan MF: Ki-67detected by MIB-1 predicts distant metastasis and tumor mortality inprimary, high grade extremity soft tissue sarcoma. Cancer, 83(3): 490-7,1998.
18. Hruban RH, S. M., Senie RT, Woodruff JM: Malignant peripheral nervesheath tumors of the buttock and lower extremity. A study of 43 cases.Cancer, 66((6)): 1253-65, 1990.
19. Hsu CH, L. C., Wang FC, Fang CL: Neurofibroma with increaseduptake of [F-18]-fluoro-2-D-glucose interpreted as a metastatic lesion.Ann Nucl Med, 17(7): 609-11, 2003.
20. Huson SM, C. D., Harper PS: A genetic study of von Recklinghausenneurofibromatosis in south east Wales. II. Guidelines for geneticcounselling. J Med Genet, 26((11)): 712-21, 1989.
21. Kinebuchi Y, N. W., Igawa Y, Nishizawa O: Recurrent retroperitonealmalignant peripheral nerve sheath tumor associated withneurofibromatosis type I responding to carboplatin and etoposide
combined chemotherapy. Int J Clin Oncol, 10((5)): 353-6, 2005.
22. King AA, D. M., Riccardi VM, Gutmann DH: Malignant peripheral nervesheath tumors in neurofibromatosis 1. Am J Med Genet, 93((5)): 388-92,2000.
23. Kourea HP, B. M., Leung DH, Lewis JJ, Woodruff JM:Subdiaphragmatic and intrathoracic paraspinal malignant peripheral nervesheath tumors: a clinicopathologic study of 25 patients and 26 tumors.Cancer, 82((11)): 2191-203, 1998.
24. Landy H, F. L., Markoe A, Patchen S, Bruce J, Marcus J, Levi A:
Extended remission of a recurrent median nerve malignant peripheralnerve sheath tumor after multimodal treatment. Case report. J Neurosurg,103((4)): 760-3, 2005.
8/10/2019 MPNST
16/27
25. Levine EA, H. T., Baucus S, Mechetner E, Mera R, Bollinger C,Roninson IB, Das Gupta TK: Evaluation of newer prognostic markers foradult soft tissue sarcomas. J Clin Oncol, 15(10): 3249-57, 1997.
26. Loree TR, N. J. J., Werness BA, Nangia R, Mullins AP, Hicks WL Jr.:Malignant peripheral nerve sheath tumors of the head and neck: analysisof prognostic factors. Otolaryngol Head Neck Surg., 122((5)): 667-72,2000.
27. Makin HJ, M. C., Simon MA: The hazards of the biopsy revisited.Members of the Musculoskeletal Tumor Society. J Bone Joint Surg Am,78(5): 656-63, 1996.
28. Masuri F, Y. R., Soshi S, Beppu Y, Asanuma K, Fujii K: A malignantperipheral nerve sheath tumour responding to chemotherapy. J Bone Joint
Surg Br, 86((1)): 113-5, 2004.
29. Otsuka H, G. M., Hubo A, Nishitani H: FDG-PET/CT findings of
sarcomatous transformation in neurofibromatosis: a case report. Ann NuclMed, 19(1): 55-8, 2005.
30. Pilavaki M, C. D., Kiziridou A, Skordalaki A, Zarampoukas T,Drevelengas A.: Imaging of peripheral nerve sheath tumors withpathologic correlation: pictorial review. Eur J Radiol, 52(3): 229-39, 2004.
31. Poyhonen M, N. S., Herva R: Risk of malignancy and death inneurofibromatosis. Arch Pathol Lab Med, 121((2)): 139-43, 1997.
32. Sabah M, C. R., Leader M, Kay E: Loss of p16 (INK4A) expressioni isassiciated with allelic imbalance/loss of heterozygosity of chromosome
9p21 in microdissected malignant peripheral nerve sheath tumors. ApplImmunohistochem Mol Morphol, 14(1): 97-102, 2006.
33. Stojadinovic A, Y. A., Brennan MF: Completely resected recurrent softtissue sarcoma: primary anatomic site governs outcomes. J Am Coll Surg,194(4): 436-47, 2002.
34. Vogel KS, K. L., Velasco-Miguel S, Meyers K, Rushing EJ, Parada LF:Mouse tumor model for neurofibromatosis I. Science, 286: 2176-9, 1999.
35. Vraa S, K. J., Nielsen OS, Sneppen O, Jurik AG, Jensen OM:Prognostic factors in soft tissue sarcomas: the Aarhus experience. Eur JCancer, 34((12)): 1876-82, 1998.
36. Wanebo JE, M. J., VandenBerg SR, Wanebo HJ, Driesen N, Persing JA:Malignant peripheral nerve sheath tumors. A clinicopathologic study of 28cases. Cancer, 71((4)): 1247-53, 1993.
37. Watson MA, P. A., Tihan T, Prayson RA, Guha A, Bridge J, Ferner R,Gutmann DH: Gene expression profiling reveals unique molecular subtypeof Neurofibromatosis Type I-associated and sporadic malignant peripheralnerve sheath tumors. Brain Pathol, 14(3): 297-303, 2004.
38. Weiss SW, G. J.: Enzinger and Weiss's Soft Tissue Tumors. Edited, St.Louis, Mosby, Inc., 2001.
39. Wong WW, H. T., Scheithauer BW, Schild SE, Gunderson LL:
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Malignant peripheral nerve sheath tumor: analysis of treatment outcome.Int J Radiat Oncol Biol Phys, 42((2)): 351-60, 1998.
40. Yang JC, C. A., Baker AR, Sindelar WF, Danforth DN, Topalian SL,DeLaney T, Glatstein E, Steinberg SM, Merino MJ, Rosenberg SA:Randomized prospective study of the benefit of adjuvant radiation therapyin the treatment of soft tissue sarcomas of the extremity. J Clin Oncol,16((1)): 197-203, 1998.
pengantar
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Ganas perifer tumor selubung saraf (MPNSTs) adalah sarkoma yangberasal dari saraf perifer atau dari sel-sel yang berhubungan denganselubung saraf, seperti sel-sel Schwann, sel perineural, atau fibroblas.Karena MPNSTs dapat timbul dari beberapa jenis sel, penampilankeseluruhan dapat sangat bervariasi dari satu kasus ke yang berikutnya.
Hal ini dapat membuat diagnosis dan klasifikasi agak sulit. Secara umum,sarkoma yang timbul dari saraf perifer atau neurofibroma yang dianggapMPNST a. The MPNST Istilah menggantikan sejumlah nama yangsebelumnya digunakan termasuk schwannoma ganas, neurofibrosarcoma,dan sarkoma neurogenik (Ref. 38).
Sebuah sarkoma didefinisikan sebagai MPNST ketika setidaknya satu darikriteria berikut terpenuhi:
Hal ini muncul dari saraf perifer
Hal ini muncul dari jinak tumor selubung saraf yang sudah adasebelumnya (neurofibroma)
Ini menunjukkan diferensiasi sel Schwann pada pemeriksaan histologis
epidemiologi
MPNSTs terdiri sekitar 5-10% dari semua sarkoma jaringan lunak. Merekadapat terjadi baik secara spontan atau dalam hubungan denganneurofibromatosis-1 (NF1).
Etiologi tidak diketahui tapi ada insiden yang lebih tinggi pada pasiendengan riwayat paparan radiasi (Ref. 1, 2, 11, dan 26). Sampai dengan50% dari MPNSTs terjadi pada pasien dengan NF1 (Ref. 9 dan 22),menunjukkan kecenderungan untuk tumor ini timbul dari neurofibromayang sudah ada sebelumnya. Studi cross sectional sebelumnya telahmenunjukkan prevalensi 1-2% dari MPNST antara pasien NF1 (Ref. 20)meskipun penelitian terbaru menunjukkan pasien ini memiliki risikoseumur hidup 10% dari akhirnya mengembangkan MPNST (Ref. 13).
Perkembangan neurofibroma plexiform telah dikaitkan dengan hilangnyaekspresi gen NF1 pada model tikus, sedangkan pengembangan MPNSTtelah terkait dengan penghinaan genetik lainnya, seperti yang melibatkanp53 dan p16 (Ref. 8, 32, dan 34) . Sementara aktivitas gen NF1 tidakindependen menyebabkan MPNSTs, itu mungkin sebenarnyamempengaruhi pasien ini untuk peristiwa semacam itu.
MPNSTs umumnya terjadi pada usia dewasa, biasanya antara usia 20 dan50 tahun. Sekitar 10-20% dari kasus telah dilaporkan terjadi di pertama 2
dekade kehidupan (Ref. 10), dengan kasus yang melibatkan sesekali bayiberusia 11 bulan usia (Ref. 12).
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Gambar 1: Sebuah foto klinis massa besar femur distal
Gambar 1: Sebuah foto klinis massa besar femur distal ...
Fitur klinis MPNSTMPNSTs biasanya hadir sebagai massa teraba membesar. Nyerimerupakan keluhan variabel. Pembesaran yang cepat terjadi lebih seringdalam pengaturan NF1 dan harus meningkatkan kepedulian terhadapdegenerasi ganas neurofibroma a. MPNSTs timbul dari saraf perifer dapatmengakibatkan berbagai pola klinis, termasuk nyeri radikuler, parestesia,dan kelemahan motorik. Kebanyakan MPNSTs terjadi dalam hubungannyadengan saraf perifer besar seperti saraf sciatic, pleksus brakialis danpleksus sakral (lihat Gambar 1 dan 2).
Gambar 2: AP dan Lateral X-Rays massa terlihat pada Gambar 1
Gambar 2: AP dan Lateral X-Rays dari massa terlihat pada Gambar 1 ...
Mereka biasanya mendalam dan sering melibatkan ekstremitas atas danbawah proksimal serta bagasi. Dermal atau plexiform datar neurofibroma,biasa ditemui pada kasus NF-1, belum ditampilkan untuk menjalanitransformasi maligna dan biasanya tidak memerlukan pemantauan ketat.Di sisi lain, tumor nodular yang lebih besar terkait dengan saraf periferbesar dan mendalam Neurofibroma plexiform luas yang memiliki potensiuntuk mengalami transformasi maligna dan harus diamati lebih rajin (Ref.14). Pada kasus yang jarang, beberapa MPNSTs dapat muncul dalampenetapan dari NF1. Sebagian besar tumor ini dianggap sarkoma bermututinggi dengan potensi untuk kambuh serta bermetastasis.
Mengacu pada Tim Sarkoma
Pentingnya merujuk pasien ke pusat perawatan tersier dengan layanansarkoma multidisiplin resmi tidak dapat ditekankan cukup. Sebuahlayanan sarkoma multidisiplin biasanya akan meninjau informasi pasien
dan merumuskan rencana perawatan dalam pengaturan konferensisarkoma formal. Perwakilan dari semua disiplin ilmu yang terlibatbiasanya akan hadir dan berpartisipasi aktif. Hal ini memungkinkan untukdialog optimal dan koordinasi yang efisien perawatan.
pencitraan
Angka 3-5
Gambar 3-5: gambar MRI dari massa jaringan lunak yang besar ...
Magnetic Resonance Imaging (MRI) adalah modalitas pencitraan pilihan.Untuk beberapa hal, MPNSTs karakteristik pencitraan dasar denganrekan-rekan mereka jinak seperti neurofibroma dan schwannomas. Ini
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termasuk bentuk fusiform dan orientasi membujur ke arah saraf. Namun,beberapa perbedaan yang penting. Tumor besar (> 5 cm), invasi pesawatlemak, heterogenitas, margin yang tidak jelas, dan edema sekitar lesilebih sugestif MPNSTs (Ref 16 dan 30.); lihat Gambar 3, 4, dan 5.
Gambar 6
Gambar 6: Axial gambar dari PET scan dan CT scan yang sesuai ...
Pencitraan dada merupakan bagian penting dari setiap evaluasi sarkomaawal. MPNSTs yang paling mungkin untuk bermetastasis ke paru-paru,diikuti oleh tulang dan akhirnya pleura. Untuk alasan ini, sebuahComputed Tomography dada adalah studi pencitraan pilihan untukmenyaring penyakit jauh. Scan tulang juga harus diperoleh untuk
membantu mengidentifikasi penyakit tulang metastatik.
FDG PET adalah modalitas pencitraan dinamis yang mengevaluasiaktivitas metabolik dengan kuantitatif menilai penggunaan glukosaintraseluler (Ref. 18). Telah terbukti andal mengidentifikasi areapeningkatan aktivitas metabolik seperti yang terlihat pada keganasan;lihat Gambar 6.
Sementara FDG PET telah terbukti berguna dalam mendeteksi metastasisatau penyakit berulang (Ref. 18), nilainya dalam membedakan tumorganas selubung saraf dari yang jinak masih belum jelas (Ref. 15, 19, dan29). Baru-baru ini, telah menyarankan bahwa teknologi 18FDG PETmemiliki relevansi prognostik. Dalam review 16 NF1 pasien denganMPNSTs, SUV (nilai serapan standar) nilai ditemukan untuk memprediksikelangsungan hidup jangka panjang dengan akurasi 94%. Kaplan-Meieranalisis survival menunjukkan waktu kelangsungan hidup rata-rata 13bulan pada pasien dengan nilai SUV di atas 3, berbeda dengan rata-ratawaktu kelangsungan hidup 52 bulan pada pasien dengan nilai SUV bawah3 (Ref. 4). Seperti pengalaman dengan teknologi FDG PET tumbuh (Ref18), klarifikasi implikasi diagnostik dan prognostik yang diharapkan.
MPNST Staging
Staging menggambarkan karakteristik tumor yang paling relevan danpada gilirannya memungkinkan untuk perencanaan yang memadai danpengobatan yang tepat. Selain itu, pementasan menawarkan informasiprognostik dan memungkinkan untuk perbandingan dalam kontekspercobaan klinis. Secara umum, sistem pementasan dirancang untukmenggambarkan baik metastasis ada atau kemungkinan mengembangkanmetastasis. Berkenaan dengan sarkoma jaringan lunak, pementasantergantung pada kelas histologis, ukuran tumor, kedalaman tumor, danada tidaknya metastasis. Dengan tidak adanya metastasis terdeteksi,
kelas histologis, ukuran tumor, dan kedalaman tumor adalah prediktorterkuat metastasis akhirnya. Tahap ini didasarkan pada studi pencitraan,
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yang menunjukkan tingkat lokal dan jauh dari penyakit, dan pada kelashistologis, yang menggambarkan karakteristik histologis sel tumorindividu.
Sejumlah sistem pementasan telah dijelaskan. Sistem pementasan yangpaling umum digunakan adalah Komite Bersama Amerika Kanker StadiumSistem Soft Tissue Sarkoma (lihat Tabel 1). Tahap I pada dasarnyamenggambarkan setiap kecil sarcoma jaringan lunak ringan tanpa buktimetastasis. Tahap II menjelaskan tumor bermutu tinggi kecil dan besartapi dangkal tumor bermutu tinggi tanpa bukti metastasis. Tahap IIImenjelaskan tumor besar bermutu tinggi yang mendalam. Tahap IVtermasuk semua tumor dengan bukti metastasis. Salah satu keterbatasansistem pementasan ini adalah bahwa hal itu tidak mencerminkan lokasi
anatomi tumor. Hal ini telah terbukti relevan, terutama dalam pengaturankekambuhan lokal (Ref. 33).
Tabel 1: The Amerika Joint Committee on Cancer (AJCC) Staging SistemSoft Tissue Sarkoma, Edisi 6
Tahap Ukuran Kedalaman kelas Metastasis
Saya Apa saja Low ada
II 5cm Superficial Tinggi Tidak ada
III> 5cm Jauh Tinggi Tidak ada
IV Apa saja Ya
* Kedalaman disebut dangkal (di atas fasia profunda) atau dalam (dalamuntuk fasia profunda). Tumor retroperitoneal dianggap dalam.
Biopsi merupakan bagian integral dari sistem pementasan. Inimenawarkan diagnosis jaringan histologis dan kemampuan untukmenentukan kelas lesi. Informasi ini, pada gilirannya, memungkinkanperencanaan yang memadai dan pengobatan adjuvant seperti radiasi ataukemoterapi. Selain itu, informasi ini dimasukkan ke dalam proses
pementasan tumor yang memberikan informasi prognostik yang berkaitandengan penyakit dan pengobatan generalisasi.
Aspirasi jarum halus atau FNAs adalah metode biopsi digunakan untukmemperoleh sel-sel individual untuk diperiksa sitologi. Hal ini dapatdilakukan dengan jarum yang sangat kecil yang lebih mudah ditoleransioleh pasien dan sering berguna untuk membangun kehadiran sel-selganas. Namun, tidak cukup besar untuk menunjukkan pola arsitekturdalam tumor dan untuk alasan ini tidak sering digunakan untuk membuatdiagnosis awal. Dalam kasus diagnosis didirikan, seperti setelah reseksi
bedah tumor, FNA sering dapat berhasil digunakan untuk sampel jaringanyang diduga menjadi penyakit kambuhan.
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Gambar 7
Gambar 7: Axial gambar dari biopsi CT-dipandu menunjukkan tepat ...
Tipe kedua dari biopsi adalah jarum inti atau tru-potong biopsi jarum,yang menggunakan berongga-bosan pengukur jarum yang lebih besaruntuk mendapatkan sampel jaringan yang lebih besar. Jenis sampelmenawarkan pemeriksaan kedua sel-sel individual serta pengaturanarsitektur sel-sel dalam bagian tertentu dari massa tumor. Informasi inisering penting dalam membangun diagnosis histopatologi. Dalam banyakpusat kanker perawatan tersier, biopsi jarum inti sering dilakukan denganbaik bimbingan CT atau gambar USG; lihat Gambar 7. Ini merupakanprosedur rawat jalan dan memungkinkan untuk pengambilan sampel
jaringan yang memadai dan meminimalkan pendarahan danmeminimalkan kontaminasi atau pembenihan jaringan surround dengansel-sel tumor. Selain itu, sering menghindari kebutuhan untuk anestesiumum. Dalam beberapa kasus biopsi terbuka formal diperlukan. Ini dapatberupa biopsi insisi, di mana sepotong kecil jaringan akan dihapus darimassa yang lebih besar tumor, atau biopsi eksisi, dalam hal ini seluruhtumor diangkat. Secara umum, biopsi insisi dianjurkan ketika sarkomayang dicurigai.
Siapa yang Harus Lakukan Biopsi
Kesalahan, komplikasi, dan perubahan hasil yang ditunjukkan untuk lebihmeningkatkan ketika biopsi dilakukan dalam lembaga mengacu sebagailawan ke pusat pengobatan sarkoma (Ref. 27). Ini lagi menggarisbawahipentingnya rujukan ke pusat perawatan tersier dengan tim sarkomamultidisiplin.
needle Biopsi
Biopsi jarum biasanya merupakan prosedur rawat jalan, yang berarti
pasien tidak harus tinggal di rumah sakit semalam. Hal ini biasanyadilakukan oleh seorang ahli radiologi intervensi dan biasanya dipandu olehsalah USG atau CT scan untuk memastikan penempatan yang tepat dari
jarum. Biasanya anestesi lokal atau obat penenang ringan disediakanuntuk meminimalkan ketidaknyamanan pasien. Setelah sampel diperolehpatolog dapat meninjau spesimen di bawah mikroskop. Sebuah reviewlengkap dari biopsi dapat memakan waktu beberapa hari atau bahkanbeberapa minggu, tergantung pada pembatasan teknis sepertipenggunaan noda khusus.
histologi
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Angka 8-9
Angka 8-9: Di bawah mikroskop ...
Penampilan umum MPNSTs adalah salah satu fasikula seluler padat yangbergantian dengan daerah myxoid. Pengaturan berputar-putar ini daerah
padat dan myxoid bercampur telah digambarkan sebagai pola marbleized(lihat Gambar 8). Sel-sel mungkin spindle berbentuk dengan kontur yangsangat tidak teratur. Atau, sel-sel dapat bulat atau fusiform dalam bentuk(lihat Gambar 9). Palisading nuklir juga telah ditunjukkan tetapi dalamwaktu kurang dari 10% kasus dan bahkan kemudian, hanya focally.Keganasan disarankan oleh fitur seperti invasi jaringan sekitarnya, invasistruktur vaskular, pleomorfisme nuklir, nekrosis, dan aktivitas mitosis.
Fitur histologis MPNST
Sekitar 80-85% dari MPNSTs adalah tumor sel spindle dengan polafasikulasi yang berisi fitur histologis mirip dengan fibrosarcoma a. Merekasering bermutu tinggi, menunjukkan 4 atau lebih angka mitosis perbidang bertenaga tinggi. Sisanya 15% dari MPNSTs terdiri dari tumoryang menunjukkan diferensiasi variabel, yang memungkinkan merekauntuk menjadi sub-diklasifikasikan sebagai entitas yang berbeda. SebuahMPNST dengan diferensiasi rhabdomyoblastic ditandai oleh diferensiasiotot saraf dan tulang. Di kategori ini adalah tumor ganas triton, yangmerujuk secara khusus untuk MPNST terjadi dalam hubungan denganrhabdomyosarcoma. Contoh lain dari MPNSTs dengan diferensiasi
termasuk schwannoma kelenjar ganas, epithelioid schwannoma ganas,dan dangkal MPNST epithelioid (Ref. 38).
S-100 telah diidentifikasi di sekitar 50 - 90% dari MPNSTs, namun polapewarnaan telah dicatat untuk menjadi fokus dan terbatas pada beberapasel. Leu-7 dan myelin protein dasar dicatat dalam 50% dan 40% darikasus masing-masing. Secara umum, kombinasi antigen digunakan untukmembantu menyingkirkan lesi sel spindle lain dan untuk mengkonfirmasidiagnosis MPNST.
Pengobatan bedah untuk MPNST
Andalan pengobatan adalah reseksi bedah. Tujuan dari operasi adalahuntuk mencapai eksisi bedah lengkap tumor dengan negatif (lebar)margin. Ini menawarkan hasil terbaik sehubungan dengan baikkekambuhan lokal dan metastasis jauh.
Terapi Radiasi
Terapi radiasi telah menjadi bagian integral dari pengendalian penyakitlokal di sebagian besar sarkoma jaringan lunak dan juga dapat digunakan
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dalam pre-operatif, intraoperatif, dan pengaturan pasca-operasi untukMPNST. Bersama dengan eksisi bedah luas, terapi radiasi menawarkantingkat kelangsungan hidup lokal dan secara keseluruhan yang miripdengan yang berikut amputasi, dan modalitas pengobatan gabungansering memungkinkan pasien pilihan untuk menjalani operasi ekstremitas-
penyelamatan yang sukses. Pengobatan sarkoma jaringan lunak denganterapi radiasi adjuvant telah menghasilkan penurunan yang signifikansecara statistik pada tingkat kekambuhan penyakit lokal. Hal ini tidak,bagaimanapun, mengalami penurunan yang berarti baik tingkatmetastasis jauh atau kelangsungan hidup secara keseluruhan (Ref 35 dan40).
Terapi radiasi sinar eksternal pra operasi diberikan sebelum reseksi
bedah. Pendekatan ini menawarkan sejumlah manfaat potensial termasukperencanaan yang akurat radiasi dan lokalisasi tumor, volume pengobatan
yang lebih kecil, dan persyaratan dosis yang lebih kecil. Perawatan pre-operatif juga menawarkan keuntungan teoritis dari "efek oksigentambahan" yang berpendapat bahwa pengobatan radiasi lebih efektifdalam pengaturan jaringan yang oksigen. Akhirnya, terapi radiasi dapatmenyebabkan nekrosis tumor besar, membuat tumpahan tumor kecilkemungkinannya dan dalam beberapa kasus membuat penyelamatanyang sukses ekstremitas secara teknis lebih mudah. Manfaat ini datangdengan biaya penyembuhan luka tertunda, delay bedah berikut perawatanradiasi, dan jaringan kurang dari yang untuk mendapatkan diagnosis.Dalam kasus seperti dorongan dosis pasca operasi iradiasi diberikan untukmargin positif.
Terapi radiasi pasca-operasi diberikan setelah reseksi bedah. Terapiradiasi pasca-operasi menawarkan eksisi pasien langsung bedah,komplikasi penyembuhan luka yang lebih sedikit, dan spesimen yang lebihbesar dari yang untuk membuat diagnosis jaringan. Kekurangan,bagaimanapun, adalah volume yang lebih besar perawatan, persyaratandosis yang lebih tinggi, dan risiko penyemaian bekas luka bedah dan tidurdengan tumor yang layak.
Ketika diantisipasi bahwa margin dekat atau mikroskopis positif akanterjadi pada saat reseksi, terapi radiasi intraoperatif dapat diberikan diruang operasi segera setelah reseksi bedah. Demikian pula, radiasidiberikan melalui kateter (tabung plastik) yang, yang tertanam di tempattidur bedah pada saat reseksi dan sarat dengan bahan radioaktif padaperiode peri-operatif adalah pilihan lain yang dapat dipertimbangkanuntuk membantu dengan margin dekat atau positif. Jenis radiasi disebutsebagai brachytherapy. Kedua metode menawarkan pengobatan fokusterkonsentrasi, kerusakan jaminan terbatas pada jaringan sekitarnya,dosis keseluruhan yang lebih kecil, dan minim atau tidak adaketerlambatan dalam pengobatan setelah reseksi. Namun, metode
pengobatan ini bekerja tanpa mengetahui hasil marjin patologi akhir.Mereka mungkin juga mengakibatkan masalah penyembuhan luka.
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kemoterapi
Kemoterapi ditujukan untuk penyakit sistemik yang terlalu kecil untukmendeteksi atau terlalu menyebar, rendering teknik pengobatan lokal
tidak efektif. Penggunaan kemoterapi hanya digunakan pada penyakitbermutu tinggi, di mana penyakit metastasis mungkin. Manfaatkemoterapi harus dipertimbangkan terhadap efek samping yang,beberapa di antaranya tidak dapat diubah. Untuk alasan ini, keputusanuntuk mengobati dengan kemoterapi agak disesuaikan dengan pasienindividu dan penyakit individu nya.
Kemoterapi dapat diberikan dalam pengaturan pra-operasi dan pasca-
operasi. Manfaat kemoterapi pra-operasi meliputi perawatan segerapenyakit micrometastatic dan potensi penyusutan tumor dalam jenis
tumor kemoterapi-sensitif tertentu. Hal ini juga telah ditunjukkan untukradiosensitize beberapa tumor, membuat protokol gabungan terapi radiasidan kemoterapi sinergis. Dalam hal ini, mungkin membantu dalam operasipenyelamatan ekstremitas-dengan membuat reseksi bedah teknis lebihmudah. Akhirnya, respon tumor terhadap kemoterapi dapat diukur reseksitumor berikut, yang dalam teori memungkinkan untuk penyesuaianprotokol pengobatan adjuvant.
Kemoterapi biasanya tidak diberikan dalam kasus lesi yang lebih kecil,yang didefinisikan sebagai kurang dari 5 sampai 8 cm dalam dimensi
maksimal. Hal ini sering dihindari dalam kasus-kasus yang terbatas padalokasi kulit atau subkutan lokal. Signifikan komorbiditas medis ataupenyakit jantung yang signifikan sering menghalangi pengobatankemoterapi. Terakhir, keputusan untuk melupakan kemoterapi kadang-kadang dibuat dalam kasus penyakit terminal yang luas, untukmenghindari kualitas memburuk hidup.
Secara umum, calon kemoterapi adalah pasien di bawah usia 65 denganfungsi jantung yang baik dan komorbiditas medis yang terbatas. Besar,dalam, tumor kelas tinggi dan tumor yang menunjukkan metastasis atau
potensi metastasis indikasi khas untuk pengobatan kemoterapi.
MPNST Prognosis
Kekambuhan dapat dibahas dalam hal penyakit lokal dan penyakit jauhatau metastasis. Tingkat kekambuhan lokal untuk MPNSTs secara historistelah dilaporkan berkisar 40-65% dan tingkat kekambuhan jauh telah
juga telah dilaporkan berkisar 40-68% (Ref. 18, 23, dan 39).Kelangsungan hidup lima tahun telah dilaporkan berkisar 16-52%.Kelangsungan hidup lebih lama telah berkorelasi dengan eksisi lengkap
bedah, ukuran tumor kecil (
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memainkan peran penting juga.
Sampai saat ini, kemajuan dalam metode pencitraan, seperti MRI dan PETtelah menyadari deteksi penyakit sebelumnya dan karakterisasi.
Kemajuan dalam imunohistokimia pada gilirannya, memungkinkan untukidentifikasi penyakit yang lebih akurat dan klasifikasi. Pengalaman denganbaik kemoterapi dan terapi radiasi telah memperluas jauh dan pendekatantim multi-disiplin untuk perawatan pasien sarkoma telah menjadi mapan.
Keuntungan masa depan kemungkinan akan berasal dari pemahamanyang lebih baik tentang genetika dan biologi molekuler dari sarkoma
jaringan lunak. Sebagai contoh, profil genetik MPNST baru-baru ini
menyarankan bahwa MPNSTs NF1 terkait dan MPNSTs sporadissebenarnya entitas yang unik yang berbeda (Ref. 37). Mendefinisikan
karakteristik pada tingkat molekuler mungkin memungkinkan untuk tesskrining yang lebih tepat, deteksi penyakit sebelumnya, dan informasiprognostik mungkin lebih handal. Relevansi klinis juga dapat diwujudkanmelalui obat rekayasa molekuler, khusus ditargetkan untukmempromosikan atau mengganggu dengan reseptor tertentu atau jalur.Glivec, misalnya, adalah tirosin reseptor kinase inhibitor yangdikembangkan untuk secara khusus menargetkan reseptor KIT dan telahmenunjukkan peningkatan yang ditandai pada pasien dengan tumorstroma gastrointestinal yang sebelumnya tidak responsif terhadappengobatan. Terapi yang sama diharapkan akan dirancang dandikembangkan untuk ganas perifer tumor selubung saraf di masa depan.