It is a malignant neoplasm arising from neurofibroma, peripheral nerve or tumor showing nerve sheath differentiation
Diagnosis of MPNST is considered if one of the three criteria are met
Tumor arising from peripheral nerve and shows no aberrant features or heterologous line of differentiation
Tumor arising from preexisting benign nerve sheath tumor eg. neurofibroma
Tumor shows features typical of malignant schwann cell tumor.
Incidence – 5% to 10% of sarcomas
Half of the cases are associated with NF1.
3% to 22%of neurofibromas undergo malignant transformation
Risk of developing malignant peripheral nerve sheath tumor in cases of Neurofibroma is 10% and in patients with symptomatic plexiform neurofibromatosis it is increased to 30%
Sites: commonly affecting the upper and lower extremities, paraspinal region, trunk and few cases are reported in head and neck.
Age: 2nd to 5th decade of life in sporadic tumors and slightly earlier age group in patients with NF1 related tumors
Sex: No sex predilection in sporadic cases but male predominance is seen cases with NF1
Radiography – similar to benign tumors, but the size larger than 5cms, irregular borders and necrosis suggesting malignancy
clinical presentation:
Presents as slowly growing mass. Pain is variable and is seen in patients with neurofibromatosis
Tumors arising from major nerve trunks may produce motor or sensory symptoms
They arise in association with major nerve trunks including Brachial plexus, Sacral plexus, and sciatic nerve
Morphology
Gross
Size – more than 5 cms
Shape – fusiform, eccentric mass
Thickening of the nerve either proximal or distal to the tumor suggests spread of neoplasm along the perineurium and epineurium
cut section – Fleshy , opaque, tan white with areas of hemorrhage and necrosis (in contrast to mucoid appearance in typical neurofibroma)
Microscopy
resembles adult type fibrosarcoma in their organization but cells have irregular contours in contrast to symmetrical spindle cells in fibrosarcoma
Cells are fusiform to spindle shaped (asymmetrically tapered spindle cells) or round having wavy, comma shaped or buckled nuclei and with lightly stained or indistinct cell borders
Cells are arranged as sweeping fascicles
Hypercellular areas with dense fascicles alternate with myxoid hypocellular zones which swirl and interdigitate with one another creating marble like affect.- characteristic pattern
Other patterns are nuclear palisading, swirling pattern, nodular and whorled arrangement
Hyaline bands and nodules which in cross section appear like rosette
Tumor shows extensive perineural and epineyral spread
Proliferating tumor cells particularly in sub endothelial space gives the appearance of tumor herniating into the vessel
Small vessels proliferating in the walls of large vessels may be noted
Rhabdomyoblastic differentiation can be seen
Malignant Triton tumor is MPNST with skeletal muscle differentiation
Glandular differentiation with or with out mucin can be seen
Heterologous elements like differentiation into bone, cartilage or angiomatous areas can occur
Areas of geographic necrosis may be present
MPNST may also contain areas with primitive neuroepithelial differentiation consisting of cords, rosettes or nests of small round cells
Epithelioid MPNST –
Rare type of MPNST not associated with neurofibroma
commonly arise from ex-schwannoma
Tumor cells are arranged in lobules and are plump and have abundant eosinophilic cytoplasm
Few foci shows tumor cells arranged in myxoid or hyalinized stroma
Immunohistochemistry
S-100 – may be patchy or even absent but strongly positive in Epithelioid MPNST and benign tumors like schwannoma and neurofibroma
SOX-10 shows variable positivity
TLE 1 – expressed in 40% of MPNSTs and is patchy (Diffuse in synovial sarcoma)
TP53 – present in more than 1/2 of MPNSTs (But absent in Neurofibroma)
Other two specific markers are – Neurofibromin and H3K27me3. Loss of both these markers is valid for MPNST
Glandular MPNST stains positive with keratin and CEA
Prognosis
It is a high grade sarcoma with distant metastasis and local recurrence
Recurrence depends upon the size of the tumor, adequacy of margins removed , and site of the tumor
Head and neck tumors and retroperitoneal tumors recur more frequently
Common metastatic site is lung, but can metastasize to liver, brain, bone and adrenal gland
MPNST associated with NF1 have worst prognosis.
MPNST is further graded as low and high grade
Low grade MPNST – Features of ANNUBP but with mitotic count of 3 – 9mitotic figures/10hpf without necrosis
High grade MPNST – Features of ANNUBP with mitotic figures >10/10hpf or 3 – 9/10hpf combined with necrosis
Malignant Triton tumor is aggressive has worst prognosis
Differential diagnosis
Atypical Neurofibromatous neoplasm of uncertain biological potential (ANNUBP) –
Schwann cell neoplasm with more than two of the following features
Cytological atypia
Loss of neurofibroma architecture
hypercellularity
<3mitotic figures/10 hpf
Cellular schwannoma-
Tumor cells show diffuse intense positivity with S-100 and SOX10 where as in MPNST they show patchy positivity or S-100 may be negative
Neurofibromin and H3K27me3 are retained in cellular Schwannoma in contrast to MPNST where it is lost
Spindle cell /Desmoplastic melanoma
Expression of P53 by desmoplastic melanoma but not by neurofibroma
HMB45, Melan A, Tyrosinase and MiTF marker expression
Synovial sarcoma: TLE 1 expression is more intense and diffuse in synovial sarcoma when compared to MPNST where it is patchy
Leiomyosarcoma:
Morphology – spindle cells with deeply eosinophilic cytoplasm and centrally placed nuclei which is cigar shaped and perinuclear halo
IHC- Smooth muscle markers like – SMA, Desmin, Caldesmin
Fibrosarcoma – presence of S-100, SOX 10 expression and loss of H3K27me3 suggest MPNST
Solitary fibrous tumor –
Greater amounts of interstitial collagen
S-100 and SOX-10 – negative
CD 34 and STAT 6 positive
Spindle cell rhabdomyosarcoma – Diffuse and strong positivity with Desmin and Myo D1.