Keywords
malignant peripheral nerve sheath tumor - diffuse scalp lesion - neurofibromatosis type 1 - clinical course - treatment outcome
Introduction
Malignant peripheral nerve sheath tumors of the scalp are rare as reported in different studies.[1]
[2]
[3] Generally, it involves extremities followed by the chest, abdomen, and neck. In all, 50% of the tumor had been reported to be associated with NF1. Although scalp MPNST are rare tumors, they have the propensity to attain giant size.[3]
[4] Clinical courses of the patient having NF1 and without these stigmata have been variably reported.[1]
[2]
[3]
[4] None of the reported studies have a sufficient number of patients to reach a particular conclusion. We tried to analyze the patient's clinical course and treatment outcomes in our series of patients.
Patient's Details
Patients with malignant peripheral nerve sheath tumors had an average age of 38.40 ± 18.48 years; the youngest patient was 19 years old, and the oldest patient was 60 years old. There were three females and two males in the study. The duration taken to grow up to the present size (> 20 cm) was nearly 6.5 months in patients having neurocutaneous stigmata of NF1. All patients were anemic, and those with NF1 presented with severe anemia for which repeated blood transfusion was given. Dull aching pain was the most typical complaint of patients ([Table 1]).
Table 1
Clinica features of the patients having malignant peripheral nerve sheath tumour
|
Patient
|
Age/sex
|
location
|
Features of NF1
|
symptoms
|
Duration of symptoms (mo)
|
Size of the tumour (largest diameter in centimeter)
|
|
1.
([Figs. 1],[2])
|
19 y/f
|
RT Temporo-parietal-occipital
|
+
|
Fungating scalp mass,
with breathlessness,
severely, anaemic, repeated transfusion given but anemia not improving preoperatively, aching pain
|
7
|
34
(34 × 28 × 24)
|
|
2.
([Figs. 3],[4])
|
23 y/f
|
Suboccipital region
|
+
|
Multilobulated scalp mass, surface erosions present, anemic
|
6
|
32
(32 × 26 × 24)
|
|
3.
([Fig. 5])
|
60 y/m
|
Occipital region
|
−
|
Multiolobulated scalp mass, with surface erosion and occasional serosanguinous discharge
|
36
|
26
(26 × 24 × 20)
|
|
4.
([Figs. 6],[7])
|
35 y/f
|
Frontal
|
−
|
Multilobulated ulcerated region
|
30
|
24
(24 × 20 × 18)
|
|
5. NA
|
55 y/m
|
Occipital and suoccipital area
|
−
|
Multilobulated, bosslated, nonulcerative
|
24
|
22
(22 × 18 × 20)
|
Abbreviations: f, female; m, male; y, year.
Scalp lesion had mixed density on noncontrast computerized tomography head. Magnetic resonance imaging (MRI) brain with MR arteriography suggested heterogeneously contrast-enhancing lesions in all patients with diffuse scalp involvement. MR angiography suggested a doubtful vascular supply from intracranial vessels, for which preoperative digital subtraction angiography (DSA) was performed. All patients had a vascular supply from the middle meningeal and superficial temporal artery and two from the occipital artery. Preoperative embolization was performed with n-butyl cyanoacrylate seeing high vascularity of the tumor. The intraoperative dural breach was noted in two patients. Total excision covering the calvaria with a rotational flap was performed. All tumors had spindle-shaped cells arranged in a palisading pattern with mucinous content interspersed in between, and they positively stained for S100. All patients were given adjuvant radiotherapy (44 GY/30 divided doses) and chemotherapy (Lipodox protocol chemotherapy). Two patients with NF1 had metastases within 12 months ([Table 2]).
Fig. 1(A) Non contrast computed tomography (NCCT) head suggests hyperdense lesion with the erosion of calvaria and intracranial extension. (B) Magnetic resonance imaging (MRI) brain with contrast suggesting contrast-enhancing lesion with noncontrast enhancing area in between. (C) Magnetic resonance arteriography (MR-arteriography) suggesting high vascularity of lesion with feeders from superficial temporal artery and middle meningeal artery. (D) Glue embolization (n-butyl cyanoacrylate) was done through the right external carotid artery to decrease vascularity.
Fig. 2(A) Multilobulated lesion involving the right fronto-temporo-parietal region. (B) Tumour mass after surgery performed. (C) Scalp defect was covered with a rotational flap and bare area with a split skin graft. (D) Histopathology with H&E staining suggesting sheets of spindle cells spread with the collagenous and mucinous matrix.
Fig. 3(A) Tumor mass of max. dimension 32 cm overlying occipital area and up to lower cervical region with lateral extension up to bilateral carotid artery. (B) Saggital T2 MRI sequence showing tumor with variable intensity overlying occipital and cervical area. (C) Axial T2 MRI sequence showing hyperdense area interspersedwith isodense suggesting cystic degeneration within the lesion. (D) Intraoperative ultrasonography revealed a lesion involving the right common carotid artery.
Fig. 4(A) Tumour bed revealing infiltration of muscles in neck region being infiltrated by the tumor which was excised completely. (B) Scalp and neck region after reconstruction following tumor excision. (C) H&E staining of tumor biopsy revealing sheets of spindle cells intermixed with sheets of collagen and mucinous matrix. (D) Immunohistochemistry suggesting S100 staining of tumor.
Fig. 5(A) Tumour overlying occipital calvaria and overhanging in the neck region. (B) NCCT head revealing tumor mass in the occipital region and overlying torcula with no obvious calvarial breach.
(C) Postoperative image showing excision of the lesion with the reconstruction of scalp defect by a rotational flap.
Fig. 6(A) MRI brain with contrast revealing lesion involving bifrontal region with patchy non-enhancing area interspersed among contrast-enhancing area suggestive of necrosis. (B) MR arteriography revealing vascular tumor supplied by the superficial temporal artery. (C) Preoperative image revealing tumor mass overlying bifrontal region and overhanging anterosuperiorly. (D) Scalp defect following tumor excision. (E) Postoperative image following rotational flap reconstruction.
Fig. 7(A) Pleomorphic spindle cells with mitotic figures and necrosis in between. (B) Focal S100 staining of MPNST. (C) MPNST with the area of necrosis seen. (D) Tumor showing high proliferative index ki67 70%.
Table 2
Radiological features and management of the patients having malignant peripheral nerve sheath tumour
|
Patient
|
Radiology
|
Preoperative embolisation
|
Surgery
|
Breach of dura/ calvaria
|
Histopathology and immunohistochemistry
|
RT/CT
|
Follow up
|
|
1
|
Diffuse heterogenous contrast enhancing lesion with erosion of calvaria
|
DSA suggested feeders from right ECA, embolisation with n-butylcyanoacrylate
|
Excision with wound cover by rotational flap
|
+
|
S-100 +ve, EMA&H-caldesmon and SMA +ve
|
Both given
|
12
(lost to follow up)
|
|
2
|
Heterogeneously contrast enhancing, infiltrating the suboocipital muscles, engulfing bilateral common carotids
|
DSA suggested few feeders from occipital artery, embolisation done
|
Excision with wound cover by rotational flap.
|
-nt
|
S-100 +ve, vimentin &actin +ve
|
Both given
|
13
(lost to follow up)
|
|
3
|
Lesion was heterointense with mild contrast enhancement
|
Moderately vascular (not embolised)
|
Excision with rotational flap
|
+
|
S-100 +ve, SMA +ve
|
given
|
16, NED
|
|
4
|
Heterogeneously contrst enhancing
|
Moderately vascular (not embolised)
|
Excision with rotational flap
|
+
|
S-100 +ve, SMA +ve
|
|
12, NED
|
|
5
|
Heterogenouly contrast enhacement
|
Moderately vascular (not embolised)
|
Excision with rotational flap
|
+
|
S-100 +ve, vimentin +ve
|
|
24, NED
|
Abbreviations: NED, no evidence of disease; +-present, –absent.
Discussion
MPNST constitutes 3 to 10% of soft tissue sarcoma. Its incidence is 0.001% in the general population. In all, 50% of the MPNST occurs in association with neurofibromatosis type 1.[1]
[2] Lifetime risk of development of MPNST in patients with NF1 is 10%. Involvement of the scalp is rare, and nearly 20 patients have been reported.[3]
[4]
The age incidence of the lesion is 20 to 50 years with male predominance.[1]
[2] In the study by Arshi et al, the mean age at detection of the lesion was 50.7 ± 22.4 years in the present study, patients were younger compared to reported studies, which suggests that MPNST can develop in younger patients also. Three females and two males suggested slight male predominance in the present study, contrary to the higher male-to-female ratio in other studies.[3]
[4] Patients with the largest lesions were females of younger age and having neurocutaneous stigmata of NF1, which suggests that patients having NF1 can present earlier with giant lesions.
Most lesions are in the occipital region, followed by the frontal, temporal, and parietal regions. The location of the lesion in the present series was extensive as it involved the frontal, temporal, parietal, and occipital regions with an average size of 27.6 ± 5.17 cm, contrary to the earlier reports where the lesion was localized and of smaller size. The average tumor dimension reported in the present study was more extensive than in other reported cases. All patients in the present series had a tumor larger than 20 cm, with one patient having a tumor size of 32 cm. Ten of the 20 patients reported earlier by different authors have lesions more than 20 cm, and the duration of onset of symptoms was shorter in their studies[5]
[6]
[7]
[8]
[9]
[10] ([Table 1]). Lesions in the present study were multilobulated and gave a double brain appearance. It indicates late detection of the lesion, but mostly it was unwillingness by the patient for treatment that led to such a large size.
NCCT head was suggestive of a large breach of the calvarias in occipital, temporal, and frontal bones in almost all patients, with evidence of a dural breach in two patients. MR angiography was suggestive of arterial supply from the middle meningeal and superficial temporal branch in all patients and suspected supply from the middle cerebral artery with tumor blush, suggesting high vascularity in two patients with NF1 ([Table 3]). Intraoperative DSA suggested blood supply from the middle meningeal and superficial temporal artery branches, which were embolized with n-butyl cyanoacrylate. Such high vascularity of the tumor had not been reported earlier in giant MPNST. MPNST despite being diffuse and large, is moderately vascular. Two patients were anemic with preoperative hemoglobin of 6 g/dL although they were transfused 8 units of blood as they had initial hemoglobin of 4 g/dL. Once the tumor was excised and two units of blood were transfused, their hemoglobin was 11 g/dL. It can be explained by ongoing blood loss inside the tumor cavity. If the tumor had not been embolized, the patient could have had severe blood loss during surgery, which could have been life-threatening. Such features have not been reported earlier in any of the giant MPNSTs reported to date, which needs mentioning.
Table 3
Reported cases of Giant Malignant peripheral nerve sheath tumor of the scalp, and present case series
|
Case report (year)
|
Sex
|
Age
|
Location
|
NF (Type-1)
|
Bone infiltration
|
Time of growth (mo)
|
Size (cm)
|
IHC (S100)
|
Treatment
|
Follow up
|
|
Garg et al (2004)[11]
|
male
|
50
|
occipital
|
NA
|
Yes
|
96
|
21 × 17
|
+
|
S + RT
|
NA
|
|
Fukushima et al (2006)[7]
|
M
|
38
|
Occipital
|
no
|
no
|
36
|
21 × 19 × 9
|
+
|
S
|
4 months (DOD)
|
|
Ge et al (2010)[8]
|
M
|
52
|
Parietal
|
yes
|
yes
|
120
|
22 × 19
|
+
|
S
|
6 months
|
|
Shintaku et al[13]
|
F
|
59
|
Scalp
|
yes
|
NA
|
18
|
12
|
−
|
S
|
18 months DOD
|
|
Chen et al (2011)[14]
|
M
|
52
|
Rt forehead
|
U
|
U
|
U
|
U
|
U
|
U
|
U
|
|
Teles et al (2012)[1]
|
F
|
56
|
Occipital
|
yes
|
no
|
3
|
15 × 14.5 × 10.5
|
+
|
S
|
NA
|
|
Wang et al (2013)[6]
|
M
|
35
|
Occipital
|
no
|
yes
|
60
|
10.07 × 9.38 × 6.49
|
−
|
S + RT
|
26 months NED
|
|
Liu et al (2016)[9]
|
M
|
52
|
Rt forehead
|
NA
|
yes
|
60
|
28 × 25 × 10
|
+
|
S
|
60 months NED
|
|
Firdaus et al (2018)[4]
|
M
|
45
|
Frontal
|
no
|
yes
|
24
|
30 × 20
|
+
|
S + RS
|
30 months DOD
|
|
M
|
49
|
Frontal
|
no
|
yes
|
36
|
6 × 5 + 8 × 8
|
+
|
S + RT
|
12 months NED
|
|
Farinha et al[3]
|
M
|
31
|
Fronto-parietal
|
no
|
yes
|
24
|
17 × 17
|
+
|
S + RT
|
|
|
Present series
|
|
Case 1
|
F
|
19
|
Temporo-parietal occipital
|
yes
|
yes
|
24
|
34 × 28 × 24
|
+
|
E + S + RT + CT
|
13 months, (mets, lost to follow up)
|
|
Case 2
|
F
|
23
|
Occipital + cervical
|
yes
|
no
|
36
|
32 × 26 × 24
|
+
|
E + S + RT
|
8 months, lost to follow up
|
|
Case 3
|
M
|
55
|
Occipital
|
no
|
yes
|
36
|
26 × 24 × 20
|
+
|
S + RT
|
16 months
NED
|
|
Case 4
|
F
|
35
|
frontal
|
no
|
yes
|
30
|
24 × 20 × 18
|
+
|
E + S + RT
|
12 months NED
|
|
Case 5
|
M
|
60
|
Occipital region
|
no
|
yes
|
24
|
22 × 18 × 20
|
+
|
S + RT
|
24 months
NED
|
Abbreviations: mets, metastatic lesions; CT, chemotherapy; E, embolization; NED-noevidence of disease; RT, radiotherapy; S, surgery & excision.
Intraoperatively, there was evidence of intradural tumor invasion at places that were noted in three patients. Although scalp MPNST achieved a giant size as reported by different authors, the intradural extension had been reported by Mullins et al.2 It suggests less invasiveness of the lesion inside the dura and intraparenchymal structure even if the duration of progression because the onset is long. Postoperative histopathology suggested S100 and vimentin positivity in all patients with high proliferation indices although such consistent association with the S100 marker had not been reported in earlier reported patients, suggestive of the origin of such tumors from perineurium. Its positivity in such patients is present in 50 to 90% of patients, and it may stain positive for smooth muscle actin, vimentin.[10 ] It has no prognostic significance. In such patients, neither it has a high diagnostic value[9] ([Table 3]).
The proximity of such giant size lesions to nearby critical neurovascular structures and microscopic deposits makes complete excision difficult, and local recurrence is inevitable. In the present series approximity of scalp MPNST to nearby critical neurovascular structure focing us to leave very small residue and residual microdeposits in nearby bony and scal margin may have caused subsequent recurrences. Different authors reported a high local recurrence rate, up to 50%, and distant metastases in nearly 20% of patients. In the present series, 40% of local recurrence with distant metastases was also noted on follow-up.[11]
[12]
[13] Radiotherapy helps in local control. However, its importance in prolonging survival is debated by different authors, especially in giant-size lesions due to uncertain safe resection of the tumor because of its infiltrative nature.[13]
[14]
[15]
[16] Kolberg et al did not find survival benefits following chemotherapy in their meta-analysis of patients with MPNST.16 Patients with large lesions and NF1 were started with chemotherapy, but recurrence and metastases could not shorten, raising doubt over chemotherapy in such lesions following surgery. Evans et al reported a 20% decrease in survival rate in patients with NF1, but Anghileri et al did not observe survival differences in patients associated with neurofibromatosis and sporadic cases.[12]
[17] In the present series, overall poor survival of the patient with scalp MPNST was due to the diffuse spread of the lesions and proximity to the critical neuro-vascular structure where complete resection could not be achieved, and the tumor biopsy report also suggested a high proliferation index. These facts were responsible for early metastases in two patients with NF1. In patients without NF1, complete surgical excision with a safe margin was achieved, and they were found to be disease-free at 2 years of most extended follow-up. It suggests that local control by total excision of the lesion is vital to the patient's survival despite the patient getting adjuvant radiotherapy and chemotherapy.
Conclusion
Patients with MPNST of the scalp in association with NF1 had fast tumor progression with high vascularity and proliferation index and have higher chances of recurrence and metastases with less response to radiotherapy and chemotherapy. Multimodal treatment with endovascular embolization helps decrease blood loss with safe resection of the tumor. Surgery and adjuvant treatment with RT and CT can improve survival if local excision of the tumor is complete. The present study is a small case series of a rare tumor and highlights essential observations; however, we need to have a more extensive patient series of patients with such lesions to reach significant conclusions.
