# Ominous Occurrence of Spinal Intradural Primary Malignant Peripheral Nerve Sheath Tumor Four Decades following Radiation Therapy for Testicular Seminoma

Authors: Osmond C. Wu; Berje H. Shammassian; Arunit J. S. Chugh; Aparna Harbhajanka; Manish K. Kasliwal
Journal: Case Reports in Neurological Medicine
 (2020)

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## Abstract

Primary intradural malignant peripheral nerve sheath tumor (MPNST) is an extremely rare diagnosis and is associated with an extremely poor prognosis. A 77-year-old man diagnosed with an intradural MPNST, more than 40 years after radiation for a testicular seminoma, is reported. Intradural MPNSTs of the spine outside the setting of neurofibromatosis is extremely rare and can masquerade as common benign nerve sheath tumors, on imaging. An older age at presentation with short duration of symptoms and prior regional radiation treatment encompassing the spine in the treatment field regardless of remoteness should alert the oncologists and neurosurgeons to the possible existence of this rare and aggressive tumor, as the management, and overall prognosis of this tumor is distinctly different compared to the usual intradural spinal tumors.


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## Body

## 1. Introduction

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive, locally invasive rare soft tissue sarcomas arising from peripheral nerves that originate from Schwann cells or pluripotent cells of neural crest origin [1, 2]. MPNSTs represent 3–10% of all soft tissue sarcomas, with an overall incidence of 0.001% in the general population that peaks in the seventh decade [2–4]. In patients with neurofibromatosis type 1 (NF1), the annual incidence is 1.6 per 1000 with a lifetime risk of 8–13% [5]. Prior radiation exposure is another important risk factor, with a reported incidence of radiation induced MPNST ranging from 5.5–11% of patients [6]. MPNSTs are usually located in the extremities, trunk, and head, and neck. Spinal MPNSTs, however, are exceedingly rare. Table 1 comprises a list of the spinal MPNSTs in the literature. While there are a few instances of spinal and paraspinal MPNST following radiation for testicular seminomas, all the cases reported occurred within 7–10 years following radiation and were mainly extradural in location [7–10]. An intradural spinal MPNST with subsequent intracranial leptomeningeal metastasis diagnosed forty years after radiation is presented in this report with a pertinent review of the literature.Table 1
Primary spinal malignant peripheral nerve sheath tumors (MPNST) reported in the literature.
Author & year
Age (yrs), sex
Location
Presentation
NF history
Radiation history
Extent of resection
Radiation therapy
Chemotherapy
Recurrence
Metastasis
Outcome
Thomeer et al., 1981 [12]
42, M
Cauda equina
Low back pain for 9 yrs with occasional L radiculopathy, impotence for 4 wks, leg weakness for 3 wks
Not specified
Total
T11-S4 2.5 Gy 4x/wk for 6 wks
Yes, 3 yrs T9-11
No
Alive at 3 yrs
Valdueza et al., 1991 [13]
40, F
Thoracic
Thoracic pain, R leg weakness
Not specified
Partial
Total 12 Gy after initial operation, total 40 Gy after spinal metastasis
No
Yes, 2 mo
Chest, pelvis, spine
Alive at 4 yrs
43, F
Thoracic
Low back pain for 1 mo, leg weakness for 2 wks
Not specified
Partial
Total 24 Gy after first operation, total 32 Gy after second operation for recurrence
No
Yes, 8 yrs
No
Alive at 10 yrs
47, M
Cervical
Neck pain radiating to R shoulder for 9 mo, R arm weakness for 1 mo
NF1
Not specified
Total
Total 10 Gy
No
Yes, 3 mos
Brain, lumbar
Dead at 18 mos
18, M
Cervical
L shoulder and arm pain for 4 mos
Not specified
Total
No
No
No
No
Alive at 8 mos
70, F
Cervical
Neck pain radiating to R shoulder for 6 mos
Not specified
Total
No
No
No
No
Alive at 7 mos
Seppälä et al., 1993
13, M
Lumbar
Paraparesis
NF1
12 yrs ago for Wilm’s tumor
Partial
Not specified
Not specified
Yes
Brain, systemic
Dead at 2 mos
13, M
Lumbar
Paraparesis
Not specified
Total
Not specified
Not specified
Yes
Systemic
Dead at 7 mos
45, F
Sacral
Not specified
NF1
Not specified
Partial
Not specified
Not specified
Yes
Systemic
Dead at 2 mos
35, M
Lumbar
Radiculopathy
NF2
Not specified
Total
Not specified
Not specified
Yes
Systemic
Dead at 18 mos
23, F
Thoracic
Not specified
Not specified
Total
Not specified
Not specified
Yes
Systemic
Dead at 8 mos
37, F
Cervical
Radiculopathy
Not specified
Total
Yes
No
Yes, 2 yrs
Systemic
Dead at 6 yrs
Celli et al., 1995 [15]
52, F
Thoracic
Pain for 8 mos, weakness
Not specified
Total
No
No
No
No
Alive at 6 yrs
68, F
Lumbar
Pain for 9 mos, weakness
Not specified
Total
No
No
No
No
Alive at 2 yrs
43, M
Lumbar
Pain for 3 mos
Not specified
Total
No
No
No
No
Alive at 6 yrs
36, F
Thoracic
Pain for 5 mos
Not specified
Total
Yes
No
Yes
No
Alive at 4 yrs
22, F
Cervical
Pain for 2 yrs, weakess, incontinence
NF1
Not specified
Total
Yes
No
Yes
Lung
Dead at 6 mos
30, M
Thoracic
Pain for 3 yrs, weakness
Not specified
Total
Yes
No
Yes
Lung
Dead at 14 mos
West et al., 1997 [7]
40, M
Sacral
Radiculopathy
8 yrs ago for testicular seminoma, 30.6 Gy
Total
No
No
Yes, 7 mos
No
Not specified
Kourea et al., 1998 [8]
11, F
Lumbar, sacral
Not specified
NF1
Not specified
Partial
Yes
Yes
Yes, 0.5 mos
Yes, location not specified
Dead at 5 mos
25, F
Lumbar
Not specified
NF1
Not specified
Partial
Yes
Yes
No
No
Alive at 18 yrs
33, F
Lumbar
Not specified
NF1
Not specified
Partial
No
No
No
Yes, location not specified
Dead at 2 mos
33, M
Lumbar
Not specified
NF1
Not specified
Partial
Yes
Yes
Yes, 3 mos
Yes, location not specified
Dead at 22 mos
31, F
Lumbar
Not specified
NF1
Not specified
partial
yes
Yes
yes, 6 mos
yes, location not specified
dead at 10 mos
37, F
Lumbar
Incidental
Not specified
Partial
No
Yes
Yes, 3 mos
No
Dead at 4 mos
40, M
Sacral
Not specified
For testicular seminoma
Total
No
No
Yes, 9 mos
Yes, location not specified
Alive at 14 mos
17, M
Thoracic
Not specified
NF1
Not specified
Partial
No
Yes
Yes
Yes, location not specified
Dead at 11 mos
19, F
Thoracic
Incidental
NF1
Not specified
Total
No
No
No
No
Alive at 35 mos
53, F
Thoracic
Not specified
For breast carcinoma
Partial
No
No
Yes, 6 mos
Yes, location not specified
Dead at 7 mo
26, M
Thoracic
Not specified
For Hodgkin’s lymphoma
Partial
Yes
No
Yes, 13 mos
Yes, location not specified
Dead at 27 mo
Acharya et al., 2001 [20]
32, M
Cauda equina
Back pain, leg weakness, bowel and bladder dysfunction
Not specified
Partial
Yes
No
No
No
Alive at 18 mos
Yone et al., 2004 [16]
4, M
Cauda equina
Low back pain, radiculopathy, bladder dysfunction
Not specified
Total
Yes
Yes
Yes
Brain, spine
Dead at 21 mos
Adamson et al., 2004 [17]
37, M
Cervical
L C6 radiculopathy
6 yrs ago for Hodgkin’s lymphoma
Partial
Yes
No
Not specified
No
Dead after 1 yr
30, F
Cervical
R Horner syndrome, R C6 radiculopathy, R tricep and wrist extensor weakness
5 yrs ago for Hodgkin’s lymphoma
Partial
No
No
Not specified
No
Dead after 1 yr
Amin et al., 2004 [9]
38, M
Cauda equina
Back pain, leg weakness, bowel and bladder dysfunction
10 yrs ago for testicular seminoma, 30 Gy/15 fractions over 3 wks
Biopsy
No
Yes, palliative
Yes, 7 mos
Not specified
Not specified
Albayrak et al., 2006 [18]
25, M
Thoracic
Paraparesis, bladder dysfunction
NF1
Not specified
Total
No
No
Yes, 7 wks
Lung
Alive at 7 wks
Chamoun et al., 2009 [14]
5, F
Cervical
Pain, gait disturbance
Not specified
Partial
Yes
Yes
Yes
Brain, thoracic and lumbar spine
Alive at 4 mos
Xu et al., 2012
8, M
Lumbar
Pain
Not specified
Total
Yes
No
Yes
Brain
Dead at 16 mos
Mitsuhara et al., 2013
47, F
Cauda equina
Back pain, R leg weakness, bowel and bladder dysfunction, altered mental status
NF2
15 yrs ago for uterine and cervical cancer, 22 Gy
Partial
Yes, 36 Gy brain and spine, additional 14.4 Gy to lumbosacral lesion/28 fractions
No
Not specified
No
Not specified
Stark et al., 2013
56, F
Sacral
L leg radiculopathy, L foot paresis
15 yrs ago for non-Hodgkin’s lymphoma
Not specified
No
Yes
Yes
Brainstem, spine
Dead at 24 mos
Wu et al., 2014
9, F
Thoracic, lumbar, sacral
R hip pain, bilateral leg weakness
NF2
Not specified
Partial
No
No
Yes
Brain
Dead at 9 mos
Li et al., 2014
33, F
Low thoracic, upper lumbar
Low back pain, R leg radiculopathy, hydrocephalus
Not specified
Partial
Yes, 28 Gy/19 fractions
No
Yes
Brain, diffuse spine
Dead at 29 mos
Lau et al., 2014 [10]
43, M
Cauda equina
Low back pain, L leg radiculopathy for 5 mos
10 yrs ago for testicular seminoma
Total
No
Yes, alternating between ifosfamide/doxorubicin and ifosfamide/etoposide
Yes, about 60 mos
Brainstem, cervical spine, renal
Dead at 5 yrs
Thomas et al., 2014
49, M
Cauda equina
Low back pain, paraparesis
Not specified
Partial
No
No
No
Brain and spine
Not specified
Baharvahdat et al., 2016
3, F
Cervical, upper thoracic
Paraplegia, bladder and bowel dysfunction
Not specified
Partial
No
No
No
Brain and spine
Dead shortly after surgery
Chou et al., 2017a
5–74 (mean 40)
76% had adjuvant therapy
38% over 2 yrs
59% alive at 2 yrs
Samancia et al., 2017
27, M
Cervical, upper thoracic
Hydrocephalus
Not specified
Partial
Yes
Yes
No
No
Not specified
Present study
77, M
Lumbar
Left hip and buttock pain for 3 mos
About 45 yrs ago for testicular cancer
Partial
No
No
No
Intracranial leptomeningeal disease
Dead at 2 mos
F: Female, Gy: gray, L: left, M: male, mos: months, NF1: neurofibromatosis type 1, NF2: neurofibromatosis type 2, R: right, wks: weeks, yrs: years.
a Multicenter series (N=29), individual patient data not available.


## 2. Case Report

### 2.1. History and Presentation

A 77-year-old man with past medical history significant for esophageal adenocarcinoma as well as testicular seminoma that was treated with conventional external bean radiation therapy (EBRT) almost 40 years back presented with three months of left hip and buttock pain in addition to left foot weakness. He had no history or clinical stigmata of neurofibromatosis.A magnetic resonance imaging (MRI) of the lumbar spine with and without gadolinium demonstrated a homogenously enhancing, well demarcated intradural extramedullary neoplasm (Figure1). An initial MRI of the cervical and thoracic spine with and without gadolinium was negative for additional lesions. While a diagnosis of benign nerve sheath tumor was suspected given typical radiological appearance, a metastatic lesion was also considered in the differential because of prior history of cancer. A metastatic work up performed to look for any additional lesions was negative.Figure 1
(a) Magnetic resonance imaging (MRI) T1-weighted sagittal image of the lumbar spine with gadolinium demonstrates a well demarcated intradural extramedullary mass. (b) Corresponding axial image.
(a)
(b)


### 2.2. Operative Course

A partial L2 and complete L3 laminectomy was performed and a midline durotomy was made. A greyish mass was found in the intradural space arising from the left L3 nerve root with obvious enlargement and involvement of the nerve root. A frozen specimen was sent early for pathological evaluation that was diagnosed as MPNST. The nerve root of interest was clearly identified both proximally and distally, which on stimulation resulted in robust electrophysiological response suggestive of origin from a motor nerve root. No obvious plane was found between the tumor and the nerve root. Given the risk of motor deficit, the nerve root was preserved with partial resection of the tumor. Final pathology confirmed the diagnosis of MPNST (Figure2).Figure 2
(a) Hematoxylin and eosin (H&E) staining showed high cellular density with marked pleomorphism and spindle cells arranged in fascicles (200x). (b) Immunohistochemistry was positive for SOX 10 (100x) and (c) S-100 (100x). (d) Ki-67 labeling revealed a high proliferative index (100x).
(a)
(b)
(c)
(d)


### 2.3. Post-Operative Course

Given the initial pathologic diagnosis on frozen section, subsequent management including reoperation with extensive resection was discussed. Given his preoperative status, the patient, and family elected to observe in the short term with consideration of further treatment options following final pathology. The patient did well initially and was discharged to a skilled nursing facility. Two weeks post-operatively, however, the patient was readmitted with encephalopathy. An MRI brain with and without gadolinium demonstrated leptomeningeal metastasis (Figure3) with cerebral spinal fluid (CSF) cytology positive for malignant cells. Given the extent of disseminated disease and his progressive worsening mental status, the family elected to pursue palliative care, and the patient died two months after his initial surgery.Figure 3
(a) Magnetic resonance imaging (MRI) T1-weighted axial image of the brain with gadolinium demonstrates leptomeningeal metastasis. (b) Corresponding sagittal image.
(a)
(b)


## 2.1. History and Presentation

A 77-year-old man with past medical history significant for esophageal adenocarcinoma as well as testicular seminoma that was treated with conventional external bean radiation therapy (EBRT) almost 40 years back presented with three months of left hip and buttock pain in addition to left foot weakness. He had no history or clinical stigmata of neurofibromatosis.A magnetic resonance imaging (MRI) of the lumbar spine with and without gadolinium demonstrated a homogenously enhancing, well demarcated intradural extramedullary neoplasm (Figure1). An initial MRI of the cervical and thoracic spine with and without gadolinium was negative for additional lesions. While a diagnosis of benign nerve sheath tumor was suspected given typical radiological appearance, a metastatic lesion was also considered in the differential because of prior history of cancer. A metastatic work up performed to look for any additional lesions was negative.Figure 1
(a) Magnetic resonance imaging (MRI) T1-weighted sagittal image of the lumbar spine with gadolinium demonstrates a well demarcated intradural extramedullary mass. (b) Corresponding axial image.
(a)
(b)


## 2.2. Operative Course

A partial L2 and complete L3 laminectomy was performed and a midline durotomy was made. A greyish mass was found in the intradural space arising from the left L3 nerve root with obvious enlargement and involvement of the nerve root. A frozen specimen was sent early for pathological evaluation that was diagnosed as MPNST. The nerve root of interest was clearly identified both proximally and distally, which on stimulation resulted in robust electrophysiological response suggestive of origin from a motor nerve root. No obvious plane was found between the tumor and the nerve root. Given the risk of motor deficit, the nerve root was preserved with partial resection of the tumor. Final pathology confirmed the diagnosis of MPNST (Figure2).Figure 2
(a) Hematoxylin and eosin (H&E) staining showed high cellular density with marked pleomorphism and spindle cells arranged in fascicles (200x). (b) Immunohistochemistry was positive for SOX 10 (100x) and (c) S-100 (100x). (d) Ki-67 labeling revealed a high proliferative index (100x).
(a)
(b)
(c)
(d)


## 2.3. Post-Operative Course

Given the initial pathologic diagnosis on frozen section, subsequent management including reoperation with extensive resection was discussed. Given his preoperative status, the patient, and family elected to observe in the short term with consideration of further treatment options following final pathology. The patient did well initially and was discharged to a skilled nursing facility. Two weeks post-operatively, however, the patient was readmitted with encephalopathy. An MRI brain with and without gadolinium demonstrated leptomeningeal metastasis (Figure3) with cerebral spinal fluid (CSF) cytology positive for malignant cells. Given the extent of disseminated disease and his progressive worsening mental status, the family elected to pursue palliative care, and the patient died two months after his initial surgery.Figure 3
(a) Magnetic resonance imaging (MRI) T1-weighted axial image of the brain with gadolinium demonstrates leptomeningeal metastasis. (b) Corresponding sagittal image.
(a)
(b)


## 3. Discussion

MPNSTs are rare entities with an incidence of 0.001%, with 20–50% of cases arising in patients with NF-1. The most common locations include the trunk, extremities, and head, and neck [2]. Primary spinal MPNSTs are extremely rare. Primary MPNSTs of the spine that are exclusively intradural extramedullary without extension into the extradural compartment are exceptionally rare. Outside the setting of NF-1, prior radiation treatment is a risk factor for development of MPNSTs. There have been few reports of MPNST following prior radiation for testicular seminomas. Most occurred after a short latent period and in an extradural location, with a purely intradural occurrence being exceptionally rare [7–10].The present case developed almost four decades after being treated with EBRT for testicular seminoma, which is a significantly longer latency period as compared to other cases previously reported. Also, the imaging features were fairly characteristic of a benign intradural extramedullary neoplasm unlike a MPNST, which is typically an irregularly-bordered heterogeneously enhancing mass often with destruction of surrounding osseous structures. Similarly, the presence of leptomeningeal spread is also rare in primary intradural MPNSTs and as illustrated in this case, portends an ominous prognosis [11]. Unique to this case, however, is the rapid development of disseminated disease two weeks after surgery. Patients in other reported cases of intradural MPNSTs with leptomeningeal spread were diagnosed with dissemination ranging from present on presentation to 24 months following initial surgery [10–19]. The authors advocate that regardless of imaging characteristics or the duration since radiation, surgeons should retain a high index of suspicion for a MPSNT. Lumbar puncture may be considered to obtain CSF to identify potential malignant cells.


## 4. Conclusion

A rare case of an intradural MPNST diagnosed more than 40 years after radiation for a testicular seminoma is reported. Intradural MPNSTs of the spine outside the setting of neurofibromatosis are extremely rare and can masquerade common benign nerve sheath tumors on imaging. Short duration of symptoms and prior regional radiation treatment encompassing the spine in the treatment field regardless of remoteness should alert the physician to the possible existence of this rare and aggressive tumor. Being cognizant of this rare pathology can help initiate appropriate work up and evaluation, allow preoperative counselling, and alter overall surgical strategy.



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*Source: 1792582-2020-01-28.xml*