Case Reports in Neurological Medicine

Case Reports in Neurological Medicine / 2020 / Article

Case Report | Open Access

Volume 2020 |Article ID 1792582 | https://doi.org/10.1155/2020/1792582

Osmond C. Wu, Berje H. Shammassian, Arunit J. S. Chugh, Aparna Harbhajanka, Manish K. Kasliwal, "Ominous Occurrence of Spinal Intradural Primary Malignant Peripheral Nerve Sheath Tumor Four Decades following Radiation Therapy for Testicular Seminoma", Case Reports in Neurological Medicine, vol. 2020, Article ID 1792582, 8 pages, 2020. https://doi.org/10.1155/2020/1792582

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

Academic Editor: Dominic B. Fee
Received16 Aug 2019
Accepted27 Nov 2019
Published28 Jan 2020

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.

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 [24]. 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 [710]. 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.


Author & yearAge (yrs), sexLocationPresentationNF historyRadiation historyExtent of resectionRadiation therapyChemotherapyRecurrenceMetastasisOutcome

Thomeer et al., 1981 [12]42, MCauda equinaLow back pain for 9 yrs with occasional L radiculopathy, impotence for 4 wks, leg weakness for 3 wksNot specifiedTotalT11-S4 2.5 Gy 4x/wk for 6 wksYes, 3 yrs T9-11NoAlive at 3 yrs
Valdueza et al., 1991 [13]40, FThoracicThoracic pain, R leg weaknessNot specifiedPartialTotal 12 Gy after initial operation, total 40 Gy after spinal metastasisNoYes, 2 moChest, pelvis, spineAlive at 4 yrs
43, FThoracicLow back pain for 1 mo, leg weakness for 2 wksNot specifiedPartialTotal 24 Gy after first operation, total 32 Gy after second operation for recurrenceNoYes, 8 yrsNoAlive at 10 yrs
47, MCervicalNeck pain radiating to R shoulder for 9 mo, R arm weakness for 1 moNF1Not specifiedTotalTotal 10 GyNoYes, 3 mosBrain, lumbarDead at 18 mos
18, MCervicalL shoulder and arm pain for 4 mosNot specifiedTotalNoNoNoNoAlive at 8 mos
70, FCervicalNeck pain radiating to R shoulder for 6 mosNot specifiedTotalNoNoNoNoAlive at 7 mos
Seppälä et al., 199313, MLumbarParaparesisNF112 yrs ago for Wilm’s tumorPartialNot specifiedNot specifiedYesBrain, systemicDead at 2 mos
13, MLumbarParaparesisNot specifiedTotalNot specifiedNot specifiedYesSystemicDead at 7 mos
45, FSacralNot specifiedNF1Not specifiedPartialNot specifiedNot specifiedYesSystemicDead at 2 mos
35, MLumbarRadiculopathyNF2Not specifiedTotalNot specifiedNot specifiedYesSystemicDead at 18 mos
23, FThoracicNot specifiedNot specifiedTotalNot specifiedNot specifiedYesSystemicDead at 8 mos
37, FCervicalRadiculopathyNot specifiedTotalYesNoYes, 2 yrsSystemicDead at 6 yrs
Celli et al., 1995 [15]52, FThoracicPain for 8 mos, weaknessNot specifiedTotalNoNoNoNoAlive at 6 yrs
68, FLumbarPain for 9 mos, weaknessNot specifiedTotalNoNoNoNoAlive at 2 yrs
43, MLumbarPain for 3 mosNot specifiedTotalNoNoNoNoAlive at 6 yrs
36, FThoracicPain for 5 mosNot specifiedTotalYesNoYesNoAlive at 4 yrs
22, FCervicalPain for 2 yrs, weakess, incontinenceNF1Not specifiedTotalYesNoYesLungDead at 6 mos
30, MThoracicPain for 3 yrs, weaknessNot specifiedTotalYesNoYesLungDead at 14 mos
West et al., 1997 [7]40, MSacralRadiculopathy8 yrs ago for testicular seminoma, 30.6 GyTotalNoNoYes, 7 mosNoNot specified
Kourea et al., 1998 [8]11, FLumbar, sacralNot specifiedNF1Not specifiedPartialYesYesYes, 0.5 mosYes, location not specifiedDead at 5 mos
25, FLumbarNot specifiedNF1Not specifiedPartialYesYesNoNoAlive at 18 yrs
33, FLumbarNot specifiedNF1Not specifiedPartialNoNoNoYes, location not specifiedDead at 2 mos
33, MLumbarNot specifiedNF1Not specifiedPartialYesYesYes, 3 mosYes, location not specifiedDead at 22 mos
31, FLumbarNot specifiedNF1Not specifiedpartialyesYesyes, 6 mosyes, location not specifieddead at 10 mos
37, FLumbarIncidentalNot specifiedPartialNoYesYes, 3 mosNoDead at 4 mos
40, MSacralNot specifiedFor testicular seminomaTotalNoNoYes, 9 mosYes, location not specifiedAlive at 14 mos
17, MThoracicNot specifiedNF1Not specifiedPartialNoYesYesYes, location not specifiedDead at 11 mos
19, FThoracicIncidentalNF1Not specifiedTotalNoNoNoNoAlive at 35 mos
53, FThoracicNot specifiedFor breast carcinomaPartialNoNoYes, 6 mosYes, location not specifiedDead at 7 mo
26, MThoracicNot specifiedFor Hodgkin’s lymphomaPartialYesNoYes, 13 mosYes, location not specifiedDead at 27 mo
Acharya et al., 2001 [20]32, MCauda equinaBack pain, leg weakness, bowel and bladder dysfunctionNot specifiedPartialYesNoNoNoAlive at 18 mos
Yone et al., 2004 [16]4, MCauda equinaLow back pain, radiculopathy, bladder dysfunctionNot specifiedTotalYesYesYesBrain, spineDead at 21 mos
Adamson et al., 2004 [17]37, MCervicalL C6 radiculopathy6 yrs ago for Hodgkin’s lymphomaPartialYesNoNot specifiedNoDead after 1 yr
30, FCervicalR Horner syndrome, R C6 radiculopathy, R tricep and wrist extensor weakness5 yrs ago for Hodgkin’s lymphomaPartialNoNoNot specifiedNoDead after 1 yr
Amin et al., 2004 [9]38, MCauda equinaBack pain, leg weakness, bowel and bladder dysfunction10 yrs ago for testicular seminoma, 30 Gy/15 fractions over 3 wksBiopsyNoYes, palliativeYes, 7 mosNot specifiedNot specified
Albayrak et al., 2006 [18]25, MThoracicParaparesis, bladder dysfunctionNF1Not specifiedTotalNoNoYes, 7 wksLungAlive at 7 wks
Chamoun et al., 2009 [14]5, FCervicalPain, gait disturbanceNot specifiedPartialYesYesYesBrain, thoracic and lumbar spineAlive at 4 mos
Xu et al., 20128, MLumbarPainNot specifiedTotalYesNoYesBrainDead at 16 mos
Mitsuhara et al., 201347, FCauda equinaBack pain, R leg weakness, bowel and bladder dysfunction, altered mental statusNF215 yrs ago for uterine and cervical cancer, 22 GyPartialYes, 36 Gy brain and spine, additional 14.4 Gy to lumbosacral lesion/28 fractionsNoNot specifiedNoNot specified
Stark et al., 201356, FSacralL leg radiculopathy, L foot paresis15 yrs ago for non-Hodgkin’s lymphomaNot specifiedNoYesYesBrainstem, spineDead at 24 mos
Wu et al., 20149, FThoracic, lumbar, sacralR hip pain, bilateral leg weaknessNF2Not specifiedPartialNoNoYesBrainDead at 9 mos
Li et al., 201433, FLow thoracic, upper lumbarLow back pain, R leg radiculopathy, hydrocephalusNot specifiedPartialYes, 28 Gy/19 fractionsNoYesBrain, diffuse spineDead at 29 mos
Lau et al., 2014 [10]43, MCauda equinaLow back pain, L leg radiculopathy for 5 mos10 yrs ago for testicular seminomaTotalNoYes, alternating between ifosfamide/doxorubicin and ifosfamide/etoposideYes, about 60 mosBrainstem, cervical spine, renalDead at 5 yrs
Thomas et al., 201449, MCauda equinaLow back pain, paraparesisNot specifiedPartialNoNoNoBrain and spineNot specified
Baharvahdat et al., 20163, FCervical, upper thoracicParaplegia, bladder and bowel dysfunctionNot specifiedPartialNoNoNoBrain and spineDead shortly after surgery
Chou et al., 2017a5–74 (mean 40)76% had adjuvant therapy38% over 2 yrs59% alive at 2 yrs
Samancia et al., 201727, MCervical, upper thoracicHydrocephalusNot specifiedPartialYesYesNoNoNot specified
Present study77, MLumbarLeft hip and buttock pain for 3 mosAbout 45 yrs ago for testicular cancerPartialNoNoNoIntracranial leptomeningeal diseaseDead 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 (), 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 (Figure 1). 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.

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 (Figure 2).

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 (Figure 3) 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.

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 [710].

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 [1019]. 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.

Abbreviations

CSF:Cerebral spinal fluid
CT:Computer tomography
EBRT:External bean radiation therapy
H&E:Hematoxylin and eosin
MPNST:Malignant peripheral nerve sheath tumor
MRI:Magnetic resonance imaging
NF1:Neurofibromatosis type 1.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

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Copyright © 2020 Osmond C. Wu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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