CASE REPORT

Multifocal spinal malignant peripheral nerve sheath tumorin an immunocompromised individual:case report and review of literature

V. R. Roopesh Kumar • Venkatesh S. Madhugiri •

Gopalakrishnan M. Sasidharan • C. V. Shankar Ganesh •

Sudheer Kumar Gundamaneni

Received: 2 August 2012 / Revised: 5 November 2013 / Accepted: 6 November 2013

� Springer-Verlag Berlin Heidelberg 2013

Abstract

Purpose Primary intraosseous spinal malignant periphe-

ral nerve sheath tumor (MPNST) is exceedingly rare.

MPNST with multifocal origin has been described to occur

in the extremities. Such a lesion has not been described to

occur in the spine. We describe a case of multifocal spinal

MPNST and to review the literature relevant to this rare

entity and its management.

Methods A 40-year-old immunodeficient patient pre-

sented with rapidly progressive paraparesis and mid back

ache.

Results Despite aggressive surgical decompression, he

developed multiple metastases 3 months after surgery.

However, he remained stable for 1 year without any

adjuvant therapy. Presently, he has received palliative

radiotherapy for spinal recurrence and cerebral metastasis.

Conclusion Multifocal spinal MPNST is a rare lesion. In

this instance, the multifocality of the disease and its odd

location could be attributed to the immunodeficiency state.

The prolonged survival could be due to an improvement in

his immune status due to HAART.

Keywords MPNST � Multifocal � Metastasis �Intraosseous � Immunodeficiency syndrome

Introduction

Malignant peripheral nerve sheath tumors (MPNSTs)

usually arise from peripheral nerve sheaths and rarely from

the coverings of the spinal nerves. Intraosseous MPNSTs

are very rare lesions; these arise mainly in the jaw bones

and occasionally in the long bones of the extremities [1, 2].

We report a patient who had a very rare combination of co-

synchronous discrete intraosseous and intradural spinal

lesions. This has not been reported hitherto.

Case report

A 42-year-old man presented with progressively worsening

mid backache since 6 weeks. Examination revealed spastic

paraparesis with power of MRC grade 2/5 in both lower

limbs. Lower limb deep tendon reflexes were exaggerated

and the plantar responses were bilaterally extensor. He had

a graded sensory loss below D9 involving all modalities of

sensation. There were no cutaneous markers of neurofi-

bromatosis type 1 (NF-1). Magnetic resonance imaging

(MRI) of the dorsal spine revealed two discrete lesions at

D7. The left-sided lesion was intradural (Fig. 1a) causing

spinal cord compression and extended into the left D7

neural foramen (Fig. 1d). The other lesion involved the

right D7 transverse process (Fig. 1a). Both lesions were

isointense on T1- and T2-weighted images (Figs. 1a, 2) and

enhanced with gadolinium administration (Fig. 1b). CT

scan revealed expansion and lysis of the cortical margins of

the D7 transverse process (Fig. 1c). He was found to be

HIV-1 positive; CD4? count was 31/ll (normal -410 to

1,590/ll) and total leucocyte count was 880 cells/mm3

(normal range 1,500–4,000 cells/mm3). He underwent D6–

D8 laminectomy and excision of both the lesions. At

V. R. Roopesh Kumar (&) � V. S. Madhugiri �G. M. Sasidharan � S. K. Gundamaneni

Department of Neurosurgery, Jawaharlal Institute

of Post-graduate Medical Education and Research (JIPMER),

2nd Floor, Super Specialty Block, Pondicherry 605006, India

e-mail: roops1975@gmail.com

C. V. Shankar Ganesh

Department of Neurosurgery, Apollo Specialty Hospital,

Chennai, India

123

Eur Spine J

DOI 10.1007/s00586-013-3103-z

surgery, a firm and vascular intradural tumor was seen

compressing the cord on the left side. This lesion was

excised in toto; the involved D7 spinal root was cut and

excised as well. A small extradural component in the

neural foramen adherent to the dura was also removed. The

dural defect was repaired with facial graft. The tumor

involving the right transverse process was excised in a

piece-meal fashion followed by thorough curettage of the

surrounding bony margins. Postoperatively, lower limb

power improved to normal over a period of 2 weeks.

Histopathologic examination of both the lesions was

diagnostic of MPNST (Fig. 3).

The patient was advised adjuvant therapy; he deferred

this due to personal problems. He was discharged on

antiretroviral therapy (HAART). Two months after sur-

gery, he developed headache and diplopia. MRI brain

revealed a metastatic lesion in the right occipital lobe

(Fig. 4b). Whole-body imaging revealed metastatic

deposits in the liver and right adrenal gland (Fig. 4a).

However, the operative region was free of tumor (Fig. 4c).

He was strongly advised to undergo adjuvant therapy;

however, due to poor family support and other constraints,

he refused and was subsequently lost to follow-up. A year

later, he presented with recurrence of pain at the operated

site. On examination, lower limb power was MRC grade

5/5 and he had no fresh neurological deficits. He was

ambulant and his Karnofsky performance score (KPS) was

100. In the interim, he reported that he had been compliant

in taking the HAART drugs; CD4? count had improved to

450 cells/ll. MRI brain and spine at this time revealed a

recurrence in the paraspinal region at D7; there was no

compression of the cord. There were two fresh cerebral

metastases—one lesion in the left temporal lobe and a

dural-based lesion over the left tentorium (Fig. 5). He

subsequently received palliative image-guided radiother-

apy (IGRT) for the spinal and cerebral metastases.

18 months after completion of radiotherapy, he remains

asymptomatic and is on regular follow-up.

Fig. 1 Preoperative imaging of the dorsal spine. a Axial T1-weighted

image showing an isointense lesion. b Axial post-contrast image

showing brilliant enhancement of the lesion (red arrow) and

significant compression of the cord (black arrow). c Axial CT image

showing thinning of the cortical margins and expansion of the right

D7 transverse process. d Coronal T1W image showing extension into

the neural foramen on the left (arrow)

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Discussion

MPNST

MPNSTs are rare malignant tumors of peripheral nerve

sheath origin occurring in 0.001 % of general population

[3]. Most of them occur in patients with NF-1 (50 %) [1].

Rarely, they arise by a malignant degeneration of a

schwannoma or ganglioneuroma. A small proportion

occurs in patients who have undergone radiotherapy for

other ailments (10 %) [3]. MPNST typically occurs in the

subcutaneous or deep tissues of the trunk (50 %), extrem-

ities (30 %) and head and neck regions (20 %) [4]. Intra-

osseous MPNSTs are rare and are mostly confined to the

mandible or maxilla and occasionally occur in the long

bones of the limbs [1, 2]. The origin of an intraosseous

MPNST is still obscure. They are thought to arise from the

small periosteal nerves that accompany the nutrient artery.

Other theories include secondary periosteal invasion by a

primarily extra-osseous tumor or a possible origin from

congenital rests of neuro-ectodermal cells [1].

Spinal intraosseous MPNST

Intraosseous MPNSTs have different clinical characteris-

tics compared to their soft tissue counterparts. They have a

wider age distribution and are not usually associated with

NF-1 [2]. These tumors also behave more aggressively;

however, this biologic aggressiveness may actually reflect

the difficulty in radical extirpation of the lesion and

achieving clear resection margins [5]. Patients with posi-

tive surgical margins have a 2.4-fold risk of developing a

local recurrence and 1.8-fold risk of dying of the disease

[6].

The spine is a rare site for intraosseous MPNST. There

have been only four reports of patients with spinal intra-

osseous MPNST [4, 5, 7, 8] (Table 1). The current report is

the fifth case in literature. 4 out of the five reported patients

with spinal intraosseous MPNST (including the present

case) developed extensive metastases within 1 year of

tumor excision. This reflects aggressive behavior. As

already postulated, this may merely reflect the difficulty in

achieving a radical resection in this location. Alternatively,

Fig. 2 Preoperative MRI spine-sagittal T2W image showing the

intradural component of the left-sided lesion

Fig. 3 a Lesion composed of a mixture of pauci and hypercellular

areas with increased vascularity (H&E 9100). b The tumor cells are

moderately pleomorphic and spindle shaped with tapering ends. The

cells are arranged in short fascicles. The tapered nuclei are evident

and are typical (H&E 9400). c The hypercellularity and mitosis are

evident (H&E 9400)

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an intraosseous origin itself may imply an aggressive bio-

logical behavior. This would warrant an exhaustive search

for metastases in these patients at presentation. A more

radical en masse excision may need to be attempted. While

this can be achieved if only the posterior spinal elements

are involved, it may be exceedingly difficult to achieve

similar results if either the anterior or lateral elements are

involved in addition.

The present case

This patient’s disease was unique compared to previously

reported cases. Two discrete tumors were found at the same

spinal level-one lesion in the intradural plane and the other

in the intraosseous plane on the contralateral side. The

presence of co-existent multiple discrete lesions implying a

multifocal origin of the tumor has not been described

Fig. 4 a MRI of abdomen

showing liver and right adrenal

gland metastasis (arrows).

b MRI brain with gadolinium

enhancement showing the right

occipital metastasis. c Post

operative MRI dorsal spine-

sagittal T2W image showing no

local recurrence

Fig. 5 a MRI at 1 year post

surgery showing recurrence at

D7 in the paraspinal area

(arrow). b MRI brain showing

fresh temporal and tentorial

dural-based metastases

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hitherto. Multifocal MPNST has been described in the

limbs but such lesions occurring in the spine are not

reported. The other unique feature is the association of HIV

infection. The only soft tissue tumor that has been classi-

cally associated with HIV infection is Epstein–Barr virus-

related meningeal leiomyosarcoma [9, 10]. The association

of immunodeficiency with MPNST is not very clear. The

only such previously case reported is that of MPNST

arising from the ethmoid sinus in a HIV-positive patient.

The multifocal origin of this lesion in an uncommon

location could be attributed to the immunodeficiency state.

In the present instance, the patient survived more than a

year despite receiving no adjuvant therapy. Although there

was progression of the disease and multiple new metastases

appeared, he remained clinically stable. It is possible that

the disease was disseminated at the time of diagnosis,

although micro-metastases would have been missed. That

the patient remained clinically stable, we postulate, could

be due to the improved immune status as a consequence of

HAART leading to a rise in the CD4? count. Adjuvant

therapy has not been shown to improve the survival [11].

Thus, it is entirely possible that the discordance between

the stable clinical status and progressive metastatic disease

could be due to an improved immune status. This would

imply that immunotherapy may be a possible tool in the

control of this cancer.

HIV and cancer

HIV infection is classically associated with an increased

risk of developing cancers such as Kaposi’s sarcoma, non-

Hodgkin’s lymphoma, and invasive cervical cancer [12].

These three malignancies have an identified viral

pathogenesis. The incidence of non-AIDS defining cancers

(NADC) has also been increasing among persons infected

with HIV as a result of increased longevity brought about

by the routine use of HAART [13]. It has also been clearly

established that the immune status of HIV-positive patients

(as reflected by the CD4? count) affects the incidence of

NADC in HIV-infected persons. Increasing CD4? counts

result in a reduced incidence of both AIDS defining and

NAD cancers [14]. It is possible that this patient’s stable

clinical status might similarly have been the result of

immune reconstitution secondary to HAART.

The association of HIV infection with soft tissue tumors

is not common. Recently, a report of a meningeal heman-

giopericytoma diagnosed in an HIV-infected individual

was published [15]. The tumor displayed aggressive

behavior and the patient developed multiple metastases and

local recurrence within a very short span of time. It is not

thought that soft tissue sarcomas have any association with

viral oncogenes. Thus, it may be possible that HIV-induced

immunosuppression would lead to accelerated tumor

growth and early metastasis of sarcomas as well.

Conclusion

Multifocal MPNST is a novel entity and not enough clin-

ical experience exists in their management. Occurrence of

MPNST in an intraosseous location should prompt an

extensive search for metastases even at the time of pre-

sentation. This would be essential for accurate staging and

to plan appropriate adjuvant therapy. Whenever possible,

radical surgical resection should be attempted considering

their more aggressive biological behavior. Immunodefi-

ciency may further adversely affect the prognosis in this

highly aggressive tumor.

Conflict of interest None of the authors has any potential conflict of

interest.

References

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Table 1 Details of the spinal MPNST cases reported in literature

Sl.

no

Author Year Age/

sex

Location Outcome

1 Khan RJ 1998 40/F C2 body Died after

1 year

2 Gnanalingam

et al.

2004 59/F D3 lamina,

pedicle

spinous

process

Multiple

mets

at 1 year

3 Miyakoshi

et al.

2007 75/F D7 lamina and

spinous

process

Died after

6 months

4 Moon et al. 2008 41/M C6–C7 D1

lamina and

spinous

process

30-month

follow-up

5 Present case 2011 42/M D7 transverse

process

Alive 18

months after

diagnosis

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predictors of non AIDS-defining cancers in men and women with

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after the introduction of HAART. J Acquir Immune Defic Syndr

62(4):414–420

14. Petoumenos K, van Leuwen MT, Vajdic CM et al (2013) Cancer,

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