Pediatr Blood Cancer 2010;54:170–172

BRIEF REPORTSuccessful Radiation Therapy for Supratentorial Primitive Neuroectodermal

Tumor and Epidermolysis Bullosa Simplex

Sejal Bavishi, BA,1 Kenneth Wong, MD,1 Thamani Delgardo, BA, RTT,1 Araz Marachelian, MD,2

and Soumen Khatua, MD2*

INTRODUCTION

Epidermolysis bullosa (EB) is a heritable skin disorder

characterized by increased skin fragility and blister formation

after minor mechanical trauma. Three major inherited forms are

EBS, junctional epidermolysis bullosa (JEB), and dystrophic

epidermolysis bullosa (DEB) [1]. Phenotypic variants range from

mild blistering largely localized to the hands and feet, to a more

severe generalized form, leading to death in early infancy. EBS is the

most common and the mildest form of EB and has three subtypes.

They are EBS-Koebner, EBS Weber-Cockayne and EBS Dowling-

Meara. Blisters in EBS usually occur in the intraepidermal area.

EBS-Koebner commonly presents at birth to early infancy and

involves the hands, feet and extremities. EBS Weber-Cockayne

commonly occurs in children and adults and presents on the palms

and soles only after a distinct traumatic event. EBS Dowling-Meara,

a severe form of EBS, occurs at or shortly after birth with a

generalized distribution of blisters [2]. Skin lesions in EBS usually

heal without scarring and extracutaneous involvement is extremely

rare. Evaluation of malignancies in EB shows that squamous cell

carcinoma (SCC) is the most serious complication of EB in adults,

especially those with DEB. By mid-adulthood, nearly all patients

with DEB will have had at least one SCC and nearly 80% will have

died of metastatic SCC despite aggressive surgical resection [3].

Central nervous system (CNS) tumors in children with EB are

extremely rare. Only one case has been reported of an infant with

JEB diagnosed with congenital rhabdoid tumor of the CNS at

autopsy [4].

Supratentorial primitive neuroectodermal tumor (sPNET) in

children are rare and represent less than 2.5% of childhood brain

tumors, with the median age at presentation of 3 years. While the

treatment for sPNETs is not well defined, current treatment involves

a multifaceted approach that includes surgery, chemotherapy, and

post-operative radiotherapy. However, sPNETs are more resistant

to conventional treatment modalities, making them less curable than

medulloblastomas. High-dose cyclophosphamide-based chemo-

therapy with stem cell support after risk-adapted craniospinal

irradiation (CSI) results in excellent event free survival (EFS) in

patients with newly diagnosed average risk (AR) sPNET [5]. Long-

term neurocognitive toxicity and development of secondary malig-

nancies are well-known complications of CSI. The tolerability of

CSI in patients with EB and the long-term complications is unknown

and has not been reported. However there are reports of radiation

delivered locally to treat SCC in patients with underlying DEB [6].

This novel case demonstrates the presentation of a patient with EBS

and sPNET and highlights the feasibility and successful use of CSI

and focal tumor bed radiation.

CASE REPORT

A 7-year-old male presented with generalized hyperpigmenta-

tion of the skin at birth. A diagnosis of EBS was confirmed by skin

biopsy. His skin blistered after minor trauma, which was managed

symptomatically using emollients and topical antibiotics. One year

prior to presentation, he started developing nonfocal headaches.

Though initially mild, they increased over the following year and

were associated with vomiting. These episodes were treated

symptomatically as sinus infections. One week prior to admission,

he developed ataxia and diplopia, with increasing intensity of

headaches. He was evaluated in the emergency department, where a

CT scan followed by an MRI showed a mixed cystic solid lesion in

the left anterior temporal lobe. Following admission, he underwent a

craniotomy and gross total resection of the left temporal lobe mass

(Fig. 1). His spine MRI and CSF cytology were negative for any

evidence of metastasis. Pathology was consistent with sPNET.

Post-operatively his symptoms improved dramatically. Following

GCSF stimulation, he underwent successful stem cell harvest. He

was then treated with conventional CSI to a total dose of 23.4 Gy in

13 fractions. CSI was followed by a focal boost to the tumor bed

using intensity modulated radiotherapy (IMRT) to a dose of 32.4 Gy

in 18 fractions. Several important precautionary measures were

taken to protect the patient’s underlying fragile skin condition from

the effects of radiotherapy. Radiation therapy was administered in

the supine position in contrast to the conventional prone position.

Epidermolysis bullosa simplex (EBS) is a heritable skin disordercharacterized by skin fragility and blistering. While its most severevariant, dystrophic epidermolysis bullosa (DEB) is associated withsquamous cell carcinoma (SCC), the development of extracutaneousneoplasms in EBS is extremely rare. We report a novel case of

supratentorial primitive neuroectodermal tumor (sPNET) in a 7-yearmale with EBS. Experience of radiation therapy and its challenges inchildren with EBS has rarely been reported. Pediatr Blood Cancer2010;54:170–172. � 2009 Wiley-Liss, Inc.

Key words: epidermolysis bullosa simplex; radiation therapy; supratentorial PNET

� 2009 Wiley-Liss, Inc.DOI 10.1002/pbc.22281Published online 16 September 2009 in Wiley InterScience(www.interscience.wiley.com)

——————1Department of Radiation Oncology, Childrens Hospital Los Angeles,

Los Angeles, California; 2Center for Cancer and Blood Disorders,

Neural Tumors Program, Childrens Hospital Los Angeles, Los

Angeles, California

The authors declare that there is no disclosure and any conflict of

interest.

*Correspondence to: Soumen Khatua, 10232 Splendor Ridge Avenue,

Las Vegas, NV 89135. E-mail: soumenkhatua@aol.com

Received 27 July 2009; Accepted 12 August 2009

The treatment couch as well as the customized head immobilization

cushion was lined with cotton padding. The HeadFix device was

fabricated with a nasal bridge rather than a conventional bite block.

Petroleum jelly was liberally applied to the upper lip, nose, and other

high friction points along with topical emollients to minimize the

effects of friction injury. His skin toxicity profile was restricted

to grades 1–2 (Fig. 2). This included small patches of moist

desquamation in his ear folds and a few subcentimeter bullae on his

occiput. Mild increase in his hyperpigmentation was seen during his

radiation, which is slowly resolving. He had minimal nausea and

vomiting, which were treated symptomatically and mild myelo-

suppression during his radiation therapy. He is currently doing well

and will begin four cycles of dose-intensive cyclophosphamide

based chemotherapy with stem cell rescue.

DISCUSSION

The association of EB with brain tumors and its treatment has not

been reported earlier. The only prior case report is of a male child

with JEB who was found to have a cerebellar atypical teratoid

rhabdoid (AT/RT) tumor at autopsy [4]. Due to the extreme rarity of

this case, the tolerability of CSI is unknown in these patients. There

are a few case reports of SCC in adult DEB patients, who were

treated with localized radiation, but the toxicity was not reported

Pediatr Blood Cancer DOI 10.1002/pbc

Fig. 1. Pre-operative (A) and post-operative (B) MRI scans showing a mass in the left temporal lobe with gross total resection. [Color figure can be

viewed in the online issue, which is available at www.interscience.wiley.com.]

Fig. 2. A: Precautionary measures taken to protect the patient’s skin are illustrated. Neotrode leads are placed inside 2� 2 gauze and saline is

poured on the gauze to prevent the adhesive on the leads from sticking to the skin. Mepitac tape is used to secure gauze in place. Marks are made in a

dot pattern to avoid irritation of the skin. B: Cotton padding is placed on top of the treatment couch as well as the custom head immobilization bag.

[Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Radiation Therapy for sPNET in a Child With EBS 171

[7,8]. The only pediatric case in the literature reported a 13-year-old

female with DEB who developed SCC, and was treated surgically

without any radiation therapy [9]. Due to the underlying delicate

condition of the patient’s skin and its propensity to blister

after minor trauma, delivering CSI with focal boost was a

therapeutic challenge from the beginning. Several known side

effects to the skin following radiation therapy include irritation,

dryness, erythema, blistering, hyperpigmentation, and desquama-

tion. It was expected that these side effects would be exacerbated in

children with EB like our patient. Using precautionary measures to

the skin as mentioned earlier and delivering radiation in the supine

position, we were able to limit the skin toxicity to grade 2. However,

it remains to be seen how children with the EB and its variants would

tolerate extended field radiation and whether long-term toxicities

would include increased incidence of SCC in these children.

Radiation therapy is an important component of the multi-

modality treatment for children with sPNET. Though similar

histologically to the medulloblastoma, the more distinct oncogenic

pathways in these tumors make them different from their

infratentorial counterparts [10]. They are very aggressive and have

been treated with intensive therapy including CSI of 36 Gy. Several

studies have supported the beneficial role of high-dose radiation

treatment of the entire neuraxis as a critical part of the multimodality

treatment for sPNET [11,12]. Though efforts have been devoted in

various studies to eliminate, delay, or reduce dose and fields of

radiation therapy, the results have met with reduced survival rates

[13–15]. Thus, 36 Gy CSI remains an integral part of the

multimodality therapeutic approach for children with these tumors.

However, a recent study using reduced dose CSI of 23.4 Gy in AR

patients followed by four cycles of high dose cyclophosphamide

based chemotherapy with stem cell rescue showed a 5-year overall

survival rate of 88� 13% survival [5]. Based on these promising

data, we treated our AR patient with a reduced dose CSI of 23.4 Gy.

This dose was hoped to reduce the long-term neurocognitive sequela

and development of secondary malignancies.

This report highlights several precautionary measures to

potentially protect the integrity of the fragile skin in pediatric

patients with EBS during radiation treatment. In addition, the case

emphasizes the importance of the genetic and pathophysiologic

associations between the development of brain tumors in children

with underlying EB. Children with EB and brain tumors require a

multimodality therapeutic approach to further define optimal

treatment strategies.

REFERENCES

1. Pai S, Marinkovich MP. Epidermolysis bullosa: New and emerging

trends. Am J Clin Dermatol 2002;3:371–380.

2. Pfender EG, Bruckner A, Conge P, et al. Basic science of

epidermolysis bullosa and diagnostic and molecular character-

ization: Proceedings of the 2nd International Symposium on

Epidermolysis Bullosa, Santiago, Chile, 2005. Int J Dermatol 2007;

46:781–794.

3. Fine JD, Johnson LB, Weiner M, et al. Epidermolysis bullosa and

the risk of life-threatening cancers. The National EB registry

experience, 1986–2006. J Am Acad Dermatol 2009;60:203–211.

4. Krous HF, Chadwick AE, Haas EA, et al. Congenital cerebellar

malignant rhabdoid tumor in an infant with junctional epidermol-

ysis bullosa. Pediatr Dev Pathol 2007;10:481–486.

5. Chintagumpala M, Hassall T, Palmer S, et al. A pilot study of risk-

adapted radiotherapy and chemotherapy in patients with supra-

tentorial PNET. Neuro Oncol 2009;11:33–40.

6. Bastin KT, Steeves RA, Richards MJ. Radiation therapy for

squamous cell carcinoma in dystrophic epidermolysis bullosa:

Case reports and literature review. Am J Clin Oncol 1997;20:

55–58.

7. Weber F, Bauer JW, Sepp N, et al. Squamous cell carcinoma in

junctional and dystrophic epidermolysis bullosa. Act Derm

Venereol 2001; 81:189–192.

8. McGrath JA, Schofield OM, Mayou BJ, et al. Epidermolysis

bullosa complicated by squamous cell carcinoma: Report of

10 cases. J Cutan Pathol 1992;19:116–123.

9. Ayman T, Yerebakan O, Ciftcioglu MA, et al. A 13-year-old girl

with recessive dystrophic epidermolysis bullosa presenting with

squamous cell carcinoma. Pediatr Dermatol 2002;19:436.

10. Inda MM, Perot C, Guillaud-Bataille M, et al. Genetic hetero-

geneity in supratentorial and infratentorial primitive neuroecto-

dermal tumours of the central nervous system. Histopathology

2005;47:631–637.

11. McBride SM, Daganzo SM, Banerjee A, et al. Radiation is an

important component of multimodality therapy for pediatric non-

pineal supratentorial primitive neuroectodermal tumors. Int J

Radiat Oncol Biol Phys 2008;72:1319–1323.

12. Timmermann B, Kortmann RD, Kuh LJ, et al. Role of radiotherapy

in supratentorial primitive neuroectodermal tumor in young

children: Results of the German HIT-SKK87 and HIT-SKK92

trials. J Clin Oncol 2006;24:1554–1560.

13. Massimino M, Gandola L, Spreafico F, et al. Supratentorial

primitive neuroectodermal tumors (S-PNET) in children: A

prospective experience with adjuvant intensive chemotherapy

and hyperfractionated accelerated radiotherapy. Int J Radiat Oncol

Biol Phys 2006;64:1031–1037.

14. Pizer BL, Weston CL, Robinson KJ, et al. Analysis of patients with

supratentorial primitive neuro-ectodermal tumours enteredinto

the SIOP/UKCCSG PNET 3 study. Eur J Cancer 2006;42:1120–

1128.

15. Johnston DL, Keene DL, Lafay-Cousin L, et al. Supratentorial

primitive neuroectodermal tumors: A Canadian pediatric brain

tumor consortium report. J Neurooncol 2008;86:101–109.

Pediatr Blood Cancer DOI 10.1002/pbc

172 Bavishi et al.