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CASE REPORT
Year : 2022  |  Volume : 18  |  Issue : 6  |  Page : 1823-1826

Challenging treatment of parameningeal rhabdomyosarcoma with leptomeningeal metastasis: Case report and review of literature


1 Department of Radiation Oncology, Akdeniz University, Antalya, Turkey
2 Department of Pediatric Oncology, Akdeniz University, Antalya, Turkey
3 Department of Radiology, Akdeniz University, Antalya, Turkey
4 Department of Pathology, Akdeniz University, Antalya, Turkey

Date of Submission10-Oct-2020
Date of Decision24-Feb-2022
Date of Acceptance11-May-2022
Date of Web Publication14-Oct-2022

Correspondence Address:
Rahmi Atıl Aksoy
Department of Radiation Oncology, Akdeniz University, Antalya
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_1491_20

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 > Abstract 


Parameningeal rhabdomyosarcomas (PM RMSs) are rarely seen childhood tumors. Their treatment might be challenging and prognosis is poor compared to other head and neck RMS. Here we report a PM RMS presenting with leptomeningeal seeding metastasis a year after diagnosis. A five-year-old girl presented with an enlarging mass protruding from the right ear and right facial paralysis. Magnetic resonance imaging (MRI) revealed a large mass extending from right external auditory canal to the temporal lobe, pterygoid fossa and nasopharynx with an intracranial component indenting the right temporal lobe and extending into the right cavernous sinus. Trucut biopsy revealed embryonal rhabdomyosarcoma. Cerebrospinal fluid (CSF) cytology was negative for malignant cells. Chemotherapy was started since it was found unresectable. At second week of chemotherapy, radiotherapy was applied to primary tumor location with intensity-modulated radiation therapy (IMRT) technique in 1.8 Gy fractions to total dose of 50.4 Gy. At week 27, MRI showed significant response. At week 36, the patient presented with vomiting and tendency to sleep. MRI was found to be compatible with meningitis and antibacterial therapy was started. At week 39, chemotherapy was stopped. But MRI performed one month later revealed linear contrast enhancements around the spinal cord compatible with leptomeningeal metastases. Chemotherapy and craniospinal irradiation were applied. But the patient did not improve and received palliative treatment. Six months after the completion of radiotherapy the patient died. Treatment of parameningeal rhabdomyosarcomas require multidisciplinary approach including surgery, radiotherapy, and chemotherapy. Prognosis is poor for patients with leptomeningeal spread.

Keywords: Chemotherapy, leptomeningeal metastasis, parameningeal rhabdomyosarcoma, radiotherapy


How to cite this article:
Aksoy RA, Güler E, Karaali K, Aksu MG, Gürer &E, Akbaş H, Özay MG. Challenging treatment of parameningeal rhabdomyosarcoma with leptomeningeal metastasis: Case report and review of literature. J Can Res Ther 2022;18:1823-6

How to cite this URL:
Aksoy RA, Güler E, Karaali K, Aksu MG, Gürer &E, Akbaş H, Özay MG. Challenging treatment of parameningeal rhabdomyosarcoma with leptomeningeal metastasis: Case report and review of literature. J Can Res Ther [serial online] 2022 [cited 2022 Dec 2];18:1823-6. Available from: https://www.cancerjournal.net/text.asp?2022/18/6/0/358610




 > Introduction Top


Rhabdomyosarcoma (RMS) is the most commonly seen soft tissue tumor of childhood which originates from skeletal muscle cells and is usually located in the head and neck, genitourinary system, and the extremities.[1] Head and neck RMSs are responsible for approximately 35% of these tumors and consist of orbital, parameningeal (skull base), and non-parameningeal (maxillofacial region) RMS.[2] Orbital and non-parameningeal RMSs have high cure rates; however, parameningeal rhabdomyosarcomas (PM RMS) are associated with low local control and overall survival rates.[3]

Risk stratification utilizes TNM staging classification (tumor size, invasiveness, location) and clinical grouping (international rhabdomyosarcoma study group) based on the degree of surgery, nodal involvement, and distant metastases. RMS commonly metastasizes to the lungs, bone marrow, and other soft tissues.[4] While leptomeningeal metastases have been rarely reported, it is a major pattern of distant failure in PM RMS. In the present study, a case of PM RMS treated with chemotherapy and radiotherapy (RT) that developed spinal metastases one year after radiotherapy was presented.


 > Case Report Top


A five-year-old girl was admitted with a mass protruding from the right external auditory canal and right peripheric facial paralysis. Magnetic resonance imaging (MRI) revealed a mass lesion, extending from the right external auditory canal, causing destruction of the petrous and apical parts of the right temporal bone, invading medial portion pterygoid fossa, right parapharyngeal space, and nasopharynx. Intracranial component of the mass was indenting the right temporal lobe and extending into the right cavernous sinus [Figure 1]. The maximum diameter of the mass within the temporal bone was 52 mm. Trucut biopsy was performed and the tumor was diagnosed as embryonal rhabdomyosarcoma [Figure 2]. Examination of cerebrospinal fluid (CSF) cytology and bone marrow biopsy were negative for malignant cells. Positron emission tomography (PET) scan revealed no metastasis. The patient was accepted as stage 3, intermediate risk parameningeal embryonal rhabdomyosarcoma.
Figure 1: Transverse T1-weighted post-contrast MRI shows a mass lesion, extending from the right external auditory canal, causing destruction of the petrous and apical parts of right temporal bone, invading medial portion pterygoid fossa, right parapharyngeal space, and nasopharynx. The mass shows marked contrast enhancement (arrows)

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Figure 2: Rhabdomyoblastic tumor cells showing infiltration in the form of burrows under the stratified squamous epithelium (HE ×100)

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Alternating chemotherapy consisting of vincristin/doxorubicin/cyclophosphamide and etoposide/ifosfamide had been started. At second week of chemotherapy, radiotherapy was applied to primary tumor location with intensity-modulated radiation therapy (IMRT) technique in 1.8 Gy fractions to total dose of 50.4 Gy. At week 27, MRI and PET scan showed significant response. The patient was evaluated by ear, nose, and throat (ENT) department and accepted as inoperable. At week 36, while patient was on chemotherapy, the patient presented with vomiting and tendency to sleep. Lumbar puncture (LP) was performed, and CSF protein and glucose was found to be 174 mg/dl and 67 mg/dl, respectively. Simultaneously, blood glucose level was 167 mg/dl, CSF cytology showed neutrophils, lymphocytes and no malignant cells were seen. MRI was reported to be compatible with meningitis with increased T2 flair intensities. CSF bacterial and tuberculosis culture, HSV serology and quantiFERON test were negative. Patient was then started on meropenem, vancomycin, and acyclovir. After meningitis treatment was completed, control LP showed that CSF protein and glucose levels returned to normal. However, three days later, she presented with headache and vomiting. Tetraventricular hydrocephalus was detected on brain tomography. Extraventricular drainage and ventriculoperitoneal shunt operation was performed due to hydrocephalus which developed during meningitis. She completed her chemotherapy protocol. One month later, she presented with vomiting and headache again. MRI showed linear contrast enhancements around the whole spinal cord, especially the cervical cord and conus medullaris, which suggested leptomeningeal metastasis. Review of previous MRI showed diffuse leptomeningeal enhancement [Figure 3] and [Figure 4]. Two cycles of irinotecan/temozolomide/vincristine and 3 cycles of temsirolimus/vinorelbine/cyclophosphamide were given. Craniospinal irradiation (CSI) was performed, and 27 Gy in 1.8 Gy fractions was given. Most critical organ in previous irradiation field was spinal cord and the dose of radiotherapy was calculated by considering spinal cord repair capacity and tolerance dose. But following treatment, the patient showed progression and received palliative treatment. Six months after the completion of the radiotherapy the patient expired.
Figure 3: Transverse T1-weighted post-contrast MRI shows leptomeningeal enhancement around brainstem, Sylvian sulci, and frontal sulci (arrows)

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Figure 4: Sagittal T1-weighted post-contrast MRI of the spine shows leptomeningeal enhancement around cervical cord (a) and conus medullaris (b)

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 > Discussion Top


Parameningeal rhabdomyosarcomas (PM RMSs) located in the paranasal sinus, infratemporal fossa or pterygopalatine fossa have poor prognosis. The Intergroup Rhabdomyosarcoma Study Group (IRSG) reported that less than 7% of localized PM RMS patients develop central nervous system (CNS) relapse. High-risk characteristics associated with meningeal spread are cranial nerve palsy, skull base erosion, and intracranial extension.[5] Wolden et al.[6] reported that local failure was higher in tumor sizes of 5 cm and larger, and that novel treatment approaches were needed in this subgroup. Our case had three risk factors since she had intracranial extension, 7th cranial nerve palsy, and had a large tumor with a maximum diameter of 52 mm.

Time of radiotherapy is controversial. The criteria for selecting PM patients for early radiotherapy has mostly been based on criteria that adversely increase the risk of failure such as unfavorable age, meningeal involvement, large tumor size, and unfavorable primary site.[7] Lucas et al.[8] reported local control rates may be compromised in selected patients with parameningeal tumors when radiotherapy is delayed and given with lower doses of cyclophosphamide. A study performed by Arndt et al.[9] reported that alternating cycles of vincristine/doxorubicin/cyclophosphamide and etoposide/ifosfamide was effective treatment in intermediate risk RMS. Our case was treated with this chemotherapy regimen. Additionally, the patient had intracranial extension and 7th cranial nerve palsy; therefore, radiotherapy was started at second week of chemotherapy.

Diagnosis of leptomeningeal metastasis can be difficult since presentation might be nonspecific.[10] Some patients experience rapid decline. When our case presented with vomiting and tendency to sleep, MRI of brain and spine were reported to be normal except increased signal intensities and her CSF findings were compatible with meningitis. But review of brain MRI suggested CNS relapse. When the meningitis process develops into PM RMS, leptomeningeal spread should be especially considered.

Donaldson et al.[11] suggested conventionally fractionated radiotherapy (CFRT, 1.8 Gy fractions to total dose of 50.4 Gy) and chemotherapy as the standard of care in group III RMS patients. In our case, maximum tumor diameter was 52 mm and radiotherapy was applied in a total of 50.4 Gy in 1.8 Gy fractions. The current Children Oncology Group study ARST1431 is assessing dose escalation to 59.4 Gy for tumors above 5 cm in an effort to improve local control for large tumors.[12]

Previously, whole brain radiotherapy (WBRT) and/or high-dose intrathecal chemotherapy were used upfront to prevent CNS relapse in patients presenting with PM RMS with high-risk features.[13] However, data showing treatment-related toxicities in patients receiving intrathecal chemotherapy and unclear benefit of WBRT or CSI led to discontinuation of CNS-directed prophylaxis.[5],[14] Recently, gross tumor volume (GTV) was defined as the extent of disease at diagnosis and the clinical target volume (CTV) was designed to allow a 1-cm margin beyond the GTV, and an additional 0.3-cm margin was added to obtain the planning target volume (PTV).[15] In our patient, radiotherapy volumes were created in a similar way.

Interval of spinal seeding and diagnosis has been reported to be a wide range. In a study by De et al.,[10] 23 cases of CNS relapse, of which 13 were PM RMS, were analyzed. CNS relapse occurred at median 12 months after diagnosis. Our case developed leptomeningeal spread one year following diagnosis as well.

Treatment of leptomeningeal metastasis is challenging and the role of CSI is controversial. In the cohort study by Brian De, 23 RMS patients with CNS relapse were analyzed. They reported that treatment of parenchymal brain metastasis generally consisted of surgical resection, stereotactic radiosurgery (SRS), WBRT, and/or CSI for patients with coexisting leptomeningeal disease. Treatment of leptomeningeal disease generally consisted of CSI and/or systemic intrathecal chemotherapy. In this cohort, patients treated with CNS-directed RT did significantly better than those who did not receive said treatment.[10] In another study, it was reported that CSI improves quality of life as it decreases neurological dysfunction.[16] Our case did not show improvement following RT and died a few months later. Toxicity of CSI should be considered in these vulnerable patient groups.[17] Yavas et al.[18] reported a case of PM RMS with leptomeningeal metastasis who developed sepsis following CSI. Choice of RT dose and field at CNS relapse can be challenging, particularly for patients who already received RT to a parameningeal site. Re-irradiation dose range in literature is wide. Brian De et al.[10] treated their diffuse leptomeningeal metastasis patients with CSI to 36 Gy. They reported no toxicities, but majority of patients survived less than 3 months. We treated our case with CSI of 27 Gy in 1.8 Gy fractions. Since spinal cord was in previous primary target volume, we considered the repair capacity and tolerance dose of spinal cord.


 > Conclusion Top


Treatment of parameningeal rhabdomyosarcomas require a multi-disciplinary approach that includes surgery, radiotherapy, and chemotherapy. The risk of meningeal spread should be determined. Prognosis is poor for patients with leptomeningeal spread. There is a need for multi-centric trials to improve treatment modalities in this vulnerable patient group.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

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Iatrou I, Theologie-Lygidakis N, Schoinohoriti O, Tzermpos F, Vessala AM. Rhabdomyosarcoma of the maxillofacial region in children and adolescents: Report of 9 cases and literature review. J Craniomaxillofac Surg 2017;45:831-8.  Back to cited text no. 2
    
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Wolden SL, Wexler LH, Kraus DH, Laquaglia MP, Lis E, Meyers PA. Intensity-modulated radiotherapy for head-and-neck rhabdomyosarcoma. Int J Radiat Oncol Biol Phys 2005;61:1432-8.  Back to cited text no. 3
    
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Raney RB Jr, Tefft M, Maurer HM, Ragab AH, Hays DM, Soule EH, et al. Disease patterns and survival rate in children with metastatic soft-tissue sarcoma. A report from the Intergroup Rhabdomyosarcoma Study (IRS)-I. Cancer 1988;62:1257-66.  Back to cited text no. 4
    
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Raney RB, Meza J, Anderson JR, Fryer CJ, Donaldson SS, Breneman JC, et al. Treatment of children and adolescents with localized parameningeal sarcoma: Experience of the Intergroup Rhabdomyosarcoma Study Group protocols IRS-II through -IV, 1978-1997. Med Pediatr Oncol 2002;38:22-32.  Back to cited text no. 5
    
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Wolden SL, Lyden ER, Arndt CA, Hawkins DS, Anderson JR, Rodeberg DA, et al. Local control for ıntermediate-risk rhabdomyosarcoma: Results from D9803 according to histology, group, site, and size: A report from the children's oncology group. Int J Radiat Oncol Biol Phys. 2015;93:1071-6.  Back to cited text no. 6
    
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Merks JH, De Salvo GL, Bergeron C, Bisogno G, De Paoli A, Ferrari A, et al. Parameningeal rhabdomyosarcoma in pediatric age: Results of a pooled analysis from North American and European cooperative groups. Ann Oncol 2014;25:231-6.  Back to cited text no. 7
    
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Lucas JT Jr, Pappo AS, Wu J, Indelicato DJ, Krasin MJ. Excessive treatment failures in patients with parameningeal rhabdomyosarcoma with reduced-dose cyclophosphamide and delayed radiotherapy. J Pediatr Hematol Oncol 2018;40:387-90.  Back to cited text no. 8
    
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Arndt CA, Nascimento AG, Schroeder G, Schomberg PJ, Neglia JP, Sencer SF, et al. Treatment of intermediate risk rhabdomyosarcoma and undifferentiated sarcoma with alternating cycles of vincristine/doxorubicin/cyclophosphamide and etoposide/ifosfamide. Eur J Cancer 1998;34:1224-9.  Back to cited text no. 9
    
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De B, Kinnaman MD, Wexler LH, Kramer K, Wolden SL. Central nervous system relapse of rhabdomyosarcoma. Pediatr Blood Cancer 2018;65:10.1002/pbc. 26710.  Back to cited text no. 10
    
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Donaldson SS, Meza J, Breneman JC, Crist WM, Laurie F, Qualman SJ, et al. Results from the IRS-IV randomized trial of hyperfractionated radiotherapy in children with rhabdomyosarcoma--A report from the IRSG. Int J Radiat Oncol Biol Phys 2001;51:718-28.  Back to cited text no. 11
    
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National Cancer Institute (NCI) and Children's Oncology Group. Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma. Available from: https://clinicaltrials.gov/ct2/show/NCT02567435. ClinicalTrials.gov Identifier: NCT02567435. [Last accessed on 2019 Aug 30].  Back to cited text no. 12
    
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Raney RB Jr, Tefft M, Newton WA, Ragab AH, Lawrence Jr W, Gehan EA, et al. Improved prognosis with intensive treatment of children with cranial soft tissue sarcomas arising in nonorbital parameningeal sites. A report from the Intergroup Rhabdomyosarcoma study. Cancer 1987;59:147-55.  Back to cited text no. 13
    
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Gasparini M, Lombardi F, Gianni MC, Massimino M, Gandola L, Fossati-Bellani F. Questionable role of CNS radioprophylaxis in the therapeutic management of childhood rhabdomyosarcoma with meningeal extension. J Clin Oncol 1990;8:1854-7.  Back to cited text no. 14
    
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Schiopu SR, Habl G, Haefner M, Katayama S, Herfarth K, Debus J, et al. Helical tomotherapy in patients with leptomeningeal metastases. Cancer Manag Res 2018;11:401-9.  Back to cited text no. 16
    
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Yavas G, Karabagli P, Paksoy Y, Yavas C, Karabagli H, Koksal Y. An aggressive parameningeal rhabdomyosarcoma with multiple spinal cord metastases: A case report and review of the literature. Childs Nerv Syst 2017;33:843-7.  Back to cited text no. 18
    


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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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