Case ReportSirolimus: A Successful Medical Treatment for Head and NeckLymphatic Malformations

Steven Curry, Andrew Logeman, and Dwight Jones

Department of Otolaryngology-Head and Neck Surgery, University of Nebraska Medical Center, Omaha, Nebraska, USA

Correspondence should be addressed to Dwight Jones; dwight.jones@unmc.edu

Received 21 November 2018; Accepted 5 March 2019; Published 24 March 2019

Academic Editor: Kamal Morshed

Copyright © 2019 Steven Curry et al. +is 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.

Lymphatic malformations are abnormalities that arise in the developing lymphatic system, most frequently presenting in the headand neck.+ey are typically treated with sclerotherapy, laser therapy, or surgery for localized lesions. Sirolimus, an inhibitor of themammalian target of rapamycin, is a relatively new medical therapy for the treatment of vascular malformations. +is case reportpresents the improvements and complications seen in a female infant who was diagnosed with a large lymphatic malformation onprenatal ultrasound and has been treated with sirolimus during the first 9 months of life.

1. Introduction

Lymphatic malformations (LMs) are slow-flow cysticanomalies that develop from abnormal embryologic for-mation of the developing lymphatic system, which enlargeby expansion of the lesion in contrast to proliferationwhich occurs in vascular tumors. LMs present most fre-quently in the head and neck and are usually present atbirth or by two years of age. Upregulation of the PI3K/Akt/mTOR pathway may be a causal factor in the developmentof these abnormal lymphatic vessels. Sirolimus, whichinhibits the mammalian target of rapamycin (mTOR) todecrease cell proliferation and lymphangiogenesis, is arelatively new medical therapy for vascular malformations[1, 2].

2. Case Presentation

A prenatal ultrasound revealed a large LM.+e mother wentinto preterm labor at 31weeks and 6 days gestational age anddelivered via c-section in association with planned exitprocedure to stabilize the airway. MRI of the neck on day oflife (DOL) 3 showed a very large multiloculated and mul-tispatial mass (Figure 1) within the left neck extending fromthe left inferior periauricular region through the upper chestwith extension across the midline (de Serres stage V).

+e lesion demonstrated hemorrhage fluid levels and as-sociated mass effect most compatible with a large mixed-cystic LM with recent hemorrhage and complete collapse ofthe visualized left lung. It measured approximately8.1× 5.7× 5.5 cm. She underwent ultrasound-guided drainplacement DOL 10 and sclerotherapy with doxycycline onDOL 11. +e drain was then removed on DOL 16. Sheunderwent tracheostomy on DOL 17 and required re-spiratory support for a total of 56 days before weaning to thetrach collar (Figure 2(a)). +e patient was started on siro-limus therapy at a dose of 0.8mg/m2 on DOL 22. Sirolimustherapy has since been maintained at a target serum troughlevel of 10 to 15 ng/mL. She was initially fed through anorogastric tube, followed by a nasogastric tube, and thenthrough a gastrostomy tube once placed on DOL 52. +epatient developed peripheral edema and hypertensionthought to be due to sirolimus and which were treated withchlorothiazide beginning on DOL 37. She developed cel-lulitis of the LM on DOL 26 and again at 5months of age,treated each time with IV antibiotics. Since discharge fromthe hospital, the patient has been followed in the otolar-yngology clinic at 3-month intervals. +e patient has nowbeen on sirolimus treatment for 8months with reduction inthe bulk of the LM. Her functional improvement includesnow being able to close her mouth around her tongue(Figure 2(b)).

HindawiCase Reports in OtolaryngologyVolume 2019, Article ID 2076798, 3 pageshttps://doi.org/10.1155/2019/2076798

3. Discussion

Treatment of LMs has typically been managed with scle-rotherapy, laser therapy, or surgery for localized lesions.Diffuse malformations present significant challenges due tothe morbidity of interventional treatments to achieve localcontrol. +ere are currently no guidelines for treatment ofLMs [3]. mTOR inhibitors, such as sirolimus, have recentlybeen used for their antilymphangiogenic properties intreating LMs [4]. A recent phase II trial showed that siro-limus is efficacious and well tolerated in patients withcomplicated vascular anomalies [1].

+is case presents the clinical improvements in an infantfemale over the first 9months of life who has been treatedwith sirolimus beginning in the first month of life followingdrainage and doxycycline sclerotherapy for a large LM of theleft neck and chest.

As an immunosuppressant, sirolimus can cause neu-tropenia and may predispose the patient to an increased riskof infection. Furthermore, lymphatic malformations areknown to become infected and hemorrhage. It has beenreported, however, that hemorrhage and infections in LMsmay be less frequent and milder after treatment with siro-limus [1]. Additionally, sirolimus may be more effective in thetreatment of LMs in younger patients [4]. In the present case,treatment with sirolimus has been effective and well toleratedin the neonatal and infant periods. +is case highlights thesuccessful medical management of a large, complex LM, whileavoiding the morbidity of surgery. Medical therapies thattarget other elements in the PI3K/Akt/mTOR pathway are

currently being studied, including PI3K inhibitors, and theymay be promising treatments in the future.

+is report was reviewed and determined to be exemptby the University of Nebraska Medical Center InstitutionalReview Board.

Conflicts of Interest

+e authors declare that they have no conflicts of interest.

Acknowledgments

+e authors would like to thank Jayme Dowdall, MD, for hercritical review of the manuscript. Research was performed atthe University of Nebraska Medical Center, Omaha, NE.

Figure 1: T1+ contrast coronal MRI demonstrates a large mixed-cystic LM extending from the left neck into the chest with recenthemorrhage, measuring 8.1× 5.7× 5.5 cm.

(a)

(b)

Figure 2: Prior to sirolimus treatment, there is significant masseffect involving the tongue, floor of mouth, and neck. After eightmonths of sirolimus treatment, the patient is able to close hermouth around her tongue and has markedly decreased mass effecton the face, mouth, and neck.

2 Case Reports in Otolaryngology

References

[1] D. M. Adams, C. C. Trenor, A. M. Hammill et al., “Efficacy andsafety of sirolimus in the treatment of complicated vascularanomalies,” Pediatrics, vol. 137, no. 2, article e20153257, 2016.

[2] A. M. Hammill, M. Wentzel, A. Gupta et al., “Sirolimus for thetreatment of complicated vascular anomalies in children,”Pediatric Blood & Cancer, vol. 57, no. 6, pp. 1018–1024, 2011.

[3] A. Maruani, O. Boccara, D. Bessis et al., “Treatment of volu-minous and complicated superficial slow-flow vascular mal-formations with sirolimus (PERFORMUS): protocol for amulticenter phase 2 trial with a randomized observational-phase design,” Trials, vol. 19, no. 1, p. 340, 2018.

[4] J. E. Strychowsky, R. Rahbar, M. J. O’Hare, A. L. Irace,H. Padua, and C. C. Trenor, “Sirolimus as treatment for 19patients with refractory cervicofacial lymphatic malformation,”Laryngoscope, vol. 128, no. 1, pp. 269–276, 2018.

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