A Rare Case of Malignant Peripheral Nerve Sheath Tumor in Neck and Role of VMAT Radiotherapy
1Department of Radiation Oncology, Batra Hospital & Medical Research Centre, Delhi, India
2-4,6-8Radiotherapy, Batra Hospital & Medical Research Centre, Delhi, India
5Department of Pathology, Fortis Flt Lt Rajan Dhall Hospital, Delhi, India
Corresponding Author: Sujata Sarkar, Department of Radiation Oncology, Batra Hospital & Medical Research Centre, Delhi, India, Phone: +91 9625589246, e-mail: firstname.lastname@example.org
Received on: 25 June 2022; Accepted on: 18 November 2022; Published on: 21 February 2023
Introduction: Malignant peripheral nerve sheath tumor (MPNST) is a rare variety of sarcoma. Its presentation is different from usual sarcomas in early presentation, aggressive behavior, high recurrence and poor prognosis. They are usually found in pelvis and extremities. Neck is an extremely rare site. About 50% cases are found in patients of nerofibromatosis type 1 (NF-1). In absence of NF-1 or any evidence of its association with nerve sheath or neurofibroma, visualization of ultrastructure features of Schwann cells in electron microscopy forms the basis of diagnosis, as S100 is weakly present in <50% cases.
Case summary: Here, we are reporting a rare case of MPNST in right side of neck in a in a 36-year-old male with NF-1.
Discussion: In literature, role of radiotherapy in MPNST has been described in general with other sarcomas. Our aim is to describe clinicopathological features and treatment with volumetric modulated arc technique (VMAT) radiotherapy in MPNST of neck.
How to cite this article: Sarkar S, Sharma R, Yotham RR, et al. A Rare Case of Malignant Peripheral Nerve Sheath Tumor in Neck and Role of VMAT Radiotherapy. Int J Head Neck Surg 2023;14(1):9-12.
Source of support: Nil
Conflict of interest: None
Keywords: Malignant peripheral nerve sheath tumor, Neck, NF-1, Sarcoma, Volumetric modulated arc technique radiotherapy.
Malignant peripheral nerve sheath tumor (MPNST) is a rare and aggressive variety of sarcoma. It usually arises from peripheral nerves or cells of the peripheral nerve sheath, like Schwann cells, perineural fibroblast, or endoneurial fibroblast.1 It constitutes 5–10% of soft tissue sarcomas, of which, only 8–16% are found in the head and neck region.1-8 They are usually found in patients with NF-1, but also can arise sporadically.8,9 They have a high rate of local recurrence and rapid disease progression leading to very poor prognosis despite aggressive therapy and complete resection.8,9 Here, we are presenting a case of MPNST in the right side of the neck in a 36-year-old male with NF-1. The aim of this paper is to present the clinicopathological features with the main focus on the role of VMAT radiotherapy, which decreases recurrence and increases survival.
A 36-year-old male presented with a complaint of swelling and pain over the right side of the neck. Computed tomography (CT) angiography showed four lesions on the right side of the neck. Lesion I was 6.2 × 5.8 × 11 cm with central necrosis having its bulk in an infraclavicular area with supraclavicular extension, displacing major vessels like superior vena cava inferiorly, right common carotid artery bifurcation superiorly, subclavian artery medially, and internal jugular vein laterally. Lesion II 2.6 × 2 × 4 cm is seen abutting arytenoid cartilage laterally. Lesion III 3.5 × 2.4 × 2.3 cm was just distal to the origin of the vertebral artery. Lesion IV was subcutaneous 16.9 × 11.8 mm on the right side of the neck (Fig. 1). Fiberoptic laryngoscopy was normal with the left vocal cord having limited mobility with the larynx pushed towards the right side. The patient underwent right radical neck dissection.
Histopathology revealed it as MPNST (Fig. 2), margins free lymphovascular invasion absent, metastatic lymph nodes 0/11. Immunohistochemistry showed S100 focally positive and negative for CD34, smooth muscle actin, and pancytokeratin. Thus, confirming it to be MPNST, stage pT3N0.
The patient was then planned for radiotherapy by VMAT to a dose of 60 Gy/30 fractions (Fr) @1 Fr/day and 5 Fr/week to the tumor bed. Preoperative gross tumor volume (GTV-red) was contoured by fusing pre-op CT scan with planning CT. Clinical target volume (CTV-pink) was contoured with a 1.5 cm margin on GTV to cover microscopic disease. Planning target volume (PTV-blue) was contoured with a 5 mm margin on CTV to account for uncertainties in beam alignment, patient positioning, or any movement (Fig. 3A). Organs at risk (OARs) were contoured including larynx, esophagus, spinal cord, brachial plexus, lungs, and heart. Planning was done via VMAT to achieve 95% coverage of PTV by prescribed dose and sparing of OARs (Fig. 3B). OARs doses were within the limit (Table 1 and Fig. 3C).
|OARs dose constraint dose achieved|
|Spinal cord max <45Gy (RTOG 0623) 38.37 Gy
Planning organ at risk volume cord max <50Gy (RTOG 0623) 44.21 Gy
RT parotid mean <26 Gy (RTOG 0912) 2.6 Gy
Lt parotid mean <26 Gy (RTOG 0912) 1.23 Gy
DARS mean <54 Gy (IJROBP 72) 22.02 Gy
Mandible max <70 Gy (RTOG 0225) 30.7 Gy
Esophagus mean <45 Gy (RTOG 0920) 19.25 Gy
Larynx mean <45 Gy (RTOG 0920) 40.15 Gy
Lt lung mean <20 Gy (RTOG 0623) 3.37 Gy
Rt lung mean <20 Gy (RTOG 0623) 10.72 Gy
Heart D100 <40Gy (RTOG 0623) 1.01 Gy
RT brachial plexus max <66 Gy (RTOG 0619) 63.4 Gy
DARS, dysphagia aspiration-related structures; OARs, organs at risk, RTOG: Radiation Therapy Oncology Group
The patient tolerated the treatment well with Common Terminology Criteria for Adverse Events (CTCAE v4.0)10 grade I fatigue, grade III dermatitis, grade I dysphagia, and no hematological toxicity during radiation. Grade III dermatitis is due to excessive skin folds owing to multiple cutaneous neurofibromas.
Now, after 2 months of follow-up, the patient still has grade II dermatitis and is on treatment.
Malignant peripheral nerve sheath tumor (MPNST) is a type of sarcoma, a malignancy of the cells that form the sheath that covers and protects peripheral nerves. It is found to grow in soft tissues like muscle, fat, tendons, ligaments, lymph and blood vessels, nerves, and other tissue that connects and supports the body. It affects five people per million per year.11 About 25–50% of people with MPNST have NF-1 and about 8–13% of people with NF-1 will get MPNST in their lifetime. Although there is no age or gender predilection, they present earlier in life than most of the sarcomas which are usually prevalent after 6th decade. The median age for sporadic MPNST is 30–60 years and that for NF-1-associated MPNST is 20–40 years.12
The mitogen-activated protein kinase (MAPK) pathway, phosphatidylinositol 3-kinases/mouse strain activated kinase (AK) thymoma/(mechanistic) target of rapamycin (PI3K/AKT/mTOR) pathway, and TP53 mutation are some of the major contributors of development of MPNST.13,16 About 10% of MPNST arise due to previous irradiation, most commonly associated with irradiation of breast cancer and lymphoma. Such MPNSTs have a poorer prognosis.17 Compared to benign neurofibromas, MPNST shows a marked increase in tumor cellularity, pleomorphism, mitotic activity, and a more organized cellular growth pattern, with a less extracellular matrix material. Heterologous elements like skeletal muscle, bone, cartilage, and blood vessels are present in approximately 15% of tumors and indicate poor prognosis.18 S100 is weakly present in <50% of cases. In absence of a history of NF-1 or gross or microscopic evidence of tumor association with nerve sheath or neurofibroma, the most reliable method of diagnosis is electron microscopy, which can identify Schwann cells.
The most common sites involved are the nerve roots and bundles in the extremities and pelvis, particularly the sciatic nerve. It’s rarely found in the head and neck region. The lung is the most common site of metastasis, seen in 50% of patients.
The 5-year survival rate of MPNST is 15–50%. They are aggressive, have a high incidence of metastasis, and have a poor prognosis. Tumor size >5 cm, p53 expression, AKT, and TOR pathway activation (identified immunohistochemically), and mesenchymal epithelial transition activation are associated with poor prognosis.13,17,19,21
Surgical resection is the standard of care.22 Due to its large size and aggressive nature, adjuvant radiation therapy (RT) has been shown to decrease local recurrence. In advanced or metastatic cases, some response is shown with doxorubicin and ifosfamide, which overall has poor survival.23
There is limited data on radiotherapy in patients of MPNST separately, even though radiotherapy can be given as a definitive treatment in unresectable cases and for palliation of symptoms in metastatic cases.24 VMAT radiotherapy aims at giving radiation to the targeted area without affecting nearby critical organs or unnecessary irradiation of surrounding areas which may again lead to the development of RT-induced sarcomas in already susceptible patients like those with NF-1. It has minimal side effects or morbidity, unlike surgery or chemotherapy. VMAT radiotherapy is an advanced technique of radiotherapy where the radiation dose is delivered continuously as the machine rotates like an arc. It accurately shapes and changes the intensity of the radiation dose as per the tumor while minimizing the dose to surrounding organs.
Malignant peripheral nerve sheath tumor (MPNST) is a very rare and aggressive variety of sarcoma, found in relatively younger adults who may achieve longer survival with proper treatment. It is even rare in the head and neck region which increases the complexity of treatment. It has a poor prognosis and high chances of recurrence even after complete resection. More case reports are required to establish a standard of care, particularly radiotherapy guidelines, which have a role in all stages of MPNST.
Sujata Sarkar https://orcid.org/0000-0001-7554-1395
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