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 Table of Contents  
CASE REPORT
Year : 2019  |  Volume : 33  |  Issue : 3  |  Page : 161-163

Atypical presentation with malignant transformation in neurofibromatosis Type 1 and strategies for managing neuropathic pain


Department of Onco-Anaesthesia and Palliative Medicine, Dr. BRAIRCH, All India Institute of Medical Sciences, New Delhi, India

Date of Submission26-Mar-2019
Date of Decision18-Jun-2019
Date of Acceptance05-Aug-2019
Date of Web Publication5-Dec-2019

Correspondence Address:
Dr. Rakesh Garg
Room No 139, First Floor, Department of Onco-Anaesthesia and Palliative Medicine, Dr. BRAIRCH, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 029
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpn.ijpn_26_19

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  Abstract 

Pain is considered as a vital parameter for any patient management. Type I neurofibromatosis (NF-1) is an autosomal dominant neurocutaneous disorder caused by loss-of-function mutations in the NF-1 gene. The presence of severe pain is an atypical feature of NF-1, and the possibility of malignant transformation with the development of a malignant peripheral nerve sheath tumor (MPNST) should be considered in such situation. These tumors are universally foreshadowed by the onset of severe pain. The present treatment options that can be used in the management of these patients have not been well described in the available literature. We report a case of NF-1 with atypical pain, its malignant transformation, and its management. This case report is unique as it attempts to correlate the mechanism and target therapeutic options in the management of pain in patients of NF with MPNST. We conclude by emphasizing that various available options for management of pain should be employed after understanding the pathophysiology behind the occurrence of pain in a clinical setting. Treatment of malignancy and management of pain should be done simultaneously.

Keywords: Atypical, malignancy, malignant peripheral nerve sheath tumor, neurofibromatosis, pain


How to cite this article:
Ahuja D, Garg R. Atypical presentation with malignant transformation in neurofibromatosis Type 1 and strategies for managing neuropathic pain. Indian J Pain 2019;33:161-3

How to cite this URL:
Ahuja D, Garg R. Atypical presentation with malignant transformation in neurofibromatosis Type 1 and strategies for managing neuropathic pain. Indian J Pain [serial online] 2019 [cited 2020 May 29];33:161-3. Available from: http://www.indianjpain.org/text.asp?2019/33/3/161/272376


  Introduction Top


Chronic pain has a multidimensional impact on the patient, immediate caregivers, and society.[1],[2] Type I neurofibromatosis (NF-1) is an autosomal dominant neurocutaneous disorder.[3] The presence of severe pain is an atypical feature of NF-1, and the possibility of malignant transformation with the development of a malignant peripheral nerve sheath tumor (MPNST) should be considered. These tumors are universally foreshadowed by the onset of severe pain.[4],[5] The present treatment options that can be used in the management of these patients have not been well described in the literature. We report a case of NF-1 with atypical pain and its management.


  Case Report Top


A 35-year-old male, known case of NF-1 presented to the pain clinic with complaints of pain and swelling over the left thigh for the past 4 months. Pain was burning in character, constant, radiating to left foot, and severe in intensity with numerical rating scale (NRS-10/10). The pain was not relieved with oral paracetamol and diclofenac. The swelling over the thigh measured 15 cm × 10 cm × 10 cm, hard and diffuse extending inferiorly till popliteal fossa. The patient developed swelling over the left thigh 2 years ago, which then gradually increased in size. Venous Doppler of the left lower limb showed a large encapsulated vascular mass (4.8 cm × 3.8 cm) seen in relation with saphenous vein on the posterior part of the thigh. The computed tomography scan revealed diffuse nodular enlargement of bilateral sciatic nerves (from the level of lumbosacral nerve roots), bilateral posterior tibial, peroneal nerves, and their distal muscular branches. Multiple cutaneous and subcutaneous nodular lesions were seen at the abdominal wall, gluteal region, bilateral thigh, legs, around the celiac trunk, and along the root of mesentery encircling the mesenteric vessels. These findings were consistent with clinical diagnosis of NF. Excision biopsy of the mass was suggestive of cellular schwannoma, and that from the cutaneous nerve was suggestive of neurofibroma. At this point of time, he reported to our pain clinic and was prescribed oral tramadol 50 mg 6 hourly, paracetamol 1 g 6 hourly, gabapentin 300 mg once a day for 3 days, followed by twice a day dosing for management of pain. He was referred to oncologists for disease management. Contrast-enhanced computerized tomography of the chest, abdomen, and pelvis revealed a large, well-encapsulated, lobulated mass in the posterior compartment of the left thigh measuring 2.9 cm × 11.4 cm having areas of necrosis within. Mass extended from the upper femur diaphysis till knee joint predominantly intermuscular involving adductor muscles without joint or vascular invasion. Elongated cystic spaces are seen in the retroperitoneum encasing the inferior vena cava, aorta with its branches and mesenteric vessels. Similar lesions were noted in the bilateral presacral region. Features were suggestive of MPNST.

On follow-up at 1 week, pain relief was inadequate (NRS-6/10). Oral tramadol and gabapentin were stopped, paracetamol 1 g 6 hourly was continued, and pregabalin 75 mg twice a day was started. The patient was found to be unsuitable for surgery due to extensive lesion. Medical oncology team decided to administer ifosfamide with mesna and epirubicin-based neoadjuvant chemotherapy. Furthermore, hemostatic radiotherapy 8 Gy1# was given to control bleeding from the mass. Due to chemotherapy toxicity, it was stopped, and hip disarticulation was advised. The patient again reported to us a week later and had adequate analgesia (NRS <2/10) with prescribed medications.


  Discussion Top


Loss of neurofibromin due to loss-of-function mutations in the NF-1 gene in 17q11.2 predisposes to increased tumorigenesis in these patients, and the clinical course may be complicated by the occurrence of tumors such as neurofibroma, gliomas (especially vestibular), MPNST, nonlymphocytic leukemia, and pheochromocytoma.[6],[7] These malignancies can appear at any age, and transformation to MPNST is the most common with an estimated risk of 8%–13%.[8],[9] In view of relation between MPNST and its origin predominantly from preexisting plexiform neurofibromas, patients of NF need to be assessed for its malignant transformation if any new symptoms such as “persistent pain lasting for longer than a month or pain that disturbs sleep, new or unexplained neurological deficit or sphincter disturbance, and alteration in the texture of a neurofibroma from soft to hard or rapid increase in the size of a preexisting neurofibroma” occur.[4] The mechanism of pain in such cases has not been conclusively elucidated.[10],[11] Pain induced by pressure (i.e., the Tinel's sign) is a feature of both benign and malignant tumors. Increase in local concentrations of Nav1.8 sodium channel leading to increased axonal transmission in response to mechanical stimulation has been suggested as the cause of pressure-induced nerve pain (ectopic mechanosensitivity) in cases of nerve sheath tumors.[5] Although attempts have been made to elucidate the mechanism of pain in MPNST, no therapeutic approaches targeting them have been recommended for the management of pain in these patients. As our patient had both rest pain and pressure-induced pain, we decided to target the implicated mechanisms of pain to achieve the highest level of analgesia possible. Paracetamol was used to inhibit the formation of the pro-inflammatory compounds such as cyclooxygenase and tumor necrosis factor-alpha.[12] The neuropathic component of pain due to neuronal excitability and ectopic activity was controlled by pregabalin.[13] This case report is unique as it attempts to correlate the mechanism and target therapeutic options in the management of pain in patients of NF with MPNST.

We conclude by emphasizing that various available options for management of pain should be employed after understanding the pathophysiology behind the occurrence of pain in a clinical setting. Treatment of malignancy and management of pain should be done simultaneously.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published, and due efforts will be made to conceal the identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Tavoli A, Montazeri A, Roshan R, Tavoli Z, Melyani M. Depression and quality of life in cancer patients with and without pain: The role of pain beliefs. BMC Cancer 2008;8:177.  Back to cited text no. 1
    
2.
Dueñas M, Ojeda B, Salazar A, Mico JA, Failde I. A review of chronic pain impact on patients, their social environment and the health care system. J Pain Res 2016;9:457-67.  Back to cited text no. 2
    
3.
Grobmyer SR, Reith JD, Shahlaee A, Bush CH, Hochwald SN. Malignant peripheral nerve sheath tumor: Molecular pathogenesis and current management considerations. J Surg Oncol 2008;97:340-9.  Back to cited text no. 3
    
4.
Ferner RE, Huson SM, Thomas N, Moss C, Willshaw H, Evans DG, et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet 2007;44:81-8.  Back to cited text no. 4
    
5.
Sughrue ME, Levine J, Barbaro NM. Pain as a symptom of peripheral nerve sheath tumors: Clinical significance and future therapeutic directions. J Brachial Plex Peripher Nerve Inj 2008;3:6.  Back to cited text no. 5
    
6.
Stumpf DA, Alksne JF, Annegers JF. Neurofibromatosis – Conference statement. National institutes of health consensus development conference. Arch Neurol 1988;45:575-8.  Back to cited text no. 6
    
7.
Korf BR. Malignancy in neurofibromatosis type 1. Oncologist 2000;5:477-85.  Back to cited text no. 7
    
8.
Yohay K. Neurofibromatosis type 1 and associated malignancies. Curr Neurol Neurosci Rep 2009;9:247-53.  Back to cited text no. 8
    
9.
Evans DG, Baser ME, McGaughran J, Sharif S, Howard E, Moran A. Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J Med Genet 2002;39:311-4.  Back to cited text no. 9
    
10.
Ogose A, Hotta T, Morita T, Yamamura S, Hosaka N, Kobayashi H, et al. Tumors of peripheral nerves: Correlation of symptoms, clinical signs, imaging features, and histologic diagnosis. Skeletal Radiol 1999;28:183-8.  Back to cited text no. 10
    
11.
Valeyrie-Allanore L, Ismaïli N, Bastuji-Garin S, Zeller J, Wechsler J, Revuz J, et al. Symptoms associated with malignancy of peripheral nerve sheath tumours: A retrospective study of 69 patients with neurofibromatosis 1. Br J Dermatol 2005;153:79-82.  Back to cited text no. 11
    
12.
Sharma CV, Mehta V. Paracetamol: Mechanisms and updates. Contin Educ Anaesth Crit Care Pain 2014;14:153-8.  Back to cited text no. 12
    
13.
Gajraj NM. Pregabalin: Its pharmacology and use in pain management. Anesth Analg 2007;105:1805-15.  Back to cited text no. 13
    




 

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