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Vascular abnormalities associated with neurofibromatosis type 1 are well described in the literature, however, arteriovenous malformation is a very rare finding in neurofibromatosis type 1. We report the case of an 11-year-old girl who presented with a soft mass on the right flank. Provisional diagnosis of plexiform neurofibroma was made on the basis of clinical and histological observations. Because the lesion was warm on palpation, imaging studies were performed to evaluate further and arteriovenous malformation was detected underlying the plexiform neurofibroma. This report emphasizes the importance of careful examination and proper investigations of the plexiform neurofibroma prior to treatment strategies to avoid future complications. The rarity of plexiform neurofibroma in association with arteriovenous malformation at the same site was also highlighted in this report.
Vascular lesions of medium and large-sized arteries and veins are a well-recognized, albeit rare, feature of neurofibromatosis type I (NF1). The renal artery is the most frequent site of involvement, and renovascular hypertension is the most common presentation. Abdominal aortic coarctation, internal carotid artery aneurysms, and cervical vertebral arteriovenous malformations (AVM) are other manifestations.[1,2] Due to the hypervascular nature of plexiform neurofibromatosis (PNF), it is difficult to distinguish whether underlying vascularity is related to PNF itself or a separate entity and these characteristics may be confusing for a diagnostician. Possibly, significant hemodynamic derangements can occur when PNF is associated with AVM. This report describes how a multidisciplinary management of these challenging lesions is technically feasible and appears to be beneficial in reducing further complications.
An 11-year-old girl presented to our clinic with a soft mass on her right flank. This lesion appeared 3 months after her birth. Since then, it had grown gradually to attain the present size, however, it bulged out rapidly in the last 3 years; recently, the patient had started to experience mild and dull aching during physical activities. Family history did not reveal any similar complaint in immediate and distant relatives. In physical examination, a corrugated and light brown to hyperpigmented mass with a protuberance was seen on the right flank area [Figure 1]. On palpation, the lesion was soft and warm with few firm nodular areas similar to that called the bag of worms. On auscultation, bruit was not detected. Further skin examination revealed multiple café au lait macules (CALMs) on her back and extremities [Figure 1], however, intertriginous freckling was absent. The case was provisionally diagnosed as NF1 and the mass as PNF. For confirmation, a skin biopsy was performed. Histological examination was consistent with neurofibroma [Figure 2a]. However, in order to find out whether the entire swelling can be justified by neurofibroma or not, preliminary ultrasound and a color Doppler was performed, which revealed a subcutaneous vascular mass with a flow resistive index (RI) of 0.49 suggesting AVM. For further evaluation, abdominal magnetic resonance imaging (MRI) with and without contrast was carried out which demonstrated a mass with heterogenic rapid enhancement in favor of AVM [Figure 3]. Other investigations including MRI of the spinal cord and eye examination were normal. The patient was referred to a vascular surgeon and the tumor was excised successfully. Histological diagnosis of the excised underlying tumor was AVM [Figure 2b]. Later, another biopsy was performed to differentiate CALMs from capillary malformations (CMs) due to their clinical resemblance and the result was consistent with CALM.
The coexistence of vascular lesions with PNF could be explained based on several reasons: (a) Schwann cells have angiogenic potential and blood vessel formation can be stimulated by a number of polypeptides, including angiogenin, transforming growth factors α and β, epidermal growth factor, and the fibroblast growth factors; additionally, less well-characterized angiogenic factors have also been described. In NF1, expression of these factors on neurofibroma cells can be found in almost all tissues but most frequently in the brain, spinal cord, and peripheral nervous system. (b) However, the underlying connection between NF1 and vascular lesions is more likely to be derived from the germline mutation causing NF1. Neurofibromin 1 activates Ras-Guanosine Triphosphatase (Ras-GTPase) resulting in abnormal signal transduction. RASA1, another Ras GTPase activator, which when mutated is associated with conditions resulting in AVMs (e.g., CM-AVM syndrome). Therefore, the two entities (PNF and AVM) occurring together spatially are likely to be related to each other.
While coincidence of PNF with AVM is very rare, such associations have been found previously on the scalp;[6,7] however, surprisingly, in our case it was located on the right flank of the patient without any invasion to or origin from the spinal cord. AVM of the brain and spinal cord in NF1, although rare, is not an uncommon association and has been described in previous reports.[8,9] They tend to be clinically silent lesions and symptoms vary depending on their type, size, and location. AVMs are usually congenital in origin but may be followed by trauma. In our patient, either origin could not be concluded definitely because it is not known whether AVM was present since birth or it formed later in recent years.
In radiological evaluation, confusion of AVM with neurofibroma may occur because of high vascularity of some neurofibromas, as well as similar appearances of neurofibroma and distended vessels as dumbbell-shaped masses in MRI. However, a distinct flow-related signal void usually indicates AVM, as was reported in our case.
Treatment of such cases is another challenge for dermatologists and surgeons. These lesions require complex preoperative and postoperative management strategies. Surgical treatment must be decided judiciously and individualized for each patient, and extreme caution should be exercised during surgery. Preoperative embolization can be employed in giant lesions to assist hemostasis during surgical resection because highly fragile vascularity of such lesions can cause intraoperative hemorrhage. In our patient, the mass was excised because of its rapid symptomatic growth to avoid future complications and restore partially normal appearance. In this case, the impression of AVM and PNF appear to be interlinked to each other due to complex deranged hypervascular nature of neurofibromas and correlated RASopathies, however, they may be separate entities located at the same site coincidently.
The present case illustrates a unique but literally expected coincidence of PNF and AVM at the same site. If such an association is left undiagnosed it can lead to dangerous bleeding and hypovolemic shock due to highly fragile vascular bed. A proper and accurate diagnostic and surgical management of such lesions is warranted.
There are no conflicts of interest.
The authors wish to thank Dr. Parisa Karami, Radiologist for her support in radiological imaging illustration.