Ipsilateral brain cavernoma under scleroderma plaque: a case report

Scleroderma is a rare disease of unknown etiology, which is characterized by thickening and hardening of skin due to an increased collagen production. A 44-year-old female patient with a scleroderma on the scalp known by our department, also presented an ipsilateral brain lesion since 2015, which was showing growth without any clinical symptomatology and the patient wanted the lesion to be removed. This atypical lesion underneath the scleroderma shows that diagnosis can be missed without brain imaging and biopsy.


Introduction
Localized scleroderma encompasses the conditions of linear scleroderma (LS) (extremity and facial), plaque or circumscribed morphea, pansclerotic and generalized morphea. By definition, localized scleroderma involves the skin and the underlying tissue [1].
The most commonly described brain lesions in LS 'en coup de sabre' are intracranial calcifications, which are characteristically ipsilateral to the skin lesions and appear as hypo intense white matter lesions on T2-weighted magnetic resonance imaging (MRI) [2][3][4].
Cerebral angiograms and magnetic resonance angiogram studies may typically show vascular involvement suggestive of vasculitis. Reports of cerebral aneurysms and other vascular malformations, as brain cavernomas [1,5,6], exist and could represent late sequelae of a vasculitic process. To our knowledge there have been no case reports published showing a brain carvernous malformation ipsilateral to the scleroderma and beneath it in the adult population. However, we found 2 case reports in pediatric series.

Patient and observation
A 44-year-old of Asian origin female was followed up in our department since December 2015. She was referred by her family doctor due to a left frontal lobe cystic lesion. The patient has been following herbal treatment for her scleroderma since she was 3 years old in China. The patient had an MRI of her brain done in China, because a Chinese medicine practitioner in Toronto told her that she might have something in the brain due to scleroderma. The scleroderma was localised in the left frontal side of her scalp ( Figure 1). She did not complain of any symptoms at that time.

Discussion
The patient had a mild increase in the lesion without any neurological deficiency and she asked for surgical treatment. Surgical indication Page number not for citation purposes 3 was probably controversial at that time, although there was an increase in tumour size. Considering that the lesion was growing and she is a young patient, we carried forward with the surgery. This present case is remarkable for several reasons, but the main one is because of the uncommon mixed presentation. To our knowledge, this is the third case report presenting with a cavernoma ipsilateral to the localized scleroderma. Fain et al. reported 2 cases in children [1]. The localized scleroderma without systemic involvement itself, is a rare entity [7]. Cavernous angiomas are clusters of abnormally dilated blood vessels. The cavernoma was located beneath the sclerodermic lesion. There is no case reported in the literature where we can find this unique feature, moreover showing a tinning of the scalp in the left frontal region. There is a theory about the pathogenesis arguing that vasculature is the primary target [8]. The pathogenic mechanisms behind neurological dysfunction associated with Linear Scleroderma and Parry-Romberg Syndrome (progressive hemifacial atrophy) remain unclear, although several theories have been proposed.
Perhaps the most plausible and widely accepted explanation is the "neurovasculitis hypothesis" based on focal MRI findings and angiographic evidence of CNS vascular changes [9][10][11]. There is the belief that a previous infection, particularly due to Borrelia Burgdorferi, has been implicated in Europe and Japan, but not confirmed in the United States [12,13]. Genetic participation in pathogenesis appears to be relatively weak, since only a 4.7% concordance between twins has been observed [14] and family studies revealed only 1.6% frequency among first-degree relatives [4,15]. However, several groups have identified polymorphisms in potential candidate genes involved in immune regulation, such as BANK1, C8orfl3-BLK, IL-23R, IRF5, STAT4, TBX21 and TNFSF4, which may underlie the pathogenesis of systemic sclerosis [16,17]. Intriguingly, many of these polymorphisms are shared with other rheumatic diseases, such as systemic lupus erythematosus. Another unique feature is that this is a reported case in a female adult with brain cavernoma, while the previous two reported cases have been described in paediatric population [1].
There are a couple of manuscripts, published by Moko et al. [18] and K. Terstegge [19], showing that asymptomatic patients with LS who received CNS imaging showed that 82-100% (n = 13) had exclusively ipsilateral lesions in the brain. None of the lesions were brain cavernous angiomas. This is the first case ever, where the brain cavernoma was resected in a patient in whom we had to find the way to make the incision avoiding the linear scleroderma.

Conclusion
This case report highlights that patients diagnosed of a Linear Scleroderma should have an MRI of the brain to exclude any underlying pathology and to be monitored yearly to check the lesion´s behaviour.   Thin walled vessels of irregular outline amidst chronic reactive gliosis and hemosiderin deposition in the neuropil