Nerve Sheath in Longstanding Fibrostenosing Crohnʼs Disease

To the Editor: Benign chest wall tumors typically manifest as slow-growing, palpable masses in asymptomatic patients. Neoplasms of neural tissue are the most common cause of paravertebral masses; neurogenic tumors in the thorax usually arise from intercostal nerves in the paravertebral region and most commonly represent schwannomas.1 The etiology of such lesions is unclear. We report a case of patient affected with Crohn's disease (CD), with an ileostomy, who was found to have a paravertebral mass at chest x-ray (CXR). A 34-year-old woman, operated on for colorectal CD 20 years before (proctocolectomy + terminal ileostomy), presented to our unit with abdominal pain. A routine CXR revealed a paravertebral, well-defined mass (Fig. 1). During anamnesis the patient reported thoracic back pain. Inflammation markers were slightly increased: erythrocyte sedimentation rate (ESR) was 28 mm/h (normal value <20 mm/h in women) and C-reactive protein (CPR) was 18 mg/L (normal value <10 mg/L). The patient underwent a total-body computed tomography (CT) scan and thoracic magnetic resonance imaging (MRI) (Fig. 2). The lesion seemed well capsulated. A CT-guided fine-needle aspiration biopsy (FNAB) showed a lesion of neural origin (S-100+). A stricture was seen ≈6 cm before the ileostomy site. MRI excluded a dumb-bell tumor (Fig. 2), so the patient underwent video-assisted thoracic surgery (VATS) to remove the paravertebral mass (Fig. 3); pathological examination of the specimen confirmed its benignity, conclusive for a schwannoma (Figs. 4, 5). Abdominal ultrasound (US) found that the thickened bowel tract (>7 cm long) was not suitable for medical therapy (fibrostenotic pattern), and an endoscopic examination through the ileostomy found the stenosis 6 cm proximal to the stoma. We planned surgical revision of the ileostomy. At surgery the small bowel presented a markedly thickened, fibrotic tract (length 15 cm) 7 cm proximal to the stoma site. We resected the fibrotic ileum and fashioned a new terminal ileostomy. Pathological examination showed an ileal recurrence of CD. At 2-year follow-up she maintains surgically induced remission control; CXR, chest MRI, and CT are negative for residual disease or recurrence; and respiratory function was assessed and showed no alterations. Routine CXR performed at the admission showing a large costoverte-bral mass in the right hemithorax. (A,B) CT-scan confirming the presence of a large costovertebral mass (A: lung window; B: mediastinum window). (C) Schematic representation of the tumor: based on CT and MRI imaging the mass does not infiltrate the thoracic spine (dumb-bell tumor excluded). (D) Detail of the CT scan showing the mass developing along the rib surface (nerve sheath). The lesion as it appeared at surgery. It was a bilobated mass growing along the rib. The resected specimen opened. Cut surface revealed a smooth, glistening, gray-white appearance, with cystic areas of hemorrhage and hyalinization. Microscopic examination displaying multifocal areas of degenerative changes, hyperchromatic nuclei, and coarse clumping of chromatin. No mitotic figures are identified. Immunohistochemistry revealed strong expression of S100A4, vimentin, and myelin basic protein. These features allowed diagnosis of “ancient schwannoma,” a tumor with prominent degenerative changes that behaves as an ordinary schwannoma. Schwannomas are encapsulated neoplasms originating from nerve sheaths, usually slow-growing, typically occurring in patients between 20 and 50 years of age. They are not always seen at radiography; CT enables more accurate assessment of tumor morphology, composition, localization, and extent.2 MRI is the preferred modality for the evaluation of chest wall tumors. Signal intensity of schwannoma on T1-weighted MR images is equal to or slightly greater than that of the muscle and on T2-weighted images is markedly greater.3 The presence of bone erosions without disruption indicates the benign nature and slow growth rate of this lesion. The extreme pain that often accompanies biopsy is further evidence of its neural origin. Cases are reported in the literature describing “alimentary symptoms” of neurogenic tumors, such as dysphagia, epigastric symptoms, flatulence, vomiting, and chronic abdominal pain.4 These symptoms are due both to tumor compression of surrounding structures and to invasion of the thoracic spine (dumb-bell tumor). In our case the mass localization was too cranial to justify abdominal pain due to spinal invasion. When a dumbbell extension is suspected or cannot be excluded, the intervention should be performed in cooperation with a neuro-surgeon and an orthopedic surgeon: if surgery confirms this condition, a lami-nectomy is required. Symptoms due to tumor compression retrogress after laminectomy. MRI excluded spinal invasion and abdominal CT showed an ileal stenosis suspect for CD recurrence, explaining the abdominal pain. Hence, laminectomy was neither required nor planned in the present case. No association between schwannoma and CD is described in the literature. Fibrogenic cytokine transforming growth factor (TGF)-β is now known to be involved in the pathogenesis of fibrostenosing CD, leading to increased S100A4 expression in ileal CD stricture stimulating the migration of fibroblasts.5 The results of recent immunohistochemical studies demonstrate the coexpression of TGF-β and glial cell line-derived neurotrophic factor in vestibular schwannoma and suggest a trophic synergism of both neurotrophic factors in this tumor6; a potential proneurogenic effect of TGF-β has been widely described in human brain and in experimental mouse models.7,8 Given the marked positivity of S100A4 in the schwannoma cells, it could be hypothesized that, in our case, TGF-β could have been involved in the pathogenesis of both diseases. Such a common pathway could be attractive to investigate further. Greater understanding of the biology of CD fibrostenosis could yield significant advances in dealing with stricturing CD. The identification of novel therapeutic targets and biomarkers would represent a revolutionary approach, potentially leading to a prevention either of strictures requiring surgery or of complications due to long-standing CD and to prolonged therapy.