Clinical features of schwannomatosis: a retrospective analysis of 87 patients

Abstract

Background: Schwannomatosis is a recently recognized form of neurofibromatosis characterized by multiple noncutaneous schwannomas, a histologically benign nerve sheath tumor. As more cases are identified, the reported phenotype continues to expand and evolve. We describe the spectrum of clinical findings in a cohort of patients meeting established criteria for schwannomatosis.

Methods: We retrospectively reviewed the clinical records of patients seen at our institution from 1995-2011 who fulfilled either research or clinical criteria for schwannomatosis. Clinical, radiographic, and pathologic data were extracted with attention to age at onset, location of tumors, ophthalmologic evaluation, family history, and other stigmata of neurofibromatosis 1 (NF1) or NF2.

Results: Eighty-seven patients met the criteria for the study. The most common presentation was pain unassociated with a mass (46%). Seventy-seven of 87 (89%) patients had peripheral schwannomas, 49 of 66 (74%) had spinal schwannomas, seven of 77 (9%) had nonvestibular intracranial schwannomas, and four of 77 (5%) had intracranial meningiomas. Three patients were initially diagnosed with a malignant peripheral nerve sheath tumor; however, following pathologic review, the diagnoses were revised in all three cases. Chronic pain was the most common symptom (68%) and usually persisted despite aggressive surgical and medical management. Other common diagnoses included headaches, depression, and anxiety.

Conclusions: Peripheral and spinal schwannomas are common in schwannomatosis patients. Severe pain is difficult to treat in these patients and often associated with anxiety and depression. These findings support a proactive surveillance plan to identify tumors by magnetic resonance imaging scan in order to optimize surgical treatment and to treat associated pain, anxiety, and depression.

Figure 1.

Histological misdiagnosis of schwannomas in a schwannomatosis patient. (A): Hemotoxylin and eosin (H&E) stain of a schwannoma with classic histology, including numerous Verocay body formations. (B): H&E stain of a cellular schwannoma. The tumor is moderately cellular, with mitoses and foci of necrosis and patternless, lacking Antoni A/Antoni B areas and Verocay bodies. This tumor can be misdiagnosed as low-grade malignant peripheral nerve sheath tumor. (C): H&E stain of schwannoma showing regions with prominent myxoid background. Myxoid schwannomas may be confused with neurofibromas. (D): Diffuse staining for S100 protein highlights the monotonous population of neoplastic Schwann cells composing the tumor, supporting the diagnosis of schwannoma.