Clinicopathological characteristics of cortical tubers in tuberous scle

Abstract

Objective To investigate the clinicopathological and molecular genetic features of cortical tubers in tuberous sclerosis complex (TSC).  Methods and Results Two girls, one was 33 months old and the other was 15 years old, presented paroxysmal strabismus and intermittent panic with convulsion of limbs. Head MRI revealed focal cortical abnormal signal and multifocal cortical suspected abnormal signals indicating focal cortical dysplasia (FCD). The implantation of intracranial electrode indicated epileptogenic zones, and multi-lobectomy was conducted to remove the epileptogenic zones. From the gross specimen, gray matter nodule and banded heterotopic gray matter were observed. Histological examination showed uneven cortical thickness and heterotopic gray matter. Part of the cortex showed giant heterocyst proliferation with big nuclei and obvious nucleoli, and involved deep white matter with calcification. Neurons with deformed nuclei, giant cells and obvious proliferation of glial cells could be seen. Immunohistochemically, the dysmorphic neurons were positive for neurofilament protein (NF) in ytoplasm, giant cells were positive for glial fibrillary acidic protein (GFAP) and vimentin (Vim) in cytoplasm, and the diffuse positivity of GFAP in cortex indicated obvious proliferation of glial cells. Combined with clinical data, Case 1 was diagnosed as cortical dysplasia in multiple lobes and one renal hamartoma, and Case 2 was diagnosed as cortical tubers in multiple lobes and heterotopic gray matter. They were diagnosed as suspected TSC. Genet detection found TSC1 gene in Case 1 had c.647_648del heterozygous mutation (nonsense mutation) and TSC2 in Case 2 had c.4672G>A heterozygous mutation (missense mutation). The diagnosis of TSC was confirmed.  Conclusions TSC presents variable clinical features. There are several overlapping features in the aspect of histological  orphology between cortical tubers and FCD Ⅱ b. The confirmed diagnosis of TSC should consider clinical manifestations, imaging and genetic testing, not only the histological and immunohistochemical features which easily led to misdiagnosis of FCD Ⅱb.

DOI: 10.3969/j.issn.1672-6731.2018.06.007