Safe marginal resection of atypical neurofibromas in neurofibromatosis type 1
Surgery; resection; peripheral nerve; ANF = atypical neurofibroma (neurofibroma with nuclear atypia); ANNUBP = atypical neurofibromatous neoplasm of uncertain biological potential; atypical neurofibroma; EMG = electromyographic; hgMPNST = high-grade MPNST; lgMPNST = low-grade MPNST; marginal margin; MPNST = malignant peripheral nerve sheath tumor; NCI = National Cancer Institute; NCV = nerve conduction velocity; neurofibromatosis 1; NF1 = neurofibromatosis type 1; NIH = National Institutes of Health; SUVMax = maximum SUV within the tumor
OBJECTIVE: Patients with neurofibromatosis type 1 (NF1) are predisposed to visceral neurofibromas, some of which can progress to premalignant atypical neurofibromas (ANFs) and malignant peripheral nerve sheath tumors (MPNSTs). Though subtotal resection of ANF may prevent malignant transformation and thus deaths with no neural complications, local recurrences require reoperation. The aim of this study was to assess the surgical morbidity associated with marginal resection of targeted ANF nodules identified via preoperative serial volumetric MRI and 18F-FDG-PET imaging. METHODS: The authors analyzed clinical outcomes of 16 NF resections of 21 tumors in 11 NF1 patients treated at the NIH Clinical Center between 2008 and 2018. Preoperative volumetric growth rates and 18F-FDG-PET SUVMax (maximum standardized uptake value within the tumor) of the target lesions and any electromyographic or nerve conduction velocity abnormalities of the parent nerves were measured and assessed in tandem with postoperative complications, histopathological classification of the resected tumors, and surgical margins through Dunnett's multiple comparisons test and t-test. The surgical approach for safe marginal resection of ANF was also described. RESULTS: Eleven consecutive NF1 patients (4 male, 7 female; median age 18.5 years) underwent 16 surgical procedures for marginal resections of 21 tumors. Preoperatively, 13 of the 14 (93%) sets of serial MRI studies and 10 of the 11 (91%) 18F-FDG-PET scans showed rapid growth (≥ 20% increase in volume per year) and avidity (SUVMax ≥ 3.5) of the identified tumor, respectively (median tumor size 48.7 cm3; median growth rate 92% per year; median SUVMax 6.45). Most surgeries (n = 14, 88%) resulted in no persistent postoperative parent nerve-related complications, and to date, none of the resected tumors have recurred. The median length of postoperative follow-up has been 2.45 years (range 0.00-10.39 years). Histopathological analysis confirmed significantly greater SUVMax among the ANFs (6.51 ± 0.83, p = 0.0042) and low-grade MPNSTs (13.8, p = 0.0001) than in benign neurofibromas (1.9). CONCLUSIONS: This report evaluates the utility of serial imaging (MRI and 18F-FDG-PET SUVMax) to successfully detect ANF and demonstrates that safe, fascicle-sparing gross-total, extracapsular resection of ANF is possible with the use of intraoperative nerve stimulation and microdissection of nerve fascicles.
Nelson Charlie N; Dombi Eva; Rosenblum Jared S; Miettinen Markku M; Lehky Tanya J; Whitcomb Patricia O; Hayes Christina; Scott Gretchen; Benzo Sarah; Widemann Brigitte C; Chittiboina Prashant
Journal Of Neurosurgery
2019
2019-10-25
Journal Article
<a href="http://doi.org/10.3171/2019.7.JNS191353" target="_blank" rel="noreferrer noopener">10.3171/2019.7.JNS191353</a>
PMID: 31653805
Detection of single mRNAs in individual cells of the auditory system.
Cochlea; Immunohistochemistry; Inner hair cell; Outer hair cell; Single-molecule fluorescence in situ hybridization; Spiral ganglion neuron
Gene expression analysis is essential for understanding the rich repertoire of cellular functions. With the development of sensitive molecular tools such as single-cell RNA sequencing, extensive gene expression data can be obtained and analyzed from various tissues. Single-molecule fluorescence in situ hybridization (smFISH) has emerged as a powerful complementary tool for single-cell genomics studies because of its ability to map and quantify the spatial distributions of single mRNAs at the subcellular level in their native tissue. Here, we present a detailed method to study the copy numbers and spatial localizations of single mRNAs in the cochlea and inferior colliculus. First, we demonstrate that smFISH can be performed successfully in adult cochlear tissue after decalcification. Second, we show that the smFISH signals can be detected with high specificity. Third, we adapt an automated transcript analysis pipeline to quantify and identify single mRNAs in a cell-specific manner. Lastly, we show that our method can be used to study possible correlations between transcriptional and translational activities of single genes. Thus, we have developed a detailed smFISH protocol that can be used to study the expression of single mRNAs in specific cell types of the peripheral and central auditory systems.
Salehi Pezhman; Nelson Charlie N; Chen Yingying; Lei Debin; Crish Samuel D; Nelson Jovitha; Zuo Hongyan; Bao Jianxin
Hearing research
2018
2018-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.heares.2018.07.008" target="_blank" rel="noreferrer noopener">10.1016/j.heares.2018.07.008</a>