Colonic ganglioneuroma

Summary A 73 year old woman with cutanous neurofibromatosis developed colonie carcinoma. The resected colon also contained multiple tubular adenomas and a polypoid ganglioneuroma. Multiple neurofibromas were seen during the operation over the serosal surface of the small intestine. Other cases of colonic ganglioneuromas and of combined neurogenic and epithelial colonic tumours are reviewed.     

The nerve sheath tumor,solitary and in von Recklinghausen's disease; A unitary mesenchymal concept

Summary The characteristic cell of peripheral nerves, the Schwann cell, is capable of forming peripheral myelin, but also of forming collagen and reticulin fibers and of being transformed into macrophages. This kind of cell has been demonstrated under circumstances in which its formation from pre-existing Schwann cells is precluded, as in regenerative foci within the brain in multiple sclerosis. It is suggested that this cell is a specilized mesenchymal element, and that it may be formed by maturation of the multipotential primitive reticular cells which give rise to other specialized mesenchymal elements in appropriate circumstances, and which are present in the brain as well as in most other tissues.It is suggested that only one type of neoplasm of specific Schwann cell origin exists, this being the same in the presence or absence of von Recklingshausen's neurofibromatosis. It may most simply be designated as the nerve sheath tumor. Von Recklinghausen's disease, however, is characterized by the occurrence of hamartomatous and degenerative phenomena, as well as the tendency to neoplasia, and these alter the appearnce of the specific nerve sheath tumor and of non-neoplastic segments of peripheral nerves. In addition, some neoplasms observed in this disease have been interpreted as of Schwann cell origin when, in fact, they are less specific fibromas originating in other connective tissue elements of a nerve, or in the extra-neural connective tissues. The term neurofibroma appears to have been applied to both of these phenomena, i.e., to degenerative, non-neoplastic changes in nerves, and to neoplasms which may not have originated in Schwann cells or even within peripheral nerves; its continued use is not warranted.

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Zusammenfassung Die für den peripheren Nerven kennzeichnende Zelle, die Schwannsche Zelle, ist imstande, sowohl Myelin vom peripheren Typ als auch Kollagen und Reticulin zu produzieren und als Makrophage tätig zu sein. Diese Fähigkeit der Zelle konnte unter solchen Umständen beobachtet werden, unter denen ihre Bildung aus autochthonen Schwannschen Zellen zwingend ausgenommen werden mußte, wie z.B. in den Foci der multiplen Sklerose im Gehirn. Es wird die Annahme vorgebracht, daß diese Zelle ein besonderes bindegewebiges Element ist, das sich durch Reifung von den multipotenten primitiven Reticulumzellen ableitet, die unter bestimmten Umständen auch andere spezielle mesenchymale Elemente produzieren, und die im Gehirn wie in den meisten anderen Geweben vorhanden sind.Ferner wird postuliert, daß es nur eine einzige Art von Geschwülsten der Schwannschen Zelle gibt, ungeachtet dessen, ob die von Recklinghausensche Neurofibromatose vorliegt oder nicht. Diese Geschwulst sollte einfach als Nervenscheidentumor bezeichnet werden. Die Recklinghausensche Krankheit ist jedoch durch das Vorkommen von Hamartomen und degenerativen Phänomenen sowie durch eine Bereitschaft zur Geschwulstbildung gekennzeichnet. Diese Momente ändern das Bild eines spezifischen Nervenscheidetumors sowie das der nichtneoplastischen Segmente des peripheren Nerven. Einige Geschwülste, die bei dieser Erkrankung vorkommen, wurden als Derivate der Schwannschen Zellreihe angesehen, während sie in Wirklichkeit weniger spezifische Fibrome sind, die ihren Ursprung von anderen Bindegewebselementen des Nerven oder des extraneuralen Gewebes nehmen. Die Bezeichnung Neurofibrom hat man anscheinend auf beide dieser Phänomene angewandt, d.h. auf Fälle, von regressiven, nicht-neoplastischen Veränderungen der Nerven und auf solche Geschwülste, die ihren Ursprung möglicherweise weder von der Schwannschen Zelle noch überhaupt im peripheren Nerven genommen hatten. Die weitere Anwendung dieser Bezeichnung erscheint unberechtigt.

     

一例散发1型神经纤维瘤病患者的NF1基因嵌合突变分析

目的 对1例散发1型神经纤维瘤病患者的NF1基因进行嵌合突变分析.方法 提取先证者外周血基因组RNA,PCR扩增NF1基因编码区序列并进行序列测定;找到突变后,基因组DNA途径证实突变,并对先证者儿子的NF1基因相应外显子也进行序列分析;针对NF1基因第51外显子已发现的突变,取先证者全血淋巴细胞、口腔上皮细胞和尿路上皮细胞基因组DNA进行PCR扩增,PCR产物T克隆及测序.结果 先证者的临床表现符合1型神经纤维瘤病.先证者外周血RNA途径检测出无义突变c.7911C＞T(p.Q2510X);基因组DNA途径证实患者外周血淋巴细胞、口腔上皮细胞和尿路上皮细胞中均有该突变,尿路上皮细胞中该突变测序信号较弱;在PCR产物的T克隆-测序中,来自先证者的血液、口腔上皮、尿液上皮细胞无义突变c.7911C＞T(p.Q2510X)突变体的重组菌分别占总数的42％、36％、12％.其儿子、正常对照不存在上述突变.结论 先证者在胚胎早期发生了NF1基因突变,使其体内部分细胞带有NF1基因突变,导致形成全身嵌合的1型神经纤维瘤病.     

Localized Tongue Amyloidosis in a Patient with Neurofibromatosis Type II

Background  

Localized Amyloidosis (AL) may rarely involve oral mucosa. This is the first known reported case describing the development of tongue AL in a 30-year-old patient with Neurofibromatosis (NF) type-2.     

The diagnostic and clinical significance of café-au-lait macules

Café-au-lait, also referred to as café-au-lait spots or café-au-lait macules, present as well-circumscribed, evenly pigmented macules and patches that range in size from 1 to 2 mm to greater than 20 cm in greatest diameter. Café-au-lait are common in children. Although most café-au-lait present as 1 or 2 spots in an otherwise healthy child, the presence of multiple café-au-lait, large segmental café-au-lait, associated facial dysmorphism, other cutaneous anomalies, or unusual findings on physical examination should suggest the possibility of an associated syndrome. While neurofibromatosis type 1 is the most common syndrome seen in children with multiple café-au-lait, other syndromes associated with one or more café-au-lait include McCune-Albright syndrome, Legius syndrome, Noonan syndrome and other neuro-cardio-facialcutaneous syndromes, ring chromosome syndromes, and constitutional mismatch repair deficiency syndrome.     

Curve evolution during bracing in children with scoliosis secondary to early-onset neurofibromatosis type 1: indicators of rapid curve progression

Background:Scoliosis secondary to neurofibromatosis type 1 (NF1) in children aged <10 years is an important etiology of early-onset scoliosis (EOS). This study was performed to investigate the curve evolution of patients with EOS secondary to NF1 undergoing bracing treatment and to analyze high-risk indicators of rapid curve progression.Methods:Children with EOS due to NF1 who underwent bracing treatment from 2010 to 2017 were retrospectively reviewed. The angle velocity (AV) at each visit was calculated, and patients with rapid curve progression (AV of >10°/year) were identified. The age at modulation and the AV before and after modulation were obtained. Patients with (n = 18) and without rapid curve progression (n = 10) were statistically compared.Results:Twenty-eight patients with a mean age of 6.5 ± 1.9 years at the initial visit were reviewed. The mean Cobb angle of the main curve was 41.7° ± 2.4° at the initial visit and increased to 67.1° ± 8.6° during a mean follow-up of 44.1 ± 8.5 months. The overall AV was 6.6° ± 2.4°/year for all patients. At the last follow-up, all patients presented curve progression of >5°, and 20 (71%) patients had progressed by >20°. Rapid curve progression was observed in 18 (64%) patients and was associated with younger age at the initial visit and a higher incidence of modulation change during follow-up (t = 2.868, P = 0.008 and <0.001, respectively). The mean AV was 4.4° ± 1.2°/year before modulation and 11.8° ± 2.7°/year after modulation (t = 11.477, P < 0.010).Conclusions:Curve progression of >10°/year is associated with younger age at the initial visit, and modulation change indicated the occurrence of the rapid curve progression phase.     

The spectrum of NF1 mutations in Korean patients with neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant disorders in humans. NF1 is caused by mutations in the NF1 gene which consists of 57 exons and encodes a GTPase activating protein (GAP), neurofibromin. To date, more than 640 different NF1 mutations have been identified and registered in the Human Gene Mutation Database (HGMD). In order to assess the NF1 mutational spectrum in Korean NF1 patients, we screened 23 unrelated Korean NF1 patients for mutations in the coding region and splice sites of the NF1 gene. We have identified 21 distinct NF1 mutations in 22 patients. The mutations included 10 single base substitutions (3 missense and 7 nonsense), 10 splice site mutations, and 1 single base deletion. Eight mutations have been previously identified and thirteen mutations were novel. The mutations are evenly distributed across exon 3 through intron 47 of the NF1 gene and no mutational hot spots were found. This analysis revealed a wide spectrum of NF1 mutations in Korean patients. A genotype- phenotype correlation analysis suggests that there is no clear relationship between specific NF1 mutations and clinical features of the disease.     

NF2/Merlin in hereditary neurofibromatosis 2 versus cancer: biologic mechanisms and clinical associations

Inactivating germline mutations in the tumor suppressor gene NF2 cause the hereditary syndrome neurofibromatosis 2, which is characterized by the development of neoplasms of the nervous system, most notably bilateral vestibular schwannoma. Somatic NF2 mutations have also been reported in a variety of cancers, but interestingly these mutations do not cause the same tumors that are common in hereditary neurofibromatosis 2, even though the same gene is involved and there is overlap in the site of mutations. This review highlights cancers in which somatic NF2 mutations have been found, the cell signaling pathways involving NF2/merlin, current clinical trials treating neurofibromatosis 2 patients, and preclinical findings that promise to lead to new targeted therapies for both cancers harboring NF2 mutations and neurofibromatosis 2 patients.     

fdg-pet in two cases of neurofibromatosis type 1 and atypical malignancies

Patients with neurofibromatosis type 1 (nf1) are at increased risk for both benign and malignant tumours, and distinguishing the malignant potential of an individual tumour is a common clinical problem in these patients. Here, we review two cases of uncommon malignancies (Hodgkin lymphoma and mediastinal germ-cell tumour) in patients with nf1. Although ¹⁸F-fluorodeoxyglucose positron-emission tomography (fdg-pet) has been used to differentiate benign neurofibromas from malignant peripheral nerve sheath tumours, fdg-pet characteristics for more rare tumours have been poorly described in children with nf1. Here, we report the role of pet imaging in clinical decision-making in each case. In nf1, fdg-pet might be useful in the clinical management of unusual tumour presentations and might help to provide information about the malignant potential of uncommon tumours.     

Neural phenotypes of common and rare genetic variants

Neuroimaging methods offer a powerful way to bridge the gaps between genes, neurobiology and behavior. Such investigations may be further empowered by complementary strategies involving chromosomal abnormalities associated with particular neurobehavioral phenotypes, which can help to localize causative genes and better understand the genetics of complex traits in the general population. Here we review the evidence from studies using these convergent approaches to investigate genetic influences on brain structure: (1) studies of common genetic variations associated with particular neuroanatomic phenotypes, and (2) studies of possible 'genetic subtypes' of neuropsychiatric disorders with very high penetrance, with a focus on neuroimaging studies using novel computational brain mapping algorithms. Finally, we discuss the contribution of behavioral neurogenetics research to our understanding of the genetic basis of neuropsychiatric disorders in the broader population.