皮肤神经纤维瘤病恶变1例

报告１例少见的皮肤神经纤维瘤病恶变。患者为一７１岁老年男性。主要表现为全身性皮肤结节，最大直径达７ｃｍ。镜检：大多表现为典型的神经纤维瘤，但部分肿瘤显示出明显的恶性特征：瘤细胞异形显著，病理性核分裂明显。免疫组化采用Ｓ－１００、Ｖｉｍ、ＮＳＥ等抗体证明其来源于神经组织。诊断为皮肤神经纤维瘤病伴恶性神经鞘瘤。     

Can segmental neurofibromatosis be considered a rare disease?

'True' segmental neurofibromatosis (SNF) is characterized by the unilateral, segmental appearance of neurofibromas and/or 'cafe au lait' spots in the absence of genetic transmission. SNF is apparently rare: only 41 cases have been described since the first report by Crowe in 1956. However, the incidence of SNF is probably higher because more and more patients have been described in the last few years and several cases have been observed by single trained authors in a short time. In 1988 and 1989 we had described two patients affected by 'true' SNF. Now we report three additional patients observed in the last two years. 'True' SNF is considered to be a consequence of a post-zygotic (hence non-transmissible) mutational event but this hypothesis is not suitable for cases with segmental lesions matching deep systemic involvement, bilateral distribution of cutaneous lesions or genetic transmission. Additional reports, with careful investigations of both systemic involvement in SNF patients and apparently unaffected relatives and with long follow-ups, will help clarify the genetics and the pathogenests of the disease.     

Solitary plexiform neurofibroma is not pathognomonic of von Recklinghausen's neurofibromatosis: a report of a case

A 42-year-old Caucasian man presented with a 1.8-cm nodule in the proximal thigh (Fig. 1) that had been slowly enlarging for approximately 5 years. The patient had no family history of neurofibromatosis. Physical examination revealed none of the other stigmata of this neurocutaneous disorder. D.A.F. performed an elliptical excision as an out-patient procedure. Grossly, the lesion was homogeneously opalescent and gelatinous. The tissue was fixed in 10% formalin and embedded in paraffin. Routine hematoxylin and eosin stained sections were prepared. The most notable feature on low power magnification was a large, circumscribed, lobular proliferation of spindle cells in a loose fibrillar background that distorted much of the dermis and subcutaneous fat (Fig. 2). On high power magnification, a population of cells with ovoid and S-shaped nuclei admixed within densely packed eosinophilic collagenous material was seen at the center of the lobule (Fig. 3A). A small amount of mucin was also present. Within this cellular area, a dense population of S-shaped spindle cells with eosinophilic cytoplasm was arranged in a parallel array forming microfascicles. At the periphery of this cellular component, a similar population of cells was arranged against a loose fibrillar background of abundant mucin (confirmed by colloidal iron stain) and scattered mast cells (Fig. 4). Lining the lobule was a compressed rim of thin, delicate collagen bundles and perineurial cells. Pleomorphic nuclei and mitotic figures were not observed. The surrounding dermis and subcutaneous tissue were unremarkable. Thickened collagen bundles at the center of the lobule could be seen with a frichrome stain. An S-100 protein immunoperoxidase stain highlighted scattered Schwann cells within the lobule (Fig. 3B), and nerve bundles adjacent to the neurofibroma served as infernal positive controls.     

Segmental neurofibromatosis: a rare or underestimated disease?

Segmental neurofibromatosis is a rare form of neurofibromatosis characterized by neurofibromas and/or'café au lait'macules limited to one or more segment of the body. A case of segment neurofibromatosis in an elderly patient is presented. Classification and genetic counseling are discussed briefly with emphasis on the possibility that because it is benign this condition may not be given sufficient consideration.     

一例合并枕部动静脉畸形和脊柱侧弯的神经纤维瘤病NF1基因突变分析

【摘要】 患者女,15岁。因全身多发咖啡斑15年、脊柱侧弯1年余就诊。1年前因枕部动静脉畸形手术切除肿物。皮肤科检查：全身散在多个大小不等咖啡斑,最大约3 cm × 4 cm,腋窝、腹股沟雀斑。全外显子测序显示,患者NF1基因第26号外显子发生碱基T杂合缺失（c.3328delT）移码突变。患者父母及弟弟均未发现该突变。诊断：神经纤维瘤病Ⅰ型合并枕部动静脉畸形和脊柱侧弯。     

1型神经纤维瘤病NF1基因突变检测

目的 检测1例1型神经纤维瘤病(NF1)患者NF1基因的突变.方法 采用PCR和DNA测序法检测1例NF1患者、2例直系亲属及100例无亲缘关系的正常人NF1基因突变.结果 在NF1患儿中检测到1个移码突变c.3822delC,患者直系亲属及100例无亲缘关系的正常对照均未检测到上述突变.结论 在该例NF1患儿中新发现1个NF1基因移码突变c.3822delC不是罕见的单核苷酸多态性,可能是致病突变,通过影响NF1基因的功能致病.     

A case of neurofibrosarcoma associated with neurofibromatosis: light microscopic, ultrastructural, immunohistochemical and biochemical investigations

A case of neurofibrosarcoma (NFS) with neurofibromatosis was studied by light microscopic, ultrastructural, immunohistochemical and biochemical methods. Histologically, spindle-shaped tumor cells with atypical hyperchromatic nuclei were arranged in a fascicular or sheet-like fashion. Electron microscopic examination revealed discontinuous basement membrane-like structures. Immunohistochemical study revealed S100 protein alpha chains in tumor cells. A biochemical analysis showed large amounts of gangliosides (sialic acid 13.5 micrograms/g wet tissue weight) in tumors. GM3 and GD3 were the major components; these results were compatible with the NFS ganglioside patterns found in our previous study. Results confirmed the diagnosis of NFS and indicate that NFS clearly has some neuroectodermal characteristics and that Schwann cells may possibly be related to its origin.     

Multiple cutaneous plexiform schwannomas as initial presentation of neurofibromatosis 2 in a 9-year-old

Neurofibromatosis 2 (NF2) is an autosomal-dominant disease caused by genetic mutations of the NF2 gene on chromosome 22. Patients are often diagnosed according to the presence of bilateral vestibular schwannomas and other tumors in the brain and spinal cord. In children, NF2 can present early with ocular findings and cutaneous tumors. We report here a 9-year-old girl who presented with multiple pigmented, slightly tender plaques on her scalp, face, and back that were revealed by histopathology to be plexiform schwannomas. We suspected NF2 and sent the patient's blood for genetic testing, which confirmed our diagnosis.     

表型温和的1型神经纤维瘤病：5个家系基因突变分析

【摘要】 目的 检测表型温和的1型神经纤维瘤病（NF1）患者的基因突变。方法 2017年6月至2020年6月于上海市奉贤区皮肤病防治所皮肤科门诊收集5例表型温和、仅有皮损的NF1先证者及其家系成员,在家系调查的基础上,观察和记录NF1的临床表型,并利用二代靶向基因测序结合Sanger测序来检测和验证致病突变。结果 5例先证者都仅有皮损（包括咖啡斑、雀斑、神经纤维瘤）,无其他系统损害;5个家系先证者共发现5种突变,分别位于NF1基因的不同外显子中,包括1个大片段缺失突变（hg38：chr17：31327199-31335928 del 8 730 bp）、1个剪切突变（c.7970+1G>T）、1个插入突变（c.3011 _3012insTATG,p.N1004fs*）、1个缺失突变（c.1754_1757delTAAC, p.T586Vfs*18）和1个无义突变（c.C503G,p.S168X）,前3种是未经报道的新突变。结论 在5个先证者表型温和的NF1家系中检测出5种突变,鉴定出3种新突变,丰富了NF1的突变谱。     

Neurofibroma-derived fibroblast-stimulating factor in the serum of patients with neurofibromatosis (von Recklinghausen's disease)

Summary The effect of serum from patients with von Recklinghausen's disease [neurofibromatosis (NF)] on the cell growth and DNA synthesis of cultured neurofibroma-derived cells (NF fibroblasts grown from explant cultures of cutaneous neurofibromas from seven NF patients, and Schwann cells from a single-cell-suspension culture of the sample from one of these patients) was examined. Serum from patients with NF, whether autologous or allogeneic, enhanced the growth and ³H-thymidine uptake of NF fibroblasts twice as much as non-NF serum. Further study revealed that a dialysable, low-molecular-weight factor isolated from pooled NF serum was responsible for the stimulation of NF fibroblasts. This factor did not influence the DNA synthesis of either dermal fibroblasts cultured from non-NF patients or of Schwann cells. In contrast, no dialysable fraction of pooled serum from healthy persons exhibited such an NF-fibroblast-stimulating activity.     

Histology of a plexiform neuroma with Vater-Pacini-lamellar-corpuscle-like structures]

From the finger of a 11 year old boy a tumor that had been present since birth was removed. Histological examination showed a great number of immature nerve bundles, and structures resembling Pacinian corpuscles. It could be shown that the organoid structures are a result of a proliferation of the so-called perineurial cells. These formations do not correspond with real tactile corpuscles, rather they can be considered as neoplastic structures of the perineurium.     

Schwannomatosis: dermatological relevance of an unusual form of neurofibromatosis type 2 (NF-2)

Four patients (three women and one man) suffering from multiple subcutaneous, painful, nodular tumors, diagnosed as multiple schwannomas of peripheral nerves (MCN), are presented. Two had radicular and VIII cranial nerve schwannomas associated with meningioma. The other two patients had only MCN. These cases were obtained from a prospective study of 30 patients with clinical criteria of neurofibromatosis (NF). The main inclusion criteria were pathological nuclear magnetic resonance (3). In 19 cases histological studies of internal neurological tumors were carried out. The four cases reported here presented fewer than six 'café au lait' spots. No hereditary background was demonstrated in these patients. Clinical and genetic investigations were insufficient to affirm that MCN or schwannomatosis is a new entity or a new form of NF. Sporadic cases of NF-2 appear more often than has been admitted before and these non-inherited forms appear to be in cases associated with MCN.     

Mechanisms of loss of heterozygosity in neurofibromatosis type 1-associated plexiform neurofibromas

Plexiform neurofibromas constitute a serious burden for patients with neurofibromatosis type 1 (NF1), a common autosomal dominant disorder characterized by pigmentary changes and tumorous skin lesions (neurofibromas). Despite the prominence of these benign tumors in NF1 patients, the mechanisms underlying the tumor-associated loss of heterozygosity (LOH) in plexiform neurofibromas have not been extensively studied. We performed LOH analysis on 43 plexiform neurofibromas from 31 NF1 patients, the largest study of its kind to date. A total of 13 (30%) plexiform neurofibromas exhibited LOH involving 17q markers. In three tumors, LOH was found to be confined to the NF1 gene region. However, in none of the tumors was a somatic NF1 microdeletion, mediated by non-allelic homologous recombination between either NF1-REPs or SUZ12 genes, detected. Thus, NF1 microdeletions do not appear to be frequent somatic events in plexiform neurofibromas. Determination of NF1 gene copy number by multiplex ligation-dependent probe amplification indicated that although tumors with smaller regions of LOH were characterized by 17q deletions, no NF1 gene copy number changes were detected in six plexiform neurofibromas with more extensive LOH. To our knowledge, mitotic recombination has not previously been reported to be a frequent cause of LOH in plexiform neurofibromas.     

Pacinian corpuscle hyperplasia in a 6-year-old girl

We present a rare case of Pacinian corpuscle hyperplasia (PCH) presenting with typical finger pain in a 6-year-old girl. As appendages in children are smaller than those in adults, diagnostic criteria are needed for pathological confirmation of PCH in pediatric patients.     

节段型神经纤维瘤病一例

患者,男,29岁。颈部咖啡斑、斑块2年。皮损组织病理示:表皮大致正常,真皮内可见境界清楚的无包膜团块,其内可见胞浆淡染的梭形细胞,细胞核扭曲变长,瘤体内散在肥大细胞。免疫组化:S-100阳性,CD34阳性。诊断为节段型神经纤维瘤病。     

Distribution of diffuse plexiform neurofibroma on the body surface in patients with neurofibromatosis 1

Neurofibromatosis 1 (NF1) is a genetic disease characterized by cutaneous, neurological and osseous abnormalities. Approximately 20% of patients develop plexiform neurofibroma (PN), resulting in impaired quality of life. To evaluate distribution of diffuse PN on the body surface, a retrospective study was conducted for 354 patients with NF1 from 2007 to 2018 in Japan. We investigated a total of 40 patients with clinically apparent superficial diffuse PN. In the cases evaluated, 57.4% of the diffuse PN were located on the trunk, 19.2% the head and neck, 12.8% the lower limbs and 10.6% the upper limbs. Remarkably, 75.0% of the diffuse PN were located on the dorsal side. The frequency was significantly higher on the trunk than on the head and neck (P = 0.026). Our findings provide useful information for giving attention to the high possibility of diffuse PN on the dorsal side before progression in childhood and for future treatment in NF1.