Superficial malignant peripheral nerve sheath tumor arising from diffuse neurofibroma in a neurofibromatosis type 1 patient

Malignant peripheral nerve sheath tumors (MPNST) are regarded as sarcomas that arise from peripheral nerves or that display differentiation along the lines of the various elements of the nerve sheath. These tumors occur in deep soft tissues, but superficial primary MPNST with a cutaneous or subcutaneous origin have rarely been reported. A 70‐year‐old woman presented with a 3–4‐year history of a slowly enlarging soft nodule on the left side of her neck. The histopathological diagnosis of the nodule was low‐grade MPNST arising from diffuse neurofibroma. There was increased cellularity, but no necrosis or mitotic activity. These histopathological findings pose difficulties in differential diagnosis from a neurofibroma with atypical histological features. We report a rare case of superficial MPNST arising from diffuse neurofibroma associated with underlying occipital bone dysplasia in a neurofibromatosis type 1 patient.     

Natural course and characteristics of cutaneous neurofibromas in neurofibromatosis 1

Neurofibromatosis 1 (NF1) is characterized by cutaneous, neurological and osseous manifestations. Most NF1 patients develop cutaneous neurofibromas. However, time‐dependent change with aging and the predilection site of cutaneous neurofibromas remain unclear. To clarify the natural course and characteristics of cutaneous neurofibromas, a retrospective study was conducted for 57 NF1 patients who were treated at the Department of Dermatology of Tottori University Hospital between January 2007 and April 2016. For each patient, we investigated the time‐dependent changes and the numbers of cutaneous neurofibromas in four body surface regions. There was a positive correlation between age and number of cutaneous neurofibromas (r = 0.75, P < 0.001). Cutaneous neurofibromas were located on the trunk (60.2%), lower limbs (16.1%), upper limbs (14.4%), and head and neck (9.2%). There was no significant relationship between each body type (e.g. obese or thin) and cutaneous neurofibromas. With respect to the year‐to‐year percentage change in cutaneous neurofibromas, the average annual rate of increase was 0.21 (range, ?0.71 to 1.2). The number of cutaneous neurofibromas had increased in approximately 61% of the patients 1 year later. Our data will enable physicians to estimate the overall state of cutaneous neurofibromas in NF1 and will be useful for handling cutaneous manifestations before they become a serious condition.     

A possible paracrine hedgehog signalling pathway in neurofibromas from patients with neurofibromatosis type 1

BACKGROUND: Hedgehogs (Hhs) and their receptors are involved in organ development as well as in tumorigenesis observed in basal cell carcinoma. Among Hhs, Desert hedgehog secreted from Schwann cells mediates the formation of peripheral nerve sheaths. However, there has been no study on the role of Hhs and their receptors in tumorigenesis of neurofibromas in neurofibromatosis type 1 (NF1). OBJECTIVES: To clarify the expression and localization of Hhs and their receptors in neurofibromas of NF1 patients. METHODS: Expression of Hhs and their receptors was studied by immunohistochemistry using neurofibromas from NF1 patients and control normal skin samples. RESULTS: In neurofibromas, CD57-positive tumour cells with delicate elongated processes were positive for the receptor PTCH2. Perineurial cells of involved nerves within neurofibromas as well as those of normal cutaneous nerves expressed Indian hedgehog and Sonic hedgehog. Schwann cells of normal cutaneous nerves were positive for PTCH2. CONCLUSIONS: Our study suggests that a paracrine Hh signalling pathway may be involved in tumorigenesis of neurofibromas in NF1.     

Genotype‐phenotype correlation in type 1 neurofibromatosis: pMet992del mutation and milder disease

A few genotype‐phenotype correlations have been described in type 1 neurofibromatosis. One deletion, p.Met992del, seems to be responsible for a mild form of the condition, in which there is absence of externally visible neurofibromas. We report a mother and a son with this mutation.     

Fetal antigen 1, a member of the epidermal growth factor superfamily, in neurofibromas and serum from patients with neurofibromatosis type 1

Fetal antigen 1 (FA1) is a 26-32 kDa glycoprotein containing six epidermal growth factor-like repeats closely related to the delta/notch/serrate proteins in Drosophila. FA1 has been shown to be involved in cell differentiation in a juxtacrine/paracrine manner. As neurofibromatosis type 1 (NF-1), also called von Recklinghausen disease, involves aberrant growth of tissues derived from the neural crest, the expression of FA1 was examined in neurofibroma skin biopsies and serum from patients with NF-1. FA1 was found in the spindle cells of all (n = 10) skin tumour specimens from adult NF-1 patients, whereas normal dermis was FA1 negative. In adults, the serum FA1 levels were significantly higher in NF-1 patients (n = 13) than in normal healthy controls (n = 177) (P = 0.037). In the group of children with NF-1 (n = 9), significantly higher serum FA1 levels were observed in those known to have complications with cerebral or spinal involvement (n = 4) (P = 0.014). The presence of FA1 in neurofibroma specimens and the elevated serum levels in patients with NF-1 suggests that FA1 may be involved in the pathogenesis of NF-1, perhaps acting as a growth promoting factor.     

Cutaneous Neurofibroma Heterogeneity: Factors that Influence Tumor Burden in Neurofibromatosis Type 1

1. Download : Download high-res image (204KB)
2. Download : Download full-size image

     

Nutritional,muscular and metabolic characteristics in patients with neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) has many reported clinical characteristics. We previously found that NF1 patients (especially men) had lower body mass index (BMI) than controls, but the reason has not been elucidated. To address this issue, a retrospectively case–control study was conducted. Anthropometric and serum chemistry data that potentially relate to BMI were collected from medical records of NF1 patients and their age‐ and sex‐matched controls. Enrollment of 98 adult patients who underwent skin surgery with NF1 (41 men, 57 women) and 173 without NF1 (74 men, 99 women) were investigated. The median BMI in male NF1 patients was significantly lower than that of the controls. Triglycerides in male NF1 patients were significantly lower than male controls, creatine kinase and lactate dehydrogenase in NF1 patients were also lower than controls, aspartate aminotransferase and alanine aminotransferase showed a lower tendency in NF1 patients, but were significantly lower in female patients. With correlation analysis, lactate dehydrogenase was moderately correlated with BMI in male NF1 patients. Creatine kinase and creatinine showed no statistical correlation with BMI in either group. Triglycerides and alanine aminotransferase showed a positive correlation with BMI in both male and female controls, but not in NF1 patients. In conclusion, only lactate dehydrogenase was moderately correlated with BMI in male NF1 patients, although results of some nutritional and metabolic parameters suggest a specific metabolism in NF1.     

A novel surgical margin (1 cm) might be from benefit for patients with dysplastic nevi,thin melanomas,and melanoma in situ: Analysis based on clinical cases

Malignant melanoma is an oncologic disease, whose current management among others includes surgical and immunological therapy. According to the current recommendations of the American Joint Committee on Cancer, the surgical excision of the primary tumor should be performed in two operative sessions, which has several consequences. The following paper will present and discuss six cases of pigmented lesions and the advantages of the one‐step melanoma surgery in their management.     

Anthropometric characteristics and comorbidities in Japanese patients with neurofibromatosis type 1: A single institutional case–control study

Neurofibromatosis type 1 (NF1) is a well‐known genetic disorder characterized by café‐au‐lait spots and neurofibromas, but many other clinical characteristics and associated comorbidities also have been reported. This study aimed to characterize NF1 further by investigating its association with anthropometric characteristics and other diseases. We performed a case–control study of 227 NF1 patients (101 male, 126 female) and a randomly selected age‐ and sex‐matched control group of 681 non‐NF1 patients (303 male, 378 female) who visited our institution in Japan. We examined adult (≥20 years) height and body mass index (BMI), and, in the total sample, allergic diseases (bronchial asthma [BA], atopic dermatitis [AD] and allergic rhinitis) and other respiratory cardiovascular and psychiatric disorders. In adults, the mean BMI was lower in the NF1 group than in the control group, and was significantly statistically different among men (P = 0.0238). In the whole sample, the prevalences of BA (P = 0.0184), AD (P = 0.0144) and valvular heart disease (P = 0.0166) were significantly greater in the NF1 group than in the control group. To date, no similar research on the BMI or the prevalence of allergic disease in NF1 patients has been reported. Our results suggest that NF1 patients tend to have lower BMI and may have alterations in specific metabolic pathways and altered allergic immunity.     

黑素瘤组织中乙醛脱氢酶1、上皮性钙黏附蛋白及尿激酶型纤溶酶原激活物受体的表达及临床意义

目的研究黑素瘤组织中乙醛脱氢酶1(aldehyde dehydrogenase 1,ALDH1)、上皮性钙黏附蛋白(E-cadherin,E-cad)及尿激酶型纤溶酶原激活物受体(urokinase-type plasminogen activator receptor,uPAR)的表达及与临床病理特征的关系。方法选择50例黑素瘤和50例色素痣患者的病变组织作为研究对象,采用免疫组化法检测病变组织中的ALDH1、E-cad及uPAR的表达情况,分析这3种蛋白表达与患者临床组织病理特征、肿瘤分期的关系。结果黑素瘤组织中ALDH1和uPAR表达阳性率分别为82.00%(41/50)和86.00%(43/50),均显著高于色素痣组(P0.05);黑素瘤组织中E-cad阳性表达率为38.00%(19/50),显著低于色素痣组(P0.05)。ALDH1、uPAR表达阳性率与患者年龄、性别、肿瘤厚度、浸润深度、是否淋巴结转移和组织病理分型均无相关性,但肿瘤厚度≥4 mm、浸润深度Ⅳ~Ⅴ、发生淋巴结转移等患者黑素瘤组织中ALDH1、uPAR表达阳性率均90%。浸润深度Ⅳ~Ⅴ的黑素瘤患者E-cad表达阳性率显著低于浸润深度Ⅰ~Ⅲ的患者(P0.05),黑素瘤患者E-cad表达阳性率与其他临床特征无相关性。结论黑素瘤在发生和进展过程中ALDH1、uPAR表达上调,E-cad表达下调,E-cad表达下调与肿瘤程度有关。     

AEG-1、P16、KI-67蛋白在宫颈癌前病变中的表达与临床意义

目的:探讨AEG-1、P16、KI-67蛋白在宫颈癌前病变中的表达与临床意义。方法:2008年2月至2015年9月选择在我院诊治的宫颈癌前病变患者98例作为癌前病变组,同期选择宫颈癌患者98例作为宫颈癌组和98例健康体检人作为对照组,取三组的宫颈样本都进行AEG-1、P16、KI-67蛋白表达的免疫组化分析,并调查了临床资料进行相关性分析。结果:AEG-1、P16、KI-67蛋白在宫颈癌组的阳性表达率分别为80.0%、93.9%和92.9%,而癌前病变组为57.1%、50.0%和57.1%,在对照组为3.1%、2.0%和4.1%,三组间对比差异有统计学意义(P0.05)。AEG-1、P16、KI-67蛋白的阳性表达与宫颈癌前病变的年龄、疾病类型、HPV感染等病理参数对比差异有统计学意义(P0.05)。直线相关性显示AEG-1、P16、KI-67蛋白表达都呈现两两正向相关性(P0.05)。结论:AEG-1、P16、KI-67蛋白在宫颈癌前病变中都呈现高表达状况,且与临床病理特征存在相关性,三者可互相作用影响宫颈癌前病变的发展状况。     

New entity, definition and diagnostic criteria of cutaneous adult T-cell leukemia/lymphoma: human T-lymphotropic virus type 1 proviral DNA load can distinguish between cutaneous and smoldering types

Adult T-cell leukemia/lymphoma (ATLL) has been divided into four subtypes up to now: (i) acute; (ii) lymphoma; (iii) chronic; and (iv) smoldering. Skin lesion(s) may be present and the cases showing less than 5% abnormal T-lymphocytes in peripheral blood without involvement of other organs, have been classified as smoldering ATLL. However, this type of ATLL with skin manifestations had a worse prognosis than that without skin lesions. This study aimed to define and distinguish cutaneous ATLL lacking nodal lymphoma and leukemic change from smoldering ATLL. We propose an entity of cutaneous ATLL, which has less than 5% abnormal T lymphocyte in peripheral blood, a normal lymphocyte count (i.e. <4 x 10(9)/L), no hypercalcemia and lactate dehydrogenase values of up to 1.5 times the normal upper limit. At least one of the histologically proven skin lesions should be present accompanying monoclonal integration of human T-cell lymphotropic virus type 1 (HTLV-1) proviral DNA in the skin lesion. Blood samples were collected from 41 HTLV-1-infected patients, 21 asymptomatic carriers, 16 patients with cutaneous ATLL and four patients with smoldering ATLL. HTLV-1 proviral loads, soluble interleukin-2 receptors and other parameters were examined in each case. HTLV-1 proviral DNA loads in smoldering ATLL group are significantly higher than those in asymptomatic carrier and cutaneous ATLL group. Cutaneous ATLL may be a distinct entity that should be separated from smoldering ATLL clinically and virologically.     

Reduced expression of actin-binding proteins,h-caldesmon and calponin h1, in the vascular smooth muscle inside melanoma lesions: an adverse prognostic factor for malignant melanoma

BACKGROUND: The structural integrity of the blood vessels such as small arteries and veins is studied less frequently in malignant tumours than is angiogenesis. Objectives To clarify the characteristics of small arteries and small veins of melanoma lesions. METHODS: We immunohistochemically investigated various types of melanocytic tumours using antibodies specific for endothelial and vascular smooth muscle cells, and analysed the relationship between the expression of these molecules in the blood vessels and the biological characteristics of the tumours. Formalin-fixed, paraffin-embedded sections of 15 cases of benign melanocytic tumours and 64 cases of malignant melanomas were investigated. RESULTS: Significant suppression of expression of h-caldesmon (h-CD) and calponin h1 (CNh1) was observed in the blood vessels of malignant melanomas compared with both benign melanocytic tumours and normal tissues. In particular, the level of h-CD expression was inversely correlated with the frequency of metastasis and positively correlated with the survival rate in patients with malignant melanoma. CONCLUSIONS: These findings suggest that alterations of the tumour vessels are an important factor for the prognosis of malignant melanoma, and that suppression of h-CD and CNh1 in the blood vessels in malignant melanoma reflects a structural fragility of the vessels, leading to their easy penetration by tumour cells. Defective expression of these molecules is likely to be an important marker for metastatic potential and for poor prognosis of melanoma.     

Trends of HIV-1 and HIV-2 prevalence among pregnant women in Guinea-Bissau, West Africa: possible effect of the civil war 1998 1999

Objectives

Sentinel surveys in Bissau, the capital of Guinea‐Bissau, have shown low prevalence of HIV‐1 but high HIV‐2 prevalence before 1998. Guinea‐Bissau experienced a civil war in 1998–1999. To examine specifically the trends of HIV prevalence from antenatal surveys in Bissau, Guinea‐Bissau in 1987–2004, and whether the civil war in 1998–1999 could have an effect on HIV prevalence levels after the conflict.

Methods

Since 1987, anonymous HIV testing in delivering women has been performed at the maternity clinic, Simão Mendes National Hospital, Bissau, as part of the national sentinel surveillance programme. Consecutive sampling was performed for approximately 3 months between September and December each year. Serological analyses were performed at the National Public Health Laboratory in Guinea‐Bissau.

Results

A total of 20 422 women were tested for HIV between 1987 and 2004. The total HIV‐1 prevalence increased from 0.0% in 1987 to 4.8% in 2004 and the total HIV‐2 prevalence decreased from 8.3% in 1987 to 2.5% in 2004. The HIV‐1 prevalence increased from 2.5% in 1997 to 5.2% in 1999, but stabilized in subsequent years.

Conclusions

There was a significant increase in HIV‐1 prevalence in the years 1987–2004 and a significant decline in HIV‐2 prevalence over the same period. The civil war in 1998–1999 may have sparked HIV‐1 transmission, as HIV‐1 prevalence more than doubled between 1997 and 1999, but there is no evidence of a long‐term effect on the trends of HIV‐1 or HIV‐2 prevalence.