Ponti Giovanni, Pellacani Giovanni, Martorana Davide, Mandel Victor Desmond, Loschi Pietro, Pollio Annamaria, Pecchi Annarita, Dealis Cristina, Seidenari Stefania, Tomasi Aldo
Department of Surgical, Medical, Dental and Morphological Sciences with interest in Transplant, Oncological and Regenerative Medicine, University of Modena and Reggio Emilia, I-41124 Modena, Italy.
Department of Genetics, University of Parma, I-43125 Parma, Italy.
Oncol Lett. 2016 Jun;11(6):3709-3714. doi: 10.3892/ol.2016.4469. Epub 2016 Apr 19.
Elephantiasis neuromatosa (EN) can arise from a plexiform neurofibroma of the superficial and deep nerves developing from a hyperproliferation of the perineural connective tissue infiltrating adjacent fat and muscles. To date, the clinical association between EN and neurofibromatosis type 1 (NF1) has been poorly defined, particularly with regard to the role of lymphatic alterations and the consequent lymphedema. The present study reports the clinical and biomolecular features of EN in a NF1 patient with the clear clinical diagnostic criteria of multiple cafè-au-lait macules, neurofibromas, EN, a positive family history and a novel NF1 germline c.1541_1542del mutation. Lymphoscintigraphy (LS) highlighted marked dermal backflow in the affected limb, hypertrophy of the ipsilateral inguinal and external iliac lymph nodes, and a bilateral lower limb lymph flow delay. These data support the hypothesis that an extensive hyperproliferative process involving perineural connective, limb soft tissues, bones and the lymphatic system can be responsible for EN in NF1 patients, on the basis of adipocyte metaplasia triggered by lymphostasis and lymphedema, and bone overgrowth and gigantism caused by chronic hyperemia. LS and magnetic resonance imaging can be efficacious tools in the diagnosis and clinical characterization of the early onset of the disease.
神经瘤性象皮病（EN）可由浅表和深部神经的丛状神经纤维瘤发展而来，该神经纤维瘤源于神经周围结缔组织的过度增殖，可浸润邻近的脂肪和肌肉。迄今为止，EN与1型神经纤维瘤病（NF1）之间的临床关联尚未明确界定，尤其是在淋巴改变和随之而来的淋巴水肿方面。本研究报告了一名NF1患者的EN的临床和生物分子特征，该患者具有明确的临床诊断标准，包括多个咖啡牛奶斑、神经纤维瘤、EN、阳性家族史以及一种新的NF1种系c.1541_1542del突变。淋巴闪烁造影（LS）显示患肢有明显的真皮回流、同侧腹股沟和髂外淋巴结肿大以及双下肢淋巴流延迟。这些数据支持这样一种假设，即基于淋巴淤滞和淋巴水肿引发的脂肪细胞化生，以及慢性充血导致的骨过度生长和巨人症，涉及神经周围结缔组织、肢体软组织、骨骼和淋巴系统的广泛过度增殖过程可能是NF1患者发生EN的原因。LS和磁共振成像可能是诊断该疾病早期发病及临床特征的有效工具。
