Cukurova University Medical Faculty, Department of Medical Oncology, Adana, Turkey.
Crit Rev Oncol Hematol. 2013 May;86(2):191-9. doi: 10.1016/j.critrevonc.2012.11.001. Epub 2012 Dec 4.
Neurofibromatosis type 1 (NF1) is a genetic syndrome that predisposes patients to benign and malignant tumor development. Patients with NF1 develop multiple neurofibromas that can transform into aggressive sarcomas known as malignant peripheral nerve sheath tumors. In contrast, malignant tumors unrelated to the nervous system rarely coexist with neurofibromatosis. The aim of this article was to present four cases of adult NF1 patients with malignant tumors unrelated to the nervous system as well as a bibliographic search for papers describing these tumors in NF1, focusing on osteosarcomas, gastrointestinal stromal tumors (GISTs), leiomyosarcomas and somatostatinomas and their genetic alterations in NF1.
Search engines such as PubMed and MEDLINE were browsed for English-language articles since 1989 using a list of keywords, as well as references from review articles. Search terms were NF1, osteosarcoma, leiomyosarcoma, somatostatinoma and GIST. Data were summarized in a table at the end of the Results section.
In our four NF1 cases, there were one osteosarcoma, one leiomyosarcoma, one somatostatinoma and GIST and one GIST. NF1 was diagnosed at an adult age when these patients were admitted to our oncology department. The results generated by the literature search yielded 75 articles about NF and GIST. We summarized the clinical characteristics of 43 patients with NF1 and somatostatinoma. Forty-five articles involving NF and osteosarcoma were found, and of these, 26 involved NF1; from these articles, we identified the clinical features of 8 patients. Twenty-five articles were found concerning NF1 and leiomyosarcoma, and of those, we summarized the clinical features of 15 patients.
Here we reviewed somatostatinomas, GISTs, osteosarcomas and leiomyosarcomas occurring in NF1 patients. Patients with NF1 who present with gastrointestinal symptoms, should be carefully evaluated carefully with a high index of suspicion of potential GISTs, periampullary and duodenal tumors. Patients with pathological fractures or bone pain along with NF1 should be carefully screened for malignant bone tumors. Patients with NF1 can develop leiomyosarcoma less frequently than other malignancies, but the association of uterine leiomyoma and NF1 may not be fortuitous. Somatic mutations were defined for frequent tumors, including neurogenic tumors and GISTs but not for sarcomas due to the complexity of underlying mechanisms of the disease and tumorigenesis. Based on the findings; all NF patients can develop malignant tumors, including the less frequently observed ones. Therefore, we recommend that new genetic studies should be performed for rare malignancies in cases of NF1.
神经纤维瘤病 1 型（NF1）是一种遗传综合征，使患者易患良性和恶性肿瘤的发展。NF1 患者会形成多发性神经纤维瘤，这些肿瘤可能会恶化为恶性外周神经鞘肿瘤，即侵袭性肉瘤。相比之下，与神经系统无关的恶性肿瘤很少与神经纤维瘤病同时发生。本文旨在介绍 4 例与神经系统无关的 NF1 成年患者的恶性肿瘤病例，并对文献中描述 NF1 中这些肿瘤的论文进行文献检索，重点关注骨肉瘤、胃肠道间质瘤（GIST）、平滑肌肉瘤和生长抑素瘤及其 NF1 中的遗传改变。
自 1989 年以来，我们使用一系列关键词在 PubMed 和 MEDLINE 等搜索引擎上搜索英文文章，并查阅综述文章的参考文献。搜索词包括 NF1、骨肉瘤、平滑肌肉瘤、生长抑素瘤和 GIST。在结果部分的末尾，将数据总结在一个表中。
在我们的 4 例 NF1 病例中，有 1 例骨肉瘤、1 例平滑肌肉瘤、1 例生长抑素瘤和 1 例 GIST。当这些患者被收入我们的肿瘤科时，NF1 在成年期被诊断出来。文献检索结果生成了 75 篇关于 NF 和 GIST 的文章。我们总结了 43 例 NF1 和生长抑素瘤患者的临床特征。共发现 45 篇涉及 NF 和骨肉瘤的文章，其中 26 篇涉及 NF1；从这些文章中，我们确定了 8 例患者的临床特征。共发现 25 篇关于 NF1 和平滑肌肉瘤的文章，其中我们总结了 15 例患者的临床特征。
在这里，我们回顾了 NF1 患者中的生长抑素瘤、GIST、骨肉瘤和平滑肌肉瘤。出现胃肠道症状的 NF1 患者应高度怀疑潜在的 GIST、壶腹周围和十二指肠肿瘤，并进行仔细评估。出现病理性骨折或骨痛并伴有 NF1 的患者应仔细筛查恶性骨肿瘤。与其他恶性肿瘤相比，NF1 患者发生平滑肌肉瘤的频率较低，但子宫肌瘤与 NF1 的关联并非偶然。由于疾病和肿瘤发生的潜在机制复杂，常见肿瘤（包括神经源性肿瘤和 GIST）存在体细胞突变，但肉瘤没有。根据这些发现，所有 NF 患者都可能发生恶性肿瘤，包括不太常见的肿瘤。因此，我们建议对 NF1 患者的罕见恶性肿瘤进行新的遗传研究。
