Tylosis with oesophageal cancer: Diagnosis, management and molecular mechanisms.
Tylosis with oesophageal cancer: Diagnosis, management and molecular mechanisms.
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DOI：
10.1186/s13023-015-0346-2
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发表时间：
2015-09-29
影响因子：
3.7
通讯作者：
Kelsell DP
中科院分区：
文献类型：
--
作者：
Ellis A;Risk JM;Maruthappu T;Kelsell DP
强直（掌跖角化过度）的特征是手部和足部皮肤的局灶性增厚，并且与发生食管鳞状细胞癌的非常高的终生风险相关。在一个大家庭中，这种风险在65岁时计算为95%，然而，一般人群中这种疾病的频率尚不清楚，可能低于1，000，000。食管病变表现为小的（2-5 mm）、白色、多倍体病变，散布于整个食管，也有口腔白斑病的描述。虽然食管癌的症状可能包括吞咽困难、吞咽痛、厌食和体重减轻，但在早期疾病中可能没有症状，这突出了这些患者内窥镜监测的重要性。食管癌伴侵填体病通常出现在中年至老年（从50多岁开始），与散发性食管癌相比，没有更早的发展。食管癌的结节病是一种常染色体显性遗传，皮肤特征完全不对称，通常在7 - 8岁时出现，但可迟至青春期出现。最近发现位于17q25.1的RHBDF 2突变是致病的。食管癌的诊断是基于阳性家族史，特征性临床特征，包括皮肤和食管病变，以及RHBDF 2突变的遗传分析。关键的管理目标是监测食管发育不良的早期发现和治疗。监测包括每年一次胃镜检查，对任何可疑病变进行活检，并对食管上、中、下段进行二次活检。这与饮食和生活方式调整建议和症状教育相结合。掌跖角化病的症状管理包括定期应用润肤剂，专业鞋类和早期治疗裂缝和额外的感染，特别是手足。对于厚皮肤的更具体的治疗是以口服类维生素A的形式提供的，这是非常有效的，但通常产生副作用，包括鼻脱落和出血，高胆固醇血症和肝功能检查异常。一旦确定了家族史，就可以向患者和家庭成员提供遗传咨询。由于受影响的个体数量有限，因此很难确定伴有食管癌的侵填体病的预后。在过去40年的监测中，利物浦家族的6例鳞状食管癌中有5例是通过内窥镜检查发现的，并通过手术切除。5例患者中有4例在就诊时患有1期疾病，并且在8年多后仍然存活。这表明筛查计划的存在改善了这些患者的预后。
Tylosis (hyperkeratosis palmaris et plantaris) is characterised by focal thickening of the skin of the hands and feet and is associated with a very high lifetime risk of developing squamous cell carcinoma of the oesophagus. This risk has been calculated to be 95 % at the age of 65 in one large family, however the frequency of the disorder in the general population is not known and is likely to be less than one in 1,000,000. Oesophageal lesions appear as small (2–5 mm), white, polyploid lesions dotted throughout the oesophagus and oral leukokeratosis has also been described. Although symptoms of oesophageal cancer can include dysphagia, odynophagia, anorexia and weight loss, there may be an absence of symptoms in early disease, highlighting the importance of endoscopic surveillance in these patients. Oesophageal cancer associated with tylosis usually presents in middle to late life (from mid-fifties onwards) and shows no earlier development than the sporadic form of the disease. Tylosis with oesophageal cancer is inherited as an autosomal dominant trait with complete penetrance of the cutaneous features, usually by 7 to 8 years of age but can present as late as puberty. Mutations in RHBDF2 located on 17q25.1 have recently been found to be causative. A diagnosis of tylosis with oesophageal cancer is made on the basis of a positive family history, characteristic clinical features, including cutaneous and oesophageal lesions, and genetic analysis for mutations in RHBDF2. The key management goal is surveillance for early detection and treatment of oesophageal dysplasia. Surveillance includes annual gastroscopy with biopsy of any suspicious lesion together with quadratic biopsies from the upper, middle and lower oesophagus. This is coupled with dietary and lifestyle modification advice and symptom education. Symptomatic management of the palmoplantar keratoderma includes regular application of emollients, specialist footwear and early treatment of fissures and super-added infection, particularly tinea pedis. More specific treatment for the thick skin is available in the form of oral retinoids, which are very effective but commonly produce side effects, including nasal excoriation and bleeding, hypercholesterolaemia, and abnormal liver function tests. Genetic counselling can be offered to patients and family members once a family history has been established. The prognosis of tylosis with oesophageal cancer is difficult to determine due to the limited number of affected individuals. In the last 40 years of surveillance, five out of six cases of squamous oesophageal cancer in the Liverpool family were detected endoscopically and were surgically removed. Four of five patients had stage 1 disease at presentation and remain alive and well more than 8 years later. This suggests that the presence of a screening program improves prognosis for these patients.