PDF(Pubmed)
Abstract：
UNASSIGNED: Constitutional mismatch repair deficiency (CMMRD) is a rare autosomal recessive disease carrying an increased risk of cancers (paediatric tumours of central nervous system, haematolymphoid malignancies along with gastrointestinal (GI) cancer(s), which are usually seen in the second and third decades), leading to syndromic presentation. Causal mutations are detected in DNA mismatch repair (MMR) genes, including MLH1, PMS2, MSH2 and MSH6 that are also known for their established role in Lynch syndrome. We describe a case of CMMRD with an earlier (first decade of life) presentation of mediastinal acute lymphoblastic lymphoma and colorectal malignancy.
UNASSIGNED: A 5-year-old boy presented with respiratory complaints, bilateral cervical lymphadenopathy, multiple café-au-lait macules (CALMs) on the lower back and history of parental consanguinity with the death of three sisters due to brain tumour within 6 months of diagnosis. Computerised tomographic scan chest revealed a huge mediastinal mass. The patient underwent a trucut biopsy of the mass. The results were significant for a pre-T-cell acute lymphoblastic lymphoma. Suspicion of CMMRD was raised based on a combination of factors described above. A panel of MMR proteins was applied on the biopsy tissue that revealed loss of nuclear expression of MLH1 and PMS2 immunostaining in tumour cells with positive external controls. While on maintenance therapy for lymphoma, about a year later, the patient developed subacute intestinal obstruction due to a stenosing polypoidal circumferential tumour in the mid-sigmoid colon found on flexible sigmoidoscopy that was followed by endoscopic biopsies and insertion of a fully covered self-expanding metallic adult biliary stent with a diameter of 10 mm and length of 6 cm leading to immediate relief of obstruction. Biopsies revealed adenocarcinoma with neuroendocrine differentiation. Metastatic tumour deposits were seen in the omentum, anterior abdominal wall and the left peritoneal wall.
UNASSIGNED: Earlier (first decade) presentation of GI malignancy warrants that an earlier screening through radiological scans for any possible tumours and MMR protein expression analysis (loss in tumour plus normal non-tumour cells) are essential in patients having CALMs and family history of paediatric tumours.
UNASSIGNED: A 5-year-old boy presented with respiratory complaints, bilateral cervical lymphadenopathy, multiple café-au-lait macules (CALMs) on the lower back and history of parental consanguinity with the death of three sisters due to brain tumour within 6 months of diagnosis. Computerised tomographic scan chest revealed a huge mediastinal mass. The patient underwent a trucut biopsy of the mass. The results were significant for a pre-T-cell acute lymphoblastic lymphoma. Suspicion of CMMRD was raised based on a combination of factors described above. A panel of MMR proteins was applied on the biopsy tissue that revealed loss of nuclear expression of MLH1 and PMS2 immunostaining in tumour cells with positive external controls. While on maintenance therapy for lymphoma, about a year later, the patient developed subacute intestinal obstruction due to a stenosing polypoidal circumferential tumour in the mid-sigmoid colon found on flexible sigmoidoscopy that was followed by endoscopic biopsies and insertion of a fully covered self-expanding metallic adult biliary stent with a diameter of 10 mm and length of 6 cm leading to immediate relief of obstruction. Biopsies revealed adenocarcinoma with neuroendocrine differentiation. Metastatic tumour deposits were seen in the omentum, anterior abdominal wall and the left peritoneal wall.
UNASSIGNED: Earlier (first decade) presentation of GI malignancy warrants that an earlier screening through radiological scans for any possible tumours and MMR protein expression analysis (loss in tumour plus normal non-tumour cells) are essential in patients having CALMs and family history of paediatric tumours.
摘要：
■体质错配修复缺陷症（CMMRD）是一种罕见的常染色体隐性遗传疾病，其癌症风险增加（中枢神经系统儿科肿瘤，血液淋巴样恶性肿瘤以及胃肠道（GI）癌症，通常在第二个和第三个十年中看到)，导致综合征表现。在DNA错配修复（MMR）基因中检测到因果关系突变，包括MLH1，PMS2，MSH2和MSH6，它们在Lynch综合征中的作用也是众所周知的。我们描述了一例CMMRD，其早期（生命的第一个十年）表现为纵隔急性淋巴母细胞淋巴瘤和结直肠恶性肿瘤。
■一名5岁男孩出现呼吸道疾病，双侧颈淋巴结肿大，下背部有多个café-au-lait黄斑（CALM），并且有父母血缘关系的历史，在诊断后的6个月内，由于脑肿瘤导致三个姐妹死亡。计算机断层扫描胸部显示巨大的纵隔肿块。患者接受了肿块活检。该结果对于前T细胞急性淋巴母细胞淋巴瘤具有重要意义。基于上述因素的组合，人们对CMMRD产生了怀疑。将一组MMR蛋白应用于活检组织，显示在具有阳性外部对照的肿瘤细胞中MLH1和PMS2免疫染色的核表达丧失。在淋巴瘤的维持治疗中，大约一年后,由于在柔性乙状结肠镜检查中发现乙状结肠中部狭窄的息肉状环状肿瘤，患者发展为亚急性肠梗阻，随后进行内窥镜活检，并插入直径为10mm，长度为6cm的完全覆盖的自扩张成人金属胆道支架，导致梗阻立即缓解。活检显示腺癌伴神经内分泌分化。转移肿瘤沉积见于网膜,前腹壁和左腹膜壁。
■胃肠道恶性肿瘤的早期（第一个十年）表现保证了通过放射学扫描对任何可能的肿瘤进行早期筛查和MMR蛋白表达分析（肿瘤丢失加上正常的非肿瘤细胞）对于具有CALM和儿科肿瘤家族史的患者至关重要。
■一名5岁男孩出现呼吸道疾病，双侧颈淋巴结肿大，下背部有多个café-au-lait黄斑（CALM），并且有父母血缘关系的历史，在诊断后的6个月内，由于脑肿瘤导致三个姐妹死亡。计算机断层扫描胸部显示巨大的纵隔肿块。患者接受了肿块活检。该结果对于前T细胞急性淋巴母细胞淋巴瘤具有重要意义。基于上述因素的组合，人们对CMMRD产生了怀疑。将一组MMR蛋白应用于活检组织，显示在具有阳性外部对照的肿瘤细胞中MLH1和PMS2免疫染色的核表达丧失。在淋巴瘤的维持治疗中，大约一年后,由于在柔性乙状结肠镜检查中发现乙状结肠中部狭窄的息肉状环状肿瘤，患者发展为亚急性肠梗阻，随后进行内窥镜活检，并插入直径为10mm，长度为6cm的完全覆盖的自扩张成人金属胆道支架，导致梗阻立即缓解。活检显示腺癌伴神经内分泌分化。转移肿瘤沉积见于网膜,前腹壁和左腹膜壁。
■胃肠道恶性肿瘤的早期（第一个十年）表现保证了通过放射学扫描对任何可能的肿瘤进行早期筛查和MMR蛋白表达分析（肿瘤丢失加上正常的非肿瘤细胞）对于具有CALM和儿科肿瘤家族史的患者至关重要。
