Crobach Stijn, Jansen Anne M L, Ligtenberg Marjolein J L, Koopmans Marije, Nielsen Maartje, Hes Frederik J, Wijnen Juul T, Dinjens Winand N M, van Wezel Tom, Morreau Hans
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Pathology, Leiden University Medical Centre, Zone L1-Q, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
Fam Cancer. 2018 Jul;17(3):415-420. doi: 10.1007/s10689-017-0055-1.
Patients synchronously or metachronously presenting with ovarian and colon cancer can pose diagnostic challenges. A primary colon carcinoma can metastasize to one or both ovaries, two independent primary tumors can arise or an ovarian carcinoma can metastasize to the colon. Clinical and immunohistochemical characterization can aid the diagnosis. Recently, we reported that in difficult cases finding pathogenic APC variants supports a colonic origin.In this case report we describe the clinical history of a female patient suspected for Lynch syndrome. She was diagnosed with a bilateral ovarian cancer at age 44, followed by the detection of a colon carcinoma 12.5 months later. Lesions of both sites showed a DNA mismatch repair deficiency with immunohistochemical loss of MLH1 and PMS2 expression without MLH1 promoter hypermethylation. In absence of germline MMR gene variants identical somatic MLH1 and CTNNB1 gene variants were found, indicating a clonal relation. MMR germline mosaicism was made unlikely by ultra deep sequencing of the MLH1 variant in DNA isolated from normal mucosa, blood, urine and saliva. Although initially being suspect for Lynch syndrome it was eventually concluded that a metachronously diagnosed colon carcinoma that metastasized to both ovaries was most likely.
同时或异时出现卵巢癌和结肠癌的患者可能带来诊断挑战。原发性结肠癌可转移至一侧或双侧卵巢，可出现两个独立的原发性肿瘤，或者卵巢癌可转移至结肠。临床和免疫组化特征有助于诊断。最近，我们报告在疑难病例中发现致病性APC变异支持结肠起源。在本病例报告中，我们描述了一名疑似林奇综合征女性患者的临床病史。她44岁时被诊断为双侧卵巢癌，12.5个月后检测出结肠癌。两个部位的病变均显示DNA错配修复缺陷，免疫组化显示MLH1和PMS2表达缺失，且无MLH1启动子高甲基化。在没有种系MMR基因变异的情况下，发现了相同的体细胞MLH1和CTNNB1基因变异，表明存在克隆关系。通过对从正常黏膜、血液、尿液和唾液中分离的DNA中的MLH1变异进行超深度测序，排除了MMR种系嵌合体的可能性。尽管最初怀疑是林奇综合征，但最终得出结论，最有可能的情况是异时诊断的结肠癌转移至双侧卵巢。
