Seya Tomoko, Tanaka Noritake, Shinji Seiichi, Yokoi Kimiyoshi, Oguro Tatsuo, Oaki Yoshiharu, Ishiwata Toshiyuki, Naito Zenya, Tajiri Takashi
Surgery for Organ Function and Biological Regulation, Graduate School of Medicine, Nippon Medical School, and Department of Surgery, Nippon Medical School Chiba Hokusoh Hospital, Japan.
J Nippon Med Sch. 2007 Aug;74(4):319-24. doi: 10.1272/jnms.74.319.
Here, we report on a patient with squamous cell carcinoma (SCC) arising from recurrent anal fistula. The patient was a 57-year-old woman who had 32-year history of having a recurrent perianal abscesses that ruptured spontaneously. Six months before her admission to our hospital, anal pain developed. She had no history of inflammatory bowel disease. Physical examination revealed three external fistulous openings at the two o'clock position, 2 cm from the anal verge. One internal opening in the lower rectum was found with proctoscopy. The patient underwent fistulectomy. Microscopic examination showed SCC arising from the anal fistula, which was accompanied by vessel invasion. The tumor was observed to be continuous from the external opening but was not exposed to the internal opening of the rectal mucosa. Because human papillomavirus (HPV) infection was suspected, immunohistochemical analysis was performed, but showed no HPV infection. Two weeks after fistulectomy, abdominoperineal resection with lymph node dissection was performed. Histopathological examination revealed no remnant cancer tissue or lymph node metastasis. She was discharged after surgery without complications. Eight years after the operation, she complained of constant pain during micturition. Urological examination revealed urinary bladder cancer, and transurethral resection of the bladder tumor was performed. Histopathological examination revealed transitional cell carcinoma of the urinary bladder. Two years later, the patient died of metastatic urinary bladder cancer, without recurrence of the fistula cancer. Because the patients mother had died of urinary bladder cancer and she herself had metachronous urinary bladder cancer in addition to fistula cancer, we investigated whether microsatellite instability (MSI) and chromosomal instability correlated with fistula cancer development. Immunohistochemical analysis of formalin-fixed, paraffin-embedded surgical tumor specimens for p53, MLH1, and MSH2 was performed. The tumor specimens showed no MLH1 expression but did show normal MSH2 expression. p53 was not expressed. Five microsatellite loci were examined using the tumor specimens to detect MSI, namely two loci with mononucleotide runs (i.e., BAT25 and BAT26) and three loci with dinucleotide repeats (i.e., APC, Mfd15, and D2S123). The tumor specimens showed alternations in the repeated sequences of two loci (i.e., BAT26 and D2S123). As a result, the tumor was classified as MSI-H (high) according to the Bethesda criteria. Our patient had MSI and one of the smallest reported SCCs arising from recurrent anal fistulae.
在此，我们报告一例源于复发性肛瘘的鳞状细胞癌（SCC）患者。该患者为一名57岁女性，有32年复发性肛周脓肿病史，脓肿会自行破溃。入院前6个月，患者出现肛门疼痛。她无炎症性肠病病史。体格检查发现，在距肛门边缘2 cm的两点位置有3个外瘘口。直肠镜检查发现直肠下段有1个内瘘口。患者接受了肛瘘切除术。显微镜检查显示SCC源于肛瘘，伴有血管侵犯。肿瘤从外口连续延伸，但未累及直肠黏膜内口。由于怀疑有人乳头瘤病毒（HPV）感染，进行了免疫组化分析，但结果显示无HPV感染。肛瘘切除术后2周，患者接受了腹会阴联合切除术及淋巴结清扫术。组织病理学检查显示无残留癌组织及淋巴结转移。术后患者无并发症出院。术后8年，患者主诉排尿时持续疼痛。泌尿外科检查发现膀胱癌，遂行膀胱肿瘤经尿道切除术。组织病理学检查显示为膀胱移行细胞癌。两年后，患者死于转移性膀胱癌，肛瘘癌未复发。由于患者的母亲死于膀胱癌，且她除了肛瘘癌外还患了异时性膀胱癌，我们研究了微卫星不稳定性（MSI）和染色体不稳定性与肛瘘癌发生是否相关。对福尔马林固定、石蜡包埋的手术肿瘤标本进行了p53、MLH1和MSH2的免疫组化分析。肿瘤标本未显示MLH1表达，但MSH2表达正常。p53未表达。使用肿瘤标本检测5个微卫星位点以检测MSI，即2个单核苷酸重复序列位点（即BAT25和BAT26）和3个二核苷酸重复序列位点（即APC、Mfd15和D2S123）。肿瘤标本显示2个位点（即BAT26和D2S123）的重复序列发生改变。结果，根据贝塞斯达标准，该肿瘤被分类为MSI-H（高度）。我们的患者患有MSI，且是报道中源于复发性肛瘘的最小SCC之一。
