Department of Surgery, Marunouchi Hospital, 1-7-45, Nagisa Matsumoto, Nagano, 390-0841, Japan.
Department of Radiology, Marunouchi Hospital, 1-7-45, Nagisa Matsumoto, Nagano, 390-0841, Japan.
World J Surg Oncol. 2023 Jun 7;21(1):172. doi: 10.1186/s12957-023-03053-2.
Alteration of chemosensitivity or tumor aggressiveness in response to chemotherapy has been reported, and liquid biopsy assessment during chemotherapy for colorectal cancers has confirmed the acquisition of mutations in various oncogenes. However, the occurrence of histological transformation seems to be extremely rare in colorectal cancers, and the few existing case reports of this transformation are from lung cancer and breast cancer. In this report, we describe the histological transformation of clinically aggressive scirrhous-type poorly differentiated adenocarcinoma of the ascending colon to signet-ring cell carcinoma in almost all recurrent tumors that were confirmed by autopsy after response to chemotherapy plus cetuximab.
A 59-year-old woman visited our hospital with whole abdominal pain and body weight loss and was diagnosed with scirrhous-type poorly differentiated adenocarcinoma of the ascending colon with aggressive lymph node metastases. The intrinsic chemosensitivity of the tumors was evident upon initiation of mFOLFOX6 plus cetuximab therapy, and right hemicolectomy was performed, and the tumor obviously remained in the peripancreatic area, paraaortic region, or other retroperitoneal areas. The ascending colon tumors mainly consisted of poorly differentiated adenocarcinoma and were not associated with signet-ring cell components except for minute clusters in a few lymphatic emboli in the main tumor. Chemotherapy was continued, and metastases were eliminated at 8 months after the operation; this response was maintained for an additional 4 months. Discontinuation of chemotherapy plus cetuximab resulted in immediate tumor recurrence and rapid expansion, and the patient died of the recurrent tumor 1 year and 2 months after the operation. Autopsy specimens revealed that almost all of the recurrent tumors exhibited transformation and consisted of signet-ring cell histology.
This case might suggest that various oncogene mutations or epigenetic changes resulting from chemotherapy, especially regimens that include cetuximab, contribute to the transformation of non-signet-ring cell colorectal carcinoma to signet-ring cell carcinoma histology and can promote the aggressive clinical progression characteristic of signet-ring cell carcinoma.
已有报道称,化疗会导致化学敏感性或肿瘤侵袭性改变,并且结直肠癌化疗期间的液体活检评估已证实各种癌基因发生突变。然而,结直肠癌的组织学转化似乎极为罕见,并且现有少数此类转化的病例报告来自肺癌和乳腺癌。在此报告中,我们描述了一例升结肠癌侵袭性硬纤维瘤型低分化腺癌在接受化疗加西妥昔单抗治疗后几乎所有复发性肿瘤均发生组织学转化为印戒细胞癌的病例。
一名 59 岁女性因全腹痛和体重减轻就诊,诊断为升结肠癌硬纤维瘤型低分化腺癌伴侵袭性淋巴结转移。开始接受 mFOLFOX6 加西妥昔单抗治疗后,肿瘤的内在化疗敏感性明显,行右半结肠切除术,肿瘤明显残留于胰周、主动脉旁或其他腹膜后区域。升结肠癌肿瘤主要由低分化腺癌组成,除少数主瘤中的淋巴血管内有微小簇外,无印戒细胞成分。继续化疗,术后 8 个月转移灶消除,该缓解状态又维持了 4 个月。停止化疗加西妥昔单抗后,肿瘤立即复发并迅速进展,患者在术后 1 年零 2 个月因复发性肿瘤死亡。尸检标本显示,几乎所有复发性肿瘤均发生转化,组织学表现为印戒细胞癌。
该病例可能提示,化疗尤其是包含西妥昔单抗的方案引起的各种癌基因突变或表观遗传改变,导致非印戒细胞结直肠癌向印戒细胞癌组织学转化,并促进了印戒细胞癌特征性的侵袭性临床进展。