TY - JOUR
T1 - Case Report
T2 - A Rare Case of Esophagogastric Junctional Squamous Cell Carcinoma After the Successful Treatment of Neuroendocrine Carcinoma: Clonal Tumor Evolution Revealed by Genetic Analysis
AU - Sato, Hiroki
AU - Saito, Takeshi
AU - Horii, Hiroshi
AU - Kajiura, Mami
AU - Kikuchi, Noriaki
AU - Takada, Nobuhisa
AU - Taguchi, Koichi
AU - Yoshida, Mika
AU - Hasegawa, Masakazu
AU - Taguchi, Hiroyuki
AU - Yoshida, Yukinori
AU - Ando, Katsuyoshi
AU - Fujiya, Mikihiro
AU - Omori, Yuko
AU - Hank, Thomas
AU - Liss, Andrew S.
AU - Gala, Manish K.
AU - Makita, Yoshio
AU - Ono, Yusuke
AU - Mizukami, Yusuke
AU - Okumura, Toshikatsu
N1 - Funding Information:
We thank Mayumi Suzuki, and Yuko Hayakawa (Sapporo Higashi Tokushukai Hospital) for the technical support regarding genetic analyses. We thank the members of the Department of Medicine at Asahikawa Medical University for carefully reading and examining the manuscript. We also would like to thank Editage (www.editage.com) for English language editing.
Funding Information:
This work was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (grant number 17K09472 to YMi, 19K17480 to HS) and by the Suhara Memorial Foundation (to YMi). The role of the funding body was to provide a budget for genetic analysis.
Publisher Copyright:
© Copyright © 2021 Sato, Saito, Horii, Kajiura, Kikuchi, Takada, Taguchi, Yoshida, Hasegawa, Taguchi, Yoshida, Ando, Fujiya, Omori, Hank, Liss, Gala, Makita, Ono, Mizukami and Okumura.
PY - 2021/9/15
Y1 - 2021/9/15
N2 - Neuroendocrine carcinoma (NEC) of the esophagogastric junction (EGJ) is a rare disease with no established treatments. Herein, we describe a case of recurrent squamous cell carcinoma (SCC) after achieving complete response to chemotherapy against NEC of the EGJ. A 67-year-old man was referred to our hospital because of epigastric discomfort. Computed tomography imaging and esophagogastroduodenoscopy revealed ulcerated tumors at the EGJ. Endoscopic biopsy revealed small tumor cells with a high nuclear/cytoplasmic ratio, suggesting small-cell NEC. Immunohistochemistry (IHC) analysis showed tumor cells with an MIB-1 index of 80%. The patient achieved complete response after 10 cycles of chemotherapy. Follow-up endoscopic examination revealed small red-colored mucosal lesions in the center of the cicatrized primary lesion. Re-biopsy detected cancer cells harboring large eosinophilic cytoplasm with keratinization and no evidence of NEC components. IHC of the cells were cytokeratin 5/6-positive and p53-negative. The tumor persisted without evidence of metastases after chemoradiotherapy, and total gastrectomy with lymph node dissection was performed. Pathological assessment of the resected specimens revealed SCC, without evidence of NEC. The patient survived without a recurrence for >3 years after the initial presentation. Somatic mutation profiles of the primary NEC and recurrent SCC were analyzed by targeted amplicon sequencing covering common cancer-related mutations. Both tumors possessed TP53 Q192X mutation, whereas SMAD4 S517T was found only in SCC, suggesting that both tumor components originated from a founder clone with a stop-gain mutation in TP53. The somatic mutation profile of the tumors indicated that that loss of heterozygosity (LOH) at the TP53 gene might have occurred during the differentiation of the founder clone into NEC, while a SMAD4 mutation might have contributed to SCC development, indicating branching and subclonal evolution from common founder clone to both NEC and SCC. The mutation assessments provided valuable information to better understand the clonal evolution of metachronous cancers.
AB - Neuroendocrine carcinoma (NEC) of the esophagogastric junction (EGJ) is a rare disease with no established treatments. Herein, we describe a case of recurrent squamous cell carcinoma (SCC) after achieving complete response to chemotherapy against NEC of the EGJ. A 67-year-old man was referred to our hospital because of epigastric discomfort. Computed tomography imaging and esophagogastroduodenoscopy revealed ulcerated tumors at the EGJ. Endoscopic biopsy revealed small tumor cells with a high nuclear/cytoplasmic ratio, suggesting small-cell NEC. Immunohistochemistry (IHC) analysis showed tumor cells with an MIB-1 index of 80%. The patient achieved complete response after 10 cycles of chemotherapy. Follow-up endoscopic examination revealed small red-colored mucosal lesions in the center of the cicatrized primary lesion. Re-biopsy detected cancer cells harboring large eosinophilic cytoplasm with keratinization and no evidence of NEC components. IHC of the cells were cytokeratin 5/6-positive and p53-negative. The tumor persisted without evidence of metastases after chemoradiotherapy, and total gastrectomy with lymph node dissection was performed. Pathological assessment of the resected specimens revealed SCC, without evidence of NEC. The patient survived without a recurrence for >3 years after the initial presentation. Somatic mutation profiles of the primary NEC and recurrent SCC were analyzed by targeted amplicon sequencing covering common cancer-related mutations. Both tumors possessed TP53 Q192X mutation, whereas SMAD4 S517T was found only in SCC, suggesting that both tumor components originated from a founder clone with a stop-gain mutation in TP53. The somatic mutation profile of the tumors indicated that that loss of heterozygosity (LOH) at the TP53 gene might have occurred during the differentiation of the founder clone into NEC, while a SMAD4 mutation might have contributed to SCC development, indicating branching and subclonal evolution from common founder clone to both NEC and SCC. The mutation assessments provided valuable information to better understand the clonal evolution of metachronous cancers.
KW - clinicopathological correlation
KW - esophagogastric junction
KW - genetic pathology
KW - multidisciplinary therapy
KW - neuroendocrine carcinoma
KW - sequential chemotherapy
KW - squamous cell carcinoma
KW - tumor genotyping
UR - http://www.scopus.com/inward/record.url?scp=85116490488&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85116490488&partnerID=8YFLogxK
U2 - 10.3389/fgene.2021.608324
DO - 10.3389/fgene.2021.608324
M3 - Article
AN - SCOPUS:85116490488
VL - 12
JO - Frontiers in Genetics
JF - Frontiers in Genetics
SN - 1664-8021
M1 - 608324
ER -