記述言語：英語   掲載種別：研究論文（学術雑誌）  

Colorectal cancer (CRC) is a heterogeneous disease that develops through stepwise accumulation of genetic alterations and progresses via several distinct pathways. However, the tumorigenesis of CRCs with BRAF non-V600E mutations remains unclear. Here, we aimed to elucidate the tumorigenesis of CRCs with BRAF non-V600E mutations, focusing on differences in mucin phenotype and genetic alterations between CRCs with non-V600E and V600E mutations. We investigated 201 patients with CRC and performed panel testing of 415 genes to identify BRAF mutations. Patients were classified into five mucin phenotypes - large-intestinal, small-intestinal, gastric, mixed, and unclassified - using immunohistochemistry for CD10, MUC2, MUC5AC, and MUC6. BRAF mutations were identified in 24 of 201 patients' samples, of which 13 (6.5%) had a V600E mutation (V600E-mutant) and 11 (5.5%) had non-V600E mutations (non-V600E-mutant). MUC5AC expression was significantly associated with V600E mutations (P = 0.040), while CD10 expression was significantly associated with non-V600E mutations (P = 0.010). The small-intestinal mucin phenotype was significantly associated with non-V600E mutations (P = 0.031), while the mixed mucin phenotype was significantly associated with V600E mutations (P = 0.027). Regarding genetic alterations, focusing on the WNT signaling pathway, APC mutation was significantly associated with non-V600E mutations (P < 0.001), while RNF43 mutation was significantly associated with V600E mutations (P = 0.020). Considering the differences in mucin phenotype and genetic alterations, different modes of tumorigenesis are assumed for CRC with BRAF V600E mutation and non-V600E mutations. These findings are important in understanding the biology and treatment strategies for BRAF-mutant CRC.

DOI： 10.1016/j.humpath.2024.02.009

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Lynch syndrome-associated endometrial cancer patients often present multiple synchronous tumors and this assessment can affect treatment strategies. We present a case of a 27-year-old woman with tumors in the uterine corpus, cervix, and ovaries who was diagnosed with endometrial cancer and exhibited cervical invasion and ovarian metastasis. Her family history suggested Lynch syndrome, and genetic testing identified a variant of uncertain significance, MLH1 p.L582H. We conducted immunohistochemical staining, microsatellite instability analysis, and Sanger sequencing for Lynch syndrome-associated cancers in three generations of the family and identified consistent MLH1 loss. Whole-exome sequencing for the corpus, cervical, and ovarian tumors of the proband identified a copy-neutral loss of heterozygosity (LOH) occurring at the MLH1 position in all tumors. This indicated that the germline variant and the copy-neutral LOH led to biallelic loss of MLH1 and was the cause of cancer initiation. All tumors shared a portion of somatic mutations with high mutant allele frequencies, suggesting a common clonal origin. There were no mutations shared only between the cervix and ovary samples. The profiles of mutant allele frequencies shared between the corpus and cervix or ovary indicated that two different subclones originating from the corpus independently metastasized to the cervix or ovary. Additionally, all tumors presented unique mutations in endometrial cancer-associated genes such as ARID1A and PIK3CA. In conclusion, we demonstrated clonal origin and genomic diversity in a Lynch syndrome-associated endometrial cancer, suggesting the importance of evaluating multiple sites in Lynch syndrome patients with synchronous tumors.

DOI： 10.1002/gcc.23231

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Solid pseudopapillary neoplasm (SPN) is a rare pancreatic tumor that typically affects young women in the body and tail of the pancreas. SPN is often asymptomatic in the early stages, so it is initially discovered as a large tumor. In this report, we experienced a case of a relatively small SPN discovered in the setting of acute pancreatitis. Because there have been few reports of SPN being discovered in the situation like our case, we report this case based on a review of the literature.

DOI： 10.1007/s12328-023-01850-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Gastric cancer is a Lynch syndrome (LS)-associated tumor, with the cumulative lifetime risk in LS patients estimated to be 5.8-13%. Hence, surveillance for gastric cancer is important for LS patients, especially in those with a family history of gastric cancer or of Asian descent. We report a very rare case of a LS patient who showed gastric metastasis from jejunal adenocarcinoma curatively resected 8 years prior. A 79-year-old female was diagnosed with a synchronous gastric submucosal tumor (SMT) and right-sided colon cancer. She was referred to our hospital as she and her family had histories of LS-associated tumors. She underwent curative intent surgery for the tumors. Postoperative histopathological examination revealed the gastric SMT was an adenocarcinoma completely covered by non-neoplastic gastric mucosa. Immunohistochemical analyses showed the gastric SMT had the same expression pattern for CDX2, cytokeratins 7 and 20 as the jejunal adenocarcinoma. Thirty-four months after surgery the patient is alive without recurrence or any other LS-associated tumors. To the best of our knowledge, this is the first report of gastric metastasis from small bowel adenocarcinoma in a LS patient. Awareness of this case may be important for gastric cancer surveillance in LS patients.

DOI： 10.1007/s12328-022-01625-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND Primary aortic sarcoma often poses diagnostic challenges for pathologists and clinicians because of a very low incidence and controversy over nomenclature and definition. We report a case of aortic angiosarcoma in association with a graft. We also conducted a clinicopathological review of cases of primary aortic sarcomas associated with implanted grafts. CASE REPORT The patient was an 82-year-old woman. She underwent thoracic endovascular aneurysm repair (TEVAR) at age 78 because of an aneurysm in the descending aorta. Approximately 4 years after the TEVAR, computed tomography revealed a type II endoleak and expansion of the aneurysm. Her c-reactive protein level rose to 34 mg/dL, and Ga scintigraphy showed 67Ga accumulation at the aneurysm. She had fever up to 39°C, and a stent graft infection was suspected. Despite administration of antibiotics, her condition deteriorated, and she died. Postmortem examination identified epithelioid aortic angiosarcoma at the aorta with aneurysm repair and the graft, and the aortic angiosarcoma invaded the left lower lobe of the lung. CONCLUSIONS Our clinicopathological review revealed that the proper clinical diagnosis was very difficult owing to confusion of aortic sarcoma after the implantation with the infected graft, atypical endoleak, or pseudoaneurysm. The histological diagnosis was ambiguous because immunohistochemical and genetic studies were not adequately conducted. Overall prognosis of aortic sarcoma is poor as most patients die within a year, with no effective treatments. It is hoped that recent projects for genomic medicine will provide useful insights about the diagnosis and treatment of these cancers.

DOI： 10.12659/AJCR.931740

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本小児外科学会  

小児副腎皮質癌は稀な悪性腫瘍である.今回我々は急性腹症で発症し,男性化徴候を契機に診断に至った小児副腎皮質癌の1例を経験したので報告する.症例は7歳女児.発熱と右上腹部痛を主訴に近医を受診し,腹部造影CTで右後腹膜に最大径11cmの腫瘤を認め当科紹介入院となった.右上腹部に圧痛と右季肋下に弾性硬の腫瘤を触知し,思春期男性様の体臭,顔面のざ瘡,陰核肥大の男性化徴候を認めた.副腎皮質癌を疑い血液内分泌検査を実施したところ血中DHEA-S 24,680ng/mlと著明高値を認めた.右副腎腫瘍に対し右副腎腫瘍摘出術を施行し,病理診断で副腎皮質癌と診断された.術後はミトタンを含む化学療法を施行した.現在術後1年4ヵ月経過し再発なく経過観察中である.副腎皮質癌は機能性腫瘍であることが多い.男性化徴候のような特徴的な症候を呈する小児の後腹膜腫瘍では本症を念頭に診断,治療を行う必要がある.(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01113&link_issn=&doc_id=20230830120006&doc_link_id=%2Fes5shoge%2F2023%2F005905%2F015%2F0892-0898%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fes5shoge%2F2023%2F005905%2F015%2F0892-0898%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：日本脳腫瘍病理学会  

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記述言語：日本語   出版者・発行元：(一社)日本病理学会  

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記述言語：日本語   出版者・発行元：(株)Gakken  

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J00235&link_issn=&doc_id=20211228110003&doc_link_id=10.15105%2FGZ.0000002624&url=https%3A%2F%2Fdoi.org%2F10.15105%2FGZ.0000002624&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif