Combined large cell neuroendocrine carcinoma and endometrioid carcinoma of the endometrium: a shared gene mutation signature between the two histological components

Abstract

A 61-year-old Japanese woman was diagnosed with FIGO Stage IB endometrioid cancer (EC) combined with large cell neuroendocrine carcinoma (LCNEC). Metastasis to the lymph nodes in the right bronchopulmonary area, mediastinum and brain were also identified. The patient eventually developed pleuritis and pericarditis carcinomatosa, and died of cancer at 51 months after surgery. Because gene aberrations in uterine neuroendocrine carcinoma are still not well understood, we examined alterations in the mutational hotspots of 50 selected cancerassociated genes. The EC and LCNEC components shared identical alterations in PTEN, PIK3CA and FGFR3. Both the EC and LCNEC components had heterozygous SBSs on CTNNB1 but at different codons (G34R in EC, and T41A in LCNEC). The altered gene signature raised a possibility that the EC and LCNEC components were derived from a common precursor lesion. The LCNEC independently obtained a significant CTNNB1 mutation and the lymph node metastasis originated from this component. Because the LCNEC component seemed to bring about the aggressive course of the disease and defined the patient outcome, further investigations are needed to elucidate the mechanism of NE carcinoma development in the endometrium.

<p>Dedifferentiated Endometrioid Carcinomas with Neuroendocrine Differentiation: A Clinicopathological and Immunohistochemical Study of Three Cases</p>

“…9 Yasuoka et al 20 found identical clonality between cervical adenocarcinoma and NEC in an X-chromosome clonality assay. Ariura et al 19 also reported identical alterations in PTEN, PIK3CA and FGFR3 in the endocrine and LCNEC components of NEC. Howitt et al 18 reported that 50% of endometrial NECs were ultramutated or hypermutated, which is more representative of other histologic types of endometrial carcinoma than canonical small cell carcinoma of the lung.…”

“…4 These neoplasms are either "pure" LCNEC or mixed with other histologic components. [5][6][7][9][10][11][12][13][14][15][16][17][18][19] Among other histologic components of endometrial LCNEC, endometrioid carcinoma is the most common histologic type, followed by serous carcinoma. Based on prior reports and our case studies, the most common clinical symptoms are postmenopausal or perimenopausal vaginal bleeding and/or abnormal vaginal discharge.…”

Pure large cell neuroendocrine carcinoma originating from the endometrium: A case report

“…The genetic profile of endometrial LCNEC is unknown. However, endometrioid carcinoma and endometrial LCNEC share a gene mutation signature with identical alterations in phosphatase and tensin homolog, PIK3CA, and fibroblast growth factor receptor 3, suggesting a common origin[ 18 ].…”

Mixed Small Cell and Large Cell Neuroendocrine Carcinoma of the Endometrium" A Case Report and Literature Review

“…Paraneoplastic syndromes such as Cushing syndrome presenting as fatigue or visual impairment have also been reported. [4][5][6][7][9][10][11][12][13][14]…”

“…High mitotic activity and extensive geographic necrosis are also appreciated. [4][5][6][7][9][10][11][12][13][14] To establish the diagnosis of NEC, a neuroendocrine growth pattern should be present in at least part of the tumor, together with expression of one or more neuroendocrine markers (Chromogranin, Synaptophysin…”