Monoclonality of Composite Large-Cell Neuroendocrine Carcinoma and Invasive Intestinal-type Mucinous Adenocarcinoma of the Cervix

Abstract

A rare case of mixed carcinoma of the cervix is reported, composed of a large-cell neuroendocrine carcinoma and an invasive intestinal-type mucinous adenocarcinoma. The large-cell neuroendocrine carcinoma was composed of solid nests, sheets, and trabeculae of medium-sized to large-sized cells, and was positive for chromogranin-A and CD56. The invasive intestinal-type mucinous adenocarcinoma showed sparsely scattered immunoreactivity for chromogranin-A. Using an X-chromosome clonality assay, these 2 components showed patterns of monoclonality. These results suggest that the large-cell neuroendocrine carcinoma may have arisen from the invasive mucinous adenocarcinoma.

Neuroendocrine Tumors of the Female Reproductive Tract: A Literature Review

“…CD56 is known to be a less specific neuroendocrine marker compared to chromogranin and synaptophysin [ 11 , 20 , 55 ]. The common coexistence of NEC and epithelial tumors along with the monoclonality of the two components implies a common cellular origin of the neuroendocrine and epithelial components [ 17 , 72 ].…”

“…An X-chromosome clonality assay showed monoclonality of both components in a case of mixed LCNEC and mucinous carcinoma. This suggests that LCNEC might have arisen from an invasive mucinous adenocarcinoma [ 17 ].…”

“…In a case of mixed LCNEC and mucinous borderline ovarian tumor, clonality analysis using the human androgen receptor gene showed monoclonality in both components, suggesting that the LCNEC might have arisen from the mucinous epithelial tumor [ 71 ]. The common coexistence of NEC and epithelial tumors, along with the monoclonality of the two components, implies a common cellular origin of the neuroendocrine and epithelial components [ 17 , 72 ]. A case of LCNEC associated with serous carcinoma revealed a different pattern of microsatellite instability in both components.…”

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

“…17 There is evidence that NEC originates from neuroendocrine cells in the endometrium as a result of "divergent differentiation". 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.…”

Endometrial neuroendocrine carcinoma frequently associated with mismatch repair deficiency

“…It has been indicated that NEC originates from NE cells of the endometrium and may result from "divergent differentiation" [5]. Yasuoka et al [18] found that both cervical adenocarcinoma and NEC showed identical clonality by using an X-chromosome clonality assay. Such observation suggests that the NEC may arise from the adenocarcinoma through a "dedifferentiation process".…”