In the endometrial neoplasia, the presence of mucinous epithelium is rare and should be paid attention. Extrauterine tumor involvement or cervix mucinous neoplasm extension should be firstly excluded[1–2]. In our study, the endometrial mucinous lesion was present in the form of poly-like growth pattern, grossly resembling primary endometrial poly. Histologic morphology exhibited complex papillary architecture and crowded glands characterized cytologically by abundant pale eosinophilic and clear cytoplasm with nuclear atypia. Although the cytologic and significant architecture features was treated as low-grade endometrioid adenocarcinoma except absence of invasive biological behavior, diffusely positivity for MUC6 and negativity for ER,PAX8 demonstrated gastric-type differentiation, suggesting possibly primary endometrial gastric lesion. In addition, the coexistent of native endometrial epithelium and mucinous cells in individual gland can be found, resembling mucinous metaplasia. These findings also give the impression of primary endometrial neoplasm. primary endometrial gastric(gastrointestinal-type) lesion is regarded as a distinct entity in a series study by Wong et al[1] they believed that benign and atypical gastric/gastrointestinal-type mucinous lesions may progress to related gastric-type adenocarcinoma, resembling the spectrum of cervix gastric-type mucinous lesions counterpart[3]. No mucinous glands was present in the myometrium in our case. On the account of the diagnostic criteria proposed by Wong et al about endometrial gastric(gastrointestinal)-type mucinous lesion, we made the diagnosis of atypical mucinous proliferation of gastric-type of the endometrium. Interestingly, in Wong et al study, these atypical endometrial mucinous lesions are closely associated with poly like our case[1]. The presentation of endometrial mucious lesion in this case strongly supported its primary because of absence of cervical and vagina involvement.
Given the presence of invasive adenocarcinoma in the appendix, appendiceal tumor extension to the uterus should be taken consider. Gastriointestinal adenocarcinoma origin mostly refer to appendiceal mucinous neoplasm in the previous literatures. We reviewed literatures about the endometrium involvement associated with appendiceal mucinous neoplasm. It is not difficult to find that the morphology of secondary endometrial mucinous was similar to that of primary appendiceal neoplasm. And the immunohistochemistry phenotype of the primary and secondary lesion was consistent, displaying the expression of intestinal type marker (CDX2,CK20) rather than primary endometrium neoplasia inmunophenotype[4–8]. Appendiceal mucinous neoplasm involving the endometrium exhibiting gastric-type differentiation is not reported in previous literatures. In present case, microscopic examination revealed focal invasion adenocarcinoma of the appendix with the characteristics of pyloric glands with pale eosinophilic cytoplasm, moderate to severe nuclear atypia. Focal immnoreactivity for MUC6 can be seen. We speculated that The Phenomenon is abnormal differentiation of tumor leading to morphological heterogeneity. This Interpretation may further suggest endometrial mucious lesion arising from appendix adenocarcinoma.
Tumors extension to the female genital tract, the ovary is commonly metastasis site. Regarding the growth pattern of appendix mucinous tumors involving the ovary, a spectrum of benign metaplastic to maligant mucinous lesions can be observed[9]. This ability of colonization native epithelium may lead to neoplasm extension[4, 5, 7, 8]. In our study, the spectrum of benign gastric-type metaplasia to atypical proliferation(boderline) in the uterus poly is observed, suggesting benign endometrial mucinous metaplasia of extrauterus tumor involvement have the equal potential of progression to borderline or even malignant, mimicking primary endometrial cancer. Atypical mucinous proliferation of gastric-type of the endometrium is proposed as the precursor lesion of primary endometrial gastric-type adenocarcinoma like cervical LEGH counterpart[3, 10]. In addition, because of the presence of ovarian mucious borderline tumor and fallopian tube mucious metaplasia in this case, synchronous and multifocal gastric mucinous metaplasia and neoplasm of the female genital tract(SMMN-FGT) can not be excluded, some studies have been described[11]. But accompanying with independently appendix neoplasm is extremely rare.
In conclusion, according to currently research, gastric-type mucinous lesions can independently or multiply occur in various sites of the female reproductive tract. The morphology of the lesions may demonstrate benign mucinnous metaplasia, atypical hyperplasia, invasive adenocarcinoma[1, 3, 12]. In regard to invasive adenocarcinoma of the appendix presenting with morphologically heterogenous with gastric-type differentiation and the morphology and immunophenotype of the endometrium associated with appendix neoplasm in this case, appendiceal adenocarcinoma involving the endometrium resembling primary endometrial gastric-type neoplasia lesion seem to be established. Therefore, one of the diagnosis criterias for gastric-type adenocarcinoma is the absence of other primary site [1, 3, 13]. Gastric-type mucinous carcinoma(GAS) in the endocervical and endometrium have revealed poor prognosis[14]. Park et al detected 21 GAS cases by next-generation sequencing, they described frequently gene mutations in GAS. Some gene features such as KMT2D, ERBB3, RNF43 mutations associated with poor prognosis in Gastriointestinal adenocarcinoma are also present in GAS[15]. Whether the appearanece of morphological heterogeneity with gastric-type differentiation in appendix adenocarcinoma show worse prognosis, the data is limited to evaluated. More cases for further studying can help to understand the biological and the molecular mechanisms of gastric-type differentiation mucinous tumor occurring in extra-stomach.