α-Fetoprotein-Producing Endometrial Carcinoma Is Associated With Fetal Gut-Like and/or Hepatoid Morphology, Lymphovascular Infiltration, TP53 Abnormalities, and Poor Prognosis: Five Cases and Literature Review

Abstract

The clinicopathological, immunohistochemical, and molecular characteristics of α-fetoprotein (AFP)-producing endometrial carcinoma (AFP+ EC) are poorly understood. From 284 cases of endometrial carcinoma in our pathology archive, we identified five cases (1.8%) of AFP+ EC with fetal gut–like (4/5) and/or hepatoid (2/5) morphology. All cases exhibited lymphovascular infiltration. In addition, 24 cases of endometrial carcinoma with elevated serum AFP levels were retrieved from the literature. The patient age ranged from 44 to 86 years (median: 63). Of 26 cases whose FIGO (International Federation of Gynecology and Obstetrics) stage and follow-up information was available (mean follow-up 24 months), 15 were stage I or II and 11 were stage III or IV. Even in stage I or II disease, death or relapse occurred in more than half of the patients (8/15). Detailed analysis of our five cases revealed that, on immunohistochemistry, AFP+ EC was positive for SALL4 (4/5), AFP (3/5), and HNF1β (4/5) in >50% of neoplastic cells and negative for estrogen and progesterone receptors (5/5), PAX8 (4/5), and napsin A (5/5). Four cases exhibited aberrant p53 immunohistochemistry and were confirmed to harbor TP53 mutations by direct sequencing. No mutation was found in POLE, CTNNB1, or KRAS. In conclusion, AFP+ EC merits recognition as a distinct subtype of endometrial carcinoma, which occurs in 1.8% of endometrial carcinoma cases, are associated with TP53 abnormalities, exhibit lymphovascular infiltration, and can show distant metastasis even when treated in early stage.

Yolk Sac Tumor Originating From Cervical Adenocarcinoma: A Case Predominated by Enteroblastic Differentiation

“…In theory, to classify these extragonadal tumors with enteroblastic differentiation but without typical yolk sac tumor morphology as a subtype of yolk sac tumor is acceptable, because the enteroblastic pattern can represent characteristic endodermal differentiation in the yolk sac tumor 2. Coexisted somatic carcinoma was very common in extragonadal yolk sac tumors 1,4, which was another reason for the controversy for the extragonadal cases. The somatic carcinoma component was often seen in the uterus or ovary tumors with yolk sac tumor component in women above 35 yr old, and most of these tumors proved somatically derived rather than germinal derived 16.…”

“…The extragonadal yolk sac tumors with typical morphology (microcystic/reticular architecture and Schiller-Duval bodies) indeed exist (12)(13)(14)(15). However, In the female reproductive system, the tumors having enteroblastic differentiation but lacking typical morphology of yolk sac tumor should be classified as "carcinomas" or "yolk sac tumors" is a question that is still being unpicked (4,9,16,17).…”

“…AEBD outside the digestive system was not well revealed, especially in the female reproductive system. It is controversial whether the tumor with enteroblastic differentiation in the female reproductive system should be classified as a yolk sac tumor or AEBD (1,4,9). Cervical adenocarcinomas can be categorized as human papillomavirus (HPV)-associated adenocarcinoma, HPVindependent adenocarcinoma, and their associated subtypes in the current WHO classification of the female genital system.…”

Yolk Sac Tumor in a Recurrence of Colonic Adenocarcinoma With Shared Mutations in APC and TP53 Genes: A Case Report

“…A small number of cases of carcinoma with a germ cell tumor component, such as choriocarcinoma and YST, have been reported in various organs, including, but not limited to, the stomach 6 , gallbladder 7 , ovary and endometrium [8][9][10] , and urinary bladder. 11 In the colon, although both are rare, choriocarcinoma 1 is more frequently reported than YST.…”

Ovarian Mucinous Carcinoma with a Yolk sac Tumor-Like Component: A Report of Three Cases with a Literature Review for Prognostic Analysis

“…17 Since conventional YSTs do not harbor TP53 mutation, 18 p53 IHC may be a helpful tool to differentiate somatically derived YST and conventional YST. 19 Previously, the frequency of YST-like differentiation in ovarian carcinomas had not been reported. In our institution, 9.5% (2/21) of the mucinous carcinomas resected between 2006 and 2020 were associated with a YST-like component.…”