Choriocarcinoma in Women

Abstract

Choriocarcinoma is an uncommon malignant neoplasm, which can be either gestational or nongestational in origin. Distinction of these subtypes has prognostic and therapeutic implications. Twenty-two tumors were genotyped using polymerase chain reaction amplification of 15 short tandem repeat loci and the amelogenin locus (XY determination). DNA patterns from tumor and maternal tissue, as well as villous tissue from any available prior or concurrent gestation, were compared, to determine gestational versus nongestational nature (containing vs. lacking a paternal chromosome complement, respectively) and the relationship between the tumor and any prior or concurrent gestation. Nineteen tumors were gestational. Of these, 14 were purely androgenetic/homozygous XX: 6 uterine tumors with a concurrent or prior genetically related complete hydatidiform mole (CHM), 4 uterine tumors without an accompanying villous component, 1 uterine cornual tumor separate from a genetically distinct second trimester intrauterine placenta, 1 ectopic ovarian tumor separate from a genetically distinct third trimester intrauterine placenta, and 2 ectopic fallopian tube tumors. Five gestational tumors were biparental: 3 (2 XX, 1 XY) intraplacental choriocarcinomas genetically related to the placenta and 2 uterine tumors without accompanying placental tissue after term deliveries (1 XX 4 weeks postpartum and 1 XYY with allelic imbalances 1 year postpartum; prior placentas not available for analysis). Three tumors were nongestational: all XX with allelic imbalances; 2 ovarian, 1 pelvic. Gestational choriocarcinoma can be androgenetic or biparental. Most are androgenetic/homozygous XX, often associated with a genetically related concurrent or prior CHM, and thus of molar-associated type. These findings support that homozygous XX CHMs are associated with some risk of significant gestational trophoblastic disease. Intraplacental choriocarcinomas are biparental and genetically related to the placenta. Biparental choriocarcinoma detected in a postpartum uterine sample is consistent with undetected intraplacental choriocarcinoma. Eutopic or ectopic androgenetic choriocarcinoma separate from a concurrent intrauterine placenta is not derived from intraplacental tumor and is consistent with either a form of dispermic twin gestation (molar-type choriocarcinoma and coexistent nonmolar fetus) or origin from an antecedent molar pregnancy. While fallopian tube tumors are usually gestational, tumors in other sites (ovary, pelvis) can be nongestational and should not be assumed to be metastatic from a regressed or occult intrauterine or intraplacental gestational tumor.

Is chemotherapy always necessary for patients with nonmetastatic gestational trophoblastic neoplasia with histopathological diagnosis of choriocarcinoma?

“…With expectant management, we were able to avoid chemotherapy exposure to over half of our patients without the development of more advanced disease, greater need of multi-agent chemotherapy or in any case of death or relapse. While withholding immediate chemotherapy from women with a histologic diagnosis of choriocarcinoma may contravene current FIGO guidelines [9], our observation of the safety of this approach is similar to other reports [12][13][14][15][16][17][18][19][20]. Pathological diagnosis of GCC in specimens from uterine evacuations following molar pregnancies or abortions, salpingectomies in suspected ectopic pregnancies, or even placentas of preterm or term deliveries are not promptly available for Brazilian patients and physicians in the public health systemtaking generally 6-7 weeks for the final pathological results.…”

“…The choice to treat these patients could be viewed as an over-treatment, since they do not show signs of active disease. Several small reports describing expectant management of patients with close clinical and hCG surveillance suggest that women with surgically evacuated choriocarcinoma may enter remission without receiving chemotherapy [12][13][14][15][16][17][18][19][20].…”

Heterotopic atypical trophoblasts mimicking ectopic choriocarcinoma coexistent with a viable intrauterine pregnancy: A diagnostic dilemma

“…Microsatellite analysis demonstrated a DNA pattern most consistent with a biparental conception. This argued against the presence of gestational choriocarcinoma, as gestational choriocarcinoma is purely androgenic (genetically paternal), except in the rare case of intraplacental choriocarcinoma (Savage et al, 2017). Intraplacental choriocarcinoma was considered highly unlikely given the early gestational age at time of presentation.…”

Transmission of a TP53 germline mutation from unaffected male carrier associated with pediatric glioblastoma in his child and gestational choriocarcinoma in his female partner

“…These tumors are often associated with an antecedent molar pregnancy but can arise after a spontaneous abortion, ectopic pregnancy, or normal pregnancy, as is suspected in this case. Genotyping of choriocarcinomas from term pregnancies frequently reveals biparental genetic contribution, suggesting these tumors are genetically related to the antecedent pregnancy ( Savage et al 2017 ). In this case, the complex copy-number profile of the choriocarcinoma tissue precluded our ability to definitively interpret the parental contribution to the tumor.…”