Failed Methotrexate-Treated Ectopic Pregnancies: Clinicopathologic Correlations

Abstract

Methotrexate (MTX) administration as an alternative to surgical therapy for unrupured ectopic pregnancies (EPs) has a 5-11% failure rate. The histologic findings in surgical specimens from patients for whom MTX therapy failed have not been exensively described. Review of pathology records from January 1991 through June 1996 revealed 12 MTX-treated tubal EPs that subsequently required surgical interention. Clinical data and histologic findings were compared with those from tubal EPs from maternalagend gestational-age-matched controls. Semiquantitative obervations of chorionic villous morphology were assessed by a senior pathologist unware of the treatment regimens. The average maternal age was 27 years and the mean gestational age was 9 weeks. Patients received one to two intramuscular injecions of MTX (50 mg/M2) and were followed up with serial serum betahuman chorinic gonadotropin (f-hCG) determinations. P-hCG levels fell from presentation to surgical intervention in 36.4% of MTX-treated patients, increased in 9.1%, and rose then fell in 54.5%. Peak r-hCG titers were significantly higher in MTX-exposed paients as compared with controls. There was no correlation between,3-hCG profile and villous morphology. Sixty-seven percent of MTX-treated EPs showed significant trophoblastic atypia as compared with 25% of control cases. Atypical villous trohoblasts had enlarged nuclei with irregular contours, smudged chromatin, and prominent nucleoli. There were no significant differences between failed MTX-exosed EPs and controls in terms of the presence or degree of villous necrosis, trohoblastic vacuolization, or embryonic development. Chorionic villous morphology in failed MTX-treated EPs showed no significant differences from that of nontreated EPs except for a trend toward increased trophoblastic atypia, features that may be confused with early gestational trophoblastic disease. Failed MTX-treated EPs may represent a subset of gestations that are resistant to MTX. As the uses of MTX are exanded to encompass the termination of early intrauterine pregnancies, the recogniion of possible treatmentrelated alterations in the histologic appearance of chorinic villi, trophoblasts, and implantation sites will be pertinent to avoid misdiagnosis.