Failed Methotrexate-Treated Ectopic Pregnancies: Clinicopathologic Correlations

Abstract

Methotrexate (MTX) administration as an alternative to surgical therapy for unruptured 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 extensively described. Review of pathology records from January 1991 through June 1996 revealed 12 MTX-treated tubal EPs that subsequently required surgical intervention. Clinical data and histologic findings were compared with those from tubal EPs from maternal-age-and gestational-age-matched controls. Semiquantitative observations of chorionic villous morphology were assessed by a senior pathologist unaware 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 injections of MTX (50 mg/M2) and were followed up with serial serum beta-human chorionic 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 patients 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 trophoblasts had enlarged nuclei with irregular contours, smudged chromatin, and prominent nucleoli. There were no significant differences between failed MTX-exposed EPs and controls in terms of the presence or degree of villous necrosis, trophoblastic 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 expanded to encompass the termination of early intrauterine pregnancies, the recognition of possible treatment-related alterations in the histologic appearance of chorionic villi, trophoblasts, and implantation sites will be pertinent to avoid misdiagnosis. Int J Surg Pathol 5(3/4): [83][84][85][86][87][88][89][90][91][92][93][94] 1997