Histopathologic patterns in isthmocele pregnancies

Isthmoceles are defects related to Caesarean section (CS) scars, known to cause secondary infertility and interfere with in-vitro fertilization in women who have had Caesarean deliveries. The etiologies are multifactorial. Isthmoceles, similar to dehiscent CS scars, can be potential sites for ectopic pregnancies and abnormal placentation. There are a few case reports of pregnancies occurring within isthmoceles. However, there is a lack of studies focusing on the histopathologic details of gestations occurring within isthmoceles. Our main aim is to address this gap by illustrating the different histopathologic patterns of products of conception and gestational trophoblastic lesions involving isthmoceles. We also aim to determine the potential clinical relevance of gestational isthmoceles. We have conducted a retrospective review study of isthmocele specimens obtained from hysteroscopic isthmoplasty and hysterectomies. We found 14 (7.4 %) isthmocele ectopic pregnancies. The involved pouches were large, wide-based, predominantly low-level endocervical mucosa-lined isthmoceles. Six patients (43 %) presented with placental site nodule and plaque, four patients (28 %) with incomplete abortus material, two patients with atypical placental nodules, one patient with an exaggerated placental site, and one patient with epithelioid trophoblastic tumor. The features were highlighted by special stains and accentuated by appropriate immunohistochemistry. Some small and focal placental site nodule gestational trophoblastic lesions were found to have been missed, overlooked or misinterpreted by the original pathologists. The presence of zonation layers, typified by a hemosiderotic inflammatory stromal band, was found to be a useful clue in order to perform deeper levels to uncover small hidden residual trophoblastic foci. The larger atypical placental site nodule and epithelioid trophoblastic cell tumor lesions were initially confused with cervical squamous cell carcinoma, which was excluded by trophoblast-specific immunomarkers. Large, wide-based, low-level endocervical mucosa-lined isthmoceles are more prone to harboring ectopic pregnancies. A history of previous scar pregnancies was found to be a risk factor for developing subsequent isthmocele ectopic pregnancies. Gestational isthmocele is a common phenomenon that exhibits a variety of histopathologic changes. Pathologists should be aware of these changes in resected isthmocele specimens in order to properly guide gynecologists in patient management and avoid potential diagnostic pitfalls.