Harvard-MIT Division of Health Sciences and Technology HST.071: Human Reproductive Biology Course Director: Professor Henry Klapholz IN SUMMARY HST 071 TROPHOBLASTIC DISEASE TROPHOBLASTIC NEOPLASIA Types of trophoblast neoplasia • Molar (always gestational) o villi • Non-molar (can be non-gestational) o No villi • Molar gestations o Errors in fertilization or meiosis o Abnormal paternal contribution to the zygote • Two categories: o Complete hydatidiform mole o Partial hydatidiform mole Partial Hydatidiform Mole • Excess tissue: o Occasionally large villi are grossly identifiable but should be < 1cm in greatest dimension • Fetal development is possible with characteristic anomalies: o IUGR o 3-4 syndactyly -hands o 2-3 syndactyly -feet o Renal, cardiac, neural structural anomalies • Histology: o Two populations villi -large + cisterns, small o Irregular outlines of villi o Villous syncytiotrophoblastic inclusions o Excess and atypical villous synctyiotrophoblast o “molar” implantation site o Embryonic/fetal development •Characterized by focal villous hydrops •Focal trophoblastic hyperppasia •Two populations of villi –large and hydropic –background of small, sclerotic and normal-sized villi –scalloped villous outlines –tangential sectioning of the villi results in stromal trophoblastic inclusions –villous surfaces may have many tiny projections of syncytiotrophoblast forming notches •Focal trophoblast hyperplasia •Mounds of syncytiotrophoblast •Nuclear atypia infrequent •Villi vessels contain nucleated RBS and often fetal tissue found •Triploid •Extra haploid DNA is paternalIN SUMMARY HST 071 TROPHOBLASTIC DISEASE Complete hydatidiform mole •Villi grossly identifiable, often >1cm in greatest dimension •No fetal development •Excess tissue •Villous hydrops •Trophoblast hyperplasia •Cistern formation •Blood vessels lacking •Mounds of mitotic cytotrophoblast •Lacy proliferation of syncitiotrophoblast •Extravillous trophoblast •Cytologic atypia •Diploid •Nuclear DNA androgenically derived Molar gestations •Complete moles -choriocarcinoma, recurrence •Partial moles -rarely persist Imprinting •Molar gestations are evidence of difference between maternal and patnernal DNA •Molar pregnancies are due to a overabundance of paternal DNA •Paternal DNA preferentially makes extraembryonic •Maternal DNA preferentially makes embryonic tissues Choriocarcinoma • Malignancy of all trophoplast lineages • Gestational or non-gestational • Presents with bleeding, toxemia • Widely metastatic • Gestational is chemosensitive • Followed with bHCG and imaging • Histology of choriocarcinoma • Biphasic trophoblast • Hemorrhage and necrosis Choriocarcinoma in situ •Can present as mass-like lesions in the placenta •Can cross the placenta to metastasize to fetus •Silent at placental presentation or widely metastaticIN SUMMARY HST 071 TROPHOBLASTIC DISEASE Placental site trophoblastic tumor •Neoplasm of intermediate trophoblast •Locally invasive, rare metastases •Mild symptoms of persistent pregnancy •No good serum markers •Therapy is hysterectomy Histology of PSTT •Mono or binucleate trophoblast •Pushing border •Massachusetts FUNDAMENTAL QUESTIONS 1. Define gestational trophoblastic disease. 2. Describe the histology of a complete mole. A partial mole. 3. What is the karyotypes of a complete mole ? A partial mole? 4. What is the malignant potential of the partial mole? The complete mole? 5. How does one follow a patient who has had a molar pregnancy? 6. What is the treatment for persistent trophoblastic disease?IN SUMMARY HST 071 TROPHOBLASTIC