Unusual pathologic form of malignant gestational trophoblastic neoplasms with low serum β-hCG levels

Objective: To investigate clinicopathological characteristics of unusual gestational trophoblastic neoplasms (GTNs) that are difficult to be clearly classified. Methods: We retrospectively reviewed 455 GTNs treated and found three unusual cases. We investigated the morphology and immunostains of all three cases. Results: The three patients aged 25-42 years, the interval from the last gestation was 21, 240, and 12 months, respectively. The patients presented vaginal irregular bleeding or amenorrhea. Their pretreatment serum β-hCG levels were 337-3,039 mIU/ml. All patients were found to have uterine neoplasms and bilateral multiple lung nodules simultaneously. All received chemotherapy, and then underwent hysterectomy. Microscopically, the tumours in all cases were monophasic differentiation with prominent atypia and abundant mitoses, and without massive hemorrhagic necrosis. Immunohistochemically, HLA-G and Mel-CAM were focally or diffusely positive, but β-hCG was marked positive in all cases widely scattered cells; hPL was scantly positive in case 1 and 3, but negative in case 2; p63 was focally positive in case 2 and scantly in case 1, but negative in case 3. Two of the patients died of multiple organs metastasis, and the other stopped further treatment because of drug resistance and was lost to follow-up. Conclusion: Our study display a group of unusual pathologic form of malignant GTNs mainly compose of monophasic trophoblasts, which present with low serum β-hCG levels and are different from classic choriocarcinoma or intermediate trophoblastic tumour. These cases are less sensitive to chemotherapy and poor prognosis. Early identification and early surgical intervention may improve the survival.