Placental site trophoblastic tumor: Immunohistochemistry algorithm key to diagnosis and review of literature
A 53-year old G0P0 presumed post-menopausal woman presented to her gynecologist with postmenopausal bleeding. She had been on oral contraceptives for birth control until approximately 12 months prior and had a six-month bleeding-free interval before the onset of intermittent spotting. Pelvic ultrasound noted thickened endometrium measuring 2.2 cm. FSH was elevated to 32.3 mIU/mL (post-menopausal = 23.0–116.3 mIU/mL), indicating of her post-menopausal status. She underwent a dilatation and curettage (D&C).\nInitial pathology was reported as poorly differentiated cancer and the patient was referred to a gynecologic oncologist. On additional review, there was suggestion of gestational trophoblastic disease. The tumor cells formed at least three discernible patterns: (1) large, well-formed, irregularly outlined syncytial aggregates, (2) smaller clusters, often linear, more uniform cells resembling cytotrophoblasts, and (3) collections of large cells with markedly enlarged hyperchromatic nuclei resembling extravillous (intermediate) trophoblasts (A–B). Frequent strong expression of multiple trophoblastic markers within these tumor cells suggested a trophoblastic neoplasm.\nQuantitative hCG was elevated to 1517.7 mIU/mL. She underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, bilateral pelvic and para-aortic lymphadenectomy and omentectomy. Intraoperatively, the tumor appeared deeply invasive and necrotic, without evidence of disease outside the uterus.\nGross examination revealed abundant friable and necrotic tumor involving 80% of the endometrial cavity, abutting the uterine serosa, and measuring 5 cm in largest dimension (A–B). Fallopian tubes, ovaries and lymph nodes were benign.\nMicroscopic examination revealed extensive tumor necrosis. The dominant pattern was cytologically bizarre, large, infiltrative single neoplastic cells (C–D). After extensive sampling, no syncytiotrophoblasts were identified. On immunohistochemical staining, human placental lactogen (hPL), a germ cell tumor marker often positive in PSTTs, was positive. Beta hCG, and placental alkaline phosphatase (PLAP) demonstrated scattered positivity. Tumor cells were positive for inhibin and negative for p63 and CK5/6. Ki-67 highlighted a few scattered positive cells. The immunohistochemical profile argued against choriocarcinoma or epithelioid trophoblastic tumor. However, extensive tumor necrosis and the dominant pattern of cytologically bizarre, large, infiltrative single neoplastic cells are atypical for PSTTs. Taken together, the neoplasm was best characterized as an unusual malignant trophoblastic tumor of intermediate cell type. The monophasic pattern of the tumor without syncytiotrophoblasts plus the immunoprofile was most consistent with PSTTs.\nThe patient underwent a CT scan that was negative for metastatic disease. Since the disease was confined to the uterus, the patient was diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I disease.\nAfter discussion with the patient, the decision was made not to pursue adjuvant therapy. Monthly serum hCG and hPL have been negative for 10 months. She remains without evidence of disease.