Objective Histologic Characterization of Trophoblastic Proliferations

Introduction/Objective Placental site nodules (PSNs) are rare intermediate trophoblastic lesions characterized by hyalinized cellular aggregates that are small, well-circumscribed, non-necrotic, and paucicellular. PSNs are generally incidental in gynecologic specimens. ETTs are malignant proliferations of intermediate trophoblasts and are generally larger, with nuclear atypia, and higher mitotic rate. Atypical placental site nodules (APSNs) are histologically intermediate between PSN and ETT and not well characterized in the literature to date. There exists room for more objective characterization of PSN and APSN. We use objective measurements to characterize trophoblastic proliferations based on size, location, mitotic rate, number of trophoblasts per high-power field (t-HPF), ki-67 index, beta-hCG, time since last pregnancy, presence of calcification or necrosis, and clinical follow-up. Methods The surgical pathology database of a single large academic institution was searched for cases of “placental site nodule,” “atypical placental site nodule,” “epithelioid trophoblastic tumor,” and “placental site trophoblastic tumor”. Clinical and morphologic data were recorded for each case. Ki-67/cytokeratin AE1/AE3 dual immunohistochemical stains were performed to assess the proliferative index of the trophoblastic cells. Results 70 cases of trophoblastic lesions (53 PSN, 4 APSN, 5 ETT, 8 PSTT) were identified. Results include: PSNs were on average 3.2 mm, 56.5 t-HPF, and 2.6% ki-67. APSNs 4.3 mm, 97.8 t-HPF, and 6.4% ki-67. ETTs 16.5 mm, 161.8 t-HPF, and 12.2% ki-67. Conclusion Objective measurements of trophoblastic lesions, as well as correlation with clinical data, may be useful for more accurate classification of these lesions, especially by those who encounter them rarely. To date, the clinical risk, optimal management, and risk for progression of APSNs are not well characterized and thus are worthy of additional study and description. For example, in our data, 14 cases originally signed out at PSN were at least 4 mm, which may re-classify them as APSN.

Endometrial Calcifications

Benign endometrial calcifications with or without bone fragments are uncommon clinicopathologic findings. They can be detected during pelvic ultrasonography or as incidental pathologic findings. They have been found to be associated with infertility and menstrual anomalies in young adult patients and in symptomatic postmenopausal women with endometrial atrophy and endometrial polyps. Its exact etiology is unknown, its pathogenesis is controversial, and its clinical importance is not fully validated. We performed a retrospective review study over 7 years and found 11 (0.4%) cases of benign endometrial calcifications. The mean patient age was 45.2 years (range = 20-66 years). All of the women complained of menstrual abnormalities and 4 complained of infertility. Six had a previous procedure of abortion, 2 had oral contraceptive pills, and 4 a course of progesterone therapy. Their size and morphology varied from heterogeneous microcalcifications of variable appearances, shattered glassy chunks to detached bones. Four cases were associated with endometrial polyps, 1 with a placental site nodule, 1 with chronic endometritis, and 1 with endometrial hyperplasia. Most showed secretory endometrial tissue and ciliated cell metaplasia. Two cases showed atrophic endometrium. Etiology and pathogenesis are multifactorial and miscellaneous. Progesterone may play a role. Heterogeneous histomorphologic patterns may carry potential pitfalls. Pathologic recognition is clinically important to reassure clinicians in symptomatic postmenopausal women, alert gynecologists to a treatable albeit rare cause of infertility in younger women, and assist in patients’ counselling. We also included cases of calcifications associated with endometrial malignancies to compare and contrast malignant endometrial calcifications with benign endometrial calcifications.

Gestational Trophoblastic Tumors: A Timely Review of Diagnostic Pathology

Context.— Gestational trophoblastic tumors include 3 distinct entities: gestational choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. Accurate diagnosis is important for clinical management of the patient. Objective.— To review clinical features and pathologic diagnosis of gestational trophoblastic tumors. Data Sources.— Literature and personal experience are the sources for this study. Conclusions.— Trophoblastic tumors are rare encounters in modern medicine, as a result of clinical practice of molar surveillance programs and early chemotherapeutic intervention for persistent gestational trophoblastic neoplasia. Diagnostic recognition of these tumors requires a high index of suspicion, awareness of their histologic characteristics, and appropriate application of immunohistochemical and molecular biomarkers. Recent attention has been given to a few precursor lesions of gestational trophoblastic tumors, including early/in situ choriocarcinoma and atypical placental site nodule.