Metrorrhagia in a 41 Year Old Woman

Jianxiong R Bao, M.D., Ph.D. and Richard Cochran, M.D.

Specimen Type:



A 41 year old woman presented with abnormal uterine bleeding. A TruTest® endometrial biopsy was performed using a Tao Brush® to sample the endometrium. Ample tissue fragments were received and were separated from the endometrial sample by filtration and submitted for histology and hematoxylin and eosin (H&E) staining.

Pathologic Features:

The histological sections revealed well circumscribed, paucicellular hyalinized nodules surrounded by fragments of endometrium (Figs. 1 & 2). High magnification showed large cells with pleomorphic, hyperchromatic bizarre nuclei and abundant eosinophilic cytoplasm, and round, eosinophilic hyaline bodies (Fig. 3).

Differential Diagnosis:

  • Placental site nodule.
  • Exaggerated placental site.
  • Placental site trophoblastic tumor.
  • Choriocarcinoma.
  • Squamous cell carcinoma.


Placental site nodule.

Placental site nodule is a rare, benign lesion of trophoblastic origin. It is often discovered as incidental findings in curettage or hysterectomy specimens performed for evaluation of irregular uterine bleeding, abnormal cervical smears, or post coital bleeding. It could be the result of the pregnancy several months to years after. Clinically, placental site nodule is small and well circumscribed. Serum hCG level returns to normal following curettage.

Microscopically, placental site nodule shows proliferation of intermediate trophoblasts, with large nuclei arranged in a syncytium. There is significant hyalinization, but no cytological atypia or increased mitotic figures. There are also cytotrophoblasts and syncytiotrophoblasts; and chronic inflammatory cells. This entity may have bizarre histologic findings and should be distinguished from other aggressive lesions like placental site trophoblastic tumor, epithelioid trophoblastic tumor or squamous cell carcinoma.

Exaggerated placental site usually presents as microscopic focus and serum hCG level returns to normal following curettage.

Placental site trophoblastic tumors are clinical large in size and are poorly circumscribed. Most cases follow normal pregnancy or missed abortion, rather than molar pregnancy. Under microscope, some cases have high cellularity, brisk mitotic figures, atypical nuclei and necrosis. There are no chorionic villi. Patients usually present with low but persistently elevated serum hCG. Most placental site trophoblastic tumors are considered as benign, but 10% of cases are malignant.

Choriocarcinoma has biphasic trophoblastic proliferation, with high elevation of serum hCG. The tumor has marked nuclear pleomorphism, hyperchromasia and prominent nucleoli, and it invades perpendicular to smooth muscle bundles. There is more tumor related hemorrhage and necrosis.

Squamous cell carcinomas, particularly those with hyalinization features may be mistaken with placental site nodule. But squamous cell carcinoma has pleomorphic nuclei, dense cytoplasm, foci of keratinization. Patients may have previous Human papilloma virus associated lesions.

In summary, placental site nodule is thought to represent unresorbed involuted placenta site. It may be present for years following a recognized or unrecognized pregnancy. Placental site nodule is a benign condition and the diagnosis is often made incidentally in a curettage specimen.


  1. Haber MH, Gattuso P, David O and Spitz D, Differential Diagnosis in Surgical Pathology (Hardcover), W.B. Saunder, Philadelphia 2002. p307-314.
  2. Mazur, MT, and Kurman, RJ, Diagnosis of Endometrial Biopsies and Curettings: A Practical Approach, 2nd ed. Springer, New York 2005.