Gestational trophoblastic disease


Placental site trophoblastic tumor

Topic Completed: 18 October 2021

Minor changes: 15 November 2021

Copyright: 2003-2021,, Inc.

PubMed Search: Placental site trophoblastic tumor[TI] free full text [SB]

Rachelle Mendoza, M.D.
Raavi Gupta, M.D.
Page views in 2020: 10,616
Page views in 2021 to date: 10,886
Cite this page: Mendoza R, Lanjewar S, Gupta R. Placental site trophoblastic tumor. website. Accessed November 27th, 2021.
Definition / general
  • Placental site trophoblastic tumor (PSTT), a rare gestational trophoblastic disease (0.25 - 5% of all trophoblastic tumors), is a neoplastic proliferation of intermediate trophoblasts at placental implantation site (Hum Pathol 1991;22:847)
Essential features
  • Consists of aggregates or sheets of large, polyhedral to round, predominantly mononucleated cells composed of implantation site intermediate trophoblastic cells
  • Characteristic vascular invasion is often present, in which the tumor cells replace the wall of myometrial vessels
  • Tumor cells are positive for HPL, CD146 and HSD3B1 but only focally positive for hCG and negative for PLAP; Ki67 index is < 30%
  • Serum beta hCG levels are low (< 1,000 mIU/mL)
  • Atypical choriocarcinoma, syncytioma, chorioepitheliosis, trophoblastic pseudotumor
ICD coding
  • ICD-O: 9104/1 - placental site trophoblastic tumor
  • ICD-11: 2C75.0 & XH1RM5 - malignant trophoblastic neoplasm of placenta and placental site trophoblastic tumor
  • Patients are usually in the reproductive age group (mean: 31 years; range: 20 to 63 years)
  • Has been thought to develop as a result of neoplastic transformation of cytotrophoblastic cells; the transformed cells assume the differentiation toward implantation site intermediate trophoblast (Lancet Oncol 2007;8:642)
  • Duplication of paternal X chromosome is considered to cause abnormal genetic overdosing and plays a role in trophoblastic proliferation; 85% of PSTT have had a female antecedent gestation (Lab Invest 2000;80:965)
  • Unknown
Diagrams / tables

Images hosted on other servers:
Origin of PSTT

Origin of PSTT

Clinical features
  • Biopsy or hysterectomy specimen
Radiology description
  • On ultrasonography, a solid mass within the endometrial cavity or in the myometrium may be identified, with more or less prominent blood vessels on color Doppler imaging; in certain cases, ultrasound may reveal an enlarged uterus with a heterogeneous echotexture, echogenic foci and cystic areas of hemorrhage
  • On MRI, a frequent observation is the distortion of the junctional zone caused by a myometrial or endometrial mass, which is typically isointense to normal myometrium on T1 weighted images and isointense to slightly hyperintense to the myometrium on T2 weighted images; a diffusely heterogeneous pattern of the uterus with loss of zonal anatomy is also observed
  • Reference: J Radiol Case Rep 2015;9:14
Radiology images

Images hosted on other servers:
Uterine ultrasound

Uterine ultrasound

Pelvic MRI

Pelvic MRI

Uterine MRI

Uterine MRI

Prognostic factors
  • Poor prognostic factors include
    • Tumor cells with clear cytoplasm, deep myometrial invasion, large tumor size, necrosis and high mitotic count (> 2.5 mitoses/mm², equating to > 5 mitoses/10 high power fields of 0.5 mm in diameter and 0.2 mm² in area) (Gynecol Oncol 2006;100:511)
    • Advanced stage, ≥ 48 months since antecedent pregnancy, age > 40 years and the presence of tumor cells with clear cytoplasm are independent predictors of a worse prognosis (Gynecol Oncol 2006;100:511)
Case reports
Gross description
Gross images

Images hosted on other servers:
Uterus with PSTT

Uterus with PSTT

Microscopic (histologic) description
  • Infiltrative growth pattern consisting of aggregates or sheets of large, polyhedral to round, predominantly mononucleated cells composed of implantation site intermediate trophoblastic cells
  • Scattered multinucleated implantation site trophoblastic cells are common
  • Tumor cells often aggregate into confluent sheets; however, at the periphery the trophoblast cells invade singly or in cords and nests, characteristically infiltrating the myometrium by separating individual muscle fibers and groups of fibers
  • Vascular invasion is often present, in which the tumor cells replace the wall of myometrial vessels; these transformed blood vessels are unique among all human solid tumors and are diagnostic for PSTT
  • Cytologically, the cells have an abundant amphophilic (and occasionally eosinophilic or clear) cytoplasm; nuclei are pleomorphic and nuclear atypia is generally pronounced, with frequent, large, convoluted nuclei and marked hyperchromasia
  • Most tumors have a low mitotic count, with 1 - 2 mitoses/mm² (equating to 2 - 4 mitoses/10 high power fields of 0.5 mm in diameter and 0.2 mm² in area) (Gynecol Oncol 2006;100:511, Int J Gynecol Pathol 2001;20:31, Clin Obstet Gynecol 1984;27:248)
  • Decidua or an Arias-Stella reaction may be present in the adjacent, uninvolved endometrium; villi are almost never identified
  • Necrosis may be present
  • Reference: Kurman: Blaustein's Pathology of the Female Genital Tract, 7th Edition, 2019
Microscopic (histologic) images

Contributed by Rachelle Mendoza, M.D.
Infiltrative pattern with necrosis

Infiltrative pattern with necrosis

Tumor cells

Cell morphology

Vascular invasion

Vascular invasion

Negative stains
Molecular / cytogenetics description
Sample pathology report
  • Uterus, cervix, total hysterectomy:
    • Placental site trophoblastic tumor (see comment)
    • Comment: The tumor is a polypoid, nodular mass infiltrating into the myometrium. It is composed mostly of mononucleated eosinophilic polygonal cells with admixed multinucleated cells, morphologically similar to intermediate trophoblastic cells. The tumor cells infiltrate in between the myometrial fibers and invades the myometrial vessel walls. Areas of tumor necrosis are identified comprising about 20% of the specimen. Mitotic activity is 1 - 2/mm² and the Ki67 index is approximately 15%. The tumor cells stain positively with HPL, MUC4 and CD146, focally positive for hCG and AE1 / AE3 and were negative for p63, p16, HMB45, S100, SMA and inhibin.
Differential diagnosis
  • Exaggerated placental site (EPS):
    • Exuberant infiltration of implantation site intermediate trophoblastic
    • Microscopic, lacks mitotic activity (Ki67 ~0%) and composed of intermediate trophoblastic cells separated by masses of hyaline
    • Usually admixed with decidua and chorionic villi and contains large numbers of multinucleated trophoblastic cells
  • Epithelioid trophoblastic tumor (ETT):
    • Grows in expansile nodular fashion, with presence of fibrillary hyaline material, extensive geographic necrosis, calcification and absence of vascular invasion
    • Positive for p63, PLAP and inhibin
  • Choriocarcinoma:
    • Comprised of trimorphic proliferation of syncytiotrophoblast, cytotrophoblast and intermediate trophoblast
    • Strong and diffuse beta hCG expression
    • Markedly elevated serum beta hCG (1,000 mIU/mL to 1,000,000 mIU/mL)
    • Increased Ki67 (> 40%)
  • Squamous cell carcinoma (SCC) of the cervix:
    • More cellular atypia with basaloid features (high nuclear to cytoplasmic ratio, nuclear hyperchromasia)
    • Positive for p16 and HPV ISH
    • Negative for HPL, CD146, MUC4, HSD3B1
    • Very elevated Ki67 index
  • Poorly differentiated carcinoma:
    • May show glandular differentiation and some variant epithelial differentiation (squamous, tubal)
  • Epithelioid smooth muscle tumors:
  • Metastatic melanoma:
    • Large nucleoli
    • Diffusely positive for melanoma markers (HMB45, melanA, S100)
Additional references
Board review style question #1

A 31 year old woman, gravida 2, para 1, presents with profuse vaginal bleeding. Prior to this, the patient had amenorrhea for about 12 weeks with uterine enlargment. Ultrasound reveals a 10 - 12 week enlarged uterus with a 4 cm polypoid endomyometrial mass. There was no intrauterine pregnancy. Serum beta hCG is < 1,000 mIU/mL. On H&E sections of the endometrial sample, the tumor shows an infiltrative growth pattern consisting of aggregates or sheets of large, polyhedral to round, predominantly mononucleated cells (representative section is shown above). Vascular invasion is present, replacing the wall of myometrial vessels. The proliferation index (Ki67) is < 30%. What is the most likely diagnosis?

  1. Choriocarcinoma
  2. Epithelioid trophoblastic tumor
  3. Placental site nodule
  4. Placental site trophoblastic tumor
Board review style answer #1
D. Placental site trophoblastic tumor

Comment Here

Reference: Placental site trophoblastic tumor
Board review style question #2
Characteristic histological features helpful in differentiating placental site trophoblastic tumor from most other neoplasms are

  1. Ability to replace and re-epithelialize the endocervical / endometrial surface epithelium
  2. Invasion and replacement of myometrial vessel walls
  3. Presence of distinct neoplastic components (triphasic tumor)
  4. Presence of extensive geographic necrosis and expression of p63
Board review style answer #2
B. Invasion and replacement of myometrial vessel walls

Comment Here

Reference: Placental site trophoblastic tumor
Back to top
Image 01 Image 02