Gestational trophoblastic disease
Nonneoplastic lesions
Placental site nodule

Topic Completed: 1 October 2017

Minor changes: 13 August 2020

Copyright: 2002-2021,, Inc.

PubMed Search: Placental site nodule

Sonali Lanjewar, M.B.B.S.
Raavi Gupta, M.D.
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Cite this page: Lanjewar S, Gupta R. Placental site nodule. website. Accessed January 23rd, 2021.
Definition / general
  • Placental site nodules (or plaques) are small and well circumscribed nodular aggregates of intermediate trophoblastic cells embedded in a hyalinized stroma
  • Represent the benign counterpart of the epithelioid trophoblastic tumor
  • Atypical placental site nodule (ASN) is a term assigned to placental site nodules with significant nuclear atypia and/or borderline proliferation index (see below)
Clinical features
  • Discovered incidentally in uterine or endocervical curettings, cervical biopsies and rarely in hysterectomy specimens
  • Placental site nodules have been detected in fallopian tubes, presumably a consequence of prior tubal pregnancy (Int J Gynecol Pathol 2003;22:362, Int J Gynecol Pathol 1997;16:219)
  • Due to small size and circumscription, these lesions are usually completely surgically excised by curettage
  • These lesions are not known to recur or progress to persistent gestational trophoblastic disease (Int J Gynecol Pathol 2001;20:31)
  • No specific treatment or follow up is necessary for this lesion
  • The behavior of atypical placental site nodule has not yet been studied
Gross description
  • Placental site nodules are small lesions, from 1 to 14 mm (average 2.1 mm)
  • Grossly, these appear as a yellow, white and necrotic appearing nodule in the endometrium or superficial myometrium
Microscopic (histologic) description
  • Small nodular or plaque-like lesions with rounded, well circumscribed borders which are surrounded by chronic inflammatory cells and occasionally decidualized stroma
  • Nodules typically are composed of haphazardly arranged extravillous trophoblast
  • Most trophoblast cells are of "immature (epithelioid) extravillous” type (p63+, CD146-); a minor component of "mature extravillous” type trophoblast (p63-, CD146+) can be seen (Mod Pathol. 2017;30(2s):301A [abstract #1210])
  • Trophoblast is usually distributed in the outer portion of nodule around a central hyalinized extracellular matrix
  • Mitotic figures are absent or rare
  • Cells vary in size and have relatively small uniform nuclei
  • Cytoplasm of the larger trophoblastic cells is abundant and eosinophilic; the smaller cells contain glycogen rich clear cytoplasm (Kurman: Blaustein's Pathology of the Female Genital Tract, 6th Edition, 2011)
  • Ki67 proliferation index is low (< 8%)
  • Atypical placental site nodules: placental site nodule with moderate to severe atypia and Ki67 proliferation index 8 - 10% (Kurman: WHO Classification of Tumours of the Female Reproductive Organs, 4th Edition, 2014)
Microscopic (histologic) images

Contributed by Sonali Lanjewar, M.D., M.B.B.S.
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Well circumscribed
nodules with
hyalinized matrix

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Haphazardly arranged intermediate trophoblasts

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Hyalinized matrix and intermediate trophoblasts

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Chorionic type intermediate trophoblasts

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Weak hPL staining

Positive stains
Negative stains
Differential diagnosis
  • Epithelioid trophoblastic tumor (ETT)
    • These are larger lesions, more cellular, have extensive necrosis and evident mitoses
    • Calcifications are typically present in ETTs and when present, lesion is more likely to be an ETT than placental site nodule
    • Cyclin E is expressed in ETT and absent in placental site nodule
    • Ki67 index is high (> 10%)
  • Squamous cell carcinoma of the cervix
    • Circumscription, abundant eosinophilic extracellular deposit and lack of mitotic activity favor a placental site nodule
    • Placental site nodules are typically negative for p16
Board review style question #1
The typical immunophenotypic profile of placental site nodule is:

  1. p63-, hPL-, cyclin E+
  2. p63-, hPL+, cyclin E-
  3. p63-, hPL+, cyclin E+
  4. p63+, hPL+, cyclin E-
Board review style answer #1
D. p63+, hPL+, cyclin E-

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Reference: Placental site nodule
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