Placenta

Gestational trophoblastic disease

Neoplasms

Choriocarcinoma



Topic Completed: 27 May 2021

Minor changes: 27 May 2021

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PubMed search: Choriocarcinoma[TI] placenta[TI]

Lawrence Hsu Lin, M.D., Ph.D.
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Cite this page: Lin LH, DeLair D. Choriocarcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/placentachoriocarcinoma.html. Accessed December 3rd, 2021.
Definition / general
  • Aggressive form of gestational trophoblastic neoplasia composed of syncytiotrophoblast, cytotrophoblast and intermediate trophoblast
Essential features
  • Triphasic neoplasm (syncytiotrophoblast, cytotrophoblast and intermediate trophoblast components)
  • Arises from previous pregnancies, more commonly after complete hydatidiform mole
  • Aggressive behavior
  • Serum human chorionic gonadotropin (hCG) is a reliable tumor marker
  • High cure rates with chemotherapy
ICD coding
  • ICD-O: 9100/3 - Choriocarcinoma, NOS
  • ICD-10: C58 - Malignant neoplasm of placenta
  • ICD-11: 2C75 & XH8PK7 - Malignant neoplasms of placenta and choriocarcinoma, NOS
Epidemiology
Sites
Etiology
Clinical features
  • Vaginal bleeding is the most common symptom
  • Can also present initially with metastatic disease, especially after nonmolar pregnancies, in the lungs (dyspnea, hemoptysis), lower genital tract (violet nodules located in the vulva, vagina or cervix), liver (abnormal liver function, intraabdominal hemorrhage) and brain (neurologic symptoms, e.g. convulsion, altered mental status)
Diagnosis
Laboratory
  • Markedly elevated hCG is a reliable marker of the disease
  • hCG levels reflect the tumor burden, therefore, they are used for diagnosis, follow up, evaluation of therapy response and screening of recurrences (Int J Gynaecol Obstet 2018;143:79, Lancet 2010;376:717)
Radiology description
Radiology images

Contributed by Lawrence Hsu Lin, M.D., Ph.D. and Deborah DeLair, M.D.
Ultrasound of uterine choriocarcinoma Ultrasound of uterine choriocarcinoma

Ultrasound of uterine choriocarcinoma

CXR with lung metastases

CXR with lung metastases

CT scan with lung metastases

CT scan with lung metastases

CT scan with brain metastases

CT scan with brain metastases

MRI scan with brain metastases

MRI scan with brain metastases

Prognostic factors
  • WHO prognostic scoring system (includes age, antecedent pregnancy, interval between diagnosis and index pregnancy, hCG levels, largest tumor size, location and number of metastasis, chemoresistance) (Int J Gynaecol Obstet 2018;143:79):
    • Low risk: ≤ 6
    • High risk: ≥ 7
    • Ultra high risk: > 12
  • FIGO anatomic staging (Int J Gynaecol Obstet 2018;143:79):
    • I: confined to uterine corpus
    • II: extending to adnexa and vagina
    • III: extending to lung
    • IV: other metastatic sites
  • Prognostic factors of poorer outcome:
    • Older age
    • Arising from nonmolar pregnancy
    • Long interval between index pregnancy and diagnosis
    • Markedly elevated hCG
    • Large tumor burden
    • Metastasis to brain and liver
    • Chemoresistance

WHO scoring system based on prognostic factors
0 1 2 4
Age, years < 40 ≥ 40 - -
Antecedent pregnancy Mole Abortion Term -
Interval months from index pregnancy, months < 4 4 - 6 7 - 12 > 12
Pretreatment serum hCG (mIU/mL) < 103 103 - 104 104 - 105 > 105
Largest tumor size (including uterus), cm < 3 3 - 4 ≥ 5 -
Site of metastases Lung Spleen, kidney Gastrointestinal Liver, brain
Number of metastases - 1 - 4 5 - 8 > 8
Previous failed chemotherapy - - Single drug ≥ 2 drugs
Case reports
Treatment
  • Chemotherapy (Int J Gynaecol Obstet 2018;143:79)
    • Choice of chemotherapy is based on the FIGO / WHO prognostic score (Int J Gynaecol Obstet 2018;143:79)
      • Low risk: single agent, including methotrexate and actinomycin D
      • High risk: multi agent, including etoposide, methotrexate, actinomycin, cyclophosphamide, vincristine (EMA-CO); etoposide, cisplatin - etoposide, methotrexate, actinomycin (EP-EMA); paclitaxel, etoposide - paclitaxel, cisplatin (TE / TP)
  • Surgery only performed in selected cases (older age, chemoresistance, uterine rupture by tumor, life threatening hemorrhage)
  • Radiotherapy is controversial; some centers use radiotherapy for brain metastatic disease (Int J Gynaecol Obstet 2018;143:79)
Gross description
  • Dark red, solid, friable tumor, with areas of hemorrhage and necrosis
  • Intraplacental choriocarcinoma can be a subtle lesion grossly and is commonly mistaken for placental infarct
  • Most common location: endomyometrium
Gross images

Contributed by Lawrence Hsu Lin, M.D., Ph.D. and Deborah DeLair, M.D.
Uterine tumor

Uterine tumor

Large uterine tumor

Large uterine tumor

Cervical involvement

Cervical involvement

Tubal tumor

Tubal tumor



Images hosted on other servers:
Intraplacental tumor

Intraplacental tumor

Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Regina Schultz, M.D., Ph.D. and Tatyana Zinger, D.O.
Solid tumor without chorionic villi

Solid tumor without chorionic villi

Triphasic neoplasm

Triphasic neoplasm

Increased mitotic activity

Increased mitotic activity

Intraplacental choriocarcinoma Intraplacental choriocarcinoma

Intraplacental choriocarcinoma

Virtual slides

Images hosted on other servers:
21 year old at 40 weeks with Zika exposure

21 year old at 40 weeks with Zika exposure

Cytology description
  • Not routinely performed
  • Clusters of cohesive atypical epithelioid cells
Electron microscopy description
  • Not routinely performed
  • Rare reports showing triphasic population: syncytiotrophoblasts, cytotrophoblasts and intermediate trophoblast
  • Syncytiotrophoblasts:
    • Complex cells with multiple, irregular and convoluted nuclei and dense and abundant cytoplasm containing dilated endoplasmic reticulum, Golgi apparatus, lysosomes and tonofilaments
    • Syncytiotrophoblast cell membranes often contain numerous microvilli
  • Cytotrophoblasts:
    • Closely spaced epithelial cells with single, large nucleus
    • Relatively simple cytoplasm with small amount of organelles and glycogen
  • Intermediate trophoblasts: intermediate sized mononuclear cells with moderately complex cytoplasm containing organelles
Molecular / cytogenetics description
Molecular / cytogenetics images

Images hosted on other servers:
STR analysis of gestational choriocarcinoma

STR analysis of gestational choriocarcinoma

STR analysis of nongestational choriocarcinoma

STR analysis of nongestational choriocarcinoma

Sample pathology report
  • Uterus, total hysterectomy:
    • Choriocarcinoma (see comment)
    • Comment: The specimen shows a highly mitotically active neoplasm arising in the endomyometrium. There is a triphasic population of atypical cells composed of syncytiotrophoblast, cytotrophoblast and intermediate trophoblast. Immunohistochemical stains show reactivity for hCG (diffuse), p63 (focal) and hPL (focal). The previous history of complete hydatidiform mole is noted, favoring the diagnosis of gestational choriocarcinoma
Differential diagnosis
  • Placental site trophoblastic tumor:
    • Composed of implantation type intermediate trophoblast, characterized by a single population of mononuclear cells with eosinophilic and amphophilic cytoplasm
    • Diffusely positive for hPL and Mel-CAM; focal positivity for hCG
  • Epithelioid trophoblastic tumor:
    • Composed of chorionic type intermediate trophoblast, characterized by a single population of mononuclear cells with eosinophilic to clear cytoplasm
    • Diffusely positive for p63; focal positivity for hCG, Mel-CAM, hPL
  • Invasive mole / hydatidiform mole / early pregnancy loss:
    • Presence of villi indicates invasive mole, molar pregnancy or early pregnancy loss
    • Nuclear atypia can be present in invasive mole, molar pregnancy and early pregnancy loss; however, extensive marked cytologic atypia favors choriocarcinoma
    • Differential diagnosis can be challenging, especially when tissue is scant; diagnosis of atypical trophoblastic proliferation can be rendered, as some cases of early choriocarcinoma cannot be histologically differentiated from atypical proliferations associated with invasive mole, hydatidiform mole or early pregnancy loss
  • Nongestational choriocarcinoma:
    • Morphologically and immunohistochemically identical to gestational choriocarcinoma
    • Prepuberal ovarian tumor favors nongestational choriocarcinoma
    • Postmenopausal mixed endometrial tumor with nontrophoblastic carcinomatous components and extrauterine tumors without uterine primary favor nongestational choriocarcinoma
    • Definite diagnosis can be reached after STR analysis; nongestational choriocarcinoma has identical alleles to the patient's and absence of partner's alleles
Board review style question #1

Which of the following serum markers is markedly elevated in the tumor above?

  1. CA125
  2. CA19-9
  3. CEA
  4. hCG
  5. hPL
Board review style answer #1
D. hCG

Comment Here

Reference: Choriocarcinoma
Board review style question #2
Which is the best tool to differentiate gestational from nongestational choriocarcinoma?

  1. Copy number analysis
  2. Immunohistochemistry
  3. Microsatellite instability status
  4. Short tandem repeat analysis
  5. Tumor mutational burden analysis
Board review style answer #2
D. Short tandem repeat analysis

Comment Here

Reference: Choriocarcinoma
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