Choriocarcinoma

Definition

Malignant tumor derived from normal or abnormal placental tissue, composed of a proliferation of cytotrophoblast and syncytiotrophoblast, without villi formation.

Clinical Features

More common where hydatidiform mole is prevalent
≈1–2% of complete moles are followed by choriocarcinoma:1
- usually preceded by complete hydatidiform mole:
May be preceded by:
- partial mole:
  - very unusual
- ectopic pregnancy
- nonmolar intrauterine abortion:
  - latent period:
    - almost always <1 year
    - rarely considerably >1 year (‘latent choriocarcinoma’)2
  - often evidence of precursor lesion of increased trophoblastic proliferation
- term pregnancy:3,4
  - may appear as one or more masses in an otherwise normal placenta or develop following the delivery 5–7
Average age at diagnosis 29 years
Relationship between incidence and prognosis and ABO groups of woman and her husband 8

Metastases

Early hematogenous metastases:
- most common sites:
  - lung
  - brain
  - liver
  - kidney
  - bowel9–11
- May:
  - be clinically solitary
  - occur in most unusual places
- Often present with massive hemorrhage 12
- Fetus rarely involved, even in widespread metastatic disease11

Gross Pathology

Tumor mass (Figs 1 and 2
Fig. 1: Uterine choriocarcinoma showing typical highly hemorrhagic appearance.
Fig. 2: Uterine choriocarcinoma showing typical highly hemorrhagic appearance.
):
- soft
- dark red
- hemorrhagic
- round
- nodular
Residual tumor in uterus of patients dying of disseminated choriocarcinoma may be inconspicuous or absent13

Morphologic Changes In Other Organs From Increased Secretion Of hCG And Other Hormones

Hyperplasia of endocervical glands
Decidual reaction (endometrial and ectopic):
- spiral arterioles fail to develop as they do in normal cycle
- appearance of mucosa similar to that after administration of progestogens13
Arias-Stella phenomenon
Bilateral enlargement of ovaries by theca-lutein cysts14
Hyperplasia of mammary lobules

Histopathology

Clusters of cytotrophoblast separated by streaming masses of syncytiotrophoblast:
- characteristic dimorphic plexiform pattern15 (Fig. 3
  Fig. 3: Intimate admixture of syncytiotrophoblast and cytotrophoblast in choriocarcinoma.
  )
Usually:
- hemorrhage
- necrosis
Villi characteristically absent

Special Stains and Immunohistochemistry

Choriocarcinoma cells:
- positive for:
  - hCG
  - keratin
- may be reactivity for:
  - hPL
  - SP1
  - CEA16

Diagnosis

‘In situ’ choriocarcinoma described arising from trophoblast of stem villi in first trimester of pregnancy18
Presence of villi said to rule out diagnosis no matter how atypical the trophoblastic cells may be:19
- but if arise from complete mole there should be a point in time at which both molar and choriocarcinomatous tissue are simultaneously present

Other Investigations

Locus-specific minisatellite probes to identify restriction fragment length polymorphisms in DNA from tumor tissue useful in:
- distinguishing gestational from nongestational (germ cell) choriocarcinoma
- documenting tumor derivation from an antecedent complete mole (by establishing the androgenetic nature of the tumor)17

Differential Diagnosis

Select up to 2 differential diagnoses to compare with Choriocarcinoma

hCG secretion can also occur in:
- nongestational choriocarcinoma
- other ovarian and testicular germ cell tumors
- melanoma
- malignant lymphoma
- carcinoma of:
  - esophagus
  - stomach
  - pancreas
  - kidney
  - liver
  - lung
  - urinary bladder
  - uterus
  - adrenal gland
  - breast
  - other sites
- Many of these tumors have tumor giant cells containing hCG20

Management

Chemotherapy

With methotrexate, actinomycin D, and chlorambucil (MAC):21
- survival rate:
  - close to 100% for cases restricted to uterus
  - ≈83% for metastatic disease22,23
- surgery alone much less effective with cure rate:
  - <20% for those accompanied by metastases 24
  - hysterectomy if:
    - preservation of reproductive function not desired
    - unresponsive to chemotherapy alone

Surgery

Useful in controlling life-threatening hemorrhage from metastatic lesions25,26

Prognosis

Microscopic grading of little value
Some attempts at correlating various patterns of growth with prognosis:27,28
- of these most convincing show improved prognosis if intense inflammatory infiltrate at interphase between tumor and stroma 29–32

Low- and high-risk patient groups (Tables 1 and 2

Table 1. NIH classification of gestational trophoblastic disease
From SGO handbook. Staging of gynecologic malignancies. Chicago, 1994, Society of Gynecologic Oncologists.
	I.	Benign GTD
		A	Complete hydatidiform mole
		B	Partial hydatidiform mole
	II.	Malignant GTD
		A	Nonmetastatic GTD
		B	Metastatic GTD
			1	Good prognosis, low risk – absence of any risk factor
			2	Poor prognosis, high risk – presence of any risk factor
				a	Duration >4 months
				b	Pretherapy level of β-hCG in serum >40,000 mIU/ml
				c	Brain or liver metastases
				d	GTD after term gestation
				e	Prior to failed therapy

Table 2. World Health Organization Prognostic Index Score for Gestational Trophoblastic Disease
* Total score is obtained by adding the individual scores for each prognostic factor. Low risk 0–4, intermediate risk 5–7, high risk ≥8. † Interval is time between end of antecedent pregnancy and start of chemotherapy.
		Score*
	Prognostic factor	0	1	2	4
	Age (y)	≤39	>39	—	—
	Antecedent pregnancy	Hydatidiform mole	Abortion	Term	—
	Interval (mo)†	4	4–6	7–12	>12
	β-hCG (IU/L)	<103	103–104	104–105	>105
	ABO groups (female×male)	—	O×A, A×O	B, AB	—
	Largest tumor, including uterine tumor	—	3–5 cm	>5 cm	—
	Site of metastases	—	Spleen, kidney	GI tract, liver	Brain
	Number of metastases identified	—	1–4	4–8	>8
	Prior chemotherapy	—	—	Single drug	Two or more drugs

) identified on basis of:

location of metastases

hCG

duration of disease 33

References

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Last updated: 12 Mar 2006