Placental Chorangiocarcinoma: Case Report with Literature Review of a Rare Entity
Nishant SAGAR1, Parul TANWAR1, Nita KHURANA1, Poonam KASHYAP2
1Department of Pathology, Maulana Azad Medical College, NEW DELHI, INDIA
2Department of Obstetrics and Gynaecology, Maulana Azad Medical College, NEW DELHI, INDIA
Keywords: Chorangiocarcinoma, Chorangioma, Trophoblastic proliferation, Placenta
Chorangiocarcinoma is an extremely rare tumor seen in the placenta, with only six cases reported in the literature so far. Its morphological
characteristics, criteria for diagnosis, and the pathophysiology remain controversial to date. Although it was predominantly considered a benign
entity, a solitary case of distant metastasis has been reported in the literature.
We present a case of this unusual tumor in the preterm placenta of a 29-year-old female. Grossly seen as a grey white nodule, microscopic
examination revealed nests of atypical trophoblastic proliferation surrounded by vascularized stroma. No evidence of basement membrane
invasion was noted. On immunohistochemistry, the trophoblastic component expressed pancytokeratin, Beta HCG, and Placental Alkaline
Phosphatase with high Ki-67 labelling index.
The present case highlights this exceedingly rare entity with emphasis on its morpho-immunohistochemical features along with a review of
Chorangiocarcinoma is an unusual malignant trophoblastic
tumor of the placenta with only six cases reported in
literature so far 1-6
. Jauniaux et al. first described
chorangiocarcinoma as a lesion showing a combination of
both vascular and trophoblastic proliferation 1
chorangiomas, on the other hand, are purely vascular
benign lesions, similar to hemangiomas elsewhere in the
. The pathophysiology of chorangiocarcinoma
is still unclear, although multiple hypotheses have been
proposed. Due to a paucity of cases, its prognosis and
management protocol also remain uncertain. We, herein,
describe the seventh case of this entity with a review of the
A twenty-nine-year-old female presented to the emergency
room at 30 weeks of gestation, with complaints of
vaginal discharge and fever for one day. The patient was
G4P1L1A2, and had a known history of moderate anemia
(Hb 9 g/dl) and hypothyroidism. A clinical diagnosis of
chorioamnionitis with premature rupture of membrane
was made. Ultrasonography (USG) revealed a small
hypoechoic lesion in the right lower abdomen in relation
to the uterine fundus with maintained uterine contour.
No other significant changes were observed on USG. The patient underwent caesarian section and delivered a
preterm baby. The placenta was sent for histopathological
examination with a clinical suspicion of chorioamnionitis.
The placenta specimen measured 13x11x2 cm with
the attached cord measuring 35 cm in length. Near the
umbilical cord insertion, a grey white nodule was present
measuring 5.5x4.5x3 cm. On gross examination, the nodule
was well circumscribed showing no evidence of infiltration
in the surrounding membranes or placental tissue. The cut
section was solid-cystic with the presence of friable areas
(Figure 1A,B). Microscopic examination of the nodule
showed multiple well-circumscribed large cellular nests
dispersed in a vascular stroma. The nests were variably
sized revealing a central area of moderately pleomorphic
cells surrounded by cuboidal cells at the periphery. These
cells in the center were polygonal in shape having a dense
hyperchromatic nucleus, irregular nuclear borders, and a
moderate amount of dense eosinophilic cytoplasm. Mitotic
figures (5-6/10hpf), apoptotic bodies, and multinucleation
was readily appreciated in these central cells. The peripheral
cuboidal cells showed minimal pleomorphism. Areas of
necrosis were identified at the center of the nests. The
intervening stroma between the nests consisted of a large
number of closely packed capillary sized vascular channels,
lined by a single layer of endothelial cells, devoid of any significant pleomorphism or atypia (Figure 2A,B). On
immunohistochemistry (IHC), the nests exhibited strong
expression of cytokeratin (AE1/AE3 clone, PathnSitu,
USA) (Figure 3C), Beta HCG (SPM105 clone, Thermo
Scientific, USA) (Figure 3A), Placental alkaline phosphate (PLAP) (PL8-F6 clone, BioGenex,USA) (Figure 3D), and a
high Ki-67 (GM001 clone, PathnSitu, USA) labelling index
(90%) but no expression of p16 (JC2 clone, DBS Pleasonton,
USA) was noted. CD34 (Qbend 10 clone, PathnSitu, USA)
highlighted the endothelial lining of the capillaries in the
intervening stroma (Figure 3B). Surrounding placenta
exhibited mild chorioamnionitis. Based on the presence
of nodular proliferation of pleomorphic trophoblastic cells
with a high proliferation index within a vascular stroma, a
final diagnosis of chorangiocarcinoma was rendered.
Click Here to Zoom
|Figure 1: A) Well-circumscribed grey-white solid nodule seen in
the placenta just below the membrane with no infiltration in the
surrounding membranes or placental tissue. B) Cut section of the
nodule showing friable and necrotic areas.
Click Here to Zoom
|Figure 2: Multiple well-circumscribed nodules in a vascular stroma with central necrosis. No evidence of infiltration into the stroma.
A) Low magnification (H&E, 100x), B) High magnification (H&E,400x).
Click Here to Zoom
|Figure 3: A) Bright beta HCG positivity in the central cells of the nodule (Beta HCG antibody, 100x). B) Stromal blood vessels
highlighted by strong expression of CD34 (CD34 antibody, 100x). C) Strong expression of pancytokeratin by the tumor nests
(PanCK antibody, 200x). D) Nests showed weak positivity for PLAP (PLAP antibody, 200x).
Chorangiocarcinoma was described, for the first time,
by Jauniaux et al. in 1988 as a tumor having features of
both chorangioma and choriocarcinoma. The authors
categorized it as a malignant gestational trophoblastic
. Later, in 1994, Trask et al. described the second
case having similar features as the first case, both being
All previously described cases of chorangiocarcinoma
were found incidentally in term or near-term pregnancies.
On macroscopic examination the tumor is seen within
the placenta and grossly resembles placental infarct
1-6. Microscopic features of chorangiocarcinoma
are not uniformly defined. The index case, described
by Jauniaux et al, in 1988, showed villous vascular
proliferation, surrounded by trophoblastic cells exhibiting
pleomorphism and increased proliferative activity, similar
to true trophoblasts 1. However, nineteen years later, in
2009, Ariel et al. described chorangiocarcinoma as having
nodules of atypical trophoblastic proliferation within a typical chorangioma. The trophoblastic component
exhibited frequent mitosis and necrosis 4.
Till date only six cases of chorangiocarcinoma have been
published in the literature (Table I). However, out of these,
only three cases had features similar to the present case
where the trophoblastic proliferation is found within the
vascular stroma rather than surrounding it 4-6.
Lastly some groups suggested calling these tumors “chorangiomas
with trophoblastic proliferations” and argued
that the number of cases might be underrepresented in
the literature. Khong presented a study on 33 placental
chorangiomas and found “chorangioma with trophoblastic
proliferation” in 15 out of 23 chorangiomas (65%) 8.
According to Khong’s definition, all of these cases fulfilled
the criteria for a chorangiocarcinoma diagnosis but the author avoided this terminology as there was no evidence of
stromal invasion. Similarly, Ogino and Redline studied 70
chorangiomas, 50% of which had associated mild to moderate
trophoblastic proliferation 7.
Except for one case, all previously described cases had
a benign course with no evidence of metastasis at the
time of delivery or during follow up 1-5. However, the
last published case of chorangiocarcinoma by Huang et
al. metastasized to the lung after three months of follow
up post-delivery, indicating its malignant nature and
justifying the term “chorangiocarcinoma” 6. Among the
7 cases discussed herein, including our case, 3 cases had
the additional morphological feature of necrosis (Table
I), which is a high-grade feature beyond just trophoblastic
proliferation. Interestingly, all of these three cases had nests of atypical trophoblastic cells within a chorangiomatous
stroma, including the case with recurrence. Therefore, there
might be two morphologic subgroups of these tumors, and
cases with this particular morphology could be followed
more carefully clinically.
The etiopathogenesis of chorangiocarcinoma remains
uncertain. Upregulation of vascular growth factors
have been hypothesized as a causative factor. However,
Gurchman et al. did not find any significant difference in
the expression of angiogenic factors (vascular endothelial
growth factor, basic fibroblast growth factor, Ang-1,
Ang-2 and Platelet-derived growth factor) in the lesion
as compared with normal villi 3. Some authors have
hypothesized that trophoblastic proliferation surrounding
chorangioma may be due to the effect of certain angiogenic
factors, but more studies are needed for confirmation 7.
The differential diagnosis of chorangiocarcinoma includes
intraplacental choriocarcinoma and metastatic cervical
squamous cell carcinoma. Vascular and stromal invasion
are frequently described in intraplacental choriocarcinoma
while it is absent in chorangiocarcinoma. Chorangiomatous
vascular proliferation is seen in chorangiocarcinoma and not
in intraplacental choriocarcinoma. However, the possibility of a chorangioma associated with a choriocarcinoma in situ
cannot be entirely excluded as discussed previously 2,4.
Cervical squamous cell carcinoma is positive for p16 and
negative for PLAP 9.
Due to the paucity of cases, the appropriate management
guidelines have not been described. The only described
metastasizing case was administered etoposide-methotrexate-
actinomysinD /etoposide-cisplatin chemotherapy and
responded well 6. The present case showed no signs of
metastasis for 6 months, after which she was lost in the follow
In conclusion, chorangiocarcinoma is a rare entity with a
handful of cases reported in the literature. Although localized
and non-infiltrative, these cases can metastasize, warranting
close follow up. Differentiation of chorangiocarcinoma
from the more common intraplacental choriocarcinoma
is imperative to avoid an unnecessary aggressive treatment
CONFLICT of INTEREST
The authors declare no conflicts of interest.
Concept: NK,PT, PK, Design: NK, PK, Data collection or
processing: NS, PT, NK, Analysis or Interpretation: NK,
Literature search: NS, Writing: NS, PT, Approval: NK.
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