Primary Gastric Choriocarcinoma
A Case Report and Review of the Literature
Zhi Liu, MD, PhD; Jose L. Mira, MD; Jose C. Cruz-Caudillo, MD
● Choriocarcinoma is a rapidly invasive, widely metastatic
human chorionic gonadotropin (HCG)–producing neo-
plasm, usually intrauterine and gestational. Primary gastric
choriocarcinoma is very rare, and its pathogenesis is still
uncertain. We report a case of primary gastric choriocar-
cinoma associated with adenocarcinoma in a 36-year-old
woman. The patient presented with gastrointestinal bleed-
ing and a gastric mass clinically suspicious of gastric ade-
nocarcinoma. Histopathologic evaluation proved the tu-
mor to be a choriocarcinoma, with a minor component of
a poorly differentiated adenocarcinoma. The patient was
treated with a standard nongestational choriocarcinoma
chemotherapy regimen. An impressive initial response was
evidenced by clinical reduction of the tumor volume and
drop of the serum b-HCG levels after the first cycle. How-
ever, the tumor rapidly recurred in the abdomen and dis-
seminated to the lungs, which were documented by new
elevation of serum b-HCG levels and computed tomo-
graphic scans despite continuing with 3 more cycles of
chemotherapy. The patient died 6 months after diagnosis.
(Arch Pathol Lab Med. 2001;125:1601–1604)
C horiocarcinoma is a rapidly invasive, widely metastatic
human chorionic gonadotropin (HCG)–producing
neoplasm, usually intrauterine and gestational. Almost all
remaining choriocarcinomas arise in ectopic pregnancies,
the gonads, or midline locations (mediastinum, retroperi-
toneum, and pineal gland) as a teratoma.1 Only rarely
have the neoplasms been reported in parenchymal organs,
such as the prostate, liver, lung, urinary bladder, nose, and
gastrointestinal tract.2 Primary gastric choriocarcinoma is
very rare, and its pathogenesis is still uncertain.
We report a case of primary gastric choriocarcinoma as-
sociated with adenocarcinoma in a 36-year-old women
and review the literature published on the clinicopatho-
logic findings and pathogenesis of this neoplasm.
REPORT OF A CASE
A 36-year-old Latin American woman presented to Texas Tech
University Medical Center, Lubbock, Tex, with chief complaints
of abdominal, chest, and back pain for 2 weeks, decreased ap-
Accepted for publication June 1, 2001.
From the Departments of Pathology (Drs Liu and Mira) and Internal
Medicine (Dr Cruz-Caudillo), Texas Tech University, Health Science
Center, Lubbock, Tex.
Reprints: Jose L. Mira, MD, Department of Pathology and Laboratory
Medicine, Texas Tech University Health Sciences Center, 3601 Fourth
St, Lubbock, TX 79430 (e-mail: pthjlm@ttuhsc.edu).
Arch Pathol Lab Med—Vol 125, December 2001
petite, weakness, and severe fatigue. Her initial evaluation dem-
onstrated melena and extremely low hemoglobin and hematocrit
levels (3.8 g/dL and 11.4%, respectively). The patient was ini-
tially admitted to the medical intensive care unit, where she had
a full workup and was found to have a gastric mass. Esophago-
gastroduodenoscopy revealed a large, fungating, noncircumfer-
ential mass with necrotic areas and stigmata of recent bleeding
in the anterior wall of the gastric body. Endoscopic biopsy spec-
imens from the tumor mass were obtained. Subsequent comput-
ed tomographic (CT) scan of the pelvis and abdomen revealed
that the mass was arising from the stomach antrum and extended
to the lesser sac and also involved the transverse colon. On her
initial evaluation, the patient also had an enlarged uterus, and
although she had undergone bilateral tubal ligation about 6 years
ago, a vaginal ultrasound was performed to rule out intrauterine
pregnancy. No evidence of such a condition was identified. Serum
b-HCG levels, however, were positive, with a quantitative value
of 68 mIU/mL. The patient had been previously healthy with a
medical history unremarkable for any significant medical illness.
Her 3 full-term pregnancies were followed by normal deliveries,
and she had no history of abortuses. She denies alcohol or to-
bacco abuse.
The patient underwent a transabdominal CT-guided true-cut
needle biopsy of the intraabdominal mass, which extended from
the stomach wall to the abdominal wall. A CT scan of her head
and chest were negative for metastatic disease. The remainder of
her workup revealed slightly elevated serum carcinoembryonic
antigen and normal a-fetoprotein levels. The patient was evalu-
ated by the surgical oncologist who considered the mass to be
unresectable. Chemotherapy was then initiated consisting of cis-
platin, etoposide, and bleomycin. The patient responded well to
the first cycle of therapy evidenced by the shrinkage of the tumor
mass and decreased b-HCG level. Despite an impressive initial
clinical response, after 3 chemotherapy cycles, CT scans of the
chest, abdomen, and pelvis were performed, which showed pro-
gression of disease and spread to the colon, stomach, and lungs.
The patient was then given one cycle of salvage chemotherapy
consisting of vinblastine, ifosfamide, and cisplatin without any
response. It was explained to the patient and family that further
chemotherapy would probably be ineffective and that other al-
ternative regimens of chemotherapy would be most likely unsuc-
cessful. It was decided not to proceed with further chemotherapy
because of progressive disease of tumor unresponsive to treat-
ment. The patient died of tumor progression at home, and an
autopsy was not performed.
PATHOLOGIC FINDINGS
Histologic evaluation of the minute, endoscopically ob-
tained gastric biopsy specimens demonstrated almost
complete replacement by a malignant neoplasm, charac-
terized by solid tumor nests and trabeculae formed by
large polyhedral tumor cells with abundant foamy baso-
philic cytoplasm and large, round hyperchromatic nuclei,
Primary Gastric Choriocarcinoma—Liu et al 1601
Figure 1. Solid tumor nests of large polyhedral tumor cells with abundant foamy basophilic cytoplasm and large, round hyperchromatic nuclei,
some exhibiting prominent single nucleoli (cytotrophoblasts). Scattered around and frequently surrounding the tumor cell nests were large, mul-
tinucleated, pleomorphic tumor cells (syncytiotrophoblasts). Only occasional, poorly formed glandular structures were focally identified (hema-
toxylin-eosin, original magnification 3200 [a] and 3400 [b]).
Figure 2. The tumor cells exhibited strong positive reaction with (a) pan-cytokeratin AE1 and AE3 (original magnification 3200 ) and (b) polyclonal
carcinoembryonic antigen antibodies (original magnification 3200).
Figure 3. a, The larger, pleomorphic and peripheral syncytiotrophoblastic cells exhibited a strong positive reaction with antibodies to b-HCG
(original magnification 3400). b, Rare tumor cells exhibit mucicarmine-positive intracytoplasmic material suggestive of glandular differentiation
(original magnification 3200).

some exhibiting prominent single nucleoli (cytotropho-
blasts). Some of the cells exhibit intensely eosinophilic, ke-
ratinous-like cytoplasm. Scattered around and frequently
surrounding the tumor cell nests were large, multinucle-
ated, pleomorphic tumor cells (syncytiotrophoblasts) (Fig-
1602 Arch Pathol Lab Med—Vol 125, December 2001
ure 1, a and b). Numerous typical and atypical mitotic
figures were identified. The tumor exhibits prominent vas-
cular invasion with frequent tumor thrombi and tumor
cells lining vascular spaces. Extensive tumor necrosis,
hemorrhage, and vascular thrombosis were also seen.
Primary Gastric Choriocarcinoma—Liu et al
Only occasional poorly formed glandular structures were
focally identified. Histologic examination of the transab-
dominal true-cut needle biopsy specimen revealed similar
features.
Immunohistochemical studies were performed on for-
malin-fixed, paraffin-embedded tissue sections from both
tumor biopsy specimens. The tumor cells exhibited strong
positive reaction with pan-cytokeratin AE1 and AE3 and
polyclonal carcinoembryonic antigen antibodies (Cell
Marque, Austin, Tex) (Figure 2, a and b). Equally strong
but focally positive reaction of tumor cells was seen with
B72.3 and epithelial membrane antigen antibodies (Cell
Marque). Some tumor cells, especially around tumor nests,
exhibited a strong positive reaction with antibodies to b-
HCG (BioGenex, San Ramon, Calif). Much stronger and
more diffuse immunostaining of tumor cells with b-HCG
antibodies was demonstrated in the tissue obtained by the
transabdominal true-cut needle biopsy specimens (Figure
3, a) compared with the endoscopically obtained gastric
biopsy specimens. Rare periodic acid–Schiff, postdiastase
digestion periodic acid–Schiff, and mucicarmine-positive
intracytoplasmic material (Figure 3, b) was demonstrated
in some tumor cells, which suggested glandular differ-
entiation.
The histologic, immunohistochemical, and histochemi-
cal features of this malignant neoplasm, along with the
elevated serum levels of b-HCG, were consistent with a
diagnosis of choriocarcinoma. The failure to identify an
intrauterine or extrauterine gestational trophoblastic tu-
mor or a nongestational gonadal or extragonadal germ cell
tumor excluded the possibility of metastatic disease in the
stomach. Only rare focal areas of the tumor exhibited ev-
idence of glandular differentiation, and although the bi-
opsy specimen may not be representative of the entire tu-
mor, it appeared that the major component of this tumor
was in fact choriocarcinoma. It was concluded that the tu-
mor represented a primary gastric choriocarcinoma with
a small component of poorly differentiated adenocarci-
noma.
COMMENT
Primary gastric choriocarcinomas are rare. They can
present in pure form, accompany adenocarcinoma, or be
associated with nontrophoblastic gonadal tissue.3,4 These
tumors may contain an undifferentiated component or
show a transition between adenocarcinoma and chorio-
carcinoma. In the study by Jindrak et al,1 the average age
of the patients with gastric choriocarcinoma was 52.6 years
in men and 60.9 years in women. The younger age and
numerical preponderance of men (17:10) may simply re-
flect reluctance on the part of pathologists to accept (and
consequently report) a primary extragenital choriocarci-
noma in women of childbearing years.1
The clinical presentation of gastric choriocarcinoma is
similar to that of gastric adenocarcinoma and includes ab-
dominal pain, anorexia, weight loss, nausea, and vomit-
ing; however, it is more frequently a cause of gastrointes-
tinal bleeding and may have some hormonal effects, such
as gynecomastia, precocious puberty, and vomiting resem-
bling that seen with pregnancy. Both radiologic and en-
doscopic evaluation demonstrates a bulky, intraluminal le-
sion that resembles gastric adenocarcinoma. Pathological-
ly, the endoscopic biopsy specimen usually reveals the ma-
lignant nature of the tumor, although precise histologic
Arch Pathol Lab Med—Vol 125, December 2001
characterization of the neoplasm may require large tissue
samples, which can only be obtained by surgery.5
Primary gastric choriocarcinoma is a rapidly growing
neoplasm, and untreated patients have an average surviv-
al of only several months.5 A treatment of choice has not
been established, because few experiences have been re-
ported. Current treatment methods include surgical inter-
vention with combined chemotherapy. Radiotherapy has
not been shown to improve the prognosis for this disease.5
Regarding the pathogenesis of primary gastric chorio-
carcinoma, several theories have been proposed, including
development from an underlying gastric teratoma, de-
layed metastasis from an intrauterine primary lesion, and
emergence from putative displaced gonadal anlage. The
most plausible explanation for the pathogenesis of gastric
choriocarcinoma was proposed by Pick in 1926. Based on
the observation that many cases of primary gastric chorio-
carcinoma were found in coexistence with an adenocar-
cinoma, in some of which a transition from adenocarci-
noma to choriocarcinoma had been demonstrated, he pro-
posed that the trophoblastic elements found in primary
gastric choriocarcinoma developed from dedifferentiation
of a poorly differentiated adenocarcinoma. A pure chorio-
carcinoma would then arise by overgrowth and elimina-
tion of the original adenocarcinoma.5 The possibility that
the normal gastric mucosa undergoes trophoblastic meta-
plasia preceding neoplastic transformation must also be
considered. Thus, not only do gastric choriocarcinomas
show similarity to gastric adenocarcinomas in age and sex
distribution and increased frequency in Japan,6 but also
choriocarcinomas arising in other organs such as bladder7
and lung display adjacent carcinoma peculiar to the in-
volved organ.
Although many investigators accepted the dedifferen-
tiation theory, many puzzling questions remain, such as
the role of HCG-producing cells normally present in the
gastric mucosa.8 It is possible that some pure choriocar-
cinomas originate de novo in HCG-producing cells of the
normal gastric mucosa without a preceding adenocarci-
noma. Yakeishi et al8 reported immunohistochemical evi-
dence of HCG-positive cells in the normal gastric mucosa
and in adenocarcinomas and choriocarcinomas in various
proportions and intensities. Because somatic cells remain
the entire genome for an organism, with differentiation
depending on repression or expression of various groups
of genes, it is conceivable that, under the profound chang-
es that occur during carcinogenesis, the gastric mucosal
cells directly develop the morphologic and functional
characteristics of a choriocarcinoma.9
It is therefore conceivable that choriocarcinomas occur
primarily in the stomach most commonly as a result of a
dedifferentiation mechanism from an underlying, poorly
differentiated adenocarcinoma, in a manner similar to
what has been demonstrated to occur in other mesenchy-
mal and epithelial tumors from different organs. The more
uncommon pure choriocarcinomas may be explained by
overgrowth of the adenocarcinoma by the choriocarcino-
ma and alternatively by de novo choriocarcinomas arising
in HCG-producing cells normally present in the stomach.
The significance of elevated serum b-HCG levels and/
or immunoreactivity of b-HCG antibodies in tumor cells
is still controversial. It has been reported that patients
with gastric adenocarcinoma and high levels of HCG in
the serum or a high density of HCG-positive cells in the
tumor tissue had a poorer prognosis or a shorter survival
Primary Gastric Choriocarcinoma—Liu et al 1603
time.10 However, other studies proposed that the existence
of b-HCG–positive cells in gastric adenocarcinomas has
no prognostic significance.8
It appears from these and other studies that the pres-
ence of an elevated serum b-HCG level and/or the pres-
ence of b-HCG immunoreactive tumor cells, independent
of intensity or density, in an otherwise routine gastric ad-
enocarcinoma is a common finding and does not have any
diagnostic or prognostic significance, since these adeno-
carcinomas behave according to their grade, stage, and
histologic type in a similar fashion to their contra part
without b-HCG–producing tumor cells. These tumors are
adenocarcinomas and in no way should be interpreted as
adenocarcinomas with choriocarcinoma differentiation.
Follow-up with evaluation of serum b-HCG levels, how-
ever, may be helpful in evaluating response to treatment
and/or recurrent disease.
Gastric choriocarcinomas, on the other hand, are rare
tumors that are characterized by the presence of a double
cell population with cytologic, histologic, architectural,
and immunohistochemical features similar to those seen
in gestational choriocarcinomas, whether presenting in its
pure form or mixed with an adenocarcinoma component.
Most reported gastric choriocarcinomas, including our
own case, exhibited a component of poorly differentiated
adenocarcinoma. This component may be almost com-
pletely overgrown by the choriocarcinoma or in rare cases
be more easily recognized. Therefore, the diagnosis of cho-
riocarcinoma should not be made merely on the basis of
the presence of b-HCG immunoreactive cells, but these
cells need to be present in the background of a tumor that
is cytologically, histologically, and biologically consistent
with the better known gestational choriocarcinoma.
Although the number of cases of well-documented gas-
tric choriocarcinomas reported to date is small, it appears
that these tumors behave more like gestational or germ
cell choriocarcinomas with rapid and extensive hematog-
enous dissemination as opposed to the preferred lym-
phatic way of adenocarcinomas. Metastatic disease fre-
quently contains pure choriocarcinoma, although mixed
chorioadenocarcinoma metastases have also been seen.
Mortality is high and survival short, with most patients
dying of disease within 6 months. Little is known about
specific treatment modalities for gastric choriocarcinoma.
Although chemotherapy seems to be the treatment of
choice, chemotherapy regimens used and proved success-
ful for gestational choriocarcinoma had not been effective
in gastric choriocarcinoma, in a way similar to nongesta-
1604 Arch Pathol Lab Med—Vol 125, December 2001
tional choriocarcinomas of either gonadal or extragonadal
origin.
Our case fits the clinical, cytologic, histologic, and im-
munohistochemical criteria for a diagnosis of primary gas-
tric choriocarcinoma. The patient was young and present-
ed with gastrointestinal bleeding and a gastric mass clin-
ically suggestive of gastric adenocarcinoma. Histopatho-
logic evaluation proved the tumor to be a choriocarcinoma
with a minor component of a poorly differentiated ade-
nocarcinoma consistent with the dedifferentiation theory
of histogenesis. The patient was treated with 4 cycles of a
standard nongestational choriocarcinoma chemotherapy
regimen with an impressive initial response evidenced by
clinical reduction of the tumor volume and drop of the
serum b-HCG levels from 131 mIU/mL at the beginning
of chemotherapy to an all time low of 9 mIU/mL after
her first cycle. However, the tumor rapidly progressed and
disseminated in a hematogenous pattern of metastatic dis-
ease despite continuing with 3 more cycles of chemother-
apy. Metastatic disease to the lungs and colon was docu-
mented by new elevation of serum b-HCG levels and CT
scans. Chemotherapy was then stopped, and the patient
died at home 6 months after initial diagnosis. Unfortu-
nately, an autopsy was not performed, so the final tumor
extent and histologic features could not be evaluated.
The report of this case of primary gastric choriocarci-
noma is important to add data to the literature regarding
this rare condition, to better understand its histopatho-
genesis, to help others in its diagnosis and management,
and eventually to improve patient treatment and progno-
sis.
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Primary Gastric Choriocarcinoma—Liu et al