Case 1 -
Laura W. Lamps
University of Arkansas for Medical Sciences
Little Rock, AR
Click on each slide thumbnail image for an enlarged view
A 35-year-old female presented to surgery clinic following two
episodes of severe upper gastrointestinal bleeding. She denied significant weight loss, nausea,
vomiting, or epigastric pain. Past medical history was significant for previous cholecystectomy,
tonsillectomy, appendectomy, and two unremarkable pregnancies. Initial laboratory evaluation revealed
mild anemia but no other abnormalities. Endoscopy was performed, and a 4 cm mass was found in the
gastric cardia; biopsy revealed poorly differentiated carcinoma. The patient was scheduled for
gastrectomy. On the day before surgery, a routine pre-operative pregnancy test was positive. Subsequent
serum ß-HCG testing was obtained, yielding a ß-HCG level of 3,473 mIu/ml, consistent with a 4-week
gestation. The patient denied pregnancy, as she was compliant on her oral contraceptive pills and had no
physical signs of pregnancy. In addition, transvaginal pelvic ultrasound showed no intra-uterine
gestation, nor evidence of ectopic pregnancy or adnexal masses. Serial ß-HCG measurements over the next
week did not change significantly. The patient ultimately underwent surgery and an H&E section of
the subtotal gastrectomy specimen is submitted for review.
Case 1 - Figure 1 - Low power view of the gastric mass shows a highly vascular, necrotic, hemorrhagic tumor
Case 1 - Figure 2 - Clusters of large tumor cells are seen within a background of dilated vessels and fibrinous debris.
Case 1 - Figure 3 - The majority of the tumor cells had bubbly purple cytoplasm with giant, bizarre nuclei.
Grossly, the partial gastrectomy specimen contained a 4 cm firm, exophytic mass in the gastric cardia,
with central ulceration and a beefy red color. The cut surface was also beefy red with numerous areas of
hemorrhage and necrosis. One of four perigastric lymph nodes was grossly positive, consisting of a 3.5
cm tumor deposit with necrosis and hemorrhage.
Microscopically, sections showed a very vascular, poorly differentiated carcinoma with extensive
hemorrhage and necrosis. The tumor showed focal areas of malignant glandular differentiation. The
majority of the tumor consisted of sheets of large, bizarre tumor cells, with cytotrophoblastic and
syncytiotrophoblastic differentiation. Extensive vascular invasion was present. A focal in situ
component was found at the periphery of the invasive tumor. The tumor filled the gastric submucosa but
did not involve the muscularis propria.
Immunostains showed the entire tumor to be strongly cytokeratin positive. Strong immunoreactivity for
ß-HCG was seen in the trophoblastic cells.
All surgical margins were negative, and one of four lymph nodes was replaced by metastatic
choriocarcinoma. However, a CT scan showed lung nodules, and needle biopsy of these lesions revealed
them to be morphologically similar to the gastric primary. Serial serum ß-HCG levels obtained after
surgery showed a significant decline, down to <0.5 mIu/ml in November of 2003. The patient returned
to her home town for postoperative chemotherapy.
Although primary gastric choriocarcinomas are quite rare,
the stomach is one of the most common sites of extragonadal, nongestational trophoblastic tumors. The
majority of cases are composed of a mixture of adenocarcinoma and choriocarcinoma; less than 25% of cases
are pure choriocarcinoma. Rare cases of typical gastric adenocarcinoma show choriocarcinomatous elements
in only in metastatic lesions.
Pathogenesis. Whether or not these neoplasms represent unusual patterns of differentiation within
adenocarcinomas, rather than true germ cell tumors, is a subject of controversy. Some authors have
proposed a theory of "retrodifferentiation" to explain trophoblastic elements in the stomach. This
theory is based on the concept of pluripotential tumor cells that, under certain poorly understood
circumstances, can differentiate in unusual directions. A small number of studies have also shown that
cells in the neck of normal antral glands, and within metaplastic foci in the stomach, express HCG, and
HCG expressing cells lacking trophoblastic morphology have also been demonstrated in typical gastric
adenocarcinomas. Therefore, there appears to be a group of HCG-producing cells in the normal stomach, as
well as in some non-neoplastic processes and typical adenocarcinomas. For these reasons, most authors
favor the concept of unusual differentiation within adenocarcinoma over that of true gastric germ cell
Clinical Features. Gastric choriocarcinoma occurs in adult patients with the same age distribution as
typical gastric adenocarcinoma and either sex may be affected. The presenting signs and symptoms are
also similar, including epigastric pain, weight loss, anemia, and melena; upper GI hemorrhage (as in this
case) is common. Some cases (such as this one) are accompanied by elevated serum ß-HCG; in these cases,
patients may be followed for postoperative recurrence by serum ß-HCG measurements.
Gastrectomy with lymph node dissection, followed by postoperative chemotherapy, is the treatment of
choice. If the tumor is metastatic at time of surgery, partial gastrectomy is sometimes performed for
palliation and control of bleeding. The number of reported cases of choriocarcinoma is insufficient to
perform a meaningful survival analysis as compared to typical gastric adenocarcinoma, but most patients
have a very poor prognosis with early metastases to lung, liver, and regional nodes. Some authors have
noted a tendency for the typical adenocarcinomatous component to metastasize to lymph nodes, while the
choriocarcinomatous component metastasizes via hematogenous routes.
Pathologic Features. Grossly, gastric choriocarcinomas are exophytic.
They are generally more beefy red and hemorrhagic than typical gastric adenocarcinomas, given their
striking vascularity. Grossly visible necrosis is also common.
Histologically, there is a mix of malignant cytotrophoblast and syncytiotrophoblast, generally admixed
with areas of typical glandular differentiation. The cytotrophoblastic elements have clear cytoplasm and
more distinct cell boundaries, whereas the syncytiotrophoblastic cells have bubbly purple or eosinophilic
cytoplasm and are often multinucleate. Intratumoral hemorrhage, necrosis, and vascular invasion are
cell types are strongly cytokeratin positive. Trophoblastic tumor cells typically show strong
immunoreactivity with HCG and weaker immunoreactivity for human placental lactogen (HPL).
The major entity in the differential diagnosis is metastatic trophoblastic tumor from other sites,
particularly gonadal or gestational primaries in women of reproductive age.
- Gastric choriocarcinomas are rare, but the stomach is one of the most common sites of extragonadal, nongestational trophoblastic tumors.
- These tumors are most often a mixture of choriocarcinoma and typical adenocarcinomatous elements.
- Immunohistochemistry shows immunoreactivity with cytokeratin, HCG, and sometimes human placental lactogen.
- Early lymph node and hematogenous metastases are common, and prognosis is poor.
- Tumor recurrence may be followed by serum ß-HCG levels.
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