—  SPECIALTY CONFERENCE  —

Gastrointestinal Pathology

Case 1 - Gastric Choriocarcinoma

Laura W. Lamps
University of Arkansas for Medical Sciences
Little Rock, AR


Click on each slide thumbnail image for an enlarged view
Clinical History
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.


Case 1 - Figure 4 - Small foci showed typical glandular differentiation.
Case 1 - Figure 5 - A large regional lymph node contained metastatic choriocarcinoma.
Case 1 - Figure 6 - ß-HCG immunostaining is strongly positive within trophoblastic tumor cells.

Pathologic Features:
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.

Diagnosis
Gastric Choriocarcinoma

Hospital Course
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.

Discussion
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 primary.

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 common.

Differential Diagnosis
All trophoblastic 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.

Summary

  1. Gastric choriocarcinomas are rare, but the stomach is one of the most common sites of extragonadal, nongestational trophoblastic tumors.
  2. These tumors are most often a mixture of choriocarcinoma and typical adenocarcinomatous elements.
  3. Immunohistochemistry shows immunoreactivity with cytokeratin, HCG, and sometimes human placental lactogen.
  4. Early lymph node and hematogenous metastases are common, and prognosis is poor.
  5. Tumor recurrence may be followed by serum ß-HCG levels.

References

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