Primary tubal choriocarcinoma

Choriocarcinoma is one of the most serious forms of gestational trophoblastic tumor. It is a malignant tumor from the epithelium of the chorionic villi. The most frequent location site is the uterus. Associated with ectopic pregnancy, it is extremely rare and in general, very aggressive. In 75% of the cases, it items from distant metastasis; therefore, a histological examination of the tubes must be performed in all ectopic pregnancies. Our patient was a 33-year-old woman who was admitted to emergency room (ER) with an intense pain in the right, iliac cavity, and limited genital bleeding. During the exploration, there was abdominal pain, with doubtful signs of peritoneal irritation. The vaginal ultrasound offered an image that was compatible with an extra uterine pregnancy in the left appendages. At emergency, right salpingectomy was performed via laparotomy. The patient was treated with polychemotherapy and contraceptives for a year, with no recurrence of the disease. Control follow-up was performed using beta-human chorionic gonadotropin (HCG) testing on a weekly basis during the first month and then bi-monthly during the first year of follow-up.     

The role of surgery in the management of gestational trophoblastic disease

Between November 1967 and December 1994, 242 patients with gestational trophoblastic disease (GTD) were treated with chemotherapy by the Gynecology Service of Memorial Hospital. Eighty-seven of the patients (35.9%) underwent at least one major operation during the course of their illness. Twenty-six patients underwent two major operations, and in five patients, three major operations were performed, for a total of 118 procedures. The most frequent procedures were: hysterectomy, 56 (47.4%); hysterotomy, 15 (12.7%); thoracotomy, 13 (11%); and craniotomy, 5 (4.2%). Twenty-nine additional procedures ranging in complexity from oophorectomy to segmental liver resection were also performed. Twenty-nine operations (24.5%) were considered to be beyond the scope of most gynecologic surgeons. The overall complete remission rate for 242 patients was 90.4%. The rate for patients who underwent a major surgical procedure was 79.3% compared to 96.7% for patients whose treatment was with chemotherapy alone.
The data demonstrate that the integration of surgery in the management of GTD patients often requires a multidisciplinary approach that in many cases can best be achieved at specialized treatment centers.     

Enhancement of immunogenicity of Jeg3 cells by ectopic expression of HLA-A*0201 and CD80

PROBLEM: The choriocarcinoma cell line Jeg3 suppresses immunity in vitro by secretion of soluble factors like leukemia inhibitory factor suppressing leukocyte activation. The cells lack expression of classical human leukocyte antigen (HLA)-A and -B alleles but express some HLA-C, and non-classical HLA-G and -E. Upon binding to killing inhibitory receptor on natural killer (NK) cells, HLA-G prevents activation of cytolytic activity. We investigated whether Jeg3 cells are capable of immune stimulation after complementation with classical HLA and T cell costimulatory signal CD80. METHOD OF STUDY: Jeg3 cells were transduced to express HLA-A*0201 and/or CD80. Parental Jeg3 or transfectants Jeg3-A2, Jeg3-CD80 or Jeg3-CD80-A2 were used to stimulate allogeneic resting and activated peripheral blood lymphocytes (PBL). The different cell lines were loaded with a HLA-A2-restricted Epstein-Barr virus (EBV) recall antigen peptide epitope and antigen presenting ability was examined. T cell lines specific for Jeg3 and transfectants were generated from HLA-A2 matched and nonmatched donors and compared for expansion, phenotypes and cytolytic activity. RESULTS: While all Jeg3 cell lines induced only marginal proliferation of resting T cells, phytohemagglutinin (PHA)-activated T cells were stimulated by CD80 or CD80-A2 expressing Jeg3. Only the transfectant Jeg3-CD80-A2 was capable of specific T cell stimulation by EBV recall antigen presentation. T cell lines of HLA-A2 non-matched donors stimulated with the Jeg3 transfectants showed significant expansion only when HLA-A2 and the costimulus CD80 were present. T cells from HLA-A2 positive donors did not expand significantly or differentially. No NK cells grew under any condition. In Jeg3-CD80-A2 stimulated T cells lines CD8+ cells expanded preferentially. These T cells exerted cytolytic activity toward all Jeg3 cell lines. CONCLUSION: Our data suggest that, in spite of immunosuppressive mechanisms, proliferative and cytolytic T cell responses are induced by Jeg3 cells when classical HLA- and/or costimulatory signals are present on the cells.     

Malignant ovarian mixed germ cell tumour: a rare combination

Ovarian germ cell tumours are very rare and affect mainly young girls and women. Due to this, the conservation of reproductive potential is of great concern. One of the most remarkable advances in oncology is in the treatment of malignant ovarian germ cell tumours. Two histological groups are distinguished: dygerminomas, equivalent to testicular seminomas, and non-dysgerminomatous tumours. We report a case of a 30-year-old nulliparous woman who presented with persistent per vaginal bleeding and was found to have a malignant mixed germ cell tumour comprising of both embryonal carcinoma and choriocarcinoma.     

Primary choriocarcinoma and human chorionic gonadotrophin‐producing giant cell carcinoma of the lung: are they independent entities?

AIMS: Human chorionic gonadotrophin (hCG) is a useful marker for chorionic proliferative disorders, such as choriocarcinoma. Although hCG synthesis in lung cancers is frequent, primary pulmonary choriocarcinoma (PCC) is rare. To clarify the differences between primary choriocarcinoma and hCG-producing giant cell carcinoma (GCC) of the lung, we compared the clinicopathological and immunohistochemical findings of these tumours. METHODS AND RESULTS: Three patients, one with PCC and two with hCG-producing GCC, were included in this study. They were all middle-aged men and habitual smokers. The growth of these tumours and the progression of the clinical courses were extremely rapid, and the patients all died within 8 months after the pulmonary tumours were found. Haemorrhagic appearance was a common macroscopic feature of the specimens obtained. Microscopically, both types of tumours mainly consisted of atypical polygonal cells. While PCC contained many syncytial trophoblast-like multinucleated cells that had strong immunoreactivity for anti-hCG, such cells were relatively few in hCG-producing GCC. These histological and immunohistochemical findings reflected the serum test result for hCG, which was higher in the case of PCC. CONCLUSIONS: There are a few differences between PCC and hCG-producing GCC, as described above. Reliable distinction between them seems to be difficult for pathologists and worthless for clinicians.     

Placental site trophoblastic tumor of the mediastinum

Choriocarcinoma has been described as the most frequent subtype of mediastinal germ cell tumors showing trophoblastic differentiation. We report a unique case of a placental site trophoblastic tumor, which developed in the mediastinum of a 14-year-old boy 2 years after the resection of a mature teratoma. The recurrent tumor was composed of a grossly hemorrhagic and necrotic mass. Histologically, diffusely infiltrating large polygonal cells with focal nodular growth and a teratomatous part containing mature intestinal, respiratory, and squamous epithelium with adjacent cutaneous adnexal structures were found. The typical morphologic features included vessel wall infiltration by the neoplastic cells with fibrinoid deposits and geographic necroses within the tumor masses. Characteristic diffuse positivity for melanoma cell adhesion molecule and human leucocyte antigen G was found on immunohistochemical investigation, confirming the diagnosis of placental site trophoblastic tumor. The patient died 1 year later after polychemotherapy. The outcome of this rare tumor is similar to the reported poor clinical outcome in patients with mediastinal choriocarcinomas.     

Intraplacental choriocarcinoma with fetomaternal transfusion

Intraplacental choriocarcinoma is very rare, and is usually found only after maternal and fetal metastatic disease is identified. The purpose of this case report is to review the incidence and findings of intraplacental choriocarcinoma. A term placenta was investigated because the newborn was born with severe anemia (Hb 3.0 g/dL). A 2 cm nodule was noted on the surface of the amniotic membrane and grossly resembled an infarction. The tumor was examined microscopically with immunohistochemical staining for the alpha- and beta-human chorionic gonadotropin (alpha-hCG, beta-hCG) subunits, human placental lactogen (hPL) and Ki-67. Microscopically, the tumor consisted of necrotic areas with proliferation of atypical trophoblastic cells and destruction of the villi and capillaries. The cells were positive for the alpha-hCG, beta-hCG subunits, hPL and Ki-67, consistent with intraplacental choriocarcinoma. The mother and newborn were investigated for the presence of metastatic disease. Computed tomography scans and magnetic resonance imaging of the mother and infant were negative for metastatic disease. Choriocarcinoma, limited only to the placenta with no evidence of metastatic disease is very rare. Primary intraplacental choriocarcinoma may frequently be overlooked or missed, and choriocarcinoma may possibly arise in the placenta more often than in retained or persistent trophoblast following pregnancy.     

Intraplacental Choriocarcinoma Associated with Viable Pregnancy: Pathologic Features and Implications for the Mother and Infant

Choriocarcinoma arising in the placenta, or intraplacental choriocarcinoma, has seldom been reported, particularly in the absence of maternal metastases. Reluctance to diagnose choriocarcinoma in the presence of chorionic villi can delay diagnosis; however, timely diagnosis of choriocarcinoma is prognostically important, both for the mother and infant. We report the clinicopathologic findings in five mothers and infants in whom choriocarcinoma was identified in the placenta. None of the mothers had a history of gestational trophoblastic disease in previous pregnancies. Three placentas were similar with a single small lesion grossly suggesting a small infarct; microscopically these consisted of infarcted areas surrounded by choriocarcinoma. These three mothers were unusual in that none had metastatic choriocarcinoma; two were treated with chemotherapy and remained disease-free; the third was lost to follow-up shortly following delivery. The remaining two mothers had known pulmonary metastases at time of delivery. One of these latter two placentas contained a large marginal lesion microscopically identified as choriocarcinoma. The fifth placenta had rare microscopic foci of choriocarcinoma, and sheets of necrotic choriocarcinoma were identified in “blood clot” submitted with the placenta. In four of the five cases the choriocarcinoma appeared to be arising from otherwise normal chorionic villi, and in no case was there invasion of the villous stroma. All of the infants survived, and none had evidence of choriocarcinoma. These cases support the concept that choriocarcinoma associated with otherwise normal pregnancy arises in the placenta and may be more common than reported. Received August 11, 1997; accepted December 8, 1997.