Serum lactic dehydrogenase: a tumor marker of ovarian dysgerminoma in a female pseudohermaphrodite

A case of a female pseudohermaphrodite who presented with a large ovarian dysgerminoma is reported. Preoperatively, markedly elevated levels of serum lactic dehydrogenase (LDH) were noted. After complete excision of the tumor, serum levels of LDH returned to normal levels. Only five other cases of dysgerminoma with elevated serum LDH have been reported. In each case, as in the present one, LDH levels were significantly higher than in any other ovarian tumor. LDH can be considered as an enzymatic tumor marker of ovarian dysgerminoma, for diagnosis, prognosis, and surveillance.     

Serum lactic dehydrogenase and its isoenzymes in patients with ovarian dysgerminoma

Lactic dehydrogenase (LDH) is a glycolytic enzyme that may be elevated in the serum of patients with gonadal and extragonadal germinomas. In this report, a case of unilateral ovarian pure dysgerminoma with remarkably elevated levels of serum LDH is presented. After complete excision of the tumor, serum LDH levels promptly returned to normal levels. Although an electrophoretic pattern of serum LDH isoenzymes was within normal limits pre-operatively, an increase in LDH-1 and 2 was found 1 week after operation. Seventeen additional examples of ovarian dysgerminomas with elevated serum LDH levels have been reported in the English literature including five cases who had high levels of two fast fractions of LDH. These data suggest that serum LDH levels and its isoenzymes pattern are useful tumor markers for diagnosis and post-therapy surveillance in patients with ovarian dysgerminomas.     

Analysis of serum CA125, CEA, AFP, LDH levels and LDH isoenzymes in patients with ovarian tumors--correlation between tumor markers and histological types of ovarian tumors

Serum CA125, CEA, AFP, LDH levels and LDH isoenzymes were analyzed in ovarian tumor patients, who were treated at Kyoto University Hospital. CA125 was positive in 10/16 (62.5%) cases of common epithelial carcinoma, especially 100% positive in serous carcinoma, but was negative in mucinous tumors. CA125 was also negative in patients with germ cell and sex cord stromal tumors. CEA was positive in 13/32 (40.6%) cases of epithelial carcinoma, most frequently elevated in patients with mucinous carcinoma, pseudomyxoma peritonei, and Krukenberg tumor. AFP was positive only in those with endodermal sinus tumors. LDH was elevated in 16/39 (41%) cases of epithelial carcinoma, but was not specific for histological types. In contrast, all 8 cases of dysgerminoma, 1 of immature teratoma and 2 of endodermal sinus tumor showed extremely elevated LDH levels. Moreover, the normal pattern or deviation to H subunit of LDH isoenzymes was seen in such cases of germ cell tumor, while deviation to M subunit was noted in epithelial and metastatic tumor patients. These data indicate that each parameter is useful as a tumor marker for the specific histological type of ovarian tumor; CA125 for non-mucinous epithelial carcinoma, CEA for mucinous tumor and Krukenberg tumor, AFP for yolk sac tumor, LDH and LDH isoenzymes for dysgerminoma and other solid germ cell tumors. In addition, preoperative diagnosis of histological types of ovarian tumors may be possible by combining these tumor markers.     

Outcome and prognostic factors in ovarian germ cell malignancies

OBJECTIVES: This study was undertaken to investigate the outcome and prognostic factors in patients with ovarian germ cell malignancies (OGCMs). METHODS: A total of 93 patients with OGCMs were retrospectively reviewed, among whom 84 patients had primary treatment at Chang Gung Memorial Hospital (CGMH) between 1984 and 2003. The other nine patients were primarily treated outside and referred for follow-up (n = 1), adjuvant chemotherapy (n = 4), or salvage therapy after recurrence (n = 4). The clinicopathological and treatment-related characteristics were analyzed for association with the occurrence of tumor persistence/recurrence or death. RESULTS: Of the study patients, 32 had dysgerminoma (DSG), 29 immature teratoma (IMT), 23 endodermal sinus tumor, 7 mixed germ cell tumors, and 1 each had choriocarcinoma and embryonal carcinoma. The median follow-up of survivors was 66 months (range, 12-236 months). The median time to recurrence or progression was 8 months. There were 11 treatment failures with 6 died of cancer. The 5-year survival rate was 97.4% for those primarily treated at CGMH. Histology (DSG/IMT versus non-DSG/IMT) (P < 0.0001) and International Federation of Gynecology and Obstetrics stage (P = 0.001) were significantly associated with treatment failure, while histology (P = 0.0004), salvage high-dose chemotherapy (HD-CT) after primary chemotherapy failed (P = 0.0405), and residual tumor after salvage surgery (P = 0.0014) were significant prognostic factors for overall survival. CONCLUSIONS: Prognosis of OGCMs is excellent if managed with standard treatment initially. Aggressive HD-CT with salvage surgery needs to be applied for recurrent/persistent disease after primary chemotherapy.     

Current therapy for dysgerminoma of the ovary

It is important that therapy of ovarian dysgerminoma be optimized because of the young age of women affected and the threat that therapy may pose to fertility. Our understanding of dysgerminoma has improved, so that treatment schemes with better therapeutic ratio may now be used. Approximately 65% of patients present with stage IA disease. For those wishing to preserve fertility, conservative surgery with close clinical, radiologic, and serologic follow-up is the treatment of choice, with chemotherapy for relapse. Cure rates should approach 100%, and fertility is usually preserved. Intra-abdominal relapse in those not wishing to preserve fertility should be treated with modest-dose pelvic and abdominal irradiation. For those patients with disease presenting in stages IB, II, and III who wish to maintain fertility, unilateral oophorectomy followed by combination chemotherapy may be curative and spare ovarian function. Otherwise, complete surgery, followed by abdominopelvic radiation therapy, is recommended. This treatment produces less morbidity than chemotherapy and will cure approximately two-thirds of patients. Chemotherapy should be used for salvage of subsequent relapse. Both radiation and chemotherapy are highly effective treatment modalities for dysgerminoma. This information, coupled with better understanding of the patterns of disease spread and improved ability to identify nondysgerminomatous elements using serum tumor markers, means that a more conservative approach can be taken to management without compromising the chance of cure. Cure rates for dysgerminoma should now approach the role of 97% achieved in the comparable tumor, testicular seminoma.     

Successful pregnancy after conservative surgery and chemotherapy for dysgerminoma of the ovary: case report]

OBJECTIVES: Considering the important improvement of surgical techniques and chemotherapy in the last few years, it is possible today, in selected cases of patients previously treated for ovarian cancer, to support their desire for motherhood, thus improving the quality of life for them. The major problem for the Gynecologic Oncologist in treating young women for ovarian tumor is the lack of statistically significant experience world-wide, because of the very few cases in which the reproductive function is preserved, and pregnancy is subsequently possible. STUDY DESIGN: The aim of this study was presentation the successful pregnancy after conservative surgery and chemotherapy for dysgerminoma of the ovary stage Ia. RESULTS: The patient age 23 was admitted to Department of Gynecology & Obstetric in Hospital of S?upsk in 1995 year with diagnosis right ovarian tumor. Right-side adnexectomy was performed initially. Histopathological examination of surgical specimen revelated dysgerminoma ovary stage Ia. Due to the clearly elevated tumor marker levels, indicating an involvement of other germ cell elements, and necrobiosis of tumor, we opted for postoperative chemotherapy instead of radiotherapy. Six cycles of BEP protocol chemotherapy was given. The follow-up included regular monitoring of the tumor markers. In the year 1998 the patient conceived and had a delivery of a normal infant at term. To date, there has been no indication towards tumor recurrence. CONCLUSION: After adequate staging and accurate information is given to the patient, conservative treatment may be safe in some women with early ovarian cancer. In early stage pure ovarian dysgerminoma conservative surgery combined with radiotherapy or chemotherapy showed high complete remission rates and excellent survival rates. For younger patients and those with gestation desires as well as patients with advanced diseases, adjuvant chemotherapy following surgery might be a better choice.     

The value of cancer antigen-125 as a tumor marker in malignant germ cell tumors of the ovary

The value of cancer antigen-125 (CA-125) as a tumor marker for malignant germ cell tumors (MGCT) of the ovary was investigated and compared with the other recognized tumor markers (human chorionic gonadotrophin (hCG), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and lactate dehydrogenase (LDH) isoenzymes. In the 10 months following June 1984, 4 new cases with MGCT and 1 patient with active disease on treatment were evaluated. In all cases prior to planned surgery the levels of CA-125 were significantly elevated. The serum values ranged from 154 to 617 U/ml (normal less than 20 U/ml). In 1 case (pure dysgerminoma) CA-125 was the only tumor marker. In 3 patients (2 mixed germ cell tumors and 1 immature teratoma) serum LDH (LD 1, 2, and 3) was elevated, and AFP was elevated in 1 of these. In the fifth case (mixed germ cell tumor), on treatment, serum AFP was used to monitor the disease. Four patients underwent cytoreductive surgery followed by combination chemotherapy. The changes in the serum levels of CA-125 paralleled those of the other tumor markers while on therapy. In our experience CA-125 is an invaluable indicator of the clinical status of the patient and could be a new tumor marker in patients with MGCT.     

Dysgerminoma with a slightly elevated alpha-fetoprotein level diagnosed as a mixed germ cell tumor after recurrence

A pure dysgerminoma shows a normal serum alpha-fetoprotein level, and mixed germ cell tumors containing endodermal sinus tumor elements have elevated serum alpha-fetoprotein levels, ranging from >100 to far higher than 1,000 ng/ml. A 40-year-old woman was diagnosed as having a stage Ia pure dysgerminoma with a slight alpha-fetoprotein elevation (11 ng/ml), after a staging laparotomy, because we could not find any yolk sac element in the original tumor. After 44 months, she had a pelvic recurrent tumor with a significant elevation of the serum alpha-fetoprotein concentration (1,520 ng/ml); histological examination of a needle biopsy specimen revealed a typical yolk sac tumor. Eventually, her initial tumor was diagnosed as a mixed germ cell tumor. The patient was successfully treated with seven courses of chemotherapy and has been disease free for 22 months. It is necessary to be aware of the possibility of a mixed germ cell tumor containing a yolk sac element, even when the alpha-fetoprotein level is only slightly elevated.     

Bleomycin, vinblastine, and cis-platinum in the treatment of advanced endodermal sinus tumor

The endodermal sinus tumor has traditionally been associated with an exceedingly poor prognosis. Three women with advanced pure endodermal sinus tumors were treated with a combination of bleomycin, vinblastine, and cis-platinum (VBC). Serum alpha-fetoprotein levels were monitored for all patients during and after therapy, and in each case the alpha-fetoprotein returned to normal range, correlating with complete clinical remission. Second-look laparotomy was negative for tumor in each case. Two patients have had no overt sign of recurrence 12 months after cessation of therapy. The third patient had post-treatment elevation of alpha-fetoprotein levels, and eventually was found to have recurrent tumor 6 months after chemotherapy was stopped. The VBC combination, previously found effective in testicular germ cell tumors, is also effective in ovarian germ cell tumors.     

Tumor chemoconversion following surgery, chemotherapy, and normalization of serum tumor markers in a woman with a mixed type germ cell ovarian tumor

BACKGROUND: Malignant germ cell tumors of the ovary are often curative after conservative surgery and adjuvant chemotherapy. Persistent tumors despite normalization of serum tumor markers may represent retroconversion to benign masses, but this is rare in ovarian tumors without teratoma elements. The management in such cases has not been defined. CASE: A young woman with a stage IIIC mixed germ cell ovarian tumor containing endodermal and dysgerminoma elements and elevated serum tumor markers underwent conservative surgery followed by chemotherapy. Residual tumor persisted on CT despite the normalization of serum tumor markers. The residual tissue was resected and contained benign tissue. CONCLUSIONS: In cases where masses persist and serum tumor markers normalize, attaining a histological diagnosis, and not chemotherapy, should be considered.     

Lactic dehydrogenase, alkaline phosphatase and human chorionic gonadotropin in a pure ovarian dysgerminoma

Pure dysgerminoma is considered to be a nonsecretary ovarian tumor. In this study serum lactic dehydrogenase, human chorionic gonadotropin, and alkaline phosphatase levels were highly elevated in a 21-year-old woman with unilateral ovarian pure dysgerminoma and fell sharply to normal levels after removal of the tumor. In order to establish the source of these elevated serum enzymes and hormone, the tumor was homogenized and the level of these substances was found to be several times higher than that of normal homogenized ovarian tissue. In addition, the presence of lactic dehydrogenase and alkaline phosphatase in the dysgerminoma cells was shown by histochemical methods. This is the first report providing evidence that pure dysgerminoma contains and secretes enzymes and hormones which may constitute tumor markers useful for the diagnosis and follow-up of patients with this type of neoplasm.     

Pure dysgerminoma of the ovary with elevated serum human chorionic gonadotropin: diagnostic and therapeutic considerations

Pure ovarian dysgerminomas with associated elevation of human chorionic gonadotropin (hCG) are rare, and their optimum management is unclear. We report here a 24-year-old woman with stage III dysgerminoma of the ovaries, with bulky intrapelvic disease, paraaortic adenopathy, and elevated pre- and postsurgical serum beta-hCG titers. Following administration of whole abdominal-pelvic and mediastinal irradiation therapy, the patient's adenopathy regressed, her serial beta-hCG titers returned to normal, and she has remained free of disease for the past 30 months. Histopathological studies revealed a pure dysgerminoma with scattered giant cells which were negative for hCG by immunoperoxidase staining. The literature is reviewed with reference to the significance of elevated hCG levels, the presence of giant cells in association with dysgerminoma of the ovary, and therapeutic implications. Serial determinations of beta-hCG titers may prove to be as valuable in the management of these patients as they are in patients with testicular tumors.     

Management of Early Ovarian Cancer: Germ Cell and Sex Cord-Stromal Tumors

Malignant ovarian germ cell tumors (OGCT) and sex cordstromal tumors (OSCST), each of which account for less than 5% of all ovarian malignancies, are much less common than epithelial ovarian cancer. In young patients suspected of having an OGCT, laparotomy is initially indicated for both diagnosis and treatment. For most patients, unilateral salpingo-oophorectomy with preservation of the contralateral ovary and the uterus is appropriate. The basis for this surgical approach is retrospective studies that show an equivalent cure rate for patients who undergo unilateral or bilateral adnexectomy. No prospective studies have compared unilateral with bilateral adnexectomy. Surgical staging is also important to determine the extent of disease, to determine prognosis, and to guide postoperative management. If metastatic disease is encountered during initial surgery for OGCT, the same principles of cytoreductive surgery that have been applied to surgically manage advanced epithelial ovarian cancer are recommended, with resection of as much tumor as is technically feasible and safe. For all OGCT patients except those with well-documented stage IA grade 1 pure immature teratoma or stage IA pure dysgerminoma, postoperative chemotherapy is indicated. The current recommended regimen for OGCT is bleomycin, etoposide, and cisplatin—a combination that appears to result in at least a 95% cure rate for stage I disease and at least a 75% cure rate for advanced-stage disease. For patients with metastatic dysgerminoma, chemotherapy, which has the advantage of preserving fertility in the majority of patients, has supplanted radiotherapy as standard treatment. For patients with OSCST, no standard therapy exists. Surgery alone is currently acceptable treatment for all patients with OSCST except those who have metastatic disease or Sertoli-Leydig cell tumors with poor differentiation or heterologous elements. Currently, platinum-based combination chemotherapy is favored for these latter patients, but the activity of such regimens appears only modest.     

Malignant germ cell tumors of the ovary

OBJECTIVE: To evaluate the efficacy of adjuvant therapy for ovarian germ cell tumors. METHODS: We reviewed records of women who had malignant germ cell tumors of the ovary from 1977-1997. RESULTS: Seventy-two women had surgical resections of malignant ovarian germ cell tumors and most received adjuvant therapy. Fifty-six women (78%) presented with stage I disease, and 16 (22%) had more advanced disease. Tumor subtypes included dysgerminoma (n = 20), yolk sac tumor (n = 8), immature teratoma (n = 29) and mixed germ cell tumor (n = 15). Surgical management of the 56 with stage I disease consisted of total abdominal hysterectomy, bilateral salpingo-oophorectomy, and extensive surgical staging in ten women, whereas a conservative surgical approach, consisting of unilateral adnexectomy with or without comprehensive surgical staging, was adopted in later years (n = 46). Fifty-six women were treated with postoperative chemotherapy, predominantly platinum-based regimens. The 5-year actuarial survival rate was 93%. None of the 36 women who presented after 1984 have died of disease. CONCLUSION: These data confirmed that platinum-based adjuvant treatments allow most women with ovarian germ cell malignancies to have conservative surgery without compromising survival.     

卵巢无性细胞瘤伴绒毛膜促性腺激素显著升高1例

卵巢无性细胞瘤是一种中度恶性的卵巢生殖细胞肿瘤,好发于年轻女性,临床发病少见,手术+铂类为主的联合化疗使该病有良好的生存预后及妊娠结局。单纯卵巢无性细胞瘤无内分泌功能,临床检测绒毛膜促性腺激素（HCG）一般为阴性,仅6%～8%含有小簇合体滋养细胞而使HCG呈低反应。本文通过分析1例单纯卵巢无性细胞瘤伴HCG值高达54 921.000 mIU/ml的临床资料,探讨该病的临床特点及诊断治疗。     

Growing teratoma syndrome after chemotherapy for a mixed germ cell tumor of the ovary

A retroperitoneal enlarging mass was detected and resected in a 24-year-old nulliparous woman after fertility-preserving surgery and adjuvant chemotherapy for a malignant germ cell tumor (MGCT) of the right ovary. This enlarging mass contained only a mature teratoma component. Alpha-fetoprotein, which was elevated to 21236.6 ng/mL before the initial surgery, persisted within normal after the completion of adjuvant platinum-based chemotherapy. The patient was diagnosed with growing teratoma syndrome. Growing teratoma syndrome originating from ovarian germ cell tumor is very rare. Only 15 cases have been reported. Surgical resection and histological confirmation of growing mass after MGCT treatment is essential before conducting salvage chemotherapy.     

Malignant ovarian germ cell tumor — Role of surgical staging and gonadal dysgenesis

Objective

To evaluate the effect of comprehensive surgical staging and gonadal dysgenesis on the outcomes of patients with malignant ovarian germ cell tumor.

Methods

We performed a retrospective review of patients with ovarian germ cell tumors who were treated at our institution between 1976 and 2012.

Results

Malignant ovarian germ cell tumors (MOGCTs) were identified in 50 females. The median age was 24 years (range 13 to 49). Of all MOGCT patients, 42% had dysgerminoma, 20% immature teratoma, 16% endodermal sinus tumor, and 22% mixed germ cell tumor. Univariate analyses revealed that the lack of surgical staging (p = 0.048) and endodermal sinus tumor (p = 0.0085) were associated with disease recurrence, while age at diagnosis, ethnicity, and stage of the disease were not. Multivariate analyses revealed that the lack of surgical staging (p = 0.029) and endodermal sinus tumor (p = 0.016) were independently associated with disease recurrence. In addition, 7 patients (14%) had 46 XY karyotype, including 6 with pure dysgerminoma and 1 with mixed germ cell tumor. Five had Swyer syndrome and 2 had complete androgen insensitivity syndrome. Concurrent gonadoblastoma was found in 5 of the patients. No difference was found in the mean age at presentation, stage distribution, or recurrence rate for MOGCT patients with or without XY phenotype.

Conclusions

Comprehensive surgical staging was associated with a lower rate of recurrence. Fourteen percent of phenotypic females with MOGCT and 29% of those with dysgerminoma had XY karyotype. The clinical outcome of these patients is similar to that of MOGCT patients with XX karyotype.     

Serum lactate dehydrogenase levels in malignant germ cell tumors of ovary

Serum lactate dehydrogenase (LDH) levels were examined in 24 patients with germ cell tumors of the ovary to evaluate the usefulness of the enzyme as a tumor maker. Lactate dehydrogenase levels were found to be significantly elevated ( P < 0.001) in these patients at the time of diagnosis as compared to the controls. Lactate dehydrogenase levels in patients with benign ovarian tumors and controls were comparable. The positive rate of LDH for malignant germ cell tumors of the ovary was 94.5%. The LDH values significantly declined in the patients who responded to treatment. Metastatic or recurrent disease resulted in increased LDH levels. The results indicate that LDH is a useful tumor marker for malignant germ cell tumors of the ovary.     

alpha-Fetoprotein as a biochemical marker in patients with gynecologic malignancy.

α-Fetoprotein (AFP) was measured by radioimmunoassay in the sera of 348 patients with gynecologic malignancies and 385 patients with benign gynecologic disease. Serum AFP was elevated (> 20 ng/ml) in 50% of patients with invasive cervical, endometrial, and ovarian cancers, and in 20% of the control population (p < 0.001). However, there was no statistical difference in the incidence of AFP elevation in patients with cervical intraepithelial neoplasia (CIN) and in those with benign gynecologic disease. Serum AFP levels returned to normal within 2 months following complete tumor excision or radiation therapy in patients without clinical evidence of persistent disease. α-Fetoprotein is an effective tumor marker in patients with ovarian germ cell tumors and may also be a useful biochemical monitor in selected patients with other types of gynecologic malignancy.     

Malignant germ cell tumors of the ovary. Pregnancy considerations

OBJECTIVE: To study the pregnancy association and malignant germ cell tumors of the ovary with regard to its effects on tumor prognosis. STUDY DESIGN:: Seventy-five patients with malignant germ cell tumors of the ovary treated at the King Faisal Specialist Hospital-Research Center (KFSH-RC) Riyadh, Kingdom of Saudi Arabia between January 1976 and December 1992, were reviewed. Data was retrieved from the medical records and the database of ovarian tumor pathology. Patients with tumor/pregnancy association were identified and correlation with obstetrical outcome and tumor prognosis analyzed. Patients who conceived after treatment were identified and their reproductive outcome described. RESULTS: Malignant germ cell tumor was associated with pregnancy in a group of ten patients. Possible tumor effects upon pregnancy in this group included operative delivery by caesarean section (n=3), mid-trimester termination (n=2), spontaneous abortion (n=1). Four patients had normal vaginal birth with no apparent tumor effects upon pregnancy. Pregnancy did not seem to influence the tumor prognosis of pure dysgerminoma (n=6), however, two patients with non-dysgerminomatous germ cell tumor (one endodermal sinus tumor and one immature teratoma) died of rapidly progressive disease during the second trimester. Two patients with advanced (stage IIIC) disease concurrent with pregnancy (one pure dysgerminoma and one mixed germ cell tumor), had normal fetal outcomes and achieved long-term survival. Amongst the 22 patients who planned to conceive after conservative surgery, with or without post-operative adjuvant chemotherapy, 12 conceived (12/22) and achieved a total of 20 pregnancies. Their outcomes included normal births (n=18) including one set of twins and hydatidiform moles (n=2). CONCLUSIONS: Our findings suggest that, (1) The association of pure dysgerminoma and pregnancy did not adversely affect the tumor prognosis or fetal outcome. However, the question remains as to whether pregnancy worsened the prognosis of non-dysgerminomatous germ cell tumors. (2) Recent platinum-based regimens of multiagent chemotherapy for germ cell tumors did not seem to affect fertility potential.