Ovarian dysgerminoma with pseudo-Meigs syndrome: A case report.

RATIONALE: Dysgerminoma is a rare malignant tumor of the ovary, more frequently occurring in young women. The main signs of pseudo-Meigs syndrome (PMS) are ascites and hydrothorax accompanying benign or malignant ovarian tumors (no fibroma or fibroma-like tumor). PATIENT CONCERNS: A 19-year-old woman with fever and chest tightness for 2 days. DIAGNOSES: Pectoral-abdominal computed tomography (CT) scan and contrast-enhanced magnetic resonance imaging revealed a large amount of right pleural effusion, a small amount of ascites, and a huge abdominopelvic mass measuring about 29.2cm × 11.8cm × 8.4 cm in the left ovary. The result of hydrothorax examination was consistent with the diagnosis of exudative pleural effusion. In addition, Rivalta-test showed a positive result and lactate dehydrogenase was elevated. The histopathological diagnosis was a giant germ cell tumor, which was consistent with dysgerminoma in terms of both morphology and immunophenotype. Based on these findings, a diagnosis of malignant ovarian neoplasm with PMS was made. INTERVENTIONS: Surgical resection of the tumor was performed. OUTCOMES: The patient recovered well after operation, and the pleural effusion and abdominal ascites vanished. No recurrence was observed during the 1-year follow-up period. LESSONS: Ovarian dysgerminoma with PMS is a rare malignant tumor of the ovary, which often occurs in young women. It should be considered in differential diagnosis of patients with a pelvic mass, ascites and pleural effusion. Early diagnosis and surgical treatment are beneficial to prolonged survival.

XY Gonadal Dysgenesis in a Phenotypic Female Identified by Direct-to-Consumer Genetic Testing.

We report a 16-year-old phenotypic female with 46,XY complete gonadal dysgenesis and metastatic dysgerminoma, unexpectedly discovered through direct-to-consumer (DTC) commercial genetic testing. This case underscores the importance of timely interdisciplinary care, including psychosocial intervention and consideration of gonadectomy, to optimize outcomes for individuals with differences of sex development. Her unique presentation highlights the implications of DTC genetic testing in a new diagnostic era and informs general pediatricians as well as specialists of nongenetic services about the value, capabilities, and limitations of DTC testing.

Anti-Muellerian hormone concentration in bitches with histopathologically diagnosed ovarian tumours and cysts.

Increased concentrations of Anti-Muellerian hormone (AMH) can indicate a granulosa cell tumour as shown in women, mares and cows. To investigate AMH to differentiate canine granulosa cell tumour from other ovarian pathologies, we evaluated the ovaries of 63 bitches. Blood serum samples were collected before surgery for AMH analysis. Ovaries were submitted for histopathological examination. Fourteen bitches showed normal ovaries. These bitches had AMH values between 0.12 and 0.99 ng/ml. In 20 bitches ovarian cysts i.e., follicular cysts (n = 8), corpora lutea cysts (n = 7), subsurface cysts (n = 5) were diagnosed. These dogs had AMH values of 0.11-2.09 ng/ml. Bitches with small luteinized follicular cysts had slightly higher AMH values than those without ovarian alteration. In 29 cases ovarian neoplasms i.e., granulosa cell tumour (n = 9), epithelial tumours (n = 16), dysgerminomas (n = 3) and one sarcoma were identified. Anti-Muellerian hormone values of bitches with an ovarian neoplasm except granulosa cell tumour ranged from 0.18 to 1.18 ng/ml. The AMH values of bitches with granulosa cell tumour ranged from 1.12 to ≤23 ng/ml and were significantly higher (p < .05) than in all of the other bitches. The cut-off of 0.99 ng/ml gave a sensitivity of 100% and a specificity of 94.44% to diagnose granulosa cell tumour. In conclusion, markedly elevated AMH concentrations in bitches are indicative for a granulosa cell tumour. However, negative testing does not rule out the existence of small one. Differentiation of GCT from luteinized follicular cysts may especially be difficult.

Ovarian dysgerminoma with normal serum tumour markers presenting in a child with precocious puberty.

A 7-year-old female child was presented to the emergency room with acute abdominal pain and vaginal bleeding. Her assessment revealed a firm large lower abdominal mass with evidence of precocious puberty with bilaterally symmetrically enlarged breast (Tanner stage B4-P1-A1). Abdominal imaging showed a well-defined soft midline pelvi-abdominal single mass measuring 7.0×12.6×11.7 cms with no ascites. Serum tumour markers including lactate dehydrogenase (LDH), beta-subunit of human chorionic gonadotropin (B-hCG) and luteinizing hormone/follicular stimulating hormone (LH/FSH) were all normal. At operation, there was a huge abdominal tumour weighing 558 grams, localized to the right ovary sparing the left ovary, uterus, lymph nodes and other abdominal organs. Unilateral right salpingo-oophorectomy was performed. Histopathologic examination revealed ovarian dysgerminoma with intact capsule; FIGO Ia. Immunohistochemical stainings were positive for placental alkaline phosphatase (PALP), CD 117(c-kit) and calretinin focally but was negative for cancer antigen-125 (CA-125), B-hCG, S-100, carcinoembryonic antigen (CEA), and leukocyte common antigen (LCA). Being fitting in the low risk classification, the wait and see protocol was selected with strict follow-up with pediatric oncologist and pediatric surgeon. Along the duration of 2 years follow up, there was no more vaginal bleeding with dramatic reduction of the breast size and no recurrence.

Elevated human chorionic gonadotropin and hyperandrogenemia in a woman with Müllerian agenesis.

BACKGROUND: Müllerian agenesis is a congenital malformation characterized by absence of the uterus, cervix, and upper vagina. A positive home pregnancy test in a woman with Müllerian agenesis mandated evaluation for malignancy. CASE: A woman with Müllerian agenesis presented with elevated levels of human chorionic gonadotropin (hCG), testosterone, and dehydroepiandrosterone sulfate. Pelvic magnetic resonance imaging (MRI), abdominal and pelvic computed tomography scan, chest computed tomography scan, brain MRI, and body positron emission tomography scan did not identify a malignancy. Human chorionic gonadotropin characterization revealed 74% hyperglycosylated and 1.6% free ß-hCG, suggesting a trophoblast-containing tumor. Interventional ovarian venous sampling and repeat pelvic MRI suggested a right adnexal source. After laparoscopic removal of a stage 1C right ovarian dysgerminoma, hCG and testosterone returned to normal. CONCLUSION: A dysgerminoma coincident with Müllerian agenesis expressed hCG before detection by MRI. Human chorionic gonadotropin molecular characterization, ovarian vein sampling, and repeat pelvic MRI led to successful treatment.

A pelvic mass on ultrasonography and high human chorionic gonadotropin level: not always an ectopic pregnancy.

A 24-year-old patient with 7-week amenorrhoea consulted for vaginal bleeding without abdominal pain. Ultrasonography revealed a 7 × 4 cm solid right pelvic mass. There was no visible intrauterine gestational sac. The serum ß-human chorionic gonadotropin (ß-hCG) level was 11 998 IU/l. Emergency laparoscopy was performed for a presumptive diagnosis of ectopic pregnancy. At laparoscopy, the right ovary was enlarged with a non-haemorrhagic 7 × 4 cm solid lesion, which was resected. The histological diagnosis was a dysgerminoma with immunohistochemistry showing nests of syncytiotrophoblastic cells, which were the origin of the hCG production. There was no pregnancy, either intrauterine or ectopic. There was no evidence of metastasis from the dysgerminoma on the positron-emission tomography scanner. The patient underwent a second procedure for surgical staging of this ovarian germ-cell tumour. This ovarian dysgerminoma was staged FIGO 1A, and the patient did not receive adjuvant therapy. There was no recurrence at the last 8-month follow-up.

Ovarian gonadoblastoma with dysgerminoma in a 15-year-old girl with 46, XX karyotype: case report and review of the literature.

OBJECTIVE: To present a challenging case of hCG positivity in a young patient and to review similar cases reported in the literature. METHODS: Literature search of gonadoblastoma cases with pure 46, XX karyotype using PubMed database. RESULTS: A 15-year-old girl with hCG positivity was investigated for the source and the initial diagnosis was an ectopic pregnancy. An ovarian tumor was identified after failed methotrexate therapy and the pathological diagnosis was gonadoblastoma with dysgerminoma. To the best of our knowledge, the case was unique in the literature for having the smallest diameter of a gonadoblastoma tumor with 46, XX karyotype. CONCLUSION: Differential diagnosis of perimenarcheal vaginal bleeding may be challenging for the clinician. Rare causes such as pregnancy both intrauterine and extrauterine and hormone producing tumors should be kept in mind.

[A case of PEP(BEP)-resistant ovarian dysgerminoma successfully treated by VeIP therapy].

Ovarian germ cell tumors are malignant tumors which commonly develop during childhood, and which are sensitive to chemotherapy. We have had a case of germ cell tumors which showed resistance to first-line PEP(BEP)chemotherapy. As second-line chemotherapy, VeIP therapy was used, because it is possible that this therapy is effective against recurrent testicular germ cell tumors. The patient was fourteen years old. She experienced acute abdominal pain and visited the hospital, where she was diagnosed with torsion of an ovarian tumor. An emergency laparotomy and right salpingoophorectomy were performed, the pathological diagnosis being stage Ia ovarian dysgerminoma G1. She was followed for two years until her serum hCG-CTP elevated to 1.4 mIU/mL. An MRI revealed an abnormal signal in the left ovary, so we diagnosed this as a recurrence of the dysgerminoma. Then she received chemotherapy PEP(BEP), but after eight months of PEP (BEP), her serum hCG-CTP was again elevated to 14.5 mIU/mL. A recurrence was detected with an MRI and PET-CT, and another laparotomy was performed. The recurrent region was detected in the left ovary. A left ovarian cystectomy was performed in which CDDP ip was used. After the operation, the patient again underwent chemotherapy. VeIP (vinblastine+ifosfamide+cisplatin)was chosen as the second-line regimen. After 6 courses of this therapy, she had a follow-up operation. No recurrence region was found in the pelvic area. She remains without recurrence of this disease 24 months after VeIP therapy. This case suggests that VeIP therapy might be an effective second-line therapy for patients with PEP(BEP)-resistant ovarian dysgerminoma.

A case of pediatric ovarian dysgerminoma associated with high serum levels and positive immunohistochemical staining of neuron-specific enolase.

A 5-year-old girl presented with a painful abdominal mass. Abdominal magnetic resonance imaging (MRI) showed 3 separate masses. Tumor markers including lactate dehydrogenase (LDH), cancer antigen-125 (CA-125), beta-subunit of human chorionic gonadotropin (beta-hCG) and neuron-specific enolase (NSE) were elevated. At operation, the main tumor arose from the left ovary and was associated with torsion, whereas the other lesions were lymph node metastases. A salpingo-oophorectomy was performed. Histopathologic examination indicated that the tumor was a dysgerminoma. Immunohistochemicallly, the cells were positive for NSE and placental alkaline phosphatase (PALP) but were negative for CA-125, beta-hCG, S-100, glial fibrillary acidic protein, and vimentin. The elevated serum levels of tumor markers improved dramatically after the operation and chemotherapy.

Laboratory markers and germ cell tumors.

The International Germ Cell Consensus Classification (IGCCC) of testicular germ cell tumors (TGCT) in 1997 included three serum tumor markers, serum lactate dehydrogenase catalytic concentration (S-LD), serum alpha fetoprotein concentration (S-AFP), and serum human chorionic gonadotropin concentration (S-hCG). The recommendation should be implemented for all patients with TGCT and is also useful for patients with ovarian and extragonadal germ cell tumors. A fourth serum tumor marker for TGCT, S-LD isoenzyme 1 (S-LD-1), is also relevant for TGCT. Patients with seminoma have a raised S-LD-1 more often than a raised S-AFP and S-hCG, whereas patients with nonseminoma have a raised S-AFP more often than a raised S-LD-1 and S-hCG. A new model combining IGCCC and S-LD-1 predicts survival better than previous staging systems. LD-1 is related to a characteristic chromosomal abnormality in all types of TGCT, a high copy number of chromosome 12p. In contrast, AFP and hCG are found mainly in nonseminomatous germ cell tumors and they related to the histologic differentiation of the tumors. The different biologic background for the serum tumor markers may contribute to the difference in their clinical behavior.

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.

Significance of serum and peritoneal fluid lactate dehydrogenase levels in ovarian cancer.

We investigated prospectively whether the detection of serum lactate dehydrogenase (LDH) and/or peritoneal fluid LDH levels may serve as a reliable biochemical marker in discriminating ovarian carcinoma from benign ovarian tumors. In this series, postoperatively 20 of 50 patients had a diagnosis of ovarian cancer while the remaining 30 patients had benign ovarian tumor. No significant difference in peritoneal fluid LDH levels was observed between patients with ovarian cancer and benign ovarian tumor (p > 0.05). Serum LDH levels in ovarian cancer patients were significantly higher than those in patients with benign ovarian tumor (p < 0.05). Statistically significant differences were not observed in LDH levels of different histological types of ovarian cancer and different stages of the disease. Serum LDH levels presented diagnostic accuracy with high specificity and may have a potential use as a biochemical marker.

Macrophage colony-stimulating factor as a marker for malignant germ cell tumors of the ovary.

We assessed the usefulness of macrophage colony-stimulating factor (M-CSF) as a serum marker for malignant germ cell tumors of the ovary. Serum levels of M-CSF were measured in 49 patients with malignant germ cell tumors and in 64 patients with mature benign cystic teratoma by an enzyme-linked immunosorbent assay. CA125 was measured by radioimmunoassay. The serum level of M-CSF was above normal (>1056 U/ml) in 44 (90%) of 49 patients with malignant germ cell tumors; the CA125 level was above the cutoff value (35 U/ml) in 34 patients (69%) (P < 0.05). The serum level of M-CSF was elevated in 20 (87%) of 23 patients with stage I disease and in all 16 patients with dysgerminoma. Only 7 (11%) of 64 patients with mature benign cystic teratoma had elevated levels of M-CSF. These results suggest that M-CSF is highly sensitive and specific for malignant germ cell tumors of the ovary, especially for dysgerminoma.

Elevated serum inhibin and tumor-associated trypsin inhibitor concentrations in a young woman with dysgerminoma of the ovary.

We describe a patient with dysgerminoma who had elevated serum inhibin, tumor-associated trypsin inhibitor (TATI), and CA 125 concentrations, which increased progressively during follow-up of the advancing disease. Inhibin levels correlated closely with disease behavior. In contrast to inhibin, serum TATI and CA 125 failed to reveal the presence of silent disease.

Ascitic positive cytology and intraperitoneal metastasis in ovarian dysgerminoma.

OBJECTIVES: To verify the pattern of the spread of tumors in ovarian dysgerminoma, with special reference to intraperitoneal metastasis, and to assess clinicopathologic factors for predicting tumor extension. METHODS: Detailed data regarding ascitic cytology, macroscopical findings at surgery, and the histopathology of the surgical specimens were retrospectively reviewed in 12 patients with dysgerminoma who were treated at Kyoto University Hospital. The relationships between the tumor extension and the period of symptoms, the serum lactic dehydrogenase (LDH) level, and the operative findings also were analyzed. RESULTS: Ascitic cytology revealed a high incidence of positivity in 6 of the 10 (60%) cases examined. Extraovarian metastases were present in 4 of the 6 (67%) cases with positive cytology, and in 1 of the 4 (25%) cases with negative cytology. Intraperitoneal metastatic nodules were detected in 5 of the 12 (42%) patients either by inspection during surgery or by postsurgical histological examination. In addition, these metastatic lesions were 5 or fewer in number and 7 mm or less in diameter, except in 1 patient with widespread disease. The presence or absence of extraovarian spread of the tumor was not significantly correlated with the period of symptom, the serum LDH level, the size of the primary tumor, or the volume of the ascitic fluid. CONCLUSION: The incidence of intraperitoneal spillage and/or metastases of dysgerminoma cells might be higher than previously reported. These findings indicate the importance of ascitic cytology and careful inspection at the time of operation, as well as the rationale of postsurgical chemotherapy for dysgerminoma of an apparently early stage.

Technetium-99m pentavalent dimercaptosuccinic acid imaging in patients with pituitary adenomas.

We studied the tumor-seeking agent technetium-99m-labeled pentavalent dimercaptosuccinic acid ([99mTc](V)DMSA) to visualize 21 growth hormone (GH)-, nine prolactin (PRL)-, two mixed GH/PRL-, six adrenocorticotrophin (ACTH)-secreting and 15 clinically non-functioning pituitary adenomas, three craniopharyngiomas and one dysgerminoma of the sella. All non-adenomas and 31 out of 53 adenomas were studied before treatment: 22 after surgery and/or radiotherapy. Eight cases of acromegaly were studied before and after chronic treatment with octreotide, whereas three cases of acromegaly, one of prolactinoma and two of non-functioning adenoma were imaged before and after adenomectomy. As a control group, 27 patients without any clinical evidence of pituitary adenoma were studied: 10 of them were operated on previously and treated with iodine-131 for metastatic thyroid carcinoma, 10 had brain tumors and the remaining seven patients had functional pituitary hypersecretion (four Klinefelter's syndrome, two primary hypothyroidism and one Addison's disease). The scintigraphy was repeated after testosterone in Klinefelter's syndrome, L-thyroxine in primary hypothyroidism and cortisone administration in Addison's disease. Seventeen GH-secreting (81%), seven PRL-secreting (78%), three ACTH-secreting (50%), 15 non-functioning (100%) and one (50%) mixed adenoma significantly concentrated [99mTc](V)DMSA, showing elevated tumor-to-background (T/B) ratios. The T/B ratios were similar in untreated and surgically treated adenomas (11.2 +/- 5.6 vs 11.8 +/- 6.2). Radiotherapy significantly lowered the [99mTc](V)DMSA uptake to 5.1 +/- 2.8 (p < 0.1 vs untreated patients). Non-adenomatous lesions of the sella turcica did not concentrate [99mTc](V)DMSA in the pituitary as well as brain tumors and 8 out of 10 metastatic thyroid cancers. The treatment with octreotide normalized GH and insulin-like growth factor I levels and reduced [99mTc](V)DMSA from 15.7 +/- 4.8 to 13.5 +/- 3.9 (p < 0.05). Conversely, adequate substitutive therapy completely inhibited the uptake of the radiotracer in Klinefelter's syndrome, in primary hypothyroidism and in Addison's disease. The [99mTc](V)DMSA scintigraphy showed an overall sensitivity of 81% (43/53) in detecting pituitary adenomas, which was increased to 95% for lesions greater than 10 mm in size. High-quality images with minimal total body radiation were obtained, enabling a good in vivo characterization of viable adenomatous tissue as well as an accurate monitoring of the effects of different therapeutic regimens.

Dysgerminoma of the ovary with hypercalcemia associated with elevated parathyroid hormone-related protein.

The purpose of the present paper is to present a rare case of dysgerminoma of the ovary with hypercalcemia showing elevation of multiple serum tumor markers including parathyroid hormone-related protein (PTH-rP). An 18-year-old unmarried woman, with ovarian dysgerminoma showing hypercalcemia and elevated serum PTH-rP, received six courses of a combination chemotherapy consisting of bleomycin, etoposide and cisplatin after her first surgery, and had no evidence of recurrence approximately 30 months after completing the chemotherapy.

Accumulation of gamma/delta T cells in human dysgerminoma and seminoma: roles in autologous tumor killing and granuloma formation.

The precise biological function of a subset of T cells bearing gamma/delta T cell receptor (TCR) remains poorly understood. The present study demonstrated the presence of gamma/delta T cells in tumor-infiltrating lymphocytes (TIL) and peripheral blood lymphocytes (PBL) of human patients with dysgerminoma and seminoma when determined by flow cytometry and in situ immunohistochemical staining. TIL contained a high percentage of gamma/delta T cells, ranging from 17.3 to 35.1%. gamma/delta T cells often accumulated within the granulomatous inflammation of tumor tissues. The majority of gamma/delta T cells were V gamma 9/V delta 2+ cells. Freshly isolated PBL, TIL and purified gamma/delta T cells showed autologous tumor killing (ATK) activity, which could be inhibited by monoclonal antibodies (mAb) against V delta 2. Furthermore, two gamma/delta T cell clones established from TIL showed cytotoxicity against autologous and allogeneic dysgerminoma, while they had low or no lytic effects on other cell types including carcinomas of ovary and tumor cell lines such as K562, Daudi and Molt-4. Lysis of autologous tumor cells by the clone was inhibited completely by anti-V delta 2 mAb and partially by mAb against CD3, LFA-1 alpha and ICAM-1 molecules, while it was resistant to anti-CD8, anti-HLA-ABC and anti-HLA-DR mAb. Supernatants produced by gamma/delta T cell clones induced adhesion, aggregation and increased DNA synthesis of monocytes and some characteristics of activated macrophages or epithelioid cells. Tumor necrosis factor (TNF)-alpha, granulocyte-macrophage colony stimulating factor (GM-CSF) and interferon (IFN)-gamma were detected in the supernatants of gamma/delta T cell clone. These results suggest that gamma/delta T cells accumulating in dysgerminoma and seminoma exhibit ATK activity through V gamma 9/delta 2 TCR and these gamma/delta T cells also play a role in the formation of granulomatous inflammation, which is associated with human dysgerminoma and seminoma.

[Usefulness of determining tumor markers CEA, CA125 and CA72-4 in blood serum of patients with ovarian carcinoma]. / Przydatnosc oznaczen markerów nowotworowych CEA, CA125 i CA72-4 w surowicy krwi chorych na raka jajnika.

Serum levels of 3 markers: CEA, CA125 and CA72-4 have been determined in 58 patients aged from 15-60 years with histologically diagnosed ovarian cancer. Serum CEA was determined by radioimmunoassay using kits POLATOM (Poland), CA72-4 was determined using kits CIS BIOINTERNATIONAL (France) and CA125 was determined by enzyme immunoassay using kits Hoffmann-la-Roche (Wien-Austria). We have observed the growth of sensitivity and specificity of serum levels: CA125 and CA72-4 if we have referred to the simultaneous elevation of CA125 and CA72-4 markers. We have observed that CA125 and CA72-4 elevated levels were proceeded clinical recurrent of the disease from 2 to 6 months.