Bilateral poorly differentiated Sertoli-Leydig ovarian tumor associated with dysgerminoma: case report.

Sertoli-Leydig cell tumors are rare stromal tumors of the ovary. They account for less than 0.5% of ovarian neoplasms. From a histological point of view, they show large diversity, making their clinical symptoms diverse as well. They are mostly unilateral, with average diameter 13.5 cm at the moment of diagnosis. Histologically, poorly-differentiated Sertoli-Leydig tumors pose a diagnostic problem, often being clinically asymptomatic which makes their detection relatively late, preventing efficient treatment, and resulting in worse prognosis. This article presents a rare case of bilateral poorly-differentiated Sertoli-Leydig ovarian tumor, characterized by heterologous histological structure, without hormonal unbalance, and without signs of defeminization and/or virilization, its diagnostics, and treatment.

[Malignant ovarian germ cell tumors--clinical characteristics and analysis of outcomes]. / Zlosliwe guzy germinalne jajnika--charakterystyka grupy chorych i analiza wyników leczenia.

OBJECTIVES: Presentation of a group of patients with diagnosed malignant ovarian germ cell tumors (MOGCT), determination of prognostic factors and outcome analysis. MATERIAL AND METHODS: We selected patients with diagnosed malignant ovarian germ cell tumors from the patient registry of Cancer Center in Warsaw from 1990 to 2001. We analyzed clinical and pathological features of the study group, as well as methods and results of treatment. RESULTS: We collected documentation of 83 patients. Most were diagnosed with dysgerminoma and immature teratoma in the early stages of development. 73 patients received adjuvant chemotherapy after surgery At the end of the first line of treatment complete response was achieved in 63 patients (75.9%). Time to recurrence ranged from 25 to 518 days (mean 176 days). The most common site of recurrence was the true pelvis. The five-year overall survival was 62.7%. Significant favorable prognostic factor was early stage of disease and the histological diagnosis of dysgerminoma. From the 46 women after fertility-sparing surgery, 8 became pregnant. CONCLUSIONS: MOGCT are a group of potentially curable, yet very aggressive malignant ovarian tumors. The main condition for obtaining good results is quick diagnosis and appropriate treatment, usually surgery associated with multidrug chemotherapy The stage of the disease remains the most important prognostic factor. Patients diagnosed with dysgerminoma are a separate group with very good prognosis.

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.

Para-aortic lymph node metastasis in malignant dysgerminoma of the ovary.

Dysgerminomas comprise approximately 2-5% of all ovarian malignancies and mostly affect young adolescent women. Primary comprehensive surgery and adjuvant chemotherapy consisting of bleomycin, etoposide, and cisplatin (BEP) are the current recommended treatment options, the latter reserved for advanced stages (FIGO II-IV). We report two patients aged 20 and 26 years who presented with an initial FIGO stage IA, but inadequately assessed. Both were subsequently diagnosed with recurrent malignant dysgerminoma and para-aortic lymph node metastasis. Neither had received comprehensive staging at initial surgery nor adjuvant radio or chemotherapy. Both needed extensive surgery and multiagent chemotherapy for survival and belong to the small percentage of FIGO IA dysgerminoma patients showing a relapse. Comprehensive initial surgery including systematic para-aortic lymphadenectomy and adjuvant chemotherapy at tertiary referral centers is needed to minimize the treatment burden.

Paediatric dysgerminoma: Results of three consecutive French germ cell tumours clinical studies (TGM-85/90/95) with late effects study.

METHODS: French patients (≤18years) treated for dysgerminoma between 1985 and 2005 in TGM-85, 90, 95 protocols were included. Treatment was based on primary unilateral oophorectomy followed by prophylactic lymph node irradiation (1985-1998) or a wait-and-see strategy (1998-2005) for localised completely resected tumours (pS1) or by platinum-based chemotherapy for advanced diseases. RESULTS: Forty-eight patients (median age 12.8 years) were included. Six patients had gonadal dysgenesis. Two had bilateral dysgerminoma. Twenty-eight patients had loco-regional dissemination, seven with para-aortic lymph nodes. None had distant metastases. Primary surgery was performed in 47/48 patients. Among the 15 patients with pS1 tumour: seven did not receive adjuvant treatment, six had lymph node irradiation and two received chemotherapy. Among the 32 patients with advanced tumour, 31 received cisplatinum-based (n = 25) or carboplatin-based (n = 8) regimen with lymph node irradiation for one of them and one did not receive adjuvant treatment. With a median follow-up of 14 years, all patients are alive in complete remission. Five events occurred: 2 contralateral dysgerminomas, 1 peritoneal relapse and 2 second neoplasms (teratoma and melanoma). Bilateral oophorectomy was necessary for 12 patients. Desire of pregnancy was expressed for 17/36 patients with unilateral oophorectomy, which succeeded in 13 cases (5 medically assisted). 2/17 had ovarian failure. The renal function was normal in 24/25 evaluated patients treated with platinum, ifosfamide or irradiation. The hearing function was evaluated on 17/36 patients treated with platinum: 12 Brock grade-0, 3 brock grade-1 and 2 grade-4. CONCLUSION: Dysgerminoma has an excellent prognosis even in advanced cases with conservative surgery and platinum-based chemotherapy. However the disease and/or treatment resulted in a high rate of bilateral oophorectomies and a significant impact on future fertility.

Radiotherapy for stage 2 testicular seminoma: the prognostic influence of tumor bulk.

Forty-nine consecutive patients with stage 2 testicular seminoma were treated with primary radiotherapy from 1968 to 1985. Overall diseases-free survival (DFS) for patients with 36 months minimum follow-up was 82% at 3 years. This figure did not decline further with time. Infradiaphragmatic bulk disease was found to be a significant prognostic factor for local and distant relapse as well as for ultimate survival. Patients with either stage 2A or 2B disease (infradiaphragmatic bulk less than or equal to 10 cm size) had a 3-year DFS of 89% compared with a 64% 3-year DFS rate for patients with stage 2C disease (infradiaphragmatic bulk greater than or equal to 10 cm size). The (local plus distant) relapse rate was 4.0% for patients with stage 2A disease, 16.7% for patients with stage 2B disease, and 33.3% for patients with stage 2C disease. The majority of distant relapses were multifocal and prophylactic mediastinal irradiation did not appear to influence either relapse rate nor overall survival. Of seven patients who relapsed, four died of progressive malignancy, two deaths were related to salvage chemotherapy, and only one patient is alive and well following successful chemotherapeutic salvage. On the basis of our experience, we recommend radiotherapy with the use of modern imaging techniques as initial treatment for patients with retroperitoneal masses less than 10 cm size. Aggressive cisplatin-based chemotherapy should be seriously considered for patients with retroperitoneal masses greater than or equal to 10 cm size, or for patients who relapse following radiotherapy.

The treatment of extragonadal seminoma.

Primary extragonadal seminoma (EGS) is a rare tumor of young adults that often presents with bulky primary tumors and metastatic disease. Long-term survival is inadequate with conventional therapy consisting of radiotherapy with or without surgery. The charts of 21 patients with EGS treated initially either with conventional therapy (group I) or with multimodality therapy including initial chemotherapy with high doses of cisplatin followed by either radiotherapy or surgery or both (group II) were reviewed. Five of the ten patients in group I developed recurrent disease and four of them eventually died of disease. Only one of 11 patients in group II died of metastatic disease and the remaining patients are free of disease with 19+ to 46+ months of follow-up. Of the six patients from group II who underwent surgical resection of apparently residual disease after chemotherapy but prior to radiotherapy, five were found to have completely necrotic tumor and one had microscopic disease on histologic examination, proving the efficacy of chemotherapy. Combined modality therapy including initial chemotherapy containing high doses of cisplatin provided rapid reduction in tumor burden and the results appeared superior to treatment that did not include initial chemotherapy.

Simple nontoxic treatment of advanced metastatic seminoma with carboplatin.

Between 1982 and 1986, 34 patients with advanced metastatic seminoma were treated with four to six courses of single-agent carboplatin administered at 400 mg/m2 every 4 weeks either on an outpatient basis or during 24-hour admissions. Patients with raised serum alphafetoprotein (AFP) or with multiple (more than three) lung metastases were excluded since these features may indicate a nonseminomatous component. In this series 20 patients were previously untreated except for orchiectomy, and 14 patients had received prior radiotherapy restricted to infradiaphragmatic nodal areas. Treatment was extremely well tolerated. No patient suffered renal damage, neurotoxicity, or ototoxicity, and there were no episodes of neutropenic septicemia, thrombocytopenic hemorrhage, or bruising. The actuarial 2-year survival was 94% (95% confidence intervals, 83% to 100%) with follow-up of 12 to 46 months from completion of carboplatin (mean, 26 months). The actuarial chance of remaining alive and free from progressive disease at 2 years was 80% (95% confidence intervals, 66% to 94%). Of six patients who relapsed, five are currently in remission 9 to 18 months after completion of salvage treatment. This level of antitumor activity is equivalent to that seen with aggressive combination regimens. Single-agent carboplatin should be considered the treatment of choice for advanced stages of malignant seminoma when limitation of toxicity is considered important; however, the rarity, especially of extranodal metastases from seminoma, leads to the need for further investigation using this approach.

Late relapse of testicular cancer.

The complete response (CR) rate of disseminated germ-cell tumors with current aggressive chemotherapy and surgical resection of localized residual disease is between 70%-80%. Most patients who relapse do so within the first year of therapy. We have observed seven patients with germ-cell tumors treated with a variety of modalities who relapsed after more than two years in CR (45-87 months). Five patients are alive after salvage therapy with follow-up too short to assess the durability of second remission. There were no features distinguishing late relapse patients from all patients treated with chemotherapy for germ-cell tumors. Follow-up in patients treated for germ-cell tumors with chemotherapy should be extended to five years before curability can be established.

Chemotherapy of metastatic seminoma: the Southeastern Cancer Study Group experience.

From 1978 to 1984, 62 patients with advanced seminoma of testicular or extragonadal origin were entered on two consecutive Southeastern Cancer Study Group (SECSG) protocols. All patients had progressive disease and were stratified according to tumor burden. Randomization on SEG 78-GU240 was cisplatin, vinblastine, and bleomycin (PVB), with or without doxorubicin; on SEG 81-GU332, randomization was to PVB or cisplatin, etoposide (VP-16), and bleomycin (PVP16B). Dosages of etoposide, vinblastine, and doxorubicin were decreased by 25% in patients who had received prior radiotherapy. Thirty patients (55%) had received prior chest and/or abdominal radiotherapy. Overall, 41 of 60 evaluable patients (68%) achieved a complete remission (CR) and 37 patients are alive and free of disease. CR was obtained in 13 of 15 patients (87%) with minimal disease, 13 of 16 (81%) with moderate disease, and 15 of 29 (52%) with advanced disease. Patients with no prior radiotherapy or limited-field (chest or abdomen) radiotherapy were more likely to achieve CR than those with prior chest and abdominal radiotherapy (75% v. 42%). Using univariate analysis, the extent of disease is the only significant prognostic factor, whereas both extent of disease and extent of prior radiotherapy are significant in a multivariate analysis. This study confirms the chemosensitivity of metastatic seminoma in a cooperative group setting and defines prognostic factors useful for comparison of other chemotherapeutic trials in seminoma.

The activity of single-agent carboplatin in advanced seminoma.

Between 1982 and 1990, 70 patients with advanced metastatic seminoma were treated with 4-6 courses of single-agent carboplatin (SAC) administered at 400 mg/m2 every 3-4 weeks. Treatment was of low toxicity and no patients suffered neurotoxicity, ototoxicity or significant renal damage. There was only one episode of neutropenic sepsis and no thrombocytopenic bleeding. The median follow-up of surviving patients was 3 years. 16 patients have relapsed and 4 of these 16 have died, thus the actuarial 3-year relapse-free survival was 77% (95% CI 65-86%), cause-specific survival was 94% (95% CI 82-99%) and overall survival was 91% (95% CI 80-96%). The risk of relapse was reduced by post-chemotherapy irradiation (PCRT) to involved nodes, occurring in 1/20 patients treated with PCRT compared with 11/31 who could have been treated but were not (P = 0.04). Of the 16 patients who relapsed, 12(75%) have been salvaged with combination chemotherapy and remain free from further relapse with a median follow-up of 18 months. Though this level of survival is equivalent to that obtained with initial cisplatin-based combination chemotherapy, the recurrence rate indicates that SAC remains an investigative treatment, except for unfit patients.

Seminoma of the testis: results of treatment and patterns of failure after radiation therapy.

Four hundred and forty-four patients with the histological diagnosis of pure seminoma were treated at The Princess Margaret Hospital between 1958 and 1976. Using the Walter Reed Hospital staging classification, 338 patients (76.1%) were Stage I, 86 (19.4%) were Stage II, and 20 (4.7%) were Stage III. The 5 year actuarial survival rate (5 yr Sa) for all stages was 87%, and for Stages I, II and III: 94%, 74% and 32% respectively. In Stage II the 5-year Sa was significantly worse when palpable abdominal disease was present (62%, vs 87% when it was absent, p less than .02). Prophylactic mediastinal irradiation was not used for patients with Stage II disease. None of 40 Stage II patients without palpable abdominal disease recurred in the non-irradiated mediastinum. Ten of 46 Stage II patients with palpable abdominal disease recurred in the mediastinum; 7 of the 10 were cured with mediastinal irradiation at the time of relapse. Prophylactic mediastinal irradiation appears unnecessary in Stage II patients. The Stage III category includes a subgroup of patients who were curable with radiation therapy:L 5/6 with supradiaphragmatic nodal disease without palpable abdominal or visceral disease were cured. Exploration of new treatment methods appears indicated for the salvage of patients recurring in sites other than the mediastinum or supraclavicular fossa and for patients presenting with visceral disease.

Management of seminoma with bulky abdominal disease.

Thirty-three cases of seminoma with palpable abdominal disease were treated at the Cancer Control Agency of B.C. between 1948 and 1983. Twenty-three had disease confined to the abdomen (Stage IIB), eight had simultaneous involvement of mediastinal and supraclavicular nodes (Stage IIIB) and two had bone or pulmonary metastases (Stage IV). Five and 10-year disease-specific actuarial survivals for the whole group were 87% and 81%, respectively. Corresponding relapse-free survival was 64%. Of the twenty-three IIB cases, 15 had primary treatment with abdominal radiation only, and eight had prophylactic mediastinal/supraclavicular radiation. Although relapse in IIB was more common in the group receiving abdominal radiation only, survival was unchanged. For the entire IIB group, 5- and 10-year disease-specific actuarial survivals were 91% and 84%, respectively, and corresponding relapse-free survival was 74%. The eight IIIB patients were treated primarily with radiation. Four patients relapsed, all in extranodal sites. Two of these died of disease. Both Stage IV patients required radiation and chemotherapy for long-term disease control. Stage IIB disease can be treated primarily with abdominal radiation, but radiation alone is inadequate when bulky abdominal disease is associated with supradiaphragmatic lymphatic spread or hematogenous metastases.

Primary chemotherapy for clinical stage II nonseminomatous germ cell testicular tumors: selection criteria and long-term results.

OBJECTIVE: To determine the treatment option for patients with low-volume stage II nonseminomatous germ cell testicular tumors (NSGCTT) that yields the best survival, is associated with the least morbidity, and avoids "double therapy"--that is, chemotherapy and retroperitoneal lymph node dissection (RPLND). DESIGN: We reviewed our institutional experience with 28 patients with stage II NSGCTT who received primary chemotherapy between August 1983 and October 1992. MATERIAL AND METHODS: The 28 study patients (mean age, 28 years; range, 20 to 52) with low-volume stage II NSGCTT were treated with bleomycin, etoposide, and cisplatin. The correlation of response rates with volume of disease and predominant histologic cell type was determined. The duration of survival was measured from the initiation of chemotherapy to the appearance of progressive disease or death or the date of last follow-up visit. RESULTS: Of the 28 patients treated, 27 (96%) achieved a complete response--20 (71%) with only chemotherapy and an additional 7 (25%) with chemotherapy plus surgical treatment. Twenty-seven patients (96%) remained free of disease after a median follow-up of 72 months. The most frequent complication was cisplatin-associated paresthesias or tinnitus which was noted in 13 patients (46%). In 11 of 15 patients (73%), attempts to have children have been successful. CONCLUSION: Excellent long-term survival rates in patients with stage II NSGCTT can be achieved with primary chemotherapy. In this series, 71% of patients were spared RPLND. The need for postchemotherapy RPLND seemed to be related to the initial metastatic tumor volume and possibly the histologic features of the primary tumor. Continued refinement in surgical techniques and chemotherapeutic regimens will necessitate the comparison of these two treatment approaches in a randomized prospective trial.

Pineal germinoma with syncytiotrophoblastic giant cells: a case with panhypopituitarism and isosexual pseudopuberty.

A previously healthy boy, aged 12 years, developed hypopituitarism due to suprasellar metastases from a pineal germinoma with syncytiotrophoblastic giant cells (SGC). Despite the hypopituitarism, the patient showed pubertal development, which was associated with abnormal levels of human chorionic gonadotropin (hCG) in the cerebrospinal fluid. This case adds support to the theory that precocious puberty in children with pineal germinomas may be due to the secretion of hCG by SGC, a minor component of the germinoma. It also illustrates the point that, although abnormal levels of circulating hCG in children with pineal tumors may indicate a diagnosis of choriocarcinoma with its encumbent poor prognosis, other pineal germ cell tumors may also secrete hCG. Although this patient had abnormal levels of hCG, his cerebral tumor exhibited behavior more commonly associated with pineal germinoma than with choriocarcinoma.

Management of primary mediastinal seminoma.

Radiation therapy has been the usual initial treatment for mediastinal seminoma in the past. However, 25 to 40 percent of patients are not cured by this therapy, and other therapy is needed. Review of case reports show that vinblastine, bleomycin, and cis-platinum are effective therapy for metastatic disease, advanced disease within the chest, or mixed germ cell tumors with nonseminomatous elements. The use of tumor markers and chemotherapy must be integrated into the staging of and therapy for primary mediastinal seminoma.

Unusual initial calcification of primary and metastatic seminomas. Detection by computed tomography.

Rare large ab initio calcifications of a primary mediastinal seminoma in a 16-year-old boy and of para-aortic nodal metastatic ovarian seminoma in a 14-year-old girl are demonstrated with CT but not with conventional radiography. They are most likely dystrophic calcifications because of the absence of other germ cell tumor components and infective granulomatous disease. Routine use of CT might detect more such calcifications in untreated seminoma.

Isoenzymes of alkaline phosphatases in seminomas. An immunohistochemical and biochemical study.

Placental alkaline phosphatase (the PLAP-like isoenzyme) and liver alkaline phosphatase (LAP) were demonstrated immunohistochemically by use of monoclonal antibodies in the tumor cells of twelve seminomas and one seminoma metastasis. Intestinal alkaline phosphatase (IAP) was not found. The PLAP-like and LAP enzymes showed high catalytic activities compared to normal testis. This is the first occasion that LAP has been demonstrated by immunochemistry in seminoma cells. The results suggest that demonstration of these tumor enzymes may be useful markers for seminomas in histopathological specimens.