Bulky mesonephric adenocarcinoma of the uterine cervix treated with neoadjuvant chemotherapy and radical surgery: report of the first case.

AIMS AND BACKGROUND: Malignant mesonephric adenocarcinoma of the uterine cervix is a rare occurrence with few cases described in the literature. Although surgery seems to be effective in the treatment of early-stage tumor, no cases describing outcomes of locally advanced stage are available. METHODS: We report the first case of a patient with International Federation of Obstetrics and Gynecologists stage IIB mesonephric adenocarcinoma undergoing neoadjuvant chemotherapy and radical surgery. CONCLUSIONS: Despite the inherent limitation of a single description of a case, our experience supports the utilization of neoadjuvant chemotherapy in patients with malignant mesonephric adenocarcinoma of the uterine cervix. Further prospective multi-institutional studies are needed.

Brain metastases and testicular tumors: long-term survival.

In this updated and expanded retrospective analysis, the treatment records of 24 patients with brain metastases from nonseminomatous germ cell testicular tumors (NSGCT's) treated at the Indiana University Department of Radiation Oncology from 1975 through 1988 were reviewed. All patients received standard cisplatin-based induction chemotherapy. These patients were divided into three groups. Group 1 (n = 10) consisted of patients who presented initially with brain metastases and had no prior systemic treatment. Group 2 (n = 4) consisted of those patients who, after achieving a complete response (CR) with cisplatin, vinblastine, and bleomycin (PVB) +/- doxorubicin, developed a relapse confined to the brain. Group 3 (n = 10) consisted of those patients who were initially treated with PVB +/- doxorubicin or bleomycin, etoposide, and cisplatin (BEP) and eventually developed progressive disease and brain metastases. Group 1 was treated with whole brain irradiation (WBRT) and PVB +/- doxorubicin or BEP. Group 2 was treated with WBRT, cisplatin-based chemotherapy +/- surgical excision. Group 3 was usually treated with WBRT palliatively. Six patients, three in Group 1 and three in Group 2, are alive and disease-free with follow-up of 5+ years from beginning WBRT. Two additional patients in Group 1 survived 5+ years from beginning WBRT before dying with disease. No patient in Group 3 survived. Patients with brain metastases who have potentially controllable systemic disease should be treated curatively with WBRT (5000 cGy/25 fractions) +/- surgical excision and concomitant chemotherapy.

Endometrioid-like variant of ovarian yolk sac tumor. A clinicopathological analysis of eight cases.

The clinical and pathological features of eight ovarian yolk sac tumors with glandular patterns resembling those of endometrioid adenocarcinoma are described. The patients ranged in age from 11 to 34 years (mean, 22 years) and presented with abdominal pain or swelling. The serum alpha-fetoprotein (AFP) level was elevated at the time of presentation or later in all seven patients in whom it was measured. Seven tumors were unilateral, one was bilateral, and three had spread beyond the ovary. There was a contralateral streak gonad in two cases. The tumors were 6-35 cm in diameter; seven were solid and cystic, and one was a unilocular cyst with a small solid nodule in the wall. Microscopic examination revealed a prominent, and in two cases, pure endometrioid-like glandular pattern that often simulated that of an early secretory endometrium. Reticular, polyvesicular-vitelline, and hepatoid patterns of yolk sac tumor were also present in five tumors; minor teratomatous foci (squamous epithelium and cartilage) were present in one. Immunohistochemical staining revealed AFP, alpha-1-anti-trypsin (AAT), and carcinoembryonic antigen within the glandular epithelium; AFP and AAT were also present in areas showing the other patterns. Three patients died of recurrent or metastatic tumor 19-60 months postoperatively; in the remaining cases, there was a tumor-free follow-up of short duration. The endometrioid-like pattern reflects an unusual form of endodermal differentiation within yolk sac tumors that should be distinguished from endometrioid carcinoma.

Malignant mesonephric tumors of the female genital tract: a clinicopathologic study of 9 cases.

Nine malignant mesonephric tumors were obtained from the consultation files of one of the authors (J.P.) over a 13-year period (1988-2001). There were 4 adenocarcinomas (ACs) and 5 malignant mixed mesonephric tumors (MMMTs). The ACs were found in the cervix (3) and vagina (1). The MMMTs involved the uterus (1), cervix (3), and vagina (1). Most patients presented with abnormal vaginal bleeding. The 4 patients with mesonephric AC ranged in age from 24 to 54 years (mean, 41 years). The tumors measured 2 to 6 cm (mean, 3.7 cm). Two ACs were stage I and two were stage II. Two of the three patients with follow-up information were alive without clinical evidence of disease at 3 and 11.5 years, and the other was alive with recurrent tumor 8.5 years postoperatively. The 5 patients with MMMTs ranged in age from 37 to 62 years (mean, 49 years). The mean size of four tumors was 5.2 cm (range, 3.5-8 cm). The uterine MMMT infiltrated the entire myometrial wall extending to the endometrial cavity where it resembled an endometrial polyp. Although the most common histologic pattern in the current series was the glandular (ductal) pattern, retiform, tubular, and solid growth patterns were also encountered. Among the MMMT subgroup, the sarcomatous component was homologous in 3 cases (endometrial stromal or spindle cell) and heterologous in the other 2 cases (skeletal muscle and cartilage). Of the 4 patients with follow-up information available, 1 (stage II) died of disease 7 months after surgery, another (stage IV) was alive with bone metastases at 3.3 years, and the other 2 patients (stages IB and IC) had no clinical evidence of disease at 1 and 3.7 years, respectively. Evidence of mesonephric hyperplasia was found in 5 (42%) cases. The MMMT that arose in the corpus presented as an endometrial polyp. In this case, histologic differential diagnosis includes serous carcinoma, endometrial stromal sarcoma, and uterine tumor resembling ovarian sex cord-stromal tumor. Immunostainings are not helpful. Mesonephric ACs often present in early stage and have better prognosis than their müllerian counterparts. Surgery alone appears to be the treatment of choice. In contrast, MMMTs may present in advanced stage and are aggressive tumors, similar to malignant mixed müllerian tumors.

Mesonephric adenocarcinoma of the uterine corpus: CD10 expression as evidence of mesonephric differentiation.

Mesonephric (wolffian) neoplasms of the female genital tract are infrequent and found in sites where embryonic remnants of wolffian origin are usually detected, such as the uterine cervix, broad ligament, mesosalpinx, and ovary. Their diagnosis is difficult because of the absence of specific immunohistochemical markers for mesonephric derivatives. We present the first report of adenocarcinoma of mesonephric type arising as a purely myometrial mass without endometrial or cervical involvement in the uterine corpus of a 33-year-old woman. The tumor showed a combination of patterns, with retiform areas, ductal foci, and small tubules with eosinophilic secretion, which merged with solid sheets of cells with a sarcomatoid appearance. Immunohistochemically, neoplastic cells were diffusely positive for cytokeratin 7, epithelial membrane antigen, and CD15 and focally positive for BerEP4 and vimentin. A hitherto unreported feature was the positivity for CD10 in neoplastic cells, which was also present in a large number of control tissues obtained from male mesonephric derivatives and female mesonephric remnants and tumors. Furthermore, CD10 was negative in controls from müllerian epithelia of the female genital tract and in their corresponding tumors. Therefore, the expression of CD10 by mesonephric remnants may be useful in establishing the diagnosis of tumors with mesonephric differentiation.

Yolk sac tumors with pure and mixed polyvesicular vitelline patterns.

Four cases of polyvesicular vitelline tumor are presented; two were of a previously unreported pure type, and the other two were mixed with endodermal sinus tumor. The morphologic features of the vesicles favor an endodermal origin, as originally proposed by Teilum. Marked specialization of the vesicular lining cells, seen ultrastructurally, suggests a differentiation toward gut structures and mature yolk sac. One case of pure polyvesicular vitelline tumor showed massive erythropoiesis. We propose that the pure tumor reflects an intermediate degree of differentiation within the selectively endodermal yolk sac tumor group, that is, a further stage of organization than the endodermal sinus tumor. In our cases of pure polyvesicular vitelline tumor, the marked degree of differentiaiton was correlated with an improved prognosis, as in the case of the possible homologue of this tumor, the yolk sac tumor of the infant testis. In contrast, the two cases of the tumor admixed with endodermal sinus tumor illustrated the low survival rate expected in the pure endodermal sinus tumor; in these cases the metastases had no polyvesicular component. Because of the significance of such a difference in prognosis we emphasize the importance of an accurate diagnosis, suggesting that a large number of sections be taken in order to demonstrate any endodermal sinus tumor component that may be present, and that the possibility of pure polyvesicular vitelline tumor always be considered in the differential diagnosis of multicystic ovarian tumors.

Management of primary germ cell tumors of the mediastinum.

Twenty-eight patients with primary malignant germ cell tumors (GCT) of the mediastinum were treated at the University of California at Los Angeles and The Johns Hopkins Hospital in the past 30 years. Of 11 patients with pure seminomas, nine (82%) are free of disease from 6 months to 15 years following therapy. The primary treatment modality in these patients was mediastinal radiation; one patient with metastatic disease had a complete remission and prolonged survival following combination chemotherapy. Seventeen patients had GCT with nonseminomatous elements. Only three (18%) are alive and free of disease. One patient treated only surgically is alive at 15 years and two patients treated with combination chemotherapy and operation are alive and free of disease at 6 months and 3 years. When analyzed by a Kaplan-Meier actuarial survival estimate, patients with nonseminomatous GCT who were treated with cisplatin-bleomycin-based chemotherapy had a median survival of 14.0 months whereas those treated with chemotherapy regimens not employing these agents had a median survival of 4.0 months (generalized Wilcoxon test, p = 0.0495). Patients with pure seminomas are effectively treated with radiation therapy. Patients with nonseminomatous tumors have a much poorer prognosis and deserve aggressive multimodality therapy with cisplatin-bleomycin-based chemotherapy.

Mediastinal yolk sac tumor. The Indiana University experience, 1976 to 1988.

Mediastinal yolk sac tumor (endodermal sinus tumor) is an extremely rare extragonadal germ cell neoplasm that has been associated with a grave prognosis. Twenty-one male patients with mediastinal yolk sac tumor received treatment at Indiana University between 1976 and 1988. Fourteen were seen after initial diagnosis, and their disease was treated with cisplatin-based chemotherapy in association with complete surgical resection if possible. Five are currently alive and disease free (36%). Seven were referred for salvage chemotherapy after relapse of their disease. Despite aggressive chemotherapy, these patients all died; they had a median survival time of 6 months. Our experience suggests that an aggressive combined modality approach with cisplatin-based chemotherapy followed by surgical resection of residual disease is the optimal management of this tumor. New regimens need to be explored for relapse of the disease after initial chemotherapy.

Endodermal sinus tumor of the mediastinum. Report of apparent cure in two patients with extensive disease.

Primary endodermal sinus tumor (EST) of the mediastinum has been regarded as a rare and rapidly fatal germ cell neoplasm. We describe two cases of extensive EST treated with a new high-dose sequential combination chemotherapy regimen (CISCA-VB) followed by radical surgical excision. They are alive at 11 and 20 months, respectively, postoperatively. These cases stand in marked contrast to previously reported series. A new approach to the management of this tumor is proposed.

Endodermal sinus tumor: report of a case associated with pregnancy.

The case of a 15-year-old black primigravida with an 18-week intrauterine gestation and concurrent endodermal sinus tumor is presented. Rationale for therapy is discussed.

Endodermal sinus tumor arising in the endometrium.

A case of primary endodermal sinus tumor (EST) of the endometrium in a 28-year-old woman is described. EST has been reported to arise in several extragonadal sites, but to the authors' knowledge this is the first documented instance of origin in the endometrium. The histologic study is verified by the detection of alpha-fetoprotein in the tumor by an immunoperoxidase-peroxidase-antiperoxidase technique reported here. Displaced germinal cells, abnormal ovum, and residual fetal tissues are considered as possible origins of the neoplasia.

Germ cell malignancies of the ovary.

Historically, ovarian germ cell malignancies carry a very poor prognosis. The use of surgery alone or in combination with radiation therapy does not appreciably increase survival. The combination of surgery, chemotherapy, and, in some instances, radiation therapy has accounted for an 89% two-year survival in 26 patients with germ cell malignancies of the ovary exclusive of "pure" dysgerminoma. Short-term chemotherapy appears as effective as the long-term therapy advocated by other investigators.

Pregnancy following removal and chemotherapy of ovarian endodermal sinus tumor.

The first reported case of successful pregnancy following unilateral adnexectomy and combination chemotherapy for nedodermal sinus tumor is presented. The rationale for conservative management of this virulent neoplasm is discussed.

Maternal and fetal survival following surgery and chemotherapy of endodermal sinus tumor of the ovary during pregnancy: a case report.

An ovarian endodermal sinus tumor was found in a patient with a 15-week intrauterine gestation. She received conservative surgery and six courses of combination chemotherapy from 16 weeks' gestation, and delivered a normal term infant at 37 weeks' gestation. Two other courses of combination chemotherapy including cisplatin were added. No residual tumor was found at subsequent exploration, and she is alive 33 months after the original diagnosis without any evidence of recurrence. We believe this is the first reported case of maternal survival past 2 years and the earliest chemotherapy done in the early second trimester of pregnancy without resulting in fetal abnormalities.

Endodermal sinus tumor of the ovary: the M. D. Anderson experience.

Forty-one patients with pure endodermal sinus tumor of the ovary who were treated at the M. D. Anderson Hospital from 1944 to 1981 are retrospectively reviewed. The median age of these patients was 19 years. The most common presenting symptom was abdominal pain, occurring in 33 patients (80%). No bilateral ovarian involvement was noted at initial surgery. With the exception of 1 patient treated by surgery alone, only patients treated with postoperative combination chemotherapy survived. Twenty-one of the 41 patients are alive and well. Sixteen of 22 patients treated with vincristine, actinomycin-D, and cyclophosphamide have survived. The roles of second-look laparotomy and alpha-fetoprotein monitoring are discussed. Optimal treatment seems to consist of surgery followed by aggressive combination chemotherapy.

Mediastinal nonseminomatous germ cell tumors: the role of combined modality therapy.

Twelve male patients with mediastinal nonseminomatous germ cell tumors were treated with chemotherapy (with or without operation and radiation therapy) between 1963 and 1980. Eight patients, treated with only chemotherapy and radiotherapy, died with a median survival from diagnosis of 6 months (range, 3 to 12 months). The 4 survivors remain alive at 12, 15, 34, and 56 months from diagnosis; all are without evidence of disease. All surviving patients were treated with surgical resection of disease either before of after chemotherapy. A major problem in the management of mediastinal nonseminomatous germ cell tumors is the persistence of local disease, which may be overcome by vigorous cytoreductive intervention. Multicenter collaboration will be required to define the optimal combined-modality approach.

Clinical dilemma in management of yolk sac tumor of childhood testis.

An "expectant" approach to management of yolk sac type testis tumors in two boys led to therapeutic failure. The rationale for such "nontherapy" in light of current knowledge is discussed. The need for more sophisticated tumor staging as well as improved chemotherapeutic approaches in treatment planning is suggested.

Management of yolk sac tumors in children.

The current trend toward minimizing treatment morbidity in children with yolk sac carcinomas is laudable. As most children will present with stage I disease and be cured by radical orchiectomy alone, careful surveillance is adequate with the knowledge that effective chemotherapy is available should tumor recur. All new yolk sac carcinomas in children should be reported to the Prepubertal Testicular Tumor Registry and should ideally be treated at institutions that have experience with surveillance protocols and pediatric oncology. In this way, prospective studies on treatment options can be initiated, and management controversies may ultimately be ironed out. In particular, more information is needed on patients more than 2 years old, as the literature to date is contradictory regarding the prognosis for these patients and the need for adjuvant therapy when the older child presents with stage I disease.

Pediatric urologic oncology.

Effective chemotherapy combined with surgery has produced excellent disease-free survival rates in most children with genitourinary malignancy. For patients with Wilms' tumor, the overall 2-year survival rate with no evidence of disease is greater than 90 per cent, and the interval of chemotherapy continues to be reduced for those children with low-stage lesions and favorable histologic patterns. In children with pelvic rhabdomyosarcoma, primary cytoreductive chemotherapy has proved to be an effective alternative to exenterative surgery. Patients with yolk-sac tumor who have localized disease need not be subjected to the potential morbidity of retroperitoneal lymph-adenectomy or the toxicity of adjuvant chemotherapy. Conversely, patients with advanced disease can be salvaged with recently developed combination chemotherapeutic regimens.

Value of tumor markers in the treatment of endodermal sinus tumors and choriocarcinomas in the pineal region.

A case of embryonal carcinoma in the pineal region of a 17-year-old boy is presented. The tumor included elements of choriocarcinoma and endodermal sinus tumor, and the use of human chorionic gonadotropin and alpha-fetoprotein as tumor markers is discussed. The markers were demonstrated both within the tumor and in the cerebrospinal fluid (CSF) and blood. The patient was treated with a postoperative program of irradiation and cancer chemotherapy, and at follow-up examination 20 months after operation no signs of residual tumor were present. It is suggested that human chorionic gonadotropin and alpha-fetoprotein should be measured in the blood and CSF before the treatment of midline tumors.