Mesonephric adenocarcinomas in female genital tract: A case series.

ABSTRACT: Mesonephric adenocarcinoma (MNAC) is a very rare tumor that originates from mesonephric duct remnants of the female genital tract. Only a few cases were reported in the literature, and most of them occurred in the cervix, extremely rare in the uterine body and ovary. MNAC was rarely reported to arise in the uterine corpus, but never was reported in the ovary. Mesonephric-like adenocarcinomas are recently suggested to describe these neoplasms arising from the uterine corpus and ovary. Due to the rareness of the disease, little is known regarding clinical characteristics, pathological diagnosis, prognosis, and optimal management strategy of MNAC in the female reproductive system. We report a series of MNACs arising from the vagina, cervix, uterine corpus, ovary, and fallopian tube, to summarize the clinical characteristics, pathological diagnosis, treatment, and prognosis.We retrospectively analyzed all MNACs in the female genital tract derived from our institute from January 2010 till January 2020. Patients' clinical details and follow-up were obtained from hospital records and scans were obtained from picture archiving and communication system.A total of 11 patients were included. The median age of onset of symptoms was 52 years. All patients underwent total hysterectomy and bilateral salpingo-oophorectomy, and lymph node dissections were performed in 7/11 (63.6%) patients. Two/eleven (18.2%) received neoadjuvant chemotherapy before surgery and 7/11 (63.6%) received adjuvant chemotherapy after primary surgery. Of the 11 patients, only 1 patient received adjuvant radiation therapy. One patient died at the end point of this study, 9 patients (81.8%) survived and 1 patient was lost to follow-up. The mean follow-up duration was 33.5 months.Although there is no consensus for the optimal treatment of this rare disease, radical surgery is considered to be the initial choice for localized lesion. Given the high malignancy, the majority of MNAC or mesonephric-like adenocarcinoma patients who underwent adjuvant chemotherapy received 4 to 8 cycles of carboplatin/paclitaxel as a first-line treatment after primary surgery with a median progression-free survival of 12 months. Treatment for recurrent disease in these patients included gemcitabine, carboplatin, and paclitaxel. Radiation was very limited in the treatment of the disease.

Mesonephric adenocarcinomas of the uterine cervix: a study of 11 cases with immunohistochemical findings.

Mesonephric adenocarcinoma is a rare variant of cervical carcinoma with relatively few, well-documented cases reported. We describe the clinicopathologic and immunohistochemical features of 11 examples of this neoplasm, which occurred in women between the ages of 35 and 72 years (mean, 52 years). Most (64%) patients had abnormal vaginal bleeding. Eight tumors were stage IB, and one each was stage IIB and IVB; in one, the stage was unknown. Microscopically, the carcinomas showed various morphologies, most commonly a small tubular pattern or a ductal pattern resembling endometrioid adenocarcinoma; one tumor had an associated malignant spindle cell component. Ten neoplasms were adjacent to hyperplastic mesonephric remnants. Follow-up in 10 cases showed six patients to be alive without evidence of recurrence after a mean of 4.8 years. The patients with stage IIB and IVB disease had local recurrences after 2.2 and 0.7 years and died of progressive disease at 3.2 and 0.8 years, respectively. In a patient with stage IB disease, a mediastinal metastasis and a malignant pleural effusion developed 5.6 years after diagnosis, and the patient died of disease at 6.2 years. Another patient with stage IB disease and a positive vaginal cuff margin that recurred locally after 1.7 years received chemotherapy and was alive and clinically free of disease at 2.5 years. Mesonephric adenocarcinomas were immunoreactive for epithelial markers (AE1/3; CK1, CAM 5.2, cytokeratin 7, and epithelial membrane antigen) (100%), calretinin (88%), vimentin (70%), androgen receptor (33%), and inhibin (30%, focal staining). No immunostaining was detected with cytokeratin 20, estrogen receptor, progesterone receptor, and monoclonal carcinoembryonic antigen. This staining profile is similar to that of mesonephric remnants and may be useful in the distinction of mesonephric carcinoma from mullerian endometrioid adenocarcinoma, with which it may be confused.

[Therapy of testicular germ cell tumors. Current status of the MAHO studies]. / Therapie testikulärer Keimzelltumoren. Aktueller Stand der MAHO-Studien.

The GPOH-MAHO trials designed in 3/82 and 7/88 for treatment of childhood testicular germ cell tumors registered 3/92 105 pts. In MAHO 82 study 57 pts. and in MAHO 88 study 48 pts. were treated. Histologically 60% of the tumors revealed yolk sac tumors (YST), 22% teratomas (TD) and 18% malignant teratomas (MTI, MTU, MTT). Beside unilateral orchiectomy, according to stage and histology a stratified chemotherapy was administered. Standard chemotherapy consisted of 4 courses VLB, BLM, DDP, after 2 courses standard chemotherapy if vital tumor was suspected: explorative laparatomy. According to laparatomy some patients received salvage chemotherapy of 3 courses VP 16, IFO and DDP. The following results were obtained: YST: 59 pts. with stage I. Of these 10 received adjuvant chemotherapy with VLB, BML, DDP. 49 pts. were followed according to wait and see policy and not treated by adjuvant chemotherapy; 8 pts. had a relapse. 5 were treated with standard chemotherapy and 1 pt. with salvage therapy. 1 pt. had stage II and another stage III. Both received standard chemotherapy. The survival of all 61 pts. is 100%. Median observation time is 4 years. TD: 25 pts. had stage I. No chemotherapy was given. The relapse free survival is 100%. Median observation time is 4 years. Malignant teratomas (MTI, MTU, MTT): 8 pts. had stage I. Of these 3 received adjuvant chemotherapy, 5 lymphadenectomy without chemotherapy. All patients survived without relapse. 8 pts. had stage II and received standard chemotherapy, of these 4 pts. had stage IIc and explorative laparotomy was done. According to the result 2 pts. received salvage therapy. All pts. survived relapse free.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical picture of tumors from the mesoblastoma group in women]. / Obraz kliniczny nowotworu z grupy mesoblastoma u kobiet.

Yolk Sac Tumor (YST) originating from the primitive reproductive cells reminds with its microscopic construction a gallbladder or an endodermal sinus thus the name endodermal sinus tumor, Yolk sac tumor, mesoblastoma vitellinum Teilum. There have been presented here two cases of YST of different locality with unusual development of one of them and rapid course in the both cases. In both discussed cases the survival period exceeds 3 months. Both patients are still alive and the period from the day of diagnosis and operation is in one case 26 months and in the second one 11 months.

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.

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 ovary: a case series with flow cytometric DNA content analysis.

Endodermal sinus tumors (EST) are rare germ cell ovarian malignancies occurring primarily in young women. A retrospective review of the Magee-Womens Hospital tumor registry revealed eight cases of pure EST and two mixed tumors in which the EST component was predominant. Mean patient age was 18.2 years. Abdominal pain was the most common presenting symptom and a pelvic mass was palpable in all patients. Four patients are currently alive and well with no evidence of disease. All were treated with surgery and combination chemotherapy. Flow cytometric DNA content analysis of paraffin-embedded tumor tissue identified similar aneuploid cell populations in three of five tumors analyzed with relative peak positions of 1.72, 1.62, and 1.70. The management of women with endodermal sinus tumor remains controversial with regard to type of chemotherapy employed and the use of second-look laparotomy. The prognosis role of flow cytometric DNA content analysis is yet to be determined.

Long-term follow-up of children with testicular tumours: surgical issues.

Testicular tumours are rare in childhood. The clinical, pathological and follow-up details of 48 children are presented. The combined approach of surgery, chemotherapy and radiotherapy is confirmed as being extremely effective. Transcrotal orchiectomy is not an appropriate surgical procedure. Testicular biopsy is detrimental to prognosis.

Prognostic factors in yolk sac tumors of the ovary. A clinicopathologic analysis of 29 cases.

Twenty-nine ovarian cancer patients with yolk sac tumors and germ cell tumors with yolk sac tissue as a component of their disease (16 endodermal sinus tumor, 11 mixed germ cell tumors, one embryonal carcinoma, and one polyembryoma) were treated with cytoreductive surgery and combination chemotherapy. Prognostic factors were investigated in this group. Patients with Stage I disease had a more favorable prognosis (P less than 0.003) than those with Stages II and IV disease. The difference in prognosis was significant in cases where residual tumor was absent (P less than 0.003) and in cases where ascites was either absent or less than 100 ml in volume (P less than 0.05). Endodermal sinus tumor with either an intestinal (P less than 0.05) or microcystic pattern (P less than 0.01) was more common in survivors than in those who died. The age, preoperative serum alpha-fetoprotein level, maximum tumor size, and tumor weight had no significant correlation with prognosis. In advanced cases, chemotherapy regimens including cisplatin gave better results than those containing vincristine, dactinomycin, and cyclophosphamide (P less than 0.05). The optimal treatment of yolk sac tumors or tumors with yolk sac tissue as a component of the ovary is discussed in light of these results.

[Clinical statistics of germinal testicular cancer].

We experienced a hundred and fifty-six cases of germinal testicular cancer at Osaka University Hospital from 1957 to 1988. Histologically, 114 cases (73.1%) were simple type, and 42 cases (26.9%) were mixed type. Eighty cases (51.3%) were seminoma, and 76 cases (48.7%) were non-seminoma. All patients of seminoma were over 20 years of age, and the mean age was 36.1 years. Non-seminoma cases were distributed as to with two peaks, one in 0 to 4 year-old and another in 20 to 39 year-old, and the mean age was 22.9 years. The seminoma/non-seminoma ratio as to clinical stages were 63 cases/48 cases in Stage 1, 6/9 in Stage 2A, 5/6 in Stage 2B and 6/13 in Stage 3. The five-year survival rate (by Kaplan-Meier's method) was 98.4% for Stage 1 (71 cases), 72.7% for Stage 2A (11 cases), 0% for Stage 2B (4 cases) and 20% for Stage 3 (5 cases) between 1957 and 1978, and 100% for Stage 1 (40 cases), Stage 2A (4 cases), Stage 2B (7 cases) and 26.8% for Stage 3 (14 cases) between 1979 and 1988. The five-year survival rate of 20 advanced cases treated mainly by PVB regimen was 100% for Stage 2 (6 cases) and 68.6% for Stage 3 (14 cases). Five advanced cases containing choriocarcinoma elements were treated by PVB regimen and its two-year survival rate was 40.0%, which was statistically worse than that (86.8%) of other histological types (p less than 0.05).

Surgical treatment for recurrent ovarian malignancies.

Eighty-nine cases of recurrent ovarian malignancies which had undergone surgical treatment were studied. Debulking surgery is of great value in the treatment of primary ovarian carcinoma, but for recurrent carcinomas success depends upon the pathological type. The 5-year survival rate was 75% for patients with immature teratomas, but only 6.1% for those with epithelial ovarian carcinomas and 3.6% with endodermal sinus tumors. Two cases of recurrent dysgerminoma were both alive and well more than 10 years after treatment. So repeated debulking is worthwhile for recurrent immature teratoma and dysgerminoma, while in cases of epithelial type or endodermal sinus tumors successful debulking surgery should be followed by some new kinds of adjuvant therapy, otherwise only failure will result.

Endodermal sinus tumor of the ovary: a paradoxical response to chemotherapy.

A patient with ovarian endodermal sinus tumor metastatic to the liver responded unusually to chemotherapy. She experienced histologically documented regression of all intraperitoneal disease with the exception of the liver metastases when given vinblastine, bleomycin, and cisplatin. She eventually died of liver failure. A review of patients with ovarian endodermal sinus tumor who either presented with initial liver metastases or had recurrent disease in the liver leads us to conclude that the liver is a preferential site for spread, that liver metastases carry an ominous prognosis, and that failure to see prompt liver metastatic tumor response after systemic chemotherapy should signal a need for a more aggressive therapeutic approach to the liver lesions.

[Clinicopathological study of malignant ovarian germ cell tumor].

In treating malignant germ cell tumors clinicopathologically at Kurume University Hospital, for 18 years, the total number of patients was 112, including 25 yolk sac tumors (YST), 10 mixed form germ cell tumors (MF), 36 dysgerminomas (DYS), 26 immature teratomas (IT), 2 choriocarcinomas (CHO) and 13 dermoid cysts with malignant transformation (DCMT). The average age of patients in each group was 25.9 years for DCMT patients. When DCMT cases were excluded, ages was closely related to the age of menarche in each patient. The 5 year survival rate for each germ cell malignancy after the first operation was 31.6% for YST cases, 20.0% for MF, 76.7% for DYS, 60.0% for IT and 50.0% for DCMT cases. Despite currently used aggressive kinds of chemotherapy, the clinical stage still had a prognostic significance in all malignant germ cell tumors except dysgerminoma. Since histological maturation of the tumor tissue following treatment courses was observed in YST and IT cases, the possibility of a relationship between prognosis and the histogenetic process was shortly 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.

Aggressive chemotherapy in endodermal sinus tumor.

Twenty-eight patients with pure or predominantly endodermal sinus tumor were studied for their clinical behavior, relation with serum alpha-fetoprotein (AFP), and response to intensive postoperative combination chemotherapy. Eight percent of the patients were younger than 20 years of age. One patient was a pseudohermaphrodite. Serum AFP was estimated in 17 patients and was elevated in all. Seven patients were treated with adjuvant chemotherapy following surgery with a cisplatin-containing combination. Five patients (71%) are alive and continue to remain free of disease, with a median survival of 28 months after treatment and an overall median survival of 34 months. Two patients treated with adjuvant chemotherapy experienced early recurrence of the disease, which was detected with a rise in serum AFP before the clinical manifestation of recurrence.

Malignant mediastinal germ-cell tumors in childhood: a report of two cases achieving long-term disease-free survival.

Two cases of malignant mediastinal germ-cell tumor are reported. Case 1 is a 20-month-old girl with endodermal sinus tumor (EST) and is, to our best knowledge, the third female pediatric case of mediastinal EST in the literature. Case 2 is a 15-year-old boy with malignant teratoma (mature teratoma with poorly differentiated squamous cell carcinoma). Both cases were treated by primary combination chemotherapy of vincristine, actinomycin D, and cyclophosphamide or vinblastine, cisplatin, and bleomycin, secondary operation (complete resection), radiation to the tumor bed, and some courses of consolidation chemotherapy. Malignant mediastinal germ-cell tumors have been considered to have a poor prognosis, being different from gonadal tumors; however, long-term survivals with no evidence of recurrence were achieved both in case 1 (for 55 months) and in case 2 (for 56 months).

Improvement in the treatment of childhood cancer: analysis of survival data from the National Children's Hospital (1965-1987).

Developments in the treatment of childhood cancer have been evaluated in patients who had been treated in the National Children's Hospital from 1965 to 1987. The total number of patients was 867, of which leukemia accounted for 376, malignant lymphoma 61, neuroblastoma 174, Wilms' tumor 55, yolk sac tumor 29, rhabdomyosarcoma 36 and hepatoblastoma 30. Patients were divided into three time intervals: the 1960s, 1970s and 1980s. A marked improvement in five-year survival was recognized in Wilms' tumor and yolk sac tumor, amounting to 80%, followed by rhabdomyosarcoma, acute lymphoblastic leukemia and malignant lymphoma. There was no improvement in patients with acute non-lymphoblastic leukemia, neuroblastoma and hepatoblastoma. Prognostic factors for neuroblastoma were further analyzed, and the age of onset and stage of disease were found to have remained constant for 23 years. Factors relating to the improvement of survival were discussed.

Cisplatin, vinblastine, and bleomycin combination chemotherapy in endodermal sinus tumor of the ovary.

The combination of cisplatin, vinblastine, and bleomycin was administered to 13 previously untreated patients with pure endodermal sinus tumor of the ovary. Twelve had unilateral salpingo-oophorectomy as initial surgery. Among 11 women whose alpha-fetoprotein (AFP) levels returned to normal after cisplatin, vinblastine, and bleomycin therapy, nine are alive with no evidence of disease after periods of 20 months to six years and two months. In two patients, AFP levels returned to normal only after the introduction of different combination chemotherapies. Hematologic toxicity was moderate. Pulmonary toxicity due to bleomycin occurred in two cases. All menstruating patients resumed normal menstrual function after the interruption of chemotherapy. Two patients delivered normal term infants.

Nongerminomatous malignant germ cell tumors in children. A review of 89 cases from the Pediatric Oncology Group, 1971-1984.

Clinical and morphologic features of 89 cases of childhood yolk sac tumor (YS) and embryonal carcinoma (EC) (29 associated with teratomas) submitted to the Rare Tumor Registry of the Southwest Oncology Group (1971-1979) or the Pediatric Oncology Group (1980-1984) between 1971 and 1984 were reviewed and submitted to statistical analysis. This review showed an improved survival for each 5-year period regardless of tumor site, no statistically significant difference between "pure" tumors and those mixed with other teratomatous components, no statistically significant difference between YS and EC in children, a better than reported prognosis for sacrococcygeal tumors occurring after the neonatal period, a particularly poor prognosis for neonatal "benign" sacrococcygeal teratomas resected without coccygectomy when they recur as YS, excellent survival for all testicular tumors regardless of age or the presence of EC, and the occurrence of mediastinal tumors in females.