Raised serum alpha-fetoprotein in Sertoli-Leydig cell tumor (androblastoma) of ovary: report of two cases

Two cases of Sertoli-Leydig cell tumor (SLCT) of the ovary associated with elevated serum alpha-fetoprotein (AFP) levels are described. A 16-year-old girl (case 1) had a Sertoli-Leydig cell tumor containing heterologous elements in the form of mucinous epithelium; AFP was demonstrated within the Sertoli cells by immunohistochemical techniques. An 11-month-old girl (case 2) had a SLCT with a retiform pattern and heterologous elements in the form of cells resembling hepatocytes; AFP was localized in the hepatocytes by immunohistochemical techniques.     

Direct laparoscopic venous sampling to diagnose a small Sertoli-Leydig tumor

BACKGROUND: Sertoli-Leydig cell tumors (SLCT) constitute only 0.5% of all primary ovarian neoplasms. We report a unique diagnostic method (selective laparoscopic venous sampling) and a rare case of a contralateral second primary tumor. CASE: A 14-year-old female presented with hyperandrogenic complaints and an increased serum testosterone. Ovarian origin was confirmed by direct laparoscopic ovarian blood sampling. A right salpingo-oophorectomy was performed. The pathological diagnosis was SLCT of intermediate differentiation. Three years later, the patient presented again with an increased serum testosterone. A solid tumor in the left ovary was excised. The pathology was SLCT of intermediate differentiation. The patient remains disease-free. CONCLUSIONS: Direct laparoscopic venous sampling is used to diagnose a small SLCT in a teenage patient.     

Alpha-fetoprotein producing ovarian clear cell carcinoma with a neometaplasia to hepatoid carcinoma arising from endometriosis: a case report

We present a rare case of alpha-fetoprotein (AFP) producing ovarian clear cell carcinoma. This is the first report of a clear cell ovarian carcinoma with hepatoid carcinoma arising from endometriosis. A 54-year-old menopausal woman had a primary ovarian carcinoma of International Federation of Gynecology and Obstetrics stage IIIc. Serum level of AFP was 4195 ng/mL. Histological examination revealed clear cell adenocarcinoma arising from endometriosis with hepatoid carcinoma. Metastatic liver and lymph node tumors were found after 25 months from the first surgery. However, the patient's serum AFP was within normal limits. The recurrent and metastatic tumors disappeared in response to combined liposomal doxorubicin and carboplatin chemotherapy. She has had a disease-free survival of 4 years. In conclusion, the patient had a clear cell ovarian carcinoma with hepatoid carcinoma arising clearly from endometriosis. The recurrent tumors did not show a component of hepatoid carcinoma. Therefore, it is possible to expect better survival with good sensitivity to chemotherapy.     

Sertoli–Leydig cell tumor presenting hyperestrogenism in a postmenopausal woman: A case report and review of the literature

ObjectiveSertoli–Leydig cell tumor (SLCT) accounts for <0.5% of all ovarian tumors, which is unusual in postmenopausal women. Postmenopausal women with SLCT usually become virilized. We report a postmenopausal woman with SLCT presenting with hyperestrogenism.Case ReportWe report a rare case of SLCT in a postmenopausal woman aged 61 years, who presented with postmenopausal bleeding, endometrial hyperplasia and mucous polyp, elevated estradiol, and decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) values, all suggesting hyperestrogenism. Transvaginal ultrasound revealed several small cyst locules, detected inside the right ovary, with a maximum diameter of 7 mm. The diagnosis was delayed because of the atypical clinical manifestation and negative serum tumor markers. The frozen section investigation revealed SLCT intraoperatively, which was confirmed by histopathological and immunocytochemical examination. The tumor was positive for inhibin-alpha, pancytokeratin, and p53 and in isolated tumor cells, positive for Ki-67.ConclusionThis case of SLCT suggests the existence of a new specific type of endocrine complex disease.     

Ovarian mucinous cystadenocarcinoma producing alpha-fetoprotein

Common epithelial ovarian tumors associated with alpha-fetoprotein (AFP) production are rare. A case of ovarian mucinous cystadenocarcinoma producing both AFP and carcinoembryonic antigen (CEA) is presented. A 53-year-old postmenopausal woman with right adnexal tumor underwent total hysterectomy and right salpingo-oophorectomy. Preoperative serum CEA and AFP levels were elevated to 660 and 1,120 ng/ml, respectively, and both decreased to their normal ranges after surgery. Histologically, the right ovarian tumor was diagnosed as a mucinous cystadenocarcinoma, composed of both intestinal-type cells and endocervical-type cells. Intestinal-type cells were identified ultrastructurally, with cells resembling neuroendocrine cells as well as gobletlike cells with many mucinous granules. Yolk sac or teratomatous components were not identified. By the immunoperoxidase technique, CEA was positive in well to moderately differentiated mucinous cells lining lumina, whereas AFP-positive cells were intermingled with CEA-positive cells in moderately differentiated epithelia.     

Molecular genetic evidence supporting the neoplastic nature of the Leydig cell component of ovarian Sertoli-Leydig cell tumors.

Sertoli-Leydig cell tumors (SLCT) comprise less than 1% of ovarian tumors. The nature of the Leydig cells has been a subject of controversy and it is unclear whether they are clonally related to the neoplasm or instead proliferate as a non-neoplastic response to the Sertoli-cell component. Twelve ovarian SLCT were identified and hematoxylin and eosin and unstained sections were prepared from formalin-fixed, paraffin-embedded tissue blocks. Tissue samples were microdissected from normal tissue, the Sertoli cell component, and the Leydig cell tumor component using the laser capture microdissection method. If present, tissue was also obtained from any heterologous component. Genomic DNA was extracted from the samples and polymerase chain reaction was used to amplify polymorphic sites at 5 loci: D16S402, TP53, IFNA, D17S855, and D11S1318. X-chromosome inactivation (HUMARA) analysis was also performed. LOH and/or nonrandom X-chromosome inactivation was observed in at least 1 of the 6 amplified loci in the Leydig cell component of 10 of the 12 tumors. LOH and nonrandom X-chromosome inactivation patterns of the Sertoli cell component and Leydig cell component were compared. Concordant allelic loss and/or matching X-chromosome inactivation patterns were observed in 8 (67%) of the 12 tumors. In 7 of these tumors similar LOH or X-chromosome inactivation was observed at 1 site. In 1 tumor similar LOH and/or X-chromosome inactivation was observed at 2 sites. Three tumors had heterologous components. The heterologous components similarly shared LOH/X-chromosome inactivation with the Sertoli cell components at 1 site in 1 case and 2 sites in 2 cases. These data suggest that, at least in some cases, the Leydig cell component of SLCT is neoplastic rather than reactive in nature, and shares a common clonal origin with the coexisting Sertoli cell component. Similarly, the heterologous components, when present, appear to share clonal origin with the Sertoli cell components.     

青少年卵巢混合性生殖细胞肿瘤一例并文献复习

卵巢恶性生殖细胞肿瘤（malignant ovarian germ cell tumor,MOGCT）来源于胚胎原始生殖细胞,好发于儿童、青少年和年轻女性,多涉及保留生育功能问题。报告1例15岁的卵巢混合性生殖细胞肿瘤病例,患者运动后突发左下腹痛,经腹彩色超声示盆腔中低回声包块,经腹腔镜探查术发现左侧卵巢巨大肿物破裂,引起腹腔内大出血。行左侧附件切除术,术后查血清甲胎蛋白（alpha fetoprotein,AFP）、糖类抗原19-9(carbohydrate antigen 19-9,CA19-9)和人绒毛膜促性腺激素（human chorionic gonadotropin,hCG）升高。病理结果示混合性生殖细胞肿瘤,以胚胎癌为主,可见绒毛膜癌成分及少许卵黄囊瘤、畸胎瘤成分。术后第11天正电子发射体层成像（positron emission tomography,PET）/CT显示无残留病灶,行平阳霉素+依托泊苷+顺铂（BEP）方案化疗4个周期,AFP、h CG于第2个周期后降至正常。至2022年2月患者月经恢复,随访至2022年5月无复发迹象。     

Solitary metastasis of a clear cell ovarian adenocarcinoma to the small bowel mucosa

Metastasis of ovarian carcinoma to the small bowel parenchyma without peritoneal dissemination is uncommon. A 63-year-old woman underwent surgery for a clear cell adenocarcinoma of the ovary and received adjuvant chemotherapy. Eighteen months after the operation, she presented with recurrent occult bowel hemorrhage without evidence of an abdominal mass. Nine months later, a rapidly growing abdominal mass was detected. Laparoscopy revealed a solitary tumor of the ileum covered with an intact serosal layer. Partial ileectomy was performed for tumor resection. Histological examination revealed cells resembling the primary ovarian tumor in the mucosal surface of the small bowel along with an intact serosa. The tumor cells were positive for cytokeratin 7 and negative for cytokeratin 20, suggesting an ovarian origin. This is the first report of solitary metastasis of an ovarian carcinoma to the small bowel parenchyma without peritoneal dissemination. Metastasis to the small bowel should be considered in ovarian carcinoma patients with occult gastrointestinal hemorrhage.     

Hepatoid carcinoma of the ovary: a case report.

A case of a right ovarian tumor in a 64-year-old patient showing high blood levels of alpha-fetoprotein (AFP) is reported. Histologically, the tumor resembled hepatocellular carcinoma with hyaline globules. Localization of AFP was detected by the immunoperoxidase method. Electron microscopically, the rough-surfaced endoplasmic reticulum had developed into a meshwork, and the mitochondria were present within this meshwork. Because a transition from adenocarcinoma to a region resembling hepatocellular carcinoma was observed, this tumor was considered to originate as a common epithelial carcinoma. In the blood, 67% of the AFP was bound with concanavalin A (Con A), and the fraction pattern obtained by lentil agglutinin affinity chromatography (LCA) was of the germ cell type. From these results, the current case may be labeled clinicopathologically a hepatoid carcinoma of the ovary as described by Ishikura and Scully.     

Recurrent Mixed Germ Cell Tumor of the Ovary Manifest as an Unexplained Elevated Maternal Serum Alpha-Fetoprotein

Primary alpha-fetoprotein secreting ovarian tumors have been detected in pregnancy by markedly elevated midtrimester MSAFP accompanied by sonographically visualized adnexal masses. We present a recurrent mixed germ cell tumor manifesting only as a moderately elevated MSAFP screen. A 23-year-old para 1–0–0–1 at 17 weeks had a MSAFP screen of 3.88 multiples of the median (MOM). Since age 13 she had been treated for primary and recurrent mixed germ cell tumor of the ovary, after which her serum AFP had been negative. Ultrasound confirmed gestational age and normal fetal anatomy. Amniocentesis revealed a normal 46, XY karyotype, AFAFP, and negative acetylcholinesterase. Monthly MSAFP levels rose throughout pregnancy without the expected plateau and fall after 30 weeks. Definitive surgery at delivery confirmed recurrent AFP-secreting tumor. The trend over pregnancy of an unexplained elevated MSAFP level may signify recurrent mixed germ cell tumor     

Ovarian thecoma with androgenic manifestations in a postmenopausal woman.

A 50-year-old woman, who presented with progressive androgenization, central obesity and severe hypertension, was initially suspected to have an adrenal virilizing tumor. Her serum testosterone level was in the male range (9.3-11.6 ng/ml) and was not suppressed with dexamethasone. Although no pathological abdominal or pelvic mass was detected, total hysterectomy and bilateral salpingo-oophorectomy was performed. Histopathological examination revealed a theca-cell tumor of the right ovary. Postoperatively the testosterone level returned to normal and the patient had regression of virilism. Our case illustrates that a virilizing ovarian tumor can be small and elude imaging studies, but may be detected by means of well-considered clinical management.     

Cushing''s syndrome due to ovarian serous adenocarcinoma secreting multiple endocrine substances: a case report and immunohistochemical analysis

BACKGROUND: Although Cushing's syndrome arises from various neuroendocrine tumors secreting adrenocorticotropin (ACTH) ectopically, ovarian carcinoma rarely causes this syndrome. CASE: A 66-year-old woman presented with facial swelling and skin pigmentation. She manifested hypercortisolemia, high plasma ACTH, and lack of dexamethasone suppression. MRI showed a solid ovarian tumor and resection of the tumor led to normalization of ACTH and cortisol levels. In addition, elevated serum vasopressin (ADH) and alpha-fetoprotein (AFP) were found, which were also normalized after removal of tumors. Pathological diagnosis was serous adenocarcinoma with neuroendocrine and hepatoid features. Immunohistochemistry detected immunoreactivity of chromogranin A, ACTH, ADH, and AFP in tumor cells. CONCLUSION: This is a very rare case of successful treatment of Cushing's syndrome arising from an ovarian adenocarcinoma secreting multiple endocrine substances.     

A sarcomatous-type peritoneal malign mixed mullerian tumor implant in association with ovarian adenocarcinoma: a case report

A rare case of a patient with a histopathological diagnosis of a sarcomatous-type peritoneal malign mixed müllerian tumor implant in association with ovarian adenocarcinoma is reported. A 52-year-old patient was referred to our clinic for an adnexal mass. At pelvic examination, an irregular, fixed, approximately 7-8 cm in size mass was detected in the right adnexal area. At transvaginal ultrasonographic examination, it was observed that there was an 80 x 70 mm sized, irregularly contoured, semisolid mass with hyperechogenous areas inside originating from the ovary in the right adnexal area. At laboratory examination tumor marker CA-125 was 280.4 U/ml (< 35), CA-15-3 was 146.5 U/ml (< 25), whereas other markers were within normal range. The patient was operated on for a right adnexal mass. A staging laparatomy procedure was applied. Postoperative histopathological diagnosis was reported as malignant mixed mullerian tumor of the ovary, with the ovarian component as poorly differentiated adenocarcinoma, and the metastatic foci over serosal surfaces as a sarcomatous component. Postoperatively six courses of adjuvant and consolidation chemotherapy were administered to the patient. Further studies are needed to set a consensus about evaluation of treatment and prognosis for this kind of pathology.     

Ovarian hepatoid carcinoma without staining for alpha-fetoprotein in the primary site

An ovarian hepatoid carcinoma associated with minimal alpha-fetoprotein (AFP) production is described. The tumor involved both ovaries, and had metastasized to the omentum, uterus and retroperitoneal lymph nodes. The neoplastic cells were arranged in sheets, had abundant eosinophilic cytoplasm, central nuclei and distinct cellular borders. Despite the morphologic similarity to the histology of a hepatocellular carcinoma, elevation of the serum AFP level was minimal, at 74.0 ng ml⁻¹ (normal range: under 20 ng ml⁻¹), and the value normalized after surgery and subsequent chemotherapy. An immunohistochemical technique revealed focal staining for albumin in the tumor tissue and AFP in the uterine metastasis. Since the primary tumor itself did not stain for AFP, it is suggested that there may be hepatoid ovarian carcinomas without AFP production, a situation found in some hepatocellular carcinomas.     

Mixed germ cell-sex cord stromal tumor with heterologous structures.

A mixed germ cell-sex cord stromal tumor developed in the right ovary of a 4-year-old girl. The patient's cells contained sex chromatin and the karyotype was 46,XX. Clinically, she exhibited mild isosexual pseudopuberty. Some of the tumor cells showed differentiation to Sertoli cells, whereas others had characteristics of germ cells. The neoplasm was composed of solid cords consisting of a mixture of the two tumor cell types and surrounded by a delicate connective-tissue network. In one small area, the tumor contained heterologous development in the form of glands and cysts lined by columnar mucinous epithelium containing numerous goblet cells and occasional argyrophilic neuroendocrine cells. Normal ovarian tissue was present at the periphery of the tumor. Electron microscopic study confirmed the presence of both Sertoli-like and germ cell-type cells. Immunohistochemical studies demonstrated vimentin positivity in both cell types (with preference for the Sertoli-like cells) and cytokeratin positivity in the Sertoli-like cells. The patient was symptom free 4 years after right oophorectomy, radiotherapy, and chemotherapy.     

A case of ovarian endometrioid adenocarcinoma with yolk sac tumor in a 35-year-old woman

Ovarian yolk sac tumor (YST) is a malignant ovarian neoplasm differentiated from primordial germ cells that occur in young age, while endometrioid carcinoma (ECA) is a müllerian epithelial tumor that usually occurs in older patients. The coexistence of an ovarian ECA and YST component is very rare. Only 12 cases have been reported until now according to a Medline search of the English literatures. We present a case of a simultaneous ECA and a YST component in a 35-year-old woman. Exploratory laparotomy was performed. The parts of both ovaries that showed an endometrioid-like glandular pattern were positive for cytokeratin 7 and negative for AFP, but the YST component was negative for cytokeratin 7 and positive for AFP. After completion of four courses of BEP chemotherapy, two courses of taxane and carboplatin chemotherapy were added. The patient failed to respond and succumbed to the disease after 12 months of follow-up.     

Bilateral Sertoli-Leydig cell tumor with heterologous elements: report of an unusual case and review of the literature

A case of bilateral ovarian Sertoli-Leydig cell tumor with heterologous elements is reported in an 18-yr-old girl with marked virilization. Panhysterectomy was performed, yet the tumor recurred shortly after the intervention. The microscopic picture was one of intermediate to poor differentiation. Despite chemotherapy, the postoperative course was rapidly malignant, and the patient died 4 wk later.     

Embryonal carcinoma of the ovary: a six-year survival.

We report a case of embryonal carcinoma, stage II, arising in the right ovary of an 18-year-old woman. The elevated serum levels of alpha-fetoprotein (AFP) and urinary human chorionic gonadotropin (hCG) rapidly normalized after conservative surgery followed by combination chemotherapy. The tumor was composed of large primitive cells and some multinucleated giant cells. AFP and hCG were demonstrated immunohistochemically in each type of cells. She has been disease-free for 6 years.     

Conservative treatment and long-term follow up of endodermal sinus tumor of the vagina

Objective

Six cases of endodermal sinus tumor (EST) of the vagina were reported focusing on the results of conservative treatment and outcome of long-term follow up.

Methods

We reviewed a cohort of six cases with EST of the vagina diagnosed and treated in our hospital. CT scan, detection of serum AFP level, examination under anesthesia and biopsy were performed before and after treatment to evaluate the tumor status. The diagnoses were confirmed by pathological and imaging findings. All patients were treated with bleomycin, etoposide and cisplatin (BEP) combination chemotherapy alone. Complete remission (CR) includes the normal level of serum AFP, no tumor detected by CT scan and the negative result of pathology. Long-term follow up was carried out according to our regulation.

Results

The mean onset age was 18.2 months. The average tumor size was 4.5 cm. Serum AFP level was markedly elevated before treatment and decreased dramatically after chemotherapy and drop to the normal level after two to three courses of chemotherapy (average 2.5 courses). The patients received averagely six courses of chemotherapy and all the six patients obtained CR. The mean follow-up time is 75.5 months and there was no evidence of recurrent disease.

Conclusion

The result of this conservative treatment for EST of the vagina is excellent. BEP chemotherapy without surgery should be considered as a good choice of treatment. Close follow up with serial determinations of serum AFP level together with imaging tests and physical examination in the first two years of follow-up are recommended.     

Mucinous cystadenoma of the ovary with functioning stroma and virilization in pregnancy: a case report and review of the literature

Virilization caused by ovarian tumors with functioning stroma during pregnancy is extremely rare and has been reported in many ovarian tumors. In mucinous cystadenomas with maternal virilization during pregnancy the stromal cells responsible for the hormone secretion resemble lutein or Leydig cells and have been referred to as luteinized stromal cells. We present a case of a 30-year-old, gravida 2, para 1, woman who presented at approximately the 38th week of pregnancy with features of virilization. At the same time, a cesarean section was performed because of fetal distress and a male weighing 3,030 g without any gross abnormalities was delivered. A large tumor of the right ovary was detected and a right salpingo-oophorectomy was performed. Histopathologically, the tumor proved to be a benign mucinous cystadenoma. Masses typically resembling lutein stromal cells or Leydig cells of the testes or ovarian hilus were found in the wall of the cyst below the mucinous epithelium. No crystalloids of Reinke were identified. The stromal component of the tumor was characterized as functioning stroma with luteinized stromal cells. The glandular mucinous epithelium showed focal positivity for human chorionic gonadotrophin. The cytoplasm of the luteinized stromal cells reacted strongly and diffusely with antiserum for vimentin. Also, the cytoplasm of the luteinized stromal cells showed focal intense positivity for synaptophysin, and focal mild positivity for human chorionic gonadotrophin. Staining results for oestrogen and progesterone receptors were negative. In conclusion, we present an unusual case of clinical virilization during pregnancy associated with an ovarian mucinous cystadenoma with functioning stroma. The virilizing manifestations disappeared after removal of the ovarian neoplasm, supporting the perception that the functioning ovarian stroma was responsible for the androgen production.