Influence of chemotherapy or liver metastasis on the immunoelectrophoretic discrimination of alpha-fetoprotein from yolk sac tumor

Chen R-J, Huang S-C, Chow S-N, Hsieh C-Y, Lin M-C, Hsu H-C. Influence of chemotherapy or liver metastasis on the immunoelectrophoretic discrimination of alpha-fetoprotein from yolk sac tumor. Int J Gynecol Cancer 1997; 7 : 486– 489.
The main purpose of this study was to determine whether chemotherapy or liver metastasis can interfere with the discrimination of yolk sac tumor alpha-fetoprotein (AFP) from that of hepatocellular carcinoma. The AFP pattern in six cases of yolk sac tumor with or without liver metastasis was studied both during and after chemotherapy using affinity immunoelectrophoresis. Six cases of hepatocellular carcinoma which werematched by AFP level with yolk sac tumors were used for comparison. The pattern produced by yolk sac tumor consists of a prominent L2 band and a light L3 band. Hepatocellular carcinoma produced a prominent L1 band and a light L3 band. The presence or absence of liver metastasis did not affect the pattern from ovarian yolk sac tumor, nor did chemotherapy interfere with the ability to discriminate between patterns. Our findings indicate that, using affinity immunoelectrophoresis, we are able to discriminate yolk sac tumor with or without liver metastasis from hepatocellular carcinoma. This discrimination is not affected by the administration of chemotherapy.     

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.     

Hepatoid carcinoma of the ovary: immunohistochemical finding of one case and literature review

Hepatoid carcinoma is a rare ovarian tumor and is thought to be a histopathologic subtype different from hepatoid type yolk sac tumor based on its pathologic features. A 63-year-old woman who had postmenopausal bleeding and lower abdominal pain was found to have right ovarian mass on pelvic examination and computed tomography. She had high serum levels of alpha fetoprotein (AFP) and CA125. Histologically, the tumor resembled hepatocellular carcinoma by architectural and cytologic features. Immunohistochemically tumor cells were immunoreactive for AFP, alpha 1 antitrypsin, and carcinoembryonic antigens.     

Alpha-fetoprotein-producing serous carcinoma of the uterus metastasizing to the ovaries, mimicking primary ovarian yolk sac tumor: a case report and review of the literature.

In the uterus, most alpha-fetoprotein (AFP) producing neoplasms belong to the categories of malignant mixed muellerian tumor, hepatoid carcinoma, and yolk sac tumor. We describe the case of a 44-year-old woman who presented with vaginal bleeding, pelvic mass, and preoperative elevated AFP serum level, clinically suggestive of a primary ovarian yolk sac tumor. However, histological examination revealed a uterine AFP-producing papillary serous carcinoma, which has metastasized to the ovaries. Upon review of the literature on primary endometrial neoplasms with AFP production, 2 categories with possibly different histogenesis and biological behavior become evident: the primary yolk sac tumor of the uterus in young patients (range, 24-49 years; mean, 34 years) and the common high grade endometrial carcinoma with yolk sac dedifferentiation or aberrant AFP production in elderly patients (range, 55-69 years; mean, 63.7 years). In addition to being only the second case of uterine AFP-producing papillary serous carcinoma, this case is unusual for its clinical and radiological presentation as well as the relatively young age of the 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.     

Hepatoid carcinoma of the ovary: a report of three cases admixed with a common surface epithelial carcinoma.

Hepatoid carcinoma of the ovary is an ovarian carcinoma that has phenotypic properties in common with hepatocellular carcinomas. However, the extent of the tumor cells' similarity to and their difference from hepatocytes is largely unknown. In addition, the precursor cell of origin for hepatoid carcinoma of the ovary has not been identified. Three cases of alpha-fetoprotein-producing hepatoid carcinoma of the ovary that were admixed with an adenocarcinoma of common surface epithelial type are reported. The hepatoid carcinomas had a trabecular architecture with canaliculi detected by polyclonal (but not monoclonal) anticarcinoembryonic antigen antibodies. A hepatic phenotype in the hepatoid tumor cells was further supported by the production of albumin mRNA by in situ hybridization. The adenocarcinomas in the three cases were mucinous (Case 1), serous (Case 2), and endometrioid (Case 3), respectively. The cytokeratin (CK) profile in both the hepatoid and adenocarcinomatous components was CK18+/CK19+/CK20+/-, whereas normal and neoplastic hepatocytes were CK18+/CK19-/CK20-. Although this study supports a hepatic phenotype in ovarian hepatoid carcinoma, the CK profile of hepatoid carcinoma differs from that of normal and neoplastic hepatocytes but resembles that of the associated common epithelial adenocarcinoma. These findings suggest that hepatoid carcinoma of the ovary is probably derived from carcinomas of surface epithelial origin by a process of neometaplasia or transdifferentiation.     

Hepatoid carcinoma of the ovary and management

The designation'hepatoid carcinoma' has been introduced as a unique type of carcinoma that arises outside the liver but resembles, to a considerable extent, hepatocellular carcinoma both histologically and immunohistochemically in its staining for alpha-fetoprotein (AFP). The minimum histological criteria of hepatoid carcinomas are the evidence of AFP production and abundant eosinophilic cytoplasm. These tumors have been reported in the ovary, the lung, the stomach, the renal pelvis, and the bladder. We, in this study, present a rare patient with primary hepatoid carcinoma of the ovary (OHC) and review the previous reports.     

Molecular heterogeneity of alpha-fetoprotein in ovarian or extragonadal yolk sac tumor]

The molecular heterogeneity of alpha-fetoprotein (AFP) in yolk sac tumor (YST) was investigated. The study included 14 sera from YST, 78 sera from primary hepatocellular carcinoma (PHC), 5 fetal yolk sac (YS) culture fluids and 4 fetal liver culture fluids. The microheterogeneity of AFP was assessed by differences in reaction with AFP carbohydrate chain and lectins, and concanavalin A (Con A), Lens culinaris hemagglutinin (LCH) and phytohemagglutinin E (PHA-E) affinity crossed-line immunoelectrophoresis was used to fractionate AFP. It was found that AFP in YST or YS had similar subfraction patterns and differed clearly from AFP in PHC or fetal liver. Characteristic features of AFP subfraction in YST or YS were the presence of a LCH weakly-reactive subfraction and a high proportion of both Con A non-reactive and PHA-E strongly-reactive subfractions. The LCH weakly-reactive subfraction was specifically found in YST or YS, but was not found at all in PHC or in fetal liver. This variant is known to exist in amniotic fluid at an early stage of gestation, and is assumed to have a carbohydrate chain with both fucose and bisecting N-acetyl-glucosamine. The present findings therefore suggest that glycosylation of AFP in YST takes place by retro-genetic differentiation toward fetal yolk sac, but not toward fetal liver, and these studies confirm the suggested yolk sac origin of ovarian, as well as extragonadal, yolk sac tumor.     

No ancillary finding is valid to distinguish a primary ovarian hepatoid carcinoma from metastatic hepatocellular carcinoma

Primary ovarian hepatoid carcinomas (POHC) are extremely rare. Especially rare are those with phenotypic properties of hepatocellular carcinoma (HCC) and an absence of clinical evidence of hepatic tumor. We report a case of a POHC with a common microscopic, immunophenotypic, and ultrastructural property of HCC in the absence of a liver mass. It is extremely difficult to differentiate POHC from metastatic HCC using any kinds of ancillary studies, with the exception of clinical identification of a hepatic tumor.     

Ovarian mucinous cystadenocarcinoma with yolk sac tumor in a 71-year-old woman.

An ovarian mucinous cystadenocarcinoma admixed with a component of yolk sac tumor was encountered in a 71-year-old woman, the first such tumor to be reported. The preoperative serum level of alpha-fetoprotein was elevated (55.6 ng/mL). A right ovarian cystic tumor, 8 cm in maximal dimension, was removed and found to have a solid component. Microscopically, the cystic lesion was a mucinous cystadenocarcinoma, whereas the solid portion was typical yolk sac tumor with microcystic, reticular, and labyrinthine patterns, Schiller-Duval bodies, scattered giant cells with bizarre nuclei, and intracellular and extracellular hyaline globules. There was no evidence of other germ cell tumor components. Yolk sac tumor showed positive reactions for alpha-fetoprotein, carcinoembryonic antigen, and alpha-1-antitrypsin but was negative for CA125, CA19-9, and human chorionic gonadotrophin. The patient died of recurrent tumor 6 months postoperatively without response to combination chemotherapy.     

Hepatoid carcinoma with serous component of the fallopian tube: a case report with immunohistochemical and ultrastructural studies.

A very rare case of hepatoid carcinoma with serous component arising in the fallopian tube of a 79-year-old woman is presented. The lesion was a 5.0-cm unencapsulated, yellowish-white soft mass. The tumor was composed of hepatoid carcinoma (90%) and serous carcinoma (10%) components. The hepatoid carcinoma was histologically characterized by a proliferation of round to polygonal cells arranged in a trabecular, tubular, sinusoidal, papillary, or solid pattern. The serous component in the fallopian tube also showed in situ lesions. Both components showed an infiltration into the surface of the left ovary, omentum, peritoneum including the pouch of the Douglas, and serosa of the colon. Immunohistochemically, the hepatoid carcinoma was positive for alpha-fetoprotein, polyclonal carcinoembryonic antigen (CEA), hepatocyte paraffin 1, albumin, epithelial membrane antigen, and cytokeratin (CAM5.2). Ultrastructurally, the cytoplasm contained abundant ribosomes, moderate amounts of mitochondria, and rough endoplasmic reticulum that developed into a meshwork and contained mitochondria within it. Microbile channel-like structures and desmosomes were occasionally observed. The association with serous carcinoma indicates mullerian origin rather than germ cell origin. The patient received chemotherapy and was alive without disease at 10 months after surgery.     

The role of tumor markers in gynecologic oncology.

Human chorionic gonadotropin is a highly sensitive and specific tumor marker for gestational trophoblastic neoplasia that accurately reflects tumor volume and the clinical course of disease. In women with endodermal sinus tumors and embryonal carcinomas, alpha-fetoprotein usually is a reliable marker, and it accurately predicts the presence of yolk sac elements in mixed germ cell tumors. CA 125 is the most widely utilized tumor marker presently available for use in patients with epithelial ovarian cancer. It has utility in monitoring therapy and differentiating benign from malignant pelvic masses. Measurement of serial CA 125 levels in postmenopausal women may facilitate screening for occult early stage disease. In the future, monoclonal antibodies that recognize tumor-associated antigens may prove useful for radionuclide imaging.     

Analysis of serum CA125, CEA, AFP, LDH levels and LDH isoenzymes in patients with ovarian tumors--correlation between tumor markers and histological types of ovarian tumors

Serum CA125, CEA, AFP, LDH levels and LDH isoenzymes were analyzed in ovarian tumor patients, who were treated at Kyoto University Hospital. CA125 was positive in 10/16 (62.5%) cases of common epithelial carcinoma, especially 100% positive in serous carcinoma, but was negative in mucinous tumors. CA125 was also negative in patients with germ cell and sex cord stromal tumors. CEA was positive in 13/32 (40.6%) cases of epithelial carcinoma, most frequently elevated in patients with mucinous carcinoma, pseudomyxoma peritonei, and Krukenberg tumor. AFP was positive only in those with endodermal sinus tumors. LDH was elevated in 16/39 (41%) cases of epithelial carcinoma, but was not specific for histological types. In contrast, all 8 cases of dysgerminoma, 1 of immature teratoma and 2 of endodermal sinus tumor showed extremely elevated LDH levels. Moreover, the normal pattern or deviation to H subunit of LDH isoenzymes was seen in such cases of germ cell tumor, while deviation to M subunit was noted in epithelial and metastatic tumor patients. These data indicate that each parameter is useful as a tumor marker for the specific histological type of ovarian tumor; CA125 for non-mucinous epithelial carcinoma, CEA for mucinous tumor and Krukenberg tumor, AFP for yolk sac tumor, LDH and LDH isoenzymes for dysgerminoma and other solid germ cell tumors. In addition, preoperative diagnosis of histological types of ovarian tumors may be possible by combining these tumor markers.     

CD56 expression in ovarian granulosa cell tumors, and its diagnostic utility and pitfalls

OBJECTIVE: The purpose of this study is to investigate CD56 staining in ovarian granulosa cell tumor and its morphological mimics in order to determine the value of CD56 staining in a diagnostic setting. MATERIALS AND METHODS: Tissue samples taken from 82 ovarian tumors, 26 extra-ovarian tumors and 11 normal ovaries were immunohistochemically stained using monoclonal anti-CD56 antibody. Ovarian tumors comprised 32 granulosa cell tumors, 3 Sertoli-stromal cell tumors, 14 fibrothecomas, 6 carcinoid tumors, 1 large cell neuroendocrine carcinoma, 17 endometrioid adenocarcinomas and 9 poorly differentiated serous adenocarcinomas. Extra-ovarian tumors comprised 22 uterine endometrial stromal sarcomas and 4 pulmonary small cell carcinomas. Normal ovaries contained 47 ovarian follicles. RESULTS: All of the 32 granulosa cell tumors, all of the 3 Sertoli-stromal cell tumors, all of the 4 small cell carcinomas, 1 of 1 large cell neuroendocrine carcinoma, 11 of 14 fibrothecomas, 5 of 6 carcinoid tumors, 17 of 22 endometrial stromal sarcomas and 7 of 9 poorly differentiated serous adenocarcinomas were positive for CD56. No immunoreactive cells were observed in 17 endometrioid adenocarcinomas or 47 ovarian follicles. All the immunoreactive cells showed membranous staining except for fibrothecomas where vague cytoplasmic staining was seen. CONCLUSION: CD56, known as a neuroendocrine marker, is a sensitive marker of granulosa cell tumors, but since granulosa cell tumors and neuroendocrine tumors may be morphologically similar, CD56 positivity represents a significant diagnostic pitfall. CD56 is useful in distinguishing between granulosa cell tumor and normal ovarian follicles or endometrioid adenocarcinoma. Lack of membranous CD56 expression in fibrothecoma may help differentiate it from granulosa cell tumor. However, CD56 is of limited use for distinguishing between granulosa cell tumor and poorly differentiated carcinoma or endometrial stromal sarcoma. Appropriate and cautious interpretation of CD56 expression should lead to a more accurate diagnosis of granulosa cell tumor.     

Cyclooxygenase 2 expression in serous tumors of the ovary.

This study was designed to investigate the expression of cyclooxygenase (COX)-2 in ovarian serous tumors (benign, borderline tumors, and carcinomas) and primary peritoneal serous carcinomas. Cases diagnosed between 1995 and 2001 were reviewed; 47 benign tumors, 6 borderline tumors, and 39 carcinomas were examined, as well as 12 normal ovaries that served as controls. Blocks were stained with anti COX-2 polyclonal antibody and staining was graded qualitatively. The staining intensity was assessed as weak (score of 1), moderate (score of 2), or strong (score of 3). Normal ovarian and tubal epithelium, inclusion cysts, benign serous tumors, and borderline tumors had a uniform score 3 staining pattern. Serous ovarian carcinomas had variable staining scores, tending to correlate with the level of tumor differentiation. Well-differentiated carcinomas had more intense COX-2 staining than poorly differentiated carcinomas, which had only weak COX-2 staining. The degree of COX-2 staining was not significantly related to overall survival. In conclusion, COX-2 expression is present in serous tumors, including benign tumors, borderline tumors, and carcinomas. Similar to the findings in other neoplasms, COX-2 expression is strongest in well-differentiated tumors and is much less evident in those that are poorly differentiated. The clinical utility of these findings is related to the potential role of nonsteroidal anti-inflammatory drugs, which are COX-2 inhibitors, in treating and/or preventing some forms of ovarian carcinoma.     

卵巢卵黄囊瘤手术和化疗后自然周期体外受精-胚胎移植成功分娩一例并文献复习

卵巢卵黄囊瘤属卵巢恶性生殖细胞肿瘤,占卵巢恶性肿瘤的1%。由于卵巢恶性生殖细胞肿瘤多见于儿童及年轻女性,故保存生育能力是关键。卵巢卵黄囊瘤对化疗药物敏感,手术联合术后辅助化疗是标准治疗方案。对于对侧卵巢和子宫未受肿瘤累及,并且有生育需求的患者均应行保留生育功能的手术。但肿瘤本身、手术和放化疗均可能造成患者不孕,术后可能需要借助辅助生殖技术助孕,本文通过1例卵巢卵黄囊瘤患者手术和术后化疗后行自然周期-体外受精-胚胎移植(NC-IVF-ET)的个案报道和文献复习,探讨卵巢卵黄囊瘤患者的生育助孕策略。     

Urothelial and ovarian carcinomas of identical cell types: problems in interpretation. A report of three cases and review of the literature

Three women, 51-69 years of age with carcinomas of the urinary bladder or ureter, had ovarian tumors of identical cell types 2 to 7 years apart. In two cases the tumors were transitional-cell carcinomas and in the third case, signet-ring-cell carcinomas. It was difficult in the cases of transitional-cell carcinoma to determine whether the ovarian tumors were metastatic or independent primary tumors. Consideration of a variety of features of our two cases and of four similar cases reported in the literature led us to the conclusion that the ovarian tumors were probably metastatic in one case, probably primary in two cases, and of unknown nature in three cases, but some degree of doubt existed in all the cases. The signet-ring-cell tumor in the ovary had the typical features of a Krukenberg tumor. Four of 11 women with signet-ring-cell carcinomas of the bladder have had ovarian metastases.     

Yolk sac tumor of the ovary associated with endometrioid carcinoma with metastasis to the vagina: a case report

BACKGROUND: Mixed yolk sac tumors of the ovary are biologically aggressive even in early stage disease. CASE: A 41-year-old woman presented with a large pelvic mass and anterior vaginal wall tumor. At surgery vaginal biopsies were performed followed by an exploratory laparotomy with resection of the mass. Pathology of the ovary revealed a primary yolk sac tumor associated with poorly differentiated endometrioid and undifferentiated carcinoma with vaginal metastasis only. She was initiated on bleomycin, etoposide, and cisplatin, with three additional cycles of etoposide and cisplatin. Initially the patient experienced a complete response, however her disease recurred and she currently is dead of her disease. CONCLUSION: To our knowledge this is the first case of a mixed ovarian germ cell tumor with vaginal metastasis.