Immunohistochemical Type Distinction of a-Fetoprotein in Various a-Fetoprotein-secreting Tumors

In order to clarify the histogenesis of a -fetoprotein(AFP)-secreting tumor tissues, formalin-fixed, paraffin-embedded serial sections of 148 tumors in various organs were examined by the peroxidase-antiperoxidase method for AFP, and paradoxical concanavalin A staining. Yolk sac-type AFP was found in yolk sac tumors, embryonal carcinomas, solid teratomas, (yolk sac) endodermal cell tumors, adenocarcinomas (stomach, ovary or lung) and metastatic liver cancers. Hepatic-type AFP was demonstrated in hepatocellular carcinomas, hepatoblastomas, solid teratomas and a stomach cancer. Yolk sac-type AFP was observed in the neighboring liver cells of metastatic liver cancers without relation to the type of AFP in primary cancers. The results from serum analyses of preoperative tumor-bearing patients (68 cases) were coincident with those from immunohistochemical stainings.     

Serum alphafetoprotein (AFP) in patients with germ cell tumors of the gonads and extragonadal sites: correlation between endodermal sinus (yolk sac) tumor and raised serum AFP

During the last 6 1/2 years, serum AFP has been determined by radioimmunoassay in 387 patients with germ cell tumors of the gonads and extragonadal sites. The histological appearances of all these neoplasms were carefully reviewed. Highly elevated levels of serum AFP were noted in patients with tumors containing endodermal sinus (yolk sac) tumor elements irrespective of the location of the neoplasm or presence or absence of metastatic disease. There was good correlation between the presence and quantity of endodermal sinus (yolk sac) tumor elements within the primary tumor or its metastases and elevated levels of serum AFP. All patients with tumors composed of pure seminoma or dysgerminoma, and teratoma, had normal serum AFP levels. Slightly elevated levels of serum AFP up to 60 ng/mg (upper limit of normal 20 ng/ml) were noted in a few patients with testicular tumors composed of pure embryonal carcinoma, whereas patients with tumors composed of or containing endodermal sinus (yolk sac) tumor elements had serum AFP levels that could be measured in 100's or 1000's of ng/ml. Serum AFP was elevated only in patients with active disease. Serum AFP was determined in 81 patients with gonadal tumors of non germ cell origin and was normal in all these patients. Serum AFP is a very good tumor marker in patients with germ cell tumors composed of or containing endodermal sinus (yolk sac) tumor, irrespective of their location. Serial serum SFP determinations can be used for diagnostic purposes, for monitoring the results of treatment, and for early detection of metastases and recurrences. Serial serum AFP determination is a useful procedure in all patients with germ cell neoplasms and is highly recommended.     

非卵黄囊瘤的AFP阳性卵巢恶性肿瘤4例临床病理观察

目的 探讨非卵黄囊瘤的ＡＦＰ阳性卵巢恶性肿瘤的病理组织形态和临床生物学行为。方法 报道４例非卵黄囊瘤的ＡＦＰ阳性卵巢恶性肿瘤,１例为单纯肝样癌,３例为有梭形细胞成分的内膜样癌（其中１例伴有肝样癌）。结果 肝样癌癌细胞的胞质内含有ＡＦＰ、ＡＡＴ和ＡＣＴ成分,而在内膜样癌癌细胞的胞质内以ｃｙｔｏｋｅｒａｔｉｎ和ＣＥＡ成分为主。由于ＡＦＰ具有免疫抑制作用,病人的预后不好。４例中３例已死亡,平均生存２５个     

Case report of a 69-year-old woman with double cancers: Primary yolk sac tumor of the right ovary and primary serous surface papillary carcinoma of the peritoneum

This extremely rare case of a 69-year-old woman with yolk sac tumor of the right ovary and serous surface papillary carcinoma (SSPC) of the peritoneum is reported. Histological diagnosis for both tumors was done according to the classifications of the Japanese Society of Pathology and Japan Society of Obstetrics and Gynecology. To confirm the histological diagnosis, both immunocytochemical studies for alphafetoprotein (AFP) and carcinoembryonic antigen (CEA), and immunohistochemical studies for AFP, CEA, CA19-9, and CA125 were performed. Serum AFP and CA125 levels were serially determined. On hematoxylin and eosin staining an endodermal sinus pattern associated with Schiller-Duval bodies was observed in the right ovarian tumor. However, papillary serous carcinoma was found on the surface of the almost normal sized left ovary and in the omental metastatic nodules.     

Multiple biochemical markers in patients with gynecologic malignancies

Plasma levels of carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and human chorionic gonadotropin (hCG) were measured in 253 patients with gynecologic malignancies and in 317 patients with benign gynecologic diseases. Plasma concentrations of each of these antigens were elevated in a significantly (p less than 0.001) greater number of patients with invasive gynecologic cancers than in the control population. Carcinoembryonic antigen was the most commonly elevated marker, followed by AFP and hCG. Prior to therapy, over 85% of patients with ovarian or cervical cancer had elevated plasma levels of one or more antigens. Specifically, CEA was most often elevated in patients with mucinous adenocarcinomas of the ovary and endocervix. Alpha-fetoprotein was most often increased in patients with germ cell or stromal tumors of the ovary and in patients with large-cell nonkeratinizing cervical cancers. In contrast, hCG concentrations were highest in patients with serious cystadenocarcinomas of the ovary and in patients with keratinizing squamous cell carcinomas of the cervix. Plasma antigen levels were directly related to tumor differentiation and stage of disease, and generally returned to normal eight to 12 weeks following therapy. Effective plasma and tumor antigen screening during initial evaluation of patients with gynecologic tumors should help to identify the most appropriate antigen for immunodetection procedures and for serial plasma determinations following therapy.     

Cisplatin, vinblastine, and bleomycin combination chemotherapy in a stage IV pure endodermal sinus tumor of the ovary--a case report of a long-term survival

Discussed is a case of a stage IV pure endodermal sinus tumor (EST) of the ovary that was treated with a PVB protocol following cytoreductive surgery. The serum alpha-fetoprotein (AFP) dosage before treatment was 83,546 ng/ml, and a complete clinical response was achieved with the disappearance of pleural effusions, ascites, and normalization of the serum AFP. A second-look laparotomy was substituted by serial AFP determinations and the patient remained free of disease for two years. Recently, complete remissions and long term survivals of patients with a stage I-II disease have been reported, though a prolonged or a complete remission of a stage IV EST of the ovary is still a rarity.     

Alpha-foetoprotein and carcinoembryonic antigen in germ cell neoplasms.

Serum alpha-foetoprotein (AFP) and serum carcinoembryonic antigen (CEA) levels were measured, serially whenever possible, in 70 patients attending the Institute of Radiotherapy, Rotterdam, on account of testicular (65) or ovarian (4) germ cell tumours or, in one case, an endodermal sinus (yolk sac) tumour in the mediastinum. In 15 patients the disease was active; in the others it was in remission. Patients with active disease had raised serum AFP levels which correlated well with disease activity; no patient without evidence of active disease had raised serum AFP levels. None of the patients with active disease was found to have raised serum CEA levels. There was no correlation between serum AFP and CEA levels in patients with germ cell neoplasms, but good correlation between serum AFP levels and disease activity. Serum CEA levels did not correlate with disease activity, and serial determinations would therefore not be useful in monitoring progress in this group of diseases.     

Mediastinal yolk sac tumor in a woman

Primary endodermal sinus tumor (yolk sac tumor) of the mediastinum is uncommon and most patients are young and male. We report a yolk sac tumor with a mature teratoma of the anterior mediastinum in a 28-year-old woman with an intrathoracic mass. Four courses of combination chemotherapy were given and the tumor was resected. The patient's serum alpha-fetoprotein (AFP) level was elevated, to more 100 000 ng/ml. To the best of our knowledge, this is the first report of serum AFP level exceeding 100 000 ng/ml in a yolk sac tumor with a mature teratoma.     

Transformation of an AFP-positive yolk sac carcinoma into an AFP-negative neoplasm. Evidence for in vivo cloning of the human parietal yolk sac carcinoma

An alpha-fetoprotein (AFP)-positive ovarian yolk sac carcinoma of typical histologic appearance was surgically removed from a 19-year-old woman. The AFP-positive tumor recurred and was treated with x-rays and cytotoxic drugs to full remission, i.e., until no clinical or biochemical signs of tumor were evident. The second recurrence, which proved to be fatal, was noticed approximately 1 year after the initial diagnosis, but was not associated with elevated levels of serum AFP. At autopsy, the widespread tumor had the histologic appearance reminiscent of murine parietal yolk sac (PYS) carcinoma. The tumor cells did not form the characteristic histologic features of the classical human yolk sac carcinoma, did not secrete AFP, and were surrounded by extensive hyalinous extracellular matrix rich in laminin and collagen. It is thus shown that recurrent human yolk sac carcinomas could change their histologic morphology due to selective outgrowth and cloning of the parietal yolk sac component. Clinical recognition of this cloning is important because the PYS carcinoma cells do not secrete AFP, and the tumor growth cannot be biochemically monitored with this classical tumor marker.     

Tumor markers AFP,CA 125, and CA 19-9 in the long-term follow-up of sacrococcygeal teratomas in infancy and childhood

Given the tendency of a proportion of sacrococcygeal teratomas (SCT) to recur, we evaluated whether serial tumor marker measurements are helpful in the management of these children. Between 1985 and 2006, 32 children with SCT were followed up for 1–15 years, and a total of 344, 197, and 193 serial samples for serum alpha-fetoprotein (AFP), CA 125, and CA 19-9 were analyzed, respectively. Six children with neonatal SCT developed eight recurrences. Serum AFP was elevated in two of two children prior to diagnosis of malignant recurrences (yolk sac tumor and adenocarcinoma), and CA 125 was elevated in one third of mature and one third of immature recurrences. CA 19-9 remained within reference values in relation to recurrences of neonatal SCT. Taken together, serum CA 125 measurements may complement the use of serum AFP in the follow-up of SCT.     

Tumor markers in testicular tumors

Serum levels of hCG, AFP, CEA and testosterone were measured in 20 patients with testicular tumors for an evaluation of their clinical significance as tumor markers. HCG was elevated in those with chorional and syncytiotrophoblastic cell tumors, but it was also detected in some cases of embryonal carcinoma and seminoma, suggesting the presence of hCG-producing elements. AFP was exclusively elevated in embryonal and yolk sac tumors. CEA and testosterone were mostly normal in all patients. HCG and AFP fluctuated in good correlation with the clinical course. Thus, hCG and AFP were valuable tumor markers for testicular tumors for the diagnosis of histological type and stage and monitoring the therapeutic effect and prognosis.     

Alpha-fetoprotein-producing non-germ cell tumours of the female genital tract

Elevated levels of alpha-fetoprotein (AFP), a foetal serum protein, occur mainly on the development of hepatocellular carcinoma (HCC) or germ cell tumours, including yolk sac tumour (YST) and embryonal carcinoma of the ovary. Rarely, other tumours of the female genital tract produce AFP. This article reviews the AFP-producing non-germ cell tumours reported in different parts of the female genital tract to date. These include different types of carcinomas and carcinosarcomas of the uterus, ovary and cervix and sex cord stromal tumours of the ovary. It is important for both pathologists and oncologists to be aware of such cases and the clinicopathological distinction from germ cell tumours, as the diagnosis would affect the management plan for the patient. The reviewed cases suggest that regardless of the patient’s age when no lesion is detected in the liver and stomach of a woman whose serum AFP level is abnormally high, the female reproductive system should be examined as a possible site of AFP-producing tumour. Biochemical, physiological and pathological features of AFP are briefly presented.     

Germ-cell tumors in patients with apparently normal testes

Germ-cell tumors occasionally occur in patients with clinically normal testes. Although data exist correlating serial serum hCG and AFP in gem-cell neoplasms of testicular origin, the literature is sparse concerning the patients presenting with clinically normal testes. Presented in this report are data to confirm the reliability and usefulness of serial serum hCG and AFP levels in those patients with extragonadal germ-cell tumors and apparently normal testes. Six patients with nonseminomatous extragonadal tumors are presented. Serial serum hCG and AFP levels correlated with the clinical course in each of the patients. The serum hCG and/or AFP decreased with response to therapy and increased with progression of disease. It is concluded that serial serum hCG and AFP determinations are very useful parameters to evaluate and follow the course of disease in this group of patients.     

鞍区罕见肿瘤的临床诊治分析

目的 探讨鞍区罕见肿瘤的临床特点及其显微手术治疗,以提高对该病的诊治水平.方法 收集经显微手术治疗的6例鞍区罕见肿瘤患者的临床资料进行回顾性分析,并结合术前肿瘤标记物甲胎蛋白(AFP)和绒毛膜促性腺激素(HCG)联合检测与术后免疫组化染色指导后续治疗.结果 本组6例患者术前全部误诊,术毕病变镜下全切2例,大部切除4例.病理诊断肿瘤5例,炎性假瘤1例,病理类型分别为平滑肌肉瘤、卵黄囊瘤、混合性生殖细胞肿瘤、胚胎癌和毛细胞性星形细胞瘤及霉菌性炎性假瘤.术前AFP或HCG在卵黄囊瘤、胚胎癌和混合性生殖细胞瘤中均有不同程度升高.随访1个月至3年,卵黄囊瘤、胚胎癌和平滑肌肉瘤患者分别在术后5、6、10个月死亡,炎性假瘤患者术后2个月出现蛛网膜下腔出血,病情危重,余生存良好.结论 鞍区罕见肿瘤以高度恶性生殖细胞肿瘤为主,病理类型复杂,术前误诊率高,临床预后差.术前AFP和HCG联合检测对指导治疗、判断预后有一定意义.

Abstract：

Objective To investigate the clinical characteristics and microsurgical managements of rare tumors in the sellar region. Methods Six rare cases of tumors in the sellar region treated by microsurgery from Jan 2000 to Jan 2010 were reviewed retrospectively.Subsequent treatments were according to the status of preoperative alpha fetal protein(AFP) and human chorionic gonadotropin(HCG) measurement as well as confirmed by histopathological examination in all six patients. Results Total resection of the tumor was achieved in 2 cases and subtotal resection in 4 cases.Postoperative histopathology confirmed that the lesions were tumors in 5 cases and fungal pseudotumor in 1 case.Moreover,variety of histological types were observed in the present series,including leiomyosarcoma,malignant yolk sac tumor,mixed germ cell tumor,embryonal carcinoma,pilocytic astrocytoma and fungal pseudotumor,respectively.The serum levels of AFP and HCG were elevated to some extent in the patients with malignant yolk sac tumor,mixed germ cell tumor or embryonal carcinoma.Follow-up was conducted in all patients for 1 month to 3 years.The patients with malignant yolk sac tumor and embryonal carcinoma as well as leiomyosarcoma died in 5,6,10 months after operation,respectively.Subarachnoid hemorrhage occurred in the case of fungal pseudotumor at 2 months sfter surgery.The other two patients were surviving well. Conclusions Rare nongerminomatous malignant germ cell tumors are predominantly susceptible to the sellar region.Furthermore,High misdiagnosis rate and poor prognosis are characteristic in the present study.Dynamic AFP and HCG detection may play an important role in the diagnosis of those non-germinomatous malignant germ cell tumors located in the sellar region.The importance of awareness of the presence of such rare lesions in the sellar region is emphasized.     

Serum alpha1-foetoprotein levels in 153 male patients with germ cell tumours.

--alpha1-Foetoprotein (AFP) levels have been measured by radioimmunoassay in the serum of 153 male patients with gonadal and extragonadal germ cell tumours. Thirty-five patients with pure seminoma, and 34 patients with teratoma but without any postoperative evidence of residual or recurrent tumour, consistently had normal serum AFP levels (less than 25 ng/ml). Of 84 patients with active teratomas, 56 (67%) had serological evidence of AFP production. Ten patients with histological evidence of pure yolk sac (endodermal sinus) tumours all had raised levels. Teratomas containing yolk sac (elements may or may not be associated with raised serum levels. Trophoblastic (choriocarcinomatous) elements in a teratoma were not normally associated with high values. Fourteen patients with teratomas had elevated levels in the absence of histologically detectable yolk sac elements. Serum AFP levels often became elevated before clinical evidence of recurrence, so that AFP can act as an effective marker of the course of the disease and its response to therapy in many patients, but recurrent or progressive disease may be present in the absence of raised levels.     

The value of serial measurement of both human chorionic gonadotropin and alpha-fetoprotein for monitoring germinal cell tumors.

Quantitative serial serum measurements of human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP) levels using sensitive double-antibody radioimmunoassays were performed in nine patients with germinal cell tumors before and during treatment. The sera of eight of the nine were found to have a hCG marker and five of the nine an AFP marker. The sera of four patients were found to have both. Serial serum levels of hCG, of AFP, or both were useful for monitoring disease activity during therapy in all nine patients. In two patients tumor masses failed to diminish during chemotherapy, but the tumor markers fell appropriately. At surgery one patient had a mature teratoma, the other a mature teratoma with a microscopic focus of an embryonal cell tumor. In one patient tumor reactivation was reflected by the emergence of only one of two previously elevated tumor markers. One patient had a rise in hCG, another a rise in both markers coincident with recurrence of tumor. Serial measurements of AFP and hCG are useful for following the response to therapy of germinal tumors, and can assist in making therapeutic decisions.     

Immunoelectrophoretic Differentiation Of Alpha-Fetoprotein In Disorders With Elevated Serum Alpha-Fetoprotein Levels Or During Pregnancy

Our study aims to make differential diagnosis by immunoelectrophoresis for some common conditions with elevated levels of serum alpha-fetoprotein (AFP). One hundred and nine cases with elevated AFP levels were included in this study: yolk sac tumor (n = S), hepatocellular carcinoma (n = 26), gastric cancer (n = 12), chronic hepatitis (n = 27) and normal pregnancy (n = 36). Lectin agarose gel electrophoresis, antibody-affinity blotting, and immunoreaction were used to identify the specific patterns of AFP in the respective conditions. The results showed that there were three possible bands: L1, L2 and L3. Yolk sac tumor produced a prominent L2 band and a light L3 band. Hepatocellular carcinoma produced a prominent L1 band and a light L3 band. Gastric cancer produced only an L1 band. Chronic hepatitis had a light L1 band and a pronounced L3 band. In pregnancy, the AFP pattern is similar to that of hepatocellular carcinoma. Immunoelectrophoresis is a useful method facilitating the differentiation of AFP origins.     

Alpha-fetoprotein (AFP)-producing ovarian tumor in an elderly woman

Apart from typical yolk sac tumors, ovarian tumors with elevated alfa-fetoprotein (AFP) are uncommon and the differential diagnosis needs to consider the hepatoid pattern of a yolk sac tumor, hepatocellular carcinoma metastatic to the ovary, hepatoid carcinoma, and other epithelial ovarian tumors. We report here an AFP-producing ovarian tumor with uncertain pathological diagnosis, which was extremely responsive to chemotherapy. A 59-year-old Japanese woman presented with lower abdominal distension and was found to have a left ovarian mass on pelvic examination and magnetic resonance imaging (MRI) scan. Laboratory tests showed serum AFP, 73 687 ng/ml; carbohydrate antigen 125 (CA125), 1599 U/ml; and carcinoembryonic antigen (CEA), 13.9 ng/ml. Total hysterectomy with bilateral salpingo-oophorectomy, partial omentectomy, and low anterior resection of the rectum was performed, without any residual macroscopic tumor. Microscopically, the tumor was characterized by a hepatoid carcinomatous component composed of solid sheets of large eosinophilic cells with pleomorphic nuclei. The pathological stage was pT2N0M0. Tumor cells were diffusely immunoreactive for AFP and cytokeratin (CAM5.2), but monoclonal CEA and CA19-9 were focally positive in the cytoplasm, while CA125 was negative. The patient was treated postoperatively with three cycles of chemotherapy consisting of bleomycin, etoposide, and cisplatin; with this regimen, serum AFP decreased to 16 ng/ml from 12 600 ng/ml just before the initiation of chemotherapy. The patient received secondary cytoreductive surgery of systemic lymphadenectomy, which revealed no evidence of residual tumor.     

The differentiation of clonal rat yolk sac tumor cell lines cultivated with dibutyryl-cyclic 3', 5'-adenosine monophosphate.

Five rat yolk sac tumor cell lines were cloned from a yolk sac tumor line which originally arose following fetectomy. The doubling time of each of the cloned tumor lines was about 50 h. All of the cloned tumor cell lines synthesized and secreted AFP and albumin but there was a gradual decrease in the synthesis of these proteins during serial passage. The cells formed clusters which looked like vitelline ducts or the parietal yolk sac and they also had basement membranes which closely resembled Reichert's membrane. When the cloned cell lines were cultivated in the presence of 1 mM dibutyryl cyclic-AMP, myotube-like and neuron-like cells appeared. Acetylcholine esterase and creatine phosphokinase activity were present when myotube-like cells were present whereas acetylcholine esterase activity predominated when neuron-like cells were present.     

Alpha-fetoprotein (AFP) Elevation Gastric Adenocarcinoma and Importance of AFP Change in Tumor Response Evaluation

Background: Elevated serum alpha-fetoprotein (AFP) levels in adults are considered abnormal. This parameteris used mostly in the diagnosis and follow-up of hepatocellular carcinomas and yolk sac tumors. Among the otherrare tumors accompanied with elevated serum AFP levels, gastric cancer is the most common. In this study, weevaluated the follow-up and comparison of the treatment and marker response of patients with metastatic gastriccancer who had elevated serum AFP levels. Materials and Methods: We performed a retrospective study, includingall consecutive patients with advanced gastric cancer, who received systemic chemotherapy with elevated AFPlevel. Results: Seventeen metastatic gastric cancer patients with elevated AFP levels at the time of diagnosis wereevaluated. Fourteen (82.4%) were males and three (17.6%) were females. The primary tumor localization wasthe gastric body in 8 (76.4%), cardia in 7 (41.2%), and antrum in 2 (11.8%). Hepatic metastasis was observed in13 (76.4%) at the time of diagnosis. When the relationship of AFP levels and carcinoembryonic antigen (CEA)response of the patients with their radiologic responses was evaluated, it was found that the radiologic responsewas compatible with AFP response in 16 (94.1%) patients and with CEA response in 12 (70.6%); however, in 5(29.4%) patients no accordance was observed between radiological and CEA responses. Conclusions: Followupof AFP levels in metastatic gastric cancer patients with elevated AFP levels may allow prediction of earlytreatment response and could be more useful than the CEA marker for follow-up in response evaluation.