A case of alpha-fetoprotein–producing adenocarcinoma of the endometrium with a hepatoid component as a potential source for alpha-fetoprotein in a postmenopausal woman

Although case reports of alpha-fetoprotein (AFP)-producing adenocarcinoma other than hepatocellular carcinoma have gradually increased in number, AFP-producing adenocarcinoma of the endometrium is very rare. The patients universally complain of abnormal vaginal bleeding. The patient presented with complaints of epigastric discomfort. No vaginal bleeding was observed. Serum AFP concentration was 453 ng/mL, and lens culinaris agglutinin-reactive AFP percentage of total AFP was increased to 67%. Radiologic imaging and endoscopy did not provide evidence of any primary carcinoma in the liver and gastrointestinal tract. To investigate the unknown origin of high AFP, Pap smear of the endometrium followed by fractional curettage was performed and revealed adenocarcinoma of the endometrium. Radical hysterectomy with pelvic lymph node dissection and partial omentectomy was performed. Histologic study showed a mixture of major AFP-negative endometrioid adenocarcinoma and minor medullary proliferation of the AFP-positive hepatoid adenocarcinoma cells with eosinophilic cytoplasm and hyaline globules. After the surgery followed by four courses of weekly carboplatin and paclitaxel administration, serum levels of AFP dropped into normal range. The possible existence of AFP-producing adenocarcinoma of the endometrium should be considered in a postmenopausal woman even if there is no vaginal bleeding, when AFP-producing tumor is clinically suspected and the imaging studies fail to confirm the diagnosis.     

肝癌术后监测血清AFP的临床意义(附70例报告)

为探讨肝癌术后监测血清甲胎蛋白(AFP)的临床意义，回顾性分析1996年2月至2002年3月间肝癌根治切除术后定期监测发现血清AFP阳性的70例患者AFP升高与肿瘤残留、复发或转移的关系。肝癌术后血清AFP升高可见于肝癌的残留或早期转移、肝癌的复发或转移、肝癌的再发以及晚期肝硬变4种情况。对肝癌患者术后定期作AFP检查，有助于检出AFP阳性肝癌患者的肿瘤残留及亚临床期复发转移，不仅适用于术前AFP阳性，而且适用于术前AFP阴性的肝癌患者。肝癌患者术后AFP下降，但不能降至正常，可能与晚期肝硬变肝脏内干细胞-卵圆形细胞代偿性增生有关。     

Fine-needle aspiration cytology of an endometrioid-like variant of yolk sac tumor.

A 36-year-old male with a history of immature teratoma and embryonal carcinoma of the testis was admitted to the hospital for abdominal pain and fever. A CT scan revealed a large right abdominal mass. The patient's serum alpha-fetoprotein (AFP) was 46.8 ng/ml (reference < 25 ng/ml). Fine-needle aspiration (FNA) of the mass revealed malignant glandular cells. Chemotherapy was instituted, followed by resection of the large abdominal mass. The tumor was grossly encapsulated, consisting of large areas of necrotic, hemorrhagic tissue surrounded by smaller, multiloculated cysts. Microscopically, the tumor had a villoglandular pattern and variably stratified tall columnar cells. A prominent feature of the columnar cells was supranuclear and subnuclear vacuolization. Intracytoplasmic PAS-positive, diastase-resistant hyaline globules were occasionally present. AFP by immunoperoxidase was prominent within the tumor. This recurrence of the previously diagnosed testicular teratoma with embryonal carcinoma represents a yolk sac tumor with components strongly resembling endometrioid carcinoma, a variant only recently described in eight cases of ovarian origin (Clement et al.: Am J Surg Pathol 1987; 11(10):767-778). We believe this is the first reported case of an endometrioid-like variant of testicular yolk sac tumor and also the first report of the FNA cytology findings in this variant.     

携带hIL-2cDNA的逆转录病毒载体的构建及其在人肝癌细胞中的特异表达研究

将人白细胞介素２（ｈＩＬ-２）ｃＤＮＡ克隆到逆转录病毒载体ＭＮＳＭ的ＰＬ位点　，分别构建了转录受ＳＶ４０早期启动子和人甲胎蛋白增强子调控的重组逆转录病毒载体ＭＮＳＩ和ＭＮＳＩＡ。用脂质体转染法将ＭＮＳＩ和ＭＮＳＩＡ分别转导ＰＡ３１７包装细胞，测质粒转染率为（５～２０）×１０~(－３)克隆／μｇＤＮＡ·１０~６细胞，病毒感染率为（５．４～４５０）×１０~４ＣＦＵ／ｍｌ。重组病毒在４μｇ／ｍｌ ｐｏｌｙｂｒｅｎｅ存在条件下感染人肝癌细胞、肾癌细胞和黑色素瘤细胞，Ｎｅｏ~Ｒ克隆经Ｓｏｕｔｈｅｒｎｂｌｏｔ分析证明ｈＩＬ－２ｃＤＮＡ转入人肿瘤细胞并整合，　Ｒ　ＮＡ斑点杂交及ＩＬ－２活性表达分析证明，人甲胎蛋白增强子可促进异源启动子启动ｈＩＬ－２ｃＤ－ＮＡ在合成甲胎蛋白的人肝癌细胞中高效特异转录和表达。该研究对肝癌特异性免疫增强基因治疗有重要意义。     

The direct early diagnosis of cystic fibrosis by the detection of the deltaF508 CFTR gene mutation in a prematurely delivered boy

The suspicion of prenatal meconium ileus syndrome was raised in a pregnancy in a family with no history of cystic fibrosis because of significantly higher maternal serum alpha-fetoprotein in the 16th and 19th week of gestation, dispersed areas with increased echogenity in the fetal abdomen, slight fetal ascites in the 24th-25th weeks of gestation, decreased amniotic fluid gamma-glutamyltranspeptidase (GGT) activity and alpha-fetoprotein level in the 25th-26th weeks, and normal 46,XY karotype of the fetus. The detection of a homozygous deltaF508 cystic fibrosis transmembrane regulator (CFTR) gene mutation, by means of PCR from a small amount of white blood cells and urine sediment cells, substantiated the diagnosis of cystic fibrosis in a prematurely delivered boy in the 28th week of gestation. The repeated sweat test was unsuccessful. The autopsy examination confirmed the diagnosis of cystic fibrosis. Fetal meconium ileus syndrome was complicated by peritonitis and by formation of a meconium pseudocyst. Direct PCR typing improves postnatal diagnostic possibilities in the early neonatal period in prematurely delivered babies when the sweat test is difficult to perform.     

Transport of Proteins Across the Human Placenta

PROBLEM: The transport of various proteins across the human placenta was investigated by comparing maternal and fetal concentrations of tetanus antigen (TT-AG), anti-tetanus (TT)-immunoglobulin G (IgG) (following maternal vaccination), IgA, human chorionic gonadotropin (hCG), human placental lactogen (hPL), and alpha-fetoprotein (AFP) at term. METHOD OF STUDY: The concentrations of the six proteins were determined using enzyme-linked immunosorbent assay in serum of maternal venous and umbilical (fetal) vein samples obtained at delivery from uncomplicated term pregnancies (n = 16). RESULTS: The ratios (mean ± standard deviation) of fetal (umbilical) to maternal level were 1.41 ± 0.33 (anti-TT-IgG), 0.91 ± 0.37 (TT-AG), 0.002 ± 0.001 (IgA), 0.003 ± 0.001 (hCG), and 0.008 ± 0.004 (hPL), while the maternal:fetal concentration ratio of AFP was 0.002 ± 0.002. IgA, hCG, hPL, and AFP showed a close correlation between maternal and fetal levels varying between r² = 0.47 to 0.73 (P < 0.004–0.0001). Because AFP is produced by the fetus while IgA originates in the mother, the appearance of small amounts of these two proteins in the maternal or fetal compartment, respectively, suggests a slow rate of diffusion following a high concentration gradient. The detection of hCG and hPL in fetal serum is also interpreted as diffusion from the maternal into the fetal blood. Anti-TT-IgG has a significantly higher concentration in the fetal as compared with the maternal serum, which is in line with the well-documented active transfer of IgG. Fetal TT-antigen levels were similar to maternal concentrations, showing a close correlation (r² = 0.74, P < 0.0001) between the two proteins. CONCLUSIONS: The correlation between maternal and fetal concentrations of various proteins like IgA (150,000 Da), hCG (42,000 Da), and hPL (21,000 Da) suggests passive diffusion of these macromolecules across the placenta from the maternal to the fetal side, albeit at a slow rate. A similar process is postulated for AFP (70,000 Da) diffusing in the opposite direction from the fetus to the mother. There was no significant difference between the transplacental fetomaternal gradient of IgA and hCG and the maternal-fetal gradient of AFP. In view of the substantially larger volume of circulating maternal as compared with fetal blood, a significantly higher rate of crossing of AFP as compared with the other proteins must be assumed. It is uncertain whether a difference in the rate of transplacental transfer in the two directions or an additional source of AFP production in the maternal compartment explains the high maternal level. Anti-TT-IgG concentration is significantly higher in fetal than in maternal serum suggesting active transfer from the mother to the fetus. Furthermore, there is considerable transfer of TT-AG and a close correlation of fetal:maternal ratios of anti-TT-IgG (150,000 Da) and TT-AG (150,000 Da) could be an indication for a specific transfer of the antigen antibody complex.     

子痫前期患者血清AFP、D-二聚体、PLGF水平对母体及妊娠结局影响

目的:分析子痫前期(PE)患者血清甲胎蛋白(AFP)、D-二聚体(D-dimer)及胎盘生长因子(PLGF)水平对母体及妊娠结局的影响。方法:将本院2016年1月-2018年9月收治的330例PE患者分轻度PE组(n=117)、重度PE组(n=213),另选同期本院住院待产的正常妊娠产妇30例为对照组,检测各组孕妇血清AFP、D-dimer、PLGF水平,绘制受试者工作特征(ROC)曲线分析对PE的诊断预测效能;Spearman相关性分析各检测指标与病情的相关性;对PE患者妊娠结局的预测效能。结果:PE组与对照组AFP比较无差异(P>0.05),但D-dimer水平PE组高于对照组,PLGF低于对照组(P<0.05);D-dimer AUC值最高(387.51μg/L),预测PE的敏感度、特异度为80.6%、100.0%;PLGF AUC值次之(217.33pg/ml),预测PE的敏感度为96.7%,高于D-dimer。不同病情严重程度的PE患者血清AFP、PLGF水平未见差异(P>0.05),但D-dimer轻度PE组低于重度PE组(P<0.05)。AFP与PE病情程度未见相关性(r=0.093,P=0.078),D-dimer与PE病情程度正相关(r=0.796,P=0.000),PLGF与PE病情程度负相关(r=0.114,P=0.031)。PE患者中,母体发生并发症、胎儿结局不良者血清D-dimer水平高于无并发症、胎儿结局良好者(P<0.05),AFP、PLGF未见差异(P>0.05);D-dimer对PE患者并发症可发挥一定预测效能,以579.53μg/L为cut-off,预测PE患者并发症的敏感度、特异度为80.9%、61.9%,另两项血清指标对妊娠结局的预测效能不佳。结论:血清AFP、D-dimer、PLGF3个指标中,D-dimer对PE的预测价值及其与PE病情的相关性最为显著,用于预测PE患者母体并发症具有一定敏感度,但特异度不佳。     

Yolk sac tumor with a unique uniform hepatoid pattern histology

Abstract Background: Yolk sac tumors (YST) exhibit several different histological subtypes and the mechanisms of cellular differentiation and prognosis of each subtype remain unknown.
Results: We report two infants with sacrococcygeal YST; one represented a typical histological subtype and the other showed a hepatoid subtype with uniform histology. The isoform of alpha-fetoprotein (AFP) in the patient with the hepatoid pattern was examined by lectin-affinity Immunoelectrophoresis and represented as a YST. but not hepatocellular, subtype. The patient with typical YST responded well to VAB-6 combination chemotherapy. However, this regimen was only partially effective to the patient with the pure hepatoid histological subtype, and an etoposide with ifosfamide and cisplatin (VIP) regimen as a salvage chemotherapy combined with complete tumor resection was useful to achieve complete remission (CR). Both of the patients have been in CR for more than four years.     

Alpha-fetoprotein and Sertoli-Leydig cell tumor

Gard GB, Mulvany N, Quinn MA. Alpha-fetoprotein and Sertoli-Leydig cell tumor. Int J Gynecol Cancer 1998; 8 : 499–503.
The association between a Sertoli-Leydig cell tumor and a raised serum alpha-fetoprotein (AFP) is an uncommon occurrence which has only been previously described in 20 patients. We report a 17-year-old patient who presented with a pelvic mass and a raised serum AFP. At laparotomy she had a FIGO stage IA moderately differentiated Sertoli-Leydig cell tumor which required no further treatment. We have reviewed the literature relating to AFP production by Sertoli-Leydig cell tumors. When serum AFP is raised at diagnosis it appears to be a reliable tumor marker, hence a baseline level should be documented on all patients with Sertoli-Leydig cell tumor.