Epithelioid trophoblastic tumor is an unusual type of trophoblastic tumor. Here we report on the clinicopathologic and immunohistochemical features of three cases of epithelioid trophoblastic tumor. All three patients were of reproductive age and presented with vaginal bleeding and mild elevation of human chorionic gonadotropin (hCG). All patients underwent a hysterectomy. The tumors consisted of epithelioid intermediate trophoblastic cells that were mononucleated and eosinophilic, or showed clear cytoplasm on microscopic examination. One case presented with a focal choriocarcinoma component. Immunohistochemically, the tumors displayed diffuse positivity for cytokeratin 18, E-cadherin, epidermal growth factor receptor, and p53 and focal positivity for p63 and hCG. However, expression of alpha-inhibin and placental alkaline phosphatase was almost negative. Tests for human placental lactogen and epithelial membrane antigen were also negative in all cases.
Alkaline Phosphatase ; Cadherins ; Choriocarcinoma ; Chorionic Gonadotropin ; Cytoplasm ; Eosinophils ; Female ; Gestational Trophoblastic Disease ; Humans ; Hysterectomy ; Inhibins ; Keratin-18 ; Mucin-1 ; Placental Lactogen ; Pregnancy ; Receptor, Epidermal Growth Factor ; Trophoblastic Neoplasms ; Trophoblasts ; Uterine Hemorrhage

Nongestational choriocarcinoma differentiation is extremely rare in breast neoplasms. It is characterized by tumor cells similar to chorionic trophoblastic cells, which react with human placental lactogen and human chorionic gonadotropin (hCG). A 56-year-old woman presented with a palpable right breast mass without past history of trophoblastic tumors. An F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scan revealed one focus with low accumulation of FDG in the right breast (maximum standardized uptake value, 1.98). The patient underwent a right mastectomy and biopsy of sentinel nodes. Microscopically, the tumor was a typical invasive ductal carcinoma with multiple foci of choriocarcinoma features. Immunohistochemistry showed that the tumor cells resembling choriocarcinoma were positive for hCG antibody, but negative for HER2/neu, estrogen receptor, and progesterone receptor. A pathologic diagnosis of breast carcinoma with choriocarcinomatous features was made. To our knowledge, this is the first report of invasive carcinoma with choriocarcinomatous features and an unusual finding of low accumulation in an F-18 FDG PET/CT scan in Korea.
Biopsy ; Breast ; Breast Neoplasms ; Carcinoma, Ductal ; Choriocarcinoma ; Chorion ; Chorionic Gonadotropin ; Electrons ; Estrogens ; Female ; Humans ; Immunohistochemistry ; Korea ; Mastectomy ; Middle Aged ; Nitriles ; Placental Lactogen ; Pregnancy ; Pyrethrins ; Receptors, Progesterone ; Trophoblastic Neoplasms ; Trophoblasts

OBJECTIVEGenistein, a major soy isoflavone metabolite (SIF), inactivates oxidation activity of bovine lactoperoxidase (LPO). Modification of the heme moiety of LPO by nitrogen-containing compounds has been shown to inactivate LPO. In contrast, SIF mediated inactivation of LPO does not involve a heme modification and the mechanism of SIF inhibition is poorly understood.

METHODSAfter inactivation of LPO by genistein in the presence of H(2)O(2), trypsin-digested LPO peptide fragments were collected and analyzed by MALDI-TOF-MS to characterize the chemical binding of genistein(s) to LPO.

RESULTSThe heme moiety of LPO was not modified by genistein. A covalent binding study showed that (3)H-genistein bound to LPO with a ratio of ∼12 to 1. After HPLC analysis and peak collection, trypsin-digested peptide fragments were analyzed by MALDI-TOF-MS. The 3H-genistein co-eluted peptide fragments (RT=24 min) were putatively identified as 199IVGYLDEEGVLDQNR214 with two bound genistein molecules or a genistein dimer (2 259 Da), 486TPDNIDIWIGGNAEPMVER504 with two bound genistein molecules or a genistein dimer (2 663 Da), and 161ARWLPAEYEDGLALPFGWTQR182 with three bound genistein molecules or a genistein trimer (3 060 Da). The fragment with a mass of 1 792 Da (RT=36 min) was identified as 132CDENSPYR139 with three genistein molecules or a genistein trimer.

CONCLUSIONSThe results suggest that LPO was inactivated by irreversible covalent binding of genistein or genistein polymers to particular peptide fragments constituting regions of the outward domain. No genistein interaction with the prosthetic heme moiety of LPO was observed.

Animals ; Cattle ; Enzyme Activation ; drug effects ; Genistein ; metabolism ; Hydrogen Peroxide ; pharmacology ; Isoflavones ; pharmacology ; Lactoperoxidase ; metabolism ; Placental Lactogen ; Protein Binding

BACKGROUND: Recent studies have suggested that implantation site intermediate trophoblasts (ISITs) and chorionic type intermediate trophoblasts (CTITs) show different immunohistochemical findings, and that each type has specific location in placentas. However, we observed that both subtypes are intimately admixed in many areas of the placentas and both types are proliferated around the infarcts. METHODS: In order to examine the site specificity in their distribution and the changes of intermediate trophoblasts (ITs), if any, in the pre-eclamptic placentas, quantitative analyses of ISITs and CTITs using p63, CD146, placental alkaline phosphatase, human placental lactogen, and alpha-inhibin were performed in normal and pre-eclamptic placentas containing infarcts. RESULTS: In the fetal membranes of both normal and pre-eclamptic placentas, CTITs and ISITs were equally identified, forming distinct layers. ISITs were predominant in the intervillous septum and basal plate, while CTITs were predominant in the subchorionic area. At the margin of infarcts in pre-eclamptic placentas, both subtypes were increased in number, forming distinct layers. CONCLUSIONS: The subtypes of ITs do not have site specificity in placentas. Increased number of ITs and zonal distribution around infarcts suggest that CTITs and ISITs have differentiation associated relationship, and the differentiation might be related to the microenvironment of placenta, such as intraplacental oxygen concentration.
Alkaline Phosphatase ; Chorion ; Extraembryonic Membranes ; Fluconazole ; Immunohistochemistry ; Inhibins ; Oxygen ; Placenta ; Placental Lactogen ; Pre-Eclampsia ; Sensitivity and Specificity ; Trophoblasts

OBJECTIVETo study the clinicopathologic features, immunophenotype, differential diagnosis and prognosis of uterine epithelioid trophoblastic tumor(ETT).

METHODSFrom 2000 to 2007, 5 ETTs cases were diagnosed in the affiliated Women's Hospital, School of Medicine, Zhejiang University. The pathologic characteristics and immunophenotype of the tumors were analyzed by histological examination and immunohistochemistry of CK18, p63, inhibin-alpha, HCG, HPL, PLAP and Ki-67. The clinical prognostic factors were evaluated based on a following-up data with a period of 11 - 50 months.

RESULTSThe overall prevalence of ETT was 0.48% among all the gestational trophoblastic diseases patients received in the same period. Five ETT patients were in the reproductive ages with a median of 33 years. Histologically, the tumor showed an invasive, nodular growth consisting of uniform mononuclear trophoblastic cells. There were zones of hyaline material in the tumour nests. Necrosis was commonly seen with a characteristic geographic pattern. Immunohistochemically, all cases displayed a diffuse CK18 and p63 positivity, to be either positive focally or negative for HCG, HPL and PLAP staining. Inhibin-alpha staining was positive or negative either in the 5 cases. Two patients died of the tumour relapse: one died after 1 year with the tumor having a high mitotic activity (averagely 15 mitotic figures per 10 high-power fields), and the other died of lung metastasis 2 years after the diagnosis.

CONCLUSIONSETT is a rare trophoblastic disease with distinct clinicopathological features and immunostaining patterns. A high mitotic index and lung metastasis are indicators for an unfavorable prognosis.

Adult ; Alkaline Phosphatase ; metabolism ; Chemotherapy, Adjuvant ; Chorionic Gonadotropin ; metabolism ; Epithelioid Cells ; pathology ; Female ; Follow-Up Studies ; GPI-Linked Proteins ; metabolism ; Humans ; Hysterectomy ; Inhibins ; metabolism ; Isoenzymes ; metabolism ; Keratin-18 ; metabolism ; Ki-67 Antigen ; metabolism ; Lung Neoplasms ; secondary ; Membrane Proteins ; metabolism ; Middle Aged ; Neoplasm Recurrence, Local ; Placental Lactogen ; metabolism ; Pregnancy ; Trophoblastic Neoplasms ; drug therapy ; metabolism ; pathology ; secondary ; surgery ; Uterine Neoplasms ; drug therapy ; metabolism ; pathology ; surgery

Pregnancy is a complex metabolic state involving dramatic alterations in the hormonal or cytokine environments (increases in estrogen, progesterone, prolactin, cortisol, human chorionic gonadotropin, placental growth hormone and human placental lactogen, TNF-alpha, resistin, leptin, and a decrease in adiponectin) as well as an increasing burden of fuel utilization by the conceptus. Metabolically, the first trimester is characterized by increased insulin sensitivity and lipogenesis. The second and third trimesters, in contrast, are characterized by insulin resistance and increased lipolysis.
Chorionic Gonadotropin ; Cytokines ; Estrogens ; Female ; Growth Hormone ; Humans ; Hydrocortisone ; Insulin ; Insulin Resistance ; Leptin ; Lipogenesis ; Lipolysis ; Placental Hormones ; Placental Lactogen ; Pregnancy ; Pregnancy Trimester, First ; Pregnancy Trimester, Third ; Progesterone ; Prolactin ; Resistin ; Tumor Necrosis Factor-alpha

Adult ; Alkaline Phosphatase ; metabolism ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cervix Uteri ; metabolism ; pathology ; surgery ; Choriocarcinoma ; metabolism ; pathology ; Chorionic Gonadotropin ; metabolism ; Diagnosis, Differential ; Female ; GPI-Linked Proteins ; metabolism ; Humans ; Hysterectomy ; Placental Lactogen ; metabolism ; Pregnancy ; Trophoblastic Tumor, Placental Site ; metabolism ; pathology ; surgery ; Uterine Cervical Neoplasms ; metabolism ; pathology ; surgery

OBJECTIVETo study the clinicopathologic features and immunophenotype of placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT).

METHODSDuring the period from 1959 to 2005, a total of 1012 cases of gestational trophoblastic disease were diagnosed in Beijing Obstetrics and Gynecology Hospital. Six cases of PSTT and a case of ETT were retrieved from the archives of Beijing Obstetrics and Gynecology Hospital. Immunohistochemical study for cytokeratin 18, human chorionic gonadotropin (hCG), human placental lactogen (hPL), Mel-CAM (CD146), placental-like alkaline phosphatase (PLAP), epithelial membrane antigen (EMA), inhibin-alpha and proliferative cell nuclear antigen (PCNA) were performed. The morphologic features and immunohistochemical findings were compared with those of the controlled group which consisted of 20 cases of early gestational villi with decidua basalis and 20 cases of hydatidiform moles with implantation site.

RESULTSThe mean age of patients with PSTT was 32.4, while the age of patients with ETT was 36. Major clinical findings included irregular vaginal bleeding and amenorrhea. Preoperative serum hCG level varied from normal to moderately elevated. Serum testosterone level was raised in 1 case. Uterine curettage could achieve an accurate pathologic diagnosis in 60% of cases. ETT involved mainly the lower uterine segment and endocervix. Histologically, PSTT cells permeated between the myometrial fibers and vessels either individually or connecting in cords or sheets in a manner reminiscent of the implantation site reaction. ETT composed of a relatively uniform population of mononuclear trophoblastic cells, clumping together in nests as the cell islets associating with eosinophilic, fibrillary and hyaline material and necrotic debris, forming a "geographic map" like pattern. Immunohistochemical study for hPL, hCG, Mel-CAM (CD146) and PLAP was most helpful for the differential diagnosis. The duration of follow-up varied from 14 months to 19 years. One case of PSTT developed metastasis in pancreas, 5 months after the operation. The remaining patients survived without tumor recurrence.

CONCLUSIONSPSTT is a tumor of implantation site intermediate trophoblasts while ETT differentiates towards chorionic-type intermediate trophoblasts. The different pathologic features and immunophenotype observed were closely related with the difference in tumor cell differentiation. An accurate pathologic diagnosis of the uterine curettage material is important for the clinical management. According to the limited follow-up data available, the clinical behavior of ETT is seemed similar to that of PSTT.

Adult ; Alkaline Phosphatase ; metabolism ; CD146 Antigen ; metabolism ; Chorionic Gonadotropin ; metabolism ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Hysterectomy ; methods ; Immunohistochemistry ; Isoenzymes ; metabolism ; Middle Aged ; Placental Lactogen ; metabolism ; Pregnancy ; Prognosis ; Trophoblastic Neoplasms ; metabolism ; pathology ; surgery ; Trophoblastic Tumor, Placental Site ; metabolism ; pathology ; surgery ; Uterine Neoplasms ; metabolism ; pathology ; surgery

OBJECTIVETo investigate the clinicopathological features of intermediate trophoblastic non-tumor lesions, and to evaluate the position of immunohistochemistry in differential diagnoses.

METHODSClinical presentation and morphological study of 15 cases of exaggerated placental site (EPS) and 4 cases of placental site nodule or plaque (PSNP) were reviewed. Immunohistochemical stains for hCG, hPL, inhibin-alpha, PLAP, CK18 and Ki-67 were performed.

RESULTSThe age of patients ranged from 25 to 40 years with an average of 31.5 years for EPS and 26 to 39 years with an average of 34.3 years for PSNP. Microscopically, EPS was characterized by cords and small sheets of implantation site intermediate trophoblasts infiltrating the endometrium, myometrium and arterial walls. The general histological structures of the endometrium and myometrium were preserved. PSNP was characterized by multiple circumscribed nodular lesions consisting of so-called chorionic-type intermediate trophoblasts and hyaline-like matrix present in the endometrium. Immunohistochemical stainings for hPL and CK18 were positive in the 15 EPS cases. Immunoreactivity for CK18, Inhibin-alpha and PLAP was detected in 4 PSNP cases. The Ki-67 labeling index in 15 EPS cases was low (< or = 5%), while Ki-67 index in 4 PSNP cases was close to 0.

CONCLUSIONSThe clinical presentation and pathological features of EPS and PSNP differ from those of trophoblastic tumors (placental site trophoblastic tumor, epithelioid trophoblastic tumor and choriocarcinoma). Immunochemical staining is of great value in their differential diagnoses.

Adult ; Diagnosis, Differential ; Endometrium ; pathology ; Female ; Follow-Up Studies ; Humans ; Hysterectomy ; methods ; Inhibins ; metabolism ; Keratins ; metabolism ; Myometrium ; pathology ; Placenta ; metabolism ; pathology ; Placenta Diseases ; metabolism ; pathology ; surgery ; Placental Lactogen ; metabolism ; Pregnancy ; Trophoblastic Neoplasms ; pathology ; Trophoblastic Tumor, Placental Site ; pathology ; Trophoblasts ; pathology ; Uterine Neoplasms ; pathology

OBJECTIVES: The purpose of this experimental study was to investigate the toxic effects of toluene on the placental functions and reproductionin the rat. In this study, the expression of placental prolactin-growth hormone (PRL-GH) and Pit-1 genes, the frequency of placental trophoblast cells, and the reproductive data were analyzed. METHODS: The pregnancy of the Sprague-Dawley rats (250+/-25 g) was determined by verifying the presence of the copulatory plug or sperm in the vaginal smear and the day on which this was observed was defined as pregnancy day 0. The pregnant rats were divided into three groups. The control group was intraperitoneally (ip) injected with sesame oil, and the other two groups were given either 150 or 750 mg/kg BW/day of toluene resuspended in sesame oil during pregnancy days 7-11 and 16-20. The rats from the three experimental groups were sacrificed on pregnancy days 11 and 20, respectively. The mRNA levels of the PRL-GH, Pit-1a and b isotype genes were analyzed by Northern blot hybridization and Reverse transcription-polymerase chain reaction (RT-PCR), respectively. The hormonal concentration was analyzed by Radioimmunoassay. The frequency of the placental trophoblast cells was determined by means of a histochemical study. Reproductive data, such as the placenta and infnat weight, pregnancy period and litter size were surveyed at pregnancy day 20 and after birth. Statistical analysis was carried out by means of the SAS program (version 8.1). RESULTS: The mRNA levels of the PRL-GH family genes were reduced in a linear fashion by exposure to toluene. The mRNA levels of the Pit-1a and b isotype genes, which induce the expression of the PRL-GH family genes, were also reduced by exposure to toluene. The placental lactogen Iv and II concentrations in the rat placenta, fetus and maternal blood were also decreased by exposure to toluene. During the last stage of gestation, exposure to a high dose of toluene reduced the frequency of the spongiotrophoblast cells that secrete the PRL-GH hormones. Reproductive data such as the placenta and infant weight, and litter size were reduced, and the pregnancy period was extended in the toluene exposed group as compared with the control group. CONCLUSIONS: Toluene disrupts the PRL-GH hormone metabolism in the rat placenta and this leads to reproductive disorder.
Animals ; Blotting, Northern ; Fetus ; Humans ; Infant ; Litter Size ; Metabolism ; Parturition ; Placenta ; Placental Lactogen ; Pregnancy ; Radioimmunoassay ; Rats* ; Rats, Sprague-Dawley ; Reproduction* ; RNA, Messenger ; Sesame Oil ; Spermatozoa ; Toluene* ; Trophoblasts ; Vaginal Smears