Diagnóstico atípico de un tumor trofoblástico del lecho placentario: presentación de un caso y revisión de la literatura / Atypical diagnosis of a trophoblastic tumour of the placental bed: presentation of a case and review of the literatura

El tumor trofoblástico del lecho placentario es una de las formas más raras de neoplasia trofoblástica gestacional. Su manifestación clínica más típica es el sangrado vaginal anormal. Debido a su rareza no existe un tratamiento óptimo estandarizado. Presentamos un caso de tumor trofoblástico del lecho placentario con un diagnóstico atípico asociado a una hemorragia posparto que requirió histerectomía obstétrica de urgencia

Placental site trophoblastic tumour is a rare form of gestational trophoblastic disease. The most common clinical manifestation is abnormal vaginal bleeding. Due to its rarity there is no optimal standardised treatment. A case is presented of placental site trophoblastic tumour after an atypical diagnosis associated with a postpartum haemorrhage that required an emergency peri-partum hysterectomy

Chorangiocarcinoma: a case report and review of the literature.

Chorangiocarcinoma is the name designated to a chorangioma with trophoblastic proliferation manifesting increased proliferative activity. Only 3 such cases have been published so far. Other studies challenged this entity by demonstrating that proliferation of the trophoblast around chorangioma is a common phenomenon. We present a case of a unique vascular lesion in a term placenta with a malignant trophoblastic component. Microscopic examination of a well-demarcated placental mass revealed a chorangioma with multiple nodules composed of pleomorphic cells displaying focal multinucleation, large areas of necrosis, and high mitotic activity. Immunohistochemical stains of these cells were strongly positive for pancytokeratin and the beta subunit of human chorionic gonadotropin and focally positive for HSD3B1. There was no invasion of the basement membrane, and no free-floating tumor cells in the intervillous space. No evidence of metastasis was found on follow-up of the mother and newborn. It is concluded that the tumor presented herein, displaying a histologically unequivocal malignant trophoblastic component in a benign chorangioma, is a true chorangiocarcinoma, and should be included within the category of gestational neoplasia as a tumor closely related to choriocarcinoma.

Epithelioid trophoblastic tumor of the lung.

Epithelioid trophoblastic tumor (ETT) is a rare type of gestational trophoblastic disease and only 25 cases have been reported so far. It was first proposed by Mazur and Kurman in 1994 as an unusual type of trophoblastic tumor that is distinct from placental site trophoblastic tumor and choriocarcinoma and has features resembling carcinoma. A case of ETT of the lung in a 38-year-old Japanese woman is reported. The patient had suffered from a hydatidiform mole at the age of 27 years, and had four normal deliveries at the ages of 24, 31, 35 and 37 years. Because no tumor lesions were detected in the uterus, the patient was suspected of having metastatic choriocarcinoma with multiple lesions in the lung accompanied by an elevated level of human chorionic gonadotropin (hCG). In order to make an exact diagnosis, a partial resection of metastatic foci in the lung was performed. Microscopically, the tumor showed hemorrhagic necrotic foci and was composed of mainly mononuclear tumor cells and some giant tumor cells resembling trophoblastic cells. Immunohistochemical examination showed that a few large cells were stained positively for hCG, and that other cells were positive for human placental lactogen, pregnancy-specific beta1-glycoprotein, cytokeratin 7 and inhibin-alpha. In the ultrastructure, the tumor cells contained large nuclei and rich organella with desmosomes and well-formed filaments. The diagnosis of ETT was confirmed from the findings as described above.

Epithelioid trophoblastic tumor: morphological and immunohistochemical study of three lung lesions.

Epithelioid trophoblastic tumor (ETT) is a term proposed for an unusual variant of trophoblastic tumor that is closely related to choriocarcinoma but shows monomorphic growth of highly atypical trophoblastic cells instead of the typical dimorphic pattern of choriocarcinoma. We report here 3 cases of ETT, all of which were lung lesions probably originating from uterine trophoblastic disease. The antecedent pregnancies of the 3 cases were hydatidiform mole, invasive mole, and term pregnancy, respectively. The tumors were composed of highly atypical mononucleate cells, which mainly involved alveolar spaces, forming nests with central eosinophilic necrosis. Multinucleate giant cells were found within the nests, but they were fewer in number than in typical choriocarcinoma. The tumors were not associated with extensive hemorrhage or necrosis, except for 1 case, in which the ETT was combined with typical dimorphic choriocarcinoma. Immunohistochemically, multinucleate giant cells and occasional mononucleate tumor cells showed positivity for human chorionic gonadotropin. Staining for human placental lactogen was positive in rare multinucleate giant cells, and in 1 case, tumor cells showed diffuse positivity for placental alkaline phosphatase. Because ETT has a remarkably epithelioid appearance in cytological and architectural features, differentiation from the epithelial malignancies is problematic. Trophoblastic markers are frequently expressed in nontrophoblastic tumors, and reactivity for those markers alone is not sufficient for exclusion of other tumors. Rather, evidence of ETT comes from a combination of morphological features, immunohistochemical study, and clinical history.

The interaction between cytotrophoblasts and their derived tumor cells.

Previous experiments demonstrated that human cytotrophoblasts and cells of the choriocarcinoma cell line JAr interact in vitro. As a result of this interaction there is an increased synthesis of CG and hPL, probably as a result of the increased CG and hPL synthesis by the cytotrophoblasts. In the present investigation we studied this interaction in greater detail and found that both cytotrophoblasts and JAr cells undergo changes in their biological properties as a result of this interaction. JAr cells and cytotrophoblasts cocultured for 72 hr were fractionated according to their size by centrifugal elutriation. The number of cells in the fraction which contain the largest cells was very significantly increased as a result of the coculture. This increase was due to an increase in the number of cells of both cell types. This fraction was the most active one in the synthesis of CG and hPL. The synthesis of DNA by the JAr nuclei in this fraction of the cocultured cells was almost completely inhibited but in the parallel fraction of the JAr cells cultivated alone the level of DNA synthesis was equal to that of all other JAr cell fractions. Heterokaryons are formed in the coculture. In these heterokaryons a factor which inhibits DNA synthesis in the cytotrophoblasts may inhibit DNA synthesis in JAr nuclei and at least be partly responsible for the inhibition of DNA synthesis observed.

[AgNOR of gastational trophoblastic tumors and its clinical significance].

A total of 120 paraffin-embedded gestational trophoblastic tumor tissue blocks was selected and divided into 5 groups: (1) 20 cases of normal chorionic villi. (2) 40 cases of hydatidiform mole with no malignant change during a following-up period of at least two years. (3) 40 cases of hydatidiform mole which developed into invasive mole or choriocarcinoma. (4) 10 cases of invasive mole. (5) 10 cases of choriocarcinoma. Nucleolar organizer regions (NORs) was Ag-stained and AgNOR dots were counted using the Plotion's method. The result showed that there was significant difference between group 1 and group 2 (P < 0.005), group 2 and group 3 (P < 0.001), group 3 and group 4 (P < 0.05). Taking the AgNOR count 4.00 as a standard, 75% of the cases in group 2 (mean = 2.730) was below this standard. The study suggested that with the increase of malignancy of trophoblastic tumor, the AgNOR count increased correspondingly. A quantitative study of AgNOR might be a useful measure to detect the early malignant change of hydatidiform mole.

New technique for processing paraffin-embedded tissue for Y chromosome fluorescence identification of trophoblastic disease.

A new reprocessing technique for Y chromosome fluorescent body (q 12 region) detection of trophoblastic disease in previously paraffin-embedded tissues is described. Deparaffinized sections were treated with pronase and trypsin for digestion, followed by hydrolysis with HCl and acetic acid, staining with quinacrine hydrochloride fluorochrome and mounting in Sørensen's phosphate buffer (pH 5.5). Use of the technique resulted in sufficient fluorescence quality and better accuracy for Y and X heterochromatin scoring. The technique yielded the same results in retrospective formalin-fixed, paraffin-embedded trophoblastic specimens as in fresh tissues. The combinations of enzymes and acids and the dosages necessary for optimal results are discussed.

O-glycosylation of the alpha-subunit does not limit the assembly of chorionic gonadotropin alpha beta dimer in human malignant and nonmalignant trophoblast cells.

Biosynthetic experiments were carried out in cultures of human malignant trophoblast cells (the JAR cell line) and in explants of normal first trimester human placental tissue to test the hypothesis that the O-glycosylation of the glycoprotein hormone alpha-subunit at Thr-39 regulates the assembly of the CG alpha beta dimer. This modification of alpha has been shown to ablate its ability to combine in vitro with the beta-subunit of bovine LH and might explain why JAR cells and placental explants secrete uncombined alpha- and beta-subunits in addition to the hCG alpha beta dimer. We have previously detected an O-linked carbohydrate chain at Thr-39 in preparations of secreted free alpha-subunit, but not dimer CG alpha from JAR culture medium. We report here evidence that the O-glycosylation of alpha does not regulate the biosynthetic assembly of the hCG dimer in cultures of JAR choriocarcinoma cells or first trimester placental explants. The intracellular precursor forms of alpha and beta that accumulate in the endoplasmic reticulum and combine in that compartment are not yet modified with O-linked carbohydrate, as determined by measurements of their [3H]galactosamine content after biosynthetic labeling of amino sugars with [3H]glucosamine. Furthermore, only half of the free alpha-subunit secreted by JAR cells and less than 10% of free alpha secreted by 10-week-old placental explants received the O-linked chain. This was shown by determining the ratio of the unglycosylated and glycosylated forms of the tryptic peptide from free alpha that contains the O-glycosylation site (residues 36-42). Based on these findings, we make the following conclusions. 1) O-Glycosylation of alpha-subunit is a late event in the secretory pathway of trophoblasts compared to the rapid combination in the rough endoplasmic reticulum of hCG subunit precursors to form alpha beta dimer. 2) Association of alpha with beta precludes the subsequent addition of the glycan to alpha at Thr-39. 3) The alpha molecules that fail to combine with beta in the endoplasmic reticulum are substrates for the later addition of O-linked carbohydrate, presumably in the Golgi complex, but only a fraction of the free alpha molecules are modified with O-linked carbohydrate.

Trophoblastic tumors: ultrastructural comparison of choriocarcinoma and placental-site trophoblastic tumor.

Ten trophoblastic tumors, including seven classical choriocarcinomas, two choriocarcinomas with atypical histology, and one placental-site trophoblastic tumor (PSTT), were studied to compare their fine structural features. Ultrastructurally, the classical choriocarcinomas showed well-defined cytotrophoblasts and syncytiotrophoblasts. The cytotrophoblasts were primitive epithelial cells, while the syncytiotrophoblasts were complex cells with multiple nuclei and dense cytoplasm containing dilated endoplasmic reticulum, lysosomes, vesicles, and tonofilaments. The syncytiotrophoblast cell membranes often contained numerous microvilli. In the choriocarcinomas, scattered intermediate trophoblasts showed features transitional between the cytotrophoblasts and the syncytiotrophoblasts, with moderately complex cytoplasm containing some of the organelles found in the syncytiotrophoblasts. Histologically, the atypical choriocarcinomas showed a predominance of mononucleate and binucleate cells and indistinct syncytiotrophoblasts. Ultrastructurally, these atypical tumors were composed largely of intermediate trophoblasts, yet contained scattered syncytiotrophoblasts with microvilli in compressed aggregates. The PSTT was composed primarily of intermediate trophoblasts that contained prominent paranuclear filaments not seen in the intermediate trophoblasts of the choriocarcinomas. Rare cells resembling syncytiotrophoblasts were found in the PSTT, but no cytotrophoblasts were observed. Immunoreactivity for human chorionic gonadotropin and human placental lactogen was found in the intermediate trophoblasts and syncytiotrophoblasts of both the choriocarcinomas and the PSTT, demonstrating functional homology between these tumors despite some ultrastructural differences. These results demonstrate ultrastructural features of trophoblastic cells that correlate with the morphologic diversity seen in these tumors by light microscopy. Furthermore, the comparisons suggest that the PSTT is composed of a distinct form of intermediate trophoblast that appears to reflect its origin from the extravillous trophoblast.

Chorangiocarcinoma: an unusual tumour of the placenta. The missing link?

A tumour occurring in an otherwise normal placenta presented the vascularity of a mature chorangioma but was surrounded by a neoplastic trophoblastic proliferation. A chorangioma with an atypical associated trophoblastic proliferation has never been reported in any of nearly 500 cases of chorangiomas described in the literature. The possibility of a combined lesion (for which we propose the term chorangiocarcinoma) is emphasized. It cannot be excluded however that chorangiomas could be, in rare cases, true neoplasms rather than hamartomas.

Proliferations and tumors of intermediate trophoblast of the placental site.

The clinical and pathologic features of proliferations and tumors of intermediate trophoblast of the placental site are reviewed. These lesions include the exaggerated placental site reaction, which is a florid form of the process that occurs normally at the placental site; a hitherto undescribed variant of this lesion, which we have designated placental site nodule, and the neoplasm of intermediate trophoblast that has been termed placental site trophoblastic tumor. Problems encountered in distinguishing these lesions from one another and from nontrophoblastic lesions, particularly in endometrial biopsy specimens and curettings, are discussed.

Placental-site trophoblastic tumor of the uterus. Clinicopathological and immunohistochemical observations of a case.

The clinicopathological features of a 28-year-old woman with placental-site trophoblastic tumor (PSTT) are described. The patient presented with severe proteinuria and was found to have a cystic uterine tumor. The serum beta-human chorionic gonadotropin (hCG) level was only slightly elevated. The tumor extended to the serosa without gross metastasis, and was resected. The specimen was composed of active intermediate trophoblasts (IT) and degenerative or inactive ITs. The former component had round to oval and vesicular nuclei, and abundant amphophilic or lightly eosinophilic cytoplasm. The latter component had irregular-shaped pyknotic nuclei and deeply eosinophilic cytoplasm. However, the tumor lacked the bilaminar (cyto- and syncytiotrophoblastic) structure that is a characteristic feature of choriocarcinoma. Immunohistochemical evaluation with human placental lactogen (hPL) and hCG antisera revealed that most of the tumor cells contained abundant hPL, whereas only a small number of cells contained hCG. This method seemed to be most helpful for the differential diagnosis of PSTT from other trophoblastic tumors or non-trophoblastic uterine tumors, and also to be useful for determining the prognostic behavior of PSTT.

Placental site trophoblastic tumor of the uterus: an ultrastructural and immunohistochemical study.

Ultrastructural and immunohistochemical studies in a case of placental site trophoblastic tumor (PSTT) of the uterus were carried out in order to define the nature of the abnormal tissue. By electron microscopy, the large cells, whether mononuclear or syncytial, showed numerous ribosomes, prominent Golgi elements, and abundant rough endoplasmic reticulum (RER) filled with granular material. Pseudopods and microvilli were found on the cell surfaces. By immunofluorescence, the well-developed filamentous cytoskeleton proved to be actin-rich. beta-HCG (human chorionic gonadotropin) and SP1 (beta 1-specific pregnancy glycoprotein) were detected in only a few tumor cells, whereas most of them stained for HPL (human placental lactogen). The present results show the secretory nature of most of the tumor cells, which resemble the intermediate trophoblast of the placental bed. Together with previous studies, they suggest that a varying spectrum of syncytiotrophoblastic differentiation exists in PSTT. Decidual, myometrial, or histiocytic cells do not seem involved in the histogenesis of the tumor tissue.

[Cell functions of cultured human choriocarcinoma following the administration of methotrexate (author's transl)].

Treatment of choriocarcinoma should be eradicated of trophoblastic cells which undergo destruction in both of primary and metastatic sites and Methotrexate (MTX) has a most effective value. While MTX is being administration to the patients, there is no determination of clear relationship between proliferation of trophoblastic cells and production of human chorionic gonadotropin (hCG). In this report, we attempted to clarify the changes of the dividing compartments in cell cycle of human choriocarcinoma in vitro in the administration of MTX (concentration in 5 x 10(-6) M and 5 x 10(-7) M) to the experimental cells. Cell samples were stained by propidium iodide (PI) and fluorescein isothiocyanate (FITC), then were measured nucleic acid and protein content by means of flow microfluorometry (FMF). MTX was remarkably increased the intensity of FITC associated with protein production, in dose that is not only killing effect to the cells but inhibition of DNA synthesis. Moreover, the most difference in both subjects were as follows; Ever when MTX in low concentration was removed after 48 hours, 50% of experimental cells recovered to the level of controls in contrast to the persistence of remarkable inhibition of DNA synthesis in high concentration.

Trophoblastic pseudotumor of the uterus: clinicopathologic report with immunohistochemical and ultrastructural studies.

The clinicopathologic feature of two cases of trophoblastic pseudotumor of the uterus are presented and compared with previously reported cases. In both cases, cancer was erroneously diagnosed. One patient, 27 years of age when first examined, presented metrorrhagia 10 months after a full-term delivery. The lesion was entirely removed by curettage and was no longer found in the hysterectomy specimen. The patient is alive and well more than 17 years after therapy. The other patient, 36 years of age at the initial examination, presented with metrorrhagia 23 months after a therapeutic abortion. The pseudotumor infiltrated the full thickness of the uterine wall. The patient is alive and well 3 years and 7 months after hysterectomy and radiation therapy. Histologically, the tumor consisted of large cells invading the myometrium in small clusters either as cords or as single cells. There were 2 mitoses/10 HPF of which some were atypical. Tumor cells containing chorionic gonadotropin (hCG) and a pregnancy-specific protein (SP1) were demonstrated immunohistochemically (alpha 2-PAG) and placental lactogen (hPL) in one case. Ultrastructurally, trophoblastic pseudotumor closely resembled cytotrophoblastic cells of the basal plate of the placenta.

Trophoblastic pseudotumor of the uterus: case report and ultrastructure.

A trophoblastic pseudotumor occurring in a young woman 6 months after a normal pregnancy is reported. Ultrastructural investigation demonstrated a close structural relationship between the infiltrating cells and those of the trophoblastic components of the normal human placenta, especially those seen in the primary villi of the developing placenta.