The human placenta becomes haemochorial at the 13th week of pregnancy.

Histological specimens of recent implantation sites are the basis of our current concept on human embryo implantation and placental development. In the Carnegie Collection maternal red blood cells were detected early in the primitive intervillous space (10th-12th day after conception). These cells were localized to the trophoblastic lacunae and originated from distended peripheral maternal sinusoids (Kaufmann, 1981). The classical theory states that progressively more and more maternal vessels are tapped. A true maternal blood flow is established around the 29th day. Dynamic investigations of human placental development in vivo are scarce and hampered by ethical considerations and the absolute requirement to refrain from using non aggressive and potentially harmful techniques. Despite these limitations such studies provide new insights that surprisingly contradict our previously and seemingly definitely established knowledge of the early phases of placental vascularization, and lead us to conclude that there is an absence of maternal blood circulation in the intervillous placental space (IVS) during the 12 first weeks of human pregnancy.

Feminizing testicular Leydig cell tumor: hormonal profile before and after unilateral orchidectomy.

The effect of chronic hyperestrogenism on gonadal function was studied in three men who had estrogen-secreting Leydig cell tumors before unilateral orchidectomy and for 11-43 months after surgery. All three men had low plasma gonadotropin and testosterone levels and increased estradiol levels. Impairment of testicular steroidogenesis was also suggested by increased progesterone to 17-hydroxyprogesterone and 17-hydroxyprogesterone to androstenedione ratios in both spermatic venous plasma and the medium of Leydig tumor cells from one patient incubated in vitro. Before surgery, spermatogenesis was abnormal in two men. Testicular endocrine function and spermatogenesis did not return to normal after surgery. During the follow-up period, plasma gonadotropin levels were high in all three men, and testosterone was low normal. Estradiol levels decreased to normal immediately after surgery and then returned to the upper normal limit. The response to hCG stimulation in one man was subnormal. We conclude that chronic hyperestrogenism produced hypothalamo-pituitary inhibition as well as direct steroidogenic blockade at the testicular level. Long term impairment of both endocrine and exocrine testicular functions may be secondary to slowly reversible (or irreversible) estrogen-induced damage to tubular and Leydig cells.

Expression of c-erbB2, TGF-beta 1 and pS2 genes in primary human breast cancers.

The presence of c-erbB2, TGF-beta 1 and pS2 mRNAs was examined in primary breast tumours. The c-erbB2 mRNA was overexpressed in 34% of the tumours. There was a positive, statistically significant correlation between c-erbB2 gene overexpression and nodal status. TGF-beta 1 mRNA was detected in 84% of the tumours, regardless of their clinical status. When possible, the c-erbB2 and TGF-beta 1 proteins were identified immunohistochemically on frozen sections from the same tumours. For TGF-beta 1, the mRNA and immunohistochemical results were divergent in 6 cases, 5 of which did contain clearly detectable mRNA but did not stain with the antibody. The pS2 mRNA was detected in 22% of the tumours and in the BT474 cell line. There was a significant correlation between the presence of pS2 mRNA and of oestrogen receptors. No statistically significant correlation was observed between pS2 and TGF-beta 1 genes expression and the clinical parameters of the tumours.

Unusual growth within a meningioma (leukemic infiltrate).

Intracranial meningiomas are generally slow-growing neoplasms. Symptoms depend on their critical intracranial location. The authors describe a case of rapidly enlarging meningioma that became symptomatic as a result of invasion by leukemic cells at the time of a blastic crisis in the context of chronic myeloid leukemia. Infiltration of an intracranial meningioma by cells from extracranial malignant neoplasms is a rare event. Even though central nervous system (CNS) or meningeal involvement is common in some hematologic malignancies, this is, to the best of our knowledge, the first report of invasion of an intracranial meningioma by leukemic cells.

Maternal vascular lesions in pre-eclampsia and intrauterine growth retardation: light microscopy and immunofluorescence.

Placental bed biopsies were performed during caesarean section in a series of 137 patients. Analysis of the morphological findings confirms that vascular physiological changes were reduced in pre-eclampsia and in normotensive intrauterine growth retardation. In pre-eclampsia, acute atherosis in the decidual segments of uteroplacental arteries was a prominent feature. Intimal thickenings of the myometrial segments of the uteromaternal arteries were also noted. Normotensive intrauterine growth retardation cases were characterized by intimal thickenings of the myometrial segments of the uteroplacental arteries. Immunofluorescent investigations have demonstrated that the deep vascular stenoses were not associated with immunoglobulin deposition while in distal arterial segments displaying acute atherosis a positive immunofluorescence for IgG and fibrin and, more irregularly, for C'3 and IgM could be noted. These findings lead us to suggest that an immunological mechanism may be involved in the pathogenesis of acute atherosis.

Perinatal features associated with placental mesenchymal dysplasia.

Six new cases of placental mesenchymal dysplasia are presented and the findings compared to those reported in 16 similar cases published in the literature. Mesenchymal dysplasia was suspected when a placental scan showed a partial mole with a fetus of normal size and normal karyotype. Three fetuses of this series and nine out of 18 cases from the literature review also presented with Beckwith-Wiedemann syndrome features. This placental anomaly is more commonly associated with a 46,XX karyotype. Comparable placental histopathological features in cases of mesenchymal dysplasia with or without congenital anomalies diagnostic of Beckwith-Wiedemann syndrome suggest that in some of these cases the overgrowth of specific fetal tissue is limited to the placenta and the fetus remains unaffected. Histological similarity between mesenchymal dysplasia and cellular chorioangioma suggests a common embryologic origin for both these placental abnormalities. Ultrasound/Doppler serial investigations indicate that the circulatory imbalance is due to hypovascularization of the dysplastic lobules, found in mesenchymal dysplasia. This induces the progressive aneurysmal and varicose dilatation of chorionic vessels, however, these anatomical transformations are not associated with a change in resistance to flow in both uterine and umbilical circulations nor with an excess of obstetrical complication when the fetus is anatomically normal.

Histological study of the materno-embryonic interface in spontaneous abortion.

In a histological study of 184 specimens of complete spontaneous abortion, the following points were delineated. In cases of anomaly or death of the conceptus, there was a reduced trophoblastic penetration into the decidua and into the spiral arteries where physiological changes were limited or absent. Trophoblastic proliferation within the columns and the outer shell was limited with frequent disruption or even disappearance of the shell. These findings seem to be related to the untimely initiation of blood flow in the intervillous space which in turn is associated with arrest of pregnancy and eventual expulsion.

Diminished expression of placental isoferritin p43 component in first trimester abnormal pregnancies.

Human placental isoferritin (PLF) is a sub-type of human ferritin mainly composed of a 43 kD protein, which has an immunosuppressive activity and may be involved in the downregulation of the maternal immune system during pregnancy. The aim of this study was to evaluate the distribution of p43 in the placental tissue of abnormal first trimester pregnancies. Samples of villous and decidual tissues were collected between 7 and 12 weeks' gestation from 28 missed abortions and eight complete moles. Samples of placental tissue from 20 normal pregnancies of similar gestational age were used as controls. The localization of p43 was determined by immunohistochemical techniques using CM-H9 monoclonal antibody. Compared to controls, specific p43 immunoreactivity was low in the villous syncytiotrophoblast of missed abortions and absent from all villous cellular types in complete moles. These findings correlate well with the low level of maternal serum PLF found previously in early pregnancy failures and molar gestation. This suggests that PLF may be involved in the pathogenesis of early pregnancy disorders related to an abnormal placentation.

Immunohistochemical localization of two endometrial proteins in the early days of human pregnancy.

Insulin-like growth factor binding protein-1 (IGFBP-1) [also known as placental protein 12(PP12)] and placental protein 14 (PP14) have been identified by specific immunostaining in early pregnancy specimens obtained 13-35 days of gestation. PP12 was evident in a discrete number of stromal decidual cells at the deciduotrophoblastic interface and under the endometrial surface epithelium. These cells did not have the rounded appearance of classic decidual cells but most often displayed cytoplasmic expansions. Staining for PP14 was strictly localized to the glandular epithelium of the endometrium. Implantation of the conceptus may be an important mechanism in the early expression of PP12 but not PP14.

Development of the early human placenta: a morphometric study.

The placentae of 46 normal pregnancies artificially terminated between 6 and 15 weeks of gestation were investigated morphologically to provide trends in early villous development. Study of the specimens included phase contrast microscopic examination and histomorphometric investigation in all cases, and scanning electron microscopy in ten cases. Histomorphometric measurements included the villous barrier thickness i.e. the distance between the intervillous space and the villous capillary lumen, the trophoblastic layer thickness and the volume fraction of each villous constituents, i.e. trophoblast, stroma and capillaries. Significant negative correlations were observed between gestational age and the villous barrier and trophoblastic thickness. The data obtained were separated into two groups, embryonic (5-10 weeks) and fetal (11-15 weeks) groups, and compared. The mean barrier thickness, the mean trophoblastic thickness, the mean volume fraction for trophoblast and the sprouting-villous index were significantly greater during the embryonic period compared with the fetal period. The mean volume fraction for the stroma and for the fetal capillaries, and the mean number of capillary profiles per villous profile were significantly smaller during the embryonic period than during the fetal period. The comparison of placental histomorphometric data obtained in cases of normal early pregnancies with those observed in cases of abnormal early pregnancies could help us to elucidate the origin of anatomical and biological changes in these cases.

Pregnancy-associated major basic protein: deposition of protein and expression of mRNA at the maternal-fetal junction in early and late gestation.

Pregnancy-associated major basic protein (pMBP) has previously been isolated from human placenta and localized to the X cell. Here we used immunofluorescence staining and in situ hybridization to determine the distribution of pMBP and pMBP mRNA throughout the maternal-fetal junction in both early gestation tissues and at term. In early gestation tissues, pMBP was present only at the placental insertion site. Specifically, pMBP was present in (a) the decidua basalis (in the extracellular space, in interstitial pools and inside endometrial glands) and (b) intracellularly within extravillous interstitial trophoblasts in the decidua, in the myometrium and surrounding but not within luminal cells of spiral arteries. At term, the placental bed showed intense extracellular pMBP staining with little intracellular pMBP. In situ hybridization showed the presence of pMBP mRNA in both the early and late gestational tissues. pMBP mRNA was present in cells in the decidua, at the decidual-myometrial junction and in cell islands. Quantitative image analysis showed statistically significant hybridization signals with the pMBP antisense probe as compared to the control/sense probe. These results indicate that pMBP mRNA is expressed and pMBP is extensively deposited at the maternal-fetal junction in early pregnancy and at term.

Placental electron microscopy and histochemistry in a case of sialic acid storage disorder.

Morphological alterations in a placenta from a case of infantile sialic acid storage disease are described. Syncytiotrophoblast, villous capillary endothelial cells, amniotic and Hofbaüer cells were filled with membrane-bound inclusions which were either electron-lucent or contained fibrillogranular material. Hydrolysis of slides with neuraminidase demonstrated at six hours Alcian blue material which was not present in normal syncytium. The possibility that a storage disorder such as sialic acid storage disease can be accurately diagnosed by electron microscopy on chorion villous sampling at nine to ten weeks is emphasized.

Morphological aspects of the placenta in HIV pregnancies.

Forty-nine placentae from HIV-seropositive mothers were collected in various hospitals in France and Belgium. Twenty [corrected] placentae with seven fetuses from interrupted pregnancies and 29 [corrected] placentae from spontaneous deliveries, including two stillborns and a set of twins, were studied morphologically. No significant abnormalities were observed in the aborted material. The placentae corresponding to deliveries presented no significant gross abnormalities but the ratio of fetal to placental weight was significantly decreased in the study group compared with the control group (6.13 versus 7.41; P less than 0.001), associated with a congestive and mature aspect of the parenchyma. Histologically a high incidence of chorioamnionitis (43 per cent) was found, contrasting with the absence of villitis. A relative villous hypercellularity was observed in the study group compared with the control group. Ultrastructural studies of 13 placentae corresponding to gestations of 10 to 40 weeks are presented. In six cases, retrovirus-like particles were found at various sites, such as villous fibroblasts, syncytiotrophoblast and endothelial cells, and in the free membranes.

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.

Immunofluorescent localization of placental lactogen, chorionic gonadotrophin and its alpha and beta subunits in organ cultures of human placenta.

Localization of human placental lactogen (HPL), chorionic gonadotrophin (HCG) and its free alpha and beta subunits in mature and immature placental villi before and during organ culture was examined with an 'indirect' immunofluorescent technique using highly specific antisera. HPL fluorescence was strictly localized to the syncytiotrophoblast and the intensity of this fluorescence increased with gestational age and decreased with the time of culture. Undissociated HCG and HCG beta immunofluorescence was localized to the syncytiotrophoblast. Maximum intensity was observed in immature placentae and was not significantly affected by the duration of culture. However, irregular and patchy HCG and HCG beta immunofluorescence was seen in the cytotrophoblasts under conditions of extensive syncytiotrophoblastic damage. HCG alpha immunofluorescence was localized in the syncytiotrophoblast of immature placentae and was more intense in mature placentae. Beginning the third day of culture, HCG alpha fluorescence increased and was also present in the cytotrophoblast. On the basis of these observations and additional data, the possibility is discussed that cytotrophoblastic cells, better preserved than the syncytiotrophoblast in case of restricted energy and oxygen supply, may actively synthesize free HCG alpha, in addition to syncytiotrophoblastic production of this subunit. By contrast, HPL, undissociated HCG, and HCG beta are mainly or exclusively eleborated in the syncytiotrophoblastic layer.

Prenatal diagnosis of a dup(3p) with holoprosencephaly.

The prenatal diagnosis of dup(3p) was made in a female conceptus, the father being a known carrier of a balanced translocation t(3;10)(p21;q26). Interruption of pregnancy at 19 weeks showed a fetus with a holoprosencephaly field defect. Two other cases of dup(3p) have been observed in the same family. The malformations were different in each of the 3 patients, suggesting a considerable degree of variability of dup(3p).

Chromosomally abnormal early ongoing pregnancies: correlation of ultrasound and placental histological findings.

The pathophysiology of placental microscopic changes in chromosomally abnormal pregnancies remains poorly understood. We have reviewed the relationship between ultrasound findings and villous histological features in a group of 25 ongoing pregnancies presenting with fetal aneuploidy at 11 to 15 weeks of gestation. The chromosomal abnormalities were diagnosed by chorion villous sampling, and the data were compared with those of a group of 25 chromosomally normal pregnancies undergoing surgical termination and matched for gestational age. The aneuploid group included 10 pregnancies with trisomy 21, nine with trisomy 18, three with triploidy, two with monosomy X, and one with trisomy 13. The overall degree of agreement between the two investigators for the histological diagnosis was good (kappa, 0.64), and the sensitivity of histology ranged between 72.0% and 80.0%. Fetal and placental edema was observed on scan in 10 and 7 cases, respectively, of the aneuploid group and was systematically associated with trophoblastic hypoplasia, stromal edema, or cavitation, reduced vascularization, and ramification of the main villous trunks. Fetoplacental hydrops was not observed in the euploid group. These findings indicate that histological changes observed in the placenta of fetuses from ongoing pregnancies presenting with aneuploidy can be linked with early fetal hydrops. The villous features in these cases are probably secondary to a reduction in the villous circulation due to a cardiovascular defect and leading to generalized stromal edema. The reduced villous branching and trophoblastic hypoplasia could be secondary to the enlargement of all villous types or to a basic defect in placental development.

Embryonic remnants of the umbilical cord: morphologic and clinical aspects.

Embryonic vestiges of the umbilical cord are classic findings in routine morphologic examination of the placenta. In order to evaluate their clinicopathologic significance, we examined samples from the fetal and placental ends of 1,000 umbilical cords and collected the principal clinical findings of the corresponding newborns. Microscopic evidence of embryonic remnants were found in 231 cases (23.1%) divided into remnants of the allantoic duct (63%), the omphalomesenteric duct (6.6%), and the embryonic vessels (30.4%), including one case of hemangioma and an accessory small artery. There were no significant clinical differences between the three vestigial groups, and no particular association with congenital malformations or perinatal complications. In 70.9% of the cases, the embryonic remnants were found at the fetal end of the umbilical cord, where most tumors of the cord develop.

Leukaemia and lymphoma of the appendix presenting as acute appendicitis or acute abdomen. Four case reports with a review of the literature.

Leukaemic and lymphomatous infiltration of the appendix is rare and even rarer is acute appendicitis as the initial manifestation. From our routine biopsy material we collected four cases of haematological malignancies presenting as acute appendicitis or acute abdomen, caused or accompanied by tumoral infiltration of the appendix. Appendicitis was the initial manifestation that allowed diagnosis of the underlying disease. The clinical histories and histological examinations of the appendices and of one autopsy are described. We report the first detailed description of acute myeloid leukaemia involving the appendix, and three cases of lymphomatous infiltration of the appendix presenting with appendicitis, and give an overview of the literature. In these days of budgetary cuts in national health services, where one may be tempted not to have seemingly commonplace cases of appendicitis histologically verified, our cases emphasize that careful histopathological examination of all appendectomy specimens should be mandatory. Despite the fact that leukaemia and lymphoma of the appendix are rare, our cases illustrate that these must be included in the differential diagnosis of acute appendicitis and that physicians and surgeons have to be aware of these conditions.

Partial mole and triploidy: screening patients with first-trimester spontaneous abortion.

OBJECTIVE: To evaluate the role of histopathology in the categorization of women at risk of trophoblastic disease after early pregnancy failure associated with triploidy. METHOD: A retrospective study of histopathologic findings on 587 first-trimester spontaneous abortions for which both histologic and karyotype results were available. The incidence of chromosomal abnormalities and placental molar changes and the proportion of agreement for histologic diagnosis of triploidy were calculated. RESULTS: An abnormal chromosome complement was found in 241 (41.1%) cases, including 75 (31.1%) with trisomy, 71 (29.5%) with triploidy, 60 (24.9%) with monosomy X, and 35 with other abnormalities. Molar transformations were found macroscopically in 20 triploidies, in six spontaneous abortions with a normal karyotype, in one trisomy, in one monosomy X, and in one tetraploidy. There was one complete hydatidiform mole. Complete agreement between two investigators was seen in 48 (67.6%) triploidy cases. Inter- and intra-observer degree of agreement for histologic diagnosis of triploidy was good to excellent. The sensitivity of histology ranged between 87.3 and 94.4%, the specificity between 81.7 and 85.9%, the positive predictive value between 83.1 and 86.1%, and the negative predictive value between 86.8 and 93.8%. CONCLUSION: Triploidy is associated with molar changes less often in the first trimester of pregnancy than in the second or third trimester. Therefore, most triploid spontaneous abortions escape detection on the basis of ultrasound or macroscopic examination. The use of standardized criteria for detection by microscopic examination is both accurate and reproducible and should play a pivotal role in screening for women at risk of persistent gestational trophoblastic disease.