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J M Lage

Publications and source records attributed to J M Lage.

At least 37 records · Page 2Linked to original sources

Acute monocytic leukemia (FAB M5) involving the placenta associated with delivery of a healthy infant: case report and discussion.

Acute leukemia seldom presents during pregnancy, and though pregnancy may not affect the course of leukemia, fetal complications and maternal mortality are high. Documented placental involvement is rare, as are metastases to the fetus. Comprehensive review of the literature reveals only a few reports of maternal or fetal leukemia with placental involvement. We encountered a case of a 45-year-old woman who presented at 29 weeks' gestation with acute monocytic leukemia with t(9;11). She was managed conservatively. Labor was induced at 33 weeks, with delivery of a healthy male infant prior to induction chemotherapy. The baby remained well at 18 months of age. The placenta showed isolated microinfarcts and an infiltrate in the basal plate of leukemic cells confirmed by immunohistochemistry. No invasion into chorionic villi was seen. Little is known about the biological significance of placental involvement and inherent defense mechanisms of the placenta in maternal cancers. Therefore, detailed histopathologic examination of the placenta should always be performed and reported in leukemic patients, regardless of fetal outcome.

Chromosomes, Human, Pair 11↗

Immunoreactivity of S100 protein, alpha-1-antitrypsin, and CD68 in adult and congenital granular cell tumors.

Some benign tumors categorized as "granular cell tumors" (GCTs) may have heterogenous origins despite their uniform morphologic appearance. Adult GCTs (the usual type), presumed to be of Schwannian origin, are reported to be positive for S100 protein (S100) and neuron-specific enolase (NSE). Congenital GCTs are S100- and NSE-negative and of unknown but probable non-Schwannian origin. To elucidate the histogenesis of adult and congenital GCT, we undertook a comparative immunohistochemical study using paraffin-embedded tissue from 10 cases of GCTs, of which 3 were the congenital type, 6 were the adult type, and 1 was an unusual multiple GCT involving the colonic mucosa. All of the GCTs were negative for keratin, smooth muscle actin, muscle-specific actin, desmin, CD57, CD15, and MAC387. All of the adult and multifocal GCTs involving the colonic mucosa were positive for S100, NSE, alpha-1-antitrypsin (A1AT), CD68, and vimentin. Congenital GCTs, on the other hand, were negative for S100 and NSE but positive for A1AT, CD68, and vimentin. Our study suggests that these two types of GCT have different histogeneses because S100 and NSE are positive in the adult type but negative in the congenital type. They share, however, a common immunophenotype of positive A1AT, CD68, and vimentin. Although this may seem to indicate a common histiocytic origin for adult and congenital GCT, another macrophage marker, MAC387, is negative. Furthermore, CD68 is closely related to the glycoprotein of the lysosomal membrane and is not completely specific for histiocytic cells; for example, it is positive in reactive and neoplastic Schwann cells. Thus, we conclude that positive immunoreactivity for A1AT and CD68 in GCT may be a reflection of the intracytoplasmic accumulation of phagolysosomes and that it does not imply a histiocytic origin for this tumors. We confirm that adult GCT is of Schwannian origin and that congenital GCT is of uncommitted mesenchymal cell origin.

Adolescent↗

Case-control study of risk factors for partial molar pregnancy.

OBJECTIVE: The purpose of our study was to identify risk factors for partial molar pregnancy from a woman's general, reproductive, and dietary history. STUDY DESIGN: Sixty-five women with pathologically confirmed partial molar pregnancy were interviewed, and their experiences were compared with those of 130 age-matched control women who had successfully completed a pregnancy with delivery of a live infant at the same hospital during the same calendar period. RESULTS: Multivariate analysis revealed that exposures which independently and significantly predicted increased risk for partial molar pregnancy included irregular cycles, pregnancy histories including only male infants among prior live births, and oral contraceptive use for > 4 years. Dietary factors previously postulated for complete molar pregnancy including protein, fat, vitamin A, or carotene were found not to be related to risk for partial molar pregnancy. CONCLUSION: Epidemiologic patterns for complete and partial molar pregnancies appear to differ somewhat; risk for partial mole is associated with reproductive history but not dietary factors.

Adult↗

Clinicopathologic variables, operative characteristics, and DNA ploidy in predicting outcome in ovarian epithelial carcinoma.

OBJECTIVE: To test the hypothesis that DNA content can predict operative morbidity and survival in patients with ovarian carcinoma. METHODS: Subjects included patients diagnosed with invasive epithelial ovarian carcinoma at Brigham and Women's Hospital between July 1987 and November 1989. Fifty-nine patients were included in this analysis. In all cases, flow cytometry was performed on fresh tissue to evaluate DNA content. The medical records were reviewed in all patients for estimated blood loss, hospitalization days, intensive care unit days, operating room time, presence and size of residual disease, grade and type of tumor, stage, size of primary tumor, lymph node status, disease status, date of last examination, and number of months of follow-up. RESULTS: Predictors for death included increasing age (P = .01), advanced stage (P = .007), the presence of malignant ascites (P = .03), residual tumor at completion of operation (P < .001), increased estimated blood loss (P < .001), increased hospitalization days (P < .001), and increased operating room hours (P < .001). When we controlled for age and stage, only estimated blood loss and residual tumor predicted poor outcome. Deoxyribonucleic acid ploidy, whether stratified as diploid or aneuploid or with DNA index cutoffs, did not predict tumor recurrence or survival rates. CONCLUSION: Deoxyribonucleic acid ploidy has not yet been proven to be of independent prognostic importance for identifying groups of patients at high risk of dying from invasive epithelial ovarian carcinoma.

Adult↗

Gestational trophoblastic disease. New approaches to diagnosis.

Although considerable progress has been made in the understanding of the biology of gestational trophoblastic tumors, future generations will undoubtedly classify our current knowledge base as basic. It is our hope that by more precisely defining the genetic basis for these diverse lesions, we may be able to develop better diagnostic, surveillance, and treatment modalities for affected patients.

Choriocarcinoma↗

Flow-cytometric analysis of nuclear DNA content in endometrial adenocarcinoma. Atypical mitoses are associated with DNA aneuploidy.

Flow-cytometric studies have demonstrated that DNA aneuploidy and proliferative activity are independent prognostic factors in endometrial carcinoma. The authors performed flow-cytometric analysis of the nuclear DNA content of 46 fresh endometrial adenocarcinomas to investigate tumor DNA ploidy and cell-cycle kinetics in relation to histologic features with known prognostic significance, mitotic activity (assessed quantitatively), and clinical features suggestive of hyperestrogenism. Thirty-five tumors (76%) were DNA-diploid, and 11 (24%) were DNA-aneuploid. DNA aneuploidy correlated significantly with two histologic features: high cytologic grade (P < .027) and five or more atypical mitoses per 50 high-power fields (P < .001). The presence of one or more atypical mitosis per 50 high-power fields, evaluated independent of DNA ploidy, was associated with stage III or IV tumors (P < .015). A low proliferative index correlated with tumors with grade 1 architecture (P < .006) and grade 1 or 2 cytology (P < .017); a high proliferative index correlated with vascular invasion by tumor (P < .027). DNA ploidy and proliferative activity did not correlate with any feature indicative of estrogenic status including age, parity, menopausal status, obesity, hypertension, diabetes, exogenous estrogen use, or endometrial hyperplasia. Therefore, in endometrial adenocarcinoma, estrogenic status does not correlate with DNA ploidy or proliferative activity; proliferative activity correlates with tumor grade; and atypical mitoses appear to be highly associated with both DNA aneuploidy and advanced tumor stage, and as such, may identify tumors with a poor prognosis.

Adenocarcinoma↗

A second case of "chorangiocarcinoma" presenting in a term asymptomatic twin pregnancy: choriocarcinoma in situ with associated villous vascular proliferation.

We report a case of "chorangiocarcinoma" (choriocarcinoma in situ in association with a villous vascular proliferation) presenting in one of dichorionic diamniotic twin placentae at term in an asymptomatic pregnancy. This case is the second reported of chorangiocarcinoma in the literature and the first case of choriocarcinoma (in situ or otherwise) in a twin pregnancy. The lesion had the gross appearance of an infarct in the presenting twin placenta. Histologic sections revealed malignant villous trophoblast in eight microscopic fields within the placental infarct. The remainder of the placenta and that of the cotwin were normal. The mother and infants had no evidence of metastatic disease 3 months postpartum. This placenta is the fourth example in the English literature of isolated choriocarcinoma in situ.

Adult↗

Gestational trophoblastic tumors: refining histologic diagnoses by using DNA flow and image cytometry.

During the past year much effort has been focused on defining the DNA content of gestational trophoblastic tumors. Flow cytometric and image analysis studies of molar pregnancies confirmed that the majority of partial hydatidiform moles were triploid, and, as expected, most complete hydatidiform moles were diploid or diploid/tetraploid. There were rather large intra- and interobserver variations in diagnosing hydropic abortuses and hydatidiform moles when the DNA content had not been assayed. Knowledge of the DNA content increased diagnostic accord. Interphase cytogenetic probes for specific chromosomes and analysis of dinucleotide repeat sequences (microsatellites) allowed determination of DNA ploidy and assignment of parental origin, respectively. Unusual cases of hydatidiform moles complicated by twin pregnancy were associated with delays in clinical diagnosis and increased rates of persistent and metastatic trophoblastic disease. Residual nodules of intermediate trophoblast, an unusual form of persistent trophoblastic disease, were relatively resistant to chemotherapy and required further surgical intervention. Though immunohistochemistry aids in distinguishing placental site trophoblastic tumor from choriocarcinoma, occasional tumors show overlapping immunohistochemical profiles.

Cytodiagnosis↗

Clinical features of multiple conception with partial or complete molar pregnancy and coexisting fetuses.

The estimated incidence of twin pregnancy consisting of hydatidiform mole and a coexisting fetus is 1 per 22,000-100,000 pregnancies. Since 1965, nine patients with this entity have been treated at the New England Trophoblastic Disease Center (NETDC), Boston. One patient had a partial hydatidiform mole coexisting with a normal placenta and fetus. The other eight patients had twin pregnancies with a complete hydatidiform mole (CHM) and coexisting fetus. We compared the clinical outcomes in these 8 patients and 14 additional published case reports of multiple gestations composed of CHM and coexisting fetuses with a group of 71 patients with singleton CHM treated at NETDC. Twelve of the 22 patients (55%) with CHM and coexisting fetuses developed persistent gestational trophoblastic tumor, requiring chemotherapy. Five of these patients developed metastases requiring multiple cycles of chemotherapy to achieve remission. The presenting symptoms of multiple conception with CHM and coexisting fetuses were similar to those in patients with a singleton conception and complete mole. However, as compared to singleton CHM, patients having a multiple conception with CHM and coexisting fetuses were diagnosed at a later gestational age, had higher preevacuation beta-human chorionic gonadotropin levels and had a greater propensity to develop persistent tumor. These data indicate that patients with multiple conceptions consisting of CHM and coexisting fetuses are at high risk of developing persistent gestational trophoblastic tumor.

Adult↗

Natural history of twin pregnancy with complete hydatidiform mole and coexisting fetus.

OBJECTIVE: To investigate the clinical features and natural history of twin conceptions consisting of complete hydatidiform mole and a coexisting fetus. METHODS: Since 1973, eight well-documented cases of twin pregnancy with complete hydatidiform mole and coexisting fetus have been treated at the New England Trophoblastic Disease Center (NETDC). The clinical features of these eight patients were compared to 71 patients with singleton complete hydatidiform mole treated at the NETDC and with the published experience of other investigators. Flow cytometric analysis of DNA content was performed in addition to histologic inspection to assist in confirming the diagnosis of twin pregnancy with complete hydatidiform mole and coexisting fetus. RESULTS: Five of the eight patients in this series developed persistent gestational trophoblastic tumor requiring chemotherapy. Three of these five patients developed metastases requiring multi-agent chemotherapy to achieve remission. The presenting symptoms of twin pregnancy with complete hydatidiform mole and coexisting fetus were similar to those in patients with a singleton complete mole. However, compared to singleton complete molar gestation, a twin pregnancy with complete mole and coexisting fetus was diagnosed at a later gestational age, had higher preevacuation beta-hCG levels, and had a greater propensity to develop persistent gestational trophoblastic tumor. CONCLUSION: Our findings indicate that patients with complete hydatidiform mole and coexisting fetus are at high risk for developing persistent gestational trophoblastic tumor.

Adult↗

Epithelial ovarian tumors of borderline malignancy: long-term follow-up.

Thirty-nine patients underwent primary surgery for epithelial ovarian tumors of low malignant potential at the Massachusetts General Hospital between 1970 and 1980. Eighty-five percent of patients were found to have Stage I disease and 15% were found to have Stage III disease. Fifty-four percent of patients had a tumor with serous histology, 39% had a tumor with mucinous histology, and the remainder of patients had tumors with an endometrioid or mixed-cell type. Second malignancies and benign ovarian tumors were frequently found concomitantly with the borderline tumors or in follow-up. Gastrointestinal and endometrial adenocarcinomas were the most common second malignancies and were frequently found associated with a borderline tumor of serous histology. Follow-up was available in all 39 patients (100%). Mean time of follow-up was 11.8 years. Sixty-nine percent of patients are clinically without evidence of disease with a mean follow-up of 14.7 years, 23% died of other causes, 5% died of disease, and 3% died with disease and sepsis. All patients dying with disease did so within 7.3 years of their primary surgery. Seven patients underwent conservative surgery, defined as preservation of some ovarian tissue. Six of 7 patients are clinically free of disease with a mean follow-up of 14.6 years; 1 patient died of other causes. No patients treated conservatively had a recurrence of their disease.

Adenocarcinoma↗

The role of DNA flow cytometry in evaluation of partial and complete hydatidiform moles and hydropic abortions.

Knowledge of the nuclear DNA content of a hydatidiform mole is extremely useful in distinguishing a partial hydatidiform mole from a complete hydatidiform mole. Flow cytometry can be applied to both fresh or frozen tissue as well as to formalin-fixed, paraffin-embedded samples. Methodologies for extracting, staining, and analyzing nuclei are relatively simple and inexpensive, and results are accurate and reproducible. The vast majority of flow cytometers currently available or in use are more than adequate for distinguishing the large difference in nuclear DNA content between partial and complete hydatidiform moles, with sophisticated modeling programs and expensive equipment being unnecessary. We recommend that the DNA content of all hydropic placentas posing diagnostic dilemmas be analyzed by flow cytometry. When combined with clinical history and careful gross and microscopic examination, nuclear DNA content should serve as a very strong indicator of final diagnosis.

Cell Nucleus↗

Choriocarcinoma in a term placenta: pathologic diagnosis of tumor in an asymptomatic patient with metastatic disease.

A clinically unsuspected choriocarcinoma arose in a term placenta. The patient was hospitalized for 3 weeks antepartum with preterm labor. She was delivered of a normal female infant at 36 weeks' gestation. Mother and infant were discharged after 3 days. The placenta, 465 g, contained multiple white nodules, a single infarct, and retroplacental hemorrhage. By microscopy, there was multifocal choriocarcinoma. No villous stromal invasion was found. The patient was readmitted 6 days postpartum with a serum beta human chorionic gonadotropin (hCG) value of 741,640 mIU/ml and lung metastases. She received 9 courses of multiagent chemotherapy and is currently free of tumor 1 year after diagnosis. The infant, 46,XX, remained clinically free of tumor although she had a serum beta hCG of 37 mIU/ml at 1 week of life. This placenta provides evidence of choriocarcinoma developing directly from mature placental villi in a chromosomally normal gestation and depicts a situation wherein choriocarcinoma is diagnosed correctly in the presence of villous tissue. It also demonstrates the utility of placental examination in clinically abnormal gestations.

Adult↗

Pericentric inversion of chromosome 16 in a large kindred: spectrum of morbidity and mortality in offspring.

Constitutional pericentric inversions of chromosome 16 are rare in the general population. We report here a large kindred who carry an inv(16)(p13q22) rearrangement. In general, individuals with the inv(16) are in good health but prone to reproductive loss. Two different types of recombinant offspring were identified in this family and analyzed at the molecular level using probes from the alpha-globin and polycystic kidney disease loci. Both were associated with serious major malformations.

Chromosome Aberrations↗

Flow cytometric analysis of nuclear DNA content in ovarian tumors. Association of ploidy with tumor type, histologic grade, and clinical stage.

The authors undertook a prospective, flow cytometric study of nuclear DNA ploidy in 140 fresh ovarian tumors. There were 43 benign tumors, 27 borderline tumors, and 70 malignant tumors. Results of DNA ploidy analysis were compared to age at diagnosis, menopausal status, tumor size, histologic type, grade, and International Federation of Gynecology and Obstetrics (FIGO) stage. Although the majority of benign tumors were diploid, 19% were aneuploid. Among the benign tumors, DNA ploidy was significantly associated with tumor type and tumor size. All borderline tumors were diploid. Of the 70 malignant tumors, 64% were aneuploid. In the malignant tumors, DNA aneuploidy had significant univariate associations with histologic type, grade, and FIGO stage. By multivariate analysis, DNA aneuploidy remained significantly associated with stage and grade, both known predictors of survival in ovarian cancer. These results indicate that DNA ploidy varies with the aggressive potential of an ovarian cancer and may, at the time of initial diagnosis, provide additional information about tumor prognosis.

Adult↗