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Biomedical subjects

J M Lage

Publications and source records attributed to J M Lage.

At least 19 recordsLinked to original sources

Tamoxifen-induced uterine abnormalities: the role of imaging.

Tamoxifen citrate is an orally administered, nonsteroidal antiestrogen agent that is widely used for the treatment of breast cancer and that has recently been found to prevent breast cancer in some high-risk populations. Tamoxifen may, however, cause adverse effects at the uterine level. In this article, the authors review (a) the histopathologic uterine changes associated with tamoxifen therapy, (b) the spectrum of uterine imaging findings in women treated with tamoxifen, and (c) the recommendations of the American College of Obstetrics and Gynecology for women treated with tamoxifen. An algorithm for imaging evaluation of the uterus in women treated with tamoxifen is presented.

Antineoplastic Agents, Hormonal↗

Precursor B-Lymphoblastic lymphoma presenting as a solitary bone tumor and mimicking Ewing's sarcoma: a report of four cases and review of the literature.

Precursor B-lymphoblastic lymphoma (B-LBL) may present as a solitary bone tumor. Fewer than 10 cases with a proven precursor B-cell phenotype have been reported in the English literature. In this report, we describe four cases of B-lymphoblastic lymphoma presenting as a localized intraosseous mass, which clinically and histologically mimicked Ewing's sarcoma. Three tumors occurred in the tibia and one in the humerus. In all four cases, the initial diagnosis was either "Ewing's sarcoma" or "consistent with Ewing's sarcoma." All four patients were female. Three were children and one was an adult; mean age was 12.5 years (range, 4 to 31 years). All had extremity pain without significant constitutional symptoms. In three cases, the tumors were osteolytic on radiographic evaluation, and in one case, osteosclerotic. Immunohistochemical stains on paraffin-embedded tissue showed that the neoplastic cells expressed terminal deoxynucleotidyl transferase, CD43, vimentin, and CD99 (MIC2 gene product) in all cases. Three cases were negative for CD45. CD79a was positive in all four cases studied; however, CD20 (L26) was positive in only two of four cases. CD3 was negative in all cases. Two cases showed focal granular cytoplasmic staining for keratin. Two cases analyzed by polymerase chain reaction (PCR) revealed clonal rearrangement of the immunoglobulin heavy chain (IgH) gene. Follow-up revealed that the three pediatric patients, who received a high-dose multiagent chemotherapy regime for LBL, are disease free at follow-up intervals of more than 1, 11, and 12 years, respectively. The adult patient died two years after diagnosis with disseminated disease. Although rare, B-lymphoblastic lymphoma should be considered in the differential diagnosis of small round cell tumors of bone. A diagnosis of Ewing's sarcoma should be made only after complete immunophenotyping and, if necessary, molecular diagnostic tests to exclude lymphoblastic lymphoma. A limited panel of antibodies can lead to an erroneous diagnosis; B-lymphoblastic lymphoma may be negative for CD45 and CD20 but positive for CD99 and even for keratin, mimicking Ewing's sarcoma. Correct diagnosis is extremely important because LBL usually is curable in the pediatric age group with appropriate therapy.

Adult↗

Hepatic (hepatocellular) adenoma of the placenta: a study of four cases.

Hepatic (hepatocellular) adenoma of the placenta is an extremely rare nontrophoblastic placental lesion of disputed histogenesis, four examples of which were diagnosed over a 10-year period. The lesions, which were incidental findings in women 21 to 30 years of age (mean, 25; median, 24.5), ranged from 0.3 to 1.0 cm in greatest dimension. Two were found within the villous parenchyma and two in subchronic locations. On cross section, two examples were tan to dark red nodules without necrosis or hemorrhagic foci, whereas two were not visible grossly. The lesions were composed of semidistinct lobules of cords and nests of polygonal epithelial cells resembling fetal liver. Extramedullary hematopoiesis was a constant feature. The lesional cells contained glycogen and were immunoreactive for cytokeratin, alpha-fetoprotein, alpha-1-antitrypsin, and carcinoembryonic antigen. Although the histogenesis of these lesions remains uncertain, an origin from displaced yolk sac elements with hepatocytic differentiation is the most likely hypothesis. It is important to distinguish hepatic adenoma of the placenta from placental cell island, heterotopic adrenocortical nodule, chorangioma, and placental metastasis of maternal and fetal malignancies.

Adenoma, Liver Cell↗

Immunohistochemical localization of carboxypeptidases E and D in the human placenta and umbilical cord.

Carboxypeptidase E (CPE) is highly concentrated in neuroendocrine tissues and is the only carboxypeptidase detected in mature secretory vesicles. Carboxypeptidase D (CPD), a carboxypeptidase with CPE-like activity, is widely distributed in tissues and is present in the trans-Golgi network. Previous work had shown that both CPE and CPD are expressed in the human placenta and that CPD is expressed at much higher levels than CPE. The present work provides evidence for the co-localization of CPE and CPD to basal plate extravillous trophoblasts and maternal uteroplacental vascular endothelial cells, chorionic villous endothelial cells, amnionic epithelial cells, and umbilical venous and arterial smooth muscle cells. Whereas the intensity of CPD immunostaining is similar in the placenta and umbilical cord, CPE staining in the placenta is much weaker than in the umbilical cord, suggesting that CPD plays a more important role in the processing of placental peptides. Immunoelectron microscopy of umbilical venous smooth muscle cells shows subcellular localization of both enzymes to the rough endoplasmic reticulum. In addition, CPE is present just subjacent to the cell membrane. The difference in cellular and subcellular localization between the two enzymes indicates that they perform distinct functions in the processing of placental peptides and proteins.

Carboxypeptidase H↗

Endometrial polyps: a comparison study of patients receiving tamoxifen with two control groups.

Many reports describe an increased frequency and unusual features of endometrial polyps and carcinomas in women treated with tamoxifen (TMX) for breast cancer. Postmenopausal women with endometrial polyps were identified by computer search of pathology files from 1990 to 1996. Medical records were reviewed, and patients were divided into three groups: 28 receiving TMX for breast cancer, 23 receiving hormone replacement therapy (HRT), and 28 untreated controls (UC). Cumulative doses (CDs) of TMX were calculated. Histologic slides of polyps were reviewed blindly and evaluated for size, metaplasias, vascularity, fibrosis, and inflammation. Carcinomas were found in 3 TMX, no HRT, and 1 UC patient. Atypical hyperplasias were found in 1 TMX, 0 HRT, and 1 UC patient. Mean polyp size was larger in the TMX group (2.9 cm) than in the HRT (1.05 cm) and UC (1.35 cm) groups, and stromal fibrosis was more prominent in TMX-related and larger polyps. Mucinous metaplasias were observed more frequently in the patients receiving TMX. No other differences were noted. The two TMX patients in whom low-grade carcinomas developed and the one with atypical hyperplasia had independent risk factors. CDs for these patients were 32.9, 36.5, and 17.6 g, respectively. A high-grade carcinoma developed in a TMX patient without constitutional risk factors at a CD of 94.9 g. On the basis of a literature review and these results, low-grade carcinomas developing after relatively low CDs of TMX may be at least partially attributable to other risk factors. The association between poorly differentiated and nonendometrioid tumors with higher TMX CDs is still speculative, but the current study suggests that they may be related to TMX. A statistically significant increase in the frequency of thyroid replacement use by TMX patients is also noted.

Aged↗

Quantitative differences in arterial morphometry define the placental bed in preeclampsia.

The purpose of this study was to quantitatively analyze normal and preeclamptic uteroplacental vasculature. Myometrial arteries from eight placental bed biopsies from uncomplicated term deliveries and 12 from proteinuric preeclampsia were characterized as uteroplacental, spiral, or basal arteries. Basal lumens within 0.2 mm radius and spiral/uteroplacental lumens within 0.4 mm radius were considered as the same artery. The biopsy area, lumen density, and arterial density (after correction for multiple lumens), lumen area, lumen perimeter, mean wall thickness, inflated diameter, and a slant factor, measuring the obliqueness of arterial transection, and ratios of lumen characteristics to mean wall thickness were analyzed. In preeclamptic cases, there were more basal lumens/mm2 and basal arteries/mm2 (P=.003, P=.03), and more spiral lumens/mm2 and spiral arteries/mm2 (P = .01, P = .03). Basal lumen area (P = .0003) and wall thickness (P = .007), and basal and spiral artery lumen perimeters and inflated diameters (for each, P = .0001, P = .048, respectively) and inflated diameter/wall ratios (P = .04, P = .05) were reduced compared with normal cases. Preeclamptic spiral and basal arteries are more tortuous or densely distributed than normal placental bed arteries, with smaller-caliber lumens and thicker walls. Failure of proper placentation may result in abnormal spatial anatomy in the placental bed. Alternatively, an anatomic variant of spiral and basal arteries may be more susceptible to hemodynamic stresses and endothelial damage and may predispose to preeclampsia.

Arteries↗

Fetal but not maternal serum cytokine levels correlate with histologic acute placental inflammation.

Our objective was to determine if placental histologic acute inflammation is related to maternal and fetal serum cytokine levels in preterm labor, using a data set previously constructed blinded to histopathologic information. To this goal in 1992, 32 consecutive patients at 20-36 weeks with progressive labor and tocolytic failure were recruited. Maternal serum sampled during the active phase of labor, and fetal (umbilical vein) serum were assayed by ELISA for levels of soluble interleukin-1 beta (IL-1 beta), soluble interleukin-2 receptor (IL-2 R), and interleukin 6 (IL-6) (T-Cell Diagnostics). Acute placental inflammation was scored by two groups blinded to clinical data, and the average scores analyzed for relationships to serum cytokine levels. Weighted kappa values, reflecting interobserver agreement in scoring of acute inflammation, were: amnion 0.84; choriodecidua 0.84; umbilical cord 0.85; and chorionic plate 0.73. Fetal levels of IL-1 beta and IL-2 R were higher with grade 3-4 acute amnionitis than with grades 0-2 (p = 0.022 and p = 0.023). Fetal levels of all three cytokines were higher in grade 3-4 umbilical vasculitis (IL-1 beta p = 0.008, IL-2 R p = 0.01, and IL-6 p = 0.03). In contrast, maternal serum cytokine levels were not associated with presence or severity of histologic evidence of acute placental inflammation. Histologic acute inflammation was not related to duration of labor, interval from membrane rupture to delivery, and presence or duration of antibiotic therapy. We conclude that fetal serum, but not maternal serum cytokine levels, are correlated with histologic evidence of acute placental inflammation, and may reflect a predominant placental origin of the cytokines.

Acute Disease↗

Immunohistochemical assessment of proliferation markers and altered gene expression in archival specimens of ovarian epithelial tumors.

Recently reported morphologic and molecular genetic evidence suggests that some ovarian carcinomas arise from their benign and low malignant potential (LMP) counterparts. In order to help reach a better understanding of ovarian tumorigenesis, we studied a wide range of gene products involved in cellular growth regulation in archival material obtained from three groups of tumors with graduated malignant potential. Immunohistochemical staining was performed for Ki-67, proliferating cell nuclear antigen (PCNA), epidermal growth factor receptor (EGFR), HER-2/neu-encoded receptor protein, p53 gene product, and multidrug resistance gene product (P-glycoprotein). The expression of EGFR, HER-2/neu-encoded receptor protein, and mutant p53 product was significantly lower in LMP tumors than in carcinomas (p < 0.05). HER-2/neu immunopositivity was more prevalent in adenocarcinomas than in LMP tumors, and the proportion of HER-2/neu-positive adenocarcinomas increased with the progression of the disease. The staining differences between LMP tumors and adenocarcinomas with antibodies against Ki-67, PCNA, and P-glycoprotein were not statistically significant. Immunohistochemical detection of EGFR, HER-2/neu, and p53 in ovarian epithelial tumor is relevant to ovarian tumorigenesis. It could serve as a powerful tool for the pursuit of retrospective studies focused on these important biologic markers.

Adenocarcinoma↗

Genetic aspects of gestational trophoblastic diseases: a general overview with emphasis on new approaches in determining genetic composition.

All gestational trophoblastic tumors are derived from a fertilization event. In the hydatidiform moles, varying degrees of excess paternal DNA lead to varying histopathologic forms of these tumors. The placental site trophoblastic tumors and the choriocarcinomas may follow normal pregnancy, abortions and hydatidiform moles, and, thus evince a wide range of genetic compositions reflecting their gestation of origin. Advances in molecular biological diagnoses now allow for the determination of the gestational or non-gestational origin of trophoblastic tumors, and, may well provide fantastic new insights into the biology of these unusual tumors.

Choriocarcinoma↗

Recurrent granulosa cell tumor of the ovary 37 years after initial diagnosis: a case report and review of the literature.

Granulosa cell tumors of the ovary (GCTs) are uncommon neoplasms that are characterized by late recurrence and high survival rates. A case of recurrent GCT presenting 37 years after initial diagnosis is reported with a review of the literature. This case illustrates an example of a very late recurrence and emphasizes the importance of the extended follow-up required for these patients.

Aged↗

Placental site nodule occurring in a fallopian tube.

The placental site nodule (PSN), a recently described benign lesion of intermediate trophoblast, is usually an incidental finding in younger women. It is a well-circumscribed, round to oval lesion that is extensively hyalinized and immunohistochemically stains for cytokeratin, placental alkaline phosphatase (PLAP), human placental lactogen (HPL) and, focally, for human chorionic gonadotropin (HCG) and epithelial membrane antigen (EMA). Thus far, the cases reported have been found in endometrial curettage or hysterectomy specimens. The pathogenesis of PSN is yet to be ascertained; however, there is wide acceptance of the fact that it represents a remnant of the placental implantation site. If this is indeed the case, it should not be surprising to find PSN occurring at sites of ectopic gestation. We describe herewith a case in which PSN was found in a fallopian tube segment resected in a postpartum tubal ligation.

Adult↗

Placental changes in a first trimester missed abortion in maternal systemic lupus erythematosus with antiphospholipid syndrome; a case report and review of the literature.

The placental lesions generally attributed to the effects of systemic lupus erythematosus (SLE) on the decidual and placental villi include decidual vasculopathy, placental infarcts and possibly intrauterine growth retardation. The maternal decidual vessels in SLE show a lesion termed "acute atherosis" which is histologically similar to acute vascular rejection in a transplanted kidney. These changes can be so extensive as to result in complete vascular occlusion, decreased placental perfusion and resultant placental villous infarction. In currettings from products of conception in the first trimester, acute atherosis is a rare finding. We describe striking decidual vasculopathy and extensive villous infarction in a case of a first trimester missed abortion in a patient with SLE who had anticardiolipin antibodies (ACL), both immunoglobulin (IgG) and IgM, and lupus anticoagulant (LA) in her serum. To the best of our knowledge, this is the first report of acute atherosis and villous infarction in a first trimester placenta in association with SLE and/or ACL and LA. Pathologists should be aware of these changes and alert clinicians to the possibility of SLE or antiphospholipid and/or anticardiolipin antibodies.

Abortion, Missed↗

Endometrial stromal sarcoma with focal smooth muscle differentiation: recurrence after 17 years: a follow-up report with discussion of the nomenclature.

In 1977, a case report was published describing a 28-year-old women with an endometrial stromal tumor that showed foci of myogenic differentiation. The term "stromomyoma" was introduced to encompass both this type of neoplasm as well as "uterine neoplasms resembling ovarian sex-cord tumors" (UTROSCTs). More than 17 years later, the tumor recurred, involving the right ovary, sigmoid colon, small bowel, abdominal wall and omentum. The histologic and electron microscopic similarities between the recurrent tumor and the primary neoplasm were confirmed. Applying the recent classification and diagnostic criteria of endometrial mesenchymal neoplasms, we have concluded that this tumor was a low-grade endometrial stromal sarcoma (LGSS). The formerly proposed term "stromomyoma" implies a benign tumor, in contrast to the obviously malignant nature of this particular tumor. Focal myogenic differentiation of LGSS is not an uncommon finding and does not warrant a separate diagnostic or prognostic entity. UTROSCTs and endometrial stromal sarcomas are two separate diagnostic entities, and combining them under an inclusive terminology is not appropriate.

Abdominal Neoplasms↗