PubMed Health⌕ Search

Biomedical subjects

E J Perlman

Publications and source records attributed to E J Perlman.

At least 73 records · Page 4Linked to original sources

Chromosome analysis of nine osteosarcomas.

Although recurrent chromosome abnormalities have been identified in several histologic subtypes of sarcomas, no consistent rearrangement has yet been found in osteosarcomas. Cytogenetic analyses of nine cases of osteosarcoma are reported, including seven newly diagnosed tumors and two recurrent tumors. There were seven high-grade osteosarcomas, one periosteal osteosarcoma, and one well-differentiated sarcoma. All tumors were studied in short-term primary culture. Modal number ranged from near diploid to near triploid. Seven tumors had complex karyotypes with multiple structural abnormalities; two had only normal karyotypes. The retinoblastoma gene on chromosome 13 and the TP53 gene on chromosome 17 have been involved in osteosarcoma. Five tumors had loss of a whole copy of chromosome 13, and three of these also had a loss of a whole copy of chromosome 17. However, these losses were observed in the setting of numerous other chromosome losses. Numerous structural abnormalities were observed, many involving additions of unidentified material, unbalanced translocations, or deletions. Structural abnormalities with similar breakpoints involving 6q, 8q, 9q, and 14p were seen in two or three tumors each. When the tumors in this series were added to the 18 published cases, the pericentromeric regions of chromosomes 1, 3, and 14, and segments 6q15-21, 8q24, 9q34, 12p13, 17p13, and 19q13, were found to be involved in five or more structural rearrangements. Molecular analyses of these chromosome regions may yield genes important in the pathogenesis of osteosarcoma.

Adolescent↗

MIC2 analysis in pediatric lymphomas and leukemias.

Monoclonal antibodies to the glycoprotein product of the MIC2 gene strongly and reliably stain primitive neuroectodermal tumors and Ewing's sarcomas, and are negative in neuroblastomas and most rhabdomyosarcomas. Therefore, these antibodies are helpful in the diagnosis of small round cell tumors of childhood (SRCT). Lymphomas also are in the differential diagnosis of SRCT, but few have been studied with respect to MIC2 protein expression. In the present study we used the 12E7 antibody to assess MIC2 expression in 82 pediatric non-Hodgkin's lymphomas. Forty lymphoblastic, 22 small noncleaved, and 20 large cell lymphomas were studied. Strong immunoreactivity was found in 37 of the 40 (93%) lymphoblastic lymphomas, whereas only one of the 22 (5%) small noncleaved lymphomas was 12E7 positive. Four of the 20 (20%) large cell lymphomas also were immunoreactive. Three 12E7+ lymphoblastic lymphomas were primary in bone and were of B-progenitor lineage; Ewing's sarcoma was included in the initial differential diagnosis of these cases. Evaluation of 125 pediatric acute lymphocytic leukemia (ALL) cases for MIC2 expression showed similar results, with all 36 T-cell ALLs showing strong expression, one of eight B-cell (Burkitt-like) ALLs showing 12E7 expression, and 62 of 81 B-progenitor ALLs showing 12E7 positivity. We conclude that among the SRCTs, MIC2 expression is not limited to Ewing's sarcoma and primitive neuroectodermal tumors, but also shows strong and reliable expression in lymphoblastic lymphomas and related leukemias. MIC2 analysis continues to be helpful in the diagnosis of SRCT, provided that a panel of antibodies is used. In addition, the possibility that MIC2 analysis may aid in the distinction of lymphoblastic lymphomas from small noncleaved lymphomas needs to be further addressed.

12E7 Antigen↗

Ewing's sarcoma--routine diagnostic utilization of MIC2 analysis: a Pediatric Oncology Group/Children's Cancer Group Intergroup Study.

Ewing's sarcoma and peripheral neuroectodermal tumor (PNET) are small blue cell tumors with no reliable positive diagnostic markers. However, Ewing's sarcoma and PNET recently have been shown to strongly express an antigen determined by the MIC2 gene, whereas other blue cell tumors of childhood for the most part do not. MIC2 analysis therefore offers a distinctive addition to the panel of immunohistochemical stains used to differentiate among small blue cell tumors of childhood, since it represents the first positive marker for Ewing's sarcoma and PNET. This study addresses the reliability of MIC2 analysis using the monoclonal antibody 12E7 on tumors registered in the current Intergroup Ewing's Sarcoma protocol. Of 244 tumors, 221 (91%) showed a diffuse strong membranous pattern. The antibody appears to withstand all the fixation variables inherent in a multi-institutional study. We conclude that MIC2 expression is highly reliable as a positive marker for the Ewing's sarcoma/PNET family of tumors when the results are interpreted in the total context with clinical and pathologic parameters.

12E7 Antigen↗

MIC2 analysis of small cell carcinoma.

Small cell carcinomas (SCCs) and peripheral neuroectodermal tumors (PNETs) are two distinct neoplasms that show considerable histologic, immunohistochemical, and clinical overlap, but differ in their therapies and prognoses. In an attempt to further diagnostically distinguish the two, 33 SSCs were analyzed from both pulmonary and extrapulmonary sites for the MIC2 gene product, a cell surface antigen strongly and reliably expressed in PNETs and Ewing's sarcoma (ES). Two of the 33 SCCs stained positively, but the staining was less intense than that seen with PNET and ES. The remaining 31 tumors did not stain. These data indicate that, in combination with a panel of immunohistochemical stains, analysis of neuroendocrine tumors for MIC2 expression may be useful in distinguishing between small cell carcinomas of both pulmonary and extrapulmonary origins and soft tissue PNETs.

12E7 Antigen↗

DNA ploidy analysis of pediatric germ cell tumors.

To determine the usefulness of DNA ploidy analysis in the biological assessment of pediatric germ cell tumors (GCTs), paraffin-embedded tissues from primary, recurrent, and metastatic neoplasms in 32 patients under age 18 were analyzed using static image cytometry. Primary sites included testis (eight), ovary (nine), sacrococcygeal region (10), central nervous system (three), and other extragonadal sites (two). The majority of the tumors were endodermal sinus tumors (ESTs) and teratomas. Of 13 teratomas, eight were diploid and five aneuploid. Immature ovarian teratomas of up to Grade II were diploid, whereas all of three Grade III immature teratomas were aneuploid. All sacrococcygeal teratomas, regardless of grade, were diploid; the development of EST in two sacrococcygeal teratomas was associated with the development of aneuploidy. Of 17 endodermal sinus tumors, five were diploid, five aneuploid, and seven tetraploid. All diploid ESTs occurred in the testis or extragonadally in patients 24 mo of age or younger. Infantile testicular ESTs were either tetraploid (one) or diploid (two), and ovarian ESTs were either aneuploid (two) or tetraploid (three). Comparing our data with that available for adult GCTs, we suggest that some pediatric GCTs may be pathogenetically distinct from adult GCTs. Adult testicular GCTs have been shown to be aneuploid, whereas infantile testicular ESTs are often tetraploid or diploid. This suggests a different pathogenesis for these groups of tumors and may explain their biological differences as well. The transformation of a sacrococcygeal teratoma into a malignant EST is poorly understood. Ploidy analysis presented suggests genetic alterations may accompany this transformation.

Adolescent↗

Primitive neuroectodermal tumor arising in the pancreas.

Peripheral primitive neuroectodermal tumors (PNETs) are extra cranial primitive small round blue cell tumors showing histologic, immunohistochemical or electron microscopic evidence of neuroectodermal differentiation. They are most commonly encountered in the soft tissue or bone in children and young adults. We report an unusual case of a PNET arising in the pancreas. A 17-yr-old male presented with a pancreatic mass and underwent a pancreatoduodenectomy. Histologically, the neoplasm was composed of sheets of small round cells that stained for cytokeratin, neuron specific enolase, and 12E7 but not muscle specific action, desmin, common leukocyte antigen, chromogranin, synaptophysin, or other islet cell markers. The diagnosis of PNET in this unusual location was confirmed by cytogenetic analysis which showed the chromosomal translocation characteristics of PNETs, t(11;12)(q24;q12). This case highlights the difficulty in the diagnosis of PNET when it is present in visceral organs where other neuroendocrine neoplasms and adenocarcinomas are more common.

Adolescent↗

Fluorescence in situ hybridization for the Y-chromosome can be used to detect cells of recipient origin in allografted hearts following cardiac transplantation.

The purpose of this study was to determine if fluorescence in situ hybridization for the Y-chromosome can be used to detect cells of recipient origin in allografted hearts following cardiac transplantation. Formalin-fixed, paraffin-embedded tissue sections of coronary arteries from two hearts surgically explanted from heart transplant recipients undergoing retransplantation because of accelerated arteriosclerosis were examined by fluorescence in situ hybridization for the presence of cells containing the Y-chromosome using a biotinylated Y-chromosome cocktail probe. In both cases, the recipients were male and the original donor hearts were obtained from female donors. Hybridization was detected in cells morphologically recognizable as infiltrating lymphocytes, macrophages, and mast cells, establishing that these cells in the donor hearts were of recipient origin. In contrast, hybridization was not detected in cardiac myocytes, in vascular smooth muscle cells, or in the majority (>95%) of endothelial cells, suggesting that these cells were of donor origin. Although hybridization was detected in rare flattened cells lining vascular lumina, these cells did not stain for factor VIII, suggesting that they were, in fact, flattened inflammatory cells and not endothelial cells. These results demonstrate that, when the recipient and donor are of the opposite sex, fluorescence in situ hybridization for the Y-chromosome can be used to detect graft chimerism in transplanted hearts.

Adult↗

Cytogenetic and ploidy analysis of prostatic adenocarcinoma.

The cytogenetic evaluation of prostatic adenocarcinoma has shown no consistent cytogenetic abnormalities. Despite manipulation of culture conditions, the majority of low-stage, untreated prostatic adenocarcinomas show a normal karyotype. We have performed cytogenetic analysis on eight primary prostate adenocarcinomas, using several control measures to increase the probability that any normal karyotype was derived from neoplastic cells rather than accompanying normal cells. Tumors were grown in media that encourages epithelial growth; DNA ploidy studies were performed before and after tissue culture; and immunohistochemical confirmation of the prostatic and epithelial nature of the cells was done following culture. Percentage of tumor on tissue sections adjacent to those submitted for culture was > 75% in all cases. Seven of eight cases were evaluable, and six cases showed no clonal abnormalities and were diploid. One tumor showed a population of tetraploid cells, without structural abnormalities. Three additional tumors showed evidence of tetraploidy by DNA analysis. One case showed nonclonal marker chromosomes and was aneuploid. This patient was pathologic Stage D. We conclude that the majority of prostatic adenocarcinomas at their inception may not show routinely detectable cytogenetic abnormalities. However, tetraploidy may play a role in the evolution of prostatic adenocarcinoma.

Adenocarcinoma↗

Cobalamin C defect associated with hemolytic-uremic syndrome.

We describe a female infant with typical features of the cobalamin C form of combined methylmalonic aciduria and homocystinuria who also had the hemolytic-uremic syndrome with thrombocytopenia, microangiopathic hemolytic anemia, hypertension, and renal failure. Review of this and other described cases of the cobalamin C defect suggests that the hemolytic-uremic syndrome is part of the phenotypic spectrum of this inborn error of cobalamin metabolism.

Female↗

Immune hemolytic anemia following heart-lung transplantation.

Immune hemolytic anemia due to minor ABO incompatibility between recipient and donor is a well-recognized occurrence in kidney and liver transplantation. In some cases, the responsible antibodies have been shown to be derived from the donor passenger lymphocytes using Gm allotyping. We report a case of acute, transient hemolysis following heart-lung transplantation in which serologic and Gm allotype studies confirmed the etiology of hemolysis.

Journal Article↗

Clinical and pathologic spectrum of 46,XY gonadal dysgenesis: its relevance to the understanding of sex differentiation.

The condition termed "46,XY gonadal dysgenesis" is characterized by a 46,XY karyotype and incomplete testicular determination. It is likely the result of a mutation in the gene for the testicular determination factor or in another gene involved in the early stages of testicular differentiation. In view of the present interest in the identification of gene(s) initiating the differentiation of the embryonic gonads into testes, we have reviewed the phenotype of 15 patients with 46,XY gonadal dysgenesis to use this information for future molecular studies. Seven patients presented a complete form, 46,XY pure gonadal dysgenesis, including streak gonads, normal Müllerian structures, and normal female external genitalia. The structure of the streak gonads in these patients presented some variation. Eight patients presented an incomplete form, 46,XY partial gonadal dysgenesis, with ambiguous external genitalia and partial development of Müllerian and Wolffian structures. Among them, 3 had bilateral dysgenetic testes, and 4 had a streak gonad on one side with a contralateral dysgenetic testis. The streak gonads showed ovarian stroma with occasional primitive sex cords devoid of germ cells. However, a primordial follicle was observed in 1 streak gonad. The dysgenetic testes showed disorganized seminiferous tubules and ovarian stroma. In some patients, the ovarian stroma was intermixed with testicular tissue, while in others, distinct ovarian and testicular portions were present. In 1 patient, the dysgenetic testis contained a focus of well-differentiated ovarian tissue with primordial follicles. Our observations support the hypothesis that streak gonads in 46,XY pure gonadal dysgenesis arise from fetal ovaries and that dysgenetic testes in the partial form in 46,XY partial gonadal dysgenesis develop from ovotestis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Vascularity of tumors in children: evaluation with color Doppler imaging.

Twenty-one tumors in 20 children were evaluated with duplex and color Doppler imaging to determine the value of the technique in assessing the origin and pattern of vascular supply and the degree of neovascularity. The origin of the vascular supply was detected correctly in 12 of 13 tumors that were subsequently resected. In five children, this aided in determining the organ from which the tumor originated, and in one child, it established the presence of a tumor by showing blood flow in the center of a suspected abscess. In 18 tumors, color Doppler imaging showed the pattern of the vascular supply. Eleven had a peripheral pattern, and seven had a central, branching pattern. Although individual tumor types appeared to have characteristic patterns of vascular supply, these were not specific enough to aid in making a specific diagnosis. When the degree of intratumor neovascularity was graded on the basis of the findings on color Doppler imaging, it agreed with the results of histologic evaluation in 16 of 19 tumors. In one tumor, neovascularity was overestimated, and in two, it was markedly underestimated. Our experience suggests that color Doppler imaging is useful in detecting the origin and pattern of vascular supply and the degree of intratumoral blood flow in a variety of solid tumors in children.

Adolescent↗

Sexual discordance in monozygotic twins.

We report on monozygotic (MZ) twins who were discordant for phenotypic sex and Ullrich-Turner syndrome (UTS). The nonviable female was hydropic with cystic hygromas, ventricular septal defect, bicuspid aortic valve, polysplenia, intestinal malrotation, and small ovaries. The male was phenotypically normal. The monochorionic, diamniotic placenta had hydropic changes limited to the UTS infant's side. Skin samples from the infants and blood from their parents were obtained for cytogenetic and molecular analysis. Karyotypes of the twins were 45,X and 46,XY. Quinacrine polymorphisms on 7 chromosomes and RFLP analysis at 8 loci showed complete identity. MZ twins discordant for phenotypic sex have been described previously. Most of these show evidence of mosaicism in a 45,X patient with a normal 46,XY cell line, and a normal 46,XY male. While the issue of mosaicism in our case cannot be fully resolved, no mosaicism was found in 50 cells analyzed cytogenetically from each culture or by PCR analysis of a Y-specific sequence. The twins probably originated from either postzygotic nondisjunction or anaphase lag, followed or accompanied by twinning. The discordant placental morphology suggests an embryonic origin of at least part of the placental mesenchymal core.

Abnormalities, Multiple↗

Blood group antigen expression in dysplasia and adenocarcinoma of the prostate.

Blood group antigens have been implicated as markers in oncogenesis; however, studies of blood group antigen expression in the prostate have yielded conflicting data. This study examined the expression of A, B, H, X, and Lewis antigens in 30 prostates removed for adenocarcinoma, by utilizing monoclonal antibodies, Ulex europaeus agglutinin I (for H type-2 chains), and the secretor status. A, B, and Ulex staining of the normal prostate most commonly demonstrated strong straining of 5-15% of cells. Staining of central and peripheral zones was similar, and nodules of hyperplasia showed no difference in staining. Antibodies to Le(a), Le(b), and X showed no staining or only pale staining of less than 10% of the normal prostatic epithelial cells. Ulex staining of intermediate and high-grade areas of tumor showed a diffuse staining pattern that was consistently greater than that of the normal glands. In contrast, low-grade tumors stained similarly to normal glands with Ulex. In 15 of 16 cases of dysplasia, Ulex staining was increased over normal and was similar to the adjacent carcinoma. A, B, Le(a), Le(b), and X antigens were negative in adenocarcinoma and dysplasia. This study supports the hypothesis that dysplasia represents a premalignant lesion; it further suggests that concomitant with malignant transformation, a disturbance occurs in enzyme activity. The result is augmentation of H type-2 expression in dysplasia and less-differentiated adenocarcinomas, and a loss of A, B, Le(a), and Leb expression in dysplasia and all carcinomas.

Adenocarcinoma↗

The pulmonary vasculature in meconium aspiration.

Some studies have suggested that pulmonary hypertension in the newborn with meconium aspiration can be attributed to a primary prenatal increase in pulmonary arterial musculature; but this concept has been controversial. To examine this question, we reviewed 62 infants autopsied at The Johns Hopkins Hospital, 24 of whom demonstrated meconium aspiration, 20 with meconium staining but no aspiration, and 18 with abruptio placentae without meconium aspiration or staining. Clinical and pathologic features were evaluated and cross-sectional arterial medial area was determined at the junction of the conducting and respiratory airways in nondistended lungs. No significant difference in arterial medial area was found between infants with meconium aspiration and those with meconium staining only or abruptio placentae. In addition, circumferentially muscularized intraacinar arteries were present in all infants with meconium aspiration and abruptio placentae, and all but one infant with meconium staining alone. Comparison of lungs with and without arterial injection and fixation in distention showed that injection does not uniformly distend vessels and that formalin distention may remove or mask meconium. The study suggests that meconium aspiration and its complications, not primary structural arterial changes, account for pulmonary hypertension in infants with meconium aspiration.

Arterioles↗

The role of the saccomano technique in sputum cytopathologic diagnosis of lung cancer.

The Saccomanno technique of sputum preparation is widely used. This study evaluates the role of this preparation in conjunction with fresh smears in the diagnosis of lung cancer. All sputum samples from September 1973 to July 1975 showing atypia were randomized and negative controls added. The Saccomanno and fresh smears were evaluated independently and blindly and classified as negative, atypical, suspicious, or cancer. When each preparation was compared with the original diagnosis, the diagnostic accuracy for 55 squamous carcinomas was similar (fresh 95%, Saccomanno 86%) but significantly less in the Saccomanno preparations of 22 small cell carcinomas (fresh 100%, Saccomanno 24%) and 26 adenocarcinomas (fresh 96%, Saccomanno 52%). Four cases negative on fresh smears were suspicious or diagnostic of cancer on the Saccomanno slides. There were no cases of small cell carcinoma in which the Saccomanno preparations added information not available on the fresh smears. The authors conclude that in conjunction with fresh smears, the Saccomanno preparation may contribute to the diagnosis of non-small cell carcinomas but does not appear to aid in the diagnosis of small cell carcinoma.

Adenocarcinoma↗

AIDS wrongly diagnosed.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗