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Biomedical subjects

E J Perlman

Publications and source records attributed to E J Perlman.

At least 19 recordsLinked to original sources
PubMed1995

Combined Leydig cell and Sertoli cell dysfunction in 46,XX males lacking the sex determining region Y gene.

We have evaluated 3 individuals with a rare form of 46,XX sex reversal. All of them had ambiguous external genitalia and mixed wolffian and müllerian structures, indicating both Leydig cell and Sertoli cell dysfunction, similar to that of patients with true hermaphroditism. However, gonadal tissue was not ovotesticular but testicular with varying degrees of dysgenesis. SRY sequences were absent in genomic DNA from peripheral leukocytes in all 3 subjects. Y centromere sequences were also absent, indicating that testis development did not occur because of a low level mosaicism of Y bearing cells. The subjects in this report demonstrate that there is a continuum in the extent of testis determination in SRY-negative 46,XX sex reversal, ranging from nearly normal to minimal testicular development.

Child↗
PubMed1995

Primary cutaneous neuroendocrine tumors. Diagnostic use of cytogenetic and MIC2 analysis.

Merkel cell carcinoma (MCC) is a primary cutaneous neoplasm most commonly involving older adults. The cell of origin is thought to be the Merkel cell, a cutaneous neurosecretory cell. However, other neuroectodermal tumors may present in the skin and may be difficult to distinguish from MCC, including peripheral neuroectodermal tumors (PNET) and metastatic small cell carcinoma. We examined a primary cutaneous tumor of an 18-year-old which was strongly positive for cytokeratin (CK), neuron-specific enolase (NSE), and 12E7, an antibody to the protein determined by the MIC2 gene. Electron microscopy showed paranuclear aggregates of filaments and no cytoplasmic processes. These findings were considered to be consistent with MCC. Cytogenetic analysis demonstrated 46,XX,der(1)t(1;3;22)(1qter-->pa34::3q28-->q11::22q 12--> qter),der(3)t(1;3)(3pter-->q11::1p35-->pter), der(22)t(3;22)(22pter-->q11::?3q29-->qter). This was confirmed by chromosome painting using probes for chromosomes 1, 3, and 22. Peripheral neuroectodermal tumors (PNETs) show a characteristic translocation involving the same breakpoint on chromosome 22 that was present in this tumor. PNETs can also be CK and NSE positive. The MIC2 gene codes for a surface glycoprotein that has been shown to be very strongly and reliably expressed in PNETs, but not in other small round blue cell tumors and not in small cell carcinoma of the lung. However, MIC2 expression has not been studied in MCC. We investigated the use of MIC2 analysis in the distinction of MCC from PNET. Five additional MCCs were stained with the monoclonal 12E7 antibody, and one additional tumor showed the strong membranous positivity reported in PNETs. Our data suggest that MIC2 analysis may be useful in differentiating between MCC and PNET. However, cases will remain for which the distinction is elusive and cytogenetic analysis may be helpful.

Adolescent↗
PubMed1995

Adherence of human immunodeficiency virus-infected lymphocytes to fetal placental cells: a model of maternal --> fetal transmission.

The precise timing and mechanism of in utero human immunodeficiency virus (HIV) infection are unknown, but transplacental transmission is likely. Term placentas from HIV+ pregnancies contain only rare HIV-infected cells whose origins and phenotypes remain controversial, and no correlation has been found between the presence of HIV in term placentas and transmission to offspring. Reports of trophoblast infectibility have not been reproducible and do not address the question of infection in the placental stroma, the cells in direct contact with fetal circulation. We report that primary cultures of fetal placental chorionic villus stromal cells, while not infectable in vitro, do support lethally irradiated HIV-infected peripheral blood mononuclear cells (PBMCs) in a form that permits rescue of HIV by activated PBMCs weeks later. Infected PBMCs adhere and become intimately associated with placental cells by a mechanism that is LFA-1 and CD4 independent but can be blocked by antibodies or soluble CD4 binding to cell surface-expressed HIV envelope. The ability to sustain infected irradiated cells was not shared by several trophoblast, fibroblast, or epithelial cell lines. This model has several features that are compatible with in utero transmission and allow testing of various agents proposed as interventions to block maternal-->fetal transmission. Placental stromal cells appear to inhibit apoptosis of HIV-infected, irradiated lymphocytes.

Antibodies, Monoclonal↗
PubMed1995

Is esthesioneuroblastoma a peripheral neuroectodermal tumor?

Esthesioneuroblastoma (ENB; olfactory neuroblastoma) is a rare, locally aggressive neoplasm of the sinonasal area and anterior cranial fossa. The histogenesis of the lesion is not clearly delineated, and the broad histological spectrum of ENB has confounded the issue. The location, histological features (neuropil, Homer Wright, and olfactory rosettes), and reported immunocytochemical reactions (neuron-specific enolase (NSE) and chromogranin (CHR) positivity) suggest that ENB may be a neural or neuroendocrine neoplasm derived from the olfactory membrane. Recent demonstration in two of three metastatic putative ENB cell lines of the 11;22 chromosomal translocation, seen in Ewing's sarcoma (ES) of bone and peripheral neuroectodermal tumors (PNET) of bone and soft tissue, has led to the conclusion that ENB may be closely related histogenetically to PNET. The overwhelming majority of cases of ES and PNET express the protein product of MIC-2, a gene located on the pseudoautosomal region of the X and Y chromosomes. This protein can be identified immunocytochemically by antibodies 12E7, HBA71, and ON13. We studied the expression of MIC-2 using the 12E7 antibody as well as multiple neural markers in 18 ENB samples obtained from the files of The Johns Hopkins Hospital. The patients ranged in age from 19 to 90 years (mean, 47.5; median, 47) and included five men and 13 women. None of the 18 specimens reacted with antibody 12E7, but 16 were positive for NSE, nine reacted to synaptophysin (SYN), and 13 showed antibodies to chromogranin (CHR). Our studies agree with the previous suggestions that ENB is a primitive neural tumor but fail to support the hypothesis that it is a member of the PNET family.

12E7 Antigen↗
PubMed1995

Ideas in pathology. Whose tumor is this? FISHing for the answer.

Errors in tissue handling and accessioning during procurement as well as in the laboratory occasionally occur; rarely these errors may result in specimen misidentification and therefore misdiagnosis. Tissue "pick-ups" or "floaters" are difficult to avoid in large, busy histology laboratories. While misidentification problems can usually be sorted out based on clinical history, they are occasionally problematic. We report two misidentified cases that presented to the Gastrointestinal Pathology Division at the Johns Hopkins Hospital and a novel method that was used to correctly solve the problem.

Adenocarcinoma↗
PubMed1995

Numerical sex chromosomal abnormalities in pineal teratomas by cytogenetic analysis and fluorescence in situ hybridization.

BACKGROUND: Central nervous system teratomas are a rare subgroup of extragonadal germ cell tumors. Previous studies show ovarian mature teratomas to be karyotypically normal; those with increasing immaturity show increasing cytogenetic abnormalities. Adult testicular teratomas, regardless of maturity, most often show the i sochromosome 12p, a consistent chromosomal abnormality seen in adult testicular germ cell tumors. This study investigates the cytogenetic abnormalities of six central nervous system teratomas by the use of routine karyotypic analysis and fluorescence in situ hybridization. EXPERIMENTAL DESIGN: Karyotypic analysis was performed on two tumors. Four additional tumors were analyzed by dual-labeled fluorescence in situ hybridization. Paraffin blocks were disaggregated, and nuclei were hybridized with both biotin- and digoxigenin-labeled probes to the centromeric domains of the X and Y chromosomes, respectively. Tumor cells were scored for X and Y copy number. Tumor ploidy was determined by image analysis of the disaggregated specimens. RESULTS: The patients (five male, one female) ranged from 2 to 25 years of age. All presented with a solitary mass in the suprasellar region. A mature teratoma was 48, XXYY; an immature teratoma was 47, XXY, dir dup 11 (q12-22). Lymphocyte analysis of the second patient showed a normal constitutional karyotype. Fluorescence in situ hybridization analysis of four additional patients showed both one mature and one immature teratoma from male hosts to have 2X and 1Y signals in the majority of the cells. An immature teratoma from a male host showed 2X and 2Y signals. The above three tumors were diploid by static image analysis. An immature teratoma from a female host showed multiple (four to six) X signals in more than 70% of the cells. Ploidy analysis was unavailable for this case. CONCLUSIONS: Although patients with Klinefelter syndrome (47,XXY) and patients with 46,XY gonadal dysgenesis show an increased incidence of germ cell tumors, numerical sex chromosomal abnormalities have not been described in extragonadal teratomas. Our results support a role for sex chromosomes in the development of central nervous system teratomas.

Adult↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗