A clinicopathologic and immunohistochemical analysis of 53 cases of medulloblastoma with emphasis on synaptophysin expression.

Synaptophysin (SYN) has been identified as an integral membrane glycoprotein of presynaptic vesicles in neurons and neuroendocrine cells, and as a marker for medulloblastoma and other neuronal tumors. SYN expression was studied with a monoclonal antibody (MAb) by the immunoperoxidase technique in 53 medulloblastomas. The expression of neuron-specific enolase (NSE), Leu-7 (LEU), S-100 protein (S100), glial fibrillary acidic protein (GFAP), neurofilament protein (NF), vimentin (VIM), cytokeratin (CKER), and desmin (DES) was also assessed with antisera and MAbs. SYN reactivity was present in 94% of tumors, whereas reactivity with other markers of neuronal differentiation was also observed: NSE (100%) and LEU (83%). Regarding the intermediate filament proteins, 38% of the cases were reactive for VIM, 21% for GFAP, and 9% for DES; none expressed NF or CKER. Eight percent were reactive for S100. Among the 53 cases, the male-female ratio was 1:3; 80% of DES-positive tumors occurred in females. The mean age was 10.5 yr, (60% diagnosed in the first decade; peak age incidence between 5 and 10 yr). Five tumors were discovered in patients older than 20 yr of age. Follow-up showed that 40% of patients developed a recurrence and 47% of patients died of tumor. No statistically significant relationship was demonstrated between patterns of immunoreactivity and prognosis. We conclude that SYN is a useful marker for medulloblastomas, indicating that this tumor is a primitive neuronal-neuroblastic neoplasm. However, it is but one of several immunophenotypic markers expressed by the medulloblastoma.

Choroid plexus neoplasms. Clinicopathologic and immunohistochemical studies.

Choroid plexus neoplasms account for less than 1% of all intracranial tumors, with papillomas (CPPs) more frequent than carcinomas (CPCs). Immunocytochemical characterization of these neoplasms has been limited. Glial fibrillary acidic protein (GFAP), S100 protein, and keratin have been variably demonstrated by others. Ten cases were identified at two hospitals over a 25-year period; six were children and four were adults. There were seven cases of CPP and three of CPC. Extracranial metastases occurred in one case of CPC and multiple local recurrences were common. Immunohistochemical examination was performed with polyclonal antibodies to keratin, alpha-fetoprotein (AFP), desmin, neurofilament, glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), and S100 protein, and with monoclonal antibodies to vimentin, 45- to 54-kd cytokeratin (CKER), and carcinoembryonic antigen (CEA). Among the seven cases of CPP, five were positive for CKER, three for keratin, two for CEA, two for NSE, and five for S100. Three cases of CPC were positive for CEA, three for CKER, and two for keratin. With one exception, when a neoplasm was positive for CEA and S100 it was also positive for CKER. Positivity for CEA in this group was associated with a more aggressive histologic pattern and heralded a worse prognosis. S100 immunoreactivity appeared to predominate in well-differentiated neoplasms. Keratin and CKER were found in both CPP and CPC, but may be useful in the distinction from ependymomas. Statistical analysis resulted in the following classification rule: If the CEA stain is positive and the S100 stain is negative, then the tumor is malignant; otherwise, the tumor is benign.

Ocular pathology in trisomy 18 (Edwards' syndrome).

A case of a full-term female with confirmed trisomy 18 who died a few hours after her delivery is presented. In addition to many severe systemic malformations, some ocular findings are described. They include cataract and hypoplasia of optic nerves in both eyes, and juxtapapillary coloboma, retinal dysplasia and Bergmeister's papilla in the left eye. The last finding is a new one in trisomy 18.

Retinoic acid embryopathy.

Retinoic acid, an analogue of vitamin A, is known to be teratogenic in laboratory animals and has recently been implicated in a few clinical case reports. To study the human teratogenicity of this agent, we investigated 154 human pregnancies with fetal exposure to isotretinoin, a retinoid prescribed for severe recalcitrant cystic acne. The outcomes were 95 elective abortions, 26 infants without major malformations, 12 spontaneous abortions, and 21 malformed infants. A subset of 36 of the 154 pregnancies was observed prospectively. The outcomes in this cohort were 8 spontaneous abortions, 23 normal infants, and 5 malformed infants. Exposure to isotretinoin was associated with an unusually high relative risk for a group of selected major malformations (relative risk = 25.6; 95 per cent confidence interval, 11.4 to 57.5). Among the 21 malformed infants we found a characteristic pattern of malformation involving craniofacial, cardiac, thymic, and central nervous system structures. The malformations included microtia/anotia (15 infants), micrognathia (6), cleft palate (3), conotruncal heart defects and aortic-arch abnormalities (8), thymic defects (7), retinal or optic-nerve abnormalities (4), and central nervous system malformations (18). The pattern of malformation closely resembled that produced in animal studies of retinoid teratogenesis. It is possible that a major mechanism of isotretinoin teratogenesis is a deleterious effect on cephalic neural-crest cell activity that results in the observed craniofacial, cardiac, and thymic malformations.