[What is known about the outcome as adults for children with fetal alcohol syndrome (FAS)/fetal alcohol spectrum disorders (FASD)?]. / Was wird aus Kindern mit fetalem Alkoholsyndrom (FAS)/fetalen Alkoholspektrumstörungen (FASD) im Erwachsenenalter?

In the field of adult psychiatry in German-speaking countries, little attention is as yet paid to the psychic defects that a fetus can sustain as a result of prenatal exposure to alcohol. Although children of alcohol-dependent mothers do present to psychiatric institutions as adults with manifold symptoms, e. g., attention deficit disorders, affective disorders or intellectual disability, fetal alcohol spectrum disorders are rarely diagnosed as an underlying cause. Appropriate therapy guidelines do not exist. Current review papers within the German-speaking countries usually stem from paediatric and adolescent psychiatry or medicine. Based on a selected review of the literature, the following paper addresses and discusses the disease entity of fetal alcohol spectrum disorders and fetal alcohol syndrome and their significance for adult psychiatry and also identifies open questions and research requirements, e. g., the development of diagnostic instruments or the establishment of diagnostic categories.

Chronic parvovirus B-19 meningoencephalitis with additional detection of Epstein-Barr virus DNA in the cerebrospinal fluid of an immunocompetent patient.

Parvovirus B19 DNA was detected by polymerase chain reaction in the brain biopsy specimen from a 67-year-old immunocompetent woman with severe chronic lymphocytic meningoencephalitis. In addition to parvovirus B19, Epstein-Barr virus DNA was identified in the CSF. Genomic material from Epstein-Barr virus was absent in the brain tissue. Clinical symptoms and CSF pleocytosis improved under long-term corticosteroid-treatment. The aetio-pathogenetic role of parvovirus B19 and the possible meaning of the additionally detected Epstein-Barr virus DNA are discussed.

Simplified immunophenotypic analysis by laser scanning cytometry.

Immunophenotypic analysis of hematologic specimens is a useful laboratory adjunct to surgical pathology and cytology to confirm or further characterize diagnoses of leukemia or lymphoma. Laser scanning cytometry is a new laboratory technology that has been adapted to perform immunophenotypic analysis of hematologic specimens, with numerous advantages as compared with flow cytometry. In order to make full use of the laser scanning cytometer's capabilities, a new method of specimen preparation and means of performing the immunofluorescent reactions was developed. The technique described in this report, specific only to laser scanning cytometry, enables panels of up to 36 different antibodies to be used on specimens as small as 50,000 total cells. The laboratory methodology is simple, requires 85% less antibody than flow cytometric methods, and allows individual cell cytologic morphology to be correlated with objective physical and fluorescent measurements on a cell-by-cell basis. Other advantages are described in the text. Over the course of nine months in our community hospital, we have used this technique clinically to analyze 172 cases of suspected leukemia or lymphoma. The method has proven remarkably useful, particularly for extremely small specimens such as fine needle aspiration biopsies.

Multiparameter analysis of DNA content and cytokeratin expression in breast carcinoma by laser scanning cytometry.

OBJECTIVE: The objective of this study was to test a new laboratory technology, laser scanning cytometry, for the purpose of performing multiparameter DNA content analysis of breast carcinomas. DESIGN: We developed a simplified method of multiparameter DNA content analysis using cytokeratin expression to positively gate epithelial cells. Over 300 consecutive cases of breast carcinoma were analyzed by multiparameter laser scanning cytometry. The first 73 cases were analyzed in parallel by single parameter flow cytometry. SETTING: The Department of Pathology, Christ Hospital and Medical Center, Oak Lawn, Ill. SPECIMENS: Three hundred eighteen consecutive cases of breast carcinoma presenting between March 1994 and December 1995. MAIN OUTCOME MEASURES: Outcome measures included the percentage of cases for which DNA content analysis could be successfully performed given the limitations of specimen size. Additionally, for the first 73 cases, laser scanning cytometry results were compared with flow cytometry results. RESULTS: All of the first 73 cases were successfully analyzed by laser scanning cytometry, but for 8 cases (11%) there was insufficient material for flow cytometry. Correlation of DNA content for the remaining 65 cases analyzed in parallel by the two methods was nearly perfect (p = .994). Five seemingly discrepant cases highlighted the importance of cytokeratin gating of epithelial cells by any technique, as well as other advantages specific to laser scanning cytometry, such as the ability to examine individual cells microscopically and correlate cytologic morphology with DNA content results. CONCLUSIONS: Laser scanning cytometry is a promising new technology for DNA content analysis of solid tissue tumors. Further work needs to be performed to validate the prognostic potential of the laser scanning cytometric assay results and to generate methodologies aimed at providing highly objective determinations of tumor cell S-phase fraction.

Multiparameter immunophenotypic analysis of fine needle aspiration biopsies and other hematologic specimens by laser scanning cytometry.

OBJECTIVE: To test the new laboratory technology of laser scanning cytometry with respect to immunophenotyping of all types of hematologic and lymphoreticular specimens and particularly those of limited size, such as fine needle aspiration biopsies and hypocellular body fluids. STUDY DESIGN: Over the course of two years, 343 hematologic and lymphoreticular specimens of all types were immunophenotyped by laser scanning cytometry using methodologies modified from those of conventional flow cytometric immunophenotyping. Results for all cases were corroborated with histology and/or cytology and, for some cases, immunohistochemistry and/or flow cytometric immunophenotyping. RESULTS: Over 98% of the 343 cases were successfully immunophenotyped by laser scanning cytometry. These included many hypocellular specimens, such as 38 fine needle aspiration biopsies and 33 body fluid specimens. CONCLUSION: Laser scanning cytometry is a new laboratory technology with several significant advantages relative to flow cytometry for immunophenotypic analysis of hematologic malignancy. The laboratory techniques are simplified, and antibody usage is reduced by 80%. Even more important, full-panel immunophenotyping with multiple antibodies can be performed on specimens as small as 50,000 cells total, making the technology particularly relevant to cytopathology. After immunophenotypic analysis, specimens can be stained for light microscopic examination, and individual cells meeting user-defined antigenic or physical characteristics can be automatically relocalized.

Gastric inlet patch containing submucosally infiltrating adenocarcinoma.

We describe a patient with an unusual segment of ectopic gastric mucosa in the proximal esophagus. The gastric heterotopia was circumferential and unusually long at 7 cm. It contained benign rugal-type folds, a stricture at the mid-portion of the gastric inlet patch was lined by normal antral-type gastric mucosa but harbored submucosally infiltrating adenocarcinoma. There was no evidence of Helicobacter pylori infection by biopsy or serologic screening. Malignancy, including submucosally infiltrating adenocarcinoma, should be considered in patients with strictures involving ectopic gastric mucosa in the proximal esophagus.

Immunophenotypic analysis of hematologic malignancy by laser scanning cytometry.

The authors tested a newly-developed computerized laser scanning cytometer (LSC) as a means of performing immunophenotypic analysis of hematologic specimens within their community hospital. Results were compared on a case-by-case basis with parallel flow cytometric and immunohistochemical data. A total of 71 specimens analyzed include 22 excised lymph nodes or other tissue biopsies, 18 peripheral bloods, 17 bone marrow aspirates, 7 body fluids, and 7 fine-needle aspiration biopsies of lymphoid tissue. The LSC proved to be a useful instrument capable of generating simultaneous two-color immunofluorescent data directly analogous to that obtained via conventional flow cytometry. However, laser scanning cytometric analysis provides advantages over flow cytometric analysis, because the LSC measures cells on a slide rather than in a fluid stream. Specifically, cells can be microscopically examined at any time--before, during, or after automated immunofluorescent analysis. In addition, specimen preparation techniques are less restricted and more cost efficient. Lastly, even extremely small and/or hypocellular specimens (such as body fluids and fine-needle aspiration biopsies) can be successfully analyzed.

Flow and image cytometric DNA analysis of postcardiac transplant lymphomas.

Organ transplant recipients and other immunodeficient individuals are at risk for the development of Epstein-Barr virus-related B-cell lymphomas. The incidence of lymphoma after cardiac transplantation ranges from 2 to 11%. To determine whether the clinical presentation, histological subtype, or clinical outcome correlated with DNA content, 17 patients with postcardiac transplant lymphoma were studied by flow and image cytometry. Their mean age was 52 yr (range: 33 to 67 yr) with a mean interval of 10 mo (range: 0.5 to 50 mo) between the time of transplantation and the diagnosis of lymphoma. Of the 17 specimens analyzed by flow cytometry, 14 (82%) were diploid and 3 (18%) aneuploid. By image cytometry, 15 (88%) were diploid and 2 (12%) aneuploid. Agreement between flow cytometry and image cytometry was 94%. No statistically significant correlation between DNA content (ploidy and % S-phase fraction) and the interval since transplantation, histological subtype, or clinical outcome could be determined. A rate of DNA aneuploidy was seen that was lower than previously reported for lymphomas with the same histological grade and cell proliferation rate occurring in immunocompetent individuals. These findings are similar to those reported for AIDS-related lymphomas.

Cytologic patterns of metastatic thymoma: diagnosis by fine-needle aspiration biopsy.

Thymomas are the most frequent primary tumors of the anterior mediastinum. These lesions are slow growing and can be locally invasive, but extrathoracic metastases are rare, occurring in less than 2% of cases. Fine-needle aspiration biopsy (FNAB) may be helpful in making the diagnosis of metastatic thymoma, with or without a clinical history of primary mediastinal thymoma. We report three cases of metastatic thymoma diagnosed by FNAB. Each case illustrates a distinctive cytologic pattern. While two of the patients had a history of histologically confirmed thymoma 11 and 13 years previously, a third patient presented with an enlarged supraclavicular lymph node and pulmonary nodules, and no prior diagnosis of thymoma. These cases demonstrate that based on distinctive cytologic patterns and features, a diagnosis of metastatic thymoma can be made with FNAB. Ancillary studies will often confirm the diagnosis.

Prostatic cystic epithelial-stromal tumors: a report of 2 new cases.

The case records of 2 patients recently treated at our medical centers with prostatic cystic epithelial-stromal tumor (ages 22 and 62 years), as well as 14 cases previously reported in the literature were reviewed to obtain a consensus as to the therapy for this uncommon malignancy. Patients with prostatic cystic epithelial-stromal tumor often present with obstructive voiding symptoms and a palpable suprapubic mass. Computerized tomography typically reveals a huge, complex retrovesical mass with displacement of surrounding pelvic and abdominal structures, which may invade locally into the bladder, ureters or rectal wall. Our experience with immunohistochemical staining of these tumors suggests an epithelial component that is positive for prostate specific antigen, prostatic acid phosphatase, epithelial membrane antigen, chorioembryonic antigen and cytokeratin, and a stromal component that is positive for vimentin, desmin, cytokeratin and myosin. Rapid recurrences are the rule in patients in whom the tumor is incompletely resected. Histological evidence of malignant transformation and distant metastases has been reported in these neoplasms. An aggressive surgical approach aimed at total removal of this pelvic tumor will be discussed.

Female urethral diverticular with clear cell adenocarcinoma.

Clear cell adenocarcinoma in a urethral diverticulum in the female is a very rare and unusual tumor. We recently treated two patients with this tumor. Their presentation, histologic evaluation, and management are reviewed in light of the limited experience in the literature.

Flow and image cytometric DNA analysis in Ewing's sarcoma.

Ewing's sarcoma is the second most common bone tumor in childhood, with an overall 5-yr survival of 40%. It is one of the poorly differentiated small spherical cell tumors frequently requiring distinction from rhabdomyosarcoma, neuroblastoma, osteosarcoma, primitive neuroectodermal tumor, and lymphoma. The majority of rhabdomyosarcomas, neuroblastomas, and osteosarcomas are aneuploid, whereas Ewing's sarcomas are usually diploid. To determine whether there is any correlation between DNA content, morphology, site, and survival in Ewing's sarcoma and extraosseous Ewing's sarcoma, 21 tumor samples were studied retrospectively (3 extraosseous Ewing's and 18 Ewing's sarcomas). The DNA analysis was performed on disaggregated paraffin-embedded tissue nuclei by flow (FCM) and image (IC) cytometry and correlated with the histology and clinical history. The DNA ploidy by FCM on 17 of 18 Ewing's sarcoma samples was 12 diploid, 1 aneuploid, and 4 tetraploid. By IC, the DNA ploidy on 16 samples was 13 diploid, 1 aneuploid, and 2 tetraploid. Three samples were nonevaluable (1 by FCM and 2 by IC). The agreement between FCM and IC was 12 of 16 (75%). The extraosseous Ewing's sarcoma tumors were 2 diploid and 1 aneuploid by IC. In this study there was no correlation between the DNA ploidy and either the histology, site, or survival.

Is DNA ploidy of prognostic significance in stage I cutaneous melanoma?

Recent studies have suggested that the presence of DNA aneuploidy in stage I cutaneous melanoma carries a poor prognosis. To see if our experience correlated with these reports, we used DNA analysis by flow cytometry of propidium iodide-stained nuclei disaggregated from formalin-fixed paraffin-embedded tissue of biopsy specimens to retrospectively study 55 patients who had cutaneous stage I melanomas. The patients had been treated from 1977 to 1987 with a mean follow-up of 5.4 years. Thirty-nine (71%) of the 55 histograms were diploid, and 16 (29%) of the histograms were aneuploid. DNA content was significantly associated with other conventional prognostic factors, including growth pattern, ulceration, pathologic stage, tumor thickness, and Clark's level. DNA aneuploidy was significantly related to disease-free survival and predicted a poorer prognosis (p less than 0.05), but when stratified for tumor thickness it lost significance. A multivariate discriminant function analysis of 12 factors in melanoma showed six factors to be independently significant in determining prognosis. DNA content (p = 0.034) ranked fifth in importance behind growth pattern (p less than 0.001), ulceration (p less than 0.001), thickness (p = 0.001), and pathologic stage (p less than 0.005). DNA content, although significantly associated with conventional prognostic factors and disease-free survival, is not the best indicator of biologic behavior of melanomas in this study. Further investigation into its usefulness is necessary before DNA content can become a routine diagnostic modality in the work-up of stage I cutaneous melanomas.

Flow and image cytometric DNA analysis in rhabdomyosarcoma.

Rhabdomyosarcoma is the most common malignant soft-tissue tumor in childhood, with an overall 3-year disease-free survival of 73%. DNA content is known to correlate with prognosis and therapy response in many cancers. To determine the role of DNA content in rhabdomyosarcoma, 23 tumor samples were studied retrospectively: 18 primary tumors and 5 post-chemotherapy recurrences or specimens obtained at second-look surgeries. The DNA analysis was performed on disaggregated paraffin-embedded tissue nuclei by flow and image cytometry and correlated with the histology and clinical history. Of the primary tumors 4 were diploid, 4 polyploid, and 10 aneuploid (9 with a single aneuploid G0G1 peak and 1 multiploid) by flow cytometry. The concordance rate between flow and image cytometry was 19 of 23 (83%); one case did not have flow cytometry available. Most embryonal rhabdomyosarcomas were aneuploid (10 of 12; 83%), and they had a high incidence of recurrence in Stages III and IV (4 of 12; 33%). Although aneuploidy in pediatric cancers may predict a therapeutic response and good prognosis, this was not supported by our findings in rhabdomyosarcoma. The tumor DNA content correlated with the clinical stage but not with the patient's clinical course or tumor histopathological type. DNA content did not appear to be as important a prognostic tool as tumor stage.

Natural history and significance of esophageal squamous cell dysplasia.

Balloon-mesh cytologic screening for esophageal cancer done in 255 asymptomatic high-risk United States veterans (age greater than 40 years, ethanol abuse for greater than 20 years, and cigarette smoking greater than 20 pack years) identified 37 patients with squamous cell dysplasia. Of the 37 patients with dysplasia, 28 were re-evaluated prospectively at 6-month intervals for up to 36 months by balloon-mesh cytology, esophagoscopy with vital staining and biopsies, chest radiographs, oropharyngeal examination, and indirect laryngoscopy. During prospective follow-up evaluation, cytology specimens were repetitively normal in 16 patients (57%), showed inflammatory changes in eight patients (29%), persisted as dysplasia in two patients (7%) (both had endoscopic and histologic evidence of esophagitis), and progressed to carcinoma in two patients (7%) (one esophageal, one laryngeal). Although histologic findings concurred with the resolution of dysplasia, biopsy specimens were characterized by a similar difficulty in distinguishing dysplasia from inflammation. Erroneous histologic diagnoses of carcinoma in situ were made in two patients with reflux esophagitis evident endoscopically and confirmed during the course of a 24-36 month follow-up period. The authors conclude that squamous cell dysplasia detected by balloon-mesh cytology is seldom a precursor of esophageal cancer in the high-risk U.S. population but, rather, is often related to esophagitis. Thus, balloon-mesh cytology has limited use as a screening method for the early detection of esophageal cancer in the United States.

Pulmonary plasma cell granuloma (inflammatory pseudotumor) with invasion of thoracic vertebra.

Plasma cell granulomas (inflammatory pseudotumors) frequently appear as localized benign tumors of the lung in patients under 30 years of age. We describe the case of a 54-year-old woman with a plasma cell granuloma originating in the left lower lobe of lung and extending into the posterior mediastinum with destruction of the T8 vertebral body and pedicle. Distinctive histologic features included granulomatous aggregation of mature plasma cells around small blood vessels and direct invasion of the posterior mediastinum with subsequent dense fibrosis and bony destruction. Immunohistochemical studies revealed polyclonal kappa- and lambda-light chains in the proliferation of plasma cells.

DNA content of Hurthle cell nodules in autoimmune thyroiditis.

Hurthle cells are found in thyroid neoplasms and in reactive nodules in thyroiditis or goitrogenic processes. Cytometric studies have evaluated Hurthle cell neoplasms but not their reactive counterparts. DNA content of Hurthle cells in 22 cases of autoimmune thyroiditis was measured by flow cytometry and image content of Hurthle cells in 22 cases of autoimmune thyroiditis was measured by flow cytometry and image processing using nuclei extracted from paraffin-embedded tissue after microdissection of the Hurthle cell nodules. All 22 autoimmune thyroiditis Hurthle cell nodules were diploid, including 16 without associated neoplasms and six with associated malignant neoplasms (four papillary carcinomas, one follicular carcinoma and one follicular adenoma with papillary carcinoma). Concordance between flow cytometry and image processing was 100%. These findings indicate that the markedly atypical Hurthle cells in autoimmune thyroiditis are diploid by DNA quantitation. This suggests that atypia in Hurthle cells due to reactive or neoplastic processes may be differentiated by quantitative DNA analysis.

Technique and interpretation of breast aspiration cytology.

FNA biopsy as a diagnostic modality in breast lesions (palpable and nonpalpable) is a safe, rapid, cost-effective, and accurate method of diagnosis of breast pathology, which is beneficial to the patient, clinician, and cytopathologist. This diagnostic service has become an integral part in the workup of breast lesions in the practice of medicine today.