Laparoscopic diagnosis of Ewing's sarcoma metastatic to the liver: case report and review of the literature.
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Biomedical subjects
Publications and source records attributed to S A Geller.
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Transgenic mice were constructed using human alpha 1-antitrypsin M and Z genomic clones. Livers of the M lineage mice showed slight cellular pleomorphism and immunohistochemically demonstrable finely granular alpha 1-antitrypsin material in hepatocytes. Z lineage mice with five gene copies per haploid mouse genome (Z#1) demonstrated fine granular alpha 1-antitrypsin material and a few large globules. In contrast, Z lineage mice with 12 gene copies per haploid mouse genome (Z#2) demonstrated hepatocytes filled with homogeneous, eosinophilic globules that were strongly reactive with diastase and periodic acid-Schiff and antibody to alpha 1-antitrypsin. Scattered microscopic polymorphonuclear leukocyte accumulations were seen that contained extracellular alpha 1-antitrypsin material, but there was neither histological nor serological evidence of mouse infectious hepatitis. In young animals, small clusters of hepatocytes lacking alpha 1-antitrypsin material were seen. These cells were the dominant population in older animals and formed nodular arrangements. Fibrosis was not demonstrable in neonatal and young animals or in any of the controls, but perisinusoidal fibrosis was seen in older Z#2 mice. Groups of hepatocytes without alpha 1-antitrypsin material showed dysplastic changes. We conclude that the transgenic mouse is a reliable and useful model in which to study the effects of alpha 1-antitrypsin in the liver because it demonstrates changes similar to those in the human disease.
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The autopsy on the patient who has died of acquired immunodeficiency syndrome (AIDS) can be of great value to the physicians who cared for the patient and to society in general. Although the AIDS virus has been shown to be significantly contagious in the clinical setting, there is no evidence thus far that it is particularly contagious in the autopsy room. Indeed, there is no documentation of a pathologist or autopsy room assistant having contracted AIDS or having seroconverted because of the performance of an autopsy on a patient with AIDS. Procedures to follow in the autopsy of the patient with AIDS are described. The hospital pathologist can safely examine the patient who has died of AIDS by using the well-established techniques for performance of the autopsy.
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Eighty (80) paraffin-embedded intestinal biopsies from 35 AIDS patients were evaluated for the presence of cytomegalovirus by use of biotinylated DNA probe, immunohistochemical assay, and routine hematoxylin and eosin (H&E) staining. Cytomegalovirus was detected in 13 biopsies (16.3%) from five patients (14.2%). The distribution of positive biopsies was one in seven esophageal biopsies, three in 19 small bowel biopsies, six in 27 colonic biopsies, and three in 17 rectal biopsies. Immunoelectron microscopy was employed to confirm the presence of CMA in four of the positive in situ hybridization cases. In situ hybridization for CMV DNA was more sensitive than immunostaining, and both proved superior to routine H&E staining in terms of sensitivity.
We have developed a transgenic mouse strain, Z#2, which represents a model for alpha 1-protease inhibitor (alpha 1-antitrypsin: alpha 1-Pi)-associated liver disease (Dycaico et al., 1988). Fifteen percent of human infants with alpha 1-Pi disease develop non-viral hepatitis which is sometimes associated with growth retardation. Such hepatitis and growth retardation tend to occur in a subset of families with other alpha 1-Pi affected members who have had non-viral hepatitis. The Z#2 mouse strain exhibits non-viral hepatitis and growth retardation. This phenotype is more pronounced in transgenic offspring of crosses between Z#2 mice and DBA/2J inbred mice, and less pronounced in transgenic offspring of crosses between Z#2 and CBA/J inbred mice. Such phenotypic differences resemble the phenotypic differences seen in human families with alpha 1-Pi-associated liver disease.
Nucleolar organizer regions (NORs) are loops of DNA encoded for ribosomal RNA production. NORs can be demonstrated in tissue sections with the use of a silver nitrate solution since they are argyrophilic (Ag-NORs). AgNORs have been shown to be increased in a variety of malignant tumors, including colonic adenocarcinoma, when compared to their benign counterparts or corresponding normal tissue. We studied 44 cases of colonic adenocarcinoma to determine whether or not correlations could be found between AgNORs and various histopathologic observations, as well as tumor cell DNA content as determined by flow cytometric analysis. We were unable to demonstrate significant correlations that would justify the use of the AgNOR technique in the daily study of colonic adenocarcinoma.
Transgenic mouse lineages were established that carry the normal (M) or mutant (Z) alleles of the human alpha 1-antitrypsin (alpha 1-Pi) gene. All of the alpha 1-Pi transgenic mice expressed the human protein in the liver, cartilage, gut, kidneys, lymphoid macrophages, and thymus. The human M-allele protein was secreted normally into the serum. However, the human Z-allele protein accumulated in several cell types, but particularly in hepatocytes, and was found in serum in tenfold lower concentrations than the M-allele protein. Mice in one lineage carrying the mutant Z allele expressed high levels of human alpha 1-Pi RNA and displayed significant runting (50% of normal weight) in the neonatal period. This lineage was found to have alpha 1-Pi-induced liver pathology in the neonatal period, concomitant with the accumulation of human Z protein in diastase-resistant cytoplasmic globules that could be revealed in the Periodic acid-Schiff reaction (PAS). The phenotype of mice in the strain expressing high levels of the Z allele is remarkably similar to human neonatal hepatitis, and this strain may prove to be a useful animal model for studying this disease.
One thousand forty-eight small (up to 6 mm) colorectal polyps, removed during colonoscopy, have been analyzed. Sixty-one percent of these small polyps were neoplastic, the remainder being equally divided between hyperplastic polyps and polypoid mucosa with normal-appearing glands. The number of polyps was evenly distributed throughout the colon. Proximally, neoplastic polyps predominated, accounting for 73% of all polyps in the right colon. This was reversed in the distal colon where non-neoplastic polyps comprised 65% of all polyps in the rectum. The incidence of carcinoma was extremely low in small colon polyps, 0.1%. All polyps should be removed when encountered during colonoscopy due to the high prevalence of adenomas among small colon polyps.
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Gallbladder adenocarcinoma (GBA) postresection 5-year survival rates are less than 5%, but when histologically confined to the mucosa or submucosa, survival rates of 64% (5 years) and 44% (10 years) have been reported. Whether any other histologic features of GBA have prognostic significance is unknown. This investigation was conducted to determine if GBA histologic grade correlates with survival. Thirty patients with advanced stage GBA participating in Eastern Cooperative Oncology Group (ECOG) treatment protocol EST-2273 served as the study material. Using glandular tumor grade criteria recommended by others, a panel of 7 ECOG pathologists categorized the GBA as either predominantly low or high histologic grade. Each patient's GBA histologic section measured no less than 1.0 X 1.0 cm. Predominant grade was defined as being that grade present in greater than 75% of the histologic section. Patient survival times by grade were calculated from date of initiation of chemotherapy until date of death. The 13-week low grade GBA patient survival was significantly longer than the 7-week high grade GBA patient survival (p less than 0.01). Stratification of patients by either high or low predominant histologic grade is recommended in future GBA treatment studies.
A quality assurance study was undertaken to examine the clinical pathology residency program at Cedars-Sinai Medical Center. During a three-month period, clinical pathology residents kept a log of all the problems encountered while "on-call." A staff pathologist rated the performance of the resident in terms of how well he or she solved each problem. Of the 109 calls evaluated, one was judged to have been handled incorrectly, and 7 others were considered to have been answered in a conditional manner. The Blood Bank generated the largest number of calls (66), and requests for blood products were the single most common call (29). The review of all on-call problems with staff pathologists proved to be a valuable educational tool, both for the residents and staff. In addition, the study served as an impetus for development of a useful program for evaluating and, if necessary, correcting decisions made by pathology residents.
Carcinoids are histologically classified as insular (A), trabecular (B) glandular (C), undifferentiated (D) or mixed. These have prognostic significance, i.e. Group 1 (most favorable, A + C); 2 (favorable, A, B, A + B); 3 (relatively unfavorable, all non A + C or A + B mixed types); and 4 (unfavorable, C, D). Midgut primaries have a better prognosis than either foregut or hindgut/cloacal primaries. Carcinoids from 114 Eastern Cooperative Oncology Group patients were studied to determine if primary site prognostic differences result from histologic prognostic group occurrence rate differences across primary sites. By primary site the following rates were observed: Foregut: 1 (0%), 2 (79.2%), 3 (12.5%), 4 (8.3%); midgut: 1 (26.7%), 2 (58.7%), 3 (6.6%), 4 (8.0%); hindgut/cloaca: 1 (0%), 2 (42.9%), 3 (42.9%), 4 (14.2%); nongut: 1 (0%), 2 (75.0%), 3 (12.5%), 4 (12.5%), p less than 0.01. The results demonstrate that primary site prognostic differences are highly dependent upon histologic prognostic group occurrence rate variations across primary sites. In addition multivariate analysis of survivorship by both histologic type (p less than 0.05) and primary site (p less than 0.05) demonstrated that each variable has independent prognostic significance.
The gall bladder mucosa is composed of neutral mucopolysaccharide and protein radical containing secretory cells, protein radical containing migratory cells, and neutral and acid mucopolysaccharides plus sialic acid containing goblet cells. The prognostic significance of histologic or histochemical parameters in gall bladder adenocarcinoma (GBA) are unknown. To determine if histochemical acid mucopolysaccharide content in GBA has prognostic value, GBA histologic sections from 26 advanced stage disease patients participating in Eastern Cooperative Oncology Group (ECOG) treatment study EST-2273 were stained with alcian blue at pH. 1.0, assessed by a pathology panel for either high (greater than 50%) or low (less than 50%) acid mucopolysaccharide content, and correlated with patient survival. Initial panel unanimous concurrence rate on acid mucopolysaccharide content was 88.9%. Median survival times from the start of chemotherapy to date of death for high acid mucopolysaccharide content GBA was 14 weeks versus five weeks for the low content GBA (P less than 0.0001). The results indicate that high acid mucopolysaccharide content in GBA significantly improves prognosis. ECOG recommends stratification by acid mucopolysaccharide content in future GBA treatment investigations.
The PVSG study is unique in that it is prospective and composed of 432 patients randomized to three treatment arms. This study also provides the opportunity for serial studies of numerous sequential biopsies. Large numbers of cases with sequential biopsies covering the entire long course are essential to appreciate the full spectrum of tissue changes in this disease. The PVSG was initiated in 1967 and in mid-1985 approximately one third of the patients are alive and on protocol. For these reasons, the results must still be considered preliminary. Pretreatment biopsies from patients randomized in the PVSG have been analyzed for total cellularity, megakaryocyte concentration, and reticulin content. Considerable variation in these elements was found in these biopsies. Sequential posttreatment biopsies from these patients have also been studied and correlated with the clinical course of the disease. None of the morphologic parameters analyzed was shown to be of prognostic significance. Early in the course of PV the marrow reticulin content is almost always normal. The length of the developmental stage is unknown and the precise timing of the clinical onset may be difficult. Therefore, the 11% of patients that showed a significant increase in reticulin on initial evaluation may have had PV longer than was indicated clinically. If large numbers of sequential biopsies are studied, an increase in reticulin content can frequently be demonstrated during the active phase of the disease and before the onset of the spent phase. Currently 39 patients (9%) have developed the spent phase, or PPMM. PPMM occurred in about the same incidence in the patients treated with myelosuppressive therapy as by phlebotomy alone, the spent phase occurring in 16 patients treated by phlebotomy alone, 11 with chlorambucil, and 12 with 32P. The course of the reticulin fibrosis is slowly progressive. There is some evidence for regression in a few patients in the erythrocytotic phase, but sampling variation cannot be completely ruled out. At this time in the study, AL has developed in 37 patients (8.6%). The incidence of AL is quite low in the phlebotomy group (three cases). Presumably this represents the natural incidence in PV unmodified by therapeutic agents. The frequency is approximately equal and quite high in the chlorambucil and 32P groups. There are 19 cases in the chlorambucil-treated group and 15 in the 32P-treated group. The leukemias that developed in the PV patients occurred either de novo or following PPMM.(ABSTRACT TRUNCATED AT 400 WORDS)