Guardians of the wax ... and the patient.
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Humans↗
Biomedical subjects
H F Frierson
Publications and source records attributed to H F Frierson.
Multiparameter digital image analysis of biliary, ampullary, and pancreatic adenocarcinomas.
Periampullary adenocarcinomas arise from pancreatic, biliary, or ampullary ductal epithelium. Their origin is difficult or impossible to discern by routine light microscopy of cytologic or small biopsy specimens. We used image analysis to describe the morphologic features of Feulgen-stained nuclei of biliary and ampullary adenocarcinomas and to compare these findings with those of pancreatic ductal adenocarcinomas. Surgically resected cases of ampullary adenocarcinoma (n = 7) and cholangiocarcinoma (n = 26) were selected on the basis of available formalin-fixed, paraffin-embedded tissue and diagnostic clinical data. Disaggregated nuclei were stained by the Feulgen reaction and analyzed using a digital image processor. Data from 15 morphonuclear parameters were assessed and compared with the results from the morphonuclear analysis of 22 pancreatic ductal adenocarcinomas. Multivariate analysis with canonical transformation of the data defined the ampullary adenocarcinomas and cholangiocarcinomas as occupying similar factorial distributions, whereas the pancreatic carcinomas were separate and distinct. Monovariate analysis identified seven parameters distinguishing pancreatic carcinoma from both ampullary carcinoma and cholangiocarcinoma, with P values < or = 0.001 and two others having P values < or = 0.01. Adenocarcinomas of ampullary or bile duct origin possess similar morphonuclear features described by image analysis. Image analysis provides a mechanism to discriminate adenocarcinomas arising from the bile ducts or ampulla from those arising in the pancreas.
Adenocarcinoma↗
Human ovarian tumors express gamma-glutamyl transpeptidase.
Gamma-glutamyl transpeptidase (GGT) is a cell surface enzyme that initiates the cleavage of extracellular glutathione, thereby providing the cell with the amino acids necessary for increased synthesis of glutathione. GGT is induced in ovarian tumor cell lines selected in vitro for resistance to cisplatin. No study has examined GGT expression in primary human ovarian tumors. We analyzed frozen sections of 80 normal human ovaries and 56 ovarian tumors for expression of GGT. Histochemical staining showed that GGT was not expressed in the cells of the follicle or surface germinal epithelium of the normal ovary. GGT was expressed in some epithelial inclusion glands and occasionally in a small subset of stromal cells. Granulosa-stromal cell tumors were largely GGT-negative. In contrast, GGT-positive neoplastic cells were observed in 33 of 45 common epithelial ovarian tumors. None of the patients had been treated with chemotherapy. Some of the tumors had only rare GGT-positive cells, while others consisted almost entirely of GGT-positive cells. Among the low malignant potential and invasive tumors, at least one-half of the cells were GGT-positive in 6 of 9 serous borderline tumors (2 with mucinous foci), 0 of 1 borderline mucinous tumor, 3 of 12 serous papillary carcinomas, 2 of 3 mucinous carcinomas, 1 of 2 endometrioid carcinomas, 2 of 2 clear cell carcinomas, 0 of 2 transitional cell carcinomas, and 4 of 5 undifferentiated carcinomas. There was no correlation between the stage of the tumor and GGT expression, indicating that a GGT-negative tumor does not become GGT-positive as it progresses to a more widely disseminated lesion. In addition, there was no correlation between serum levels of CA 125 and GGT expression. These data show that GGT is expressed in many common ovarian epithelial neoplasms. We are currently following the response of these patients to chemotherapy to determine if expression of GGT serves as a marker for identifying neoplasms with enhanced resistance to platinum-based therapy.
Adenocarcinoma, Mucinous↗
Histologic grade of locally advanced infiltrating ductal carcinoma after treatment with induction chemotherapy.
Multiagent chemotherapy is often used to treat patients with locally advanced infiltrating breast carcinoma before mastectomy. One of the most important prognostic factors, histologic grade, may be altered by induction chemotherapy. Because locally advanced infiltrating breast carcinomas are frequently diagnosed by fine-needle aspiration, histologic grade can be determined in the mastectomy specimens only after chemotherapy. Histologic grade, with its three components, was examined in 30 mastectomy specimens after induction chemotherapy for infiltrating ductal carcinoma and compared with findings in available pretreatment incisional biopsy specimens. Histologic grade for the 24 axillary lymph node-positive carcinomas treated with induction chemotherapy was compared with the grade for 24 axillary lymph node-positive ductal cancers that had been treated by surgery only. Complete, partial, or no clinical response was seen in 4 (13%), 21 (70%), and 5 (17%) patients after chemotherapy. In six of seven tumors, there was complete agreement between biopsy and postchemotherapy mastectomy specimens in grade and in scores for the three components. Half of the 24 node-positive tumors from patients treated with chemotherapy and 21% of node-positive neoplasms from patients treated initially with surgery had a mitotic count score of 1. In these two node-positive groups, 71% of tumors from patients treated with surgery and 92% of cancers from patients treated with induction chemotherapy showed a nuclear pleomorphism score of 3. For these two groups, however, there were no statistically significant differences in histologic grade or in any of its three components.
Adult↗
Detection of Epstein-Barr viral RNA in sinonasal undifferentiated carcinoma from Western and Asian patients.
Undifferentiated carcinoma of the nasopharynx has a well-known association with Epstein-Barr virus (EBV), but only an inconsistent relationship has been identified in undifferentiated carcinomas occurring at other sites. We investigated 22 formalin-fixed, paraffin-embedded cases of sinonasal undifferentiated carcinomas (SNUCs) occurring in Western and Asian patients. A highly sensitive in situ hybridization method was performed using an antisense oligonucleotide probe to the EBER1 gene of EBV. We identified EBV RNA in seven of 11 SNUCs from Asian patients, but in none of the Western SNUC patients (0/11). The EBER1 signal was present in all or virtually all of the tumor cell nuclei in the seven EBV-RNA-positive Asian SNUCs. The latent membrane protein-1 (LMP1) of EBV was not identified in any of the five positive cases tested. Our results suggest that genetic predisposition or environmental/geographical cofactors play an important role in determining the strength of the association of SNUC with EBV.
Adult↗
Cytokeratin in anaplastic large cell lymphoma.
A B-cell anaplastic large cell lymphoma, confirmed by immunohistochemistry and Southern blot immunoglobulin gene rearrangement analysis, contained neoplastic cells that were immunoreactive for cytokeratin using antibodies CAM 5.2, M20, MAK 6, and KS-B17.2. Bands corresponding to cytokeratin 18 and cytokeratins 18 and 8 were seen on Western blot immunoanalysis using antibodies KS-B17.2 and CAM 5.2. The lymph node also contained cytokeratin-positive extrafollicular fibroblastic reticulum cells. Although it is possible that the presence of cytokeratin in the cells of anaplastic large cell lymphoma represented phagocytosed filaments from the reticulum cells, it is more likely that the cytokeratins were synthesized by the malignant cells. The finding of cytokeratin in anaplastic large cell lymphoma, although infrequent, adds to the confusion in the diagnosis of this pleomorphic neoplasm.
Aged↗
Bismuth subsalicylate suppression of Helicobacter pylori in nonulcer dyspepsia: a double-blind placebo-controlled trial.
Gastritis caused by Helicobacter pylori (HP) is common in patients with nonulcer dyspepsia (NUD), but an etiologic relationship between the histologic lesion and clinical symptoms is unproven. HP is inhibited by bismuth subsalicylate (BSS), a traditional remedy for dyspeptic complaints. The aim of this study was to assess the short- and long-term effects of BSS on HP, gastritis, and symptoms in patients with NUD. One hundred twenty-six patients with NUD who were shown to be infected with H. pylori (HP+) were enrolled. There was a two-week placebo run-in period to eliminate placebo responders. Fifty patients remained symptomatic and were randomly assigned to therapy with either BSS liquid or a matching placebo. EGD, biopsy, and clinical evaluations were performed at entry, at week 5 (end of therapy), at week 9 (four weeks after therapy), or at time of symptomatic relapse. Twenty-seven patients received placebo and 23 patients received BSS. BSS suppressed H. pylori in 15/23 patients (65%) and eradicated it in one patient, whereas the placebo had no effect on H. pylori. Gastritis improved during therapy with BSS but relapsed by week 9. There was no significant change in level of dyspeptic symptoms during or after treatment, although one month after the end of treatment, the patients in the BSS group consistently had lower symptom scores and fewer symptomatic days for all symptoms measured. The study confirms that BSS given for three weeks suppresses but does not usually eradicate H. pylori. Such short-term suppression of H. pylori heals gastritis but does not result in clinical improvement.
Adult↗
Grade and flow cytometric analysis of ploidy for infiltrating ductal carcinomas.
Although many studies have found that ploidy as determined by flow cytometry correlates with grade for invasive mammary carcinomas, only a few groups of investigators have evaluated ploidy for infiltrating ductal carcinomas exclusively. In this study ploidy, as analyzed in fresh tumor specimens, was compared with grade (using the Bloom and Richardson grading scheme modified by Elston and Ellis) and each of its three components (tubule formation, nuclear pleomorphism, and mitotic rate) for 118 infiltrating ductal carcinomas. Two thirds of the neoplasms were DNA aneuploid, including 4% that were hypodiploid, 14% that were tetraploid, 8% that were hypertetraploid, and 12% that were multiploid. Ploidy correlated with nuclear pleomorphism (P = .004), mitotic rate (P = .001), and grade (P = .0007), but not with tubule formation (P = .09). Forty percent of grade I, 71% of grade II, and 83% of grade III neoplasms were DNA aneuploid. Ploidy was also compared with the results of combining nuclear pleomorphism with mitotic rate to form a five-part modified Bloom and Richardson scheme (MBRS grades I to V). The frequencies of DNA aneuploidy for tumors that were MBRS grades I, II, III, IV, and V were 25%, 65%, 66%, 73%, and 89%. This relationship was significant (P = .0006). When MBRS grades II, III, and IV neoplasms were combined and compared with MBRS grade I tumors and MBRS grade V carcinomas, the differences in frequency of DNA aneuploidy among these three groups also were significant (P = .00007). These results show that ploidy correlates with the grade of infiltrating ductal carcinoma and that nuclear pleomorphism and mitotic rate are more important than tubule formation for predicting the likelihood of DNA aneuploidy.
Breast Neoplasms↗
The relationship of Epstein-Barr virus to infection-related (sporadic) and familial hemophagocytic syndrome and secondary (lymphoma-related) hemophagocytosis: an in situ hybridization study.
Many cases of hemophagocytic syndrome have been associated with viral infections, particularly Epstein-Barr virus (EBV), but the pathogenesis of the syndrome remains unclear. We have examined lymph node, spleen, liver, and bone marrow sections from 12 cases, including four cases of proven or probable infection-related hemophagocytic syndrome (IHPS), three cases of familial hemophagocytic syndrome (FHPS), and five cases of secondary hemophagocytosis associated with T-cell malignant lymphoma (SHPC), for EBV RNA using a sensitive and specific in situ hybridization technique. Epstein-Barr virus RNA was detected in seven of 12 cases (58%), including three cases of IHPS, one case of FHPS, and three cases of SHPC. Numerous EBV-positive cells were detected in two cases of IHPS (in multiple anatomic sites) and in one case of FHPS (in the spleen). Diffuse EBV positivity also was noted within the neoplastic cells of one case of SHPC. Rare to occasional EBV-positive cells were found in multiple sites in another case of IHPS and within admixed, reactive lymphoid cells in two cases of SHPC. The results indicate that numerous EBV-positive cells can be identified in some cases of IHPS, FHPS, and SHPC, suggesting a pathogenetic role for the virus. However, the absence of EBV from a proportion of cases of IHPS and FHPS in this study suggests that other infectious agents also play a role in the pathogenesis of this syndrome.
Adolescent↗
Comparative immunohistochemical study of primary and metastatic carcinomas of the liver.
Distinguishing primary hepatocellular carcinoma (HCC) from metastatic carcinomas to the liver is often difficult, if not impossible, particularly in needle biopsy and fine-needle aspiration specimens. In an attempt to identify a specific immunohistochemical profile that would distinguish HCC from metastatic carcinomas, we studied 56 HCCs, 8 cholangiocarcinomas, and 24 metastatic adenocarcinomas with monoclonal antibodies to alpha-fetoprotein (AFP), keratin (AE1, AE3, and CAM5.2), Leu-M1, human milk fat globule (HMFG-2), tumor-associated glycoprotein-72(B72.3), epithelial specific membrane antigen (Ber-EP4), and BCA-225 (CU-18). Both monoclonal and polyclonal (mCEA and pCEA) antibodies to carcinoembryonic antigen also were used. Metastatic adenocarcinomas were often positive for CU-18(71%), Leu-M1 (75%), B72.3 (50%), HMFG-2 (67%), Ber-EP4(83%) and mCEA(71%). Using these antibodies, the frequency of positivity for HCC was 9%, 16%, 11%, 20%, 36%, and 11%, respectively. CU-18 was the only monoclonal antibody in which there was a significant difference in positive rates between HCC and metastatic adenocarcinomas. Most HCCs (71%) revealed a bile canalicular staining pattern with pCEA. Because this staining pattern was absent in metastatic carcinomas, pCEA appears to be useful in confirming a diagnosis of HCC. AE1, AE3 and CAM5.2 antibodies were not useful in distinguishing HCC from metastatic carcinomas. Each cholangiocarcinoma shared a staining profile similar to that of metastatic carcinomas.
Adenocarcinoma↗
Sinonasal undifferentiated carcinoma: a ray of hope.
In 1987, we published a case series of a newly-described, highly malignant neoplasm, termed sinonasal undifferentiated carcinoma, in which treatment results were poor. In this updated study, we report the followup for the original three surviving patients and for six additional cases whose tumors were diagnosed between January 1987 and October 1991. These data suggest that the prognosis for patients with localized disease may be better than originally described.
Carcinoma↗
Chromosome 11q13, c-erbB-2, and c-myc amplification in invasive breast carcinoma: clinicopathologic correlations.
To determine the frequency and clinicopathologic correlates of chromosome 11q13 amplification in breast carcinoma, DNA from 50 invasive tumors was analyzed by Southern blot hybridization using probes for the 11q13 loci bcl-1, PRAD1, hst1, EMS1, and GST-pi, as well as oncogenes c-erbB-2 and c-myc. Sixteen tumors (32%) were amplified for one or more loci. Seven tumors (14%) showed amplification of 11q13 loci; six of these were coamplified with either c-erbB-2 (three), c-myc (two), or both (one). Nine additional tumors (18%) were amplified for c-erbB-2, and three of these were coamplified with c-myc. None showed c-myc amplification alone. Tumors with 11q13 amplification showed equivalent degrees of bcl-1, PRAD1, hst1, and EMS1 amplification, delineating an approximately 800-kb amplicon. GST-pi was inconsistently amplified, evidence that it lies outside the amplicon defined by bcl-1 and EMS1. Amplification of 11q13 was unassociated with patient age, tumor size, axillary lymph node status, hormone receptors, DNA content, histologic grade, mitotic rate, nuclear pleomorphism, or tubule formation. c-myc amplification correlated with the lack of tubule formation (p = 0.04), whereas c-erbB-2 amplification correlated with axillary lymph node positivity (p = 0.04), high histologic grade (p = 0.003), increased nuclear pleomorphism (p = 0.008), and a high mitotic rate (p = 0.02). The frequency of coamplification of 11q13 loci, c-myc, and c-erbB-2 contradicts previous proposals that amplification of these genes occurs in independent subsets of breast carcinoma. Extended clinical followup will be necessary to determine whether 11q13 amplification has prognostic utility in invasive breast cancer.
Adult↗
Immunohistochemical analysis of proliferating cell nuclear antigen (PCNA) in infiltrating ductal carcinomas: comparison with clinical and pathologic variables.
PC10, a monoclonal antibody directed against proliferating cell nuclear antigen (PCNA), was used to study the percentage of cells and range of immunopositivity in formalin-fixed paraffin-embedded tissues of 39 infiltrating ductal carcinomas. The percentage of immunostained nuclei was compared to the results of seven clinical and pathologic variables and also to each of the three components of tumor grade. The range of percent positivity was 3% to 85% (median: 36%). There was no statistically significant correlation between percent PCNA positivity and patient age, axillary lymph node status, estrogen or progesterone receptor levels, ploidy, tubule formation, or nuclear pleomorphism. Significant correlations were seen between percent PCNA positivity and tumor size (p = 0.03), grade (p = 0.0005), and mitotic rate (p = 0.0001). These data suggest that, in studies examining PCNA immunoreactivity as a potentially important prognostic parameter for patients with infiltrating ductal carcinoma, tumor size and either grade or mitotic count must be considered as variables in the multivariate statistical analysis.
Antibodies, Monoclonal↗
Medullary carcinoma of the breast. Identification of lymphocyte subpopulations and their significance.
Fifty-two infiltrating breast carcinomas with medullary features (BCMF) were studied immunohistochemically to determine the immunophenotype of the mononuclear tumor inflammatory cells (MTIC) in formalin-fixed, paraffin-embedded material. The neoplasms were also examined for Epstein-Barr virus (EBV) DNA by the polymerase chain reaction (PCR). BCMF were independently classified as medullary carcinoma (MC) or infiltrating ductal carcinoma (IDC) by six observers according to the criteria of Pedersen et al. DNA from 35 BCMF was successfully amplified using PCR, but all were negative for EBV DNA. These included, by 4/6 consensus diagnosis, 16 MC, 18 IDC, and one BCMF which failed to achieve consensus diagnosis. MTIC were present to a mild degree in 19 BCMF (37%) and to moderate to severe degrees in 33 (63%). MTIC were predominantly (> or = 75%) lymphocytic in 31 BCMF (13 MC, 16 IDC, two without consensus diagnostic agreement), and plasmacytic in 10 (six MC, four IDC); equal proportions of lymphocytes and plasma cells occurred in 11 (six MC, five IDC). Lymphocytic MTIC were mostly CD45RO+/CD3+ T-cells in nearly all cases, and showed a predominant CD3+/CD4+ and CD3+/CD4- immunophenotype in 36% and 64% of cases, respectively. Natural killer cells (CD57+) and histiocytes (MAC 387+) were virtually absent. The number, cell type, and T-cell subsets of the MTIC were unrelated to consensus diagnosis, axillary lymph node status, or overall survival. EBV is unassociated with MC, despite the histologic similarities of MC to EBV-associated lymphoepithelial lesions of other organs.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Chest wall mass in rheumatoid arthritis.
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Arthritis, Rheumatoid↗
Octreotide reduces enteral protein losses in Ménétrier's disease.
A 47-yr-old man with Ménétrier's disease presented with profound enteral protein losses documented by 51Cr-albumin stool studies. There was no response to anticholinergics, H2-receptor antagonists, or proton pump inhibition. Subcutaneous octreotide acetate, 100 micrograms bid, resulted in clinical improvement with rapid resolution of enteral protein losses. Octreotide was continued for 12 months. During an additional 5-month follow-up period without therapy, the patient remained improved clinically with low to normal serum proteins, despite the persistence of gastric rugal hypertrophy. The evidence that octreotide resolved enteral protein losses and eliminated the need for urgent gastrectomy in our patient warrants a trial of this drug for other patients with Ménétrier's disease.
Albumins↗
Vaginal telangiectasias: unusual presentation of the Osler-Weber-Rendu syndrome.
BACKGROUND: The Osler-Weber-Rendu syndrome (hereditary hemorrhagic telangiectasia) is an autosomal dominant disorder of blood vessels associated with mucocutaneous telangiectasis and arteriovenous malformations of internal organs. CASE: A 23-year-old woman was found on routine gynecologic examination to have asymptomatic vaginal telangiectasias, a previously unreported initial site of involvement in this syndrome. CONCLUSION: The finding of asymptomatic vaginal telangiectasias on routine pelvic examination should alert the clinician to the possibility of the Osler-Weber-Rendu syndrome.
Adult↗
Quantitative criteria for clonality in the diagnosis of B-cell non-Hodgkin's lymphoma by flow cytometry.
Fifty-three cases of B-cell non-Hodgkin's lymphoma (BNHL) and 41 cases of non-BNHL lesions were retrospectively evaluated for the quantitative features of restricted surface light chain expression, pan B-cell antigens, pan T-cell antigens, and T-helper and T-suppressor phenotype using flow cytometry. Decision limit analyses were applied to multiple quantitative indices of immunophenotype to establish criteria for the detection of clonal proliferation associated with BNHL or non-BNHL conditions. Two data expressions (percent population and relative ratios) were simultaneously analyzed. The percent population measures were amenable to parametric analyses; the ratio data were amenable to nonparametric analyses only. Acceptable diagnostic specificity and sensitivity were obtained using decision limits of 75% kappa light chain and 65% lambda light chain for the detection of clonal proliferations associated with BNHL. Comparable diagnostic criteria for light chain ratios of 3:1 and 2:1 were similarly confirmed for cases of kappa clonal and lambda clonal proliferations, respectively. Neither the percent of B-cells present nor the ratio of T-helper cells to T-suppressor cells were of utility in the diagnosis of BNHL. These data confirm the numerical criteria for clonality previously obtained by cell counting studies of immunocytochemical preparations and characterize quantitative criteria for aid in the diagnosis of BNHL based on restricted surface light chain expression as measured by flow cytometry.
Antigens, Differentiation, B-Lymphocyte↗