Showing papers in "American Journal of Clinical Pathology in 1998"
TL;DR: A pathologic classification applicable to the surgical pathology of bronchiolitis is presented and the anatomy of the small airways is discussed, and a variety of clinical, radiologic, and functional patterns ofBronchiolar disease are presented.
Abstract: Bronchiolitis represents a cellular and mesenchymal reaction involving bronchioles. The interplay between the cellular infiltrate and the mesenchymal reaction affects the lumen size, lamina propria, muscular layer, and bronchiolar adventitia. The result is a variety of clinical, radiologic, and functional patterns of bronchiolar disease. The anatomy of the small airways is discussed, and a pathologic classification applicable to the surgical pathology of bronchiolitis is presented. The classification is practical and includes asthma, chronic obstructive pulmonary disease, cellular bronchiolitis, respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease, bronchiolitis obliterans (including bronchiolitis obliterans with intraluminal polyps and constrictive bronchiolitis), dust-related small airway fibrosis, and (postinflammatory) bronchiolar scarring and peribronchiolar fibrosis.
182 citations
TL;DR: Findings may be useful in predefined differential diagnostic settings involving the distinction between primary and metastatic ductal cancers of the breasts, skin, and salivary glands, because of the striking homologies between such tumors at structural and protein-synthetic levels of comparison.
Abstract: Morphologic mimicry among human malignant neoplasms is a well-known phenomenon in surgical pathology; both undifferentiated and "committed" neoplasms may exhibit this trait. One particularly common group of histologic simulants includes ductal carcinomas of the breasts, the cutaneous appendages, and the salivary glands. One hundred three tumors in this structural cluster were analyzed microscopically and immunohistologically to codify points of potential pathologic similarity and difference. All the lesions were typified by irregularly permeative clusters and cords of atypical polygonal cells with variable luminal differentiation. A proportion of primary neoplasms in each site demonstrated in situ ductal components; in the absence of the latter elements, however, it was not possible to make topography-related morphologic distinctions among them. Immunostains for gross cystic disease fluid protein-15 (GCDFP-15), carcinoembryonic antigen, S100 protein, c-erbB-2 oncoprotein, estrogen receptor protein, and progesterone receptor protein also showed largely overlapping phenotypes in each of the three tumor categories, with selected exceptions. These differences were elucidated through paired chi 2 analysis and included a statistically significant infrequency of GCDFP-15 in eccrine sweat gland carcinomas, a paucity of carcinoembryonic antigen in breast cancers, and an absence of estrogen receptor protein in salivary duct carcinomas. Such findings may be useful in predefined differential diagnostic settings involving the distinction between primary and metastatic ductal cancers of the breasts, skin, and salivary glands. Nevertheless, because of the striking homologies between such tumors at structural and protein-synthetic levels of comparison, it is mandatory that all available clinicopathologic information be used in this context.
180 citations
TL;DR: Long-term use of proton pump inhibitors may be associated with the presence of small gastric fundic gland polyps and hyperplastic polyps, and a prospective study is required to establish their incidence, natural history, and clinical significance.
Abstract: Since 1992 there have been reports of proton pump inhibitors being associated with fundic gland-type gastric polyps. Endoscopic and histologic characteristics and natural history of these polyps have not been clearly defined. We performed a retrospective study of patients on long-term treatment with proton pump inhibitors who developed gastric polyps. Gastric polyps developed in 17 (10 males and 7 females, 7.3%) of the 231 patients who underwent 2 or more upper endoscopies for complicated gastroesophageal reflux disease and who were receiving long-term treatment with proton pump inhibitors. The mean interval of proton pump inhibitor use after which an endoscopy revealed gastric polyps was 32.5 months. In 1 patient, discontinuation of treatment resulted in disappearance of the polyps within 3 months. The polyps recurred 4 months after the treatment was restarted. Endoscopy established that typical polyps were generally small (<1 cm), sessile, multiple, and whitish pink with a mottled partially translucent surface. The polyps were most often present in the proximal/midgastric body. Of the 15 polyps removed endoscopically, 9 were of the fundic gland type, 4 were of the hyperplastic type, and 2 were of the inflammatory type. Eight of 9 polyps with typical endoscopic appearance were of the fundic gland type. None of the polyps contained dysplasia or carcinoma. Long-term use of proton pump inhibitors may be associated with the presence of small gastric fundic gland polyps and hyperplastic polyps. A prospective study is required to establish their incidence, natural history, and clinical significance.
178 citations
TL;DR: Adventitious sporulation was found in 9 of 9 infections caused by Paecilomyces species, 7 of 10 infections causing by Fusarium species, and in the single case of infection caused by Acremonium strictum.
Abstract: Nontraditional human pathogenic fungi, including Fusarium, Paecilomyces, and Acremonium species, have been increasingly documented as agents of infection in immunocompromised patients and, occasionally, in normal hosts. Although definitive identification of these fungi requires culture, they often can be identified provisionally in tissue sections by a combination of histologic features, including hyaline septate hyphae and characteristic reproductive structures known as phialides and phialoconidia. These morphologic characteristics, although familiar to mycologists, are easily overlooked by histopathologists; as a result, Fusarium species and Paecilomyces lilacinus are frequently misidentified in tissue sections as Aspergillus or Candida species. We identified 19 culture-proved cases of infection with species of Fusarium, Paecilomyces, or Acremonium; retrospectively reviewed histologic specimens stained by routine hematoxylin and eosin, Gomori methenamine silver, and/or periodic acid-Schiff stains; and delineated morphologic criteria that will help pathologists make a preliminary identification of these fungi by histopathology. Adventitious sporulation was found in 9 of 9 infections caused by Paecilomyces species, 7 of 10 infections caused by Fusarium species, and in the single case of infection caused by Acremonium strictum. Histologic recognition of these morphologies may help clinicians select appropriate initial antifungal treatment and manage the infection.
173 citations
TL;DR: Primary central nervous system lymphomas are rarely associated with Epstein-Barr virus and in immunocompetent patients they express bcl-2 at a relatively low rate, and from the standpoint of their biologic characteristics, they are very similar to systemic diffuse large B-cell lymphomas.
Abstract: We reviewed 72 primary central nervous system lymphomas occurring in immunocompetent patients. The cases were reviewed for clinical data, histology, immunophenotype, bcl-2 and p53 expression, and Epstein-Barr virus association. Follow-up was available for 40 patients included in the Groupe Ouest Est d'etude des Leucenies et Autres Maladies du Sang (GOELAMS) lymphomes cerebraux primitifs (LCP 88) trial. Each diagnosis, requiring a consensus among at least 3 pathologists, was performed according to the recent Revised European-American Lymphoma classification and equivalents in the updated Kiel classification. Tumors were predominantly classified as diffuse large B-cell lymphomas. There were 3 T-cell lymphomas and 1 Hodgkin lymphoma. The proteins bcl-2 and p53 were expressed in 35% and 16% of the tested cases, respectively. Epstein-Barr virus was not found by in situ hybridization except in the case classfied as a cerebral localization of Hodgkin disease. No significant association was found between subtypes, bcl-2 or p53 expression, and patient survival. From the standpoint of their biologic characteristics, primary central nervous system lymphomas are very similar to systemic diffuse large B-cell lymphomas. In contrast to AIDS-related primary central nervous system lymphomas, primary central nervous system lymphomas are rarely associated with Epstein-Barr virus and in immunocompetent patients they express bcl-2 at a relatively low rate.
152 citations
TL;DR: Immunophenotyping studies are helpful in the determination of myeloid lineage, however, they are not sufficiently specific alone to be useful in precisely identifying either FAB or cytogenetically defined disease subtypes.
Abstract: Immunophenotyping has become common in the diagnosis and classification of acute leukemias and is particularly important in the proper identification of cases of minimally differentiated acute myeloid leukemia (AML-M0). To evaluate the immunophenotype of adult AML, 106 cases were studied by cytochemical analysis and by flow cytometry with a panel of 22 antibodies. The results were compared with the French-American-British (FAB) Cooperative Group classification, as well as with available cytogenetic data on each case. CD45, CD33, and CD13 were the most commonly expressed antigens (97.2%, 95.3%, and 94.3%, respectively). Lymphoid-associated antigens were expressed in 48.1% of cases. CD20 was the most commonly expressed lymphoid antigen (17%), although often expressed in only a subpopulation of leukemic cells, followed by CD7 (16%), CD19 (9.8%), CD2 (7.5%), CD3 (6.7%), CD5 (4.8%), and CD10 (2.9%). Some immunophenotypes correlated with FAB type, including increased frequency of CD2 expression in AML-M3; lack of CD4, CD11c, CD36, CD117, and HLA-DR expression in AML-M3; increased frequency of CD20 and CD36 expression and lack of CD34 expression in AML-M5; increased frequency of CD5 expression in AML-M5a; and increased frequency of CD14 expression in AML-M5b, when compared with all other AMLs (P < .05). When compared with AML-M5b, AML-M5a demonstrated a lack of CD4 expression and a high frequency of CD117 expression. Complete morphologic and cytogenetic agreement between AML-M3 and t(15;17) was present, and four of five cases of AML-M4Eo demonstrated inv(16). The remaining case of M4Eo was characterized by a 6;9 translocation, and two other inv(16) cases were not classified as M4Eo. Expression of CD2 was present in two t(15;17) cases and in one inv(16) case, but expression of this antigen was not restricted to AML cases with these karyotypic abnormalities. Similarly, expression of CD19 was not specific for t(8;21) AML. All t(8;21) leukemias demonstrated M2 morphology. With the exception of M3, M4Eo, and a subgroup of M2 leukemias, the FAB classification does not appear to define cytogenetically distinct disease groups in adult AML. Immunophenotypically distinct profiles were identified in the M3 and M5 morphologic groups of the FAB classification. Immunophenotyping studies are helpful in the determination of myeloid lineage. In general, however, they are not sufficiently specific alone to be useful in precisely identifying either FAB or cytogenetically defined disease subtypes.
148 citations
TL;DR: It is found that cycle-arrested osteosarcoma cells are positive for Ki-67 even when they are arrested in G1/S or G2/M by using synchronizing inhibitors, by inducing p21(Waf1/Cip1) in a tetracycline-regulated expression system or by inducing wild type p53 and p21 after inflicting DNA damage.
Abstract: Ki-67 is a proliferation marker that is often used to estimate the growth fraction of tumors and other tissues. This antigen is expressed during all phases of the cell cycle but not in quiescent G0 cells. Many studies fail to indicate that the Ki-67 antigen can be expressed even when DNA synthesis is blocked. We studied the expression of the antigen Ki-67 in cycle-arrested osteosarcoma cells. We found that these cells are positive for Ki-67 even when they are arrested in G1/S or G2/M by using synchronizing inhibitors, by inducing p21(Waf1/Cip1) in a tetracycline-regulated expression system or by inducing wild type p53 and p21 after inflicting DNA damage. Our results show that not all cells containing the Ki-67 antigen are actively proliferating cells and we advise against the use of Ki-67 in studies on cells that overexpress p53 or p21.
133 citations
TL;DR: Biochemical alterations suggest that the increases in serum troponins after the infarction parallel the decreases in tissue concentrations of trop onins, which are similar in all nonischemic zones.
Abstract: We studied the distribution of cardiac troponins I (cTnI) and T (cTnT) in ischemic left ventricular (LV) tissue in 7 infarct zones, 7 remote nonischemic LV areas, and 7 nonischemic areas each from the right ventricle and circumflex in an acute coronary artery occlusion dog model to correlate myocardial loss of troponins with infarct size 3 weeks after the infarction and to determine whether the decrease of troponins in ischemic myocardium can be used to assess the infarct size in dogs after coronary occlusion. The serum profiles for time vs mean cTnI and cTnT concentrations in 6 dogs after occlusion showed peak concentrations at 1 day and 5 days, respectively. The concentrations of troponins were similar in all nonischemic zones. However, cTnI and cTnT decreased significantly in the LV ischemic tissues. Loss of cTnT, but not cTnI, in ischemic LV tissues correlated significantly with infarct size 3 weeks after the infarction. Biochemical alterations suggest that the increases in serum troponins after the infarction parallel the decreases in tissue concentrations of troponins.
133 citations
TL;DR: It is indicated that strong linear membrane-related labeling for epithelial membrane antigen and silver-labeled nucleolar organizer region-positive material that occupies 0.6677 microm2 or more of the nucleus in an atypical in situ mesothelioma lesion of the pleura are found consistently in neoplastic mesothelial cells.
Abstract: In biopsy tissue, discrimination between reactive mesothelial hyperplasia and epithelial mesothelioma can pose a major problem for the surgical pathologist. Confidence in the diagnosis is often proportional to the amount of tissue available for study and depends largely on findings of invasion and the extent and cytologic atypia of the lesion, because there is no marker specific for the mesothelium and that discriminates consistently among normal, hyperplastic, and neoplastic mesothelial tissue. Therefore, mesothelioma in situ is diagnosable only when invasive epithelial mesothelioma is demonstrable in the same specimen, in a follow-up biopsy specimen, or at autopsy. Comparison of 22 cases of mesothelioma in situ that fulfill these requirements for diagnosis with 141 invasive mesotheliomas and 78 reactive mesothelioses indicates that strong linear membrane-related labeling for epithelial membrane antigen and silver-labeled nucleolar organizer region-positive material that occupies 0.6677 microm2 or more of the nucleus in an atypical in situ mesothelial lesion of the pleura are found consistently in neoplastic mesothelial cells. Although these findings may engender suspicion of mesothelioma in situ in high-risk persons, the criteria for diagnosis of pure mesothelial lesions of this type are still under study. Mesothelioma in situ should be considered proved only when unequivocal invasion is identified in a different area of the pleura or at a different time; a diagnosis of pure mesothelioma in situ should not be made in patients not exposed to asbestos.
113 citations
TL;DR: Evidence that alpha-L-fucose is critically important for cell-cell and cell-matrix adhesion in a variety of normal and pathologic processes, particularly neoplasia is reviewed.
Abstract: Alpha-L-fucose is a 6-carbon deoxyhexose that is commonly incorporated into human glycoproteins and glycolipids. It is found at the terminal or preterminal positions of many cell-surface oligosaccharide ligands that mediate cell-recognition and adhesion-signaling pathways. These include such normal events as early embryologic development and blood group recognition and pathologic processes including inflammation, infectious disease recognition, and neoplastic progression. Fucosylated oligosaccharide ligands mediate cell-cell adhesion through binding to cell-surface selectins (calcium-dependent binding proteins) and calcium-dependent interactions with other cell-surface carbohydrate counterligands. A number of fucose-containing "natural ligands" are common to inflammatory and malignant cell processes. We review evidence that alpha-L-fucose is critically important for cell-cell and cell-matrix adhesion in a variety of normal and pathologic processes, particularly neoplasia. Current results suggest that alpha-L-fucose provides the essential structure that enables carbohydrate ligands to bind to selectins and to carbohydrate counterligands and thereby alter cellular homeostasis.
111 citations
TL;DR: Low levels of positive-strand HCV RNA were detected in a single hepatic lymphoma, suggesting the presence of the virus in residual hepatocytes, and the antigen-driven properties of HCV-associated B-cell malignant neoplasms may be considered for hepatic MALT-type lymphoma.
Abstract: Hepatitis C virus (HCV) infection may be complicated by non-Hodgkin's lymphoma. We describe eight cases of B-cell extranodal non-Hodgkin's lymphoma occurring during the course of chronic HCV-related hepatic disease (low-grade of mucosa-associated lymphoid tissue [MALT]-type; diffuse large cell; Burkitt; diffuse small cell). Some were localized to the liver (2), liver and spleen (1), spleen (1), peritoneal cavity (1), parotid gland (1); others manifested in the nasopharynx (1) and eyelid (1) but were accompanied by nodal disease. Four lymphomatous specimens available for molecular analysis exhibited clonal immunoglobulin gene rearrangements, lacked bcl-2, bcl-6, c-myc genes and p53 alterations, and did not contain replicative intermediate HCV RNA, as documented by a strand-specific reverse transcriptase-polymerase chain reaction. Low levels of positive-strand HCV RNA were detected in a single hepatic lymphoma, suggesting the presence of the virus in residual hepatocytes. The antigen-driven properties of HCV-associated B-cell malignant neoplasms may be considered for hepatic MALT-type lymphoma, which probably originated from lymphoid tissue acquired during long-standing HCV infection.
TL;DR: This study further supports the recommendation to use 3.2% sodium citrate concentration, because 60% of the optimum filled volume for PT and 70% ofThe optimumfilled volume for APTT are acceptable.
Abstract: We evaluated the effect of sample volume and citrate concentration on results of routine coagulation assays (prothrombin time [PT] and activated partial thromboplastin time [APTT]). The study was performed on samples obtained from healthy persons and patients receiving oral anticoagulant therapy. Standard evacuated tubes (3.2% and 3.8% sodium citrate) were filled to varying total sample volumes ranging from 3.0 to 5.0 mL, and results of routine coagulation tests were compared. Underfilling may significantly affect the APTT and PT, resulting in artifactual prolongation of results. This effect is most pronounced in samples drawn into 3.8% citrate. By using 3.8% citrate, there is a statistically significant difference in the results of PT assays in the samples less than 80% filled compared with those that are 100% filled. For APTT assays performed on samples drawn into 3.8% citrate, a statistical difference occurred at less than 90% filled. This effect was less pronounced when samples were drawn into 3.2% sodium citrate. We found no statistically significant difference in PT results from a 3.2% citrate tube between fill volumes of 60% and 100% and none for APTT results between fill volumes of 70% and 100%. This study further supports the recommendation to use 3.2% sodium citrate concentration, because 60% of the optimum filled volume for PT and 70% of the optimum filled volume for APTT are acceptable.
TL;DR: MIB-1 proliferative rate and bcl-2 positivity may prove to be useful markers for poor prognosis in prostate carcinoma.
Abstract: Predicting the clinical behavior of prostate carcinoma can be difficult; one approach is to identify molecular prognostic markers. We evaluated proliferative rate (MIB-I antibody) and expression of bcl-2, p53, and retinoblastoma (pRB, proteins, which have cell cycle-related functions, in 208 consecutive radical prostatectomy specimens. Values were correlated with histopathologic parameters (Gleason tumor score, tumor amount, capsule invasion, and involvement of surgical margins, seminal vesicles, or lymph nodes) and with recurrence-free survival (4-year median follow-up). A high MIB-1 proliferative rate was associated with all of the measured histopathologic parameters, p53 overexpression with tumor amount, and pRB expression with positive lymph nodes. pRB and p53 expression levels were not associated with differences in recurrence-free survival. A high MIB-1 proliferative rate and bcl-2 positivity were associated with increased recurrence, both considered individually, and also independently and additively when examined together and with the most predictive histopathologic factors (Gleason tumor score and seminal vesicle involvement). MIB-I proliferative rate and bcl-2 positivity may prove to be useful markers for poor prognosis in prostate carcinoma
TL;DR: The high-mobility group proteins are reviewed with an emphasis on the HMGI subfamily, and the potential role of these proteins in human tumorigenesis is discussed.
Abstract: The high-mobility group (HMG) proteins are a family of nonhistone chromatin-associated proteins that have an important role in regulating chromatin architecture, as well as in regulating gene expression. The gene encoding one HMG protein, HMGI-C, is frequently rearranged or overexpressed by chromosomal translocations in common benign mesenchymal tumors including lipomas, leiomyomas, fibroadenomas, pleomorphic adenomas, aggressive angiomyxomas, and pulmonary hamartomas. The HMGI-C translocations involve many different translocation partners and are remarkable for their low risk of progression to malignancy. Recently, another member of this subfamily, HMGI(Y), has also been shown to be rearranged in lipomas and pulmonary chondroid hamartomas. Given the high frequency of these benign mesenchymal tumors, it is likely that translocations involving the HMGI subfamily are one of the most common chromosomal rearrangements in human neoplasia. The HMG proteins are reviewed with an emphasis on the HMGI subfamily, and the potential role of these proteins in human tumorigenesis is discussed.
TL;DR: This study shows that in association with the well-described cytoplasmic and architectural features, nuclear parameters are valuable discriminants between chromophobe renal cell carcinoma and renal oncocytoma.
Abstract: Chromophobe renal cell carcinoma and renal oncocytoma have overlapping morphologic, histochemical, immunohistochemical, and ultrastructural features; however, their distinction is critical inasmuch as the former neoplasm has a malignant potential and the latter is widely believed to be a benign tumor In this study, we investigated the potential utility of nuclear features in differential diagnosis Nuclear contours, nuclear chromatin pattern, binucleation or multinucleation, pleomorphism, and mitotic activity were assessed semiquantitatively in routine H&E-stained sections from 16 cases of chromophobe renal cell carcinoma and 21 cases of renal oncocytoma All cases of chromophobe renal cell carcinoma were found to have wrinkled, "raisinoid" nuclei in varying proportions, whereas all renal oncocytomas had predominantly round, relatively uniform nuclei Binucleation or multinucleation was significantly more common in chromophobe renal cell carcinoma Nuclear chromatin tended to be coarser in chromophobe renal cell carcinoma and nucleoli were seen more commonly in renal oncocytoma Of the renal oncocytomas, 19% had distinct foci of "degenerative" nuclear atypia with pleomorphism This type of atypia was absent in chromophobe renal cell carcinoma Our study shows that in association with the well-described cytoplasmic and architectural features, nuclear parameters are valuable discriminants between chromophobe renal cell carcinoma and renal oncocytoma Frequent binucleation and "raisinoid" nuclei with perinuclear halos, resulting in "koilocytoid atypia," is highly characteristic of chromophobe renal cell carcinoma
TL;DR: Given the widespread use of NSAIDs, pathologists should consider NSAID-associated colitis along with Crohn disease and infectious-type colitis in the histologic differential diagnosis of focal active colitis.
Abstract: We describe the histologic findings of biopsies performed on specimens from 14 patients with nonsteroidal antiinflammatory drug (NSAID) associated colitis Thirteen patients had endoscopially patchy colitis with small erosions in different parts of the colon One patient had diffuse colitis extending from the rectum to the midtransverse colon Histologically, 8 patients had a mixed inflammatory infiltrate, 4 had predominantly neutrophilic inflammation, and 2 had predominantly lymphocytic inflammation Seven patients had erosions Eight patients had crypt architectural disarray, but none had crypt architectural distortion or granulomas The histology of NSAID-associated colitis is similar in our experience to that of Crohn disease and infectious-type colitis It shares no features with ulcerative colitis Given the widespread use of NSAIDs, pathologists should consider NSAID-associated colitis along with Crohn disease and infectious-type colitis in the histologic differential diagnosis of focal active colitis
TL;DR: Ber-EP4 seems to be helpful in separating epithelial pleural mesotheliomas from lung adenocarcinomas from other tumors metastatic to the pleura, but its value is more limited and depends largely on the site of origin of the metastatic tumor.
Abstract: Although most studies have indicated that Ber-EP4 immunostaining can assist in differentiating epithelial pleural mesotheliomas from adenocarcinomas that metastasize to the pleura, the percentage of positive cases has varied greatly among different studies. Authors of a recent publication concluded that Ber-EP4 has no diagnostic utility in separating these conditions. To determine whether Ber-EP4 has any value in distinguishing mesothelioma from adenocarcinoma, 70 formalin-fixed epithelial pleural mesotheliomas, 20 pulmonary adenocarcinomas, 59 nonpulmonary adenocarcinomas, 4 squamous cell carcinomas of the lung, 6 transitional cell carcinomas, and 31 adenocarcinomas of unknown origin that metastasized to the pleura were stained with this antibody. Reactivity was observed in 18 (26%) of 70 mesotheliomas and in all 20 (100%) of the pulmonary adenocarcinomas, in 55 (93%) of the 59 nonpulmonary adenocarcinomas, in 4 (100%) of 4 squamous cell carcinomas of the lung, in 4 (67%) of 6 transitional cell carcinomas, and in 26 (84%) of 31 adenocarcinomas of unknown origin that metastasized to the pleura. The staining in the mesotheliomas was focal and restricted to a limited number of cells, in contrast with staining in the pulmonary adenocarcinomas in which it was invariably diffuse. The extent of the staining in the nonpulmonary adenocarcinomas and the metastatic adenocarcinomas of unknown origin was less consistent--negative or focal in some cases and diffuse in others. Therefore, while Ber-EP4 seems to be helpful in separating epithelial pleural mesotheliomas from lung adenocarcinomas, its value in distinguishing mesotheliomas from other tumors metastatic to the pleura is more limited and depends largely on the site of origin of the metastatic tumor.
TL;DR: Staining for p53 was more common in DMM than in FP, but the difference was not statistically significant, and the concordance in interpreting the p53 stains by the same 3 pathologists was moderate.
Abstract: We studied 31 patients with fibrotic pleural lesions and classified them as desmoplastic malignant mesothelioma (DMM) or fibrous pleurisy (FP) using predetermined histologic criteria, including a paucicellular fibrotic pleural lesion with a storiform pattern or the "patternless pattern " of Stout, plus 1 or more of the following: invasion of chest wall or lung, bland necrosis, frankly sarcomatoid areas, and distant metastases. Staining for p53 was performed in 22 cases. Follow-up was obtained on all cases and compared with the histologic diagnoses. For 24 cases, the consensus diagnosis was DMM; 19 of these displayed frankly sarcomatoid areas, 16 showed invasion, and 8, bland necrosis. Of the 24, 23 patients died of disease and 1 was alive with disease. The remaining 7 cases were classified as FP, and all were alive without disease. The concordance among 3 pathologists using the criteria was excellent. Staining for p53 was more common in DMM than in FP, but the difference was not statistically significant. The concordance in interpreting the p53 stains by the same 3 pathologists was moderate. The distinction between DMM and FP in a predominantly fibrotic pleural lesion can be made in most cases with adequate sampling and the use of specific criteria.
TL;DR: It is intended to provide a comprehensive overview of the usefulness and limitations of FNAB in the diagnosis of soft tissue sarcomas, including a reappraisal of diagnostic criteria.
Abstract: The diagnosis of soft tissues sarcomas by fine-needle aspiration biopsy (FNAB) is controversial and relatively underused. We believe that the lack of acceptance by many clinicians and pathologists may be related to several factors. First, in comparison with other forms of cancer, soft tissue sarcomas are rare, constituting less than 1% of all malignant neoplasms. As a consequence, most pathologists lack extensive experience with the histopathologic and cytopathologic features of sarcomas. Furthermore, possibly no other subspecialty field of pathology is associated with a more bewildering spectrum of histomorphologic appearances. Because a diagnosis of malignant neoplasm may result in adverse consequences (eg, amputation), the pathologist involved with a soft tissue tumor diagnosis, especially with small biopsy specimens such as FNAB specimens, may be reluctant to give a specific diagnosis. Finally, of the pathologists with experience in the diagnosis of soft tissue sarcoma, many have been reluctant to endorse FNAB as a reliable procedure for establishing a definitive diagnosis. Nevertheless, FNAB among adequate specimens seems to have a diagnostic sensitivity and specificity of up to 95% for the determination of malignancy.False-positive and false-negative results approach approximately 4% (not including inadequate samples). If inadequate samples are included, false-negative rates may approach 10% to 15%. In this review, it is our intent to provide a comprehensive overview of the usefulness and limitations of FNAB in the diagnosis of soft tissue sarcomas, including a reappraisal of diagnostic criteria.
TL;DR: MIB-1 proliferation index is a simple and reliable tool to predict the clinical outcome of the neuroendocrine tumors of the pancreas and might be useful for determining the prognosis for an individual because of the significant decrease in survival when the index is higher than 4%.
Abstract: The expression of the cell-cycle-associated Ki-67 antigen by MIB-1 monoclonal antibody was retrospectively assessed in 35 surgically resected neuroendocrine tumor specimens of the pancreas embedded in paraffin. The MIB-1 proliferation index was correlated with the classification of the neuroendocrine tumors of the pancreas proposed by Kloppel et al. Four prognostic factors showed a significant correlation with MIB-1: local invasion, metastases, tumor differentiation, and production of insulin. However, analysis by the Cox Proportional Hazards Regression Model showed that only local invasion was an independent predictor of outcome. Finally, our study showed a statistically significant increase in the number of deaths and a statistically significant decrease in survival time when the MIB-1 proliferation index was higher than 4%. We conclude that MIB-1 proliferation index is a simple and reliable tool to predict the clinical outcome of the neuroendocrine tumors of the pancreas. The index might be useful for determining the prognosis for an individual because of the significant decrease in survival when the index is higher than 4%.
TL;DR: Old-fashioned low-technology autopsies can uncover many important diagnoses missed by modern high-technology medicine, according to this and similar studies suggest.
Abstract: To determine the current frequency of discovering important diagnoses at autopsy, the diagnoses made in all complete or "no head" autopsies during 1994 at a major tertiary care transplantation referral center were retrospectively compared with the diagnoses made antemortem. Of 176 autopsies, 79 (44.9%) revealed 1 or more undiagnosed causes of death. Of the 123 undiagnosed causes of death, 13 were sole immediate causes of death, 72 were one of multiple immediate causes, 22 were intervening causes, and 16 were underlying causes. The causes of death were as follows: infections, 34; infarctions, 11; malignant neoplasms, 8; pulmonary emboli, 7; gastrointestinal ulcers, 7; hemorrhages, 6; thromboses, 3; amyloidosis, 1; genetic hemochromatosis, 1; and cardiac tamponade, 1. Of 35 autopsies of transplant recipients, 16 (46%) disclosed undiagnosed causes of death, compared with 63 (44.7%) of 141 autopsies of patients who had not received transplants. Approximately two thirds of the undiagnosed causes of death were judged to be treatable conditions. This and similar studies suggest that old-fashioned low-technology autopsies can uncover many important diagnoses missed by modern high-technology medicine.
TL;DR: It is concluded that anti-CD31 immunostaining in carcinomas and mesotheliomas is rare and should be included in diagnostic immunohistochemical panels when vascular tumors enter the differential diagnosis.
Abstract: CD31 is a specific and sensitive marker of endothelial differentiation. Previous reports have described its immunoreactivity in large series of soft tissue neoplasms, as well as its comparison with other available and commonly used endothelial markers. CD31 reactivity in carcinomas or mesotheliomas has been incompletely addressed, however. Hence, we applied anti-CD31 (JC70/A, DAKO, Carpinteria, Calif) to 290 previously characterized neoplasms by using a modified avidin-biotin-peroxidase complex technique following microwave epitope retrieval. Seven carcinomas showed plasmalemmal-based immunoreactivity (2 papillary thyroid carcinomas, 2 mucoepidermoid salivary gland carcinomas, 1 cutaneous adnexal tumor, 1 cutaneous squamous cell carcinoma, and 1 esophageal squamous cell carcinoma); the remaining 283 lesions were negative for this marker. We conclude that anti-CD31 immunostaining in carcinomas and mesotheliomas is rare. These findings support the concept that CD31 is a reliable marker of endothelial differentiation and should be included in diagnostic immunohistochemical panels when vascular tumors enter the differential diagnosis.
TL;DR: An overall assessment of malignancy or the criteria of chromatin clumping, increased nuclear:cytoplasmic ratio, and either nuclear molding or loss of honeycombing are reproducible cytologic criteria that accurately predict malignancies in bile duct brushings.
Abstract: Recent studies based on multivariate analysis have identified cytologic features that may be of value in the diagnosis of malignancy in bile duct brushings. We sought to assess the reproducibility and accuracy of these criteria. Three different observers used 4 sets of criteria that included 9 cytologic features to review 165 bile duct brushing specimens with available follow-up data. An overall assessment of malignancy and evaluation for the presence of chromatin clumping had excellent reproducibility (3-way kappa values of 0.708 and 0.629, respectively). Evaluation for the presence of enlarged nuclei, increased nuclear:cytoplasmic ratio, nuclear molding, and loss of honeycombing showed moderate reproducibility. An overall assessment of malignancy was a better predictor of the presence of malignancy than any other criteria, with a sensitivity of 36.2% and a specificity of 95%. Retrospective analysis demonstrated that the criteria of chromatin clumping, increased nuclear:cytoplasmic ratio, and either nuclear molding or loss of honeycombing had similar sensitivity and specificity as the overall assessment of malignancy (sensitivity = 35.2%, specificity = 95%). An overall assessment of malignancy or the criteria of chromatin clumping, increased nuclear:cytoplasmic ratio, and either nuclear molding or loss of honeycombing are reproducible cytologic criteria that accurately predict malignancy in bile duct brushings.
TL;DR: The TEST 1 was easy to use, had a satisfactory operative practicability required minimal maintenance, and reduced contact with potential biohazards, whereas there was a significant decrease in ESR data when the samples were stored at 4 degrees C for up to 24 hours.
Abstract: We evaluated performance of the TEST 1 (SIRE Analytical Systems, Udine, Italy), a fully automated analyzer for the measurement of the erythrocyte sedimentation rate (ESR). Intra-assay reproducibility was satisfactory for a wide range of ESR values, whereas there was a significant decrease in ESR data when the samples were stored at 4 degrees C for up to 24 hours. We compared TEST 1 with the Westergren ESR method approved by the International Council for Standardization in Haematology (ICSH) and with the Diesse Ves-Matic analyzer Linear regression analysis comparing the TEST 1 and the ICSH reference method yielded satisfactory correlations for K3 EDTA- and sodium citrate-anticoagulated samples. Bland-Altman analysis showed no evidence of a systematic bias between the TEST 1 and the reference method. A close correlation was found between the TEST 1 system and the Diesse Ves-Matic analyzer despite a significant positive systematic bias. Reference values for men and women were analyzed according to nonparametric statistics. The TEST 1 was easy to use, had a satisfactory operative practicability required minimal maintenance, and reduced contact with potential biohazards. This system enables the determination of ESR with any common standard-sized tube; the use of samples anticoagulated with K3 EDTA can widely reduce the workload in clinical laboratories.
TL;DR: Endoscopy is a valuable tool in the diagnosis and management of duodenal lesions and biliary strictures and it complements tissue biopsy in cases of bile duct stricture and cytologic results showed the following sensitivity and specificity.
Abstract: Endoscopy is a valuable tool in the diagnosis and management of duodenal lesions and biliary strictures. We assessed the value of cytology in the evaluation of these lesions and analyzed the causes of discrepancy among clinical, histologic, and cytologic parameters. The study included 118 patients with duodenal ulcers, ampullary neoplasms, or biliary strictures who were examined between 1975 and 1995; 120 cytologic examinations were performed. The specimens included brushings of the duodenum (DB, n = 50), ampulla (AB, n = 32), and biliary ducts (BB, n = 38). Endoscopic biopsies performed concurrently included the duodenum (n = 37), the ampulla (n = 22), and the biliary ducts (n = 23). Comparison of cytologic and histologic results showed the following sensitivity and specificity: DB, 40% and 97%, respectively; AB, 100% each; BB, 75% and 93%, respectively. The DB, AB, and BB revealed malignant neoplasms in 2 of 5, 7 of 7, and 6 of 8 cases, respectively. Twenty-three duodenal neoplasms were diagnosed by either modality and included 11 adenocarcinomas, 9 villous tumors, 2 metastatic renal cell carcinomas, and 1 large cell non-Hodgkin's lymphoma. Endoscopic brush cytology is an effective means of diagnosing ampullary neoplasms, and it complements tissue biopsy in cases of bile duct stricture. Location, predominance of tumor-induced stroma, an extramucosal growth pattern, sampling error, and interpretative experience influence the diagnostic evaluation. Cytologic diagnosis of an adenoma does not exclude an underlying malignant neoplasm in ampullary tumors. In some instances, it may be difficult to distinguish between villous tumors with severe dysplasia and adenocarcinomas by cytology alone.
TL;DR: Reduced E-cadherin expression detected in optimum technical conditions (frozen samples and quantitative immunohistochemistry) is an independent indicator of poor survival in node-negative patients and may be clinically relevant for the treatment of patients with breast carcinomas.
Abstract: E-cadherin immunodetection was performed on frozen sections, using an immunoperoxidase procedure and with computer-assisted analysis of digitized colored microscopic images in a series of 179 breast carcinomas. Quantitative immunocytochemical assays were correlated with follow-up (129 months). The results showed that reduced E-cadherin immunocytochemical expression in tumors (cut point, 4%) significantly correlated with shorter overall survival in node-negative patients (Kaplan Meier log rank test). But E-cadherin immunostained expression (cut point, 4%) did not correlate with metastasis-free or recurrence-free survival. In multivariate analysis (Cox proportional hazards regression model), E-cadherin prognostic significance for overall survival in node-negative patients was independent of the tumor size, grade, and histologic type. The results suggest that reduced E-cadherin expression detected in optimum technical conditions (frozen samples and quantitative immunohistochemistry) is an independent indicator of poor survival in node-negative patients and may be clinically relevant for the treatment of patients with breast carcinomas.
TL;DR: One CD5 antibody clone (CD5/54/B4) specifically identified 30% of thymic carcinomas but also labeled occasional other neoplasms, while the other antibody (clone 4C7) identified 62% of rheumatoid arthritis patients.
Abstract: We studied 109 thymic tumors and 423 other neoplasms for immunocytochemical expression of CD5 in paraffin-embedded tissue using 2 monoclonal antibodies One of the antibodies (clone CD5/54/B4) labeled 7 (29%) of 24 thymic carcinomas but did not stain any of the other neoplasms In contrast, the other antibody (clone 4C7) labeled 15 (62%) of 24 thymic carcinomas, 2 (2%) of 84 thymomas, 3 (8%) of 37 lymphomas, and 14 (4%) of 386 other tumors Among the lymphomas, 4C7 labeled 2 of 4 peripheral T-cell lymphomas and 1 of 4 anaplastic large cell lymphomas Clone 4C7 produced strong labeling of reactive T lymphocytes, whereas CD5/54/B4 staining of these cells was weak or absent No other normal cells seemed to stain with either antibody In conclusion, one CD5 antibody clone (CD5/54/B4) specifically identified 30% of thymic carcinomas The other CD5 antibody (clone 4C7) identified 62% of thymic carcinomas but also labeled occasional other neoplasms
TL;DR: Recommendations for the administration of RhIG, the dose required in various circumstances, prenatal and postnatal serologic testing of the obstetric patient, and the methods used to determine the degree of fetomaternal hemorrhage or the amount of Rh-positive RBCs in the circulation are summarized.
Abstract: The use of Rh immune globulin (RhIG) has dramatically decreased the incidence of hemolytic disease of the fetus and newborn resulting from the production of anti-D by an Rh-negative woman. However, despite the widespread use of RhIG, instances of Rh immunization continue to occur, most likely through failure to administer RhIG when indicated or in the appropriate dose. This utilization gap can be closed only through continued active surveillance by health care providers. The following report summarizes recommendations for the administration of RhIG, the dose required in various circumstances, prenatal and postnatal serologic testing of the obstetric patient, and the methods used to determine the degree of fetomaternal hemorrhage or the amount of Rh-positive RBCs in the circulation.
TL;DR: Results of this study show that cTnI is the better marker for the detection of acute ischemic myocardial injury and increased levels of cTNI can be found in reversible and irreversible myocardials injury in this model.
Abstract: To study the comparative value of the levels of cardiac troponin I (cTnI), creatine kinase-MB isoenzyme (CK-MB), and myoglobin in the detection of acute ischemic myocardial injury, we serially measured plasma concentrations of these cardiac proteins in 12 pigs with myocardial ischemia subtending severe coronary artery stenoses and in 5 pigs with a sham operation performed, but without coronary artery stenosis. In the stenosis group, flow in the left anterior descending (LAD) artery was reduced by 36% and maintained for 24 hours (n = 3), 7 days (n = 6), or 4 weeks (n = 3). Flow in the coronary artery was measured by a flowmeter, and regional left ventricular dysfunction was monitored by echocardiography. Myocardial infarction was identified with triphenyltetrazolium chloride staining. All pigs with stenosis of the LAD had significant ultrastructural abnormalities consisting of loss of myofibrils and an increase in mitochondria and glycogen deposition. Cardiac proteins were released in all pigs with stenosis of the LAD artery during the development of myocardial ischemia; the levels of cTnI, CK-MB, and myoglobin increased significantly relative to the baseline. The sensitivity and specificity for cTnI were higher than for CK-MB or myoglobin. Results of this study show that cTnI is the better marker for the detection of acute ischemic myocardial injury. Increased levels of cTnI can be found in reversible and irreversible myocardial ischemic injury in this model.
TL;DR: Capillary electrophoresis was more sensitive than agarose gel electrophoreis for the identification of monoclonal proteins in serum and the immunosubtraction method seems technically simpler and more automated than immunofixation and represents a useful additional approach for immunotyping monoconal proteins.
Abstract: Capillary zone electrophoresis and immune adsorption were evaluated for identification of serum protein abnormalities and immunotyping of monoclonal proteins. A 7-capillary, electrophoresis instrument and solid phase immunosubtraction reagents were used in a prospective study of 1,518 patients. Serum protein electrophoresis was performed by agarose gel electrophoresis and capillary electrophoresis and interpreted with regard to identification of abnormalities consistent with monoclonal gammopathies. The agarose gel electrophoresis had a sensitivity and specificity of 91% and 99%, respectively, whereas capillary electrophoresis gave results of 95% and 99%. Immunotyping of the monoclonal proteins was performed by immunofixation and immunosubtraction. Capillary electrophoresis was more sensitive than agarose gel electrophoresis for the identification of monoclonal proteins in serum. In addition, the immunosubtraction method seems technically simpler and more automated than immunofixation and represents a useful additional approach for immunotyping monoclonal proteins.