Showing papers in "American Journal of Clinical Pathology in 1983"

Role of Antibody to S100 Protein in Diagnostic Pathology

Abstract: Normal tissues and various tumors were examined for S100 protein, using anti-S100 protein antiserum, in an immunoperoxidase reaction. Among normal tissues, in addition to the previously reported presence of S100 protein in some neurons, glial, and Schwann cells of the nervous system, melanocytes and Langerhans cells of the skin, interdigitating reticulum cells of lymph nodes, and chondrocytes, we demonstrated it in myoepithelial cells and ducts of sweat glands, salivary glands, and the breast, serous glands of the lung, fetal neuroblasts, and sustentacular cells of the adrenal medulla. Among neoplasms, S100 protein previously has been reported in neurogenic tumors, melanomas, and neuroblastomas; we have demonstrated it in mixed sweat gland tumors, histiocytosis X, pleomorphic adenomas of the salivary gland, medullary carcinomas of the breast, bronchioloalveolar carcinomas of the lung, sustentacular cells of pheochromocytomas, teratomas of the ovary, and tumors of cartilage (enchondromas, osteochondromas, and chondrosarcomas). With S100 protein producing tumors, a normal progenitor cell was identified, indicating that demonstration of S100 protein in tumors confirmed their origin.

Improved Classification of Anemias by MCV and RDW

Abstract: New automated blood cell analyzers provide an index of red cell volume distribution width (RDW) or heterogeneity and a histogram display of red cell volume distribution We have developed a classification of red cell disorders, based on mean corpuscular volume (MCV) or red cell size, heterogeneity, and histograms, to guide diagnosis from the peripheral blood analysis The distinction of iron deficiency anemia from heterozygous thalassemia or the anemia of chronic disease and the detection of early iron and folate deficiency is improved Red cell volume distribution histograms identify red cell fragmentation or agglutination, dimorphic populations, and artifactual counting of lymphocytes as red cells We recommend the use of these new variables in the initial classification of anemia by the practicing physician

Immunopathologic characterization of a monoclonal antibody that recognizes common surface antigens of human ovarian tumors of serous, endometrioid, and clear cell types.

Abstract: A murine monoclonal antibody, OC125, reacts with a surface component of ovarian tumor cells from humans, but fails to react with normal adult ovarian cells. The spectrum of reactivity of OC125 in ovarian tumors from humans was defined by testing cryostat tissue sections from 60 selected ovarian tumors by indirect immunofluorescence. OC125 stained 7/7 benign, and borderline serous ovarian tumors, 19/23 (83%) serous adenocarcinomas, 2/2 mixed serous and endometrioid carcinomas, 2/3 endometrioid carcinomas, 1/4 clear cell carcinomas, and 2/2 undifferentiated carcinomas. No reactivity was found in eight mucinous ovarian tumors or any of the other 11 epithelial sex cord, germ cell, on hematopoietic tumors tested. In neoplastic cysts, papillae, and glands, the staining was most intense on the luminal surface or in subjacent cytoplasm. Cells in solid sheets also showed peripheral staining. Within a reactive tumor, both negative and positive cells could be found, intimately intermixed. There were no differences in these staining patterns between tissues from primary and metastatic sites. The expression of the OC125 antigen was not related to the degree of malignancy as judged by pathologic criteria. Although mucinous tumors lacked reactivity with OC125, seven of eight mucinous adenomas and adenocarcinomas bound a monoclonal antibody against carcinoembryonic antigen (CEA). Thus, OC125 recognizes a common antigen in some but not all ovarian tumors of serous, clear cell, endometrioid, or undifferentiated type. OC125 may prove useful in the pathologic and cytologic identification of certain types of ovarian tumor cells. Its lack of reactivity with mucinous tumors suggests these belong in a distinct subgroup of ovarian epithelial tumors.

An atypical subcutaneous infection associated with acquired immune deficiency syndrome.

Abstract: Cases of acquired immune deficiency syndrome (AIDS) continue to be reported at an alarming rate. As the numbers of cases increase, so too does the list of unusual manifestations associated with this syndrome. We report here a patient with AIDS who, during his clinical course, had a previously undescribed, histologically atypical, subcutaneous infection develop. Light microscopic, electron microscopic, and microbiologic data are presented. The cause and pathogenesis of this lesion are discussed.

Laboratory Diagnosis of Lupus Inhibitors: A Comparison of the Tissue Thromboplastin Inhibition Procedure with a New Platelet Neutralization Procedure

Abstract: The introduction of the activated partial thromboplastin time (APTT) as a screening test has resulted in increased recognition of circulating anticoagulants. The most frequently encountered inhibitor is the lupus-type anticoagulant. However, criteria for differentiation of this inhibitor are not well-established. We evaluated the ability of two procedures, tissue thromboplastin inhibition (TTI) and a new platelet neutralization procedure (PNP), to differentiate between various types of coagulation inhibitors. The TTI, widely used for the diagnosis of lupus anticoagulants, proved to be nonspecific. The PNP specifically separated lupus-type inhibitors from Factor VIII, X, and V inhibitors. The PNP may be a useful test for the diagnosis of lupus anticoagulants.

A High Prevalence of Hypomagnesemia and Hypermagnesemia in Hospitalized Patients

Abstract: The prevalence of hypomagnesemia and hypermagnesemia among hospitalized patients was studied by determining magnesium levels in 621 serum samples randomly selected from those submitted to the clinical chemistry laboratory for a biochemical test panel. The reference range for serum magnesium was established in this study as 1.2 to 1.9 mEq/L from measurements of serum magnesium on 341 healthy volunteers. Hypomagnesemia (less than 1.2 mEq/L) was present in 68 patients or 11.0%, and hypermagnesemia (greater than 1.9 mEq/L) occurred in 58 patients or 9.3%. The degree of association between hypomagnesemia and hypocalcemia was assessed by measuring serum magnesium on a separate group of 61 patients with hypocalcemia (corrected calcium less than 8.6 mg/dL). Hypomagnesemia was present in 23.3% of patients hypocalcemic in the absence of renal failure; this proportion was higher significantly than the 11.0% who were hypomagnesemic in the hospitalized patient group (P less than 0.025).

Ulex europaeus I lectin as a marker for tumors derived from endothelial cells.

Abstract: Some skin and soft tumors, which generally are assumed to be derived from endothelial cells or blood vessels, were characterized with fluorochrome-labeled Ulex europaeus I agglutinin (UEA I), recently shown to bind specifically to endothelial cells in various normal human tissues. The staining pattern was compared with that obtained with immunostaining using antibodies against factor-VIII-related antigen (FVIII-RAG), a known marker for endothelial cells. The results showed that UEA-I is a specific and a more sensitive marker for the endothelial cells in benign vascular lesions as compared with anti-FVIII-RAG. UEA-I also stained many neoplastic cells of endothelial sarcomas, which generally were negative for FVIII-RAG. Melanomas, anaplastic carcinomas, and other types of sarcomas were negative for both UEA-I and FVIII-RAG. The results suggest that UEA-I lectin is a specific and sensitive adjunct tool in demonstrating endothelial cells and endothelial derivation of human tumors.

Lymphocyte Subsets in Normal Human Lymphoid Tissues

Abstract: A series of B, T, natural killer (NK) cell, and monocyte-specific monoclonal antibodies was used to determine the localization of lymphocyte subpopulations in frozen tissue sections of human lymph node, spleen, tonsil, and thymus by means of an immunohistochemical technic. In thymus, most cortical thymocytes reacted with Leu 1, Leu 2a, Leu 3a, Leu 4, Lyt 3, OKT3, and OKT6 antibodies. Except for OKT6, Leu 2a, and Leu 3a, these antibodies also reacted with medullary thymocytes. The majority (70-80%) of medullary thymocytes reacted with Leu 3a and a smaller fraction (20-30%) with Leu 2a antibody. The staining pattern of thymic medulla approximates the staining pattern of peripheral T cells. In peripheral lymphoid tissues, the majority of cells in the paracortical region of lymph node and in the periarteriolar sheath of spleen stained with Leu 1, Leu 4, OKT3, and Lyt 3 antibodies. Staining with Leu 3a and Leu 2a identified 60-80% and 20-40% of total T cells, respectively, as defined by Lyt 3 positivity. In addition, a substantial number of Leu 3a+ and Leu 7+ cells were found in the germinal centers of secondary follicles. This finding supports the importance of these subsets of lymphocytes in regulation of the human immune response. Leu 2a+ cells were rare in tissues with prominent follicular hyperplasia, but appeared in considerable number in the red pulp of spleen. In the mantle zone of lymphoid follicles, the majority of lymphocytes were positive for IgM, IgD, and B1. Approximately 60-70% of these cells bore kappa chain and 30-40% lambda chain immunoglobulin. The extracellular substance in germinal centers was positive for B1, IgG, IgM, kappa, and lambda. The majority of germinal center cells appeared to contain no surface or cytoplasmic immunoglobulins. Small mononuclear cells bearing OKM1 marker were abundant in the marginal zone of white pulp and in the red pulp of spleen but, rarely were observed in other portions of lymphoid tissues. OKM1 also reacted with granulocytes. Leu 7+ (NK) cells were rare in the thymus, but frequent in the GC of secondary follicles. The distribution of Leu 7+ cells did not correspond to staining with Lyt 3 and Leu 2a.

Primary Neuroendocrine Carcinomas of the Skin (Merkel Cell Tumors): A Clinical, Histologic, and Ultrastructural Study of Thirteen Cases

Abstract: Neuroendocrine carcinomas of the skin have recently been recognized, and clinicopathologic information on these tumors is accumulating rapidly. We studied 13 such lesions by light and electron microscopy, and eight were subjected to immunohistochemical analysis. The ages of the patients (five women and eight men) ranged from 24 to 84 years. Nine patients had neoplasms occurring in sun-exposed areas; one patient had metachronous symmetric lesions on the arms, and another had antecedent hypohidrotic ectodermal dysplasia. Eight tumors metastasized, and six spread to regional or distant lymph nodes. Three patients died with visceral metastases to the liver, bones, and brain. All patients had their primary tumor confined to the corium and subcutaneous tissue without involvement of overlying epidermis. Tumor cells were round and uniform in size, with delicate nuclear chromatin and a high mitotic rate. An organoid growth pattern was seen in all tumors, with focal trabeculation and rare rosette formation. Ultrastructurally, peripheral cytoplasmic dense-core granules were evident, and perinuclear filament whorls could be seen in all 13 tumors. The latter feature was stable, even in specimens taken from paraffin blocks for electron microscopy. Immunoperoxidase studies failed to reveal serotonin, calcitonin, or adrenocorticotrophin within tumor cells.

An Immunoperoxidase Investigation of S-100 Protein in Granular Cell Myoblastomas: Evidence for Schwann Cell Derivation

Abstract: Five cases of granular cell myoblastoma have been studied for detection of the neuroectodermal protein S-100. Immunoperoxidase staining on paraffin sections, using an antibody raised against calf brain S-100 protein, was utilized to demonstrate positive cytoplasmic and nuclear reactivity in all cases. Negative staining in adjacent muscle and connective tissue elements was contrasted to in situ control staining of Schwann cells in peripheral nerves and staining of Langerhans cells and melanocytes in overlying stratified epithelia. These observations are interpreted as support for possible Schwann cell origin of granular cell myoblastomas.

The use of antikeratin antibodies in the diagnosis of human neoplasms.

Abstract: The presence of intracellular keratin was examined in 230 human neoplasms using indirect immunofluorescence on fresh frozen, acetone-fixed sections. The use of antikeratin antibodies raised in rabbits against human callus and purified by affinity chromatography proved to be a rapid, sensitive, and reliable method of demonstrating keratin. Epithelial tissues and epithelial-derived neoplasms were found to contain keratin, whereas tissues and neoplasms of mesenchymal, lymphoreticular, or neural crest origin did not contain intracellular keratin. This technic is a useful adjunct for the surgical pathologist in the diagnosis of poorly differentiated neoplasms. Its application either confirmed, modified, or in several instances, changed the original light microscopic impression. The modified or changed diagnoses were confirmed by transmission electron microscopy.

Definition of Clinically Relevant Lactic Acidosis in Patients with Internal Diseases

Abstract: In order to define clinically relevant lactic acidosis, 12 biochemical variables, eight clinical symptoms and signs, leading diagnoses, and mortality were evaluated prospectively in approximately 2,000 unselected patients with internal diseases, consecutively admitted to the hospital. Patients with incomplete data sets were not considered. Of those patients who repeatedly were admitted to the hospital during the time of the study, only the first admission was included for statistical analysis. In addition to 11 definitions of lactic acidosis given in the literature, sequential cluster analyses of the biochemical variables were used to estimate the incidence of lactic acidosis in 1,467 patients. Depending upon which definition was used, 0.5-3.8% of all patients were classified as suffering from lactic acidosis, with a mortality rate ranging from 30-88%. From this study it is concluded that a limit of less than or equal to 7.35 for pH and of greater than 5-6 mmol/L for the concentration of lactate in whole blood will minimize false-negative or false-positive classifications.

Heterogeneity of serum creatine kinase activity among racial and gender groups of the population.

Abstract: To develop reference ranges for creatine kinase (CK) appropriate for the patient population served by this hospital, levels of serum CK were measured in 1,537 individuals in our employee population. There was substantial heterogeneity in mean, median, and range of CK levels among the several race/gender subgroups in the population studied. The race/gender subgroups could be placed into three broad groups: a high CK group, composed solely of black men; an intermediate CK group, consisting of nonblack men plus black women; and a low CK group, comprised of nonblack women. Mean CK level of the high CK group was twice that of the intermediate CK group, which, in turn, was twice that of the low CK group. Differences in mean CK values among the subgroups placed into either the intermediate CK group or the low CK group were not significant when tested with analysis of variance. Therefore, practical reference ranges for these groups are as follows: 52-520 U/L for the high CK group; 35-345 U/L for the intermediate CK group; and 25-145 U/L for the low CK group.

Lymphadenopathy in Homosexual Men. Morbid Anatomy with Clinical and Immunologic Correlations

Abstract: This is a study of the histopathologic features of lymph nodes removed from eleven young, homosexual men, all of whom presented with lymph node enlargement of more than 3 months' duration, accompanied, in the majority of cases, by fever and weight loss. Reactive follicular and sinusoidal hyperplasia were the main findings in 10 patients. The medullary sinuses were packed with monomorphic round sinusoidal cells associated with neutrophils. In one of the 10 patients, granulomas packed the subcapsular sinuses, especially. Another patient presented with lymphoid-depleted nodes with absent germinal centers and a prominent vascular skeleton; this latter feature made it difficult to distinguish this picture from the nodal form of Kaposi's sarcoma. All patients had a history of sexual promiscuity and used "recreational" drugs. Nine of 10 patients had deficient cellular immunity and inverted T-cell helper/suppressor ratios. The only patient with normal cellular immunity had nodal granulomas. Humoral immunity was normal in all patients.

Selective IgA deficiency in blood donors

Abstract: The frequency of selective IgA deficiency was determined in a healthy population of 6,240 blood donors. Screening for IgA deficiency was performed by double-diffusion analysis in agarose gel. Confirmation testing was performed with the more sensitive passive hemagglutination inhibition assay. Prevalence of IgA deficiency, characterized by a serum level of below 50 mg/L, was 0.30% (1 in 328), which is the highest prevalence of selective IgA deficiency reported in a healthy population. Antibodies to IgA were detected in sera of 36.8% of the blood donors with selective IgA deficiency, which also is the highest prevalence of anti-IgA antibodies reported in any previous study. The literature on IgA deficiency in healthy populations is reviewed. Current concepts in treatment of IgA-deficient patients requiring blood products are described.

The Role of Anticoagulation in the Measurement of Platelet Volumes.

Abstract: The effect of anticoagulation on platelet size stability was studied using blood collected in seven different anticoagulants and stored at room temperature for up to eight hours. The mean platelet volume (MPV) value was most stable in blood collected in 15% ACD and ACD/Na2EDTA. In blood collected in Na2EDTA, K3EDTA, or 11.9% ACD, there was an increase in MPV in the first two hours, after which the MPVs remained stable up to eight hours. Sodium citrate and heparin proved unreliable for the measurement of platelet volume. Platelet counts were stable (less than 5% variation) in all anticoagulants except heparin, which had 16% variation for the eight hours of study. Simultaneously, RBC counts and mean corpuscular volume (MCV) measurements were stable in all seven anticoagulants, with sodium citrate producing the most variation. A negative correlation was observed between MCV and pH of the anticoagulated blood. WBC counts showed less than 3% variation in all anticoagulants except sodium citrate and heparin. Separate experiments demonstrated that electrolyte composition, pH, tonicity, and method of calcium chelation all influenced the stability of the MPV. Of the anticoagulants studied, ACD/Na2 EDTA appeared to provide the best conditions of anticoagulation for both routine clinical and research laboratory measurement of the MPV. It inhibited platelet activation but left the platelets in their normal discoid shape. Platelets could be removed from the anticoagulant and studied in functional assays for up to eight hours after blood drawing. Both platelet counts and MPVs remained stable in blood collected in ACD/Na2 EDTA anticoagulant for up to eight hours at room temperature. In 52 volunteers studied, an inverse correlation (r = -0.72, P less than 0.001) was observed between platelet count and MPV, suggesting that the circulating platelet mass may be a more important indicator of platelet homeostasis than either the platelet count or the mean platelet volume alone.

Histiocytosis-X: in situ characterization of cutaneous infiltrates with monoclonal antibodies.

Abstract: Cutaneous lesions in three cases of histiocytosis-X were studied by light microscopy, electron microscopy, and immunoperoxidase technics. In each case, Birbeck granule-containing histiocytosis-X cells infiltrated the epidermis and were apposed to lymphocytes. The histiocytosis-X cells and normal Langerhans cells stained with anti-T6 and anti-I1 (Ia-like) antibodies but were negative with anti-T3, anti-T8, anti-M1, and anti-lysozyme antibodies. In addition, the histiocytosis-X cells also stained with anti-T4 antibodies, which react with T-cells associated with helper/inducer phenotype. This study supports the hypothesis that histiocytosis-X cells are abnormal Langerhans cells. The presence of T4/T6-positive cells in cutaneous disease may be a marker for abnormal Langerhans cells.

Cytomegalovirus encephalitis in acquired immunodeficiency syndrome

Abstract: A 38-year-old black man died from acquired immunodeficiency syndrome (AIDS) after a 15-month course. The autopsy revealed a pancolitis and a pneumonia caused by cytomegalovirus (CMV). Exceptionally, there also was a periventricular encephalitis caused by the same organism. Identification of the virus was aided by immunoperoxidase methods.

Neuron-specific enolase in neuroendocrine tumors of the thymus, bronchus, and skin.

Abstract: In order to better define the use of neuron-specific enolase (NSE) as a marker for neuroendocrine neoplasms, we studied 11 thymic carcinoid tumors, three bronchial small-cell carcinomas (all with cutaneous metastases), and 10 trabecular carcinomas of the skin for its presence, using the peroxidase-antiperoxidase (PAP) technic with an antiserum directed at NSE. All 11 carcinoid tumors stained positively, as did two of the bronchial small-cell carcinomas and seven of the trabecular carcinomas. We conclude that PAP staining for NSE content may be a useful adjunct to morphologic analysis in diagnostically identifying the tumors we studied and that our results support the concept of a functionally unified APUD system, as reflected in the tumors originating from it. Nevertheless, because of the vagaries of the PAP method, exemplified by the results in our small series, it cannot be relied upon as a sole indicator that a tumor contains NSE and is therefore neuroendocrine. Also, since it is hypothesized that NSE is present in all tumors of this type, staining for its presence would seem to be of little benefit in distinguishing primary from secondary neuroendocrine tumors or in identifying the origin of metastatic lesions that have a neuroendocrine histologic appearance.

Immunohistochemical Demonstration of Laminin, the Major Glycoprotein of Basement Membranes, as an Aid in the Diagnosis of Soft Tissue Tumors

Abstract: Forty-eight benign and malignant soft tissue tumors were investigated immunohistologically for the presence of laminin, a glycoprotein of basement membranes The results showed intense laminin positivity in schwannomas and neurofibromas and less intense positivity in leiomyomas and leiomyosarcomas, whereas fibrous histiocytomas and fibrosarcomas generally were negative It is suggested that immunohistochemical demonstration of laminin is a valuable aid in the differential diagnosis between tumors derived from fibroblasts and Schwann cells, and a potential aid in the differential diagnosis between tumors originating from fibroblasts and those from smooth muscle cells In addition to the expression seen in the tumors, all vascular walls were positive for laminin Therefore, demonstration of laminin also can be used to examine the vascular pattern of tumors

Disseminated Mycobacterium Avium-intracellulare Infection in Homosexual Men with Acquired Cell-mediated Immunodeficiency: A Histologic and Immunologic Study of Two Cases

Abstract: Disseminated Mycobacterium avium-intracellulare infections were found at autopsy in two homosexual men in whom acquired cell-mediated immunodeficiencies and marked decreases in the subpopulation of lymphocytes expressing the T-helper phenotype were well-studied. The histologic manifestations were similar to those found in lepromatous leprosy, also known to be associated with cell-mediated immunodeficiency. Possible correlations between the cellular immunodeficiency in our patients and an increased susceptibility to Mycobacterium avium-intracellulare infection as well as the unusual histologic manifestation of the mycobacterial infection are examined.

Peripheral T-cell lymphoma: a clinicopathologic study of nine cases.

Abstract: The clinicopathologic features of nine cases of peripheral T-cell lymphoma were analyzed. Although the youngest patient was 18 years old, the median age was 59.8 years. They usually presented with widespread disease and had an aggressive course. Seven have died with a median survival of 10.9 months. Five cases were of mixed cell type, sharing certain histopathologic features that we believe are characteristic of peripheral T-cell lymphomas. Three cases were of large cell type; one was a small cell (PDL) type. This latter patient lived symptom-free without treatment for over 3 years, despite stage III disease. Another patient, whose tumor had nodular sclerosis-like fibrosis, is in complete remission two years after chemotherapy for stage III B disease. Because peripheral T-cell lymphoma is morphologically heterogeneous, it may be clinically heterogeneous as well. We believe that classification according to a modified Rappaport system may clarify possible variations in biologic behavior.

The nature and origin of proliferated bile ductules in alcoholic liver disease.

Abstract: Proliferation of bile ductules is commonly seen in expanded portal tracts and periportal areas in many conditions, including advanced alcoholic liver disease. Such ductules are usually tortuous and irregular and composed of cuboidal cells. They frequently have poorly defined lumens. The epithelial cells are similar to those of normal bile ductules and small bile ducts; however, cells that appear intermediate between duct epithelial cells and hepatocytes are frequently identified by light and electron microscopy. The origin of the ductular cells from hepatocytes may be confirmed by the demonstration of the markers of hepatocytes, such as glycogen and glucose-6-phosphatase activity in some proliferated bile ductules. In addition, alcoholic hyalin is occasionally recognizable in the epithelial cells of bile ductules. The majority of periportal bile ductules appears to have been derived from transformation of hepatic cords rather than multiplication of preexisting bile ducts. The proliferated bile ductules seem to communicate between the bile canaliculi and the interlobular bile ducts.

Reactive lymphoid hyperplasia with single class (monoclonal) surface immunoglobulin.

Abstract: Lymphoid tissues from 12 patients were diagnosed as reactive lymphoid hyperplasia, but surface immunoglobulin studies revealed monoclonal (single class) immunoglobulin staining patterns. Infectious, autoimmune, and immunodeficient conditions were diagnosed on the basis of histology and clinical features. Such surface immunoglobulin restriction has been used as an indicator of a neoplastic lymphoid proliferation, but the cases of these patients, in whom the histologic diagnosis was benign, emphasize the importance of a multiparameter approach to diagnosis. Although at the time of this report none of the patients still available to follow-up study have developed known lymphoid neoplasms, the possibility that monoclonal SIg patterns are a harbinger of neoplastic disease makes continuing follow-up of such patients important.

Bacterial meningitis. Effect of antibiotic treatment on cerebrospinal fluid.

Abstract: The effects of full short-term antibiotic treatment on cerebrospinal fluid (CSF) findings were studied retrospectively in 68 children with acute bacterial meningitis. The features of CSF at admission were compared with those of the CSF obtained after 44-68 hours of therapy. Except in one case with H. influenzae and one case with pneumococcal meningitis, all CSF cultures were negative in the repeat specimen. In three of 16 children with meningococcal meningitis, the CSF glucose levels became normal in the second specimen. In all remaining 65 children, however, full intravenous antibiotic treatment for 44-68 hours did not alter the biochemistry and cytology of the CSF, which retained its "bacterial" character. From these findings it may be discerned that partial antibiotic treatment is even less likely to distort a 'bacterial' CSF.

Cross-reactivity with normal antigens in commercial anti-cea sera, used for immunohistology - the need for tissue controls and absorptions

Abstract: The demonstration of carcinoembryonic antigen (CEA) in serum and in tissue sections may be of value in diagnosis and follow-up of several malignant tumors. Anti-CEA sera, however, cross-react with normal antigens, also present in tumors. The staining patterns of three commercially produced anti-CEA sera were investigated on sections of benign and malignant tissues, using an indirect immunoperoxidase technic. All three anti-CEA sera tested showed cross-reactions. A rapid, simple, and reproducible immunoabsorption was developed. After absorption, the reactivity of the sera with normal colon mucosa and carcinomas of the colon remained positive, whereas sections of benign tissues were negative. Moreover, four of ten breast cancers, positive with unabsorbed antisera, became negative after absorption. These findings stress the importance of immunohistochemical negative and positive controls. The use of well-absorbed commercial anti-CEA sera can lead to more uniform results, exchangeability of results, and a better understanding of the value of this tumor marker.

Renal oncocytoma and its congeners.

Abstract: Although the morphologic criteria for separating renal oncocytomas from renal carcinomas with overlapping features are not established completely, the distinction is crucial because of the marked difference in prognosis. Of the 247 renal carcinomas observed at our hospital since 1947, six had sufficient morphologic features of oncocytoma to pose potential difficulty in diagnosis. We term this group the “congeners of renal oncocytoma.” Both the congeners and our 10 oncocytomas were well-circumscribed tumors, varied considerably in size, and were composed of cells with granular, pink-red cytoplasm. The congeners lacked the diffuse organoid packeting of cells, characteristic of oncocytoma. Additional features that helped separate individual congeners from oncocytomas included yellow-tan rather than brown-red gross color, necrosis, pleomorphism, ballooned cytoplasm, or clear cells. Our studies indicate that some renal carcinomas have fields identical to oncocytoma, and frozen section, needle biopsy, or aspiration cytology from such an area could lead to a misdiagnosis.

The Assessment of Laboratory Tests in the Diagnosis of Acute Appendicitis

Abstract: A comparison of laboratory tests was undertaken in 106 patients admitted to the emergency room with the tentative diagnosis of acute appendicitis and who subsequently underwent appendectomy. The tests examined included the total white blood cell count, manual differential count, cytochemical differential count, and C-reactive protein. The sensitivity, specificity, efficiency, and predictive value of these tests in the diagnosis of acute appendicitis were calculated. The cytochemically determined neutrophil count, when greater than the upper limit of the reference interval of either 75% or 7.88 X 10(9)/L, and the total white blood count greater than the upper limit of the reference interval of 10.5 X 10(9)/L were the single best tests for the diagnosis of acute appendicitis with the highest sensitivities of all tests examined (81-84%). The manual differential count and C-reactive protein showed significantly lower sensitivities. Test combinations also were examined. The combinations consisted of two or more tests joined by an "or" rule, i.e., if any one of the individually linked tests of the combination is above the reference interval, the combination is considered as indicating acute appendicitis. When either of the following test combinations were utilized--(1) total white count greater than 10.5 X 10(9)/L or cytochemical neutrophils greater than either 75% or 7.88 X 10(9)/L or CRP greater than 1.2 mg/dL; (2) total white count greater than 10.5 X 10(9)/L or manual bands greater than either 11% or 1.15 X 10(9)/L or CRP greater than 1.2 mg/dL--the sensitivity of the combination in the diagnosis of acute appendicitis approached 100% with a specificity in the range of 50%. We suggest that these test combinations may be useful in deciding which patients need further observation and reexamination prior to surgery. We also suggest the need for further studies to assess the usefulness of these tests in other types of acute inflammation and infection.

Evaluating the clinical efficacy of laboratory tests.

Abstract: The worth of a laboratory test depends on its ability to answer a clinical question of consequence for patient management. Although the need for formal prospective trials for the evaluation of therapeutic modalities has been widely recognized, relatively little attention has been given to the evaluation of diagnostic modalities. Inadequate test evaluations may result in biased conclusions about test performance. Evaluations of the clinical efficacy of laboratory tests should be formalized and include the following steps: (1) choose subjects who are representative of the clinical population to whom the test is ultimately to be applied; (2) perform all tests being evaluated on all the subjects and all tests on an individual subject at the same point in his clinical course; (3) determine the true answer to the clinical question by rigorous and complete means independent of the test or tests being studied; and (4) evaluate and compare test performance at all decision levels using receiver operating characteristic (ROC) curves.

A Study of Optimal Reaction Conditions for an Assay of the Human Alternative Complement Pathway

Abstract: The optimal conditions for performance of a sensitive functional assay for the human alternative complement pathway were studied. The serum dilution causing 50% lysis of rabbit erythrocytes in magnesium EGTA buffer is designated the APH50 titer. Optimal reaction conditions for the assay were p H 7.2, incubation temperature 37°C, incubation time 60 minutes, and magnesium concentration 0.002 m. Lowering the ionic strength of the buffer from 0.150 m to 0.0125 M increased APH50 titers nearly 2.5-fold, but decreased the reproducibility of titers. Significant fluid-phase conversion of C3 at 37°C in low ionic strength buffer was demonstrated by crossed Immunoelectrophoresis. Using the optimal reaction conditions, in normal ionic strength buffer the mean APH50 ± SD for 45 normal adults was 25.3 ± 5.7 U/mL. Heparin, an inhibitor of the alternative pathway, decreased APH50 by 50% at a concentration of 100 U heparin/mL serum, and totally abolished alternative pathway hemolytic activity at 1,000 U heparin/mL serum, while lowering CH50 titers to a much lesser degree. When increasing doses of zymosan were used for complement activation in vitro , the per cent APH50 depletion at low doses of zymosan was at least twice the per cent depletion of CH50 or antigenic P, B, and C3. A striking dichotomy between nearly complete APH50 depletion and normal or near normal CH50 and hemolytic C4 levels was documented for a human burn patient and for a baboon infused with a lethal dose of Escherichia coli lipopolysaccharide. Therefore, we documented a substantially greater sensitivity of APH50 than of conventional complement determinations for detecting complement consumption by alternative pathway activators.