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The IgG1 monoclonal antibody, 44-3A6, was raised against the human lung adenocarcinoma cell line, A549. It has been shown to react with a 40,000 MW protein found on the cell surface, which is preserved in formalin-fixed paraffin-embedded tissues. A recent study of pulmonary carcinomas utilizing immunohistochemical methods showed exclusive binding to lung adenocarcinomas, subsets of neuroendocrine tumors, some carcinoids and a subset of large cell carcinomas. Reactivity was not seen in squamous cell carcinomas and small cell neuroendocrine carcinomas. In addition, melanomas, sarcomas and hematologic malignancies do not express this antigen. We now report on the reactivity pattern of 44-3A6 in adenocarcinomas of nonpulmonary primary sites and in normal adult organs. Strong diffuse staining of neoplastic cells in adenocarcinomas of the stomach, colon, pancreas, gallbladder and breast was noted. Adenocarcinomas arising in the endometrium, ovary, kidney, prostate, thyroid and liver were either negative or showed weak and/or focal reactivity. Strong staining patterns were even noted in adenocarcinomas which had an 'undiffer-entiated' component; i.e., lacking well-defined glandular elements.Immunoreactivity was noted in epithelial cells in several tissues from which these adenocarcinomas arose including the bronchial tract, stomach, small intestine, pancreas and colon, whereas epithelial cells from the endometrium, kidney, ovary, prostate and thyroid were negative or showed diffuse weak immunoreactivity. Our findings indicate that monoclonal antibody 44-3A6 recognizes an epithelial antigen on subsets of normal as well as transformed glandular epithelia. The differential pattern of expression of its target antigen probably reflects differences in tumor genesis and/or differentiation. Copyright © 1988 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Pseudosarcoma of the oesophagus previously has been well documented in only six patients. The present case history illustrates the characteristics originally described by Stout of a polypoid lesion composed of sarcoma-like cells adjacent to squamous cell carcinoma. Earlier reports have postulated that the sarcomatous cells represent an unusual stromal proliferation in response to the adjacent squamous cell carcinoma. Another theory has been that the two cellular elements represent two separate lesions occurring coincidentally. Routine microscopic examination of the present lesion revealed it to be composed principally of pleomorphic spindle-shaped cells with areas of larger, more rounded cells resembling squamous carcinoma. However, electron microscopic examination of this tumour revealed that the sarcomatous cells contained tonofibrils and particularly desmosome-associated tonofibrils. These findings, we believe, definitely establish that the sarcoma-like cells originate from squamous epithelium. It is postulated that cells of both the sarcomatous and carcinomatous elements may be derived from the basal elements of the epithelium and this may account for the relatively benign clinical behaviour of this tumour. [ABSTRACT FROM PUBLISHER]

This article focuses on immulogical aspects of goodpasture's syndrome. Goodpasture's syndrome, now recognized as a distinct clinical-pathological entity usually affecting young men, is a characterized by initial haemoptysis, pulmonary infiltration anemia, renal failure and a rapidly fatal course. Some cases have been shown to fellow a viral infection. Pulmonary haemorrhage, interstitial pneumonitis and severe glomerulonephritis are the typical autopsy findings. The demonstration of disposition of 7-globulin in the glomerular basement membrane suggested that an immunological mechanism might be responsible for the renal manifestations of the disorder.

Presents a case study of a patient with Gaucher's disease who developed bleeding secondary to thrombocytopenia. Clinical presentation of the patient; Analysis of platelet survival and sequestration; Types of Gaucher's disease; Incidence of thrombocytopenia related to Gaucher's disease.

Background: Cognitive dysfunction due to delirium or dementia is a common finding in acutely ill geriatric patients, but often remains undetected. A brief and sensitive clinical identification method could prevent errors or complications while evaluating the mental status of elderly patients., Aims: To evaluate the usefulness and clinical implications of the revised simplified short-term memory recall test (STMT-R) in geriatric patients admitted in the emergency department; with age, gender, dementia history, serum albumin, underlying diseases and clinical outcome used as comparative factors., Methods: Mini-mental state examination and STMT-R scores were initially compared and a positive correlation was observed (r = 0.66, p < 0.001). Subsequently, 885 inpatients aged over 50 years underwent STMT-R evaluation between October 2014 and September 2015. We considered as cognitive dysfunction STMT-R scores ≤ 4 of a maximum score of 8., Results: Among enrolled patients, 52.2% were female and the mean age was 78.9 years. There were 159 patients who were unable to complete the test (incomplete testing group). We observed cognitive dysfunction in 460 patients, while 266 did not have cognitive dysfunction. There were significant differences between those with and without cognitive dysfunction in terms of age, dementia history, underlying respiratory diseases, and hospital outcome., Conclusion: Cognitive dysfunction at admission can have a negative effect on the hospital outcomes of elderly patients. Age, a history of dementia and underlying respiratory diseases may also influence cognitive functional decline.

We evaluated the sensitivity and specificity of 10 monoclonal and two polyclonal antibodies for distinguishing epithelioid mesothelioma from adenocarcinoma (AdCA) using immunohistochemistry (IHC). The antibodies were directed against the mesothelial-associated antigens mesothelin, calretinin, cytokeratin 5, thrombomodulin, Wilms' tumor-1 (WT-1) gene product and HBME-1, and the nonmesothelial antigens Lewis-Y blood group (antibody BG8), MOC-31, BerEp4, CD15, and carcinoembryonic antigen (CEA) family. The 133 tumors evaluated included 65 malignant epithelioid mesotheliomas, 22 lung AdCAs, 27 ovarian serous carcinomas, 24 breast carcinomas, and five gastric carcinomas. Diagnoses were based on clinical, histologic, ultrastructural, and/or IHC findings. Calretinin had the best sensitivity for mesothelioma (95%), followed by HBME-1 (84%), WT-1 (78%), cytokeratin 5 (76%), mesothelin (75%), and vimentin and thrombomodulin (68%). Thrombomodulin had the best specificity for mesothelioma (92%), followed by cytokeratin 5 (89%), calretinin (87%) vimentin (84%), and HBME-1 (45%). When ovarian carcinomas were excluded from the analysis, the specificity of mesothelin and WT-1 for the diagnosis of mesothelioma increased to 90 and 81%, respectively. The sensitivity of the nonmesothelial antigens for AdCA was organ dependent, with BG8 performing best in the breast cancer group (96%), and BerEp4, BG8, MOC-31 performing best in the lung cancer group (100%). The specificity of the nonmesothelial antigens for AdCA was 98% for BG8 and CEA, 97% for CD15, 95% for BerEp4, and 87% for MOC-31. A novel statistical analysis technique employing logic regression analysis identified a three-antibody immunohistochemical panel including calretinin, BG8, and MOC-31, which provided over 96% sensitivity and specificity for distinguishing epithelioid mesothelioma from AdCA.

Despite the fact that immunohistochemistry is widely used in routine diagnostic work and is a very common part of scientific reports in pathology and cytology, its standardization still lags behind. Interpretation of immunostains should be based on microanatomic distribution of the staining, proportion of positively stained cells, staining intensity, if relevant, and cutoff levels. These parameters should be shown to be reasonably reproducible and should be clearly defined in publications. Uniformity in the setting of thresholds could probably benefit from interlaboratory control materials containing defined amounts of the target antigen. Reliable and precise quantitative immunohistochemistry requires the use of control materials containing defined amounts of the target antigen and processed alongside the specimen combined with automated computer-assisted microspectrophotometry. Application of these suggestions is hoped to improve standardization and to facilitate communication in the field of immunohistochemistry.

Although immunohistochemistry is routinely performed by many pathology laboratories, its standardization still lags behind. A major cause of variation in the reproducibility of immunohistochemical staining is induced by tissue fixation and, to a lesser degree, tissue processing. This report, stemming from the first meeting of the International Consensus Group on Standardization and Quality Control (ICGSQC) in Nice, France, summarizes the problem and suggests solutions to begin to achieve standardization of fixation and processing. Most laboratories use neutral-buffered formalin (10%) for tissue fixation which introduces cross-links, whereas coagulative fixatives are less popular. Problems with formalin fixation comprise delay of fixation and variations in the duration of the fixation mainly. Solutions to these problems could be to start fixation soon (<30 min) after surgical removal of the tissue and to avoid overfixation (>24-48 hrs). For tissue processing, the most important problem is inadequate tissue dehydration prior to paraffin embedding. This can be prevented by preparing all solutions freshly every week, depending on the volume of tissue processed. If consistently applied, these procedures could eliminate some of the sources of variation in immunohistochemical stains.

Three cases of lympho-histiocytoid mesothelioma, a rare variant of pleural sarcomatoid malignant mesothelioma, are described. Histologically, the neoplasms were characterized by a diffuse discohesive proliferation of atypical histiocytoid cells intermixed with a marked lymphocytic and lesser plasmacytic infiltrate. One case initially was misdiagnosed as a ganglioneuroma, a second case was misinterpreted as malignant lymphoma, and a third case was sent in consultation with the differential diagnosis of inflammatory pseudotumor vs mesothelioma. Immunohistochemical studies showed strong and generalized expression of cytokeratins and vimentin by the neoplastic histiocytoid cells in all 3 cases. Two cases were positive for calretinin, one of which also was positive for HBME-1, thrombomodulin, and LeuM1. None of the cases stained with the epithelial glycoprotein markers carcinoembryonic antigen, B72.3, and Ber-EP4, or the blood group antigen, BG-8. The immunophenotype of the lymphoplasmacytic infiltrate revealed predominantly reactive, mature T cells, with fewer polytypic plasma cells, histiocytes, and B cells. In lymphohistiocytoid mesothelioma, as in the usual examples of sarcomatoid mesothelioma, the demonstration of cytokeratin expression by the neoplastic cells is the most useful diagnostic finding that allows exclusion of other neoplasms with which this entity may be confused.

Two cases of pleomorphic angiomyolipoma (AML) composed of bizarre epithelioid smooth muscle cells located in the gastrointestinal tract are reported. One involved the appendix of a 6-year-old girl, and the second the cecum of a 22-year-old woman. In both instances the tumor cells were immunoreactive for HMB-45 and A103. To the best of our knowledge, this peculiar variant of an AML has not previously been recognized in this location. Int J Surg Pathol 8(1):67-72, 2000

We report 2 cases of follicle center non-Hodgkin lymphoma (NHL) and Warthin tumor involving the same site. Case 1 is a 68-year-old woman with Warthin tumor and grade 1 follicular NHL involving a periparotid lymph node. She had localized NHL and was treated with radiation therapy; dissemination developed 54 months later. Case 2 is a 55-year-old man with a 17-year history of a parotid mass with gradual enlargement during the last 5 years. Surgical excision revealed Warthin tumor and grade 1 follicular NHL involving the right parotid gland and surrounding lymph nodes. Immunohistochemical studies supported the diagnosis of NHL in both cases; the neoplasms were positive for CD20 and BCL-2 and negative for CD3. Polymerase chain reaction analysis done on paraffinembedded tissue of case 1 revealed monoclonal immunoglobulin heavy chain gene rearrangement and bcl-2/JH fusion DNA sequences diagnostic of the t(14;18)(q32;q21). The small size of the Warthin tumor in case 1, clearly arising in lymph node, supports the hypothesis that Warthin tumor arises from heterotopic salivary gland ducts within lymph nodes. The localized NHL in both patients suggests that the NHL initially arose in the lymph node involved by Warthin tumor, and, thus, the Warthin tumor may have provided a source of long-term antigenic stimulation from which a monoclonal B-cell population subsequently arose.

Variation in tissue fixation, processing, and staining is largely responsible for poor reproducibility of estrogen receptor (ER) immunohistochemistry assays. A frozen, agar-suspended pellet of MCF-7 cells with known ER content was added to each of 55 samples of invasive breast carcinoma (IBC), serving as a control. Image analysis determined percentages of positive area (positive nuclei per total nuclei analyzed) and positive stain (sum of optical density of the positive nuclear area divided by sum of the optical density of all nuclei studied) of MCF-7 cells and IBC. MCF-7 cells had a mean value of 150 fmol/mg of ER by dextran-coated charcoal analysis. Image analysis of MCF-7 cells included with the 55 cases showed a mean positive area of 70.81. Positive staining from the IBC cases ranged from 0 to 98.5. By using the known ER content and the positive area of the MCF-7 cells, a conversion factor was used to translate the positive area of the clinical specimens to a femtomole equivalent, which for the 55 IBCs ranged from 0 to 1,790 (mean, 187). Inclusion of a control with known femtomole quantity of ER provides an internal standard for quality control and ER quantitation.

The CD5 antigen is a T-cell associated marker that is also usually expressed by two B-cell neoplasms, chronic lymphocytic leukemia/small lymphocytic lymphoma and mantle cell lymphoma. We observed CD5 antigen expression in a subset of cases of intravascular large B-cell lymphoma (IVLBL), and we report here five cases. The patients, two men and three women, ranged in age from 59 to 81 years. Biopsy specimens were obtained from kidney, lung, bone marrow, abdominal wall, and neck, the latter involving a lymphangioma. All of the cases had histologic features typical of IVLBL, with large and atypical lymphoid cells located predominantly within blood vessels. Immunohistochemical studies performed using routinely fixed, paraffin-embedded tissue sections showed that the neoplastic cells were B cells, positive for the CD20 antigen and negative for the CD3 or CD43 antigens. All cases were also positive for the CD5 antigen. One case had an immunoglobulin heavy chain gene rearrangement shown by using a polymerase chain reaction method. The finding of CD5 antigen expression in a subset of IVLBL cases adds to other evidence in the literature suggesting that IVLBL is a heterogeneous entity. We considered the possibility that these cases were related to or represented unusual histologic forms of transformation from either chronic lymphocytic leukemia/small lymphocytic lymphoma or mantle cell lymphoma. All of the cases, however, were negative for the CD23 antigen and cyclin D1 (bcl-1) protein, which is evidence against this interpretation. The biologic significance of CD5 antigen expression in cases of IVLBL is uncertain. These neoplasms might arise from a separate lineage of CD5-positive B cells or from a specific, early stage of B-cell differentiation. Alternatively, some investigators have suggested that CD5 antigen expression by B cells is a marker of activation.