Specificity of antibody HMB-45.
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Adenocarcinoma↗
Biomedical subjects
G A Herrera
Publications and source records attributed to G A Herrera.
Successful renal transplantation after cyclosporine-associated hemolytic-uremic syndrome following bilateral lung transplantation.
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Adult↗
An autopsy study of the peritoneal cavity from patients on continuous ambulatory peritoneal dialysis.
Sixteen autopsies were performed on patients aged 56 +/- 15 (SD) years who were on continuous ambulatory peritoneal dialysis (CAPD) for 834 +/- 766 (SD) days. Lactate-buffered dialysate and povidone-iodine antiseptic were used in all cases. Multiple peritoneal sections were taken to evaluate peritoneal membrane thickening, inflammation, neovascularization, fibrosis, and adhesions. Peritoneal thickening, inflammation, or adhesions were not related to sex, race, or etiology of renal failure. Time on dialysis was also not a direct determinant of peritoneal adhesions or neovascularization. Peritonitis episodes correlated with chronic peritoneal serosal changes. This study supports the hypothesis that peritoneal alterations in patients on CAPD are related to episodes of peritonitis.
Adult↗
C-erb B-2 amplification in cystic renal disease.
Gene amplification (overexpression) of c-erb B-2 was tested in a variety of cystic renal diseases, renal cell neoplasms (adenomas and carcinomas) and end stage kidneys without cysts. C-erb B-2 encodes a receptor-like protein that shares homology with, but is distinct from the epidermal growth factor (EGF) receptor. A monoclonal antibody that immunoprecipitates a protein of approximately 185 kD from a lysate of NIH/3T3 cells transfected with the c-erb B-2 gene was utilized for testing. Simple renal cysts, cystic renal dysplasia, autosomal recessive polycystic kidney disease (ARPKD), and non-cystic, essentially normal kidneys failed to show c-erb B-2 overexpression. In contrast, autosomal-dominant polycystic kidney disease (ADPKD), acquired (dialysis-associated) cystic disease (ACD), non-cystic end stage kidneys and renal cell neoplasms revealed overexpression of c-erb B-2 with some frequency (40% or more of cases tested). Three cystic disorders revealing c-erb B-2 overexpression also showed platelet-derived growth factors (PDGFs) expression in similar locations (cyst lining and adjacent tubules). Other growth factors [insulin-like growth factor (IGF-I), fibroblast growth factor (FGF) and beta transforming growth factor (TGF beta)] were not noted to be overexpressed in either c-erb B-2 positive or negative cystic diseases. C-erb B-2 may be a marker related to the proliferative/growth capabilities of selected cystic diseases, including potential for associated genesis of benign and malignant renal cell tumors.
Adenoma↗
Soft tissue myofibroblastomas.
Five well-circumscribed solitary soft tissue tumors composed of myofibroblasts are described and termed myofibroblastomas. By light microscopy these lesions are characterized by short, intersecting, or crisscrossing fascicles of spindle cells, sometimes associated with foci of necrosis and/or mitotic activity with less than three mitoses per 10 high power fields. Myofibroblastomas show well-defined myofibroblastic differentiation ultrastructurally with peripheral myofilaments and vimentin, actin, and desmin immunocytochemistry positivity. The five tumors described occurred in patients of various age groups, including one congenital, and in a variety of soft tissue locations. It is important to recognize this benign soft tissue neoplasm to avoid confusion with other soft tissue tumors and to separate this lesion from other myofibromatosis. This study elucidates the spectrum of light microscopic, ultrastructural, and immunocytochemistry findings of soft tissue myofibroblastomas and establishes this soft tissue tumor as a specific clinico-pathologic entity.
Actins↗
HMB-45 detection in adenocarcinomas.
Several studies have suggested that HMB-45 is a specific marker for melanoma, presumably due to its ability to detect a glycoprotein that is present in premelanosomes. The present study was conducted to evaluate whether HMB-45 is an absolutely specific antigenic determinant for melanoma and the role that testing with this antibody has in the differential diagnostic workup of amelanotic melanoma vs adenocarcinoma. Formaldehyde solution-fixed, paraffin-embedded tissue samples from 52 adenocarcinomas (primary or metastatic) and five melanomas (two primary and three metastatic) were immunostained with the use of a commercially available monoclonal antibody (MoAb), ie, HMB-45 (Enzo), a polyclonal antibody to S100 protein, a wide-spectrum keratin polyclonal antibody, and a keratin MoAb, ie, AE1/AE3. Approximately 10% (ie, 9.6%) of the adenocarcinomas (five cases) expressed HMB-45 with varied intensity and distribution. Positive primary tumors (n = 3) included one each from the breast, colon, and kidney; positive metastatic tumors (n = 2) included one each from the breast and endometrium. Fifty-two percent of the adenocarcinomas were positive for S100 protein. One renal carcinoma was negative for both keratins when tested with the AE1/AE3 MoAb and polyclonal antibody (Dako). This was the only adenocarcinoma that was negative when the keratin polyclonal antibody (Dako) was used. All but one additional adenocarcinoma demonstrated keratin expression when the AE1/AE3 MoAb was used for testing. This study showed that HMB-45 is not absolutely specific for melanoma. HMB-45 may react with some adenocarcinomas, at least when tested with the commercially available MoAb (Enzo). This fact, in conjunction with aberrant keratin expression by some melanomas and S100 protein expression by adenocarcinomas and other neoplasms other than melanomas, should be considered when antibody panels are evaluated in the workup of poorly differentiated tumors. However, HMB-45 appears to be the most specific marker that is available at the present time for supporting a diagnosis of melanoma.
Adenocarcinoma↗
Spectrum of glomerular and tubulointerstitial renal lesions associated with monotypical immunoglobulin light chain deposition.
The purpose of this study was to characterize the spectrum of renal lesions associated with plasma cell dyscrasias from a population of patients who had renal disease identified by kidney biopsy. Thirty-six patients (2.6% of 1361 kidney specimens examined over 6 years) had evidence of monotypical light chain with or without concomitant heavy chain deposition. A variety of lesions was found, including (a) AL-amyloid and glomerular nonamyloid light chain deposition manifesting as nodular, membranoproliferative, mesangioproliferative, and "minimal-change" glomerulopathies; (b) fibrillary glomerulopathy; (c) tubulointerstitial lesions (cast nephropathy, acute tubular necrosis, and tubulointerstitial nephritis); and (d) vascular (arterioles and small and medium-sized arteries) lesions. AL-amyloid was the most common renal lesion (39%), nonamyloid deposition occurred second most commonly (33%), and cast nephropathy ("myeloma kidney") was third most frequent (14%). Clinical and laboratory manifestations of a plasma cell dyscrasia were frequently subtle. Immunoelectrophoresis of both serum and urine did not demonstrate a monotypical light chain or immunoglobulin in almost 35% of this population. Thus, the correct diagnosis was not considered in the majority of these patients before biopsy. Progressive deterioration of renal function was common with all of the lesions, except for proximal tubule injury, which tended to improve over the period of study. Renal biopsy with careful examination for monotypical light chain with or without associated heavy chain deposition using immunofluorescence or immunoelectron microscopy was crucial in identifying and characterizing the varied lesions associated with lymphoplasmacytic disorders.
Amyloid↗
Light microscopic, ultrastructural and immunocytochemical spectrum of malignant lacrimal and salivary gland tumors, including malignant mixed tumors.
Ten malignant myoepithelial tumors of the salivary glands and one of lacrimal gland origin were studied by light, electron microscopy and immunocytochemistry. The light microscopic appearance of the tumors varied from primarily spindle cell neoplasms (two cases), to others with predominantly epithelial components (four cases) and mixed varieties (five cases). Therefore, they can be confused with other epithelial and mesenchymal neoplasms. The electron microscopic spectrum varied from tumors with widespread and typical myoepithelial differentiation (i.e. myofilament bundles at the cell periphery, attachment plaques and intercellular junctions) to some with diffusely distributed filaments, without associated spindle densities but with attachment plaques, and others with evidence of duct formation and containing scattered cells showing intracytoplasmic tonofilaments. Often the tumors revealed mixed ultrastructural features; the relative numbers of the different cellular components was variable. The eleven neoplasms were S-100 protein, actin and keratin positive, either focally or diffusely, with varying degrees of intensity. Ten of the eleven tumors were positive for vimentin and nine of ten tested expressed carcinoembryonic antigen. Only two of nine were focally positive for glial fibrillary acidic protein. The study emphasizes the variable light microscopic appearances of these neoplasms and their immunocytochemical and ultrastructural spectrum. Accurate determination of myoepithelial differentiation sometimes requires careful evaluation of the light, ultrastructural and immunocytochemical findings. If all three diagnostic modalities are not utilized, it is likely that some of these neoplasms will be improperly classified.
Actin Cytoskeleton↗
Tumor of the atrioventricular nodal region. A clinical and immunohistochemical study.
Autopsy specimens of 17 tumors of the atrioventricular nodal region were studied. Sudden death occurred in 14 children and adults; seven of these patients had a history of atrioventricular block or syncope. Three tumors were incidental findings in infants with other congenital anomalies; diaphragmatic agenesis, pulmonary hypoplasia, and Meckel's diverticulum in one patient; mitral atresia in one; and congenital hydrocephalus, ventricular septal defect, patent ductus arteriosus, coarctation of the aorta, and patent omphalovitelline duct in the third. Immunohistochemical stains demonstrated strong positivity for carcinoembryonic antigen in 13 of 13 cases, B72.3 antigen in 5 of 7 cases, and cytokeratin in 11 of 11 cases. Twenty control cases of mesothelioma and mesothelial hyperplasia were all negative for B72.3; one showed focal carcinoembryonic antigen staining. Ultrastructural analysis of one case demonstrated short rudimentary microvilli not characteristic of mesothelial cells. We conclude that so-called mesotheliomas of the atrioventricular nodal region are not of mesothelial origin, because of strong carcinoembryonic antigen positivity and occasional positivity with B72.3, as these antibodies react with glycoproteins found in endodermally derived tissue and generally not with mesothelial tissue. Conduction system tumors are most likely congenital rests of endodermal origin, can be associated with other congenital anomalies, and often cause symptoms of heart block and sudden death.
Adolescent↗
Ultrastructural immunogold labeling patterns--image processing, mapping and quantitative microanalysis of antigenic sites in renal biopsies and neoplasms.
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Adenocarcinoma↗
S-100 protein expression by primary and metastatic adenocarcinomas.
S-100 protein has been used as a marker of various lesions, including peripheral nerve sheath, cartilaginous and salivary gland tumors, chordomas, histiocytosis X, and melanomas, among others. The list of neoplasms that can express S-100 protein continues to expand. It has been suggested that staining for S-100 protein may be of aid in the differential diagnosis of amelanotic melanoma versus poorly differentiated tumors. Three hundred fifty primary and metastatic adenocarcinomas from various sites were immunostained for S-100 protein with the use of a commercially available polyclonal antibody. Forty-two percent of the adenocarcinomas tested expressed S-100 protein to varying degrees. The relative incidence of S-100-positive tumors varied with the primary sites, some expressing S-100 protein more often than others. A primary neoplasm able to express S-100 protein was usually associated with metastatic foci also expressing this marker. However, occasionally, a primary S-100-positive tumor was associated with metastasis that lacked expression of S-100. This study emphasizes the importance of testing for a panel of tumor markers in the evaluation of poorly differentiated tumors and cautions on possible difficulties that may arise in the interpretation of immunocytochemistry results.
Adenocarcinoma↗
Neuroendocrine differentiation in prostatic carcinomas. A retrospective autopsy study.
Neuroendocrine differentiation in prostatic neoplasms has in the past been considered extremely uncommon. The histologic neuroendocrine patterns reported previously vary from small cell to carcinoidlike to mixed adenocarcinoma--small cell or carcinoid. The majority of the tumors reported are of the mixed variety. We reviewed 2648 autopsies, revealing 69 prostatic carcinomas, eight with neuroendocrine differentiation (five mixed adenocarcinoma--small-cell carcinoma, two "pure" small cell, and one "pure" carcinoidlike). The mean patient age was 69.5 years. One patient presented with markedly elevated serum corticotropin and another was severely hypercalcemic with elevated serum parathyroid hormone level. Three neoplasms were incidental autopsy findings. The mean survival time, after diagnosis, was 19 months for the other patients. Three of the cases were examined ultrastructurally and showed cytoplasmic processes containing membrane-bound granules in the neuroendocrine component. The areas with neuroendocrine differentiation were positive for markers as follows: neuron-specific enolase, seven of eight; prostate-specific antigen (PSA), none of eight; chromogranin A, seven of eight; synaptophysin, four of eight; and calcitonin, four of eight. Those neoplasms mixed with an adenocarcinoma component showed well-defined PSA positivity in the glandular elements. This study suggests that neuroendocrine differentiation in prostatic neoplasms may be more common than previously thought. Often, the areas with neuroendocrine differentiation are considered to represent poorly differentiated adenocarcinoma. It is important to recognize neuroendocrine components in prostatic carcinomas owing to prognostic and potential therapeutic implications.
Adenocarcinoma↗
Unusual pigmented vesical lesion in a middle-aged woman.
Excess lipofuscin deposition in tissues is a phenomenon observed in normal aging. The amount of lipofuscin in myocardium, liver, skeletal muscle, and adnexal skin structures varies considerably with age and increases in older individuals. In addition, lipofuscin deposition occurs in association with specific, non-age-related processes; these include melanosis coli, the so-called brown bowel syndrome, and the black thyroid. Localized lipofuscinosis has also been described in the gallbladder, esophagus, and fallopian tubes. The present article adds lipofuscinosis vesicalis to the list of entities characterized by focal lipofuscin deposition. All cases have a characteristic gross appearance that is somewhat variable from entity to entity and in some cases may suggest clinically an ominous pathologic process.
Adult↗
Ultrastructural immunolabeling: the next logical step.
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Humans↗
Phenotypic cytoskeletal heterogeneity in melanoma, a challenge to the surgical pathologist evaluating a poorly differentiated neoplasm: an illustrative case.
Characterization of poorly differentiated neoplasms can be a challenging task for the surgical pathologist. It is essential that the entire spectrum of immunomorphologic findings of various tumors be recognized to avoid improper characterization of a given neoplasm, which may in turn adversely affect patient management. Tumor characterization is complicated by the immunomorphologic transformations that malignant cells may undergo by virtue of which they may depart from expression of expected features and acquire new, unexpected characteristics. Traditionally, amelanotic melanomas have been difficult to characterize because of the diversity of their light microscopic morphology (epithelioid, spindle, and combined varieties). As a result, several other neoplasms are usually considered in the differential diagnosis. This report describes a primarily spindle-cell amelanotic melanoma that created a diagnostic dilemma, which could only be resolved by combining the information obtained from extensive evaluation by means of several diagnostic techniques. This case also stresses the phenotypic heterogeneity of the cytoskeleton of malignant melanomas and therefore their varied immunomorphologic characteristics.
Cell Nucleus↗
Unusual pigmented vesical lesion in a middle-aged woman (UP 1990;14:529-535)
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Female↗
Ultrastructural immunolabeling: a general overview of techniques and applications.
Ultrastructural immunolabeling techniques combine the advantages of routine electron microscopy and detection of antigenic epitopes, the latter of which is customarily done by immunocytochemistry at the light microscopic level. In surgical pathology, immunocytochemistry has become routine to approach the differential diagnosis of difficult cases. Immunoelectron microscopy has been used primarily for research purposes or for addressing specific questions in diagnostic pathology. Ultrastructural immunolabeling is extremely useful in those instances in which the ultrastructural and immunocytochemical findings are not pathognomonic and are subject to interpretation. Preembedding and postembedding labeling techniques have been described in the literature. Preembedding techniques are not as applicable to diagnostic work, however. Their use remains rather limited to applications in which the antigen to be labeled cannot maintain its viability when exposed to fixatives. Even in such cases a new methodology--the LifeCell process--has emerged; this technique cryofixes tissues, thereby maintaining antigenic integrity. After cryofixation, a postembedding labeling technique can be utilized. Immunogold and peroxidase methods are used for labeling. Immunogold methods elegantly mark reaction sites with preservation of underlying morphology. Postembedding immunogold methods are used by most individuals working in the field. Ultrastructural labeling techniques are rapidly moving from classification as exclusively research tools to the diagnostic arena.
Cryopreservation↗
Ultrastructural immunolabeling in diagnostic surgical pathology: illustrative cases.
Ultrastructural immunolabeling techniques can be reproducibly applied to resolve diagnostic dilemmas in surgical pathology. The technique utilized for processing and labeling the cases presented in this article is simple and reproducible. The specimens were fixed in Carson-Millonig phosphate-buffered 4% formaldehyde fixative and embedded in LR White resin following a well-described protocol. Immunogold labeling allows precise localization of antigenic sites without compromise of the underlying ultrastructural morphologic findings; thus detailed immunomorphologic assessment is achieved. Immunoelectron microscopy techniques permit clarification of doubtful immunocytochemistry results by labeling antigenic epitopes in cases in which light microscopy immunocytochemistry techniques fail to show unequivocal positive results (probably as a consequence of small amounts of detectable antigen present in the tissues). Not only does ultrastructural labeling permit identification of focally positive reactions essential for accurate diagnosis in a given case, but it also localizes the antigenic determinants to specific cellular sites, providing immunomorphologic correlation. The specificity of the interpreted results can then be judged accordingly. Overall, ultrastructural immunolabeling is more sensitive than light microscopic immunocytochemistry. Ultrastructural immunolabeling can play a crucial role in the characterization of some tumors that cannot be accurately classified with other diagnostic techniques, even when combined.
Calcitonin↗