bromochloroacetic-acid and Pheochromocytoma

In daily routine pathology of the adrenal glands three tumor entities are important: adrenocortical tumors, adrenomedullary tumors and metastases. The differentiation of these three main tumor types can often be difficult structurally but immunostaining enables a definite diagnosis in nearly all cases. Adrenocortical tumors are positive for steroidogenic factor 1 and melan-A and always negative for chromogranin A whereas adrenomedullary tumors express chromogranin A but never keratin. A broad spectrum of antibodies is available for the identification of metastases and even the rare epithelioid angiosarcomas. For adrenocortical tumors, adenomas and carcinomas can be differentiated using three scoring systems and the Ki-67 index in adenomas should not exceed 3%. Using scoring systems and the Ki-67 index approximately 90% of cortical tumors can be differentiated into benign or malignant tumors. For pheochromocytomas two scoring systems are used for differentiating benign and malignant tumors but the results are less dependable.

Topics: Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Adrenal Glands; Adrenal Medulla; Adrenocortical Adenoma; Biomarkers, Tumor; Chromogranin A; Humans; Keratins; MART-1 Antigen; Pheochromocytoma; Steroidogenic Factor 1

In most cell types intermediate or 10-mm filaments (IF) are a major cytoskeletal organization and, thus, directly or indirectly influence the structural appearance of the cytoplasm. In line with the cell type-specific expression patterns of different IF proteins in normal animal and human tissue, IF typing distinguishes the major tumor groups, as documented by results with several hundred human tumors classified by conventional histologic methods. Carcinomas are characterized by cytokeratins, sarcomas of muscle cells by desmin, nonmuscle sarcomas by vimentin, and gliomas by glial fibrillary acidic protein. Furthermore, certain tumors originating from the sympathetic nervous system, e.g., ganglioneuroblastoma, pheochromocytoma, and at least some neuroblastomas, are characterized by the presence of neurofilaments. Carcinomas can often be further subdivided with regard to their possible derivation by examining their cytokeratin profiles. The IF type characteristic of the cell of origin seems to be kept not only in the primary tumor but usually also in solid metastases. In general, tumors do not acquire additional IF types. Therefore, IF typing can provide an unambiguous and rapid characterization in certain cases, that are difficult to diagnose by conventional techniques. Some useful examples are the small cell tumors of childhood and the discrimination between undifferentiated carcinoma and lymphoma. IF typing of a few tumors has already led to a revision or reconsideration of the original light microscopic diagnosis. The combined results indicate that at least certain carcinomas, as well as certain other tumor types, seem to arise by the selective multiplication of a particular and identifiable cell type present in the normal tissue. The procedure is not restricted to tumor material. IF typing of Mallory bodies, Alzheimer's disease tangles, certain myopathies, and the cells of the amniotic fluid offers further interesting applications. Thus, IF typing should become a valuable new tool both in histology and surgical pathology.

Topics: Amniotic Fluid; Animals; Carcinoma; Cells, Cultured; Cytoskeleton; Desmin; Embryo, Mammalian; Fluorescent Antibody Technique; Ganglioneuroma; Glial Fibrillary Acidic Protein; Glioma; Humans; Intermediate Filament Proteins; Keratins; Muscular Diseases; Neoplasm Metastasis; Neoplasms; Neuroblastoma; Pheochromocytoma; Sarcoma; Vimentin

The aim of this study was to make immunohistochemical analyses with Inhibin alpha-subunit, Melan A and MNF116 (pan-Cytokeratin antibody) in pheochromocytomas, because immunohistochemistry is useful for the distinction between adrenal tumors.. We used 20 patients with pheochromocytomas submitted to laparoscopic (n=19) or classical (n=1) surgery and we have explored immuno-staining with Inhibin alpha-subunit, Melan A and MNF116 in these tumors. This can be helpful when we cannot make the distinction between adrenal tumors.. Pheochromocytomas did not stain with Inhibin alpha-subunit, Melan A and MNF116.. In our study, Inhibin alpha-subunit, Melan A and MNF116 were not sensitive for pheochromocytomas.

Topics: Adrenal Gland Neoplasms; Female; Humans; Inhibins; Keratins; Male; MART-1 Antigen; Metanephrine; Middle Aged; Normetanephrine; Pheochromocytoma

Paraganglioma of the urinary bladder is rarely encountered and its biologic behavior is uncertain. The authors sought to determine the prognostic factors that would predict patient outcome.. The Mayo Clinic experience over 53 years with paraganglioma of the bladder was reviewed. All histologic slides from 16 patients were reviewed by the authors. Eight cases were examined immunohistochemically with cytokeratin (AE1/3, cytokeratin 7, and cytokeratin 20), vimentin, S-100 protein, neuroendocrine markers (chromogranin, synaptophysin, and neuron specific enolase), p53 protein, and MIB-1. DNA ploidy was determined by digital image analysis in formalin fixed, paraffin embedded tissue. The mean follow-up was 6.3 years (range, 0.4-16.4 years).. Paraganglioma usually occurred in young adult women (mean age, 45 years; range, 16-74 years). The male-to-female ratio was 1 to 3. The common symptoms and signs were hypertension and hematuria. The tumors were usually located intramurally in the lateral and posterior wall of the bladder and were multifocal in 3 cases (18%). Seven patients were treated by transurethral resection, eight by partial cystectomy, and one by radical cystectomy. T classification was T1 (1 patient), T2 (9 patients), T3 (2 patients), and T4b (4 patients). At the time of diagnosis, one patient had distant metastasis and one had regional lymph node metastasis. One patient developed metastasis 1 year after diagnosis and died of the disease 1.5 years later. None of the patients with T1 or T2 tumors had recurrence or tumor progression. All tumors were aneuploid. The mean MIB-1 labeling index was 1.5% (range, 0.03-7.0%). The tumor cells displayed immunoreactivity for S-100 protein and neuroendocrine markers and were negative for p53 (except 1 case) and cytokeratin.. Paraganglioma of the urinary bladder occurs mostly in young adult women. Patients with tumor of advanced classification (>/=T3) are at risk of recurrence, metastasis, and dying of the disease, whereas patients in this study with T1 or T2 disease had favorable outcomes after complete tumor resection.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; DNA, Neoplasm; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Middle Aged; Nerve Tissue Proteins; Paraganglioma; Pheochromocytoma; Ploidies; Prognosis; Retrospective Studies; S100 Proteins; Tumor Suppressor Protein p53; Urinary Bladder Neoplasms; Vimentin

To examine whether adrenal phaeochromocytomas and extra-adrenal paragangliomas are immunoreactive for commercially available and routinely used cytokeratin antibodies.. 18 extra-adrenal paragangliomas and seven adrenal phaeochromocytomas were stained with CAM 5.2, AE1/3, and 34 beta E12 following microwave antigen retrieval of formalin fixed tissue.. A single case from the cauda equina was positive for both CAM 5.2 and AE1/3. In addition, two other cases--an intravagal and an orbital paraganglioma--also showed strong immunopositivity with CAM 5.2 and AE1/3. All phaeochromocytomas were negative with all epithelial markers.. Cauda equina paragangliomas are known to stain with cytokeratins; however, occasional paragangliomas from other sites may also be immunoreactive with cytokeratins. If the results of immunohistochemistry are not interpreted in the clinical and morphological context, the failure to recognise that extra-adrenal paragangliomas may on occasion react with anticytokeratin antibodies may lead to their being confused with metastatic carcinomas.

Topics: Adolescent; Adrenal Gland Neoplasms; Adult; Aged; Carotid Body Tumor; Cauda Equina; Child; Cranial Nerve Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Male; Microwaves; Middle Aged; Orbital Neoplasms; Para-Aortic Bodies; Paraganglioma, Extra-Adrenal; Peripheral Nervous System Neoplasms; Pheochromocytoma; Staining and Labeling; Vagus Nerve

For a study of histogenesis of intestinal carcinoids a collection of 5 classical small intestinal carcinoids, 6 appendiceal carcinoids and 9 pheochromocytomas, were evaluated. The tumors were identified by routine morphology, silver staining and chromogranin immunocytochemistry and were then examined with regard to the expression of intermediate filaments of cytokeratin type. Eight different antisera identifying individual or combinations of cytokeratins were employed. All classical small intestinal carcinoids displayed cytokeratin immunoreactivity and an almost identical cytokeratin reaction was observed in the normal enterocytes of the small intestinal mucosa. Of the individual cytokeratin types, number 18 was most heavily expressed. The appendiceal carcinoids, like the pheochromocytomas, almost totally lacked a cytokeratin staining despite a positive reaction in the mucosa of the appendix. This, in agreement with some previous studies, indicates that the small intestinal carcinoids are histogenetically related to the epithelial cells of the intestinal mucosa, while the appendiceal carcinoids have a different histogenesis and are more like pheochromocytomas. The appendiceal carcinoid may represent a distinct type of intestinal paraganglioma. This offers one explanation for the different biological behavior of appendiceal carcinoids in comparison with the other intestinal carcinoids.

Topics: Adrenal Gland Neoplasms; Appendiceal Neoplasms; Carcinoid Tumor; Humans; Immunohistochemistry; Intestinal Mucosa; Intestinal Neoplasms; Intestine, Small; Keratins; Pheochromocytoma; Staining and Labeling

Keratin 8 (Endo A) is expressed in simple epithelia, together with keratin 18 (Endo B). Filaments formed by this keratin pair are the first cytoskeletal elements induced during mouse embryogenesis. We have isolated Endo A cDNA clones from lambda gt11 libraries prepared with mRNA isolated from PCC4 embryonal carcinoma (EC) cells. Sequencing of three overlapping cDNAs and of a genomic clone allowed us to determine the complete sequence of the Endo A message. Analysis of the protein sequence deduced showed that the Endo A protein presented all the characteristics of intermediate filaments, including an alpha-helical central rod domain and nonhelical N- and C-termini. In the rod domain, the degree of similarity to the other members of the basic keratin family was high. A high degree of homology to keratin 8 of other species was observed, even in the non-helical domains. During these analyses, we found clones extending upstream of the normal 5' end of the mRNA. Sequence comparison between these cDNAs and the 5' upstream region of the Endo A gene suggested that they corresponded to transcripts initiated at an upstream alternative promoter. These observations supported previous results showing the presence of Endo A transcripts initiated upstream of the normal 5' end in mouse morulae and blastocysts.

Topics: Amino Acid Sequence; Amphibians; Animals; Base Sequence; Cattle; Cell Line; DNA; Keratins; Mice; Molecular Sequence Data; Pheochromocytoma; RNA, Messenger; Sequence Homology, Nucleic Acid; Transcription, Genetic

The cytoskeleton of the rat cultured cell line PC12, which is widely used in cell biology as a model system for neuron-like differentiation, displays an unusual combination of intermediate-sized filaments (IFs). As determined by electron microscopy, immunolocalization, and biochemical analyses, these cells contain, in addition to neurofilaments, an extended meshwork of bundles of cytokeratin IFs comprising cytokeratins A and D, equivalent to human cytokeratin polypeptides Nos. 8 and 18, irrespective of whether they are grown in the presence or absence of nerve growth factor. The two IF systems differ in their fibrillar arrays, the neurofilaments being concentrated in perinuclear aggregates similar to those found in certain neuroendocrine tumors of epithelial origin. We conclude that PC12 cells permanently co-express IFs of both the epithelial and the neuronal type and thus present an IF combination different from those of adrenal medulla cells and pheochromocytomas, i.e., the putative cells of origin of the line PC12. The IF cytoskeleton of PC12 cells resembles that of various neuroendocrine tumors derived from epithelial cells. The results show that the development of a number of typical neuronal differentiation features is compatible with the existence of an epithelial type IF cytoskeleton, i.e., cytokeratins. The implications of these findings concerning the validity of the PC12 cell line as a model for neuronal differentiation and possible explanations of the origin of cells with this type of IF co-expression are discussed.

Topics: Animals; Cell Differentiation; Cell Line; Cytoskeleton; Epithelium; Immunologic Techniques; Intercellular Junctions; Intermediate Filament Proteins; Intermediate Filaments; Keratins; Microscopy, Electron; Molecular Weight; Neurofilament Proteins; Neurons; Pheochromocytoma; Rats; Vimentin