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Biomedical subjects

N Vigneswaran

Publications and source records attributed to N Vigneswaran.

At least 37 records · Page 2Linked to original sources

Merkel cell carcinoma of the labial mucosa. An immunohistochemical and ultrastructural study with a review of the literature on oral Merkel cell carcinomas.

Merkel cell carcinoma is a rare cutaneous neuroendocrine tumor that occurs predominantly in the head and neck region of older patients. An 88-year-old white man had an erythematous, umbilicated tumor on his lower lip, which on histopathologic examination showed solid sheets of infiltrating basaloid round cells with a high mitotic index. Globular, paranuclear immunostaining for low-molecular-weight cytokeratins (Nos. 8, 18, and 19) and neurofilament was observed. On ultrastructural examination, the tumor cells demonstrated paranuclear whorls of intermediate filament aggregates and occasional electron-dense granules. This unique cytokeratin- and neurofilament-staining pattern with coexpression enabled the Merkel cell carcinoma to be differentiated from other small cell malignant tumors that included metastatic neuroendocrine carcinomas from other regions. The follow-up 1 year after surgery and radiation showed that the patient remained disease free. Review of the literature revealed 11 cases of oral Merkel cell carcinomas with a predilection for the labial mucosa of older men. The mode of treatment and the clinical course of these cases are also presented, with an update on therapeutic management of Merkel cell carcinomas.

Aged↗

Retinal hemangioblastoma. A histologic, immunohistochemical, and ultrastructural evaluation.

The authors evaluated the histologic, immunohistochemical, and ultrastructural characteristics of two eyes with retinal hemangioblastoma from patients with von Hippel-Lindau and von Hippel disease. Results of histologic evaluation showed the eyes to have degenerative changes and residual retinal hemangioblastoma. Immunohistochemical stains performed for MAC-387, factor XIIIa, lysozyme, alpha 1 anti-chymotrypsin (histiocyte markers), factor VIII-associated antigen, ulex europeaus (endothelial markers), neuron-specific enolase, chromogranin, neurofilament (neuroectodermal/neural/neuroendocrine markers) and glial fibrillary acid protein (glial marker) showed normal retinal vascular endothelium, neurons, and glial cells to stain where expected. Vascular endothelium in the retinal hemangioblastomas stained for factor VIII and ulex europeaus. Interstitial cells in the stroma of the tumors failed to stain for the histiocyte markers, chromogranin, and neurofilament. The stromal cells stained for glial fibrillary acid protein and neuron specific enolase. Ultrastructural findings in both eyes included endothelial/pericyte-lined vascular channels, elongated stromal cells, and plump, vacuolated stromal cells with ultrastructural features consistent with glial cells. This study supports the concept that retinal hemangioblastoma is composed of a proliferation of capillaries and glial cells.

Adolescent↗

Cytokeratin expression in corneal endothelium in the iridocorneal endothelial syndrome.

The immunocytologic characteristics of two formalin-fixed, paraffin-embedded corneas from patients with the iridocorneal endothelial (ICE) syndrome and unaffected control corneas were studied. Binding of polyclonal antisera to Factor VIII, S-100 protein, involucrin, neuron specific enolase (NSE), and the lectins peanut agglutinin and Ulex europaeus agglutinin-1 was performed using the standard peroxidase-anti-peroxidase method. We detected reactive patterns of monoclonal antibodies to cytokeratins (34BE12 is a 56-58 kD mouse IgG reactive to stratified epithelia; Pkk1 is a 44-54 kD mouse IgG reactive to simple epithelia; and KL1 is a 55-57 kD mouse IgG reactive to epidermis and simple epithelia) using the standard avidin-biotin complex method. Staining properties were similar for the polyclonal antisera, lectins, NSE, and chromogranin in corneas with ICE syndrome and in the controls. However, the cytokeratins 34BE12, Pkk1, and KL1 were detected in the endothelium of the corneas with the ICE syndrome but not in the controls. These findings suggest that various cytokeratins are expressed in the corneal endothelium in the ICE syndrome that are not expressed in unaffected corneal endothelium.

Antibodies, Monoclonal↗

Phenotyping of immunocompetent cells in normal labial and palatal salivary glands and in non-autoimmune sialadenitis.

Different types of inflammatory cells in healthy major and minor salivary glands (SG), including those in labial and palatal non-autoimmune sialadenitis, were quantified immunohistochemically. Plasma cells, mainly IgA type predominated in all SG types, with the smallest number seen in the palatal glands. The numbers of common leukocyte antigen (CLA) reactive lymphocytes were greater in major SGs than in minor ones and were predominantly UCHL1 positive T cell type. Macrophages and neutrophils were absent in palatal glands, rarely present in labial ones and usually present in major SGs. Increases in the number of IgG and IgM plasma cells and lymphocytes (CLA+) which include both UCHL1+ T and L26+ B cell types, were found in non-autoimmune labial and palatal sialadenitis. There was no significant correlation between the number of the inflammatory cells and the degree of glandular atrophy in both labial and palatal non-autoimmune sialadenitis. Increase in their number represents a protective response of these glands in contrast to the inflammatory cells in major autoimmune sialadenitis playing there a pathogenetic role.

Antigens, Differentiation↗

Immunohistochemical characterization of epithelial cells in human lacrimal glands. I. Normal major and accessory lacrimal glands.

Expression patterns of cytokeratins (CKs), actin, lactoferrin (Lf), lysozyme (Ly), vimentin, and S-100 protein were immunohistochemically examined in paraffin sections from eight normal major and accessory lacrimal glands (LGs). Luminal duct cells and a number of secretory cells stained with the antibodies (ABs) KL1 and Pkk1 (CK 7, 8, 17, 18), while basal duct and myoepithelial cells reacted with the AB 34 beta E12 (CK 5). Myoepithelial cells expressing CK 5 and actin were restricted to acini and intralobular ducts, and their number was greater in major LGs than accessory ones. Lf and Ly were found in 50%-75% of acini and intralobular ducts. Vimentin was absent in parenchyma of LGs. S-100 protein reaction was observed in a number of acinar and luminal duct cells of major LGs whereas epithelia of accessory LGs remained negative. Distribution patterns of CKs, Lf, and Ly in major and accessory LGs are identical. The difference with respect to the number of myoepithelial cells as well as S-100 protein reactivity between major and accessory LGs reactivity appeared to be relevant to the differences in their secretory mechanisms and local environment.

Actins↗

Immunohistochemical characterization of epithelial cells in human lacrimal glands. II. Inflammatory and neoplastic lesions of lacrimal glands.

The distribution of cytokeratins (CK), actin, lactoferrin (Lf), lysozyme (Ly), vimentin and S-100 protein was immunohistochemically investigated in paraffin-embedded specimens of five inflammatory and five neoplastic lesions of lacrimal glands (LGs). Atrophic acini in dacryoadenitis reacted with antibodies (ABs) KL1 and Pkk1 (CK 7, 8, 17, 18) in a manner similar to ducts. Apart from myoepithelial cells and some luminal-duct cells, the remaining epithelia in dacryoadenitis were negative with AB 34 beta E12 (CK 5). The number of AB HHF35 (actin)-positive myoepithelial cells was not altered in dacryoadenitis. Epithelia in dacryoadenitis reacted weakly but consistently with Lf while revealing weak and inconsistent staining for Ly. Vimentin was negative in epithelial cells in dacryoadenitis except in one case. S-100 protein was detected only in epithelia of inflammatory major LGs. Epimyoepithelial islands in lymphoepithelial proliferation reacted variably for CKs, Lf, Ly and vimentin and remained negative for actin and S-100. In pleomorphic adenomas, neoplastic cells showing duct-like differentiation (luminal) reacted consistently with CK 7, 8, 17, 18 and S-100 protein and inconsistently with CK 5, Lf and Ly but remained negative for actin and vimentin. Other neoplastic cells (ovoid/peripheral cells) stained consistently for CK 5, vimentin and S-100 protein and focally for CK 7, 8, 17, 18, actin, Lf and Ly. Spindle-form neoplastic cells found in the stroma exhibited vimentin and S-100 protein and, less frequently, actin. Determination of these antigens in pleomorphic LG adenomas may help to evaluate their prognosis.

Actins↗

Immunohistochemical and ultrastructural study of histiocytosis X and non-X histiocytoses.

The diagnostic reliability of ultrastructural and immunohistochemical examinations on routinely processed biopsy specimens of cutaneous histiocytic proliferations (histiocytosis X, n = 7; juvenile xanthogranuloma, n = 4; necrobiotic xanthogranuloma, n = 2; traumatic granuloma of the tongue, n = 1) was evaluated. S-100 protein, peanut agglutinin, and the antibody Mac-387 were used as markers for histiocytes. The frequency of Birbeck granule-containing cells in seven histiocytosis X lesions did not correspond with the number of S-100+ or peanut agglutinin+ cells. All neoplastic histiocytosis X cells were positive for S-100 protein and peanut agglutinin but were negative for Mac-387. Histiocytes of juvenile xanthogranuloma, necrobiotic xanthogranuloma, and traumatic granuloma were strongly positive for Mac-387 but were negative for S-100 protein and peanut agglutinin, except for the peanut agglutinin-reactive Touton giant cells. Mac-387 reliably differentiates histiocytic proliferations of the monocyte/macrophage system from those of the dendritic cell system. For the diagnosis of histiocytosis X, both S-100 protein and peanut agglutinin positivity in histiocytes is as reliable as ultrastructural demonstration of Birbeck granules.

Adult↗

Abnormalities of keratinocyte maturation and differentiation in keratosis palmoplantaris striata. Immunohistochemical and ultrastructural study before and during etretinate therapy.

Keratoderma striatum (Brünauer-Fuhs type) with linear keratotic elevations on the palms and small islets (areata form) on the soles is a rare form of palmoplantar keratoderma (PPK). An immunohistochemical and ultrastructural study has been performed to characterize the altered keratinization and maturation patterns in this disease before and during complete clinical remission on therapy with etretinate. Anticytokeratin antibody KL1 showed no significant difference in reaction pattern either between healthy controls and PPK or following therapy. Earlier expression of both filaggrin and involucrin was found in PPK in comparison with the controls. During etretinate therapy the filaggrin pattern returned to normal, whereas the altered involucrin pattern was not influenced. Ultrastructural investigations before treatment revealed tightly packed tonofibrils (TF) and large masses of keratohyalin (KH) granules with abnormal configuration. During therapy the TF and KH granules were reduced in number and size. KH granules now showed frayed borders. Moreover, a transitional cell zone, focal parakeratosis with lipid droplets, and dyskeratotic cells became apparent. The normalization of filaggrin pattern accompanying the clinical remission of these lesions implies a role of this keratinocyte differentiation protein in the pathogenesis of these lesions. Since etretinate is assumed to act at a very late stage of epidermal differentiation, there was no influence on the altered expression of involucrin during etretinate therapy. Despite the clinical remission, fine structural abnormalities persisted, indicating that the deviations from the normal keratinocyte differentiation program in PKK occur very early.

Adult↗

Alteration of cell surface carbohydrates associated with ordered and disordered proliferation of oral epithelia: a lectin histochemical study in oral leukoplakias, papillomas and carcinomas.

Cell surface carbohydrates in healthy oral mucosa (n = 15), leukoplakias without (n = 48) and with (n = 62) dysplasia, oral papillomas (n = 6) and squamous cell carcinomas (SCCs) (n = 40) were examined using the lectins peanut agglutinin (PNA), Ulex europaeus agglutinin I (UEA I), soybean agglutinin (SBA), Helix pomatia agglutinin (HPA), and Griffonia simplicifolia agglutinin I (GS I-B4). Binding of these lectins in formalin-fixed, paraffin-embedded tissues was demonstrated using either the peroxidase-anti-peroxidase (PAP) method or the avidin-biotin method. Healthy oral epithelia revealed binding sites for these lectins mostly in the suprabasal keratinocytes with occasional PNA binding also in their basal cells. Unlike healthy mucosa, a number of leukoplakias without and with dysplasia revealed receptor sites for UEA I also in their basal layer. Only those keratinocytes undergoing squamoidal differentiation exhibited SBA binding. Staining patterns of UEA I and SBA did not vary significantly between either leukoplakias without and with dysplasia or papillomas and SCCs. Conversely, a reduction or lack of binding sites for PNA (Gal beta 1-3GalNAc), HPA (D-GalNAc alpha) and GS I-B4 (alpha D-Gal) was observed more frequently in leukoplakias with dysplasia and SCCs contrasting their counterparts lacking epithelial dysplasia. Cell surface glycosyl residues play an important role in the regulation of cell proliferation and epithelial growth. Aberrant glycosylation in oral dysplastic leukoplakias and carcinomas leading to the lack of the relevant terminal sugar residues from their cell surface carbohydrates is probably a major reason for the hyper-/disordered proliferation.

Carbohydrate Metabolism↗

[Cytologic methods in dermatology].

Cytology is a simple, fast, and inexpensive procedure yielding a high degree of diagnostic accuracy-provided the examiner has a good deal of experience. It has not yet become generally accepted in the diagnosis of skin diseases, since biopsies are very easy to perform, and histopathology is still more reliable than cytology. Modern techniques such as electron microscopy, immunofluorescence, immunocytochemistry with polyclonal and monoclonal antibodies, immunoelectron microscopy, DNA flow cytometry, and in situ hybridization have considerably increased the potentials of cytology and will certainly help to win general recognition in dermatology, as well.

Biomarkers, Tumor↗

[Beta-2-microglobulin expression in oral lichen planus].

In 15 patients suffering from oral lichen planus (OLP), we took biopsies of both involved and noninvolved oral mucosa. The specimens were immunohistochemically studied with regard to the expression of beta-2-microglobulin (beta 2-M). In contrast to noninvolved mucosa, we proved definite beta 2-M expression in keratinocytes from OLP lesions. Our findings agree with the assumption that an autoimmunological process is involved in the pathogenesis of OLP.

Adult↗

A comparative lectin histochemical study of major and minor salivary glands with special reference to the labial glands.

There is debate about the nature of the secretory cells in labial salivary glands. To characterize their basophilic acini the binding patterns of different lectins were examined in these glands (n = 30) and compared with those of major salivary glands (n = 10) and palatal salivary glands (n = 20). Binding in formalin-fixed paraffin-embedded sections was revealed using either anti-lectin antibodies and the peroxidase-antiperoxidase method or biotinylated lectins and the avidin biotin method. Binding of peanut agglutinin was seen in all basophilic acini of labial glands, whereas serous acini of major glands were completely negative. Focal binding of soybean agglutinin was seen in all basophilic acini of labial glands in addition to diffuse binding in mucous acini of all salivary glands, whereas serous acini were mostly negative. Conversely, there was binding of Ulex europaeus agglutinin I in all mucous and serous acini of all glands except for the basophilic acini of labial glands. Bandeiraea simplicifolia agglutinin I and Helix pomatia agglutinin bound to all basophilic and most mucous acini of labial glands, and to most mucous acini of major salivary glands, whereas only a few serous acini of major glands were reactive with both lectins. Pretreatment with neuraminidase yielded binding sites for peanut agglutinin in most of the serous acini of major glands and mucous acini of labial glands, and increased B. simplicifolia agglutinin I and H. pomatia agglutinin binding in the serous acini of major glands. Thus the different lectin binding patterns, particularly the differences in the reaction patterns of peanut, soybean and U. europaeus agglutinin I, showed that the basophilic acini of labial glands reacted more like mucous acini.

Histocytochemistry↗

Are differences in filaggrin expression suitable for discriminating benign, premalignant and malignant skin lesions? An immunohistochemical study.

The differential diagnosis of benign and malignant skin lesions may pose considerable difficulties. Therefore, 137 formalin-fixed paraffin-embedded biopsies of various benign, premalignant and malignant skin tumours were examined immunohistochemically for the presence of filaggrin using the monoclonal anti-filaggrin antibody AKHl. The proliferating cells of both benign and malignant tumours were negative for filaggrin. Most of the benign tumours exhibited an intense filaggrin-positive granular layer identical to the adjacent healthy skin whereas benign conditions such as irritated seborrhoeic keratoses and clear cell acanthomas were completely devoid of filaggrin. Keratoacanthomas revealed an inconsistent staining pattern for filaggrin. Premalignant and malignant lesions including basal cell carcinomas were either focally positive or completely negative for filaggrin. The absence or presence of filaggrin in these lesions did not correspond to the degree of dysplasia. Moreover, none of these conditions gave a staining pattern for filaggrin to be used for the histological differential diagnosis of these skin lesions.

Diagnosis, Differential↗

Comparison of cytokeratin, filaggrin and involucrin profiles in oral leukoplakias and squamous carcinomas.

As the distribution pattern of cytokeratin (CK), filaggrin and involucrin has recently been suggested to discriminate between benign and malignant epithelial growths, biopsies of healthy oral mucosa, leukoplakias without and with dysplasia and squamous cell carcinomas were examined immunohistochemically using a panel of 4 monoclonal antibodies (AB) against different cytokeratin polypeptides (34 beta E12, KL1 and Pkk1) and filaggrin as well as a polyclonal AB to involucrin. Major and statistically significant differences were observed in the profiles of CKs (except Pkk1), filaggrin and involucrin between leukoplakias without and with epithelial dysplasia. However, the alteration in the expression of CKs, filaggrin and involucrin proved to be not a constant feature in leukoplakias with dysplasia as a considerable portion (20-25%) of them revealed the profiles of CKs, filaggrin and involucrin similar to those of benign leukoplakias, and vice versa. Immunostaining of these antigens did not define the diagnosis of dysplasia in leukoplakias more precisely than grading in conventional histology can do so far. However, immunohistochemical sensitivity in detecting a broad range of variation in the abnormal maturation patterns of keratinocytes in leukoplakias with dysplasia can be used to divide these lesions into subgroups to elucidate their prognosis in follow-up studies.

Carcinoma, Squamous Cell↗

Localization of epithelial markers and defence proteins in minor and major salivary glands.

Immunohistochemical demonstration of cytokeratin (CK), tissue polypeptide antigen (TPA), carcinoembryonic antigen (CEA), lactoferrin (Lf), lysozyme (Ly) and secretory component (SC) was performed in major salivary glands (MaSG), labial and palatal salivary glands (LSG, PSG). CK and TPA were demonstrated in ductal cells of all SGs. In addition, binding of anti-CK (Mw-56 Kd) antibody (AB) KL I was seen in all serious acini of MaSG, basophilic acini and demilunes of LSG and in some mucous acini of PSG. Binding of anti-CK (Mw 44-54 Kd) AB-PKK I, another polyclonal anti-CK (Mw 55-67 Kd) AB-PCK and anti-TPA AB was demonstrated in all basophilic acini of LSG, basophilic portions of mucous acini in PSG and not in acini of MaSG. Significant differences were observed in the expression of CEA, Ly, Lf and SC between acini of MaSG and MiSG which probably reflects different functions of these glands.

Antibodies, Monoclonal↗

Immunohistochemical study of palatal salivary glands of denture wearing patients.

The binding pattern of antibodies against different cytokeratin (CK) polypeptides, tissue polypeptide antigen (TPA), carcinoembryonic antigen (CEA), lactoferrin (Lf), lysozyme (Ly) and secretory component (SC) in palatal glands (PSG) of long-term denture wearing patients has been studied to investigate immunohistochemically the localization of these marker proteins in normal PSG and in denture-induced sialadenitis of PSG. The study included palatal gland biopsies from 28 patients (15 f, 13 m; mean age 59 years), 17 of them with normal PSGs, 8 with focal obstructive sialadenitis, and 3 with diffuse sialadenitis. Presence of CK and TPA was found in all intra- and extraglandular salivary ducts, in the basophilic portions of acini, in some mucous acini, and in all atrophic acini. Increased expression of CEA and Lf was observed in inflammed areas of PSG which, on the other site, were devoid of Ly and SC. In the mucous acini of healthy PSG considerable basal Ly immunoreactivity was seen. SC was localized in almost all ductal cells and in some acinar cells. Appearance of Lf in the ductal cells of PSG indicates an early sign of palatal sialadenitis. Some distinctions in the expression pattern of the marker proteins between the mucous acini of major salivary glands and PSG point to differences in the functional activities of either group of salivary glands.

Denture, Complete, Upper↗

Cross-reaction of a monoclonal anti-filaggrin antibody with glycogen.

A mouse monoclonal anti human filaggrin antibody was found to bind keratohyaline granules of normal epidermis as well as of premalignant and malignant lesions in formalin-fixed tissue sections. In addition, an unexpected binding of this antibody with cells containing glycogen and other PAS positive substances was found, which could be abolished by adsorption of the anti-filaggrin antibody with glycogen or pretreatment of the sections with diastase.

Antibodies, Monoclonal↗