bromochloroacetic-acid and Acantholysis

Topics: Acantholysis; Aged; Female; Humans; Hyperkeratosis, Epidermolytic; Ichthyosis; Keratins

We present a case of a patient with long-standing hyperpigmented macules and erythematous papules over his chest, abdomen, back and arms, suggestive of Dowling-Degos disease (DDD). In addition, there were hyperkeratotic papules, alternating red and white nail-bed discolouration, and V-shaped nail notching consistent with Darier disease (DD). Histology showed findings consistent with DDD and DD on separate specimens. The lack of acantholysis in areas of filiform hyperpigmented rete ridges ruled out Galli-Galli disease (GGD). DDD results from mutations in the genes encoding keratin 5 (KRT5), protein O-glucosyltransferase 1 (POGLUT1) or protein O-fucosyltransferase 1 (POFUT1), while DD results from mutations in the ATP2A2 gene. Both genes are present on chromosome 12. In this case, the patient presented with features of both DDD and DD, which suggests that either a cooperating mutation or a mutation in an unrelated gene locus may underlie the findings in this patient.

Topics: Acantholysis; Acneiform Eruptions; Chromosomes, Human, Pair 12; Darier Disease; Humans; Hyperpigmentation; Keratins; Male; Middle Aged; Mutation; Nail Diseases; Pedigree; Skin Diseases, Genetic; Skin Diseases, Papulosquamous

The pemphigus family of autoimmune bullous disorders is characterized by autoantibody binding to desmoglein 1 and/or 3 (dsg1/dsg3). In this study we show that EGF receptor (EGFR) is activated following pemphigus vulgaris (PV) IgG treatment of primary human keratinocytes and that EGFR activation is downstream of p38 mitogen-activated protein kinase (p38). Inhibition of EGFR blocked PV IgG-triggered dsg3 endocytosis, keratin intermediate filament retraction, and loss of cell-cell adhesion in vitro. Significantly, inhibiting EGFR prevented PV IgG-induced blister formation in the passive transfer mouse model of pemphigus. These data demonstrate cross-talk between dsg3 and EGFR, that this cross-talk is regulated by p38, and that EGFR is a potential therapeutic target for pemphigus. Small-molecule inhibitors and monoclonal antibodies directed against EGFR are currently used to treat several types of solid tumors. This study provides the experimental rationale for investigating the use of EGFR inhibitors in pemphigus.

Topics: Acantholysis; Animals; Animals, Newborn; Cell Adhesion; Cells, Cultured; Desmogleins; Desmosomes; Detergents; Disease Models, Animal; ErbB Receptors; Female; Gene Expression Regulation; Humans; Immunoglobulin G; Keratinocytes; Keratins; Male; Mice; Mice, Inbred C57BL; Microscopy, Confocal; Microscopy, Fluorescence; p38 Mitogen-Activated Protein Kinases; Pemphigus; RNA, Small Interfering; Signal Transduction

The autoimmune blistering skin disease pemphigus vulgaris (PV) is caused primarily by autoantibodies against desmosomal cadherins. It was reported that apoptosis can be detected in pemphigus skin lesions and that apoptosis can be induced by PV-IgG in cultured keratinocytes. However, the role of apoptosis in PV pathogenesis is unclear at present. In this study, we provide evidence that apoptosis is not required for acantholysis in PV. In skin lesions from two PV patients, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positivity, but not cleaved caspase-3, was detected in single keratinocytes in some lesions but was completely absent in other lesions from the same patients. In cultures of human keratinocytes (HaCaT and normal human epidermal keratinocytes), PV-IgG from three different PV patients caused acantholysis, fragmented staining of Dsg 3 staining, and cytokeratin retraction in the absence of nuclear fragmentation, TUNEL positivity, and caspase-3 cleavage and hence in the absence of detectable apoptosis. To further rule out the contribution of apoptotic mechanisms, we used two different approaches that are effective to block apoptosis induced by various stimuli. Inhibition of caspases by z-VAD-fmk as well as overexpression of Fas-associated death domain-like interleukin-1beta-converting enzyme (FLICE)-like inhibitory proteins FLIP(L) and FLIP(S) to inhibit receptor-mediated apoptosis did not block PV-IgG-induced effects, indicating that apoptosis was not required. Taken together, we conclude that apoptosis is not a prerequisite for skin blistering in PV but may occur secondary to acantholysis.

Topics: Acantholysis; Amino Acid Chloromethyl Ketones; Anoikis; Apoptosis; Biopsy; CASP8 and FADD-Like Apoptosis Regulating Protein; Caspase 3; Cell Line; Cell Nucleus Shape; Cysteine Proteinase Inhibitors; Desmoglein 3; DNA Fragmentation; Humans; Immunoglobulin G; Immunohistochemistry; In Situ Nick-End Labeling; Keratinocytes; Keratins; Pemphigus; Transfection

Although it is accepted that pemphigus antibody binding to keratinocytes (KCs) evokes an array of intracellular biochemical events resulting in cell detachment and death, the triggering events remain obscure. It has been postulated that the binding of pemphigus vulgaris IgG (PVIgG) to KCs induces "desmosomal" signaling. Because in contrast to integrins and classical cadherins, desmoglein (Dsg) molecules are not known to elicit intracellular signaling, and because PV patients also produce non-Dsg autoantibodies, we investigated the roles of both Dsg and non-desmoglein PV antigens. The time course studies of KCs treated with PVIgG demonstrated that the activity of Src peaked at 30 min, EGF receptor kinase (EGFRK) at 60 min, and p38 MAPK at 240 min. The Src inhibitor PP2 decreased EGFRK and p38 activities by approximately 45 and 30%, respectively, indicating that in addition to Src, PVIgG evokes other triggering events. The shrinkage of KCs (cell volume reduction) became significant at 120 min, keratin aggregation at 240 min, and an increase of TUNEL positivity at 360 min. Pretreatment of KCs with PP2 blocked PVIgG-dependent cell shrinkage and keratin aggregation by approximately 50% and TUNEL positivity by approximately 25%. The p38 MAPK inhibitor PD169316 inhibited these effects by approximately 15, 20, and 70%, respectively. Transfection of KCs with small interfering RNAs that silenced expression of Dsg1 and/or Dsg3 proteins, blocked approximately 50% of p38 MAPK activity but did not significantly alter the PVIgG-dependent rise in Src and EGFRK activities. These results indicate that activation of p38 MAPK is a late signaling step associated with collapse of the cytoskeleton and disassembly of desmosomes caused by upstream events involving Src and EGFRK. Therefore, the early acantholytic events are triggered by non-Dsg antibodies.

Topics: Acantholysis; Antigens; Autoantibodies; Cell Adhesion; Cell Shape; Cells, Cultured; Cytoskeleton; Desmoglein 1; Desmoglein 2; Desmosomes; DNA Fragmentation; Enzyme Inhibitors; ErbB Receptors; Humans; Imidazoles; Keratinocytes; Keratins; MAP Kinase Signaling System; p38 Mitogen-Activated Protein Kinases; Pemphigus; Pyrimidines; src-Family Kinases; Time Factors

Pemphigus vulgaris (PV) blistering occurs as a result of the disruption of intercellular contacts among keratinocytes, or acantholysis. The hallmark of PV acantholysis in vitro is considered to be the retraction of keratin intermediate filaments (KIF) onto the nucleus, which parallels with loss of cell-cell adhesion and rounding up of keratinocytes. However, the fine morphological changes of keratinocytes as well as the fate of cell adhesion structures cannot be appreciated on immunofluorescence by the simple cytokeratin staining. In this paper, we show that acantholytic dysmorphisms are sharply investigated by using PV IgG as a primary antibody on metabolically quiescent living cells. Indeed, PV IgG recognise a wide spectrum of molecules and enabled us to monitor the main changes occurring in acantholytic keratinocytes, including cell shrinkage with the appearance of prickle-like processes, detachment of keratinocytes from one another and collapse of cytoskeleton-bound proteins along nuclear periphery. This method has wider applications as it could be useful for staining cell periphery of keratinocytes and changes in cell shape. Furthermore, images displayed clear and sharp contours because living cell microscopy allows to avoid antigen distortion due to cell manipulation, which usually precedes the immunolabelling.

Topics: Acantholysis; Cell Line, Transformed; Cell Shape; Cell Size; Fluorescein-5-isothiocyanate; Fluorescent Dyes; Humans; Immunoglobulin G; Intermediate Filaments; Keratinocytes; Keratins; Microscopy, Fluorescence; Pemphigus; Staining and Labeling; Time Factors

Acantholytic carcinoma is a subtype of squamous carcinoma, characterized by tubular and alveolar formations as a consequence of the acantholysis. We report a case of vulvar squamous acantholytic carcinoma (VSAC) in a 69-year-old woman, who was admitted to our institution for vulvar pruritus and the presence of a large, bilateral, exophytic, and ulcerated lesion, measuring 7 x 8 cm. The patient had never received vulvar or pelvic radiation therapy. Pathological examination with an immunohistochemical study showed features of VSAC and high p16 protein expression. Molecular study by polymerase chain reaction amplification of DNA tumor revealed a weakly positive signal for human papillomavirus. In conclusion, our case, which is the first case of VSAC with polymerase chain reaction analysis and immunohistochemical expression of p16 protein, suggested that this neoplasm could be related to human papillomavirus infection.

Topics: Acantholysis; Aged; Carcinoma, Squamous Cell; Cyclin-Dependent Kinase Inhibitor p16; DNA, Viral; Female; Humans; Immunohistochemistry; Keratin-14; Keratins; Papillomaviridae; Papillomavirus Infections; Polymerase Chain Reaction; Tumor Virus Infections; Vimentin; Vulvar Neoplasms

Pemphigus vulgaris (PV) is an autoimmune blistering disease caused by IgG autoantibodies against desmoglein 3 (Dsg3). In this study, we characterized the ultrastructural localization of in vivo-bound IgG, Dsg3, and desmoplakin during the process of acantholysis in an active mouse PV model, using post-embedding immunoelectron microscopy. In non-acantholytic areas of keratinocyte contact, IgG labeling was restricted to the extracellular part of desmosomes, and was evenly distributed throughout the entire length of the desmosome. The distribution of in vivo IgG was similar to that of anti-Dsg3 labeling in the control mouse. Within the acantholytic areas, there were abundant split-desmosomes with keratin filaments inserted into the desmosomal attachment plaques. These split-desmosome extracellular regions were also decorated with anti-Dsg3 IgG and were associated with desmoplakin staining in their cytoplasmic attachment plaques. No apparent split-desmosomes, free of IgG-labeling were observed, suggesting that Dsg3 was not depleted from the desmosome before the start of acantholysis in vivo. Desmosome-like structures (without keratin insertion) were found only on the lateral surfaces of basal cells, but not on the apical surfaces at the site of acantholytic splits. These findings indicate that anti-Dsg3 IgG antibodies can directly access Dsg3 present in desmosomes in vivo and cause the subsequent desmosome separation that leads to blister formation in PV.

Topics: Acantholysis; Animals; Autoantibodies; Cadherins; Cytoskeletal Proteins; Desmoglein 3; Desmogleins; Desmoplakins; Desmosomes; Disease Models, Animal; Immunoglobulin G; Keratinocytes; Keratins; Mice; Mice, Mutant Strains; Microscopy, Immunoelectron; Pemphigus

Topics: Acantholysis; Actins; Cell Communication; Connexin 43; Desmosomes; Gap Junctions; Humans; Intercellular Junctions; Keratins; Pemphigus; Skin

Primary squamous cell carcinoma of the breast is a rare clinical entity. Two large review series found only five cases out of a total of 8351 breast malignancies. This case report presents a patient with metaplastic, pseudoangiosarcomatous carcinoma or acantholytic variant of a squamous cell carcinoma of the breast. This diagnosis was based on the histological finding of highly atypical, acantholytic squamous cells. Because the tumor stained positive for keratin and negative for factor VIII, the diagnosis of angiosarcoma was ruled out. Although only scattered case reports have been published on this histological variant, these tumors tend to follow an aggressive course.

Topics: Acantholysis; Breast Neoplasms; Carcinoma, Squamous Cell; Female; Humans; Keratins; Middle Aged

Transient acantholytic dermatosis is often associated with excessive sweating, fever, and bed confinement. The pathogenesis of this disease has been postulated to be poral occlusion of damaged eccrine intraepidermal ducts. Histological and immunohistochemical and ultrastructural studies were performed on 10 biopsies from 10 patients with transient acantholytic dermatosis. Immunoreactions for carcinoembryonic antigen and cytokeratin-7 to identify eccrine duct epithelium were performed on all 11 biopsies. In addition, 5 of the biopsies were immunoreacted for cytokeratin 8. All immunoreactions were reviewed independently by two observers to determine extent of reactivity and whether it correlated with areas of epidermal acantholysis. Among the 11 biopsies, 8 showed acantholysis not associated with eccrine duct outflow tracts. In 2 biopsies the acantholysis was consistently associated with acrosyringea; in one case acantholysis was inconsistently associated with eccrine outflow tracts. Epidermal acantholysis in patients with Grover's disease is associated with the outflow tracts of eccrine ducts in a subgroup of patients. Although leakage of sweat from occluded sweat ducts in acrosyringia may be the mechanism operating in a subgroup of patients with Grover's disease, this does not appear to be the subgroup of patients in whom Grover's disease develops in the setting of being bedridden and/or sweating.

Topics: Acantholysis; Adult; Aged; Aged, 80 and over; Biopsy; Carcinoembryonic Antigen; Eccrine Glands; Humans; Immunohistochemistry; Keratin-7; Keratins; Male; Middle Aged; Sweat Gland Diseases

Acantholysis is a feature of disorders such as Hailey-Hailey disease and Darier's disease. Immunocytochemical studies have shown internalization of desmosomal components after acantholysis. Basal cytokeratins show suprabasal expression in lesional Darier's disease. The exact mechanisms of acantholysis are still unclear. Cantharidin induces blistering, with suprabasal keratinocyte acantholysis, possibly by protease activation. Plasmin has been implicated in the pathogenesis of acantholysis in Darier's disease and Hailey-Hailey disease. We examined the distribution of desmosomal components, proteases and cytokeratins in cantharidin blisters, to compare them with those previously found in Darier's disease and Hailey-Hailey disease. Two drops of cantharidin collodion were applied to the skin of five normal volunteers. A 4-mm punch biopsy of the blister was taken, and snap frozen. Sections were stained with antibodies to desmosomal proteins (dp) 1/2, dp 3, desmosomal glycoproteins (dg) 1, 2/3, extracellular carbohydrate residues, using the lectins peanut agglutinin (PNA) and soybean agglutinin (SBA), proteases and cytokeratins. Acantholytic cells were stained diffusely with dp1/2; there was markedly reduced or absent peripheral staining for dp3, dg1, dg2/3, PNA and SBA. There was no clumping of stain. Plasminogen, fibrinogen and urokinase were expressed in some acantholytic cells. Basal keratin markers were expressed suprabasally in acantholytic cells. These results are similar to those previously obtained in Darier's disease, but different from the staining obtained in Hailey-Hailey disease. Extracellular glycosylated portions of adhesion molecules may be lost after acantholysis, perhaps as a result of conformational changes, internalization of extracellular domains, or proteolysis. The changes in the expression of plasminogen, fibrinogen, urokinase and cytokeratins in acantholytic cells in cantharidin-induced blisters are, as in Darier's disease and Hailey-Hailey disease, probably secondary to acantholysis, and changes in the shape of cells. We conclude that cantharidin blisters may be a useful model for the study of acantholysis in Darier's disease.

Topics: Acantholysis; Cantharidin; Cell Adhesion Molecules; Cytoskeletal Proteins; Desmoplakins; Fibrinogen; Humans; Immunohistochemistry; Keratins; Models, Biological; Peptide Hydrolases; Plasminogen; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator

We have examined the action of cantharidin on the skin of patients with Darier's disease, and used immunohistological techniques to determine the distribution of desmosomal components, keratin intermediate filaments, and proteases in cantharidin-induced blisters. Cantharidin induced acantholysis, but the presence of acantholysis did not trigger the development of the characteristic warty, dyskeratotic papules in patients with Darier's disease. The distribution of desmosomal components, keratins and proteases within the acantholytic keratinocytes in the cantharidin-induced blisters was similar to that previously found in acantholytic cells within lesions of Darier's disease: peripheral staining for extracellular desmosomal components was reduced; some desmosomal components were detected diffusely in the acantholytic cells; basal cell keratin markers were expressed by some suprabasal acantholytic cells, and plasminogen was detected in association with acantholytic cells. Cleavage of desmosomes did not reveal the underlying abnormality in Darier's disease.

Topics: Acantholysis; Adult; Basement Membrane; Cantharidin; Collagen; Cytoskeletal Proteins; Darier Disease; Desmoplakins; Desmosomes; Female; Fibrinogen; Humans; Immunohistochemistry; Keratinocytes; Keratins; Male; Middle Aged; Plasminogen; Skin; Urokinase-Type Plasminogen Activator

Injury to epidermis and other stratified epithelia triggers profound but transient changes in the pattern of keratin expression. In postmitotic cells located at the wound edge, a strong induction of K6, K16, and K17 synthesis occurs at the expense of the keratins produced under the normal situation. The functional significance of these alterations in keratin expression is not known. Here, we report that overexpression of a wild-type human K16 gene in a tissue-specific fashion in transgenic mice causes aberrant keratinization of the hair follicle outer root sheath and proximal epidermis, and it leads to hyperproliferation and increased thickness of the living layers (acanthosis), as well as cornified layers (hyperkeratosis). The pathogenesis of lesions in transgenic mouse skin begins with a reorganization of keratin filaments in postmitotic keratinocytes, and it progresses in a transgene level-dependent fashion to include disruption of keratinocyte cytoarchitecture and structural alterations in desmosomes at the cell surface. No evidence of cell lysis could be found at the ultrastructural level. These results demonstrate that the disruption of the normal keratin profile caused by increased K16 expression interferes with the program of terminal differentiation in outer root sheath and epidermis. They further suggest that when present at sufficiently high intracellular levels, K16, along with K6 and K17, appear capable of inducing a reorganization of keratin filaments in the cytoplasm of skin epithelial cells.

Topics: Acantholysis; Amino Acid Sequence; Animals; Cell Adhesion; Cytoskeleton; Desmosomes; Epidermis; Female; Gene Expression Regulation; Hair; Humans; Keratinocytes; Keratins; Male; Mice; Mice, Transgenic; Microscopy, Electron; Molecular Sequence Data; Phenotype; Skin Diseases

To investigate the mechanisms by which cutaneous plasminogen activator (PA) may be regulated, we have tested cultured keratinocytes for the presence of PA inhibitors. Using biosynthetic labeling experiments with 35S-methionine in conjunction with specific antibody precipitation, we have shown that human keratinocytes in culture synthesized and secreted both PA inhibitor 1 and PA inhibitor 2. PA inhibitor 1 was present in conditioned media in the inactive form, but it could be detected with reverse phase autography. PA inhibitor 2 was detected by its ability to form complexes with 125I-uPA. Potential therapeutic relevance for cutaneous PA inhibitor 2 was suggested in skin organ culture experiments which demonstrated that purified PA inhibitor 2 from human placenta was able to prevent the acantholytic changes induced by pemphigus IgG.

Topics: Acantholysis; Cells, Cultured; Culture Techniques; Epidermal Cells; Epidermis; Glycoproteins; Humans; Immunoglobulin G; Keratins; Pemphigus; Plasminogen Activators; Plasminogen Inactivators; Skin Diseases; Urokinase-Type Plasminogen Activator

Focal acantholytic dyskeratosis (FAD) is considered an incidental histological finding of unknown etiology. It has been described in association with only few pathological conditions. To the best of our knowledge, we report the first case of focal acantholytic dyskeratosis occurring in condyloma acuminata.

Topics: Acantholysis; Adult; Biopsy; Condylomata Acuminata; Genital Diseases, Male; Humans; Keratins; Male; Skin Diseases

The role of plasminogen activator (PA) in the pathogenesis of acantholysis in canine pemphigus vulgaris (PV) was evaluated using differentiated cultures of canine oral keratinocytes. Both the secreted and cell-associated PA activity in cultured canine keratinocytes were completely inhibited by specific anti-urokinase antibodies. Anti-tissue type PA antibodies did not inhibit either secreted or cell-associated PA activity. Immunoblots and fibrin zymography revealed a single 57,000 molecular weight urokinase-type PA in the conditioned media of the canine oral keratinocytes. Incubation of the differentiated cultures with PV Ig resulted in a significant increased in the levels of PA activity and both canine and human PV Ig were effective at inducing acantholysis typical of that seen in the clinical disease. The addition of urokinase inhibitor to the cultures treated with PV Ig prevented the development of acantholysis. These data strongly support the conclusion that PA is involved in acantholysis which is the cardinal feature of PV.

Topics: Acantholysis; Animals; Antibodies; Cells, Cultured; Dogs; Epidermis; Immunoglobulins; Keratins; Pemphigus; Plasminogen Activators; Plasminogen Inactivators; Urokinase-Type Plasminogen Activator

Focal acantholytic dyskeratosis (FAD) is a distinctive histologic pattern characterized by suprabasilar clefts surrounding dermal papillae (villi), acantholytic and dyskeratotic cells at all levels of the epidermis, hyperkeratosis, and parakeratosis. The features of FAD are typically seen in Darier's disease, warty dyskeratoma, and transient acantholytic dermatosis; they are also present in a variety of cutaneous neoplastic and nonneoplastic lesions. FAD, however, has not been previously described in lesions of inflammatory dermatoses. We report a case of FAD occurring in lesions of pityriasis rubra pilaris (PRP). To the best of our knowledge, this is the first reported case of this kind. We also review the pertinent literature.

Topics: Acantholysis; Epidermal Cells; Humans; Keratins; Male; Middle Aged; Pityriasis Rubra Pilaris; Skin Diseases

Ultrastructural localization of pemphigus vulgaris antigen-antibody complexes and their fate during acantholysis were studied in epidermal sheets obtained from the area surrounding the bullae and in acantholytic cells in blister fluid. The distribution of pemphigus vulgaris antibodies already bound to the keratinocytes in early acantholytic lesions was detected with ferritin-conjugated goat antihuman IgG. Ferritin particles were observed on the surface of keratinocytes with particular affinity for desmosomal structures. The acantholytic cells in the blister fluid bound only a small number of ferritin particles on their surface. During incubation at 37 degrees C, pemphigus vulgaris antigen-antibody complexes on the surface of separated desmosomes were internalized and recognized in cytoplasmic vesicles. Endocytosis of separated desmosomes also was observed in vivo when freshly obtained epidermal sheets were immediately processed for routine electron microscopic study. These findings suggest that pemphigus vulgaris antibodies are densely located on desmosomes and that the antigen-antibody complexes, together with other serum proteins on the keratinocyte surface, are internalized by a process of endocytosis.

Topics: Acantholysis; Binding Sites, Antibody; Epidermis; Humans; Keratins; Pemphigus; Skin Diseases

A case of a 70-year-old man with several dome-shaped tumors with acantholysis was reported. The histopathological findings of these black-brownish colored tumors on the back were compatible with seborrheic keratosis, consisting of basaloid and squamoid cells. Although three cases reported by Tagami et al. (1978) and Uchiyama et al. (1986) showed intraepidermal epithelioma-like tumor nests in the acanthotic lesions, our case was thought to correspond to another variant of seborrheic keratosis with acantholysis.

Topics: Acantholysis; Aged; Biopsy; Dermatitis, Seborrheic; Humans; Keratins; Keratosis; Male; Skin Diseases

Using the Combi-ring-dish (CRD), a new culture device, organotypic cultures of human epidermal keratinocytes were grown on bovine eye lens capsules. In these highly differentiated cultures, typical suprabasal acantholysis was induced by pemphigus vulgaris antibodies. This in vitro pemphigus vulgaris model may be used to analyse keratinocyte-derived factors causing acantholysis in experimental pemphigus.

Topics: Acantholysis; Animals; Antibodies; Cattle; Cells, Cultured; Cytological Techniques; Epidermis; Humans; Keratins; Microscopy, Electron; Pemphigus

An 11-year-old girl affected by keratosis punctata palmaris et plantaris, histologically showing focal acantholytic dyskeratosis, is described. This case demonstrates that keratosis punctata palmaris et plantaris may represent a new clinical expression of persistent multiple focal acantholytic dyskeratosis.

Topics: Acantholysis; Biopsy; Child; Female; Humans; Keratinocytes; Keratins; Keratoderma, Palmoplantar; Skin; Skin Diseases

Two patients with Darier's disease--diagnosed clinically by the presence of characteristic keratotic papules in seborrheic areas--were biopsied for light- and electron-microscopic studies. Light microscopy revealed typical histologic features of Darier's disease. Ultrastructural studies showed the presence of cytoplasmic processes projecting from the basal keratinocytes (basal keratinocyte herniations) into the underlying dermis through small defects in the basal lamina, which was intact in some areas but in other locations showed thickening, irregularity, and replication. Widening of the lamina lucida with partial or complete disappearance of hemidesmosomes were noted in many areas.

Topics: Acantholysis; Basement Membrane; Biopsy; Darier Disease; Desmosomes; Humans; Intermediate Filaments; Keratins; Microscopy, Electron; Skin

Darier first described dyskeratotic cells as infectious agents, but he later wrote that they were caused by abnormal keratinization. He grouped various inflammatory, infectious, and neoplastic skin diseases under the term "dyskeratoses." It is argued herein that the dyskeratotic cell and the so-called dyskeratoses have not been defined in a consistent manner because Darier's concepts were incorrect. Darier's dyskeratotic cell is classified here as one type of necrotic keratinocyte. Some conditions in which dyskeratotic and necrotic keratinocytes occur are described.

Topics: Acantholysis; Cell Survival; Darier Disease; Epidermis; France; History, 19th Century; History, 20th Century; Keratins; Skin Diseases; Skin Neoplasms; Terminology as Topic

This article describes 31 examples of acantholytic acanthoma, a newly recognized, solitary, benign cutaneous tumor. Acantholytic acanthoma was typically an asymptomatic, keratotic papule or nodule. Patients ranged in age from 32 to 87 years (median 60 years); the ratio of men to women was 2:1; the most frequent clinical diagnosis was keratosis; and half of the growths were on the trunk of the body. Histologically, the lesions showed hyperkeratosis, papillomatosis, and acanthosis. Acantholysis was an outstanding finding in all cases; the patterns resembled pemphigus vulgaris, pemphigus vegetans, superficial pemphigus, or Hailey-Hailey disease, but no patient had evidence of any of these disorders. The term acantholytic is used because acantholysis is the outstanding histologic feature in these neoplasms; acanthoma was chosen because the growths are benign tumors of epidermal keratinocytes. The relationship of acantholytic acanthoma to acantholytic blistering disease is similar to that of solitary lichen planus-like keratosis to lichen planus and epidermolytic acanthoma to bullous congenital ichthyosiform erythroderma.

Topics: Acantholysis; Adult; Aged; Aged, 80 and over; Diagnosis, Differential; Epidermis; Female; Humans; Keratins; Male; Middle Aged; Papilloma; Skin Diseases; Skin Neoplasms

Topics: Acantholysis; Adult; Darier Disease; Epidermis; Female; Humans; Keratins; Skin Diseases

Histopathological, cytomorphological and electron microscopic analyses in a case of fogo selvagem are reported. Contradictory to the light microscopical findings, the acantholysis as seen with the electron microscope involves the basal layer but not the subcorneal layers--at least not the most superficial part of the granular layer. A conspicuous disintegration of the tonofilament-desmosome complexes give rise to the concomitant dyskeratosis. This aberrant process, including an association between retracing tonofilaments and defective Odland bodies, results in the terminal stage of monstrous defective and specific keratohyalin. In cytoplasm, target-like structures similar to virions of the herpes virus group were observed. The dynamics of the pathological process is discussed.

Topics: Acantholysis; Aged; Cytoplasm; Epidermis; Humans; Keratins; Male; Microscopy, Electron; Skin; Skin Diseases; Skin Diseases, Vesiculobullous

Topics: Acantholysis; Carcinoma, Squamous Cell; Cell Membrane; Cytoplasm; Desmosomes; Epithelial Cells; Epithelium; Extracellular Space; Humans; Keratins; Langerhans Cells; Melanins; Mitochondria; Organoids; Ribosomes; Skin Neoplasms

In biopsies from the oral mucosa of 235 cases in which the diagnosis was lichen planus, keratosis or leukoplakia, mitotic values were calculated for the stratum basale (M.V. basal) and the stratum spinosum (M.V. spinous). The mean M.V. basal was significantly different from the mean M.V. spinous in the keratosis and leukoplakia groups, but not in the lichen planus group. Within the keratosis and leukoplakia groups, M.V. basal and M.V. spinous were significantly correlated. When each of the mean M.V.s was compared with the M.V.s for the other diagnostic groups, various significant differences were found. The M.V.s were examined in relation to the type of keratinization, the presence of acanthosis or atrophy, and the patient's age, but the M.V.s were not significantly related to these features.

Topics: Acantholysis; Age Factors; Atrophy; Epithelium; Humans; Keratins; Keratosis; Leukoplakia, Oral; Lichen Planus; Mitosis; Mouth Diseases; Mouth Mucosa

Topics: Acantholysis; Carcinoma in Situ; Electrons; Humans; Keratins; Microscopy, Electron; Pemphigus