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PubMed1989

Altered keratin expression in benign and malignant skin diseases revealed with monoclonal antibodies.

We studied keratin expression in benign epidermal skin diseases, and in Bowen's disease by using three monoclonal cytokeratin antibodies. In adult normal skin, these antibodies bind only to the follicular epithelium (PKK1), the basal keratinocytes (PKK2), or the suprabasal cells in interfollicular epidermis (KA5). Additionally, in fetal epidermis, the PKK1 antibody reacts with basal keratinocytes. In psoriasis and lichen planus, the PKK2 antibody distinctly revealed all epidermal cell layers by immunostaining. However, a negative basal cell-like layer was revealed in both lesions with the KA5 antibody. In pityriasis rubra pilaris, the basal cell layer was uniformly stained with the PKK2 antibody, but only some keratinocytes in upper cell layers showed fluorescence and, in chronic eczema, the 3-4 lowest epidermal cell layers were reactive. The PKK1 antibody did not stain interfollicular keratinocytes in any of the benign proliferative skin diseases studied. In Bowen's disease, a heterogeneous staining pattern with varying intensity among individual cells was seen with all of the antibodies used. Our results suggest different changes in keratin expression in chronic benign and malignant epidermal diseases that may reflect the mechanisms behind these changes.

Antibodies, Monoclonal↗
PubMed1993

Expression patterns of loricrin in dermatological disorders.

Loricrin is a glycine-, serine-, and cysteine-rich protein expressed very late in epidermal differentiation in the granular layers of normal human epidermis. Subsequently, loricrin becomes cross-linked by the activity of transglutaminases TGK/E as a major component of the cornified cell envelope by N epsilon-(gamma-glutamyl)lysine isopeptide bonds. In this study, 115 biopsy specimens from patients with various cutaneous diseases with a morphologically altered epidermal differentiation were analyzed with use of immunohistology with antibodies to loricrin and to involucrin. In addition, antibodies to filaggrin were used for ichthyotic lesions. In contrast to involucrin, loricrin expression was consistently down-regulated in agranulotic, parakeratotic keratinization as observed in psoriasis, dermatitis, pityriasis lichenoides, porokeratosis, or precancerous and malignant squamous lesions. High levels of loricrin were found in hypergranulotic and hyperorthokeratotic epidermis as observed in lichen planus, benign papillomas, and pseudocarcinomatous hyperplasia. Eleven biopsy specimens from patients with ichthyosis vulgaris showed a normal staining in the granular layers. Our results demonstrate that loricrin expression is closely linked to an orthokeratotic phenotype of human epidermal keratinization. The different expression patterns of loricrin and involucrin provide further evidence that these proteins are regulated by different mechanisms and serve different functions during terminal epidermal differentiation.

Filaggrin Proteins↗
PubMed1997

Papular urticaria: a histopathologic study of 30 patients.

Papular urticaria is the result of hypersensitivity (id-reaction) to bites from certain insects such as mosquitoes gnats, fleas, mites, and bedbugs. Papular urticaria is common in childhood and is characterized by symmetrically distributed pruritic papules and papulovesicles. Scratching causes erosions and ulcerations. Pyoderma is common. Lesions occur in crops. The histopathologic features of papular urticaria are inadequately documented. In a prospective study we recorded the histopathologic features of 30 patients (female, 18; male, 12) with papular urticaria. Their ages ranged from 6-343 months (median = 21 months, mean = 37.73 months). Features that presented in more than 50% of cases included mild acanthosis, mild spongiosis, exocytosis of lymphocytes, mild subepidermal edema, extravasation of erythrocytes, a superficial and deep mixed inflammatory cell infiltrate of moderate density, and interstitial eosinophils. We recognized lymphocytic (n = 4), eosinophilic (n = 9), neutrophilic (n = 7), and mixed (n = 9) subtypes. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections from 10 cases and revealed abundant T-lymphocytes (CD45RO, CD3) and macrophages (CD68) in all cases. B-lymphocytes (CD20) and dendritic antigen-presenting cells (S100) were absent. Direct immunofluorescence staining was conducted on cryostat-prepared sections from 26 specimens. Deposition of IgA, IgG, IgM, C3, and fibrin could not be demonstrated. The histopathologic differential diagnosis of papular urticaria includes other spongiotic dermatitides, pityriasis lichenoides et varioliformis acuta, the pruritic papular eruption of human immunodeficiency virus disease, and papulonecrotic tuberculid. Papular urticaria with marked spongiosis and a dense inflammatory cell infiltrate cannot be reliably distinguished from arthropod bites on clinical and histopathologic grounds. The present study provides morphologic and immunohistochemical evidence that a type I hypersensitivity reaction plays a central role in the pathogenesis of papular urticaria. The putative antigen remains undetermined.

Adolescent↗
PubMed1997

Erythema elevatum diutinum: a clinicopathological study of eight cases.

Erythema elevatum diutinum (EED) is a rare cutaneous condition that initially presents as leukocytoclastic vasculitis (LCCV) of the skin and later resolves with fibrosis. In addition to the LCCV, EED may show features reminiscent of other entities. For example, it may mimic lesions of dermatofibroma, granuloma annulare, granuloma faciale, or dermatitis herpetiformis. For this study, we reviewed the clinical records and 13 skin biopsies in eight patients with EED. One of the patients had concurrent pityriasis rubra pilaris, and another developed lesions of EED following and at the sites of mosquito bites; these associations have not been noted previously. In addition to such typical histopathological features as diffuse dermal involvement by neutrophils, eosinophils, and leukocytoclastic vasculitis, we also found two unusual patterns. The first was characterized by palisaded necrotizing granulomas, as previously described and associated with Churg-Strauss granuloma; the second condition simulated a pyogenicgranuloma--like lesion.

Adult↗
PubMed1994

The histologic spectrum of mycosis fungoides/Sézary syndrome (cutaneous T-cell lymphoma). A review of 222 biopsies, including newly described patterns and the earliest pathologic changes.

We studied 222 skin biopsies of mycosis fungoides and Sézary syndrome (cutaneous T-cell lymphoma [CTCL]) to document the huge histologic spectrum and to evaluate the earliest histologic changes. Our results indicate that CTCL produces practically all of the patterns used for diagnosing inflammatory skin disease: superficial or superficial and deep perivascular without epidermal changes; spongiotic; psoriasiform, with or without a lichenoid infiltrate; interface, including lichenoid without vacuolar alteration, lichenoid with vacuolar alteration, and vacuolar alteration without a lichenoid infiltrate; follicular, with or without mucin; nodular and diffuse; vasculitis; vesicular; and panniculitis. Unusual examples resembling granuloma annulare, gyrate erythema, lichen planus, and pityriasis lichenoides were seen. To further document the spectrum within each pattern, we analyzed many variables, such as lymphocytic atypia, epidermotropism, epidermal contour, and composition of the dermal infiltrate. Common clues to the diagnosis of CTCL include epitheliotropism with little spongiosis; lymphocytes lined up along the basal layer; hyperconvoluted lymphocytes; and broad areas of slight hyperorthokeratosis that is compact or laminated, with subtle interspersed parakeratosis. Less common clues include Pautrier's microabscesses; granulomatous foci; coexistence of plasma cells and eosinophils; and rounded, hyperplastic rete ridges adjacent to flattened rete. The earliest changes of CTCL appear to be a sparse, superficial perivascular infiltrate with slight or no epidermal hyperplasia and with rare lymphocytes in the lower epidermis, especially the basal layer, often with hyperconvoluted nuclei. Our findings support the hypothesis that CTCL develops sui generis, rather than from another chronic dermatosis.

Adolescent↗
PubMed2002

Malassezia species in skin diseases.

Since the taxonomic revision carried out in 1996, enlarging the genus Malassezia to comprise seven different species, a number of studies have investigated from different points of view -- mycological, molecular and immunological -- the relationships of these species with the pathologies associated with lipophilic yeasts, as well as its presence in healthy skin. From these studies, it now appears clear that Malassezia globosa is the main species associated with pityriasis versicolor, which is the only cutaneous disease in which the involvement of Malassezia is undisputed. Nevertheless, this species can also be found in normal skin, in which the predominant species is Malassezia sympodialis. In the remaining dermatological disorders related to Malassezia, the role of these yeasts is controversial. In seborrhoeic dermatitis, atopic dermatitis and folliculitis, several studies have focused on the immunological aspects that could explain the pathogenic mechanism. In other diseases, such as confluent and reticulate papillomatosis, neonatal pustulosis, otitis and onychomycosis, the presence or significance of Malassezia is still a matter of dispute.

Dermatomycoses↗
PubMed2002

A T-cell receptor gamma polymerase chain reaction assay using capillary electrophoresis for the diagnosis of cutaneous T-cell lymphomas.

Detection of clonal T-cell receptor gamma rearrangements by polymerase chain reaction (TCRgamma PCR) followed by high-resolution electrophoresis has now become a valuable tool in the diagnosis of cutaneous T-cell lymphoma (CTCL). The identification of clonal TCRgamma PCR products by fluorescent fragment analysis (FFA) on a capillary DNA sequencer is described here and compared with an established hetero-duplex temperature gradient gel electrophoresis (HD-TGGE). Of 55 CTCL derived lesional skin samples, clonality was obtained in 46 samples by FFA (83.6%) and in 45 samples by HD-TGGE (81.8%). Of 35 control skin specimens from various nonmalignant dermatoses, two samples (pityriasis lichenoides chronica) showed clonality by both methods, one sample (chronic dermatitis) only by FFA. The sensitivity of FFA was established using three clonal T-cell lines and peripheral blood mononuclear cells. The detection limit for clonal material was approximately 1% to 2.5% in mixtures of DNA and 1% to 3% in cell dilutions. For cell dilution series, we confirmed a linear correlation between the clonal/polyclonal peak-size ratios and the portion of clonal cells up to about 10%. Thus, the initial ratio between mono-and polyclonal template is correctly displayed by FFA within that concentration range. In conclusion, FFA on capillary DNA sequencer is a well-suited separation technique in TCRgamma PCR-based clonality analysis also exhibiting quantitative properties.

Clone Cells↗
PubMed2004

Assessment of T-cell clonality via T-cell receptor-gamma rearrangements in cutaneous T-cell-dominant infiltrates using polymerase chain reaction and single-stranded DNA conformational polymorphism assay.

Discerning the pathologic significance of cutaneous T-cell infiltrates can pose a diagnostic challenge for dermatopathologists. Reactive conditions such as drug-associated lymphomatoid hypersensitivity and lymphomatoid lupus erythematosus can demonstrate lymphoid atypia and a phenotype resembling cutaneous T-cell lymphoma (CTCL). Further, lymphoid dyscrasias such as pityriasis lichenoides chronica, large plaque parapsoriasis, and atypical pigmentary purpura confuse the picture because they not only mimic CTCL but also represent prelymphomatous states with inherent malignant potential. Although the emergence of a dominant clone has been considered a clue indicative of a T-cell dyscrasia, there are reports concerning the identification of monoclonality in biopsies of reactive lymphoid infiltrates. We have conducted a modified single-stranded DNA conformational polymorphism (SSCP) assay using paraffin-embedded, formalin-fixed tissue on 92 T-cell-rich biopsies to determine the relative specificity and sensitivity of this methodology. In addition, laser capture microdissection (LCM) was performed on 22 of the 92 samples to isolate the area of interest and to compare its specificity and sensitivity with those SSCP assays performed without LCM. We found that monoclonality or oligoclonality is 86% specific for preneoplastic and neoplastic states, whereas the finding of polyclonality appears to be relatively specific for a reactive process. Some cases of reversible T-cell dyscrasia produced a molecular profile mimicking lymphoma or prelymphomatous states by virtue of monoclonality or oligoclonality. Although LCM appears to improve the sensitivity for detecting preneoplastic conditions, the relative specificity appears to be the same as that encountered with routine SSCP.

Clone Cells↗
PubMed1985

Purification and in vitro growth of human epidermal basal keratinocytes using a monoclonal antibody.

We have made a new monoclonal antibody, EL-2, and used it with an immunorosetting procedure combined with Ficoll-Hypaque gradient centrifugation to purify and culture basal keratinocytes. Immunofluorescence of cell suspensions and immunoperoxidase staining of tissue sections demonstrate that EL-2 reacts with malignant cell lines, activated lymphocytes and monocytes, and basal keratinocytes. Sequential immunoprecipitation studies demonstrate that monoclonal antibodies EL-2 and 4F2 detect the same membrane protein. However, we have extended previous studies by making the new observation that both EL-2 and 4F2 react with cultured melanocytes. Basal keratinocytes were purified from single-cell epidermal suspensions by incubation with EL-2 followed by rosetting with rabbit antimouse IgG antibodies covalently linked to bovine red blood cells. Rosetting (basal) keratinocytes were separated from EL-2 negative cells by Ficoll gradient centrifugation. We obtained basal keratinocyte populations of greater than 90% purity as assessed by reactivity with EL-2 and another basal keratinocyte-specific monoclonal antibody, HCl. Langerhans cell, fibroblast, and melanocyte contamination was negligible. Cultures of basal keratinocytes were enriched in EL-2-reactive cells throughout the entire 19 days of culture studied. EL-2 is being used to characterize disorders of keratinocyte proliferation; EL-2 reacted with both squamous and basal cell carcinomas. EL-2 stained only the basal layer of lesional skin from patients with psoriasis, pityriasis rubra pilaris, and Darier's disease. Purification of basal keratinocytes will be important in biochemical and functional studies of normal skin and in establishing long-term keratinocyte lines from normal cells.

Antibodies, Monoclonal↗
PubMed1984

Clinical observations, virologic studies, and treatment trials in patients with epidermodysplasia verruciformis, a disease induced by specific human papillomaviruses.

We have studied 11 patients with the papillomavirus-induced disease epidermodysplasia verruciformis (EV). Clinical diagnostic features are widespread, long-lasting, pityriasis versicolor-like macules and flat, wart-like papules, both usually occurring in early childhood, with the subsequent development in the third decade of multiple skin cancers of the Bowenoid in situ and squamous cell types, primarily in sun-exposed skin. Virologic studies using the methods of immunofluorescence microscopy, restriction endonuclease analysis, and DNA blot hybridization have shown benign lesions to be associated with one or several types of the human papillomaviruses (HPVs) specifically associated with EV (at least 15 types recognized on the basis of sequence homology studies of molecularly cloned genomes). Skin cancers in these patients were associated with the genomes of either HPV-5, HPV-8 or HPV-14, suggesting that these three viruses are potentially oncogenic. A genetic factor appears to play a role in the pathogenesis of EV, since 5 of our patients were children of consanguineous parents and 2 had siblings also suffering with EV, suggesting a recessive inheritance pattern. Treatment of 4 EV patients with an oral retinoid resulted in partial temporary improvement of benign lesions, and the treatment of 2 patients with intralesional interferon injections into multiple Bowenoid cancers in situ has resulted in the disappearance of these lesions. Finally, EV serves as a model for studying the interplay of oncogenic viruses, genetic and immunologic factors, and sunlight in the production of skin cancer in humans.

Adult↗
PubMed1988

Epidermodysplasia verruciformis in a patient with Hodgkin's disease: characterization of a new papillomavirus type and interferon treatment.

A new human papillomavirus (HPV) was discovered in disseminated, macular, pityriasis versicolor-like lesions on the skin of the neck, face, scalp, and pubic region of a 42-year-old male suffering from Hodgkin's disease. Histopathology revealed features characteristic of epidermodysplasia verruciformis (ev). In contrast to classical ev, the lesions were almost exclusively seen in previously irradiated and UV-exposed skin areas. Papillomavirus capsid antigen was demonstrated with the genus-specific antiserum and the patient's serum, which had IgM and IgG antibody titers. HPV DNA was isolated from biopsies and cloned into the vector pIC20H. It proved to be related to ev-associated viruses, showing 23% cross-hybridization with DNA of the closest relative HPV14. The new HPV type was named HPV46. The genome was physically mapped and colinearly aligned with HPV8 DNA to establish its gene organization. Interferon treatment of the patient did not significantly change the clinical picture nor was the concentration of viral DNA per lesion affected. However, no virus capsid antigen was detectable after starting treatment.

Adult↗
PubMed1979

Epidermodysplasia verruciformis versus disseminated verrucae planae: is epidermodysplasia verruciformis a generalized infection with wart virus?

Recently it has been shown that epidermodysplasia verruciformis is induced by human papilloma/virus different from the papilloma/virus of warts, and that 2 distinct viruses-designated HPV-3 and HP-4--are responsible for it. Ten cases of epidermodysplasia verruciformis were found to have been caused by HPV-3. Clinically and histologically, as well as in the often depressed cell-mediated immunity they closely resembled long-standing verrucae planae, also caused by HPV-3. Contrariwise, in epidermodysplasia verruciformis caused by HPV-4 there are characteristic red, red-brown, and depigmented, pityriasis versicolor-like plaques, and malignant transformation seems almost inevitable. Cases due to HPV-3 may be abortive or even regressive, or stationary, and hard to distinguish from flat warts. No malignant conversion was seen in patients infected only with HPV-3, whereas it occurred in 2 patients infected with both viruses: HPV-3 and HPV-4. Pigmented plaques are the most important adverse prognostic sign in EV induced by HPV-3.

Animals↗
PubMed1980

A potentially oncogenic human papillomavirus (HPV-5) found in two renal allograft recipients.

We have observed 2 immunosuppressed renal allograft recipients with skin lesions induced by human papillomavirus type 5 (HPV-5). One recipient had multiple pityriasis versicolor-like (PV-like) skin lesions on his arms and trunk, and multiple Bowenoid in-situ skin cancers. The other had 2 warty lesions on the back of her fingers. Structural antigens of human papillomavirus type 5 (HPV-5) were identified in benign lesions from both patients by immunofluorescence. The histologic and ultrastructural features observed in lesions from both patients were similar to those previously seen in HPV-5-induced lesions occurring in patients with the rare disease epidermodysplasia verruciformis (EV). The severe form of EV is characterized by HPV-5-induced PV-like lesions, multiple skin cancers, and usually depressed cell-mediated immunity. The picture seen in one of our renal allograft recipients recalls this severe form of EV. HPV-5, until now, has been found only in EV patients. The role of this potentially oncogenic virus in skin cancers which are known to occur with increased frequency in immunosuppressed renal allograft recipients must be determined.

Adult↗
PubMed1977

Induction of hyphae in cultures of Pityrosporum by cholesterol and cholesterol esters.

The effect of cholesterol and cholesterol esters on Pityrosporum cultures has been studied. A mixture of 0.25% to 2.0% of cholesterol:cholesteryl stearate:glyceryl monostearate (2.0:1.5:2.0) added to Bacto Yeast Morphology Agar plus oleic acid was able to induce hyphae in cultures of both Pityrosporum orbiculare and P. ovale. This result is discussed with respect to the cholesterol effect on cell membranes and to the occurrence of cholesterol and cholesterol esters in the scaling patches of Pityriasis versicolor.

Cell Membrane↗
PubMed2006

Dermoscopy in epidermodysplasia verruciformis.

BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare autosomal recessive genodermatosis characterized by an impairment of cellular immunity. It clinically manifests as widespread, long-lasting, pityriasis versicolor-like macules and flat, wart-like papules, usually occurring in early childhood. There is a risk of development of multiple skin cancers in the third decade, primarily in sun-exposed skin. EV-associated human papillomaviruses have been implicated in a number of cutaneous lesions in non-EV populations, such as seborrheic keratoses or psoriasis. They have also been implicated in the development of nonmelanoma skin cancer, especially in immunosuppressed patients. Patients affected with EV are not able to eliminate oncogenic viruses within lesions, leading to a malignant transformation. OBJECTIVE: To describe the dermoscopic characteristics of EV cutaneous tumors by performing histopathologic correlation. METHODS AND MATERIALS: Cutaneous lesions and tumors from two patients affected by EV were included. Clinical and dermoscopic images were obtained and excision with ulterior histopathology was performed in all suspicious tumors and characteristic lesions. RESULTS: Dermoscopy and histology of pityiriasis versicolor-like macules, wart-like papules, seborrheic keratosis-like tumors, psoriasis-like plaques, collision tumors, and Bowen in situ carcinoma are described. CONCLUSIONS: Dermoscopy in EV tumors correlated with histopathologic findings and improved the differential diagnosis of tumors in this disease.

Adolescent↗
PubMed2004

The clinical importance of demodex folliculorum presenting with nonspecific facial signs and symptoms.

Demodex folliculorum (D. folliculorum), found in the pilosebaceous unit, is the most common ectoparasite of humans. Various clinical forms such as pustular folliculitis, papulopustular scalp eruptions, perioral dermatitis, and blepharitis have been defined, although in general, the disease has been classified into three main groups as "pityriasis folliculitis", "rosacea-like demodicidosis", and granulomatous rosacea-like "demodicidosis gravis". Our aim was to test for the presence of D. folliculorum in pathogenic numbers in patients who came to our clinic with non-specific symptoms such as facial itching with or without erythema, seborrheic dermatitis-like or perioral dermatitis-like lesions, papulopustular lesions, and an acneiform clinical appearance without telengiectasia or flushing. Twenty-eight (87.5%) female and 4 male (12.5%), patients and 33 age-and-sex matched healthy subjects enrolled in this study. D. folliculorum was sought in the lesion sites using the non-invasive method known as the Standardised Skin Surface Biopsy (SSSB). The discovery of more than five parasites in an area of 1 cm2, was evaluated as pathogenic. For treatment, 5% permethrine cream was applied twice daily for 15 to 30 days. The clinical symptoms of the patients were classified into clinical groups and evaluated as facial itching in 2 (6.3%), nonspecific erythema and itching in 21 (65.6%), erythema and pityriasiform squamous lesions in 3 (9.4%), acneiform in 3 (9.4%), papulopustular lesions in 1 (3.1%), granulomatous rosacea-like in 1 (3.1%), and perioral dermatitis-like symptoms in 1 (3.3%), D. folliculorum density was determined as 5>D/cm2 in all clinical lesions. A significant clinical healing and density of D. folliculorum at <=5 D/cm2 was determined in all but two patients after treatment. We consider that D. folliculorum presentation with different symptoms and signs than classical forms is not rare. For this reason, we suggest that it is useful to test for D. folliculorum in patients with non-classical presentations like facial itching, itching accompanied by non-specific erythema, itching and non-specific pityriasiform squamous lesions, and acneiform lesions.

Administration, Cutaneous↗
PubMed1975

Secondary syphilis: a clinico-pathological review.

The histological appearances found in biopsies from fifty-seven patients with secondary syphilis have been correlated with the clinical morphology of the eruptions. Considerable variation of histological pattern was encountered, and the frequency with which some of the classically described changes were found to be absent or inconspicuous is stressed. Of particular interest were the findings that, in nearly one-quarter of the biopsies, plasma cell infiltration was either absent or very sparse, and that vascular damage was seen in less than half. Where present, the vessel changes were almost entirely confined to swelling of the endothelial cells. Proliferation of the endothelial cells was most uncommon. The epidermis was very frequently involved in the inflammatory process. Exocytosis, spongiosis, parakeratosis, and acanthosis were the most frequent changes. No consistent histological difference between papular and papulo-squamous lesions could be found but macular lesions demonstrated more superficial and less intense dermal infiltration as well as less severe epidermal involvement. In late secondary lesions, the infiltrate became granulomatous, but in other respects the duration of the exanthem could not be correlated with the pathology. The differential diagnosis from pityriasis lichenoides and other inflammatory dermatoses is discussed and the value of histopathology in the diagnosis of secondary syphilis is emphasized.

Adolescent↗
PubMed1976

Sarcoidosis in a child, presenting as an erythroderma with keratotic spines and palmar pits.

A case of sarcoidosis with generalized erythroderma, exfoliation and micropapule formation in a 6-year-old boy is presented. Follicular spiny keratoses, resembling those seen in pityriasis rubra pilaris, and palmo-plantar pitting were among the other extraordinary features in this case. The epidermis overlying the widespread sarcoid granulomata showed parakeratosis, lymphocytic infiltration and degeneration of the basal layer.

Child↗