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Skin homeostasis is controlled by a complex interplay between tightly regulated transcription factors and signaling pathways. MYB is a transcription factor expressed in hair follicle progenitor cells and found overexpressed in adnexal skin tumors. However, the biological consequences of deregulated MYB expression in the skin remain poorly understood. To address this, we generated transgenic mice that overexpress MYB in epidermal and follicular keratinocytes. These mice exhibited a normal hair coat after birth but gradually developed alopecia, accompanied by altered follicular differentiation, disrupted hair cycle, and a marked depletion of hair follicle stem cells. Additionally, transgenic mice developed massive epidermal hyperplasia and hyperkeratosis. Global expression profiling not only confirmed that the skin of these mice exhibited transcriptomic features of alopecia and epidermal differentiation, but also revealed features of psoriasis and the inflammatory response. The latter was further confirmed by the increased T-cell infiltration found in the skin of transgenic mice. Overall, these results suggest that tight regulation of MYB expression in the skin is critical to maintain skin homeostasis., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Avelumab is an anti-programmed cell death ligand 1 (PD-L1) antibody approved for treatment of Merkel cell carcinoma (MCC) and locally advanced or metastatic urothelial carcinoma. It shares a similar side effect profile to other immune checkpoint inhibitors, including immune-related adverse reactions in the skin. These adverse skin reactions can present as a morbilliform exanthem, lichenoid dermatitis, vitiligo, autoimmune bullous disorder, among others., Case Presentation: We describe a patient with advanced MCC successfully treated with avelumab who developed acute onset diffuse lichen planus-like keratoses (LPLK) at sites of existing seborrheic keratoses (SK) and lentigines. Histopathology of an affected SK revealed papillomatous epidermal hyperplasia with lichenoid interface changes, numerous dyskeratotic keratinocytes and intermittent hypergranulosis. The findings resembled lichen planus (LP) arising in an SK. Onset of the skin symptoms corresponded with an inflammatory cancer response (clinical pseudo-progression), and the eruption improved as overall tumor burden decreased. The patient's pruritus was treated with topical steroids and cyrotherapy for individual symptomatic lesions., Conclusion: Diffuse LPLK is a distinct immune-related reaction pattern associated with PD-L1/PD-1 checkpoint blockade. This is an important side effect to be aware of as LPLK frequently mimic keratinocytic neoplasms. Further observation is needed to assess the prevalence and significance of this immune therapy-associated adverse reaction.

A subgroup of the transient receptor potential (TRP) channels, including vanilloid 1 (TRPV1), TRPV2, TRPV3, TRPV4, and TRP ankyrin 1 (TRPA1), is expressed in cutaneous peptidergic somatosensory neurons, and has been found in skin non-neuronal cells, such as keratinocytes. Different cancer cells express TRPs, where they may exert either pro- or antitumorigenic roles. Expression and function of TRPs in skin cancers have been, however, poorly investigated. Here, we have studied the distribution and expression of TRPs by immunohistochemistry and messenger RNA (mRNA) in human healthy skin and human keratinocytic tumors, including intraepidermal proliferative disorders (solar keratosis (SK) and Bowen's disease), and non-melanoma skin cancer (NMSC; basal cell and squamous cell carcinomas). Similar TRPV1, TRPV2, and TRPV3 staining was found in keratinocytes from healthy and tumor tissues. TRPA1 staining was increased solely in SK samples. However, the marked TRPV4 staining and TRPV4 mRNA expression, observed in healthy or inflamed skin, was abrogated both in premalignant lesions and NMSC. In a human keratinocyte cell line (HaCaT), TRPV4 stimulation released IL-8, which in turn downregulated TRPV4 expression. Selective reduction in TRPV4 expression could represent an early biomarker of skin carcinogenesis. Whether the cytokine-dependent, autocrine pathway that results in TRPV4 downregulation contributes to NMSC mechanism remains to be determined.

Background: Olmsted syndrome is a rare congenital skin disorder presenting with periorifical hyperkeratotic lesions and mutilating palmoplantar keratoderma, which is often associated with infections of the keratotic area. A recent study identified de novo mutations causing constitutive activation of TRPV3 as a cause of the keratotic manifestations of Olmsted syndrome., Methods: Genetic, clinical and immunological profiling was performed on a case study patient with the clinical diagnosis of Olmsted syndrome., Results: The patient was found to harbour a previously undescribed 1718G-C transversion in TRPV3, causing a G573A point mutation. In depth clinical and immunological analysis found multiple indicators of immune dysregulation, including frequent dermal infections, inflammatory infiltrate in the affected skin, hyper IgE production and elevated follicular T cells and eosinophils in the peripheral blood., Conclusions: These results provide the first comprehensive assessment of the immunological features of Olmsted syndrome. The systemic phenotype of hyper IgE and persistent eosinophilia suggest a primary or secondary role of immunological processes in the pathogenesis of Olmsted syndrome, and have important clinical consequences with regard to the treatment of Olmsted syndrome patients.

Background: Epidermal keratinization disorders comprise a heterogeneous group of skin diseases that share the common feature of abnormal epidermal maturation, often leading to a disturbed stratum corneum., Objective: To describe two cases of an unusual disorder of epidermal keratinization., Methods: The clinical features of two unrelated patients with a long-standing widespread cutaneous eruption are described. Histopathologic examination and immunohistochemical studies were performed on skin biopsy specimens., Results: The eruption was characterized by symmetric erythematous, flat, discrete papules with a polygonal shape and fine scaling. The papules covered most of the skin surface and, in some areas of the trunk, they were arranged along the lines of cleavage, parallel to the ribs. There was no facial, mucosal, nail, or palmoplantar involvement; the teeth and hair were normal. The first patient had a sister with an identical eruption, and a brother of the second patient was said to have similar skin lesions. Histopathology revealed well-demarcated areas of compact eosinophilic orthokeratotic hyperkeratosis overlying a slightly acanthotic epidermis. Lesional skin showed weaker immunoexpression for connexin 43 compared with normal skin., Limitations: Only two patients and one sibling were investigated., Conclusion: We propose the name "saurian papulosis" to describe this newly described clinicopathologic entity., (Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Literature data analysis, providing an exact explanation of the lichen planus pathogenesis, as well as its transition into other rare forms such as Keratosis lichenoides chronica or Graham Lassueur Piccardi Little Syndrome are scant, or totally missing. The chronological course of the disease, known in the literature as lichen planus, varies. Some patients develop Lichen planus or lichen nitidus and there is no logical explanation why. It is also not clear why single patients initially develop ulcerative lesions in the area of the mucosa and only in a few of them these lesions affect the skin. Antigen Mimicry and Epitope Spreading could be the possible pathogenic inductor in cases of lichenoid dermatoses, as well as the cause for their transition into ulcerative, exanthematous or other rare forms. The Epitope Spreading is probably not the leading pathogenetic factor in lichen planus but a phenomenon which occurs later. This manuscript analyzes some basic pathogenic aspects and presents some possible medical hypotheses regarding the heterogenic clinical picture and pathogenesis of lichen planus and lichenoid like pathologies of the skin which, in the near future should be analyzed in details in order to clarify several dilemmas the clinical dermatologist has to face.

Combined interstitial lung disease and the presence of 'mechanic's hands' could be a clinical clue in the early diagnosis of the rare disease, amyopathic antisynthetase syndrome for which anti-Jo-1 antibody is a useful diagnostic tool. The case is reported of a patient who suffered from shortness of breath and dry cough, with pulmonary fibrosis on CXR and CT scan, and interstitial pneumonitis on trans-bronchial biopsy. She was also positive for anti-Jo-1 and anti-Ro antibodies. 'Mechanic's hands' were noted bilaterally but with no evidence of myopathy in either the electromyogram or on muscle biopsy. The patient was treated with prednisolone and her clinical picture, including the 'mechanic's hands' and lung fibrosis, subsided gradually, suggesting that the sign may be a useful follow up tool in this disease. Early diagnosis and corticosteroid therapy could be beneficial for these patients.

Objective: In this study the safety and efficacy of imiquimod 5% cream for the treatments of actinic keratoses in kidney, heart and liver transplant recipients is evaluated., Background: Growing populations of organ transplant recipients face increased risk of developing actinic keratosis (AK) and skin cancer secondary to continuous systemic immunosuppressive therapy. Imiquimod 5% cream is an effective option for the treatment of AK, but the safety of topical immune stimulation in immunocompromised patients has not been widely evaluated., Methods: A total of 43 patients in six European transplant centres applied two sachets of topical imiquimod or vehicle cream three times per week to a 100 cm(2) field. Dosing continued for 16 weeks regardless of lesion clearance. Patients were assessed for safety variables that included adverse events, local skin reactions, laboratory results, vital signs, dosage of immunosuppressive medication and indication of graft rejection. A blinded independent expert committee was responsible for safety monitoring and final safety assessment., Results: No graft rejections or trends for a deterioration of graft function were detected. No meaningful trends were observed in laboratory results. Among patients randomized to imiquimod, the complete clearance rate was 62.1% (18/29); for vehicle patients, the complete clearance rate was 0% (0/14). Clinical clearance was confirmed histologically in all cases., Conclusions: Imiquimod appears to be a safe alternative for the treatment of multiple actinic keratoses in patients with solid organ transplants. Efficacy was within the range previously observed in nontransplanted populations.

Background: Feeding with pulverized konjac glucomannan (PKGM) suppresses the development of eczema and hyper-IgE production in NC/Nga mice, a model of atopic dermatitis. This study aimed to examine the effects of PKGM on scratching behavior and skin inflammatory immune responses in NC/Nga mice., Methods: Four-week-old NC/Nga mice were maintained for 8 or 9 weeks on diet containing PKGM. Scratching behavior and clinical symptoms were evaluated every 2 weeks. Effects of PKGM on cutaneous inflammation were evaluated by histopathological analysis. Local expression levels of substance P and proinflammatory cytokines were measured by ELISA., Results: An increase in scratching behavior was evident from 6 weeks of age in control mice, but this symptom was dose-dependently inhibited in PKGM-fed mice. Continuous PKGM feeding then significantly inhibited eczematous skin lesions including hyperkeratosis, dermal mastocytosis and eosinophilia. Concomitantly, cutaneous overproductions of substance P, IL-10, IL-4, and TNF-alpha were all suppressed in PKGM-fed mice., Conclusions: PKGM feeding markedly suppressed development of scratching behavior, substance P expression with mastocytosis, and skin inflammatory immune responses in NC/Nga mice., (2007 S. Karger AG, Basel)

Objective: To provide evidence that lymphomatoid keratosis should be categorized as an epidermotropic subtype of cutaneous lymphoid hyperplasia., Design: Clinicopathological, immunohistochemical, and molecular biological studies of epidermotropic and dermal bandlike infiltrates of lymphocytes without necrotic keratinocytes, Civatte bodies, or Max-Joseph spaces and solar lentigo or seborrheic keratosis adjacent to the lesion, but with epidermal hyperplastic change (clinically scaly plaque) in cases of lymphomatoid keratosis. Conventional histopathologic study as well as immunohistochemical examinations for CD1a, CD3, CD4, CD8, CD20, and CD79a and S100 protein and genotypic examinations were performed., Setting: University departments comprising 2 sections of dermatology and 1 section of pathology., Main Outcome Measures: Ratio of T to B cells and of CD4(+) to CD8(+) cells, and the phenotype of epidermotropic cells were evaluated. Gene rearrangement of the immunoglobulin heavy chain gene and T-cell receptor (TCR)-beta and TCRgamma genes was also investigated by the polymerase chain reaction method., Results: Immunohistochemically, epidermotropic CD20(+) and/or CD79a(+) cells were present. In the upper dermal lymphocytic infiltrates, the CD3(+)/CD79a(+) cell ratio ranged from 5:5 to 8:2. The CD4(+)/CD8(+) cell ratio was within normal limits. Rearrangements of the TCRgamma gene were demonstrated in 2 cases and of the TCRbeta gene in 1 case., Conclusions: Our results indicate that lymphomatoid keratosis is a clinically benign keratotic lesion but histologically malignant, simulating mycosis fungoides. Immunohistochemical findings showed a reaction pattern in all cases, but genotypical examination showed some clonal dermatoses. Therefore, "lymphomatoid" keratosis should be classed as a pseudolymphoma, namely, a subtype of cutaneous lymphoid hyperplasia with epidermotropism.

Background: Nonmelanoma skin cancer represents a significant cause of morbidity in organ transplant recipients (OTRs). Cutaneous malignancies, mainly invasive squamous cell carcinoma and its precursor actinic keratosis (AK), appear approximately 5-10 years after organ transplantation. Impaired wound healing and high recurrence rates in immunocompromised patients treated with destructive therapies such as cryosurgery or topical 5-fluorouracil represent frequently known complications., Objectives: To evaluate the safety and efficacy of imiqimod 5% in the treatment of AKs in OTRs., Methods: Six OTRs (two kidney, two heart, one lung and one liver) with extensive AKs were treated with imiquimod 5% cream two to three times weekly in an open-label uncontrolled, nonrandomized pilot study., Results: In five of six patients treated with imiquimod 5% cream all AK lesions were cleared after 12-16 weeks. One patient showed partial response. Local adverse events at the site of application included erythema, oedema and mild erosion. No wound infection or scarring was observed in any of these patients. All graft-related laboratory parameters were stable during and after treatment. Immunosuppressive therapy remained unchanged throughout the treatment., Conclusions: These results suggest that imiquimod 5% cream may be useful for the local treatment of precancerous AK lesions in OTRs.

Background: The surgical advances made in the area of organ transplantation along with the use of more efficacious immunosuppression have meant an increase in patient survival. This longer-living transplant population has started to exhibit cutaneous problems, some of which lead to an increased mortality while others lead to a decline in the quality of life., Objectives: The primary objective was to determine the different types of cutaneous lesions encountered in the adult liver transplant population. Secondary objectives were to determine the impact, if any, of the duration of transplant, the type of immunosuppression involved and the degree of sun exposure and skin phototype, on the skin cancers encountered in this transplanted population., Methods: Two dermatologists examined 100 consecutive liver transplant recipients (LTRs) attending the transplant outpatient department. Skin examination included the face and whole body and lesions found were categorized into the following groups: cutaneous malignancies, squamoproliferative lesions, cutaneous infections and others that did not fall into any of these categories., Results: The reasons for organ transplantation were numerous. The mean age at transplantation was 42.5 years. The average time since transplantation was 5.5 (range 0.75-16 years). Four patients developed skin cancers; among them there were a total of seven skin cancers (one squamous cell carcinoma, six basal cell carcinomas). Fungal infections accounted for 19% of all cutaneous infections seen, viral infections 2% and bacterial infections 5%. Triple-drug immunosuppressive therapy (ciclosporin A, azathioprine and prednisolone) was used in 35% of LTR patients, while dual therapy (tacrolimus and prednisolone) was used in 48% and monotherapy (tacrolimus) was used in 17% of LTRs., Conclusions: Immunosuppressive therapy is believed to be one of the most important risk factors in the development of skin cancer in solid organ transplant recipients. The relatively low prevalence of skin cancer in our liver transplant population may in part be explained by the relatively high percentage of recipients on dual and monotherapy (48% and 17% respectively), and the shorter duration of therapy. Our study suggests that although LTRs are at higher risk of developing nonmelanoma skin cancer than the general population, the risk is comparable with other solid organ transplant recipients.

Background: Imiquimod 5% cream is a topically applied immune response modifier that has been shown to give effective treatment of actinic keratosis (AK). The therapeutic effects of imiquimod are likely to involve the provocation of a cutaneous immune response against abnormal cells, an assumption based on a strong correlation between complete clearance rates and the severity of the local skin reactions (erythema, oedema, erosion/ulceration, weeping/exudation and scabbing/crusting); however, no clinical studies have conclusively proved this mechanism., Objectives: To determine the nature of cellular infiltrates induced by the application of imiquimod to AK lesions and to study cells involved in the cutaneous immune response., Methods: Eighteen patients participated in this phase I, randomized, double-blind, parallel group, vehicle-controlled study. Enrolled patients were randomized in a 2 : 1 ratio to receive imiquimod cream or vehicle cream and applied study cream to five lesions on the scalp, forearm or upper trunk once daily, three days per week for up to 16 weeks. Each patient had punch biopsies of two distinct AK lesions: a lesion was biopsied before treatment to obtain baseline biomarker levels, and a different lesion was biopsied after 2 weeks of treatment. Biopsy specimens were examined using routine and immunohistochemical staining., Results: The imiquimod group showed statistically significant increases from baseline to week 2 in tissue biomarker levels for CD3, CD4, CD8, CD11c, CD86/CD11c, CD68, HLA-DR and TUNEL. No significant differences were seen for the vehicle group. Complete clearance of all treated AK lesions was achieved in five of 11 (45%) imiquimod patients and in none of six vehicle patients., Conclusions: Imiquimod stimulates a cutaneous immune response characterized by increases in activated dendritic cells and CD4+ and CD8+ T cells.

Benign lichenoid keratosis, otherwise known as lichen planus-like keratosis, is a common, cutaneous entity that is often confused with cutaneous malignancy. Few studies have examined the multiple clinical and pathologic guises of this entity, particularly within the context of clinical pathologic correlation or magnitude of this study. We examined the epidemiologic, clinical, and pathologic attributes of 1040 consecutive cases of benign lichenoid keratosis referred for pathologic examination at a busy laboratory over an entire year. Clinical parameters assessed included the age, anatomic location, gender, and multiplicity of the lesions. Pathologic attributes were assessed yielding discernment of five different subtypes that included a classic type, bullous type, atypical type with cytologically atypical lymphocytes, an early or interface type, and a late regressed or atrophic type. The results yielded an average age at presentation of 59.5 years with an age range of 36 to 87 years. The gender frequency was 76% female, 24% male. The trunk was the most common location (76%), followed by the extremities (33%) and head and neck (7%); 8% of patients presented with two lesions and less than 1% with three lesions prompting consideration of lichen planus. The classic, atypical, and bullous forms of the disease clinically presented with erythematous papule/plaque(s). The early or interface type showed erythematous to hyperpigmented brown macules and the regressed or atrophic type presented as violaceous papules or irregularly distributed macular pigmentation; 81% of the lesions showed the classic histology consisting of epidermal acanthosis with a band-like lichenoid lymphocytic infiltrate. Variable numbers of plasma cells, eosinophils, and neutrophils were identified as well as epidermal parakeratosis distinguishing these lesions from typical lichen planus. The bullous variant showed intraepidermal or subepidermal bullous cavities with a dense associated lymphocytic infiltrate and increased numbers of necrotic basilar layer keratinocytes. The atypical variant showed features of the classic type with scattered enlarged CD-3, CD-30 (+) lymphocytes possessing hyperchromatic, irregular nuclei. The early interface type showed single lymphocytes aligned along the dermoepidermal junction without epidermal acanthosis and adjacent lentigo. The regressed or atrophic variant showed epidermal atrophy with papillary dermal scarring, patchy lymphocytic infiltrates and melanin incontinence. The clinicopathologic spectrum of benign lichenoid keratosis is broad and encompasses several unrelated entities. An awareness of its expanded presentation is essential to avoid misdiagnosis and may serve as an important forerunner of pathogenic discernment.

Background: The keratinocytic hyperproliferative lesions include non-tumorigenic, pre-tumorigenic (actinic keratoses, AK), and tumorigenic (squamous cell carcinomas, SCC) conditions. Although mononuclear inflammatory cell infiltrate (MICs) is a constant feature in these lesions, their immunophenotypic characterization is still incomplete. We hypothesized that the development of non-tumorigenic, pre-tumorigenic, and tumorigenic keratinocytic hyperproliferative lesions is associated with alterations in the mononuclear inflammatory cell infiltrate in response to altered antigenicity of the lesional cells. This study tries to test this hypothesis and to characterize MICs in these lesions., Methods: Fifty lesions (non-tumorigenic lesions, 29; AK, 9 and SCC, 12) were examined using immunoperoxidase staining methods and antibodies targeting histiocytes (CD68), T cells (CD3), B cells (CD20), and T cells with cytotoxic potential (TIA-1)., Results: As compared to the normal skin, the development of the keratinocytic hyperproliferative lesions (normal skin; non-tumorigenic; AK and SCC) was associated with a statistically significant increase (p = <0.05) in: (1) CD20+ B lymphocytes (0.0 +/- 0.0 vs. 3.1 +/- 0.5 vs. 7.5 +/- 0.3 vs. 14.5 +/- 5.5); (2) CD68 histiocytes (4.0 +/- 1.0 vs. 26.5 +/- 3.9 vs. 23 +/- 1.9 vs. 41.3 +/- 6.8); (3) CD3+ T lymphocytes (3.0 +/- 1.1 vs. 58.3 +/- 10.3 vs. 54.5 +/- 0.2 vs. 41.0 +/- 16.0); and (4) TIA-1+ cytotoxic T cells (1.8 +/- 0.4 vs. 2.9 +/- 0.7 vs. 9.6 +/- 1.1 vs. 13.7 +/- 5.2)., Conclusions: The increase in the number of infiltrating mononuclear cells in all pathologic lesions compared to normal skin may reflect increased antigenicity of the lesional cells. Both humoral and cell mediated immunity are involved in these lesions.

Epidermal activation of Erk MAPK is observed in human psoriatic lesions and in a mouse model of psoriasis in which beta1 integrins are expressed in the suprabasal epidermal layers. Constitutive activation of the upstream kinase MEK1 causes hyperproliferation and perturbed differentiation of human keratinocytes in culture. It is not known, however, whether Erk activation in differentiating keratinocytes is sufficient to trigger hyperproliferation of basal keratinocytes and a skin inflammatory infiltrate. To investigate this, we expressed constitutively active MEK1 in the suprabasal epidermal layers of transgenic mice. Proliferation in the epidermal basal layer was stimulated and epidermal terminal differentiation was perturbed. Some older mice also developed papillomas. There was a large increase in T lymphocytes, dendritic cells, and neutrophils in the skin. The effects of suprabasal MEK1 on basal keratinocytes and leukocytes, cells that were transgene negative, suggested that MEK1 activity might stimulate cytokine release. Transgenic keratinocytes expressed elevated IL-1alpha and crossing the mice with mice overexpressing the IL-1 receptor in the epidermal basal layer led to exacerbated hyperproliferation and inflammation. These data suggest that activation of MEK1 downstream of beta1 integrins plays an important role in epidermal hyperproliferation and skin inflammation.

Background: In the counterattack model of tumorigenesis, it has been proposed that tumours develop resistance to attack from Fas ligand (FasL)-expressing cytotoxic T cells by downregulating Fas (immune escape), while at the same time upregulating FasL expression to induce apoptosis in Fas-expressing T cells (counterattack)., Objectives: The aim of this study was to examine Fas and FasL expression on tumour cells and infiltrating T cells during the progression of actinic keratoses (AK), the benign precursor lesion, to squamous cell carcinoma (SCC)., Patients and Methods: Samples of AK (n = 20) and SCC (n = 20) were collected from immunocompetent patients attending dermatology clinics. Double-label immunohistochemistry was performed on frozen sections using mouse monoclonal antibodies to Fas or FasL, simultaneously with a rabbit polyclonal antibody to either CD3 or cytokeratin, markers of T cells and keratinocytes, respectively. Cell densities and the optical density of tumour Fas expression were measured using image analysis., Results: FasL-expressing T cells were observed in nine of 19 SCCs, compared with three of 20 AKs (P < 0.05). FasL-expressing tumour cells were found in nine of 18 SCCs, compared with only one of 20 AK specimens (P < 0.005). There was no difference in the number of Fas-expressing T cells infiltrating AK and SCC. Fas expression by keratinocytes, measured by optical density, was lower in SCC (range 0.1-40, median 17) compared with AK (range 4-62, median 25) (P < 0.05)., Conclusions: These results suggest that the greater numbers of FasL-expressing T cells infiltrating into SCC compared with AK are targeting Fas-expressing tumour cells. As AK cells progress to SCC, they subvert this T-cell-mediated killing of tumour cells by downregulating their Fas expression (immune escape). Furthermore, tumour cells upregulate their expression of FasL, possibly as a counterattack measure to induce apoptosis in the increased number of tumour-infiltrating T cells. Thus changes in Fas/FasL-mediated interactions between T cells and tumour cells occur during the progression of AK into SCC.

Background: Regression is a phenomenon present in a variety of cutaneous lesions. It is likely that similar immunologic mechanisms explain the phenomenon of spontaneous regression occurring in the various lesions., Methods: Twenty-seven specimens, nine each of halo nevus, keratoacanthoma, and benign lichenoid keratosis, including three examples each of predominantly early, mid, and late regression were examined with antibodies to HLA-II, CD1a, CD3, CD4, CD8, CD20, CD34, CD56, and CD68., Results: Epidermotropism of inflammatory cells, including CD1a positive, CD68 positive, CD3 positive, and CD8 positive cells, was present in benign lichenoid keratosis and keratoacanthoma, but not in halo nevus. In halo nevus, the nests of halo nevus cells tended to be infiltrated by CD1a positive, CD68 positive, CD3 positive, and CD8 positive cells. The blood vessels exhibited endothelial cell swelling with luminal narrowing and disruption within the dermis of all lesions. The CD1a positive cells were increased in number in lesional epidermis except in keratoacanthoma lesions where the density of CD1a positive cells was increased in the epithelial lip, but decreased within the epithelial portion of the keratoacanthoma proper. Conversely, the CD8 positive cells were scarce in the dermis below the epithelial lip of the keratoacanthoma, but increased in the dermis of the neoplastic epithelium. CD1a positive cells were also seen throughout the dermal portion of the lesion, particularly at the lesion base. In halo nevus, the CD1a positive cells and CD68 positive cells within the lesions were larger than those in non-lesional skin, indicating activation. The composition of the inflammatory infiltrate varied within each lesion type according to stage of regression, but T-lymphocytes predominated., Conclusion: Cytotoxic T-cells may be the final common denominator of regression in benign lichenoid keratosis, keratoacanthoma, and halo nevus. In halo nevus, cytotoxic T-cells may play the predominant role in regression. In keratoacanthoma and benign lichenoid keratosis, cytotoxic T-cells play a pivotal role, but additional mechanisms may also be involved in the phenomenon of regression. Benign lichenoid keratoses progress through stages of regression accompanied by varying proportions of inflammatory cells, including CD3, CD4, and CD8 positive T-lymphocytes, natural killer cells, macrophages and Langerhans cells.

Skin cancers in both immunosuppressed and immunocompetent populations are associated with epidermodysplasia verruciformis human papillomavirus (EV-HPV) DNA. However, little is known about the prevalence of EV-HPVs in actinic keratoses in immunocompetent individuals. Actinic keratoses from 114 patients were classified as low-grade ( n=76) or high-grade ( n=38) according to the extent of histological atypia. HPV DNA was amplified from 54 frozen and 60 paraffin-embedded biopsy specimens by nested polymerase chain reaction (PCR) with several consensus and type-specific primers. PCR products were sequenced for typing. These results were compared with HPV detection in skin cancers ( n=20) and Bowen's disease ( n=18). A broad spectrum of EV-HPV types including oncogenic HPV5 and HPV8 and partially characterized sequences were detected in actinic keratoses and cutaneous cancers. In actinic keratoses a higher prevalence of EV-HPV DNA was found in frozen tissues than in formalin-fixed tissues (85% vs 67%). There was no difference between the low- and high-grade actinic keratoses either in terms of EV-HPV DNA prevalence or the results of serological study using HPV8 virus-like particles. The detection rate of EV-HPVs was lower in skin cancers and Bowen's disease. This would suggest involvement of EV-HPVs in the early stages of cutaneous oncogenesis.

Actinic keratoses are a common problem in the population, and one of the most common conditions treated by dermatologists. Risk factors for the development of actinic keratosis are those associated with increased sun exposure and increased susceptibility to sun exposure such as low latitude, working outdoors, light skin, and history of sunburn. The role of the immune system is clear from the frequency of actinic keratoses in transplant patients. There is strong evidence that actinic keratoses can progress to squamous cell carcinoma, underscoring the need to identify and treat patients at risk.

With sensible patient education, the multitude of benefits that topical retinoid therapy can provide may be enjoyed. Hopefully, retinoid therapy will heighten awareness of the detrimental effects of sun exposure and motivate future generations to become "sun smart." Evidence-based medicine, current research, and case studies can arm practitioners with the resources and guidance to effectively provide current, innovating therapies for a variety of dermatologic conditions. With the strategic use of topical retinoids, several dermatologic conditions can be addressed concurrently.

Background: Human papillomavirus (HPV) may play a role in the pathogenesis of non-melanoma skin cancer (NMSC) in epidermodysplasia verruciformis (EV) patients, but in the general population no specific HPV types have been associated with these lesions. Objectives To examine the spectrum of HPV types present in the skin and tumours of Australian patients with NMSC or solar keratosis (SK)., Methods: Biopsies from tumours, and cotton swab samples of perilesional skin and buttock skin from each of 59 Australian patients with basal cell carcinoma (BCC), squamous cell carcinoma (SCC) or SK were tested for HPV DNA by polymerase chain reaction (PCR) using HPV consensus (FAP) primers and by type-specific primers for HPV 38 and candidate HPV 92. The identification of HPV type from consensus PCR was performed by sequencing and comparison with GenBank., Results: In total, 49 of 59 (83%) patients harboured HPV DNA, which was detected in 28 of 64 (44%) biopsies, 48 of 64 (75%; P < 0.001) perilesional swabs and 36 of 59 (61%; P = 0.04) buttock swabs. Forty-five different HPV types/putative types were detected: 15 were previously characterized HPV types, 17 were earlier described putative types and 13 were new putative types. In addition, six subtypes and four variants of HPV sequences were identified. HPV types within the B1 group (EV HPV types) were found in 26 of 64 (40%) lesions, 44 of 64 (69%) perilesional swabs and 35 of 59 (59%) buttock swabs. HPV 38 was detected in 23 of 59 (39%) patients, and was found in seven of 16 (43%) SKs, but was less common in SCCs [three of 23 (13%); P = 0.037] and BCCs [four of 25 (16%); P = 0.056]. Candidate HPV 92 was found in seven of 59 (12%) patients., Conclusions: A broad spectrum of HPV types, the majority from the B1 group, was found in skin of Australian patients with skin tumours. HPV 38 was found significantly more often in SK than in SCC. However, the role of cutaneous HPV infection in the pathogenesis of NMSC remains elusive.

Background: Squamoproliferative lesions are common in patients who are immunosuppressed, particularly in recipients of solid organ transplants. Histologic features in such biopsy specimens may differ from those of otherwise healthy patients. Actinic keratoses (AKs) in transplant recipients may possess pathologic characteristics that suggest that they arose in an immunosuppressed host., Objective: We evaluated 30 randomly selected AKs from 25 recipients of solid organ transplants and compared their histologic features to those of 50 AKs from 45 patients who were not immunosuppressed., Methods: Tissue samples were categorized by sex, patient age, and site of biopsy. Sixteen separate histologic criteria were evaluated in a blinded fashion in each specimen. Statistical analysis was performed between the two groups with and without controlling for the age of the patient., Results: The transplant group was significantly younger (54.8 years) than the nontransplant group (70.0) and contained more men (88%) than women (51%). AKs from transplant recipients were statistically more likely to demonstrate bacterial colonization, confluent parakeratosis, hyperkeratosis, increased mitotic activity, and verrucous changes. After controlling for age only, hyperkeratosis failed to be more prevalent in the transplant group., Conclusion: Certain histopathologic features are more common in AKs of immunosuppressed transplant recipients and may be used to distinguish between those removed from otherwise healthy persons.

An 81-year-old woman presented with a round erythematous macule with keratotic scales on her left hand. The skin specimen histologically showed hypergranulosis and apoptotic keratinocytes in the epidermis with lichenoid infiltration of lymphocytes. Parakeratosis seen in the hyperkeratotic cornified layer indicated lichen planus-like keratosis, as distinguished from lichen planus. Direct immunofluorescence study revealed the linear deposition of IgM in the basement membrane zone; IgG, IgA and C3 were not detected.

Background: Lichenoid keratosis (LK) is a rather frequent skin lesion that has some histologic features similar to lichen planus (LP). The clinical and histopathologic characteristics of LK and differential tools from LP are not yet fully established., Objective: The purpose of this study was to investigate the clinical and histopathologic characteristics of LK., Methods: A clinical survey was done with 17 patients diagnosed as having LK. We reevaluated biopsy materials of 17 patients diagnosed during the past 10 years at Asan Medical Center, Seoul, Korea. We performed an immunohistochemical staining in 17 cases of LK and 7 cases of LP using 5 antibodies for CD3, CD4, CD8, CD20, and cutaneous lymphocyte-associated antigen (CLA). Standard streptavidin-biotin peroxidase method using the monoclonal antibodies with 3-amino-9-ethyl-carbazole was used., Results: The male/female ratio was 1:1.1. The mean age at diagnosis was 54.9 years. The face was the most commonly affected site, followed by the arm and forearm, dorsum of hand, chest, trunk, abdomen, and leg. The lesions were predominantly solitary (76.5%); 1 patient had 4 lesions; 3 patients (17.6%) had numerous lesions. The lesions ranged in size from 0.4 to 2.0 cm. Histopathologically, all the cases showed characteristic lichenoid infiltrates of lymphocytes, occasional parakeratosis, and apoptotic bodies in the epidermis without nuclear atypia of keratinocytes. LK could be reclassified into 3 patterns by means of histopathologic findings: LP-like (11/17), seborrheic keratosis-like (3/17), and lupus erythematosus-like (3/17). Immunohistochemical studies revealed that infiltrated epidermal and dermal lymphocytes in LK consisted mainly of CD8(+) T cells and partly CD20(+) B cells. In LP, epidermal lymphocytes were mainly CD8(+) T cells and dermal lymphocytes were CD4(+) or CD8(+) T cells. Interestingly, CLA was strongly expressed in LP but not expressed in LK., Conclusion: We reclassified LK as follows: LP-like LK, seborrheic keratosis-like LK, and lupus erythematosus-like LK. Immunohistochemical stains for CLA as well as CD4 and CD8 may be valuable tools in the differential diagnosis between LK and LP.

Objective: To investigate anti-crypt keratin (CK) immunologic histochemical changes in children with chronic tonsillitis., Method: Removed tonsilla were fixed by 10% formaldehyde. Immunologic histochemical method was used to determine the changes of anti-broad spectrum (KD 68, 56, 56, 50) CKSP., Result: In 230 cases, obvious keratosis was 90.9%, no keratosis was 9.1%, 3 cases were found with fungus filaments and bacteria in the bottom of crypts. Anti-broad spectrum and hypermolecule CK of tonsil cryptic epithelium were positive reaction, anti-broad spectrum CK of cryptic keratosis in all cases was positive reaction., Conclusion: During the period of episode, cryptic epitheliums of tonsilla was destroyed repeatly, therefore, immunoglobulin production was reduce. Because the immune function of tonsilla was reduced, bacteria and virus might be invade into organism. This reduplicative malignant circles must be interrupted or blocked only by tonsillectomy.

Epidermodysplasia verruciformis-associated human papillomaviruses (EV-HPVs) are possibly involved in the development of actinic keratoses and may play a part in the pathogenesis of squamous cell carcinoma (SCC) of the skin, as the DNA of these viruses is frequently detected in biopsies of such lesions. Properly designed epidemiological studies, using serological tests to investigate the role of infection with EV-HPVs in cutaneous oncogenesis, are still rare. An IgG-specific enzyme-linked immunosorbent assay using virus-like particles composed of the major capsid protein L1 of the EV-specific HPV 8 (HPV 8 VLPs) was developed and used to test the seroprevalence of HPV 8 in 114 inhabitants of a tropical island, of whom 13 had developed SCC, and 19 had developed basal cell carcinoma. Gender, age, eye and hair colour, sun exposure and number of actinic keratoses were recorded for all individuals. The presence of antibodies against HPV 8 VLPs was associated with the development of large numbers of actinic keratoses. After adjusting for gender, age, eye and hair colour, and sun exposure, the odds ratio to develop 37 (the median in this dataset) or more actinic keratoses in the presence of antibodies against HPV 8 VLPs was 2.3 (95% confidence interval: 1.0; 5.3). Similarly, after adjustment for the same factors, the presence of these antibodies was associated with SCC with an odds ratio of 3.1 (0.74; 13.3), but the small number of individuals with SCC does not permit any definite conclusions. The presence of these antibodies did not appear to be associated with basal cell carcinoma as, after adjustment for the same factors, the odds ratio was 0.73 (0.23; 2.4). This study provides serological evidence that infection with EV-HPVs may play a part in the pathogenesis of actinic keratoses. The role of EV-HPVs in the development of SCC, however, remains to be elucidated.

The distribution of T (CD3), B (CD79) lymphocytes, immunoglobulin (IgG, IgM and IgA)-producing plasma cells, macrophages (lysozyme, Mac387) and MHC Class II antigen was analysed in the inflammatory infiltrate associated with 19 equine squamous cell carcinomas (SCCs) and six cases of precancerous lesions (actinic keratosis). The SCCs came from the penis (11 cases), conjunctiva (four), skin (two), nasal cavity (one) and oral cavity (one). Seven cases were well-differentiated and 12 moderately differentiated. Nine cases showed no invasion of peritumoral deep tissues (locally invasive), whereas the remaining 10 cases were highly invasive. An abundant inflammatory infiltrate was associated with the majority of the SCCs and with lesions of actinic keratosis. This infiltrate was composed mainly of CD3(+)T lymphocytes, CD79(+)B cells and numerous IgG(+)plasma cells; IgM- and IgA-producing plasma cells were scarce and variable, respectively. Macrophages were usually numerous. Macrophages, lymphocytes, intra-epithelial dendritic cells and fibroblasts expressed MHC Class II antigen. No significant correlation was found between the nature of the inflammatory infiltrate and the SCC histological grade or degree of invasion, suggesting that the local anti-tumour immune response failed to prevent tumour invasion or metastasis. MHC Class II was expressed by a variable number of neoplastic epithelial cells in four SCCs, all of which were only locally invasive. In addition, in areas where SCC cells expressed Class II antigen, numerous CD3(+)T lymphocytes were present and some of them were associated with degenerate tumour cells. These findings suggest that the expression of MHC Class II by neoplastic cells induces an improved local anti-tumour immune response., (Copyright 1999 Harcourt Publishers Ltd.)

We describe a 67-year-old man with lichen planus-like keratosis associated with anti-230 kDa bullous pemphigoid antigen (BPAG1) autoantibody. The patient had noticed solitary dark brown macule more than 6 years previously on his left chest. Histological findings showed hypergranulosis, irregular acanthosis, liquefaction degeneration of basal cells, band-like infiltration of lymphocytes at the subepidermal portion, and a cleft at the basement membrane zone (BMZ), resulting in the formation of subepidermal blisters. Direct immunofluorescence findings of perilesional skin showed a linear deposition of IgG at BMZ. On indirect immunofluorescent study using normal human skin, circulating IgG autoantibody to BMZ was present in the patient's serum at a titer of 1:80. The antigen located on the epidermal site of normal skin split by 1M NaCl was reacted with the patient's serum. Immunoblot analysis using epidermal extracts demonstrated the presence of IgG antibody directed to BPAG1 in the patient's serum. These observations suggest that the presence of an antibody to BPAG1 could be caused by the damage of basal cells following lichen planus-like keratosis.

We present five cases of a hitherto unreported cutaneous neoplasm. The tumors appeared as solitary slow-growing flesh-colored nodules arising in young and middle-aged adults. They were located on the trunk, the upper extremities, and the face, and did not recur after complete excision. Clinically, they were diagnosed as dermal nevus, Spitz's nevus, fibroma, or neurofibroma. Histology revealed polypoid flat-dome-shaped lesions with a sharply demarcated matrix consisting of coarse hyalinized collagen bundles arranged in a prominent storiform pattern and separated by mucin-containing clefts. Despite a low overall cellularity, the tumors contained numerous, occasionally bizarre-shaped, multinucleate giant cells with crowded vesicular nuclei and a pale staining foamy cytoplasm, as well as plump fibroblastlike cells with analogous nuclear morphology. Atypical nuclei or mitotic figures were not observed. The cells were strongly positive for vimentin but negative for cytokeratin, smooth muscle actin, desmin, S-100 protein, CD34, factor XIIIa, and the macrophage markers KP1, Mac 387, and Ki-M1p, suggesting a fibroblastic origin. Based on the overall architecture, we conclude that these tumors probably represent a distinctive variant of solitary circumscribed storiform collagenoma (sclerotic fibroma) and propose the designation of giant cell collagenoma.

Chronic lymphocytic leukemia involves the skin in a small percentage of patients and may portend an ominous prognosis in some patients. We report a series of eight biopsies from seven different patients in which the cutaneous leukemic infiltrate was confined exclusively to the region immediately surrounding primary epithelial neoplasms including squamous cell carcinoma (6), basal cell carcinoma (1) and actinic keratosis (1). The malignant lymphocytes appear to constitute a host response to these neoplasms and do not appear to suggest a rapid downhill course for these patients. These observations serve to 1) suggest a new pattern of cutaneous involvement by leukemic cells and 2) offer some insights into potential cellular trafficking patterns of these neoplastic cells.

The immunohistochemical expression of CD3, CD4, CD8 and MHC class II antigens in the cellular inflammatory infiltrate associated with early and advanced ovine squamous cell carcinomas (OSCC), as well as actinic keratosis was analyzed. The majority of the peritumoral and intratumoral lymphocytes reacted with the anti-human CD3 polyclonal antibody. The number of CD8+ T lymphocytes increased in advanced OSCC compared with that of actinic keratosis and early OSCC, whereas the number of CD4+ lymphocytes was similar in early and advanced OSCC. Tumor cells were unreactive with the anti-MHC class II antibody, but the majority of the mononuclear cellular infiltrate expressed this antigen in early and advanced tumors.

Trichilemmal keratosis (TK) is an uncommon epidermal tumor that exhibits a keratinizing surface with the formation of a cutaneous horn and that clinically resembles a hyperkeratotic actinic keratosis. Histologically, there is verrucous hyperplasia of the epidermis with orthokeratotic hyperkeratosis. TK is characterized by abrupt keratinization without formation of a granular cell layer, in the same manner as that in which the outer root sheath keratinizes (trichilemmal keratinization). The epidermis is acanthotic and contains pale-staining keratinocytes. Epithelial lobules and small trichilemmal cysts are connected to the thickened epidermis. We describe the clinical, histologic, and immunohistochemical findings of two cases of TK.

p53 immunoreactivity was examined in 132 cutaneous non-melanoma tumours from renal transplant recipients and in 114 histologically matched specimens from immunocompetent individuals. Skin lesions examined included 52 viral warts, 50 dysplastic keratoses, 51 intraepidermal carcinomas (IEC), 50 invasive squamous cell carcinomas (SCC) and 43 basal cell carcinomas (BCC). Overall, 51% (51/101) pre-malignant skin lesions and 45% (42/93) non-melanoma skin cancers (NMSC) showed p53 immunoreactivity, with extensive (> 50% cells positive) p53 staining in 27% (27/101) of pre-malignant and 20% (19/93) of malignant lesions. 17% (9/52) viral warts showed p53 immunoreactivity, but this was limited to focal or basal p53 staining. p53 immunoreactivity in all tumours was less in transplant than in non-transplant patients and this reached statistical significance for SCCs (p = 0.03).

This study examined the histological changes and local cellular immune response induced within the lingual mucosa in an allogeneic F1 hybrid rat model of graft-versus-host disease (GvHD) with a view to studying oral lymphocyte-epithelial cell reactions. Highest levels of disease, as reflected by both a GvHD index and the extent of the oral mucosal changes, were obtained using primed donor (Lewis rats) splenocytes and irradiated hosts (Lew/Da rats). The lingual mucosae of test animals were characterised by irregular epithelial keratosis, an absence of basal cell liquefaction and a diffuse inflammatory cell infiltrate, histological features consistent with an oral lichenoid tissue reaction. Immunohistochemical studies showed that mucosal involvement was characterised by infiltration of the lamina propria by NK cells (CD8+, CD5-), "activated" cells (CD25+) and T cells (CD5+) with selective migration of the latter, including a CD5+, CD8- subset (helper/inducer T cell), into the epithelium. Epithelial expression of Ia was invariably associated with these inflammatory cell infiltrates and correlated with the GvHD index. These findings suggest the presence of local mucosal T cell activation in the absence of detectable epithelial cell damage, which may be equivalent to the early initiating events in the pathogenesis of oral lichen planus. However, whilst experimental graft-versus-host disease appears to be a useful model for studying lymphocyte-epithelial interactions, the induced oral mucosal changes are more consistent with a lichenoid reaction rather than lichen planus.

Hyperkeratotic spicules are a rare disorder that has been associated with different types of malignancies. An association with multiple myeloma raises the question of a relation between the monoclonal component and skin manifestations. We describe hyperkeratotic spicules in a 61-year-old man with a monoclonal gammopathy of undetermined significance. Immunofluorescence and immunoelectron microscopic findings demonstrated the deposition of the monoclonal immunoglobulin at the dermoepidermal junction. Our findings support previous reports that the association between hyperkeratotic spicules and monoclonal gammopathy is not fortuitous and may be related to particular properties of the monoclonal immunoglobulin.

Integrins constitute a group of transmembrane proteins which mediate cell-cell and cell-matrix interactions. Previous studies have shown both increased and decreased expression of integrins in relation to malignancy and invasion. In the present study, we investigated integrin distribution in cutaneous tumors by using monoclonal antibodies on frozen tissue sections. Antibodies to integrin subunits alpha v, alpha 3, alpha 4, alpha 5, alpha 6, beta 1 and beta 3 were used. The study was designed to explore (i) the association between integrin expression and the tumor type, and (ii) the effect on the integrin expression of the location of the tumor, i.e. whether it grows intraepidermally or within various compartments of the dermis (papillary or reticular). Beta 1, beta 3 and alpha 3 were strongly or moderately expressed in the epithelial and stromal cells of basal cell carcinomas (BCC), seborrheic keratoses, solar keratoses, dermatofibromas (DF), and showed a variable expression in the nevic cells of benign and dysplastic nevocellular nevi. alpha v and in alpha 5 appeared strongly expressed in the stromal cells of BCC and DF, while only a focal, often weak staining was seen in nevic cells and in the epithelial cells of BCCs. In some nevocellular nevi, they were only expressed, together with alpha 4, in the deep-seated nevic cells in the reticular dermis. alpha 6 was expressed by tumor cells of BCCs and nevocellular nevi only within the dermo-epidermal junction. In seborrheic keratosis and solar keratosis a basement membrane-associated staining pattern for alpha 6 was seen in the basal cell layer, with focal discontinuities in solar keratosis.(ABSTRACT TRUNCATED AT 250 WORDS)

The clinical and histological features of 'mechanic's hands' are described in a patient with polymyositis characterized serologically by antibodies to histidyl tRNA synthetase (Jo-1). Although described in the past in association with polymyositis, these distinctive cutaneous lesions have only recently been associated with the 'anti-synthetase syndrome'. It is becoming apparent that recognition of subsets within the spectrum of polymyositis/dermatomyositis characterized by certain clinical and serological features not only have prognostic significance, but also may provide insights into mechanisms of disease.

A commercially available antibody to proliferating cell nuclear antigen was used to characterize and compare proliferating cell populations in paraffin sections of benign, premalignant, and malignant lesions of human epidermis using routine immunohistochemical techniques. Three patterns emerged. An ordered pattern was found in prurigo nodularis and keratoacanthoma, wherein moderately and strongly positive nuclei were distributed in a continuous, basal-suprabasal layer of relatively uniform thickness. There was graded loss and ultimate extinction of PCNA staining in progressively more superficial epidermal cells. A basal dysplastic pattern was found in actinic keratosis and squamous cell carcinoma. Nuclei of essentially all dysplastic cells of both categories expressed PCNA, with a preponderance of strongly positive nuclei. These were localized to basal-suprabasal zones that were often expanded. Loss of PCNA reactivity toward the surface was often abrupt. Bowen's disease exhibited a diffuse dysplastic pattern, wherein large numbers of moderately and strongly positive nuclei, in random array, were present in essentially full thickness distribution. In many fields, however, a layer of cytologically bland basal cells, with faint or no nuclear staining, was interposed between dysplastic epithelium and dermis. This study has demonstrated that proliferating cell populations in epidermal lesions can be assessed with simple, inexpensive methods. There were consistent differences between the proliferating cell populations of the various entities studied, differences that can be reasonably correlated with other known clinical, microscopic, and biologic features of the lesions. This technique should provide an interesting new avenue for study of diverse cutaneous diseases.

Renal transplant recipients who have skin cancer potentially related to human papillomavirus were HLA typed with a special focus on HLA-A11, which in nonimmunosuppressed patients is negatively associated with the occurrence of virus-related carcinoma of the cervix. We found also a negative association between HLA-A11 and skin cancer; none of the 66 transplant recipients with skin cancer were positive for HLA-A11. As HLA-A11 seems to have a protective effect against skin cancer, we speculate that antigens induced by squamous cell carcinomas and possibly also by human papillomavirus may be efficiently presented through HLA-A11 to cytotoxic T cells. We also investigated a possible influence of other HLA alleles on the susceptibility of renal transplant recipients to skin cancer. The frequency of HLA-B27 was significantly higher in the transplant recipients with skin cancer, with a relative risk of 3.4 relative to healthy controls. No significant differences were found for other HLA class I or class II antigens.

A monoclonal antibody (ES3A) was raised against a mouse graft-versus-host reaction (GVHR) model. This antibody was against basal cell cytoplasm and reacted with an acidic (pI 6.2) 50 kDa keratin of human epidermis. However, ES3A reacted with several lower layers of epidermal cells in psoriasis and seborrhoeic keratosis. Acanthotic seborrhoeic keratosis showed varying patterns even in a single lesion. If combined with FACS analysis, ES3A-positive cells could be quantified. Normal skin showed 28%, while psoriasis and seborrhoeic keratosis showed 44% and 51%, respectively. ES3A-positive compartments of the acanthotic type of seborrhoeic keratosis were larger than those of the hyperkeratotic type. ES3A may be suitable for quantification of germinative or proliferative cells.

A 24-year-old woman, presenting with cystic fibrosis, developed superficial actinic porokeratosis. Immunosuppression due to cystic fibrosis may be either the cause of or the exacerbating factor in superficial actinic porokeratosis in our patient.