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Background: Oral lichen planus is a well-known chronic inflammatory mucocutaneous disorder, which has clinical and histological presentation that mimics oral lichenoid reaction. According to the fifth edition of WHO, both conditions are considered as oral potentially malignant disorders. Recent studies on oral potential disorders documented deregulation of some signaling molecules related to the Wnt/β-catenin pathway. Therefore this study aimed to compare the immune expression of β-catenin & CD163 in dysplastic /non-dysplastic cases of Oral lichen planus & oral lichenoid lesion. In addition, a statistical correlation between both immune markers was done regardless of the type of the study group., Methods: Four study groups were designated as 2 groups of Oral lichen planus (one dysplastic & one non -dysplastic) and the other 2 groups were oral lichenoid lesions (one dysplastic & one non -dysplastic). Ten cases in each group were collected and investigated by immunohistochemistry. The area percent of beta catenin and also counting of m2 macrophages expressing + CD163 marker was calculated in the study groups., Results: The Statistical analysis highlighted a statistically significant difference between the studied groups. Moreover, Pearson correlation test reported a significant moderate positive correlation between beta catenin & CD163 expression in the studied cases., Conclusion: Our findings supported new perceptions of the mechanism by which tumor associated macrophage specific β-catenin signaling promotes the aggressive behavior of oral potential malignant disorders., Clinical Relevance: Evidence of the relationship between beta catenin and M2 macrophages (+ CD163) may enhance the development of macrophage-based strategies for treatment and improve the prognosis of such cases., (© 2024. The Author(s).)

Background: Oral lichen planus is a T-cell-mediated chronic inflammatory disease affecting approximately 1% to 2% of the population, the etiology of which is currently unknown. The objectives of this study were to observe if senescence occurs in oral lichen planus, through the assessment of the immunohistochemical expression of a novel marker for senescence called Senescence marker protein-30 or regucalcin, and compare the expression to that in oral lichenoid reaction and non-specific inflammation., Subjects and Methods: The study material consisted of 30 cases of oral lichen planus, 15 cases of oral lichenoid reaction and 15 cases of non-specific inflammation. The number of positive cells in ten randomly selected high power fields were counted in the epithelium and the connective tissue separately and the mean was determined., Results: Mann-Whitney U test was used to statistically analyze if there was any significant difference in the expression of Senescence marker protein-30 between oral lichen planus, oral lichenoid reaction and non-specific inflammation. Even though a greater expression was seen in the oral lichen planus cases than oral lichenoid reaction, the difference in both the epithelium and connective tissue was not statistically significant., Conclusion: This study shows that in addition to the already known mechanisms like apoptosis and increased cell proliferation rates, the activated T-lymphocytes may also trigger a senescent change in the cells of oral lichen planus. As with the other mechanisms, this is also seen only in a small proportion of the cases., Competing Interests: None

Cutaneous immune-related adverse events (irAEs) are a known consequence of immune checkpoint inhibitor (ICI) therapy and may exhibit a spectrum of morphologic features both clinically and histologically. Lichenoid dermatitis associated with ICI therapy (LD-ICI) is the most frequently encountered histopathologic type of irAE biopsied by dermatologists. There is frequent clinical and histologic overlap between irAEs and several reactive and neoplastic dermatologic disorders; thus, clinical information is essential. LD-ICI with histologic, immunohistochemical, and molecular features typical of mycosis fungoides (MF) are unique. Here, we report a patient who developed LD-ICI with MF-like morphologic features with monoclonal T-cell receptor gene rearrangement on consecutive biopsies during ICI therapy. The development of monoclonal LD-ICI is important for clinicians and pathologists to recognize in patients receiving ICI therapy., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Non-communicable inflammatory skin diseases (ncISD) such as psoriasis or atopic eczema are a major cause of global disease burden. Due to their impact and complexity, ncISD represent a major challenge of modern medicine. Dermatology textbooks describe more than 100 different ncISD based on clinical phenotype and histological architecture. In the last decades, this historical description was complemented by increasing molecular knowledge - and this knowledge is now being translated into specific therapeutics. Combining the enormous advances made in lymphocyte immunology and molecular genetics with clinical and histological phenotyping reveals six immune response patterns of the skin - type I immune cells cause the lichenoid pattern characterized by immune-mediated cell death of keratinocytes; type II immune cells underlie the eczematous pattern with impaired epidermal barrier, infection and eosinophils as well as the bullous pattern with loss of epithelial integrity; Th17 cells and ILC3 mediate the psoriatic pattern characterized by acanthosis, high metabolic activity and neutrophils; dysbalance of regulatory T cells causes either the fibrogenic pattern with rarefication of cells and dermal thickening or the granulomatous pattern defined by formation of granulomas. With more and more specific therapeutic agents approved, classifying ncISD also according to their immune response pattern will become highly relevant. This review defines the six immune response patterns of ncISD and highlights therapeutic strategies targeting key lymphocyte mediators., (© 2017 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Immune checkpoint agents targeting programmed cell death-1 protein (PD1) or cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) receptors are increasingly utilized in treatment of advanced malignancies. However, these immunotherapies are commonly associated with idiosyncratic cutaneous adverse reactions. Thus, recognition and awareness of these reactions are necessary., Methods: We reviewed the skin biopsies of all patients on anti-PD1 therapy with or without ipilimumab who developed lichenoid inflammation and included those with microscopic suprabasal or intraepidermal clefts., Results: Four patients presented with interface dermatitis with microscopic intraepidermal clefts. In 2 patients, the clefts were well developed and had some acantholytic cells while the other 2 appeared to be spongiosis or inflammation related. Immunofluorescence was negative in 1 patient. None of them had clinical findings in keeping with paraneoplastic pemphigus (PP) and the symptoms improved with either topical corticosteroid or withdrawal of immunotherapy., Conclusions: Lichenoid drug reaction occurring in patients receiving anti-PD1 therapy may be associated with microscopic suprabasal or intraepidermal clefting. The clinical course was similar to lichenoid drug reactions without clefting even though some lesions may resemble PP microscopically., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Distinguishing regressed lichen planus-like keratosis (LPLK) from regressed melanoma can be difficult on histopathologic examination, potentially resulting in mismanagement of patients., Objective: We aimed to identify histopathologic features by which regressed melanoma can be differentiated from regressed LPLK., Methods: Twenty actively inflamed LPLK, 12 LPLK with regression and 15 melanomas with regression were compared and evaluated by hematoxylin and eosin staining as well as Melan-A, microphthalmia transcription factor (MiTF) and cytokeratin (AE1/AE3) immunostaining., Results: (1) A total of 40% of regressed melanomas showed complete or near complete loss of melanocytes within the epidermis with Melan-A and MiTF immunostaining, while 8% of regressed LPLK exhibited this finding. (2) Necrotic keratinocytes were seen in the epidermis in 33% regressed melanomas as opposed to all of the regressed LPLK. (3) A dense infiltrate of melanophages in the papillary dermis was seen in 40% of regressed melanomas, a feature not seen in regressed LPLK., Conclusions: In summary, our findings suggest that a complete or near complete loss of melanocytes within the epidermis strongly favors a regressed melanoma over a regressed LPLK. In addition, necrotic epidermal keratinocytes and the presence of a dense band-like distribution of dermal melanophages can be helpful in differentiating these lesions., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To dissect the aberrant microRNA profile of oral lichenoid disorders (OLD) by analyzing the larger set of OLD samples tested so far., Materials and Methods: MicroRNA expression profiles were assessed using TLDA card in 32 samples (16 OLD, 8 OSCC, and 8 control). The findings were validated using RT-qPCR in an independent cohort of 91 samples., Results: We identified 20 differentially expressed microRNAs in OLD, of which several are functionally related to cell proliferation, response to organic substances, or immune processes. Further validation of the top-ranked microRNAs revealed that they were all aberrantly expressed in OLD., Conclusion: We have identified a new microRNA signature associated with OLD that may provide a meaningful basis for better understanding the physiopathology of the disease. In addition, we validated seven microRNAs whose expression was shown to be higher in OLD tissue in comparison with the control and OSCC tissues., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The aim of this study was to evaluate prolidase activity and oxidative stress in patients with oral lichen planus (OLP) and oral lichenoid contact reactions (OLCR) using serum and salivary samples and to compare these biomarkers with each other as well as with a group of healthy subjects in order to be able to opine their role in the estimation of OLP and OLCR., Patients and Methods: Eighteen recently diagnosed patients with OLP, 32 patients with OLCR and 18 healthy controls with matched periodontal status were recruited to the study. Prolidase activity, lipid peroxidation product malondialdehyde (MDA), sialic acid (SA), and advanced oxidation protein products (AOPPs) levels in both serum and saliva were determined. Additionally, salivary flow rate and its buffering capacity were estimated. Statistical analyses were performed using the chi-square test, t-test, Mann-Whitney U-test, and Spearman's rho correlation coefficient., Results: No statistically significant differences were observed between the study groups and the control group regarding to the basic characteristics and the periodontal status (P > 0.05). There were no statistically significant differences between OLP and OLCR groups regarding to the distribution of lesions' type, severity, and location (P > 0.05). No significant differences were found between the two study groups with regard to Prolidase activity, MDA, SA, and AOPPs (P ˃ 0.05), whereas statistically significant differences were found between the two study groups and the control group with regard to all evaluated parameters except of serum prolidase (P ˂ 0.01). Moderate correlation was found between salivary MDA and the OLP/OLCR lesion severity, whereas a weak correlation was observed between serum SA and the OLP/OLCR lesion severity (P ˂ 0.05)., Conclusions: The findings of this study suggest an increased prolidase activity and oxidative stress and imbalance in the antioxidant defense system in biological fluids of patients with OLP and OLCR when compared with the healthy subjects. Both OLP and OLCR patients revealed almost similar prolidase activity and oxidative stress levels although these two conditions have different etiopathogenesis., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Lichen striatus (LS) and linear lichen planus (LLP) are separate uncommon disorders belonging to linear inflammatory dermatoses. The immunotyping of inflammatory cells has been investigated in LS and lichen planus (LP), but epidermal proliferation and differentiation have little been described in LS and LLP., Methods: The clinical and pathological data of eight patients with LS and seven with LLP were retrospectively collected. Immunotyping of infiltrated cells and expression of Ki-67, K16, involucrin, and filaggrin were stained by immunohistochemistry in skin lesions of these patients and normal skin of eight healthy controls., Results: Dermal infiltrates contained primarily CD3+ and CD68+ cells in three groups. CD4+ cells were predominantly located in the perivascular area, while CD8+ cells were frequently close to the junctional zone. Compared with control skin, epidermal and dermal CD1a+ cells, and dermal CD3+, CD4+, CD8+, and CD68+ cells were increased in LS and LLP (P < 0.05), while Ki-67+ cells were significantly high in LLP (P < 0.05) but not in LS. K16 and involucrin expression in LLP were more extensive than in LS, and filaggrin expression was similar between both entities., Conclusions: Our results indicate that the predominance of CD8+ cells and increased epidermal proliferation and abnormal keratinization are present in both dermatoses, although the levels of the above indexes are mild in LS as compared to LLP. These two entities might be due to the interaction of infiltrated cells and keratinocytes, and CD8+ cells could play a pivotal role in their pathogenesis., (© 2016 The International Society of Dermatology.)

Although recent research on the pathogenesis of allergic skin diseases such as atopic dermatitis has focused on defects in skin genes important for maintaining skin barrier function, the fact that excreted sweat has an overwhelmingly great capacity to increase skin surface hydration and contains moisturizing factors has long been ignored: the increase in water loss induced by these gene defects could theoretically be compensated fully by a significant increase in sweating. In this review, the dogma postulating the detrimental role of sweat in these diseases has been challenged on the basis of recent findings on the physiological functions of sweat, newly recognized sweat gland-/duct-related skin diseases, and therapeutic approaches to the management of these diseases. We are now beginning to appreciate that sweat glands/ducts are a sophisticated regulatory system. Furthermore, depending on their anatomical location and the degree of the impairment, this system might have a different function: sweating responses in sweat glands/ducts located at the folds in hairy skin such as on the trunk and extremities could function as natural regulators that maintain skin hydration under quiescent basal conditions, in addition to the better-studied thermoregulatory functions, which can be mainly mediated by those at the ridges. The normal functioning of sweat could be disturbed in various inflammatory skin diseases. Thus, we should recognize sweating disturbance as an etiologic factor in the development of these diseases., (© 2016 S. Karger AG, Basel.)

The aim of this article was to compare the expression of p53 protein in oral lichen planus (OLP) and oral lichenoid reaction (OLR). The study population consisted of 65 patients--31 diagnosed with OLP and 34 with OLR. The results showed more p53 positive cases in the OLP group than in the OLR group. However, the difference between the 2 groups was not statistically significant (P = 0.114). The most common immunolocalization was observed at the basal cell layer. Due to the chance of potential future malignancy, follow-up for all cases is recommended.

Background: Sox10 is a transcription factor associated with neural crest development. Its expression has been reported in melanocytes and peripheral nerve sheath cells and their associated tumors., Objective: To assess Sox10 sensitivity in benign and malignant melanocytic neoplasms of various histologic subtypes and to discern the specificity of Sox10 in distinguishing between melanocytic neoplasms and fibrohistiocytic and histiocytic mimickers., Methods: Sox10 expression was examined by immunohistochemistry in 145 cases of formalin-fixed paraffin-embedded tissue, including benign and malignant melanocytic lesions of various histologies and stages (n = 83), fibrohistiocytic and histiocytic lesions (n = 33), and peripheral nerve sheath tumors (n = 19), among others (n = 10)., Results: Immunoreactivity with Sox10 was observed in 100% (83/83) of benign and malignant melanocytic lesions of various subtypes, as well as in 100% (19/19) of benign and malignant peripheral nerve sheath lesions. Among the fibrohistiocytic proliferations and histiocytoses examined, Sox10 was negative in all cases (0/33). Sox10 expression did not vary by histologic subtype in nevi or melanoma; however, both the percentage of tumor nuclei demonstrating Sox10 expression and the intensity of expression were inversely correlated with malignant potential (nevi, melanoma in situ, invasive and metastatic melanoma) (P < .001, P = .016, respectively). Malignant peripheral nerve sheath tumors also showed decreased mean Sox10 expression and decreased intensity of expression when compared with benign counterparts (P < .001, P = .021, respectively)., Limitations: This is a retrospective study with 145 cases included., Conclusions: Sox10 is a highly sensitive marker for melanocytic proliferations and may be useful diagnostically when the differential diagnosis includes fibrohistiocytic and histiocytic proliferations demonstrating S100 expression., (Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Pseudomelanocytic nests in the setting of lichenoid inflammation can mimic atypical melanocytic proliferations. Both melanocytic and cytokeratin immunohistochemical stains may be utilized to differentiate these entities. Unlike true melanocytic nests, pseudomelanocytic nests contain Melanoma Antigen Recognized by T-cells 1 (MART-1)/ Melan-A-positive cells and cells positive for pan-cytokeratins, CD3 and/or CD68. Recently, rare (1-2 cells/nest) microphthalmia- associated transcription factor (MiTF)-positive cells were also reported in pseudomelanocytic nests. We present a 48-year-old man with a 2 × 3 cm violaceous to hyperpigmented, non-blanching, polygonal patch on the neck. Histopathology showed focal epidermal atrophy, irregularly distributed junctional nests and a lichenoid infiltrate with colloid bodies. Immunoperoxidase studies revealed occasional pan-cytokeratin and MART-1/Melan-A-positive staining in nests as well as focal S-100 protein-positive cells. Importantly, the majority of nests showed numerous cells positive for MiTF and SOX10 (>2 cells/nest and some the majority of cells). This combined staining pattern confounds the above-described immunohistochemical distinction between pseudo and true melanocytic nests. Clinically felt to represent unilateral lichen planus pigmentosus/erythema dyschromicum perstans and not malignant melanoma in situ, this lesion highlights the importance of clinicopathologic correlation and suggests either a new melanocytic entity or a novel pattern of benign melanocytic reorganization in a subset of lichenoid dermatitides., (Copyright © 2011 John Wiley & Sons A/S.)

Several case reports have discussed the difficulty in differentiating junctional pseudomelanocytic nests as a result of lichenoid inflammation from a true melanocytic neoplasm. Even immunohistochemistry can be misleading in these cases with both Melan-A and Mart-1 frequently resulting in false positivity as a result of nonspecific labeling of nonmelanocytic cells containing melanosomes. We present a series of 2 similar cases which were initially misdiagnosed as melanoma in situ likely as a result of Mart-1 positivity of the pseudomelanocytic nests. However, in our review, a significant lichenoid reaction was apparent at the dermal-epidermal junction. Staining with microphthalmia-associated transcription factor (MITF) showed a normal density of melanocytes along the dermal-epidermal junction and failed to uniformly label the Mart-1-positive pseudomelanocytic nests. In both patients, medications frequently resulting in fixed drug eruptions were identified, and a final diagnosis of fixed drug eruption was rendered in both cases. In light of these findings we suggest MITF is a more useful marker for evaluating lentiginous proliferations along the dermal-epidermal junction particularly when dealing with the differential diagnosis of lichenoid reaction with pseudomelanocytic nests versus melanoma in situ.

Background: FoxP3 is the most specific available marker for regulatory T cells (Tregs). Tumor-associated FoxP3-positive Tregs have been identified in various neoplasms, including cutaneous T-cell lymphoma (CTCL). FoxP3 expression in CTCL varies across groups; few studies have compared CTCL with inflammatory conditions., Methods: Lesional skin biopsies from 20 patients with CTCL [13 mycosis fungoides (MF); 7 Sézary syndrome (SS)] and 22 with inflammatory dermatoses (11 spongiotic; 11 lichenoid or interface) were examined for FoxP3 expression by immunohistochemistry. Epidermal FoxP3-positive lymphocytes were counted as a percentage of the total epidermal CD3-positive T-cell population., Results: FoxP3-positive T cells composed the minority of infiltrate in all major categories. Lower numbers of epidermal FoxP3-positive T cells were observed in CTCL, particularly MF, than in inflammatory dermatoses (P < .001). CTCL neoplastic T cells did not express FoxP3., Conclusion: FoxP3-positive T cells are less frequently encountered in MF than in inflammatory dermatoses. FoxP3-positive T cells occur in higher proportions in the dermis than in the epidermis and probably correlate with coexisting inflammatory components. CTCL neoplastic cells do not typically express a Treg phenotype and are associated with low numbers of FoxP3-positive Tregs in the infiltrate. FoxP3 expression by immunohistochemistry may aid histologic evaluation of these conditions.

We encountered recently 3 cases with a histopathologic diagnosis of melanoma in situ on sun-damaged skin (male = 2, female = 1; median age: 59 years; range: 52-60 years). The diagnosis was based mainly on the finding of actinic elastosis in the dermis and increased number of melanocytes in the epidermis and was confirmed by strong positivity for Melan-A in single cells and in small nests ("pseudomelanocytic nests"), located at the dermoepidermal junction. Indeed, examination of slides stained with hematoxylin and eosin revealed the presence of marked hyperpigmentation and small nests of partially pigmented cells at the dermoepidermal junction, positive for Melan-A. The histologic and especially the immunohistochemical features were indistinguishable from those of melanoma in situ on chronic sun-damaged skin. In addition, a variably dense lichenoid inflammation was present. Clinicopathologic correlation, however, showed, in all patients, the presence of a lichenoid dermatitis (phototoxic reaction, 1 case; lichen planus pigmentosus, 1 case; and pigmented lichenoid keratosis, 1 case). Our cases clearly show the histopathologic pitfalls represented by lichenoid reactions on chronic sun-damaged skin. Immunohistochemical investigations, especially if performed with Melan-A alone, may lead to confusing and potentially disastrous results. The unexpected staining pattern of Melan-A in cases like ours raises concern about the utility of this antibody in the setting of a lichenoid tissue reaction on chronic sun-damaged skin. It should be underlined that pigmented lesions represent a paradigmatic example of how immunohistochemical results should be interpreted carefully and always in conjunction with histologic and clinical features.

Background: Lichenoid graft-versus-host disease (liGVHD) histologically shares several common features with other lichenoid dermatoses, such as cutaneous lupus erythematosus and lichen planus (LP), which collectively show a junctional infiltrate of cytotoxic lymphocytes with liquefaction of the basal layer ("interface dermatitis"). Because recent studies have shown a role for type I interferon (IFN)-associated inflammation, including lymphocyte recruitment via CXCR3 <-> ligand interaction in cutaneous lupus erythematosus and LP, we hypothesized that similar mechanisms might also be involved in liGVHD., Methods: Ten representative lesional skin biopsies taken from patients with different subsets of chronic cutaneous graft versus host disease (GvDH) were recovered from the authors' archives. Eight LP specimens and 5 punch biopsies taken from healthy skin were analyzed for control purposes. Immunohistochemistry was performed to characterize the lesional infiltrate (CD3, CD4, CD8, CD20, CD56, or CD68), to analyze type I IFN signaling (MxA), and to investigate expression of the IFN-inducible chemokines CXCL9 and CXCL10 and their ligand CXCR3. In situ hybridization was performed to visualize IFNalpha expression on the mRNA level., Results: Our analyses revealed striking similarities between the inflammatory pattern seen in LP and liGVHD. Both disorders presented with a predominantly T-cellular inflammation with CD8(+) lymphocytes affecting the basal epidermal layer. The majority of lesional lymphocytes expressed the chemokine receptor CXCR3. The corresponding chemokines CXCL9 and CXCL10 were found in the epidermis and within the inflammatory infiltrate. Analyses of MxA and IFNalpha mRNA expression supported a role for type I IFNs in these conditions., Limitations: This study was limited by the number of well characterized cases in our archives. In situ hybridization was realizable only in single cases., Conclusion: Our results support the hypothesis that CXCR3 <-> ligand-mediated lymphocyte recruitment is involved in cutaneous liGVHD. The fact that CXCL10 was seen in precisely those areas with extensive liquefaction of the basal epidermis supports a role of this chemokine for the development of the typical histologic "interface" pattern.

Background: Lupus erythematosus (LE) is an autoimmune disease of unknown cause. Prevalence of oral involvement in patients with LE is uncertain but may vary from 9 to 45% in patients with systemic disease and from 3 to 20% in patients with chronic cutaneous involvement., Methods: Incidence of oral lesions of LE and their clinical aspects were investigated. Their histopathologic features were analyzed, and the status of epithelial maturation was assessed through the expression patterns of cytokeratins., Results: Twenty-six patients (from 188 examined) presented oral lesions of LE. Most of them were females (19) with systemic disease (11). Clinical aspects of these lesions varied, and lips and buccal mucosa were most affected. Histologically, lesions revealed lichenoid mucositis with perivascular infiltrate and thickening of basement. Cytokeratins profile showed hyperproliferative epithelium, with expression of CK5/6, and CK14 on all epithelial layers, CK16 on all suprabasal layers and CK10 on prickle cell layers only., Conclusions: Oral lesions of LE show a variety of aspects, and their microscopic features are of a lichenoid mucositis with deep inflammatory infiltrate. Cytokeratins expression patterns are of hyperproliferative epithelium, and this phenomenon must be analyzed in relation to the inflammatory cytokines for a better understanding of the mechanisms of the disease.

A small proportion of cases diagnosed as oral lichen planus (OLP) and oral lichenoid lesions (OLL) can undergo malignant transformation. Some authors, however, stand that only dysplastic lichenoid lesions, not true OLP, have the potential to progress to oral squamous cell carcinoma (OSCC). The histologic diagnosis is a subjective resource and is not always accurate in differentiating OLP from OLL. Thus, this study attempted to evaluate the malignant potential of lesions diagnosed as OLP and as OLL without dysplasia. The Streptavidin-biotin method of immunohistochemistry was used for the staining with p53 and Ki67 in 22 cases of OLP and 27 cases diagnosed as OLL. Ki67 immunoexpression was not statistically different between OLP and OLL (p = 0.353), but, p53 staining showed a significant contrast (p = 0.036). A higher average of staining was detected in the group of OLP. The study showed that apparently a diagnosis of OLP or OLL makes no difference for the patient regarding malignant transformation, although in OLP p53 showed a higher index of expression, probably related to the intensity of inflammatory infiltrate.

Background: Spongiotic and lichenoid dermatitides are frequently stained with periodic acid-Schiff (PAS) stains to check for the presence of dermatophytes. PAS+ structures without a septate morphology are often seen with lichenoid dermatitides, however, their nature has not been previously characterized., Methods: Fifteen consecutive biopsies of lichenoid and five spongiotic dermatitides were stained with hematoxylin and eosin (H&E), PAS, and antibodies to CD1a., Results: Twelve of 15 lichenoid and none of the five spongiotic dermatitis showed PAS+ structures in the stratum corneum. Distinct septation or branching was not identified in these PAS+ structures. Eleven of 15 from the lichenoid group, but none from the spongiotic group, showed CD1a+ structures in the stratum corneum. This staining pattern suggests that the intracorneal structures represent the dendritic processes of Langerhans' cells (LCs) within the stratum corneum., Conclusions: PAS+ and CD1a+ structures are present in the stratum corneum of lichenoid, but not in spongiotic, dermatitis. This study morphologically confirms extension of LC dendrites into the stratum corneum in lichenoid but not in spongiotic dermatitides.

Keratinocyte hyperproliferation, inflammatory infiltrates, neoangiogenesis and alterations in cytokine levels are hallmarks of psoriatic skin. Matrix metalloproteinases (MMPs) have been associated with the remodeling of the extracellular matrix during inflammation, neovascularization, and malignant transformation. We have previously shown that particularly MMP-12 is abundantly expressed by macrophages and MMP-9 in macrophages and neutrophils of psoriatic lesions. In this work the expression of two novel metalloproteinases, MMP-19 and MMP-28, was investigated in psoriatic lesional and non-lesional skin. MMP-19 protein was detected by immunohistochemistry in 28/29 samples in keratinocytes in the same regions as Ki67 (marker of proliferating keratinocytes) and p63 (marker of keratinocyte stem cells). Immunosignaling was also seen in endothelial cells and fibroblasts. Furthermore, MMP-19 mRNA was upregulated in psoriatic keratinocytes and skin as assessed by quantitative real-time polymerase chain reaction. In lichen planus and lichenoid chronic dermatitis, MMP-19 staining was found in keratinocytes in areas where the basement membrane was abnormal. MMP-28 was not detected in psoriatic or non-lesional skin. Our results suggest that keratinocytes as well as the previously reported cell types (smooth muscle, endothelial and macrophages) can express MMP-19 in psoriasis and lichen planus. Upregulation of MMP-19 in keratinocytes may be influenced by changes in the architecture of the basement membrane zone.

Loss of CD7 expression by neoplastic lymphocytes is considered a distinguishing characteristic of mycosis fungoides (MF) and cutaneous T-cell lymphoma. Reports to date examining for the CD7 immunophenotype in MF have been performed on fresh-frozen tissue. In this study, we used a paraffin-reactive antibody directed against CD7 to determine its range of expression in MF and to compare these results with those in controls. Examining 22 cases of MF and 61 controls, we found minimal CD7 expression by lymphocytes in MF and in a few cases of benign inflammatory dermatosis (BID). The lowest mean CD7 counts (as a percentage of total lymphocytes) were found in MF (patch stage: 5% +/- 5%, range: 0-10; plaque and tumor stages: 15% +/- 5%, range: 5-25), and these counts were significantly lower than those for BID (35% +/- 20%, range: 5-80; p = 0.001). By logistic regression analysis, low CD7 expression (<10% lymphocytes labeling) had sensitivity and positive predictive values of 80% and 72%, respectively, and specificity and negative predictive values of 93% and 96%, respectively, for the diagnosis of patch stage MF. False-positive results were found for spongiotic dermatitis. Moreover, spongiotic dermatitides exhibited a progressive decrease in mean CD7 counts from acute to subacute to chronic stages (50% versus 35% versus 30%, respectively). In conclusion, minimal CD7 expression is a specific finding for MF. Benign inflammatory infiltrates can also show low CD7 expression, however, which rarely matches that of patch stage MF. Progressive loss of CD7 expression in BID is the likely consequence of expansion of antigen-selected CD3+CD4+CD7- T cells. These inflammatory CD4+CD7- T cells may represent the physiologic counterpart to the neoplastic lymphocyte of MF.

The cause of progressive dermal sclerosis, proliferation of fibroblasts, and collagen deposition in scleromyxedema is unknown. We analyzed the heparan sulphate proteoglycans (HSPG) in cutaneous nodules from a patient with scleromyxedema in order to ascertain their role in the binding of fibroblast growth factor (FGF) and promoting signaling complex assembly. Total heparan sulphate (HS) was detected with a monoclonal antibody to HSPG on paraffin sections. Binding of FGF to HS was assessed using FGF-2 followed by anti-FGF-2 antibody. The formation of HS-mediated signaling complex was studied using soluble FR1-AP, which contains the extracellular domain of FGF receptor-1 linked to alkaline phosphatase (AP) and monoclonal anti-AP-antibody. Anti FGF-2 and anti-AP antibodies were visualized using the DAKO Envision Plus system. The dermal nodule of scleromyxedema contained ample HS and these bound FGF-2 and FR1-AP. Specificity was confirmed by prior incubation with heparitinase (no staining) and omission of FGF-2 (no staining). Increased amounts of HSPG were present in the dermal nodules of scleromyxedema compared to adjacent normal dermis and these bound FGF-2, immobilized the soluble receptor protein FGFR-1 and, therefore, formed a ternary complex composed of HSPG, FGF-2 and FGFR-1 in vitro. Since this complex resembles the signaling complex formed on live cells, HSPG in the nodules of scleromyxedema are in a configuration that promotes FGF activity.

Acantholytic foci have been reported several times in pityriasis rubra pilaris (PRP). Lichenoid tissue reactions were also mentioned in the literature regarding PRP. We report a 58-year-old patient who, after having colon cancer, had PRP with biopsies showing acantholytic lesions and a heavy lichenoid lymphocytic infiltration. Investigation by serial sectioning of the acantholytic lesion suggested an involvement of the intraepidermal eccrine duct and further investigation with carcinoembryonic antigen (CEA) staining demonstrated a CEA-positive eccrine duct in the acantholytic foci. We suggest that acantholysis in PRP is induced by proteolytic enzymes, urea, and other substances in eccrine sweat in keratin-plugged acrosyringia. This patient had a combination of three relatively rare features of PRP-acantholysis, lichenoid reaction, and a cancer background.

Apolipoprotein E (apoE) is one of the amyloid associated proteins that is found in the amyloid plaque of Alzheimer's disease and systemic amyloidosis. ApoE might play an important part in the etiology of Alzheimer's disease by functioning as a "pathologic chaperone" to promote the formation of amyloid filaments. In this study, we investigated whether apoE is associated with amyloid deposits of primary localized cutaneous amyloidosis using immunohistochemistry, immunogold electron microscopy, and immunoblotting. The subjects consisted of 12 patients with lichen amyloidosus and one patient with macular amyloidosis. Light microscopically, amyloid deposits in the dermal papillae were round in shape and stained with Congo red. Immunohistochemically, apoE was detected in amyloid deposits in all the cases examined. Immunogold electron microscopy showed apoE immunoreactivity on the amyloid deposition. Immunoblots of amyloid-positive skin showed 35K and 14K proteins, which were taken to be apoE and its fragment, respectively. In normal skin extract, only the 35K protein was detected by the anti-human apoE. Moreover, the intensity of the amyloid-positive skin sample was stronger than that of the normal skin sample. Monoclonal anti-cytokeratin antibody reacted with the 45K protein of the amyloid-positive skin extract. These results indicate that apoE is a component of primary localized cutaneous amyloidosis, and that it might play an important role in primary localized cutaneous amyloidosis.

Background: A new antibacterial quinolone, sparfloxacin (SPFX), frequently causes photosensitive dermatitis and sometimes induces a treatment-resistant lichenoid tissue reaction (LTR)., Objective: We attempted to determine the factors that induce LTR in SPFX-induced photodermatitis., Methods: Thirteen patients with SPFX photosensitive dermatitis were studied clinically and histopathologically., Results: Six of the 13 patients had acute dermatitis with epidermal spongiosis and focal epidermal HLA-DR and intercellular adhesion molecule-1 (ICAM-1) expression with CD4+ cell infiltration. The other seven displayed LTR with basal cell liquefaction degeneration and diffuse epidermal HLA-DR and ICAM-1 expression associated with CD8+ cells. The seven patients with LTR were exposed to UV and SPFX for more than 2 weeks after the appearance of their initial eruption, whereas the six patients with acute dermatitis were treated within 2 weeks. The acute dermatitis lesions cleared significantly within 2 weeks, but the LTR lesions persisted for more than 6 weeks., Conclusion: Patients with quinolone-induced photosensitivity should be treated within 2 weeks of onset to prevent LTR.

Scleromyxedema is a rare fibromucinous connective tissue that can be associated with systemic changes, such as myopathy, neurologic defects, esophageal dysmotility, paraproteinemia, and restrictive lung disease. We describe a fatal case of scleromyxedema in which neurologic, cardiac, gastrointestinal, and muscle changes were present. At autopsy, mucin was found in the papillary dermis of skin and in coronary and pulmonary vessels, but was absent from the brain, kidneys, heart, gastrointestinal tract, esophagus, liver, thyroid, lymph nodes, bone marrow, and pancreas. Because the pathogenesis of scleromyxedema may not always be attributable to mucin deposition, the role of circulating factors in the development of systemic manifestations warrants further investigation.

Background: Perforin (Pf), a pore-forming protein, is a cytolytic protein of killer cells. Its deposition in lesioned skin has not been studied., Objective: The purpose of this study is to show Pf deposition in the lesioned skin and Pf expression in the dermal infiltrates of various inflammatory skin diseases., Methods: Frozen specimens obtained from 29 patients with 5 different diseases were immunohistochemically stained., Results: Granular deposition of Pf was found in the lesioned skin in 2 out of 5 cases of viral vesicles and in 3 out of 7 cases of erythema multiforme. In the cases with Pf deposition, the percentages of Pf+ cells in the dermis were higher than in those without deposition., Conclusion: Pf released from natural killer cells or cytotoxic T lymphocytes may play a role in tissue damage.

We report a case of beta 2-microglobulin-induced amyloidosis. The patient was a 40-year-old man suffering from non-amyloid nephropathy, who had been treated by haemodialysis for 20 years. Lichenoid skin lesions, consisting of groups of pin-head-sized shiny papules, were present on the arms and trunk. On histological examination, amyloid deposits were present, principally in the dermal papillae, but also around the sweat ducts and hair follicles. The amyloid displayed potassium-permanganate-resistant Congo red affinity, and green birefringence under polarized light. Immunohistochemically, beta 2-microglobulin was demonstrated in the lesions, confirming that they were a manifestation of beta 2-microglobulin-associated amyloidosis. Skin lesions of this type have not been reported previously in beta 2-microglobulin-associated amyloidosis.

Scanning electron microscopy with immunogold labeling revealed that epidermal keratinocytes expressed ICAM-1 (intercellular adhesion molecule-1) and HLA-DR molecules on their surfaces in patterns that differed in mycosis fungoides (MF) and lichenoid reaction (LR). ICAM-1 molecules, visualized as deposits of gold particle, were visualized as clusters adjacent to the junctions interconnecting the keratinocytes of MF lesions. LFA-1 (leukocyte function-associated antigen-1) molecules were seen as granules on the surfaces of all infiltrates, most of which also expressed ICAM-1. HLA-DR molecules were seen continuously along the borders of the individual keratinocytes, thus producing a cobblestone appearance on the epidermal undersurface. In contrast, ICAM-1 and HLA-DR were found only sparsely on the undersurface of the epidermis from LR. These findings may help to explain the differing histological features of MF and LR: ICAM-1 molecules present on the intercellular junctions of MF epidermis lead the LFA-1-bearing cells to migrate into the interspaces, thus producing epidermotropism. These cells aggregate by means of co-expressed ICAM-1 to thus produce Pautrier's microabscess. In LR, the minimal expression of ICAm-1 on the epidermal undersurface leaves most infiltrates within the dermis, thus producing a band-like infiltrate.