Patterns of Antinuclear Antibodies in a New Variant of Endemic Pemphigus in El Bagre, Colombia, Colocalizing with Antigens against MIZAP, ARVCF, p0071, and Desmoplakins I and II.

BACKGROUND: A new variant of endemic pemphigus foliaceus (EPF) has been documented, El Bagre-EPF. We aimed to study antinuclear antibodies (ANAs) in these patients. METHODS: We performed a case-control study, testing 57 patients affected by this disease and 57 controls from the endemic area matched by work activity and demographics. The participants were evaluated clinically as well as by detection of ANAs utilizing HEp-2 cells. We utilized Triton-induced partial permeabilization of the cell membranes, allowing for the visualization of intracellular and intranuclear antigens. We also immunoadsorbed the ANAs using synthetic peptides to elucidate the nature of the ANA. RESULTS: We detected the presence of a new pattern of ANAs. The new pattern of ANAs was seen in 24% of the El Bagre-EPF patients, compared to our controls (P < 0.001). The new ANA pattern consisted of a thin nuclear and nucleolar rim, finely speckled nucleolar, nuclear membrane pores stains, and a positive intranuclear stain directed against small nuclear components, as well as cytoplasmic deposits of autoantibodies were also observed. The new ANAs pattern perfectly colocalized with commercial antibodies to miocardium-enriched zonula occlusans-1 associated protein (MIZAP), armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF), p0071 and desmoplakins I-II (all from Progen Biotechnik). Additionally in 14% of patients with El Bagre-EPF forme fruste and hyperpigmented clinical presentations, a classic homogeneous ANA pattern was observed with autoantibodies specific for Ro, La, Sm, and double-stranded DNA antigens. Immunoadsorption with peptide-based sequences from MIZAP, ARVCF, p0071 and desmoplakins I-II removed the new ANA pattern. CONCLUSIONS: We describe a new pattern of ANAs in El Bagre-EPF, colocalizing with autoantibodies directed against MIZAP, ARVCF, p0071, and desmoplakins I-II.

Extrusion of pilosebaceous units into blisters of patients affected by a new variant of endemic pemphigus in El Bagre, Colombia, South America.

BACKGROUND: A new variant of endemic pemphigus foliaceus is present in El Bagre, Colombia, and surrounding municipalities (El Bagre-EPF) that affects the skin and in some presentations affects other organs with autoantibodies directed against cell junctions. METHODS: We studied 200 El Bagre-EPF patient perilesional skin biopsies, as well as 200 skin biopsies from normal controls in the endemic area. RESULTS: We observed blister extrusions of sebaceous glands or entire pilosebaceous units via the isthmus in 23% of the patients and not in the controls. CONCLUSIONS: The extrusion of hair follicular unit contents is consistent with our previous pathologic findings of autoreactivity to these units, and their observed clinical decrease in patients affected by El Bagre-EPF.

The Biomechanical Performance of the Latest All-Inside Meniscal Repair Devices.

PURPOSE: To evaluate the biomechanical characteristics of recently introduced meniscal repair devices with a hand-tied, inside-out meniscal suture in a human meniscus model. METHODS: In detached adult human menisci, vertical longitudinal cuts were created 3 mm from the synovial-meniscal junction, simulating a bucket-handle meniscal tear. Each cut was repaired using a single device. Group 1 received a vertical mattress suture of No. 2-0 OrthoCord; group 2, TrueSpan device with PEEK (polyether ether ketone) anchors containing No. 2-0 OrthoCord suture; group 3, TrueSpan device with biodegradable poly-lactide-co-glycolide (PLGA) anchors containing No. 2-0 OrthoCord suture; group 4, Meniscal Cinch II device; group 5, AIR meniscal repair device; and group 6, FasT-Fix 360 device. All samples were preloaded at 5 N and cycled 200 times between 5 and 20 N. The specimens that survived cyclic loading were destructively tested at 12.5 mm/s. Endpoints included maximum load, displacement, stiffness, and failure mode. RESULTS: The mean failure loads were as follows: 95.8 N for OrthoCord suture, 87.1 N for TrueSpan with PEEK, 84.6 N for TrueSpan with PLGA, 48.6 N for Meniscal Cinch II, 72.3 N for AIR, and 68.1 N for FasT-Fix 360. Repairs performed with OrthoCord suture (P = .002) and both TrueSpan devices (P < .03) but not the FasT-Fix 360 device or AIR device were statistically significantly stronger than Meniscal Cinch II repairs. Mean cyclic displacement measured 1.1 mm for OrthoCord, 1.5 mm for TrueSpan with PEEK, 1.5 mm for TrueSpan with PLGA, 2.1 mm for Meniscal Cinch II, 1.1 mm for AIR, and 1.4 mm for FasT-Fix 360. The Meniscal Cinch II device showed more displacement than all other devices (P < .05). The FasT-Fix 360, AIR, and Meniscal Cinch II devices failed by anchor pullout from the peripheral meniscus. OrthoCord and both TrueSpan devices failed by suture pulling through the bucket-handle tissue. CONCLUSIONS: OrthoCord suture is stronger than the AIR, FasT-Fix 360, and Meniscal Cinch II devices. The TrueSpan device with PEEK and TrueSpan device with PLGA are stronger than the Meniscal Cinch II device. The Meniscal Cinch II device failed during cyclic loading with greater cyclic displacement than the AIR device, FasT-Fix 360 device, OrthoCord, and TrueSpan device with PEEK. The Meniscal Cinch II, AIR, and FasT-Fix 360 devices failed by anchor pullout, whereas OrthoCord and both TrueSpan devices failed by suture pull-through. CLINICAL RELEVANCE: Some newly introduced all-inside meniscal repair devices show inferior failure strength compared with earlier versions that might adversely impact clinical outcomes.

Editorial Commentary: Glenoid Track Instability Management Score or Instability Severity Index Score-Will This Decrease Latarjet Abuse?

Open treatment of anterior shoulder instability using a coracoid transfer, such as the Latarjet procedure, is associated with low recurrence rates but with significant complications such as nerve injury, arthrosis, and graft osteolysis. However, an arthroscopic Bankart procedure, although less invasive and with a low complication rate, has the possibility of a higher recurrent instability rate. Scoring systems such as the Instability Severity Index Score, created to select patients for an arthroscopic Bankart procedure or coracoid transfer, have varying levels of success. Often, the scoring system selects a relatively high percentage of patients for the coracoid transfer, possibly undermining its widespread adoption. The relation between glenoid and humeral bone loss has produced the concept of "on-track" and "off-track," which impacts recurrent instability rates. Merging the on-track and off-track concept with the new Glenoid Track Instability Management Score may produce an algorithm that more accurately assesses the need for the Latarjet procedure or arthroscopic stabilization.

Involvement of the Areae Compositae of the Heart in Endemic Pemphigus Foliaceus.

BACKGROUND: A new variant of endemic pemphigus foliaceus in El Bagre (El Bagre-EPF), Colombia, South America, shares features with Senear-Usher syndrome and occurs in an endemic fashion. Patients affected by El Bagre-EPF have heterogeneous antigenic reactivity not only to the skin but to other organs, including the heart. Here we test for autoantibodies to the areae compositae of the heart (structure consisting of typical desmosomal amalgamated fascia adherens molecules) and evaluate any possible clinical correlation. METHODS: A case-control study comparing 45 patients and 45 controls from the endemic area, matched by demographics including age, gender, weight, work activities, and comorbidities, was performed. Direct and indirect immunofluorescence, immunohistochemistry, confocal microscopic studies, and echocardiogram studies were completed. RESULTS: The main clinical abnormally seen in the El Bagre-EPF patients was left ventricular hypertrophy in 15/45 patients, compared with no such findings in the control population (P < 0.1). Seventy percent of El Bagre-EPF patients and none of the controls displayed polyclonal autoreactivity using different immunoglobulins and complement to the areae compositae of the heart using different methods and antibodies (P < 0.1). CONCLUSIONS: Patients affected by El Bagre-EPF demonstrated autoantibodies to the areae compositae of the heart. This finding was associated with left ventricular hypertrophic cardiomyopathy. The areae compositae may play a role in cell junction tension and the El Bagre-EPF patients' autoantibodies possibly disrupting these junctions and thereby contributing to the left ventricular hypertrophy.

Membrane attack complex (C5b-9 complex or Mac), is strongly present in lesional skin from patients with endemic pemphigus foliaceus in El Bagre, Colombia.

BACKGROUND: El Bagre endemic pemphigus foliaceus (El Bagre-EPF) is a new variant of endemic pemphigus foliaceus present in the El Bagre area of Colombia, South America. Here, we investigate the presence of complement/C5-b9 in lesional skin of patients and matched controls from the endemic area. We also aim to compare the patient's autoantibody levels using indirect immunofluorescent titers (IIF) and correlate with the lesional presence of complement/C5b-9. METHODS: A case-control study was carried out by testing for the presence of complement/C5b-9 in lesional skin in 43 patients affected by El Bagre-EPF, as well as 43 matched, healthy controls from the endemic area. Skin biopsies were obtained and evaluated via hematoxylin and eosin staining, and immunohistochemistry. RESULTS: The presence of complement/C5b-9 was observed in all cases of the patients affected by El Bagre-EPF and was not observed in the controls from the endemic area (P < 0.001). The patients' autoantibody titers utilizing IIF for IgG and IgM showed correlation between higher autoantibody titers and stronger intensity of staining with complement/C5-b9 staining (P < 0.001). CONCLUSION: Patients affected by El Bagre-EPF have lesional deposition of complement/C5b, which correlates with disease severity and previously established serologies.

A Biomechanical Comparison of Six Suture Configurations for Soft Tissue-Based Graft Traction and Fixation.

PURPOSE: The purpose of this study was to compare 6 different graft fixation techniques to determine the preparation speed, fixation security, biomechanical strength, and resultant tissue trauma. METHODS: Six different techniques (10 samples each): #2 OrthoCord Krackow stitch, #2 FiberWire Krackow stitch, SpeedTrap, WhipKnot, Loop-in-loop stitch were created in the distal 3 cm of 9 cm bovine flexor tendons. The proximal 3 cm tendon segment was clamped in a testing machine and the distal suture ends secured by pneumatic grips. 3 preload cycles (10N-100N) and 50N static load was followed by 500 cycles (50N-200N) and then loaded to failure. Graft preparation times, 100 and 500 cycle displacement, maximum failure load, stiffness, and failure mode were recorded. RESULTS: Representative graft preparation times were: OrthoCord Krackow (247s), FiberWire Krackow (401s), FiberLoop (177s), SpeedTrap (42s), WhipKnot (39s), Loop-in-loop (45s). No WhipKnots survived cyclic loading. 100 cycle displacements were: OrthoCord Krackow (11.5 ± 3.9 mm), FiberWire Krackow (8.9 ± 1.2 mm), FiberLoop (14.2 ± 6.1 mm), SpeedTrap (8.8 ± 2.5 mm), Loop-in-loop (10.4 ± 2.9 mm). FiberLoop displaced significantly more than all others (P = .016). Maximum failure loads were: OrthoCord Krackow (364 ± 24N), FiberWire Krackow (375 ± 45N), FiberLoop (413 ± 95N), SpeedTrap (437 ± 65N), WhipKnot (153 ± 42N), Loop-in-loop (329 ± 112N). The most common failure mode was suture breaking. FiberWire containing constructs (Krackow and FiberLoop) shredded or cut through ("cheese wiring") prior to failure in a majority. CONCLUSIONS: SpeedTrap, WhipKnot and Loop-in-loop were quickest to create (under 1 minute). The Krackow, SpeedTrap, WhipKnot, and Loop-in-Loop did not damage the tendon during cyclic loading. SpeedTrap and Krackow had the least displacement. FiberLoop displaced more than all other groups (P = .016). No WhipKnot completed cyclic loading. The SpeedTrap (437N) and FiberLoop (413N) had the highest ultimate strength. CLINICAL RELEVANCE: While the SpeedTrap and FiberLoop are the strongest techniques, the FiberLoop shreds the tendon, displaced the most, and took longer to create. Based on these results, the SpeedTrap demonstrates the best overall performance.

Subclinical oral involvement in patients with endemic pemphigus foliaceus.

BACKGROUND: We have described a variant of endemic pemphigus foliaceus (EPF) in El Bagre area known as pemphigus Abreu-Manu. Our previous study suggested that Colombian EPF seemed to react with various plakin family proteins, such as desmoplakins, envoplakin, periplakin BP230, MYZAP, ARVCF, p0071 as well as desmoglein 1. OBJECTIVES: To explore whether patients affected by a new variant of endemic pemphigus foliaceus (El Bagre-EPF) demonstrated oral involvement. MATERIALS AND METHODS: A case-control study was done by searching for oral changes in 45 patients affected by El Bagre-EPF, as well as 45 epidemiologically matched controls from the endemic area matched by demographics, oral hygiene habits, comorbidities, smoking habits, place of residence, age, sex, and work activity. Oral biopsies were taken and evaluated via hematoxylin and eosin staining, direct immunofluorescence, indirect immunofluorescence, confocal microscopy, and immunohistochemistry. RESULTS: Radicular pieces and loss of teeth were seen in in 43 of the 45 El Bagre-EPF patients and 20 of the 45 controls (P < 0.001) (confidence interval [CI] 98%). Hematoxylin and eosin staining showed 23 of 45 El Bagre-EPF patients had corneal/subcorneal blistering and lymphohistiocytic infiltrates under the basement membrane zone and around the salivary glands, the periodontal ligament, and the neurovascular bundles in all cell junction structures in the oral cavity; these findings were not seen in the controls (P < 0.001) (CI 98%). The direct immunofluorescence, indirect immunofluorescence, confocal microscopy, and microarray staining displayed autoantibodies to the salivary glands, including their serous acini and the excretory duct cell junctions, the periodontal ligament, the neurovascular bundles and their cell junctions, striated muscle and their cell junctions, neuroreceptors, and connective tissue cell junctions. The autoantibodies were polyclonal. IgA autoantibodies were found in neuroreceptors in the glands and were positive in 41 of 45 patients and 3 of 45 controls. CONCLUSIONS: Patients affected by El Bagre-EPF have some oral anomalies and an immune response, primarily to cell junctions. The intrinsic oral mucosal immune system, including IgA and secretory IgA, play an important role in this autoimmunity. Our data contradict the hypothesis that pemphigus foliaceus does not affect the oral mucosa due to the desmoglein 1-desmoglein 3 compensation.

Patients affected by endemic pemphigus foliaceus in Colombia, South America exhibit autoantibodies to optic nerve sheath envelope cell junctions.

BACKGROUND: The majority of the patients affected by a new variant of endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre EPF or pemphigus Abreu-Manu), have experienced vision problems; we have previously reported several ocular abnormalities. METHODS: Here, we aimed to investigate reactivity to optic nerves in these patients. We utilized bovine, rat and mouse optic nerves, and performed immunofluorescence and confocal microscopy to test for optical nerve autoreactivity. We tested 45 patients affected by this disease and 45 controls from the endemic area matched by age, sex and work activity. RESULTS: Overall, 37 of the 45 patient sera reacted to the optic nerve envelope that is composed of leptomeninges; the reactivity was polyclonal and present mostly at the cell junctions (P < 0.001). The immune response was directed against optic nerve sheath cell junctions and the vessels inside it, as well as other molecules inside the nerve. No control cases were positive. Of interest, all the patient autoantibodies co-localized with commercial antibodies to desmoplakins I-II, myocardium-enriched zonula occludens-1- associated protein (MYZAP), armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF), and plakophilin-4 (p0071) from Progen Biotechnik (P < 0.001). CONCLUSION: We conclude that the majority of the patients affected by pemphigus Abreu-Manu have autoantibodies to optic nerve sheath envelope cell junctions. These antibodies also co-localize with armadillo repeat gene deleted in velo-cardio-facial syndrome, p0071 and desmoplakins I-II. The clinical significance of our findings remains unknown.

Autoantibodies to full body vascular cell junctions colocalize with MYZAP, ARVCF, desmoplakins I and II and p0071 in endemic pemphigus in Colombia, South America.

BACKGROUND: We previously described a new variant of endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre-EPF). METHODS: Here we aimed to investigate disease autoreactivity to vessels in all body organs/systems. We compared 57 patients and 57 controls from the endemic area, matched by demographics, age, sex, and work activity. We performed immunofluorescence, immunohistochemistry, confocal microscopy, immunoblotting, indirect immune electron microscopy studies, and autometallographic studies. We performed ultrasonography on large patient arteries, investigating for vascular anomalies. In addition, we reviewed autopsies on seven patients who died affected by El Bagre-EPF. We immunoadsorbed any positive vessel immunofluorescence with desmoglein (Dsg1), investigating for new autoantigens. RESULTS: Overall, 57/57 patients affected by El Bagre-EPF displayed autoantibodies to vessels in all the organs/systems of the body via all methods (P < 0.01). The autoreactivity was polyclonal, and the patient's antibodies colocalized with commercial antibodies to desmoplakins I and II, p0071, ARVCF, and MYZAP (all from Progen Biotechnik, Germany; P < 0.01; all present at cell junctions). Immunoadsorption with Dsg1 on positive vessel immunofluorescence showed that the immune response against the vessels was directed against non-Dsg1 antigen(s). Autometallographic studies showed deposits of metals and metalloids in vessel cell junctions and in erythrocytes of 85% of patients (P < 0.01). CONCLUSIONS: Immune response to these vascular antigens is likely altering endothelial cells and vessel shapes, thus disturbing hemodynamic flow. The flow alterations likely lead to inflammation and may play a role in the atherogenesis often seen in these patients.

Cardiac rhythm and pacemaking abnormalities in patients affected by endemic pemphigus in Colombia may be the result of deposition of autoantibodies, complement, fibrinogen, and other molecules.

BACKGROUND: We previously showed that one-third of patients affected by endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre-EPF), display autoreactivity to the heart. OBJECTIVE: The purpose of this study was to investigate rhythm disturbances with the presence of autoantibodies and correlate them with ECG changes in these patients. METHODS: We performed a study comparing 30 patients and 30 controls from the endemic area, matched by demographics, including age, sex, weight, work activities, and comorbidities. ECG as well as direct and indirect immunofluorescence, immunohistochemistry, and confocal microscopic studies focusing on cardiac node abnormalities were performed. Autopsies of 7 patients also were reviewed. RESULTS: The main ECG abnormalities seen in the El Bagre-EPF patients were sinus bradycardia (in one-half), followed by left bundle branch block, left posterior fascicular block, and left anterior fascicular block compared with the controls. One-third of the patients displayed polyclonal autoantibodies against the sinoatrial and/or AV nodes and the His bundle correlating with rhythm anomalies and delays in the cardiac conduction system (P <.01). The patient antibodies colocalized with commercial antibodies to desmoplakins I and II, p0071, armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF), and myocardium-enriched zonula occludens-1-associated protein (MYZAP; Progen Biotechnik) (P <.01). CONCLUSION: One-third of the patients affected by El Bagre-EPF have rhythm abnormalities that slow the conduction of impulses in cardiac nodes and the cardiac conduction system. These abnormalities likely occur as a result of deposition of autoantibodies, complement, and other inflammatory molecules. We show for the first time that MYZAP is present in cardiac nodes.

Cell junction protein armadillo repeat gene deleted in velo-cardio-facial syndrome is expressed in the skin and colocalizes with autoantibodies of patients affected by a new variant of endemic pemphigus foliaceus in Colombia.

BACKGROUND: We previously described a new variant of endemic pemphigus foliaceus in El Bagre, Colombia, South America (El Bagre-EPF, or pemphigus Abreu-Manu). El Bagre-EPF differs from other types of EPF clinically, epidemiologically, immunologically and in its target antigens. We reported the presence of patient autoantibodies colocalizing with armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF), a catenin cell junction protein colocalizing with El Bagre-EPF autoantibodies in the heart and within pilosebaceous units along their neurovascular supply routes. Here we investigate the presence of ARVCF in skin and its possibility as a cutaneous El Bagre-EPF antigen. METHODS: We used a case-control study, testing sera of 45 patients and 45 controls via direct and indirect immunofluorescence (DIF/IIF), confocal microscopy, immunoelectron microscopy and immunoblotting for the presence of ARVCF and its relationship with El Bagre-EPF autoantibodies in the skin. We also immunoadsorbed samples with desmoglein 1 (Dsg1) ectodomain (El Bagre-EPF antigen) by incubating with the positive ARVCF samples from DIF and IIF. RESULTS: ARVCF was expressed in all the samples from the cases and controls. Immunoadsorption with Dsg1 on positive ARVCF immunofluorescence DIF/IIF cases showed that the immune response was present against non-desmoglein 1 antigen(s). Overall, 40/45 patients showed colocalization of their autoantibodies with ARVCF in the epidermis; no controls from the endemic area displayed colocalization. CONCLUSIONS: We demonstrate that ARVCF is expressed in many areas of human skin, and colocalizes with the majority of El Bagre-EPF autoantibodies as a putative antigen.

Periodic Acid-Schiff Staining Parallels the Immunoreactivity Seen By Direct Immunofluorescence in Autoimmune Skin Diseases.

BACKGROUND: In many countries and laboratories, techniques such as direct immunofluorescence (DIF) are not available for the diagnosis of skin diseases. Thus, these laboratories are limited in the full diagnoses of autoimmune skin diseases, vasculitis, and rheumatologic diseases. In our experience with these diseases and the patient's skin biopsies, we have noted a positive correlation between periodic acid-Schiff (PAS) staining and immunofluorescence patterns; however, these were just empiric observations. In the current study, we aim to confirm these observations, given the concept that the majority of autoantibodies are glycoproteins and should thus be recognized by PAS staining. AIMS: To compare direct immunofluorescent and PAS staining, in multiple autoimmune diseases that are known to exhibit specific direct immunofluorescent patterns. MATERIALS AND METHODS: We studied multiple autoimmune skin diseases: Five cases of bullous pemphigoid, five cases of pemphigus vulgaris, ten cases of cutaneous lupus, ten cases of autoimmune vasculitis, ten cases of lichen planus (LP), and five cases of cutaneous drug reactions (including one case of erythema multiforme). In addition, we utilized 45 normal skin control specimens from plastic surgery reductions. RESULTS: We found a 98% positive correlation between DIF and PAS staining patterns over all the disease samples. CONCLUSION: We recommend that laboratories without access to DIF always perform PAS staining in addition to hematoxylin and eosin (H&E) staining, for a review of the reactivity pattern.

Immunofluorescence Patterns in Selected Dermatoses, Including Blistering Skin Diseases Utilizing Multiple Fluorochromes.

BACKGROUND: Autoimmune vesiculobullous disorders represent a heterogeneous group of dermatoses whose diagnosis is made based on clinical history, histologic features, and immunopathologic features. The most commonly used techniques for the diagnosis of these diseases are direct and indirect immunofluorescence (DIF and IIF), including salt-split processing. NaCl split skin is used to determine the level of blister formation, and the localization of autoantibodies relative to the split. Classically, immunofluorescence has been performed with one fluorochrome in the diagnosis of autoimmune bullous skin diseases. AIMS: To compare DIF and IIF of the skin, using a single fluorochrome versus multiple fluorochromes. MATERIALS AND METHODS: We studied 20 autoimmune skin disease cases using fluorescein isothiocyanate (FITC) alone, in comparison to multiple fluorochromes (with or without DNA counterstaining). RESULTS: The use of multiple fluorochromes helped to simultaneously visualize reactivity in multiple skin areas, in contrast to using FITC alone. CONCLUSIONS: Using multiple fluorochromes allows simultaneous labeling of two or more antigens within the same cell/or tissue section, assists in colocalization of unknown antigens with known molecules, and helps in ruling out "background" staining.

Palmar and plantar lichen planus: a case report and review of the literature.

Palmoplantar lichen planus is an uncommon dermatosis. We present a case of 38-year-old Caucasian male with a history of pruritic, scaly lesions on the right plantar foot. Physical examination revealed whitish plaques and numerous spiny hyperkeratotic papules and focal scaling. A biopsy demonstrated orthohyperkeratosis and acanthosis of the epidermis. Immunohistochemical staining revealed positivity within the epidermis and/or lichenoid infiltrate with CD3, CD8, CD45, CD68, myeloid histiod antigen, BCL2, p27, p53, HLA-DPDQDR, metallothionein and tissue inhibitor of metalloproteinases 1. The diagnosis of PPLP was thus confirmed; this case illustrates that PPLP should be considered in the differential diagnosis of uncommon foot dermatoses with a significant junctional inflammatory component.

Markers for Sebaceoma Show a Spectrum of Cell Cycle Regulators, Tumor Suppressor Genes, and Oncogenes.

BACKGROUND: Sebaceoma is a tumor for which the causative oncogenes are not well-understood. Sebaceomas demonstrate some histopathologic features similar to basal cell carcinoma (BCC), such as palisading borders and basaloid cells with additional features, including foamy cytoplasm and indented nuclei. AIMS: We examine multiple cell-cycle, oncogene, and tumor suppressor gene markers in sebaceomas, to try to find some suitable biological markers for this tumor, and compare with other published studies. MATERIALS AND METHODS: We investigated a panel of immunohistochemical (IHC) stains that are important for cellular signaling, including a cell cycle regulator, tumor suppressor gene, oncogene, hormone receptor, and genomic stability markers in our cohort of sebaceomas. We collected 30 sebaceomas from three separate USA dermatopathology laboratories. The following IHC panel: Epithelial membrane antigen (EMA)/CD227, cytokeratin AE1/AE3, cyclin D1, human breast cancer 1 protein (BRCA-1), C-erb-2, Bcl-2, human androgen receptor (AR), cyclin-dependent kinase inhibitor 1B (p27(kip1)), p53, topoisomerase II alpha, proliferating cell nuclear antigen, and Ki-67 were tested in our cases. RESULTS: EMA/CD227 was positive in the well-differentiated sebaceomas (13/30). Cyclin-dependent kinase inhibitor 1B was positive in tumors with intermediate differentiation (22/30). The less well-differentiated tumors failed to stain with EMA and AR. Most of the tumors with well-differentiated palisaded areas demonstrated positive staining for topoisomerase II alpha, p27(kip1), and p53, with positive staining in tumoral basaloid areas (22/30). Numerous tumors were focally positive with multiple markers, indicating a significant degree of variability in the complete group. CONCLUSIONS: Oncogenes, tumor suppressor genes, cell cycle regulators, and hormone receptors are variably expressed in sebaceomas. Our results suggest that in these tumors, selected marker staining seems to correlate with tumor differentiation; that is, well-differentiated tumors as a group stained with EMA and AR, and palisaded areas demonstrated consistent p53, topoisomerase II alpha and p27(kip1) staining. In contrast, less well-differentiated areas stained with a different spectrum of markers.

Tumor-suppressor Genes, Cell Cycle Regulatory Checkpoints, and the Skin.

The cell cycle (or cell-division cycle) is a series of events that take place in a cell, leading to its division and duplication. Cell division requires cell cycle checkpoints (CPs) that are used by the cell to both monitor and regulate the progress of the cell cycle. Tumor-suppressor genes (TSGs) or antioncogenes are genes that protect the cell from a single event or multiple events leading to cancer. When these genes mutate, the cell can progress to a cancerous state. We aimed to perform a narrative review, based on evaluation of the manuscripts published in MEDLINE-indexed journals using the Medical Subject Headings (MeSH) terms "tumor suppressor's genes," "skin," and "cell cycle regulatory checkpoints." We aimed to review the current concepts regarding TSGs, CPs, and their association with selected cutaneous diseases. It is important to take into account that in some cell cycle disorders, multiple genetic abnormalities may occur simultaneously. These abnormalities may include intrachromosomal insertions, unbalanced division products, recombinations, reciprocal deletions, and/or duplication of the inserted segments or genes; thus, these presentations usually involve several genes. Due to their complexity, these disorders require specialized expertise for proper diagnosis, counseling, personal and family support, and genetic studies. Alterations in the TSGs or CP regulators may occur in many benign skin proliferative disorders, neoplastic processes, and genodermatoses.

Palmar and plantar lichen planus: a case report and review of the literature

Palmoplantar lichen planus is an uncommon dermatosis. We present a case of 38-year-old Caucasian male with a history of pruritic, scaly lesions on the right plantar foot. Physical examination revealed whitish plaques and numerous spiny hyperkeratotic papules and focal scaling. A biopsy demonstrated orthohyperkeratosis and acanthosis of the epidermis. Immunohistochemical staining revealed positivity within the epidermis and/or lichenoid infiltrate with CD3, CD8, CD45, CD68, myeloid histiod antigen, BCL2, p27, p53, HLA-DPDQDR, metallothionein and tissue inhibitor of metalloproteinases 1. The diagnosis of PPLP was thus confirmed; this case illustrates that PPLP should be considered in the differential diagnosis of uncommon foot dermatoses with a significant junctional inflammatory component.