Bullous pemphigoid (BP) is a blistering autoimmune disease mainly observed in elderly patients. Several triggers are known for this autoimmune disease and some drugs are known to be a cause of BP. ...However, there are only few case reports on the induction of BP under adalimumab therapy. Other autoimmune diseases, such as lupus erythematosus, are also known to occur under TNF inhibition. Here, we report on an 81-year-old patient who received adalimumab for ulcerative colitis and subsequently developed BP. Other causes of BP (tumors, other drugs, viral or toxoplasma infections) were excluded. We initiated a topical and systemic therapy (prednisolone 1 mg/kg/day) and stopped the adalimumab injections. The patient’s symptoms resolved quickly and we were able to taper corticosteroid therapy. This rare case highlights the importance to monitor for autoimmune events during TNF inhibition.
The aim of this study was to investigate the clinical, histopathologic, and immunologic differences of oral squamous cell carcinoma of never-smokers/never-drinkers and smokers/drinkers. ...Immunohistochemical staining for CD4, CD8, FoxP3, CD1a, and p16 was performed in 131 oral squamous cell carcinomas from smokers/drinkers and never-smokers/never-drinkers. Associations of smoking/drinking status with clinicopathologic data, immunohistochemical antibody expression, and survival were examined. Oral squamous cell carcinoma in never-smokers/never-drinkers was associated with the female gender (
< 0.001). Never-smokers/never-drinkers were older at diagnosis than smokers/drinkers (
< 0.001). Never-smokers/never-drinkers had more tumors in the maxilla, mandible, and tongue (
< 0.001). Pre-existing oral potentially malignant disorders appeared to be more common in never-smokers/never-drinkers (
< 0.001). Perineural invasion was more common in smokers/drinkers (
= 0.039). Never-smoking/never-drinking was associated with better overall survival (
= 0.004) and disease-specific survival (
= 0.029). High CD4+ T cell infiltration was associated with never-smoking/never-drinking (
= 0.008). Never-smokers/never-drinkers also showed increased CD8+ T cell infiltration (
= 0.001) and increased FoxP3+ Treg infiltration (
= 0.023). Furthermore, the total group of tumor-infiltrating lymphocytes was associated with never smoking/never drinking (
= 0.005). To conclude oral squamous cell carcinoma of the never-smokers/never-drinkers appears to be a distinct type of tumor, as it appears to have unique clinical and pathologic features and a more immunogenic microenvironment.
TWIK-related acid-sensitive potassium channels TASK1 and TASK3, as well as the G-protein-coupled receptors GPR31 and GPR151, are proton-sensitive membrane proteins. They can be activated or inhibited ...by low extracellular pH (pHe), which is a hallmark of the tumor microenvironment in solid tumors. However, the role of these channels in the development of skin tumors is still unclear. In this study, we investigated the expression profiles of TASK1, TASK3, GPR31 and GPR151 in squamous cell carcinomas (SCCs), basal cell carcinomas (BCCs), nevus cell nevi (NCN), and malignant melanomas (MMs). We performed immunohistochemistry using paraffin-embedded tissue samples from patients and found that most skin tumors express TASK1/3 and GPR31/151. The results show that BCCs are often negative for GPR31/151 as well as for TASK1/3, while nearly all SCCs express these markers. MMs and NCN show similar expression patterns. However, some tumors show a decreasing TASK1/3 expression in deeper dermal tumor tissue, while GPCRs were expressed more evenly. The lower frequency of GPR31/151 and TSAK1/3 expression in BCCs when compared to SCCs is a novel histological feature distinguishing these two entities. Moreover, BCCs also show lower expression of GPR31/151 and TASK1/3 as compared to NCN and MMs.
The understanding of macrophages and their pathophysiological role has dramatically changed within the last decades. Macrophages represent a very interesting cell type with regard to ...biomaterial-based tissue engineering and regeneration. In this context, macrophages play a crucial role in the biocompatibility and degradation of implanted biomaterials. Furthermore, a better understanding of the functionality of macrophages opens perspectives for potential guidance and modulation to turn inflammation into regeneration. Such knowledge may help to improve not only the biocompatibility of scaffold materials but also the integration, maturation, and preservation of scaffold-cell constructs or induce regeneration. Nowadays, macrophages are classified into two subpopulations, the classically activated macrophages (M1 macrophages) with pro-inflammatory properties and the alternatively activated macrophages (M2 macrophages) with anti-inflammatory properties. The present narrative review gives an overview of the different functions of macrophages and summarizes the recent state of knowledge regarding different types of macrophages and their functions, with special emphasis on tissue engineering and tissue regeneration.
Invasion of the mandibular bone is frequent in oral squamous cell carcinoma (OSCC), which often results in extensive ablative and reconstructive procedures for the patient. The purpose of this ...single-center, retrospective study was to identify and evaluate potential biomarkers and risk factors for bone invasion in OSCC. Initially, in silico gene expression analysis was performed for different HNSCC tumor T-stages to find factors associated with invasive (T4a) tumor growth. Afterwards, the protein expression of bone-metabolizing MMP-27, TNFRSF11B (Osteoprotegerin, OPG), and TNFSF11 (RANKL) was investigated via Tissue Microarrays (TMAs) for their impact on mandibular bone invasion. TMAs were assembled from the bone–tumor interface of primary OSCCs of the floor of the mouth and gingiva from 119 patients. Sixty-four carcinomas with patho-histological jaw invasion (pT4a) were compared to 55 carcinomas growing along the mandible without invasion (pT2, pT3). Tissue samples were additionally evaluated for patterns of invasion using the WPOI grading system. Statistical analysis of in silico data revealed decreased MMP-27 mRNA expression to be strongly associated with the pT4a-stage in OSCC, indicating invasive tumor growth with infiltration of adjacent anatomical structures. Our own clinico-pathological data on OSCCs presented a significant decrease of MMP-27 in tumors invading the nearby mandible (pT4a), compared to pT2 and pT3 tumors without bone invasion. Loss of MMP27 evolved as the strongest predictor of mandibular bone invasion in binary logistic regression analysis. To our knowledge, this is the first study investigating the role of MMP-27 expression in OSCC and demonstrating the importance of the loss of MMP-27 in mandibular bone invasion.
Solid tumors have an altered metabolism with a so-called inside-out pH gradient (decreased pH
< increased pH
). This also signals back to tumor cells via proton-sensitive ion channels or G ...protein-coupled receptors (pH-GPCRs) to alter migration and proliferation. Nothing, however, is known about the expression of pH-GPCRs in the rare form of peritoneal carcinomatosis. Paraffin-embedded tissue samples of a series of 10 patients with peritoneal carcinomatosis of colorectal (including appendix) origin were used for immunohistochemistry to study the expression of GPR4, GPR65, GPR68, GPR132, and GPR151. GPR4 was just expressed weakly in 30% of samples and expression was significantly reduced as compared to GPR56, GPR132, and GPR151. Furthermore, GPR68 was only expressed in 60% of tumors and showed significantly reduced expression as compared to GPR65 and GPR151. This is the first study on pH-GPCRs in peritoneal carcinomatosis, which shows lower expression of GPR4 and GPR68 as compared to other pH-GPCRs in this type of cancer. It may give rise to future therapies targeting either the TME or these GPCRs directly.
A study was performed to investigate histological changes in capsules formed around silicone breast implants and their correlation with the clinical classification of capsular contracture defined by ...the Baker score. For histological classification, the authors used the classification introduced by Wilflingseder, which identifies four grades of contracture.
The study included 24 female patients (average age, 40 +/- 12 years) with capsular contracture after bilateral cosmetic breast augmentation with smooth silicone gel implants (Mentor, Santa Barbara, Calif.). The Baker score was determined preoperatively for each patient. Samples of capsular tissue were obtained from all patients for histologic and immunohistochemical analyses. Capsular thickness, age of the collagen fibers, presence of synovia-like metaplasia on the inner surface of the capsule, number of histiocytes, giant cells, and other inflammatory cells, amount of silicone, foreign body granulomas, and capsule calcification were evaluated.
There was a positive correlation between capsular thickness (p < 0.05) and Baker score. Silicone-containing deposits were found in all four histological capsule types. A trend toward greater capsular thickness was documented in patients with severe inflammatory reaction. These patients also had more clinical symptoms. Greater capsular thickness was associated with a higher number of silicone particles and silicone-loaded macrophages in the peri-implant capsule.
The authors demonstrated a positive correlation (p < 0.05) between the clinical classification (Baker score I to IV) and the histological classification introduced by Wilflingseder (Wilflingseder score I to IV). An exact histological classification is needed to describe precisely the morphological changes in capsular contracture.
Key Clinical Message
Early and complete surgical resection is the most important therapeutic and diagnostic measure. Adjuvant radiation is suggested for malign phyllode tumors, phyllode tumors larger ...than 10 cm or those with a low distance to the resection margins.
Phyllodes tumors are rare fibroepithelial tumors of the breast. Histologically, they are usually classified as benign, borderline or malignant, though these classifications do not necessarily reflect the clinical course of the disease. These tumors may stay undetected for years, or show sudden and rapid progression. There is currently no consistent therapy recommendation based upon histological findings, the localization of the tumor and/or whether it is recurrent. Using the examples of three patients, we show how courses and therapy may differ widely, and discuss this in the context of the current state of the literature.
58 year old patient presenting with borderline phyllodes tumor.
Synthetic macroporous biomaterials are widely used in the field of skin tissue engineering to mimic membrane functions of the native dermis. Biomaterial designs can be subclassified with respect to ...their shape in fibrous designs, namely fibers, meshes or fleeces, respectively, and porous designs, such as sponges and foams. However, synthetic matrices often have limitations regarding unfavorable foreign body responses (FBRs). Severe FBRs can result in unfavorable disintegration and rejection of an implant, whereas mild FBRs can lead to an acceptable integration of a biomaterial. In this context, comparative in vivo studies of different three-dimensional (3D) matrix designs are rare. Especially, the differences regarding FBRs between synthetically derived filamentous fleeces and sponge-like constructs are unknown. In the present study, the FBRs on two 3D matrix designs were explored after 25 days of subcutaneous implantation in a porcine model. Cellular reactions were quantified histopathologically to investigate in which way the FBR is influenced by the biomaterial architecture. Our results show that FBR metrics (polymorph-nucleated cells and fibrotic reactions) were significantly affected according to the matrix designs. Our findings contribute to a better understanding of the 3D matrix tissue interactions and can be useful for future developments of synthetically derived skin substitute biomaterials.
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