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Skin and Connective Tissue Diseases - Top 30 Publications

Insulin-like growth factor 1 gene polymorphism in women with breast cancer.

Breast cancer is a disease of unknown etiology; however, the major risk factors are genetic alterations. Studies have demonstrated an association between insulin-like growth factor 1 (IGF-1) gene polymorphism and cell proliferation and reduced apoptosis, in addition to its role in breast cancer growth and aggressiveness. Two polymorphic variants of the IGF-1 gene are highlighted in association with breast cancer, rs6220 and rs7136446, although controversy exists as to this relationship. The current study included 137 women (68 breast cancer cases and 69 controls without breast cancer) who had 3 ml of peripheral blood drawn for the study of genomic DNA extracted from leukocytes using the genotyping technique by real-time polymerase chain reaction. The CC genotype (rs7136446) was present in 4 women (5.9%) from the case group and in 2 (3.0%) women from the control group (p = 0.67), while the GG genotype (rs6220) occurred in 8 (11.5%) women from the case group and in 5 (7.2%) women from the control group (p = 0.75). No statistically significant difference was observed between the CC genotype of variant rs7136446 in premenopausal case and control women (p = 0.31), thus as there was also no significant difference between case and control postmenopausal women (p = 1.00). Concerning the GG genotype of rs6220, it occurred in 6 (14.2%) premenopausal case and 4 (8%) control women (p = 0.71) and no difference was found in postmenopausal women (p = 1.00). In the current study, IGF-1 gene polymorphism of SNP variants rs6220 and rs7136446 had no statistically significant association with breast cancer, both in premenopausal and postmenopausal women.

Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis.

Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis.

Presentation of calcinosis cutis universalis in mixed connective tissue disorder: an encounter during hip arthroplasty.

A woman aged 23 years with a diagnosis of mixed connective tissue disorder presented with left groin pain extending over 6 months. Workup revealed avascular necrosis of the femoral head (Grade 3) secondary to systemic lupus erythematosus and chronic steroid intake. An uncemented total hip arthroplasty was considered as the patient was only in the third decade of life. During the preop workup, careful clinical assessment had revealed multiple subcutaneous nodules affecting the extensor musculature limited to the gluteal region, anterior and posterior aspects of the thigh. The diagnosis of calcinosis cutis universalis was made after a CT revealed calcified nodules in the subcutaneous, subfascial and muscular planes. A total hip arthroplasty using the posterior approach was performed with minimal trauma to the calcified nodules and thereby preventing a source of persistent drainage and reducing morbidity due to infection.

Mycobacterium szulgai infection in the flexor sheath of the right index finger in an immunocompetent patient.

A 53-year-old woman was identified with Mycobacterium szulgai infection in the flexor sheath of the right index finger. Tissue was debrided at operation, and the patient was successfully treated with appropriate antimicrobials. M. szulgai is a rare cause of non-tubercular mycobacterium infection worldwide, and there are currently no clear guidelines on diagnosis and management. This is the first case reporting M. szulgai infection in the flexor sheath of the right index finger of a non-immunocompromised patient in the UK.

Orthostatic Intolerance and Postural Orthostatic Tachycardia Syndrome in Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome, Hypermobility Type: Neurovegetative Dysregulation or Autonomic Failure?

Background. Joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT), is a hereditary connective tissue disorder mainly characterized by generalized joint hypermobility, skin texture abnormalities, and visceral and vascular dysfunctions, also comprising symptoms of autonomic dysfunction. This study aims to further evaluate cardiovascular autonomic involvement in JHS/EDS-HT by a battery of functional tests. Methods. The response to cardiovascular reflex tests comprising deep breathing, Valsalva maneuver, 30/15 ratio, handgrip test, and head-up tilt test was studied in 35 JHS/EDS-HT adults. Heart rate and blood pressure variability was also investigated by spectral analysis in comparison to age and sex healthy matched group. Results. Valsalva ratio was normal in all patients, but 37.2% of them were not able to finish the test. At tilt, 48.6% patients showed postural orthostatic tachycardia, 31.4% orthostatic intolerance, 20% normal results. Only one patient had orthostatic hypotension. Spectral analysis showed significant higher baroreflex sensitivity values at rest compared to controls. Conclusions. This study confirms the abnormal cardiovascular autonomic profile in adults with JHS/EDS-HT and found the higher baroreflex sensitivity as a potential disease marker and clue for future research.

Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Rheumatoid Arthritis.

Objective. Tumor necrosis factor (TNF) increases circulating osteoclast (OC) precursors numbers by promoting their proliferation and differentiation. The aim of this study was to assess the effect of TNF inhibitors (TNFi) on the differentiation and activity of OC in rheumatoid arthritis (RA) patients. Methods. Seventeen RA patients treated with TNFi were analyzed at baseline and after a minimum follow-up period of 6 months. Blood samples were collected to assess receptor activator of nuclear factor kappa-B ligand (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations. Quantification of serum levels of bone turnover markers, in vitro OC differentiation assays, and qRT-PCR for OC specific genes was performed. Results. After TNFi therapy, patients had reduced RANKL surface expression in B-lymphocytes and the frequency of circulating classical CD14(bright)CD16(-) monocytes was decreased. Serum levels of sRANKL, sRANKL/OPG ratio, and CTX-I were reduced in RA patients after TNFi treatment. Moreover, after exposure to TNFi, osteoclast differentiation and activity were decreased, as well as the expression of TRAF6 and cathepsin K. Conclusion. We propose that TNFi arrests bone loss and erosion, through two pathways: direct reduction of osteoclast precursor numbers and inhibition of intracellular signaling pathways acting through TRAF6.

Milestone clinical trials of the National Surgical Adjuvant Breast and Bowel Project (NSABP).

The National Surgical Adjuvant Breast and Bowel Project (NSABP) has made significant contributions in reducing the extent of breast surgery and in improving outcomes of patients with early-stage breast cancer through the conduct of large randomized clinical trials evaluating local and systemic therapy. In 2014, the NSABP merged with two other US National Cancer Institute-funded cooperative groups, the Radiation Therapy Oncology Group (RTOG) and the Gynecologic Oncology Group (GOG), to form NRG Oncology. The combined organization has 218 member institutions with more than 600 affiliate centers located throughout the United States, Canada, Puerto Rico, and other international sites. Over the past half century, the NSABP has entered more than 150,000 women into clinical trials of breast cancer treatment and breast cancer prevention. Many of these trials have been instrumental in establishing new standards of care for patients with breast cancer.

ABCB5-ZEB1 Axis Promotes Invasion and Metastasis in Breast Cancer Cells.

ABCB5 belongs to the ATP-binding cassette (ABC) superfamily, which is recognized for playing a role in the failure of chemotherapy. ABCB5 has also been found to be overexpressed at the transcriptional level in a number of cancer subtypes, including breast cancer. However, the exact mechanism ABCB5 uses on cancer cell metastasis is still unclear. In the present study, we demonstrate that ABCB5 expression was increased in metastatic tissues when compared with nonmetastatic tissues. ABCB5 can significantly enhance metastasis and epithelial-mesenchymal transition (EMT), while knockdown of ABCB5 inhibited these processes. Microarray analysis indicated that ZEB1 may function as a downstream factor of ABCB5. Furthermore, the expression of ZEB1 in tissues is positively relevant to ABCB5 in breast cancer. Knocking down ZEB1 inhibits ABCB5 ectopic expression-induced migration and invasion, as well as EMT. Taken together, these results helped to realize the oncogene functions of ABCB5 in breast cancer cells and provided a new direction in treating breast cancer.

RNA Interference of IQ Motif Containing GTPase-Activating Protein 3 (IQGAP3) Inhibits Cell Proliferation and Invasion in Breast Carcinoma Cells.

Breast cancer is a highly prevalent disease affecting women. The association of IQ motif containing GTPase-activating protein 3 (IQGAP3) and breast cancer is poorly defined. Here we reported that IQGAP3 is a key regulator of cell proliferation and metastasis during breast cancer progression. The expression of IQGAP3 was significantly increased in breast tissues compared to nontumor tissues at both protein and mRNA levels. Furthermore, IQGAP3 had a high expression level in ZR-75-30 and BT474 compared to other breast cancer cell lines. Depletion of IQGAP3 through RNA interference in ZR-75-30 and BT474 significantly inhibited cell proliferation. More importantly, IQGAP3 silencing in breast cancer cells notably repressed cell migration and invasion. Further analysis suggested that inhibition of cell proliferation and metastasis was associated with some proteins, including p53, MMP9, Snail, CDC42, p-ERK1/2, KIF2C, KIF4A, PCNA, and Twist. Since expression of IQGAP3 seems to be associated with the pathogenesis of breast cancer and suppression of it can inhibit cancer cell growth and metastasis, IQGAP3 may be a potential therapeutic target in human breast cancer.

Use of a biodegradable, oversized stent in a child with tracheomalacia secondary to vascular external compression.

We describe the implantation of an absorbable, custom-made stent of polydioxanone to treat tracheomalacia in a 5-month-old patient with extrinsic compression by a double aortic arch. The use of an absorbable, oversized stent treated the tracheal collapse caused by vascular compression, avoided removal procedures, and allowed the infant's growth. The use of an oversized stent prevented stent migration and gave minimal problems of granulation.

Triethylenetetramine Synergizes with Pharmacologic Ascorbic Acid in Hydrogen Peroxide Mediated Selective Toxicity to Breast Cancer Cell.

Breast cancer is characterized by overexpression of superoxide dismutase (SOD) and downregulation of catalase and more resistance to hydrogen peroxide (H2O2) than normal cells. Thus, relatively high H2O2 promotes breast cancer cell growth and proliferation. However, excessive intracellular H2O2 leads to death of breast cancer cells. In cancer cells, high level ascorbic acid (Asc) is able to be autoxidized and thus provides an electron to oxygen to generate H2O2. In the present study, we demonstrated that triethylenetetramine (TETA) enhances Asc autoxidation and thus elevates H2O2 production in MCF-7 cells. Furthermore, Asc/TETA combination significantly impaired cancer cell viability, while having much milder effects on normal cells, indicating Asc/TETA could be a promising therapy for breast cancer. Moreover, SOD1 and N-acetyl-L-cysteine failed to improve MCF-7 cells viability in the presence of Asc/TETA, while catalase significantly inhibited the cytotoxicity of Asc/TETA to breast cancer cells, strongly suggesting that the selective cytotoxicity of Asc/TETA to cancer cells is H2O2-dependent. In addition, Asc/TETA induces RAS/ERK downregulation in breast cancer cells. Animal studies confirmed that Asc/TETA effectively suppressed tumor growth in vivo. In conclusion, TETA synergizes pharmacologic Asc autoxidation and H2O2 overproduction in breast cancer cells, which suppresses RAS/ERK pathway and results in apoptosis.

Myxoedema in a patient with achondroplasia in rural area of Guatemala.

A 43-year-old indigenous Guatemalan woman with achondroplasia presented to our clinic with chronic fatigue and generalised oedema. She had limited contact with the formal healthcare system. However, 1 year prior, she had sought medical evaluation from a private physician. Her symptoms had been attributed to a combination of heart failure and physical disability due to the musculoskeletal complications of her achondroplasia. She was lost to follow-up due to inability to pay for further testing or treatment. On initial laboratory evaluation in our clinic, she was found to have a thyrotropin level greater than assay. With initiation of oral levothyroxine supplementation, her dyspnoea and oedema completely resolved. The case illustrates how indigenous patients in rural Guatemala experience many barriers to accessing high-quality medical care. As a result, presentations of common illnesses are often very advanced and definitive diagnoses and treatments are frequently delayed.

Analysis of novel Sjogren's syndrome autoantibodies in patients with dry eyes.

Dry eye is a common problem in Ophthalmology and may occur for many reasons including Sjogren's syndrome (SS). Recent studies have identified autoantibodies, anti-salivary gland protein 1 (SP1), anti-carbonic anhydrase 6 (CA6) and anti-parotid secretory protein (PSP), which occur early in the course of SS. The current studies were designed to evaluate how many patients with idiopathic dry eye and no evidence of systemic diseases from a dry eye practice have these autoantibodies.

CD40 Ligand Is Increased in Mast Cells in Psoriasis and Actinic Keratosis but Less So in Epithelial Skin Carcinomas.

The expression of CD40 ligand (CD40L) in mast cells was investigated in biopsies from lesional and non-lesional skin samples of patients with psoriasis, actinic keratosis (AK), basal cell carcinoma, and squamous cell carcinoma using a sequential double-staining technique. The percentage of CD40L(+) mast cells was higher in the lesional than in the non-lesional skin (p < .003). Interestingly, this percentage was lower in both carcinomas than in psoriasis and actinic keratosis (p < .025). Cells immunopositive for CD40 receptor were increased in all lesion types but especially so in carcinomas. The results suggest a dysregulated anti-tumoral immune response by mast cell CD40L in skin carcinomas.

Alexithymia in different dermatologic patients.

Alexithymia is a personality trait characterized by difficulties in differentiating and describing feelings. Research indicates that alexithymia can be considered as a possible risk factor for a variety of medical conditions. The purpose of our study was to compare and assess the prevalence of alexithymia in patients with psoriasis, alopecia areata, vitiligo and acne vulgaris. 120 consecutive subjects referred to dermatologic clinic with psoriasis, alopecia areata, vitiligo and acne vulgaris and 30 subjects selected from hospital staff and relatives of patients were enrolled in patient and control groups of our study respectively. Toronto Alexithymia Scale (TAS-20) was used to assess the prevalence of alexithymia. Statistical analysis showed significant differences between the vitiligo, alopecia areata, psoriasis patients and the control group in terms of alexithymia score (p≤0.05), but did not find any significant difference between acne patients and control group (p=0.06). This study has demonstrated high score of alexithymia in patients with psoriasis, alopecia areata and vitiligo compared with control group; however, such association was not found in individuals with acne vulgaris. Hence it is proposed that the evaluation and management of alexithymia would better the treatment of skin disorders and improve the quality of life in patients.

MicroRNAs mediate therapeutic and preventive effects of natural agents in breast cancer.

MicroRNAs (miRNAs) are a set of non-coding small RNA molecules that play a critical role in regulation of protein coding genes in cells. MiRNAs have been extensively studied as novel biomarkers, therapeutic targets, and new drugs in various human diseases. Breast cancer is a one of the leading tumor types significantly affecting women health worldwide. Over the past decade, a number of natural agents, such as paclitaxel and curcumin, have been applied for treatment and prevention of breast cancer due to their relatively low toxicity. However, the mechanisms of action have not been completely understood. Investigation on miRNAs is able to potentially provide a novel insight into better understanding the anticancer activities of these natural products. Given that a single miRNA can target multiple genes, theoretically, those genes involved in a certain phenotype can be clustered with one or a few miRNAs. Therefore, pleiotropic activities of natural agents should be interpreted by interactions between selected miRNAs and their targets. In this review, we summarize the latest publications related to the alterations of miRNAs by two natural agents (paclitaxel and curcumin) that are currently used in intervention of breast cancer, and conclude that the mechanism involving the regulation of miRNA expression is one of the keys to understand pleiotropic activities of natural agents.

Antifungal and antioxidant activities of Coleonema album and C. pulchellum against skin diseases.

Coleonema album (Thunb) Bart. & H. L. Wendl (Rutaceae) has been used in the formulation of skincare products, and the Khoisan people rub it on their skin to add luster. Coleonema pulchellum I. Williams has received less attention in the South African traditional medicine.

Differential Site-Based Expression of Pentose Phosphate Pathway-Related Proteins among Breast Cancer Metastases.

Purpose. We aimed to investigate the expression of pentose phosphate pathway- (PPP-) related proteins in metastatic breast cancer and its relationship with clinicopathologic factors. Methods. Tissue samples from 126 metastatic breast cancers were included in a tissue microarray. Expression of PPP-related proteins [glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconolactonase (6PGL), 6-phosphogluconate dehydrogenase (6PGDH), and nuclear factor erythroid 2-related factor (NRF2)] was determined by immunohistochemistry. Results. G6PDH (p = 0.011) and cytoplasmic NRF2 (p = 0.001) showed the highest expression in brain metastases. Human epidermal growth factor receptor (HER-2) positivity was associated with G6PDH (p < 0.001) and cytoplasmic NRF2 (p = 0.015) positivity. A high Ki-67 labeling index (LI) was correlated with nuclear NRF2 positivity (p = 0.037), and HER-2-positive luminal B type was associated with G6PDH positivity (p = 0.001). On multivariate Cox analysis, independent risk factors of short overall survival were 6PGL positivity in bone metastasis (HR 4.180, 95% CI 1.160-15.06, p = 0.029) and low Ki-67 LI in lung metastasis (HR 11.853, 95% CI 1.841-76.30, p = 0.009). Conclusion. Differential expression of PPP-related proteins correlated with different prognoses and metastatic sites, with the highest expression in brain metastases, and could be a potential therapeutic target.

Management of aromatase inhibitor induced musculoskeletal symptoms in postmenopausal early Breast cancer: A systematic review and meta-analysis.

Aromatase Inhibitors (AI) are widely used for the adjuvant treatment of hormone receptor positive breast cancers in the post-menopausal population. AI are often associated with significant joint and muscular symptoms; symptoms that are commonly referred to as aromatase inhibitor-associated musculoskeletal syndrome (AIMSS). AIMSS adversely impacts health-related quality of life of many patients, and reduces AI compliance. Although there are informal practice recommendations, the limited current level of evidence for management of AIMSS for breast cancer patients on aromatase inhibitors has made development of formal guidelines challenging, and remains an unmet need. This is the first systematic review to consider the evidence for all pharmacological and non-pharmacological interventions in the treatment of AIMSS, including physical therapy, acupuncture and complementary therapies.

Pembrolizumab's non-cross resistance mechanism of action successfully overthrown ipilimumab.

The incidences of melanomas are increasing by leaps and bounds across the globe despite early detection and intervention. The numbers of patients dying from metastatic melanoma have been continually increased over the past thirty years. It has been considered as one of the most therapy-resistant malignancies due to the cross-resistant mechanism developed by the metastatic cells. With time, many new therapies came and they failed miserably. Ipilimumab, a monoclonal antibody that works to activate the immune system by targeting CTLA-4 proved to be a boon for advance melanoma very recently. But it could not stand firmly against the resistant metastatic skin cancer cells. Now, the new skin cancer drug named pembrolizumab proved as a new miraculous molecule. It's a humanized monoclonal antibody that blocks a biological pathway called programmed cell death-1 (PD-1), which melanoma cells activate to suppress the immune system. This antibody has surpassed ipilimumab at all the stages of clinical trials because of its non-cross resistant mechanism to malignant cells. The present review critically analyses the reasons of efficacy success of pembrolizumab over ipilizumab shown at various stages of clinical trials.

From General Aberrant Alternative Splicing in Cancers and Its Therapeutic Application to the Discovery of an Oncogenic DMTF1 Isoform.

Alternative pre-mRNA splicing is a crucial process that allows the generation of diversified RNA and protein products from a multi-exon gene. In tumor cells, this mechanism can facilitate cancer development and progression through both creating oncogenic isoforms and reducing the expression of normal or controllable protein species. We recently demonstrated that an alternative cyclin D-binding myb-like transcription factor 1 (DMTF1) pre-mRNA splicing isoform, DMTF1β, is increasingly expressed in breast cancer and promotes mammary tumorigenesis in a transgenic mouse model. Aberrant pre-mRNA splicing is a typical event occurring for many cancer-related functional proteins. In this review, we introduce general aberrant pre-mRNA splicing in cancers and discuss its therapeutic application using our recent discovery of the oncogenic DMTF1 isoform as an example. We also summarize new insights in designing novel targeting strategies of cancer therapies based on the understanding of deregulated pre-mRNA splicing mechanisms.

Immunoglobulin G4-related disease and its skin manifestations.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory condition characterized by tissue infiltration with IgG4(+) plasma cells and an elevated serum IgG4 level. It usually occurs in middle-aged or older patients, with male predominance, and can involve multiple organs synchronously or metachronously. Patients with IgG4-RD generally respond to steroid therapy. IgG4-related skin lesions are typically erythematous and itchy plaques, subcutaneous nodules, or papules like prurigo nodularis located on the head and neck areas. Histologically, lymphoplasmacytic infiltrates with abundant IgG4+ plasma cells are seen in the dermis and/or subcutaneous tissue. The skin condition of IgG4-RD does not necessarily exhibit infiltration of IgG4(+) plasma cells, which is a prerequisite for IgG4-related skin disease, but such skin lesions without infiltration by IgG4(+) plasma cells can be included in the skin manifestations of IgG4-RD.

Topics in histopathology of sweat gland and sebaceous neoplasms.

This article reviews several topics regarding sweat gland and sebaceous neoplasms. First, the clinicopathological characteristics of poroid neoplasms are summarized. It was recently reported that one-fourth of poroid neoplasms are composite tumors and one-fourth are apocrine type lesions. Recent progress in the immunohistochemical diagnosis of sweat gland neoplasms is also reviewed. CD117 can help to distinguish sweat gland or sebaceous tumors from other non-Merkel cell epithelial tumors of the skin. For immunohistochemical differential diagnosis between sweat gland carcinoma (SGC) other than primary cutanesous apocrine carcinoma and skin metastasis of breast carcinoma (SMBC), a panel of antibodies may be useful, including p63 (SGC(+) , SMBC(-) ), CK5/6 (SGC(+) , SMBC(-) ), podoplanin (SGC(+) , SMBC(-) ) and mammaglobin (SGC(-) , SMBC(+) ). Comparison of antibodies used for immunohistochemical diagnosis of sebaceous carcinoma (SC) suggests that adipophilin has the highest sensitivity and specificity. Some authors have found that immunostaining for survivin, androgen receptor and ZEB2/SIP1 has prognostic value for ocular SC, but not extraocular SC. In situ SC is rare, especially extraocular SC, but there have been several recent reports that actinic keratosis and Bowen's disease are the source of invasive SC. Finally, based on recent reports, classification of sebaceous neoplasms into three categories is proposed, which are sebaceoma (a benign neoplasm with well-defined architecture and no atypia), borderline sebaceous neoplasm (low-grade SC; an intermediate tumor with well-defined architecture and nuclear atypia) and SC (a malignant tumor with invasive growth and evident nuclear atypia).

Nail neoplasms.

Nail neoplasms include all tumors occurring in the nail or periungual apparatus tissue. While some nail tumors can be similar to tumors located on the skin, others are unique. Both benign and malignant lesions can affect the nail apparatus. In particular, early malignant tumors like melanoma and squamous cell carcinoma can present similarly to onychomycosis or benign melanonychia and frequently missed by clinicians. Therefore, physicians should be aware of nail structures and the characteristics of nail tumors. Our review covers the normal nail structure and the most common nail tumors from benign to malignant.

Mimickers of classic acantholytic diseases.

Acantholysis is a commonly encountered histological pattern which typically generates a differential of the pemphigus variants, Hailey-Hailey, Darier's and Grover's diseases. In addition to these diseases, the dermatologist and dermatopathologist must be aware of entities that mimic classic acantholytic dermatoses and of rare disease variants, which are characterized by acantholysis.

What is new in the histogenesis of granulomatous skin diseases?

A granuloma is a form of inflammation, which predominantly consists of macrophages. It typically develops when the immune system attempts to enclose substances that are usually insoluble and cannot be eliminated to prevent the spread of these substances to the other body compartments. According to the source of the substances, granulomatous diseases can be divided into two groups: infectious and non-infectious. The mechanisms of infectious granuloma formation have been widely investigated because of its easy reproducibility in experimental models, both in vivo and in vitro. On the contrary, mechanisms of non-infectious granuloma formation have not been well investigated because of the difficulty to reproduce this formation in experimental models. In this article, we review our recent understanding of the histogenesis and pathogenesis of granuloma formation, confirmed from studies of infectious granulomas, and we present potential hypotheses of the histogenesis and pathogenesis of non-infectious granulomas based on clinical investigations.

Advances in histopathological diagnosis of keratoacanthoma.

Keratoacanthoma is a common epithelial lesion, but its nature is controversial. Although a distinct crateriform appearance is a hallmark of keratoacanthoma, other benign or malignant skin lesions may show a similar architecture. Moreover, as lesions diagnosed as conventional keratoacanthoma may show malignant behavior, some authors consider keratoacanthoma to be a variant of squamous cell carcinoma, whereas others consider it as a distinct self-resolving squamous proliferative lesion. The controversy seems to originate from the diverse behavior of keratoacanthoma-like epithelial lesions. However, a reproducible histopathological classification criterion has been recently proposed in the diagnosis of keratoacanthoma-like epithelial lesions, and its validity is supported by several reports that deal with the natural course or molecular aspects of these lesions. This article attempts to provide a comprehensive review on recent insights and advances in the histopathological diagnosis of keratoacanthoma or related lesions, as well as summary of related published works.

Folliculosebaceous neoplasms: A review of clinical and histological features.

Numerous benign and occasionally malignant tumors arise from the folliculosebaceous apparatus. Confusing terminology, rarity of malignant variants and overlapping histological features can lead to diagnostic uncertainty. This review highlights the clinical and histopathological features that help to classify these entities, as well as the various syndromes associated with certain members of this large family of tumors.

Cutaneous side-effects of biologics in immune-mediated disorders: A histopathological perspective.

Advances in understanding molecular mechanisms and targets in immune regulation have led to the widespread use of biologic targeted therapies, and, as such, reformed the course of many disabling diseases. However, with their expanded use, various side-effects, including cutaneous, have emerged. Many times a clear-cut relationship exists between the drug and the clinical manifestations; however, when a biopsy is warranted, various histopathological patterns may be observed and may cause confusion to the dermatopathologist. The aim of this review is to shed light on the different histopathological patterns observed as a manifestation secondary to biologics.