Systematic review of Mohs micrographic surgery in children: Identifying challenges and practical considerations for successful application.

BACKGROUND: Few data exist to guide the application of Mohs micrographic surgery (MMS) in the pediatric population. OBJECTIVE: We sought to summarize the clinical characteristics of children undergoing MMS, identify challenges that limit the use of MMS in this population, and examine how these challenges can be overcome. METHODS: A systematic review of PubMed and EMBASE, from inception of databases to November 2, 2019, identified all cases of pediatric skin lesions treated with MMS. RESULTS: A total of 111 patients were included. The median patient age was 11 years (range 6 weeks to 17 years). The most commonly treated tumor was dermatofibrosarcoma protuberans (n = 62), followed by basal cell carcinoma (n = 30). The most common location was the head and neck (n = 34), followed by the trunk (n = 28) and the extremities (n = 23). The most commonly cited challenges in the application of MMS in children included patient cooperation, concerns for the safety of prolonged general anesthesia, availability of a MMS service in the pediatric setting, and access to a histopathology laboratory experienced in MMS sectioning. LIMITATIONS: Many articles did not report specific patient characteristics. CONCLUSION: Multiple obstacles limit the application of MMS in pediatric patients. This review describes practical methods to circumvent these obstacles to facilitate the appropriate use of MMS in children.

Beyond Skin Tumors: A Systematic Review of Mohs Micrographic Surgery in the Treatment of Deep Cutaneous Fungal Infections.

BACKGROUND: Deep cutaneous fungal infections (DCFIs) can cause significant morbidity in immunocompromised patients and often fail medical and standard surgical treatments because of significant subclinical extension. Although rarely considered in this setting, Mohs micrographic surgery (MMS) offers the advantages of comprehensive margin control and tissue conservation, which may be beneficial in the treatment of DCFIs that have failed standard treatment options. OBJECTIVE: To review the benefits, limitations, and practicality of MMS in patients with DCFIs. METHODS: A systematic review of PubMed and EMBASE was conducted to identify all cases of fungal skin lesions treated with MMS. RESULTS: Eight case reports were identified consisting of a total of 8 patients. A majority of patients had a predisposing comorbidity (75%), with the most common being a solid organ transplant (n = 3, 37.5%). The most commonly diagnosed fungal infection was phaeohyphomycosis (n = 5, 62.5%), followed by mucormycosis (n = 2, 25%). No recurrence or complication post-MMS was noted at a mean follow-up of 11.66 months. CONCLUSION: Although not a first-line treatment, MMS can be considered as an effective treatment alternative for DCFIs in cases of treatment failure and can be particularly helpful in areas where tissue conservation is imperative.

Erythema multiforme-like eruption associated with plant-induced allergic contact dermatitis in a pediatric patient: A case report.

An 11-year-old boy presented to the emergency department 5 days after playing in the forest. His initial eruption, consistent with allergic contact dermatitis to poison ivy, progressed into target lesions involving his extremities, palms, upper trunk, and face, consistent with an erythema multiforme-like eruption. This report details the case and reviews the literature concerning this atypical and potentially underreported complication of plant-induced allergic contact dermatitis.

Facial hair enhancement with minoxidil-an off-label use.

Minoxidil was first introduced in the 1970s as an anti-hypertensive medication. Hypertrichosis and scalp hair regrowth were noted by users, and the topical formulation of minoxidil was later approved by the Food and Drug Administration for androgenic alopecia and female pattern hair loss. Since then, minoxidil has been used off-label for various hair loss conditions and cosmetic outcomes. There are a multitude of informal reports on online communities presenting personal anecdotes regarding minoxidil's effectiveness as a facial hair enhancement tool; however, this has been seldom discussed in the literature. In this report, we will present a case of identical twin males, one of which used topical 5% minoxidil for over a year on the beard and mustache area, while the other abstained from using the medication.

Intravascular diffuse large B-cell lymphoma with acquired ichthyosis: A case report.

Intravascular diffuse large B-cell lymphoma is an exceedingly rare subtype of B-cell lymphomas. This cancer is often associated with poor prognosis and can be lethal if left untreated. Intravascular diffuse large B-cell lymphoma is divided into three variants: the 'classical variant', the hemophagocytic syndrome-associated variant or 'Asian variant', and the 'cutaneous variant', according to the clinical presentation and affected organs. We present a unique case of 'classic variant' intravascular diffuse large B-cell lymphoma with cutaneous findings, peripheral nervous system involvement and acquired ichthyosis in a patient of Asian descent. This case highlights the importance of a prompt dermatology consultation in the diagnosis of intravascular diffuse large B-cell lymphoma. As bone marrow biopsy is often negative, clinicians must recognize the cutaneous findings and acknowledge that skin biopsy can be an essential tool to establish the diagnosis rapidly. Additional finding making this case unique is the concurrent presence of acquired ichthyosis, which has only been previously reported in one case of intravascular diffuse large B-cell lymphoma.

An unusually indolent well-differentiated Wilson-Jones angiosarcoma: A case report.

Cutaneous angiosarcomas are rare soft tissue tumours originating from hematogenous vasculature that are aggressive and carry a poor prognosis. We describe the case of a 73-year-old man with a low-grade well-differentiated angiosarcoma. Our case distinguishes itself from those previously reported in the slow progression and important delay to the presentation of 30 months and survival time of 5.5 years. Additionally, its severe clinical appearance (T2 stage) but milder pathological picture (T1 stage) is very uncommon. A repeat biopsy is warranted when results are inconclusive and there is a high clinical suspicion of angiosarcoma.

Vulvar swelling and the timely diagnosis of Crohn's disease: A case report.

Children with vulvar swelling often present to multiple physicians and face a prolonged period of ambiguity and extraneous treatments. Here, we report a case of an 8-year-old girl who presented to the dermatology clinic with a 2-month history of vulvar swelling and was ultimately diagnosed with Crohn's disease. Although extra-intestinal manifestations are common in inflammatory bowel diseases, they rarely present before an existing diagnosis. This report highlights this potential early manifestation and demonstrates how timely diagnosis leads to improved outcomes for patients, their families, and healthcare systems.

Narrowband ultraviolet B therapy for refractory immune-related lichenoid dermatitis on PD-1 therapy: a case report.

Treatment with programmed cell death 1 inhibitors is associated with a wide range of cutaneous immune-related adverse events, with lichenoid eruptions representing one of the major cutaneous toxicities. We describe the case of an 81-year-old man with metastatic melanoma treated with pembrolizumab who subsequently developed a delayed-onset generalized lichenoid dermatitis. After failing multiple lines of systemic immunosuppression, narrowband ultraviolet B (NBUVB) phototherapy three times per week for 17 sessions resulted in a significant clinical response in his cutaneous eruption and was well tolerated. NBUVB is a safe, lower-cost modality that induces local, skin-specific immunosuppression without the toxicities of traditional systemic immunosuppressive agents. To date, this is the first report of use of NBUVB in immune-related lichenoid dermatitis resistant to multiple standard therapies.

A case of toxic epidermal necrosis-like cutaneous eruption as the first manifestation and clue to the diagnosis of systemic lupus erythematosus: A case report.

We present a rare case of a 61-year-old woman presenting with a widespread erosive eruption on her torso and extremities. Although the lesions were histologically compatible with toxic epidermal necrolysis, clinically the patient was hemodynamically stable, had no mucosal involvement and had no relevant medical history or potentially incriminating medications. Further investigations uncovered a new diagnosis of systemic lupus erythematosus, with this toxic epidermal necrolysis-like eruption being the first presentation of the disease. This case highlights the importance of broadening the differential diagnosis in patients presenting with acute widespread cleavage of the epidermis, using the spectrum of acute syndrome of apoptotic pan-epidermolysis as a reference.

Tannin extracted from Sumac inhibits vascular smooth muscle cell migration.

BACKGROUND: Vascular smooth muscle cell (VSMC) migration is integral in the pathogenesis of atherosclerosis. Sumac (Rhus coriaria) berries are believed to have atheroprotective effects. Therefore, Sumac, which is a rich source of tannin antioxidants, was tested for its capacity to inhibit VSMC migratory activity. MATERIALS & METHODS: Tannin was extracted and purified from ground Sumac. Cultured rat carotid VSMCs were treated with different concentrations of tannin. After 10 days of tannin treatment, VSMC migratory activity in response to platelet-derived growth factor-BB was measured by transmembrane migration assay. An equal number of VSMCs was loaded on top of the inserts and at the bottom of the wells. After fixation and staining, cells migrating through the inserts and cells seeded at the bottom of the wells were counted. RESULTS: A significant reduction (62%) of VSMC migration was evident in tannin-treated cells. To rule out any possible toxicity and cell death, cells at the bottom of the wells were also counted. No difference between the tannin-treated group and the controls was observed in the number of cells seeded at the bottom of the wells. CONCLUSION: Our data suggest that tannin extracted from Sumac possesses potent antimigratory activity. Sumac may have potential for the prevention or treatment of atherosclerosis and its clinical manifestations. Further experiments, especially in vivo, are required to examine the atheroprotective effect of Sumac.

Contact Allergy to Polymyxin B Among Patients Referred for Patch Testing.

BACKGOUND: Polymyxin B is not included in most standard contact allergen series. The aim of this study was to determine the prevalence of contact sensitization to polymyxin B in a population of patients referred for patch testing. METHODS: A retrospective cohort study design was used to collect data on 795 patients referred to the contact dermatitis clinic of the McGill University Health Centre, as well as to the office of one of the authors (L.M.), between March 2014 and November 2015. Patients were patch tested to the North American Contact Dermatitis Group baseline series and polymyxin B sulfate 3% in petrolatum. RESULTS: Out of 795 tested individuals, 18 were allergic to polymyxin B, for a prevalence of 2.3%. The eruptions affected almost all body parts, but mostly the face. The degree of reaction ranged from 1+ to 2+. Isolated reactions to polymyxin B occurred in 9 (50%) patients, whereas reactions to bacitracin and polymyxin B were seen in the other 9. Only 1 patient reacted to bacitracin, polymyxin B, and neomycin (11.1%). Most reactions (12/18) were from past exposure to polymyxin B. CONCLUSIONS: Allergic reactions to polymyxin B are not rare, and this antibiotic warrants inclusion in the standard patch testing series.

Ectopic expression of cancer-testis antigens in cutaneous T-cell lymphoma patients.

PURPOSE: The pathogenesis of cutaneous T-cell lymphoma (CTCL) remains only partially understood. A number of recent studies attempted to identify novel diagnostic markers and future therapeutic targets. One group of antigens, cancer-testis (CT) antigens, normally present solely in testicular germ cells, can be ectopically expressed in a variety of cancers. Currently, only a few studies attempted to investigate the expression of CT antigens in CTCL. EXPERIMENTAL DESIGN: In the present work, we test the expression of CT genes in a cohort of patients with CTCL, normal skin samples, skin from benign inflammatory dermatoses, and in patient-derived CTCL cells. We correlate such expression with the p53 status and explore molecular mechanisms behind their ectopic expression in these cells. RESULTS: Our findings demonstrate that SYCP1, SYCP3, REC8, SPO11, and GTSF1 genes are heterogeneously expressed in patients with CTCL and patient-derived cell lines, whereas cTAGE1 (cutaneous T-cell lymphoma-associated antigen 1) was found to be robustly expressed in both. Mutated p53 status did not appear to be a requirement for the ectopic expression of CT antigens. While T-cell stimulation resulted in a significant upregulation of STAT3 and JUNB expression, it did not significantly alter the expression of CT antigens. Treatment of CTCL cells in vitro with vorinostat or romidepsin histone deacetylase inhibitors resulted in a significant dose-dependent upregulation of mRNA but not protein. Further expression analysis demonstrated that SYCP1, cTAGE1, and GTSF1 were expressed in CTCL, but not in normal skin or benign inflammatory dermatoses. CONCLUSIONS: A number of CT genes are ectopically expressed in patients with CTCL and can be used as biomarkers or novel targets for immunotherapy.

Analysis of STAT4 expression in cutaneous T-cell lymphoma (CTCL) patients and patient-derived cell lines.

Deregulation of STAT signaling has been implicated in the pathogenesis for a variety of cancers, including CTCL. Recent reports indicate that loss of STAT4 expression is an important prognostic marker for CTCL progression and is associated with the acquisition of T helper 2 cell phenotype by malignant cells. However, little is known about the molecular mechanism behind the downregulation of STAT4 in this cancer. In the current work we test the expression of STAT4 and STAT6 via RT-PCR and/or Western Blot in CTCL lesional skin samples and in immortalized patient-derived cell lines. In these malignant cell lines we correlate the expression of STAT4 and STAT6 with the T helper (Th) phenotype markers and test the effect of Histone Deacetylase (HDAC) inhibitors and siRNA-mediated knock down of miR-155 on STAT4 expression. Our findings demonstrate that STAT4 expression correlates with Th1 phenotype, while STAT6 is associated with the Th2 phenotype. Our results further document that STAT4 and STAT6 genes are inversely regulated in CTCL. Treatment with HDAC inhibitors upregulates STAT4 expression, while at the same time decreases STAT6 expression in MyLa cells. Also, siRNA-mediated knock down of miR-155 leads to upregulation in STAT4 expression in MyLa cells. In summary, our results suggest that loss of STAT4 expression and associated switch to Th2 phenotype during Mycosis Fungoides progression may be driven via aberrant histone acetylation and/or upregulation of oncogenic miR-155 microRNA.

Ectopic expression of embryonic stem cell and other developmental genes in cutaneous T-cell lymphoma.

Cutaneous T-cell lymphoma (CTCL) is a potentially devastating malignancy. The pathogenesis of this cancer remains poorly elucidated. Previous studies focused on analysis of expression and function of known oncogenes and tumor suppressor genes. However, emerging reports highlight that it is also important to analyze the expression of genes that are ectopically expressed in CTCL (e.g., embryonic stem cell genes (ESC), cancer testis (CT) genes, etc.). Currently, it is not known whether ESC genes are expressed in CTCL. In the current work, we analyze by RT-PCR the expression of 26 ESC genes, many of which are known to regulate pluripotency and promote cancer stem cell-like phenotype, in a historic cohort of 60 patients from Boston and in a panel of 11 patient-derived CTCL cell lines and compare such expression to benign inflammatory dermatoses that often clinically mimic CTCL. Our findings document that many critical ESC genes including NANOG, SOX2, OCT4 (POU5F1) and their upstream and downstream signaling members are expressed in CTCL. Similarly, polycomb repressive complex 2 (PRC2) genes (i.e., EZH2, EED, and SUZ12) are also expressed in CTCL lesional skin. Furthermore, select ESC genes (OCT4, EED, TCF3, THAP11, CHD7, TIP60, TRIM28) are preferentially expressed in CTCL samples when compared to benign skin biopsies. Our work suggests that ESC genes are ectopically expressed together with CT genes, thymocyte development genes and B cell-specific genes and may be working in concert to promote tumorigenesis. Specifically, while ESC genes may be promoting cancer stem cell-like phenotype, CT genes may be contributing to aneuploidy and genomic instability by producing aberrant chromosomal translocations. Further analysis of ESC expression and function in this cancer will greatly enhance our fundamental understanding of CTCL and will help us identify novel therapeutic targets.