A Comparison of Preoperative Telephone Call Versus Mailed Educational Materials on Patient-Reported Outcomes in Mohs Micrographic Surgery.

BACKGROUND: Preoperative education has uncertain benefits on the preparedness and satisfaction of patients undergoing Mohs micrographic surgery (MMS). OBJECTIVE: We sought to determine the effect of a preoperative telephone call on preparedness and satisfaction in patients undergoing same-day office consultation and MMS. MATERIALS AND METHODS: All new patients ( N = 208) scheduled for same-day office consultation and MMS were mailed a standardized preoperative packet. Approximately half of those patients were randomly selected to also receive a preoperative phone call. On the day of the surgery, patients completed an anonymous preoperative and postoperative survey assessing their preparedness and satisfaction with the preoperative education received. RESULTS: There was no significant difference in patient preparedness between the letter only (LO) and phone call and letter study groups. There was a significant difference in preoperative satisfaction-a higher percentage of LO patients were "somewhat satisfied" or "not satisfied" with the preoperative education received ( p = .013). CONCLUSION: Preoperative phone consultation, in addition to mailed educational materials, did not have a statistically significant effect on patient preparedness in patients undergoing MMS; however, there was a trend toward increased satisfaction with the preoperative education provided in patients who received a preoperative phone call.

BerEP4-Negative Basal Cell Carcinoma: An Immunophenotype Not to Forget.

ABSTRACT: Basal cell carcinoma (BCC) is the most common cancer worldwide. Although not typically metastatic, BCC can be locally destructive. BerEP4 is an antibody against CD326, an epithelial cell adhesion molecule (EpCAM) that is expressed on epithelial progenitor cells and carcinomas. BerEP4 has been reported to have a 100% positive sensitivity in basal cell carcinomas, but a much lower sensitivity for a variety of other carcinomas, including clear cell renal cell carcinoma and metastatic renal cell carcinoma. A 74-year-old woman presented with a BerEP4-negative, but anti-renal cell antibody-positive BCC, and the stark clinical implications of misdiagnosis. This case stresses the importance of considering BerEP4-negative BCC, even when other abnormal features are present.

Radiation-Induced Eccrine Squamous Syringometaplasia With Perineural Invasion.

ABSTRACT: Eccrine squamous syringometaplasia (ESS) is a benign metaplastic reaction of eccrine ducts that occurs in response to injury and can be a histologic mimic of squamous cell carcinoma (SCC). Reported is an 82-year-old man undergoing Mohs surgery for presumed SCC diagnosed in a field of radiation dermatitis. After 3 Mohs stages, the peculiar squamous proliferation was recognized as ESS and the procedure was aborted. Complicating the interpretation of the Mohs frozen section was the presence of perineural invasion because perineural invasion has not been previously reported to occur with ESS. The histologic features used to distinguish ESS from SCC are discussed.

Lenalidomide-induced symmetrical drug-related intertriginous and flexural exanthema.

Symmetric drug-related intertriginous and flexural exanthema (SDRIFE) is a cutaneous drug reaction that presents with symmetrical erythema in the flexures. The reaction typically appears hours-to-days after drug exposure but has been reported to occur months after drug initiation. Diagnostic criteria include cutaneous reaction after exposure to a systemic drug, erythema of the gluteal region and/or V-shaped erythema of the inguinal areas, involvement of an additional intertriginous site, symmetry, and absence of systemic involvement. The rash typically presents as macular erythema. However, variations in morphology have been reported including papules, pustules, vesicles, and bullae. The histopathology of SDRIFE is non-specific and the diagnosis is made clinically. Cessation of the causative drug leads to gradual rash resolution. Beta-lactam antibiotics are the most implicated medications but case reports describe SDRIFE following monoclonal antibodies, chemotherapeutic agents, and various other medications. We present a patient with SDRIFE secondary to lenalidomide, an immunomodulatory agent. This case highlights the importance of considering SDRIFE in the differential diagnosis of patients presenting with intertriginous erythema.

Kaposi sarcoma: What to do with a negative human herpesvirus 8 immunohistochemical stain?

Kaposi sarcoma (KS) is an intermediate vascular sarcoma that can cause significant morbidity and mortality in patients if left untreated. It is associated with human herpesvirus 8 (HHV-8) infection. Definitive diagnosis is supported by classic histopathology including slit-like vascular spaces, spindle cells, lymphocyte infiltration, and extravasated red blood cells on H&E stain and positive immunohistochemical (IHC) staining for HHV-8. We present a challenge we encountered in detecting HHV-8 by IHC in a mucosal lesion demonstrating classic histopathology for KS.

Assessment of Pain, Healing Time, and Wound Contraction in Postoperative Auricular Defects Healing Secondarily With and Without the Use of a Porcine Xenograft, a Pilot Study.

BACKGROUND: Postoperative auricular defects heal well with secondary intention healing (SIH); however, potential complications include postoperative pain, perichondritis, and chondritis. OBJECTIVE: To compare postoperative pain and wound healing in auricular defects healing by secondary intention with and without the placement of a porcine xenograft. MATERIALS AND METHODS: Twenty-one subjects were enrolled in the study. The primary outcome was self-reported pain, measured on a 0 to 10 scale for 14 postprocedure days. Secondary outcomes included time to greater than 90% of reepithelialization and degree of wound contraction. RESULTS: There was a 1 to 2 point difference in median pain scores between the porcine graft and control groups during postoperative days 4 to 7, 12, and 13. Time to 90% or greater reepithelialization was not statistically different between groups (p = .94). The average wound contraction was 34.1% for the porcine group and 34.0% for the control group (p = .95). CONCLUSION: In this pilot study, overall pain scores were low in both groups. Placement of a porcine xenograft resulted in a slight reduction of median pain compared with traditional SIH. Patients in the control group were more likely to require analgesics. Similar rates of reepithelialization and degree of wound contracture were observed.

Toxic Epidermal Necrolysis: A Review of Past and Present Therapeutic Approaches

Toxic epidermal necrolysis (TEN) is an immune mediated, severe cutaneous adverse drug reaction characterized by epidermal detachment affecting greater than 30% body surface area. The mortality rate of TEN exceeds 20% and is usually caused by infection and respiratory compromise. Withdrawal of the causative drug, supportive care, and adjuvant therapy improve prognosis. Over the past decade, randomized controlled trials and meta-analyses have supported a role for cyclosporine, tumor necrosis factor alpha inhibitors, and combination therapy with intravenous immune globulin and corticosteroids. This review summarizes the medical management of TEN in adult patients.

Early onset drug-induced hypersensitivity syndrome with lymphopenia, hepatitis, and normal eosinophils induced by BRAF/MEK inhibitor after immune checkpoint inhibitor therapy.

Targeted therapy (BRAF/MEK inhibitors) is frequently employed in the treatment of metastatic melanoma following immune checkpoint inhibitor therapy inefficacy or intolerance. Although BRAF inhibitors are commonly associated with cutaneous eruptions, they rarely cause severe cutaneous adverse drug reactions such as drug-induced hypersensitivity syndrome (DIHS). Drug-induced hypersensitivity syndrome is a severe drug reaction characterized by extensive eruption often seen in conjunction with fever, facial edema, lymphadenopathy, eosinophilia, atypical lymphocytosis, and variable visceral organ injury characteristically beginning 2-8 weeks after initiating the causative drug. We report a case of atypical DIHS with reduced latency, mucosal involvement, lymphopenia, normal eosinophils, and no lymphadenopathy that occurred secondary to vemurafenib and cobimetinib therapy following melanoma progression while on pembrolizumab. Previous immune checkpoint inhibitor therapy has been associated with atypical DIHS in patients on BRAF/MEK inhibitors. Early recognition of the atypical clinical features of this hypersensitivity reaction is important so that drug discontinuation and corticosteroids can be initiated early.

Postoperative Pain After Mohs Surgery: Physician Perceptions and How Those Perceptions Influence Opioid Prescribing Practices.

BACKGROUND: Little is known about dermatologists' perceptions of postoperative pain and how those perceptions correlate with patient-reported pain and opioid prescribing. OBJECTIVE: To determine dermatologists' accuracy in predicting postoperative pain compared with patient-reported pain and how physicians' perceptions affect opioid prescribing practices. METHODS AND MATERIALS: A prospective observational study in which patients undergoing Mohs surgery rated pain on the Numerical Rating Scale (0-10). Using the same scale, the physician predicted how much pain the patient would experience postoperatively on the evening of surgery. All analgesic medications taken in postoperative period were recorded. RESULTS: A total of 316 patients completed the study (70% completion rate). Physician predictions were correlated with patient-reported pain (p < .001; r = 0.29) and were within 2 points of patient-reported pain in 70% of cases. When physicians overestimated patient-reported by ≥3 points, they were not more likely to prescribe opioids (p = .8094). Physicians predicted higher pain for patients who were prescribed opioids (p = .0002). CONCLUSION: Dermatologists were fairly accurate at predicting postoperative pain. Dermatologists were not more likely to prescribe opioids when pain was overpredicted.

Unusual Case of a Caruncular Oncocytoma.

ABSTRACT: Oncocytomas are benign neoplasms that are most often found in the salivary glands and kidneys. Ocular oncocytoma typically present as an asymptomatic dark blue papule on the lacrimal caruncle. Histologically, the tumor is composed of oncocytes, cells notable for eosinophilic cytoplasmic granules representing large quantities of dysfunctional mitochondria. The neoplastic proliferation may be partially or totally encapsulated and may be surrounded by myoepithelial cells. Discussed is the pathophysiology and histopathology of an ocular oncocytoma from the right lacrimal caruncle of a 68-year-old man. The patient complained of a foreign body sensation and tearing associated with a purpuric 1 × 1-mm papule of the right caruncle that had been present for 6 months. An excisional biopsy showed an oxyntic neoplasm with small cystic glandular spaces associated with goblet cells and mucin, confirmed by mucicarmine stain. Given the rarity of ocular oncocytomas and presence of mucin, exclusion of an endocrine mucin-producing sweat gland carcinoma was necessary. Peripheral myoepithelial cells noted on p63 immunostaining are seen in both endocrine mucin-producing sweat gland carcinoma and oncocytomas. However, endocrine mucin-producing sweat gland carcinoma is excluded by the presence of goblet cells, the uniform oxyphilic cytoplasm of the epithelial cells, and the negative immunohistochemical staining for neuron-specific enolase, chromogranin, synaptophysin, estrogen receptor, and progesterone receptor. Complete surgical excision is the treatment of choice for oncocytomas. This case highlights the clinical and histopathological presentation of ocular oncocytomas and raises awareness of this rare entity for both the practicing dermatologist and dermatopathologist.

Utility of the Human Papillomavirus Vaccination in Management of HPV-associated Cutaneous Lesions.

Human papillomavirus (HPV)-induced cutaneous disease is a common complaint for patients presenting for dermatology evaluation. Infection by HPV is the major etiologic factor in the development of cutaneous warts, epidermodysplasia verruciformis, and possibly a subset of cutaneous squamous cell carcinoma. Carcinoma of the genitourinary tract, most notably cervical carcinoma, is the most severe manifestation of infection with specific serotypes of HPV. For this reason, the HPV immunization (Gardasil) was developed in 2006 and upgraded in 2018 to a nonavalent formulation that includes serotypes 6, 11, 16, 18, 31, 33, 45, 52, 58. While immunization is highly effective at preventing infection with serotypes included in the formulation, it is less clear if the immunization can aid in managing active HPV infection. This review examines the available literature regarding the role of HPV immunization in managing common warts, genital warts, keratinocyte carcinoma, and epidermodysplasia verruciformis.

Management of surgical soft tissue defects of the lower extremities.

Management of post-operative soft-tissue defects on the lower legs is challenging owing to arterial and venous insufficiency, poor skin quality including epidermal and dermal atrophy, insufficient tissue laxity, and increased risk of infection. This paper highlights the management of post-operative soft-tissue defects on the lower extremity that cannot be closed primarily or by reconstruction with a local flap. A systematic review of the literature was performed using the National Library of Medicine (NLM) PubMed online database. Articles were included if they reported the management of post-operative lower extremity soft-tissue defects with secondary intention healing, full-thickness skin graft, split-thickness skin grafts, or skin substitutes. Sixty-three articles were included for analysis. There are several options for managing surgical defects on the lower legs and the method chosen should depend on various factors, including the quality of the skin, vascularity and size of the defect, medical history of the patient, and the experience of the surgeon.

Dermatologic Applications and Safety Considerations of Janus Kinase Inhibitors.

Janus kinase inhibitors, also known as JAK inhibitors or jakinibs, represent a new class of medication that have broad potential to treat dermatologic disease. Currently, the only FDA-approved dermatologic indication for this class of medications is psoriatic arthritis; however, their utility in treating other immune-mediated skin conditions including atopic dermatitis, vitiligo, alopecia areata, and systemic and cutaneous lupus is actively being investigated. Overall, these drugs appear to be well-tolerated and have a safety profile similar to that of other biologics commonly used in dermatologic practice, although an increased risk of thromboembolism has been associated. While risk of mild infection and herpes zoster appears to be increased regardless of JAK selectivity, risk of thrombosis and malignancy based on the subtype of JAK inhibition remains to be seen. Certainly, safety concerns warrant further investigation; however, early data from ongoing clinical trials offer promise for the broad utility of these medications within future dermatologic practice.

New Treatments for Hereditary Angioedema.

Hereditary angioedema is characterized by severe, episodic edema of the subcutaneous and mucosal tissue. The disease carries significant morbidity and mortality due to involvement of the gastrointestinal tract and upper airway. Recent advances in the treatment of hereditary angioedema include new techniques used to isolate and purify human-derived C1 inhibitor, the production of a recombinant form of C1 inhibitor, and the development of drugs that target the kallikrein-kinin pathway. This paper reviews the mechanisms, efficacy, and adverse reactions associated with these medications.

Basal cell carcinoma with intravascular invasion: A case report and review of the literature.

The significance of basal cell carcinoma (BCC) invading the intravascular space is unknown. We report a case of an infiltrative BCC on the scalp that showed evidence of both intravascular and perineural invasion. The tumor locally recurred in the bone marrow space 4.5 years following the initial procedure. Since recurrence and metastasis of BCC can be delayed for many years, we recommend long term follow-up for tumors showing aggressive features.

Functionalization of peptide nucleolipid bioconjugates and their structure anti-cancer activity relationship studies.

In the search for more potent peptide-based anti-cancer conjugates the generation of new, functionally diverse nucleolipid derived D-(KLAKLAK)2-AK sequences has enabled a structure and anti-cancer activity relationship study. A reductive amination approach was key for the synthesis of alkylamine, diamine and polyamine derived nucleolipids as well as those incorporating heterocyclic functionality. The carboxy-derived nucleolipids were then coupled to the C-terminus of the D-(KLAKLAK)2-AK killer peptide sequence and produced with and without the FITC fluorophore for investigating biological activity in cancer cells. The amphiphilic, α-helical peptide-nucleolipid bioconjugates were found to exhibit variable effects on the viability of MM.1S cells, with the histamine derived nucleolipid peptide bioconjugate displaying the most significant anti-cancer effects. Thus, functionally diverse nucleolipids have been developed to fine-tune the structure and anti-cancer properties of killer peptide sequences, such as D-(KLAKLAK)2-AK.

B7H6-derived peptides trigger TNF-α-dependent immunostimulatory activity of lymphocytic NK92-MI cells.

The rise of biologics that can stimulate immune responses towards the eradication of tumors has led to the evolution of cancer-based immunotherapy. Representatively, B7H6 has been recently identified as a protein ligand on tumor cells that binds specifically to the NKp30 receptor and triggers NK cell-derived cytokine production, which ultimately leads to tumor cell lysis and death. In an effort to develop effective immunotherapy approaches, the rational design of a novel class of immunostimulatory peptides (IPs) derived from the binding interface of B7H6:NKp30 is described in this study. The IPs comprised the B7H6 active site sequence for NKp30 binding and immunostimulatory activity. An aminohexanoic acid linker was also introduced at the N-terminus of the peptides for FITC-labeling by Fmoc-solid phase peptide synthesis. The peptides were characterized by LCMS to confirm identities and purities >95%. The secondary structures of the peptides were examined by CD spectroscopy in H2 O, PBS and a H2 O:TFE mixture which demonstrated versatile peptide structures which transitioned from random coil (H2 O) to α-helical (PBS) and turn-type (H2 O:TFE) conformations. Their biological properties were then evaluated by flow cytometry, enzyme-linked immunosorbent assays (ELISAs), and cell death assays. The occupancy of the synthetic peptides to a human NK cell line demonstrated comparable binding relative to the natural NKp30 ligand, B7H6, and the human anti-NKp30 monoclonal antibody (mAb), in a concentration dependent manner. A competitive binding assay between the human anti-NKp30 mAb or B7H6, and the synthetic peptides, demonstrated partial displacement of the ligands upon anti-NKp30 mAb treatment, suggesting NKp30 receptor specificities by the synthetic peptides. Moreover, the immunostimulatory activity of B7H6 was demonstrated by the secretion of the pro-inflammatory cytokines tumor necrosis factor-alfa (TNF-α) and interferon gamma (IFN-γ) by the human NK cell line. The immunostimulatory effects of IPs on the NK cells was assessed by the production of TNF-α alone as IFN-γ was undetectable. In a cell death assay, the IPs were found to be nontoxic, without any observable evidence of early or late stage apoptosis within the NK92-MI cells. Taking these findings together, this novel class of synthetic peptides may prove to be a promising lead in the development of a peptide-based immunotherapy approach, especially against B7H6 expressing tumors. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 658-672, 2016.

Synthesis, characterization, and biological activity of poly(arginine)-derived cancer-targeting peptides in HepG2 liver cancer cells.

The solid-phase synthesis, structural characterization, and biological evaluation of a small library of cancer-targeting peptides have been determined in HepG2 hepatoblastoma cells. These peptides are based on the highly specific Pep42 motif, which has been shown to target the glucose-regulated protein 78 receptors overexpressed and exclusively localized on the cell surface of tumors. In this study, Pep42 was designed to contain varying lengths (3-12) of poly(arginine) sequences to assess their influence on peptide structure and biology. Peptides were effectively synthesized by 9-fluorenylmethoxycarbonyl-based solid-phase peptide synthesis, in which the use of a poly(ethylene glycol) resin provided good yields (14-46%) and crude purities >95% as analyzed by liquid chromatography-mass spectrometry. Peptide structure and biophysical properties were investigated using circular dichroism spectroscopy. Interestingly, peptides displayed secondary structures that were contingent on solvent and length of the poly(arginine) sequences. Peptides exhibited helical and turn conformations, while retaining significant thermal stability. Structure-activity relationship studies conducted by flow cytometry and confocal microscopy revealed that the poly(arginine) derived Pep42 sequences maintained glucose-regulated protein 78 binding on HepG2 cells while exhibiting cell translocation activity that was contingent on the length of the poly(arginine) strand. In single dose (0.15 mM) and dose-response (0-1.5 mM) cell viability assays, peptides were found to be nontoxic in human HepG2 liver cancer cells, illustrating their potential as safe cancer-targeting delivery agents.