We described an extensive network of cortical pyramidal neurons in the human brain with abundant acetylcholinesterase (AChE) activity. Emergence of these neurons during childhood/adolescence, attainment of highest density in early adulthood, and virtual absence in other species led us to hypothesize involvement of AChE within these neurons in higher cortical functions. The current study quantified the density and staining intensity of these neurons using histochemical procedures. Few faintly stained AChE-positive cortical pyramidal neurons were observed in children/adolescents. These neurons attained their highest density and staining intensity in young adulthood. Compared with the young adult group, brains of cognitively normal elderly displayed no significant change in numerical density but a significant decrease in staining intensity of AChE-positive cortical pyramidal neurons. Brains of elderly above age 80 with unusually preserved memory performance (SuperAgers) showed significantly lower staining intensity and density of these neurons when compared with same-age peers. Conceivably, low levels of AChE activity could enhance the impact of acetylcholine on pyramidal neurons to counterbalance other involutional factors that mediate the decline of memory capacity during average aging. We cannot yet tell if elderly with superior memory capacity have constitutively low neuronal AChE levels or if this feature reflects adaptive neuroplasticity.

Differentiating melanocytic hyperplasia (MH) on photodamaged skin from junctional lentiginous melanocytic proliferations (JLMP), early evolving melanoma in situ (MIS), or the periphery of a lesion of MIS on staged excision can be challenging. Although previous cross-sectional studies have elucidated important criteria for distinguishing MH on photodamaged skin from more concerning lesions, this study highlights a technique to treat JLMP and MIS with staged mapped excision and baseline scouting biopsies of adjacent nonlesional photodamaged skin to assist in determination of surgical margin clearance. Additionally, we compare the lesional and photodamaged control biopsies from the same patient to evaluate relevant histologic criteria that may be used to distinguish MH in photodamaged skin from JLMP/MIS, while minimizing confounding factors. There was a statistically significant difference (P ≤ 0.05) found for melanocyte density, irregular melanocyte distribution, melanocyte clustering, follicular infundibulum involvement, and nesting. However, criteria such as nesting, epithelioid cells and melanocyte clustering were seen in both photodamaged skin and MIS. These findings underscore the fact that histologic features of photodamaged skin can overlap with the histopathological features of MIS. Of all of the criteria evaluated, melanocytic density was the most objective histologic criterion and did not show overlap between the sun-damaged and JLMP/MIS groups. K E Y W O R D S atypical junctional melanocytic hyperplasia, lentigo maligna, melanoma in situ, scouting biopsy, slow Mohs, staged excision How to cite this article: Speiser J, Tao J, Champlain A, et al. Is melanocyte density our last hope? Comparison of histologic features of photodamaged skin and melanoma in situ after staged surgical excision with concurrent scouting biopsies.

Cutaneous adverse effects are a common manifestation that can occur from the use of medications, which can present with mild to life threatening outcomes. Acute Generalized Exanthematous Pustulosis (AGEP) is a dermatologic condition characterized by numerous non-follicular sterile pustules on a background of edematous erythema, and is believed to be induced by a drug reaction. It is estimated that the incidence of AGEP is one to five per million per year. The most common offending drugs are antibiotics. However, we report a case of Pepcid (Famotidine)-induced AGEP. An 82 year-old African American female with a known medical history of HTN, GERD, eczema, and glaucoma was brought to the ER after being found to be lethargic and difficult to arouse from sleep in her home. She had chief complaints of chills, fatigue, and dry skin with an accompanied rash. She was previously hospitalized two months prior and was diagnosed with Eczema status post skin biopsy. Her condition was shown to be exacerbated when her dosage of Famotidine was increased for symptomatic treatment of GERD. She was since taken off famotidine, however her rash persisted and consistently developed over time. The skin rash was found on the trunk, extremities, face, and scalp sparing the palms, soles, and mucosal membranes of the mouth. There was marked neutrophilia, slight eosinophilia, and decreased creatinine clearance. The pustules had disappeared by the 8th day of admission leaving dry skin and scarring. This case is to bring attention to an uncommon skin manifestation caused by a drug that has not had many documented cases of causing AGEP. AGEP is theorized to be a T cell mediated neutrophilic inflammation. CD4+ T cells produce copious amounts of CXCL8 and GM-CSF which induce neutrophil chemotaxis and reduce neutrophil apoptosis, respectively, resulting in an accumulation of neutrophils in the tissue. Though rare, AGEP should be considered in patients that are developing cutaneous manifestations with Famotidine treatment.

Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) used to treat imatinib-resistant chronic myelogenous leukemia (CML), as well as other Philadelphia chromosome-positive lymphoproliferative disorders. While the most commonly reported cutaneous side effects with this therapy include a morbilliform eruption, skin exfoliation, and skin irritation, pigmentary abnormalities have also been observed, albeit much more rarely. We present the case of a 72-year-old South Asian male with CML who presented with new-onset hypopigmentation of his face and scalp three years after a dose increase of dasatinib therapy, in the setting of newly discovered borderline hypovitaminosis D. Dasatinib and the other TKIs are believed to induce dyschromias via modulation of the c-kit receptor and its associated signaling pathway, which is involved in melanocyte survival, proliferation, and migration.

Introduction: Male gender, age, fair skin, ultraviolet radiation and immunosuppression are known risk factors for BCC. However there is limited understanding of the impact of these risk factors with increasing frequency of BCC development. In this study, we sought to investigate the association of gender, age, BCC subtype, distribution and immunosuppressant use with increasing frequency of BCCs. Methods: We performed a retrospective cohort study of 3,392 BCCs biopsied in 1,419 patients between 2005 and 2015 at Stanford Hospital and Clinics. Results: During the 10-year observational period, 53.3% patients were diagnosed with single BCC; 38.8% patients developed 2 to 5 BCCs; 7.8% patients developed 6 or more BCCs (high frequency BCCs or hfBCCs). We found that as the number of BCC increased, the proportion of male patients also significantly increased. Adjusting for age, race, and follow-up duration, male sex was associated with a 1.18 fold-increase in risk of 2 or more BCCs (p ¼ 0.007) and a 2.40-fold increase in risk of 6 or more BCCs (p < 0.001) using logistic regression. Multivariate regression analysis adjusted for age, gender, race, and transplant status also showed that patients with history of azathioprine had 5.22 fold-increase in risk for developing 6 or more BCCs (95% CI 1.31 e 20.81, p ¼ 0.019) compared to single BCC. Mycophenolate, cyclosporine, sirolimus, and tacrolimus did not change the risk of BCC. Conclusion: The data implicates the continued high risk of male gender on the development of numerous BCCs. In addition, azathioprine is associated with increased risk of hfBCCs. Continued clinical surveillance is needed to identify and understand this subset of patients who develop BCC at high frequency.

Keratinocyte carcinomas (KCs) are now an epidemic in The United States of America, especially in elderly patients. KCs, including basal cell carcinoma and squamous cell carcinoma, can lead to disfigurement and occasionally death. However, the lower mortality rate associated with KC compared with melanoma allows for increased flexibility in the selection of treatment. Flexibility in treatment is particularly important in the elderly given that this patient population often has medical comorbidities that should be considered. These patients may have multiple KCs, higher risk tolerance to recurrence, and different concerns about cosmetic outcomes compared with their younger counterparts. We review treatment options for KCs and how the selection of each option may affect the elderly patient.

Background:Case reports suggest photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is an effective treatment for refractory mycosis fungoides (MF). No prospective trials have examined the use of ALA-PDT in MF. Objective:We aimed to assess the efficacy of ALA-PDT in refractory MF. Methods:This was a prospective study at Mayo Clinic in Scottsdale, Arizona in patients ≥ 18 years with plaque-stage treatment-refractory MF. Monthly sessions of ALA with blue light PDT were administered for up to six months. Responses were measured by Composite Assessment of Index Lesion Severity (CAILS) and Physician Global Assessment (PGA). Ad hoc analysis with modified CAILS (mCAILS) was performed, eliminating hyperpigmentation from scoring. Results:Eleven patients (30 total lesions) were treated. Six patients completed the trial per protocol. Objective response rates were 36.4% by PGA (10.9-69.2%), 18.2% by CAILS (2.3-51.8%), and 36.4% by mCAILS (10.9-69.2%). Limitations:Five patients did not complete all six PDT cycles per protocol, possibly accounting for reduced efficacy. Conclusion:ALA-PDT with blue light irradiation was moderately effective and well tolerated in refractory plaque stage MF. Lower response rates compared to similar trials may be partially explained by utilization of strict lesional assessment criteria and other variations in methodology. Disclosures Mangold: MiRagen:Research Funding;Sun Pharma:Research Funding;Elorac:Research Funding;Kirin:Membership on an entity's Board of Directors or advisory committees;Solagenix:Research Funding. OffLabel Disclosure: Photodynamic therapy is a two-step therapy in which a drug that acts as a photosensitizer is administered to target a diseased tissue, followed by illumination with visible light to activate the drug and destroy the target tissue. PDT has been used to treat internal cancers as well as treatment of cancer and precancer of the skin.

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