Publications by authors named "Scott R Florell"

94 Publications

Functional Impairment of Skin Appendages Due to Peripheral Nerve Involvement by .

Open Forum Infect Dis 2020 Oct 12;7(10):ofaa419. Epub 2020 Sep 12.

Leprology-Venereology Service, Muhimbili National Hospital, Dar es Salaam, United Republic of Tanzania.

In the earliest stage of infection, bacteria parasitize fine fiber twigs of autonomic peripheral nerves supplying efferent impulses to appendages of the skin. This obligate intracellular pathogen invades Schwann cells, the glial cells of peripheral nerves. Intracellular events inhibit Schwann cell physiology in complex ways, which include demyelination and dedifferentiation. Ultimately, axons embraced by their surrounding dysfunctional glia are damaged by poorly understood mechanisms. Loss of nerve conduction impairs the functions of skin appendages including hair growth, sebaceous gland secretion, sweating, and skin pigmentation. At the clinical level, these changes may be subtle and may precede the more obvious anesthetic skin lesions associated with Hansen's disease. Recognizing the early signs of skin appendage malfunction may aid in diagnosis leading to initiation of antimycobacterial treatment. Effective therapy administered early during infection may prevent irreversible peripheral nerve destruction, the presage for morbid complications of leprosy.
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http://dx.doi.org/10.1093/ofid/ofaa419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566401PMC
October 2020

Aspirin Protects Melanocytes and Keratinocytes against UVB-Induced DNA Damage In Vivo.

J Invest Dermatol 2021 Jan 20;141(1):132-141.e3. Epub 2020 Jun 20.

Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Dermatology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Oncological Sciences, University of Utah, Salt Lake City, Utah, USA. Electronic address:

UVR promotes skin cancer through multiple mechanisms, including induction of inflammation, oxidative stress, and DNA damage such as 8-oxoguanine and cyclobutane pyrimidine dimers. We investigated whether the anti-inflammatory activities of aspirin (acetylsalicylic acid [ASA]) could protect against UVB-induced DNA damage and skin carcinogenesis. ASA reduced UVB-induced 8-oxoguanine and cyclobutane pyrimidine dimers in Melan-A melanocytes and HaCaT keratinocytes. Skin from UVB-irradiated C57BL/6 mice receiving 0.4 mg ASA daily by gavage exhibited less inflammation, fewer sunburn cells, and reduced 8-oxoguanine lesions than skin from irradiated control animals. ASA similarly reduced UVB-induced sunburn cells, 8-oxoguanine, and cyclobutane pyrimidine dimer lesions in skin of melanoma-prone TN mice, and this was associated with decreased prostaglandin E in plasma and skin. These effects of ASA, however, did not delay melanoma onset in TN mice exposed to a single neonatal dose of UVB. In SKH1-E mice prone to squamous cell carcinoma, ASA reduced plasma and skin prostaglandin E levels and indices of UVB-induced DNA damage and delayed squamous cell carcinoma onset induced by chronic UVB. These results indicate that ASA can protect against UVB-induced inflammation in skin and reduce UVB-induced DNA damage in both melanocytes and keratinocytes. These effects translated into greater chemopreventive efficacy for UVB-induced squamous cell carcinoma than melanoma mouse models.
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http://dx.doi.org/10.1016/j.jid.2020.06.003DOI Listing
January 2021

Rapidly progressive and fatal case of extragenital cutaneous epithelioid angiosarcoma with visceral involvement.

JAAD Case Rep 2020 Jan 24;6(1):33-36. Epub 2019 Dec 24.

Department of Dermatology, University of Utah, Salt Lake City, Utah.

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http://dx.doi.org/10.1016/j.jdcr.2019.09.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938824PMC
January 2020

ASA Suppresses PGE in Plasma and Melanocytic Nevi of Human Subjects at Increased Risk for Melanoma.

Pharmaceuticals (Basel) 2020 Jan 2;13(1). Epub 2020 Jan 2.

Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA.

Potential anti-inflammatory and anticarcinogenic effects of aspirin (ASA) may be suitable for melanoma chemoprevention, but defining biomarkers in relevant target tissues is prerequisite to performing randomized controlled chemoprevention trials. We conducted open-label studies with ASA in 53 human subjects with melanocytic nevi at increased risk for melanoma. In a pilot study, 12 subjects received a single dose (325 mg) of ASA; metabolites salicylate, salicylurate, and gentisic acid were detected in plasma after 4-8 h, and prostaglandin E2 (PGE) was suppressed in both plasma and nevi for up to 24 h. Subsequently, 41 subjects received either 325 or 81 mg ASA (nonrandomized) daily for one week. ASA metabolites were consistently detected in plasma and nevi, and PGE levels were significantly reduced in both plasma and nevi. Subchronic ASA dosing did not affect 5" adenosine monophosphate-activated protein kinase (AMPK) activation in nevi or leukocyte subsets in peripheral blood, although metabolomic and cytokine profiling of plasma revealed significant decreases in various (non-ASA-derived) metabolites and inflammatory cytokines. In summary, short courses of daily ASA reduce plasma and nevus PGE and some metabolites and cytokines in plasma of human subjects at increased risk for melanoma. PGE may be a useful biomarker in blood and nevi for prospective melanoma chemoprevention studies with ASA.
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http://dx.doi.org/10.3390/ph13010007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168893PMC
January 2020

Use of the Pigmented Lesion Assay to rapidly screen a patient with numerous clinically atypical pigmented lesions.

JAAD Case Rep 2019 Dec 20;5(12):1048-1050. Epub 2019 Nov 20.

Department of Dermatology, University of Utah School of Medicine, Salt Lake City, Utah.

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http://dx.doi.org/10.1016/j.jdcr.2019.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872771PMC
December 2019

Histologic criteria for assessing surgical margins in melanoma in situ.

J Am Acad Dermatol 2020 04 19;82(4):e133-e134. Epub 2019 Nov 19.

Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City; Department of Dermatology, University of Utah Health Sciences Center, Salt Lake City.

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http://dx.doi.org/10.1016/j.jaad.2019.10.080DOI Listing
April 2020

Cutaneous T-Cell Acute Lymphoblastic Leukemia and the Expression Pattern of Terminal Deoxynucleotidyl Transferase Immunostaining in Mycosis Fungoides and Spongiotic Dermatitis.

Dermatopathology (Basel) 2019 Jul-Sep;6(3):182-188. Epub 2019 Sep 4.

Department of Dermatology, University of Utah, Salt Lake City, Utah, USA.

Background/aims: T-cell acute lymphoblastic leukemia (T-ALL) is an uncommon, aggressive malignancy that rarely presents in the skin and is generally not considered as part of the differential diagnosis by dermatologists and dermatopathologists. We describe an unusual case of T-ALL presenting with folliculocentric, erythematous papules on the face, histologically resembling mycosis fungoides (MF). Immunostaining for terminal deoxynucleotidyl transferase (TdT) was positive in tumor cells, supporting the diagnosis of cutaneous involvement by T-ALL. TdT is a nuclear enzyme expressed by immature lymphoid malignancies, but the expression pattern of this marker is not well characterized in the skin. We aimed to assess TdT staining in skin biopsies with similar-appearing lymphocytic infiltrates.

Methods: We evaluated the immunostaining profile of TdT in a cohort of 23 patients, including 13 cases of MF and 10 cases of spongiotic dermatitis.

Results: The lymphocytes in the MF and spongiotic dermatitis cases lacked nuclear staining for TdT. Nonspecific, granular, cytoplasmic staining was observed in a small number of background cells.

Conclusions: TdT may assist dermatopathologists in discriminating malignant infiltrates of T-ALL from other conditions.
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http://dx.doi.org/10.1159/000501581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787418PMC
September 2019

Histopathologic vasculitis from the periulcer edge: A retrospective cohort study.

J Am Acad Dermatol 2019 Dec 27;81(6):1353-1357. Epub 2019 Aug 27.

Department of Dermatology, University of Utah School of Medicine, Salt Lake City, Utah. Electronic address:

Background: Histopathologic vasculitis is often reported in periulcer specimens, but the frequency and clinical significance of this finding have not been evaluated.

Objective: We evaluated the sensitivity, specificity, negative predictive value, and positive predictive value of histopathologic vasculitis from the periulcer edge for detecting ulcers due to cutaneous vasculitis.

Methods: We performed a retrospective chart review of patients with leg ulcers at a tertiary hospital between 2009 and 2016. Histopathologic slides were evaluated by 2 dermatopathologists who were blinded to the etiology of ulcer. Focal vasculitis was defined as involvement of fewer than 3 vessels.

Results: Vasculitis at the periulcer edge was seen in 51.6% of the specimens (32 of 62). Of the specimens with histopathologic vasculitis, focal vasculitis was seen in the majority of specimens (71.9% [23 of 32]), whereas diffuse vasculitis was observed in 28.1% (9 of 32). Periulcer vasculitis yielded a high sensitivity (100% [95% confidence interval, 29%-100%]). Furthermore, the specificity was low (50.9% [95% confidence interval, 38.1%-63.6%]) for detecting vasculitis-induced ulcers.

Limitations: Small number of vasculitis-induced ulcers.

Conclusion: Focal vasculitis from the periulcer edge is a nonspecific finding and provides little diagnostic value in determining the etiology of lower leg ulcers. Emphasis should be placed on the combination of clinical history and examination, histology, and laboratory findings when diagnosing ulcers.
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http://dx.doi.org/10.1016/j.jaad.2019.04.011DOI Listing
December 2019

Pretibial Pruritic Papular Dermatitis: A Comprehensive Clinical and Pathologic Review of Cases at a Single Institution.

Am J Dermatopathol 2020 Jan;42(1):16-19

Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UT.

Background: Studies characterizing clinical and pathologic details of pretibial pruritic papular dermatitis (PPPD) are scarce. Several cases of PPPD at our institution have displayed lymphocyte atypia and CD30 positivity, resembling lymphomatoid papulosis (LyP). We explore the clinical and histological spectrum of PPPD, with emphasis on lymphocyte atypia.

Methods: Retrospective observational study of 40 archived pathological specimens (hematoxylin/eosin, CD3, CD20, and CD30 immunohistochemistry) from 38 PPPD patients in an academic center. Clinical photographs were available in 22 cases.

Results: Microscopic epidermal changes were focal, but common (spongiosis 75%, parakeratosis 90%, interface changes 43%, Langerhans cell microgranulomas 25%, multinucleated keratinocytes 55%, Civatte bodies 55%, erosion 20%, and more than focal irregular psoriasiform hyperplasia 37%) and certain dermal changes were universal (papillary dermal fibrosis 100%, stellate fibroblasts 100%, and multinucleated fibroblasts 93%). At least focal lymphocyte atypia was present in all cases. Lymphocytes were almost exclusively CD3 T cells with rare CD20 B cells. Up to 30% of lymphocytes exhibited weak CD30 staining. Clinically, all cases exhibited discrete papules, but plaques and erosions were not uncommon.

Limitations: As a retrospective series, clinical images were not available for all cases.

Conclusion: This study suggests a broader histological and clinical spectrum of PPPD than previously described. Epidermal changes are common in PPPD, as are atypical lymphocytes and focal CD30 positivity. Although the papular clinical appearance, lymphocyte atypia, and focal CD30 positivity may resemble LyP, the relatively low number of atypical lymphocytes, low intensity of CD30 staining, and absence of spontaneous resolution help to distinguish PPPD from LyP.
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http://dx.doi.org/10.1097/DAD.0000000000001460DOI Listing
January 2020

Midline Anterior Neck Inclusion Cyst.

J Pediatr 2019 Aug 17;211:220. Epub 2019 Apr 17.

Department of Dermatology, University of Utah, Salt Lake City, Utah.

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http://dx.doi.org/10.1016/j.jpeds.2019.03.038DOI Listing
August 2019

Pure testicular choriocarcinoma presenting as a friable hemorrhagic nodule on the lip.

JAAD Case Rep 2018 Aug 15;4(7):705-707. Epub 2018 Aug 15.

Department of Dermatology, University of Utah School of Medicine, Salt Lake City, Utah.

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http://dx.doi.org/10.1016/j.jdcr.2018.05.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098204PMC
August 2018

Peri-prosthetic tissue reaction to discontinuation of negative pressure wound therapy around porous titanium percutaneous devices.

J Biomed Mater Res B Appl Biomater 2019 04 7;107(3):564-572. Epub 2018 May 7.

Orthopaedic Research Laboratories, George E. Wahlen, Department of Veterans Affairs Medical Center, University of Utah Orthopaedic Center, Salt Lake City, Utah, 84148.

Negative pressure wound therapy (NPWT) has been reported to limit epithelial downgrowth, one of the failure mechanisms of percutaneous devices. In a previous study, when NPWT was applied for 4 weeks (NPWT Group) to porous coated titanium percutaneous devices, downgrowth (5 ± 4%; mean ± one SD) was significantly reduced compared to untreated controls (Untreated Group) (16 ± 6%; p ≤ 0.01). However, it was unclear whether this beneficial effect was sustained when NPWT was discontinued. In order to test this, porous coated titanium percutaneous devices were implanted into 6 hairless guinea pigs. Post-surgery, animals received 4 weeks of NPWT treatment followed by 4 weeks of no treatment (Discontinued Group). At necropsy, the devices and surrounding tissues were harvested and processed. Quantitative downgrowth measurements and qualitative analyses of tissue characteristics were performed, and compared to historical controls (NPWT and Untreated Groups). The Discontinued Group, at 8 weeks, had significantly more downgrowth than the NPWT Group at 4 weeks (23 ± 3% vs. 5 ± 4%; p ≤ 0.01). At 8 weeks, the Discontinued Group qualitatively appeared to exhibit reduced numbers of blood vessels and increased degree of fibrosis compared to the NPWT Group at 4 weeks. This study suggests that NPWT will only be an effective treatment for limiting downgrowth if used continuously. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 564-572, 2019.
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http://dx.doi.org/10.1002/jbm.b.34148DOI Listing
April 2019

A Nonsynonymous Variant in the GOLM1 Gene in Cutaneous Malignant Melanoma.

J Natl Cancer Inst 2018 12;110(12):1380-1385

Genetic Epidemiology, Department of Internal Medicine, University of Utah, Salt Lake City, UT.

Background: Statistically significant linkage of melanoma to chromosome 9q21 was previously reported in a Danish pedigree resource and independently confirmed in Utah high-risk pedigrees, indicating strong evidence that this region contains a melanoma predisposition gene.

Methods: Whole-exome sequencing of pairs of related melanoma case subjects from two pedigrees with evidence of 9q21 linkage was performed to identify the responsible predisposition gene. Candidate variants were tested for association with melanoma in an independent set of 454 unrelated familial melanoma case subjects and 396 unrelated cancer-free control subjects from Utah, and 1534 melanoma case subjects and 1146 noncancer control subjects from Texas (MD Anderson) via a two-sided Fisher exact test.

Results: A rare nonsynonymous variant in Golgi Membrane Protein 1 (GOLM1), rs149739829, shared in two hypothesized predisposition carriers in one linked pedigree was observed. Segregation of this variant in additional affected relatives of the index carriers was confirmed. A statistically significant excess of carriers of the variant was observed among Utah case subjects and control subjects (odds ratio [OR] = 9.81, 95% confidence interval [CI] = 8.35 to 11.26, P < .001) and statistically significantly confirmed in Texas case subjects and control subjects (OR = 2.45, 95% CI = 1.65 to 3.25, P = .02).

Conclusion: These findings support GOLM1 as a candidate melanoma predisposition gene.
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http://dx.doi.org/10.1093/jnci/djy058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292789PMC
December 2018

Capillary hemangioma associated with dermal atrophy masquerading as a deep fungal infection.

Dermatol Online J 2018 Mar 15;24(3). Epub 2018 Mar 15.

Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, Utah.

Hemangiomas are benign vascular neoplasms which arise in early adulthood. Herein we present a 79-year-old woman with a hemangioma of the lower flank masquerading as a cutaneous manifestation of a systemic fungal infection upon initial histological analysis. Decreased elastin and collagen within the lesion likely accounted for the clumping and splaying of the capillaries into "hyphae-like" structures. Loss of dermal elastic tissue and collagen apparently concentrated the capillary proliferation into an unusual morphology mimicking the hyphal structures. Through additional staining methods the lesion was confirmed to be an unusual presentation of a capillary hemangioma.
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March 2018

Cellular and ultrastructural characterization of the grey-morph phenotype in southern right whales (Eubalaena australis).

PLoS One 2017 7;12(2):e0171449. Epub 2017 Feb 7.

Huntsman Cancer Institute, Salt Lake City, Utah, United States of America.

Southern right whales (SRWs, Eubalena australis) are polymorphic for an X-linked pigmentation pattern known as grey morphism. Most SRWs have completely black skin with white patches on their bellies and occasionally on their backs; these patches remain white as the whale ages. Grey morphs (previously referred to as partial albinos) appear mostly white at birth, with a splattering of rounded black marks; but as the whales age, the white skin gradually changes to a brownish grey color. The cellular and developmental bases of grey morphism are not understood. Here we describe cellular and ultrastructural features of grey-morph skin in relation to that of normal, wild-type skin. Melanocytes were identified histologically and counted, and melanosomes were measured using transmission electron microscopy. Grey-morph skin had fewer melanocytes when compared to wild-type skin, suggesting reduced melanocyte survival, migration, or proliferation in these whales. Grey-morph melanocytes had smaller melanosomes relative to wild-type skin, normal transport of melanosomes to surrounding keratinocytes, and normal localization of melanin granules above the keratinocyte nuclei. These findings indicate that SRW grey-morph pigmentation patterns are caused by reduced numbers of melanocytes in the skin, as well as by reduced amounts of melanin production and/or reduced sizes of mature melanosomes. Grey morphism is distinct from piebaldism and albinism found in other species, which are genetic pigmentation conditions resulting from the local absence of melanocytes, or the inability to synthesize melanin, respectively.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0171449PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295704PMC
August 2017

A Phase II Randomized Placebo-Controlled Trial of Oral N-acetylcysteine for Protection of Melanocytic Nevi against UV-Induced Oxidative Stress In Vivo.

Cancer Prev Res (Phila) 2017 Jan 5;10(1):36-44. Epub 2016 Dec 5.

Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, Utah.

Oxidative stress plays a role in UV-induced melanoma, which may arise from melanocytic nevi. We investigated whether oral administration of the antioxidant N-acetylcysteine (NAC) could protect nevi from oxidative stress in vivo in the setting of acute UV exposure. The minimal erythemal dose (MED) was determined for 100 patients at increased risk for melanoma. Patients were randomized to receive a single dose (1,200 mg) of NAC or placebo, in double-blind fashion, and then one nevus was irradiated (1-2 MED) using a solar simulator. One day later, the MED was redetermined and the irradiated nevus and a control unirradiated nevus were removed for histologic analysis and examination of biomarkers of NAC metabolism and UV-induced oxidative stress. Increased expression of 8-oxoguanine, thioredoxin reductase-1, and γ-glutamylcysteine synthase modifier subunit were consistently seen in UV-treated compared with unirradiated nevi. However, no significant differences were observed in these UV-induced changes or in the pre- and postintervention MED between those patients receiving NAC versus placebo. Similarly, no significant differences were observed in UV-induced changes between subjects with germline wild-type versus loss-of-function mutations in the melanocortin-1 receptor. Nevi showed similar changes of UV-induced oxidative stress in an open-label post-trial study in 10 patients who received NAC 3 hours before nevus irradiation. Thus, a single oral dose of NAC did not effectively protect nevi from UV-induced oxidative stress under the conditions examined. Cancer Prev Res; 10(1); 36-44. ©2016 AACR.
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http://dx.doi.org/10.1158/1940-6207.CAPR-16-0162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5219848PMC
January 2017

Cutaneous carcinosarcoma: a series of six cases and a review of the literature.

J Cutan Pathol 2017 Jan 18;44(1):34-44. Epub 2016 Nov 18.

Department of Dermatology, University of Utah, Salt Lake City, UT, USA.

Background: Cutaneous carcinosarcoma is a rare tumor with distinct malignant epithelial and mesenchymal cell populations. The histologic subtypes of epithelial and mesenchymal components in cutaneous carcinosarcoma are variable, as an assortment of carcinomatous and sarcomatous patterns have been described in the literature.

Methods: Clinical information was obtained from patient charts and archival slides were retrieved and reviewed.

Results: We present a novel series of six distinct cases of cutaneous carcinosarcoma and review the literature. Our cases consisted of basal cell, pilomatrical, squamous cell, and trichoblastic variants. These cases occurred in elderly men on sun exposed skin with treatment and follow up was available for 4 of 6 cases. The four cases were treated with Mohs micrographic surgery with mean follow up of nine months.

Conclusion: We report six cases of cutaneous carcinosarcoma with distinctive clinical and histologic characterization not previously described in a single series.
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http://dx.doi.org/10.1111/cup.12843DOI Listing
January 2017

Acute Presentation of Tender Papules and Plaques in a Patient With Leukemia.

JAMA Dermatol 2016 05;152(5):571-2

Department of Dermatology, University of Utah School of Medicine, Salt Lake City.

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http://dx.doi.org/10.1001/jamadermatol.2015.5253DOI Listing
May 2016

microRNAs in Psoriasis.

J Invest Dermatol 2016 Feb;136(2):365-371

Department of Pathology, University of Utah, Salt Lake City, Utah, USA. Electronic address:

Psoriasis is a chronic inflammatory skin condition resulting from a complex interplay among the immune system, keratinocytes, susceptibility genes, and environmental factors. However, the pathogenesis of psoriasis is not completely elucidated. microRNAs represent a promising class of small, noncoding RNA molecules that function to regulate gene expression. Although microRNA research in psoriasis and dermatology is still relatively new, evidence is rapidly accumulating for the role of microRNAs in the pathogenesis of psoriasis and other chronic inflammatory conditions. In this article, we present a comprehensive review of what is known about microRNAs and their role in the pathogenesis of psoriasis.
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http://dx.doi.org/10.1038/JID.2015.409DOI Listing
February 2016

Disseminated Mycobacterial Infection After International Medical Tourism.

Open Forum Infect Dis 2015 Apr 17;2(2):ofv054. Epub 2015 Apr 17.

Departments of Medicine ; Public Health and Preventative Medicine , Oregon Health and Sciences University , Portland.

International travel for the purpose of receiving medical care is increasing. We report a case of disseminated mycobacterial infection after fetal stem cell infusion.
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http://dx.doi.org/10.1093/ofid/ofv054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4567086PMC
April 2015

Sandpapery Skin.

JAMA Dermatol 2015 Nov;151(11):1251-2

Department of Dermatology, University of Utah School of Medicine, Salt Lake City.

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http://dx.doi.org/10.1001/jamadermatol.2015.2339DOI Listing
November 2015

Benign melanocytic lymph node deposits in the setting of giant congenital melanocytic nevi: the large congenital nodal nevus.

J Cutan Pathol 2015 Nov 18;42(11):832-9. Epub 2015 Sep 18.

Department of Dermatology, University of Utah, Salt Lake City, UT, USA.

Background: Benign melanocytic rests are a frequent finding in superficial lymph nodes removed during sentinel lymph node biopsies for melanoma. Whereas the histopathology of these deposits is well understood, very little is known regarding melanocytic lymph node deposits in the setting of giant congenital melanocytic nevi.

Methods: We analyzed lymph nodes removed from the drainage basin of giant congenital melanocytic nevi in three patients who had developed melanoma within their giant congenital nevi.

Results: Two of three patients showed widespread, capsular and parenchymal melanocytic deposits in multiple nodes (9 of 11 nodes in one patient and 6 of 8 in the other). Melanocytes were small, non-mitotically active and resembled those in the associated giant congenital melanocytic nevus. Melanocytes were arranged singly and in small nests ∼0.05 mm in diameter, with some larger sheets up to 1 mm. Nodal melanocytes stained for Melan A and S100 on immunohistochemical evaluation, but showed negative or minimal HMB-45 reactivity.

Conclusions: Evaluation of lymph nodes in the setting of giant congenital melanocytic nevi is complicated by the presence of often numerous, parenchymal melanocytic nevic deposits. Bland cytology and minimal or absent HMB-45 staining may be helpful in differentiating these nodal melanocytic nevi from metastatic melanoma. We term this phenomena large congenital nodal nevus.
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http://dx.doi.org/10.1111/cup.12580DOI Listing
November 2015

The role of thioredoxin reductase 1 in melanoma metabolism and metastasis.

Pigment Cell Melanoma Res 2015 Nov 20;28(6):685-95. Epub 2015 Aug 20.

Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA.

Although significant progress has been made in targeted and immunologic therapeutics for melanoma, many tumors fail to respond, and most eventually progress when treated with the most efficacious targeted combination therapies thus far identified. Therefore, alternative approaches that exploit distinct melanoma phenotypes are necessary to develop new approaches for therapeutic intervention. Tissue microarrays containing human nevi and melanomas were used to evaluate levels of the antioxidant protein thioredoxin reductase 1 (TR1), which was found to increase as a function of disease progression. Melanoma cell lines revealed metabolic differences that correlated with TR1 levels. We used this new insight to design a model treatment strategy that creates a synthetic lethal interaction wherein targeting TR1 sensitizes melanoma to inhibition of glycolytic metabolism, resulting in a decrease in metastases in vivo. This approach holds the promise of a new clinical therapeutic strategy, distinct from oncoprotein inhibition.
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http://dx.doi.org/10.1111/pcmr.12398DOI Listing
November 2015

Chronic, Painful, Nonhealing Ulcer on the Right Arm Following Minor Trauma.

JAMA Dermatol 2015 Jul;151(7):787-8

Department of Dermatology, University of Utah Health Sciences Center, Salt Lake City.

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http://dx.doi.org/10.1001/jamadermatol.2014.5373DOI Listing
July 2015

Clinical validation of a gene expression signature that differentiates benign nevi from malignant melanoma.

J Cutan Pathol 2015 Apr 13;42(4):244-52. Epub 2015 Apr 13.

Myriad Genetic Laboratories, Inc., Salt Lake City, UT, USA.

Background: Histopathologic examination is sometimes inadequate for accurate and reproducible diagnosis of certain melanocytic neoplasms. As a result, more sophisticated and objective methods have been sought. The goal of this study was to identify a gene expression signature that reliably differentiated benign and malignant melanocytic lesions and evaluate its potential clinical applicability. Herein, we describe the development of a gene expression signature and its clinical validation using multiple independent cohorts of melanocytic lesions representing a broad spectrum of histopathologic subtypes.

Methods: Using quantitative reverse-transcription polymerase chain reaction (PCR) on a selected set of 23 differentially expressed genes, and by applying a threshold value and weighting algorithm, we developed a gene expression signature that produced a score that differentiated benign nevi from malignant melanomas.

Results: The gene expression signature classified melanocytic lesions as benign or malignant with a sensitivity of 89% and a specificity of 93% in a training cohort of 464 samples. The signature was validated in an independent clinical cohort of 437 samples, with a sensitivity of 90% and specificity of 91%.

Conclusions: The performance, objectivity, reliability and minimal tissue requirements of this test suggest that it could have clinical application as an adjunct to histopathology in the diagnosis of melanocytic neoplasms.
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http://dx.doi.org/10.1111/cup.12475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681167PMC
April 2015

Predictive value of biopsy specimens suspicious for melanoma: support for 6-mm criterion in the ABCD rule.

J Am Acad Dermatol 2015 Mar 10;72(3):412-8. Epub 2015 Jan 10.

Department of Dermatology, University of Utah, Salt Lake City, Utah; Huntsman Cancer Institute, Salt Lake City, Utah.

Objective: Clinical detection of melanoma can be challenging. The number of biopsy specimens performed to diagnose 1 melanoma is a measure of efficiency of skin cancer detection, but few data are available to describe this measure from US health care. We studied the diagnosis of melanoma among biopsy specimens of clinically concerning pigmented lesions at an academic dermatology department.

Methods: We searched for all biopsy specimens that were performed because of clinical suspicion of melanoma in 2013. Characteristics of the patient, lesion, and clinician performing the biopsy, and the final pathology diagnosis were recorded.

Results: A total of 2643 biopsy specimens from 2213 patients submitted by 43 providers were included. Melanoma was diagnosed in 165 cases (positive predictive value 6.4%, 95% confidence interval 5.5%-7.4%). Older age (P < .001), male gender (P = .045), and nontrunk location (P < .001) were predictors of higher probability of melanoma detection. Lesions larger than 6 mm in size had higher positive predictive value 11.5% (8.8%-14.1%) than smaller lesions 2.6% (1.6%-3.6%).

Limitations: Factors influencing the decision to biopsy a lesion may be difficult to evaluate retrospectively.

Conclusion: At an academic medical center, 16 clinically concerning lesions were biopsied to diagnose 1 melanoma. Biopsy specimens of clinically concerning pigmented lesions larger than 6 mm on older men had the highest yield.
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http://dx.doi.org/10.1016/j.jaad.2014.11.030DOI Listing
March 2015

Neutrophilic sebaceous adenitis with intralobular Demodex mites: a case report and review of the literature.

Am J Dermatopathol 2015 Apr;37(4):315-8

A 61-year-old white man presented with a 1-week history of an asymptomatic erythematous, annular plaque with minimal scale limited to the nasal bridge. Histological examination showed a mixed infiltrate of lymphocytes and neutrophils within sebaceous glands. The clinical and histopathological presentation was consistent with a diagnosis of neutrophilic sebaceous adenitis. Several Demodex brevis mites were present deep within the affected sebaceous lobules. Demodex brevis mites are uncommon inhabitants of sebaceous glands of the nose, presenting more commonly on other body sites. The cause of neutrophilic sebaceous adenitis is unknown, but the presence of D. brevis in affected sebaceous glands in this case suggests a possible association.
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http://dx.doi.org/10.1097/DAD.0000000000000099DOI Listing
April 2015

Adequacy of 5-mm surgical excision margins for non-lentiginous melanoma in situ.

J Am Acad Dermatol 2014 Oct;71(4):835-8

Department of Dermatology, University of Utah Health Sciences Center, Salt Lake City, Utah; Department of Oncological Sciences, University of Utah Health Sciences Center, Salt Lake City, Utah; Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, Utah. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2014.06.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4167347PMC
October 2014

Secondary diffuse large B-cell lymphoma after chemotherapy for acute myeloid leukemia: looking for the unexpected diagnosis.

Am J Dermatopathol 2014 Jul;36(7):e125-8

Departments of *Dermatology, and † Pathology, University of Utah, Salt Lake City, UT.

Development of Epstein-Barr virus (EBV) positive lymphoproliferative disorders in patients with immunosuppression has become more frequently reported. A patient with acute myeloid leukemia was treated to remission, when on follow-up 9 months after his initial diagnosis, he was noted to have a generalized rash and lymphadenopathy. Evaluation of skin and bone marrow biopsies was suggestive of a relapsed leukemia, and treatment was initiated. Fever evaluation revealed a high load of EBV in his blood. A lymph node biopsy and retrospective examination of his skin and bone marrow revealed an EBV-positive diffuse large B-cell lymphoma with no recurrence of acute myeloid leukemia. His chemotherapy-induced immunosuppression likely predisposed him to develop this EBV-positive diffuse large B-cell lymphoma. This case highlights the need to consider a broader differential and immunohistochemical profiling of these neoplasms to avoid misdiagnosing complex oncology patients.
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http://dx.doi.org/10.1097/DAD.0000000000000027DOI Listing
July 2014