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4.
Cutis ; 104(2): 103-105, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31603962

RESUMO

Dermatology hospitalists (DHs) provide consultative care to inpatients with skin conditions. In this study, we surveyed current members of the Society for Dermatology Hospitalists (SDH) regarding barriers to care, current and ideal compensation models, and overall job satisfaction to evaluate the overall job satisfaction of DHs and further describe potential barriers to inpatient dermatology consultations.

5.
Am J Dermatopathol ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31592864

RESUMO

Significant communication occurs between pathologists and clinicians through the dermatopathology report. Our objective was to describe clinician preference about reporting of the margin status of skin biopsies of nonmelanoma skin cancers. An anonymous survey was sent to 243 medical providers who submitted specimens to a single institution university medical center; 50 complete responses from attending-level providers and advance practice providers were received. The majority (96%) of those surveyed indicated margins should be reported on skin biopsies of neoplasms, particularly nonmelanoma skin cancers (basal cell carcinoma 96% and squamous cell carcinoma 92%) and atypical nevi (96%). When asked about particular language used to describe the margin status, some phrasing led to more variance in respondents' clinical management decisions, with 96%-98% of respondents making the same decision when presented with "unambiguous" terms and 58%-84% of respondents making the same decision when presented with "ambiguous" language (P < 0.001). Respondents generally preferred "unambiguous" margin descriptions when shown an involved margin (70% vs. 30%, P < 0.001) but accepted "ambiguous" language when the margin was clearly uninvolved (68% vs. 32%, P = 0.015). Most respondents (88%) desire inclusion of treatment recommendations in dermatopathology reports. Microscopic descriptions were highly utilized, particularly by nondermatology trained clinicians (97% vs. 80%, P = 0.09). Clinicians desire inclusion of margins for skin biopsies in dermatopathology reports, at least in some circumstances. The choice of language used to describe the margin status in dermatopathology reports has important implications for patient care. Margin descriptors that are unclear or ambiguous may lead to more variance in clinical management.

6.
Int Wound J ; 16(6): 1440-1444, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31475449

RESUMO

Accurate and prompt diagnosis of skin ulcers is critical to optimise management; however, studies in hospitalised patients are limited. This retrospective review of dermatologic consultations included 272 inpatients with skin ulcers between July 2015 and July 2018 in four U.S. academic hospitals. The median age was 54 years and 45% were male. In 49.3% of the patients, skin ulcers were considered the primary reason for admission. Ulcers of 62% were chronic and 49.6% were located on the lower extremities. Pyoderma gangrenosum (17.3%), infection (12.5%), and exogenous causes (11.8%) were the leading aetiologies; 12% remained diagnostically inconclusive after consultation. Diagnostic agreements pre-dermatology and post-dermatology consult ranged from 0.104 (n = 77, 95% CI 0.051-0.194) to 0.553 (n = 76, 95% CI 0.440-0.659), indicating poor-modest agreement. This study highlights the diagnostic complexity and relative incidences of skin ulcers in the inpatient setting.

7.
Dermatol Online J ; 25(7)2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31450279

RESUMO

Angioimmunoblastic T-cell lymphoma (AITL) is a rare form of non-Hodgkin lymphoma often accompanied by autoimmune and paraneoplastic phenomena. Up to 50% of patients with AITL present with skin manifestations. This case series highlights two cases of AITL presenting with unusual cutaneous findings: one with a medium-vessel vasculitis and another with a chronic urticarial eruption. Clinicians should consider AITL in the differential diagnosis of vasculitis or urticaria refractory to standard treatment.

8.
Blood ; 134(6): 515-524, 2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31164331

RESUMO

The primary cutaneous CD30+ lymphoproliferative disorders are a family of extranodal lymphoid neoplasms that arise from mature postthymic T cells and localize to the skin. Current classification systems recognize lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma, and borderline cases. In the majority of patients, the prognosis of primary cutaneous CD30+ lymphoproliferative disorders is excellent; however, relapses are common, and complete cures are rare. Skin-directed and systemic therapies are used as monotherapy or in combination to achieve the best disease control and minimize overall toxicity. We discuss 3 distinct presentations of primary cutaneous CD30+ lymphoproliferative disorder and present recommendations for a multidisciplinary team approach to diagnosis, evaluation, and management of these conditions in keeping with existing consensus guidelines.


Assuntos
Antígeno Ki-1/genética , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia , Adulto , Idoso , Biomarcadores , Biópsia , Terapia Combinada/métodos , Feminino , Humanos , Antígeno Ki-1/metabolismo , Transtornos Linfoproliferativos/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Cutâneas/etiologia , Avaliação de Sintomas , Resultado do Tratamento
9.
Front Oncol ; 9: 260, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31032224

RESUMO

Skin directed therapies (SDTs) serve important roles in the treatment of early stage cutaneous T-cell lymphoma (CTCL)/mycosis fungoides (MF), as well as managing symptoms and improving quality of life of all stages. There are now numerous options for topical therapies that demonstrate high response rates, particularly in early/limited MF. Phototherapy retains an important role in treating MF, with increasing data supporting efficacy and long-term safety of both UVB and PUVA as well as some newer/targeted methodologies. Radiation therapy, including localized radiation and total skin electron beam therapy, continues to be a cornerstone of therapy for all stages of MF.

10.
J Clin Oncol ; 37(9): 693-702, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30726175

RESUMO

PURPOSE: Merkel cell carcinoma (MCC) is an aggressive skin cancer often caused by the Merkel cell polyomavirus. Clinical trials of programmed cell death-1 pathway inhibitors for advanced MCC (aMCC) demonstrate increased progression-free survival (PFS) compared with historical chemotherapy data. However, response durability and overall survival (OS) data are limited. PATIENTS AND METHODS: In this multicenter phase II trial (Cancer Immunotherapy Trials Network-09/Keynote-017), 50 adults naïve to systemic therapy for aMCC received pembrolizumab (2 mg/kg every 3 weeks) for up to 2 years. Radiographic responses were assessed centrally per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. RESULTS: Among 50 patients, the median age was 70.5 years, and 64% had Merkel cell polyomavirus-positive tumors. The objective response rate (ORR) to pembrolizumab was 56% (complete response [24%] plus partial response [32%]; 95% CI, 41.3% to 70.0%), with ORRs of 59% in virus-positive and 53% in virus-negative tumors. Median follow-up time was 14.9 months (range, 0.4 to 36.4+ months). Among 28 responders, median response duration was not reached (range, 5.9 to 34.5+ months). The 24-month PFS rate was 48.3%, and median PFS time was 16.8 months (95% CI, 4.6 months to not estimable). The 24-month OS rate was 68.7%, and median OS time was not reached. Although tumor viral status did not correlate with ORR, PFS, or OS, there was a trend toward improved PFS and OS in patients with programmed death ligand-1-positive tumors. Grade 3 or greater treatment-related adverse events occurred in 14 (28%) of 50 patients and led to treatment discontinuation in seven (14%) of 50 patients, including one treatment-related death. CONCLUSION: Here, we present the longest observation to date of patients with aMCC receiving first-line anti-programmed cell death-1 therapy. Pembrolizumab demonstrated durable tumor control, a generally manageable safety profile, and favorable OS compared with historical data from patients treated with first-line chemotherapy.

12.
J Cutan Pathol ; 46(2): 134-137, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30328131

RESUMO

We present a case of a widespread fixed drug eruption histologically mimicking CD8 positive cutaneous T-cell lymphoma (CTCL). CTCL has several potential histological and clinical mimics, and accurate diagnosis relies on a combination of clinicopathological correlation and molecular studies. We add generalized fixed drug eruption to the list of possible CTCL mimics.


Assuntos
Antirretrovirais/efeitos adversos , Linfócitos T CD8-Positivos/patologia , Erupção por Droga/patologia , Infecções por HIV/tratamento farmacológico , HIV-1 , Linfoma Cutâneo de Células T , Neoplasias Cutâneas , Antirretrovirais/administração & dosagem , Infecções por HIV/patologia , Humanos , Linfoma Cutâneo de Células T/induzido quimicamente , Linfoma Cutâneo de Células T/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/patologia
13.
Am J Dermatopathol ; 41(5): 343-346, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30461422

RESUMO

In the United States, chronic ulcers affect 6.5 million people, with a cost of ≈$20 million annually. The most common etiology of chronic ulcers in the United States is venous stasis, followed by arterial insufficiency and neuropathic ulcers. Less common causes of chronic ulcers include infection, inflammatory etiologies such as vasculitis and pyoderma gangrenosum, and neoplastic causes. Obtaining skin biopsy and tissue culture can be helpful in diagnosing unusual causes of chronic ulcers; however, there are little data on the diagnostic utility of skin biopsy in rendering a definitive diagnosis of the etiology of chronic ulcers. A retrospective study of all skin ulcers biopsied during a 10-year period at the University of Washington was undertaken. Re-excisions and surgical wounds were excluded. A total of 270 ulcer biopsy specimens were included. In 48% of cases, no specific diagnosis could be rendered histologically. 44.8% of chronic ulcers biopsied were due to atypical causes, with neoplasms (basal cell carcinoma, squamous cell carcinoma, melanoma, and cutaneous T-cell lymphoma) being the most common. Vasculitis and pyoderma gangrenosum each represented 1.5% of rendered diagnoses. Concomitant skin culture was performed in 28.9% of cases, and special stains [acid-fast bacilli, Brown and Brenn (B&B), Grocott's methenamine silver, and periodic acid-Schiff stains] were performed in 34.0%. Although more than half (49 of 78) of tissue cultures were positive, only 6.8% (12 of 175) of special stains on tissue sections were positive. We conclude that although the etiology of many ulcers cannot be determined by routine histology alone, skin biopsy of ulcers remains a critical part of the workup given that when a specific cause can be determined, atypical etiologies, including neoplasms, represent a significant proportion of chronic ulcers. Limitations of our study include referral bias. Our results also confirm the higher diagnostic yield of conventional tissue culture compared with special tissue stain biopsies of skin ulcers.


Assuntos
Úlcera Cutânea/classificação , Úlcera Cutânea/diagnóstico , Adulto , Idoso , Biópsia , Células Cultivadas , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Úlcera Cutânea/etiologia
14.
Clin Cancer Res ; 25(4): 1185-1195, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30093453

RESUMO

PURPOSE: G100 is a toll-like receptor 4 (TLR4) agonist that triggers innate and adaptive antitumor immune responses in preclinical models. This pilot study assessed the safety, efficacy, and immunologic activity of intratumoral (IT) administration of G100 in patients with Merkel cell carcinoma (MCC). PATIENTS AND METHODS: Patients with locoregional MCC (n = 3; cohort A) received neoadjuvant IT G100 (2 weekly doses at 5 µg/dose) followed by surgery and radiotherapy; patients with metastatic MCC (n = 7; cohort B) received 3 doses in a 6-week cycle and could receive additional cycles with/without radiotherapy. RESULTS: IT G100 was safe and feasible in both neoadjuvant and metastatic settings. Treatment-related adverse events were mostly grade 1 or 2 injection-site reactions. IT G100 led to increased inflammation in the injected tumors with infiltration of CD8+ and CD4+ T cells and activation of immune-related genes. These proinflammatory changes were associated with local tumor regression and appeared to promote systemic immunity. All 3 cohort A patients successfully completed therapy; 2 patients remain recurrence free at 44+ and 41+ months, including 1 with a pathologic complete response after G100 alone. In cohort B, 2 patients achieved sustained partial responses, both lasting 33+ months after 2 cycles of therapy. CONCLUSIONS: In this first-in-human study, IT G100 induced antitumor immune responses, demonstrated acceptable safety, and showed encouraging clinical activity.See related commentary by Marquez-Rodas et al., p. 1127.

15.
J Immunother Cancer ; 6(1): 131, 2018 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-30482247

RESUMO

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive skin cancer that frequently responds to anti-PD-1 therapy. MCC is associated with sun exposure and, in 80% of cases, Merkel cell polyomavirus (MCPyV). MCPyV-specific T and B cell responses provide a unique opportunity to study cancer-specific immunity throughout PD-1 blockade therapy. METHODS: Immune responses were assessed in patients (n = 26) with advanced MCC receiving pembrolizumab. Peripheral blood mononuclear cells (PBMC) were collected at baseline and throughout treatment. MCPyV-oncoprotein antibodies were quantified and T cells were assessed for MCPyV-specificity via tetramer staining and/or cytokine secretion. Pre-treatment tumor biopsies were analyzed for T cell receptor clonality. RESULTS: MCPyV oncoprotein antibodies were detectable in 15 of 17 (88%) of virus-positive MCC (VP-MCC) patients. Antibodies decreased in 10 of 11 (91%) patients with responding tumors. Virus-specific T cells decreased over time in patients who had a complete response, and increased in patients who had persistent disease. Tumors that were MCPyV(+) had a strikingly more clonal (less diverse) intratumoral TCR repertoire than virus-negative tumors (p = 0.0001). CONCLUSIONS: Cancer-specific T and B cell responses generally track with disease burden during PD-1 blockade, in proportion to presence of antigen. Intratumoral TCR clonality was significantly greater in VP-MCC than VN-MCC tumors, suggesting expansion of a limited number of dominant clones in response to fewer immunogenic MCPyV antigens. In contrast, VN-MCC tumors had lower clonality, suggesting a diverse T cell response to numerous neoantigens. These findings reveal differences in tumor-specific immunity for VP-MCC and VN-MCC, both of which often respond to anti-PD-1 therapy.


Assuntos
Carcinoma de Célula de Merkel/tratamento farmacológico , Carcinoma de Célula de Merkel/etiologia , Poliomavírus das Células de Merkel/imunologia , Infecções por Polyomavirus/complicações , Infecções por Polyomavirus/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Infecções Tumorais por Vírus/complicações , Infecções Tumorais por Vírus/imunologia , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Linfócitos B/metabolismo , Biomarcadores Tumorais , Carcinoma de Célula de Merkel/diagnóstico , Humanos , Imunomodulação/efeitos dos fármacos , Ativação Linfocitária/imunologia , Terapia de Alvo Molecular , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Especificidade do Receptor de Antígeno de Linfócitos T/genética , Especificidade do Receptor de Antígeno de Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Resultado do Tratamento
16.
J Cutan Pathol ; 45(11): 864-868, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30054925

RESUMO

Talimogene laherparepvec (T-VEC) is a novel intralesional oncolytic genetically modified herpes simplex virus type 1 vector for the treatment of unresectable cutaneous, subcutaneous, and nodal melanoma. Although immunological therapies such as T-VEC offer therapeutic promise, they carry a risk of immune-related adverse events (irAEs), the full spectrum of which is incompletely understood. We report a 63-year-old previously healthy man with cutaneous melanoma of the right ankle and progressive right lower extremity in-transit metastases despite systemic therapy with immunomodulatory and molecularly targeted treatments. T-VEC treatment resulted in a complete pathologic response on scouting biopsies. Biopsy of the right lateral calf showed lobular and septal panniculitis with lymphoplasmacytic infiltrate and lipophages. Gomori methenamine silver (GMS) stain and acid-fast bacilli (AFB) stains were negative, and no polarizable foreign material was noted. T-VEC was discontinued due to complete pathologic response and, in part, concern for development of irAEs including this panniculitis and an early concomitant autoimmune colitis. This case highlights a previously unreported irAE with this novel treatment for advanced cases of melanoma.


Assuntos
Antineoplásicos/administração & dosagem , Melanoma/terapia , Terapia Viral Oncolítica/efeitos adversos , Paniculite/etiologia , Neoplasias Cutâneas/terapia , Herpesvirus Humano 1 , Humanos , Masculino , Pessoa de Meia-Idade
17.
Lasers Surg Med ; 50(3): 183-193, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29356051

RESUMO

BACKGROUND: In clinical dermatology, the identification of subsurface vascular and structural features known to be associated with numerous cutaneous pathologies remains challenging without the use of invasive diagnostic tools. OBJECTIVE: To present an advanced optical coherence tomography angiography (OCTA) method to directly visualize capillary-level vascular and structural features within skin in vivo. METHODS: An advanced OCTA system with a 1310 nm wavelength was used to image the microvascular and structural features of various skin conditions. Subjects were enrolled and OCTA imaging was performed with a field of view of approximately 10 × 10 mm. Skin blood flow was identified using an optical microangiography (OMAG) algorithm. Depth-resolved microvascular networks and structural features were derived from segmented volume scans, representing tissue slabs of 0-132, 132-330, and 330-924 µm, measured from the surface of the skin. RESULTS: Subjects with both healthy and pathological conditions, such as benign skin lesions, psoriasis, chronic graft-versus-host-disease (cGvHD), and scleroderma, were OCTA scanned. Our OCTA results detailed variations in vascularization and local anatomical characteristics, for example, depth-dependent vascular, and structural alterations in psoriatic skin, alongside their resolve over time; vascular density changes and distribution irregularities, together with corresponding structural depositions in the skin of cGvHD patients; and vascular abnormalities in the nail folds of a patient with scleroderma. CONCLUSION: OCTA can image capillary blood flow and structural features within skin in vivo, which has the potential to provide new insights into the pathophysiology, as well as dynamic changes of skin diseases, valuable for diagnoses, and non-invasive monitoring of disease progression and treatment. Lasers Surg. Med. 50:183-193, 2018. © 2018 Wiley Periodicals, Inc.


Assuntos
Angiografia , Dermatopatias/diagnóstico por imagem , Tomografia de Coerência Óptica , Humanos , Microvasos/diagnóstico por imagem
19.
J Cutan Pathol ; 44(9): 798-800, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28627008

RESUMO

We present a case of tissue invasive Trichophyton rubrum (T. rubrum) histologically mimicking blastomycosis in a patient with kidney transplant on chronic immunosuppression. Invasive dermatophyte infections are rare, and present a diagnostic challenge to the dermatopathologist due to atypical clinical and histopathological presentations.


Assuntos
Blastomicose/diagnóstico , Diagnóstico Diferencial , Hospedeiro Imunocomprometido , Tinha/imunologia , Humanos , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Tinha/diagnóstico , Tinha/patologia , Transplantados , Trichophyton
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