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A 66-year-old immunocompromised man presented with cellulitis around the left eye that was initially concerning for necrotizing fasciitis. Exam findings were remarkable for exquisite periocular tenderness with rigid, immobile eyelids resulting from severe erythema, edema, and induration. Given the concern for orbital compartment syndrome and a necrotizing infection, the patient was taken urgently to the operating room for debridement of the eyelid skin as well as an urgent lateral canthotomy and cantholysis. His eye exam revealed 360° of hemorrhagic chemosis, no relative afferent pupillary defect, and an ipsilateral elevated intraocular pressure of 35 mm Hg. No visual acuity measurement could be obtained secondary to the patient's altered mental status. His intraocular pressure normalized after treatment with antihypertensive drops and further extension of the canthotomy. Histopathological analysis showed extensive neutrophilic infiltrate of the dermis which was compatible with a diagnosis of Sweet's syndrome.
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Pressão Intraocular , Síndrome de Sweet , Masculino , Humanos , Idoso , Síndrome de Sweet/diagnóstico , Síndrome de Sweet/complicações , Síndrome de Sweet/patologia , Órbita/patologia , Celulite (Flegmão)/complicações , Pálpebras/patologiaRESUMO
Immune checkpoint inhibitors are associated with a spectrum of cutaneous immune-related adverse events. While maculopapular eruptions are the most common cutaneous adverse event, scleroderma can rarely develop. Herein, we report a case of new-onset scleroderma associated with avelumab treatment in the setting of metastatic squamous cell carcinoma of the lung. The pathophysiology of immune checkpoint inhibitor-induced scleroderma is not completely understood. A proposed mechanism is discussed along with the clinical presentation of symptoms and associated therapeutic response in cancer treatment. This case contributes to the few existing reports of immune checkpoint inhibitor-induced scleroderma to better understand the implications in the management of cutaneous immune-related adverse events.
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Cutaneous melanocytic tumor with CRTC1::TRIM11 fusion (CMCT) is a recently described entity with only 13 cases reported in the literature. Histopathologically, the neoplasm consists of atypical epithelioid to spindled cells that form a well-circumscribed nodule usually confined to the dermis and subcutis with cytological features including large vesicular nuclei with prominent nucleoli and abundant eosinophilic cytoplasm. Immunohistochemistry shows variable expressivity of melanocytic markers. Currently, there are limited data regarding long-term outcomes of this newly described entity. Most cases have done well, but there is one case reported with an adverse event. Hence, further studies are needed to accurately classify this tumor. Definitive diagnosis is made by laboratory evidence of CMCT. Herein, we report the first case of CMCT with epidermal involvement in the youngest patient known to be affected to date.
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Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Fusão Gênica , Fatores de Transcrição/genética , Melanócitos/patologia , Biomarcadores Tumorais , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/genéticaRESUMO
To improve understanding of the genetic signature of early-stage melanomas in Veterans, hotspot mutation profiling using next-generation sequencing (NGS) was performed on melanoma tissue samples from patients at the Iowa City Veterans Affairs Medical Center (VAMC). Genetic analysis identified BRAF (36.3%), TP53 (25.9%), NRAS (19.3%), CDKN2A (11.1%), KIT (8.1%), and BAP1 (7.4%) mutations with the highest prevalence. Although common variants in BRAF were detected at lower rates than what is reported for the general population, 55.6% of cases showed activating mutations in the RAS/RAF pathways. Variants in TP53 and KIT were detected at higher rates than in the general population. Veterans with prior history of melanoma were at significantly higher odds of having TP53 mutation (OR = 2.67, p = 0.04). This suggests that TP53 may be a marker for recurrent melanoma and possibly alternative exposures in the military population. This study provides new information regarding the genetics of melanoma in a Veteran population and early-stage melanomas, highlighting risk factors unique to this population and contributing to the conversation about preventing melanoma deaths in US Military personnel.
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BACKGROUND: Psychocutaneous disorders are often attributed to stimulant medications, yet this relationship has never been fully elucidated. Literature on psychocutaneous disorders largely focuses on clinical presentation and treatment rather than disease etiology or exacerbation. OBJECTIVE: To determine whether patients presenting with psychocutaneous disorders display high rates of stimulant use and psychiatric comorbidity. METHODS: We undertook a retrospective cohort study of patients with psychocutaneous disorders presenting to a single center. It was hypothesized that these patients would have high rates of stimulant use and psychiatric comorbidity. Following analysis of baseline demographics, the patients were assigned to 1 of 2 groups: those with a psychotic disorder and those with a neurotic disorder. RESULTS: Sixty percent of the patients (n = 317) with psychocutaneous disease had recently used a stimulant and more than 80% (270 of 317) carried an additional psychiatric diagnosis. The neurotic disorder group (n = 237) was younger and had higher rates of stimulant use. The psychotic disorder group (n = 80) had higher rates of psychosis, medical comorbidity, and illicit stimulant drug use. LIMITATIONS: The predominantly Caucasian population may limit generalizability of findings as may the retrospective nature. CONCLUSIONS: Patients with psychocutaneous disease have high rates of stimulant use and most have at least 1 psychiatric comorbidity.
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Estimulantes do Sistema Nervoso Central , Transtornos Relacionados ao Uso de Substâncias , Estimulantes do Sistema Nervoso Central/efeitos adversos , Comorbidade , Humanos , Estudos Retrospectivos , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
Skeletal muscle regeneration (SMR) encompasses a sequence of events that unfolds after injury to muscle fibers. Nearby satellite cells become activated and function as precursor muscle cells by proliferating and differentiating into myoblasts, which eventually fuse to form myotubes and ultimately mature muscle fibers. Compared to other forms of mesenchymal repair, SMR has higher morphologic heterogeneity with the potential to show histopathologic similarities to sarcomas and other malignancies. It is important to recognize SMR and settings in which this can occur to avoid misdiagnosis. We report two cases where a diagnosis of SMR was made from tissue taken from locations previously treated with Mohs micrographic surgery followed by myofascial flap reconstruction. In both cases, histopathologic features identified with hematoxylin and eosin as well as immunostaining were used to support the diagnosis of SMR. These cases highlight the importance of recognizing this clinic entity to ensure accurate diagnosis.
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Músculo Esquelético/fisiologia , Procedimentos de Cirurgia Plástica/métodos , Regeneração , Sarcoma/patologia , Cicatrização , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Cirurgia de Mohs , Sarcoma/diagnóstico , Neoplasias Cutâneas/cirurgia , Retalhos CirúrgicosRESUMO
Currently, several targeted therapy regimens are approved as first-line treatment in V600E/K-mutant advanced and metastatic melanoma. Patients with the third most common pathologic variant in the BRAF gene, V600R, were not included in BRAF/MEK inhibitors clinical trials, so there is lack of information about the clinical characteristics and predictive value of this mutation in systemic therapy of unresectable disease. We retrospectively reviewed clinical BRAF mutation testing results and the records of melanoma patients at the University of Iowa Hospitals and Clinics from 2011 to 2017. DNA from formalin-fixed, paraffin-embedded tumor specimens were sequenced using a next-generation sequencing panel or dye terminator sequencing covering exon 15 of the BRAF gene. The study protocol was approved by the University of Iowa Institutional Review Board. Nine patients (5.3% of 168 cases with BRAF mutation) were found to have the V600R mutation. We report our experience in treatment of seven patients with V600R-mutant melanoma, whose clinical records were available for review. Four patients in our cohort received BRAF inhibitors. Three patients demonstrated partial objective response to BRAF/MEK targeted therapy. V600R-mutant melanoma accounts for a significant number of cases even in single-institution practices. We believe that testing for BRAF-mutation status should include rare variants of this mutation. From our experience, the high rate of ulceration, male predominance and advanced age at diagnosis are features of melanoma with V600R mutation, which are similar to those reported for V600K mutation. We observed objective response to BRAF/MEK inhibitors in three cases with V600R variant.
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Melanoma/genética , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/genética , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Melanoma/patologia , Mutação , Estudos Retrospectivos , Neoplasias Cutâneas/patologiaRESUMO
Multiple cutaneous side effects have been reported with the use of immunotherapies including programmed cell death protein 1 inhibitors. We report 2 patients who presented with papillary dermal elastolysis presenting as multiple, skin-colored, wrinkled papules and atrophic macules following an inflammatory eruption in the setting of combination chemotherapy with nivolumab and cabiralizumab. These two cases highlight a novel finding, elastolysis in the setting of chemotherapy with nivolumab and cabiralizumab.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Toxidermias , Pigmentação da Pele/efeitos dos fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Derme/metabolismo , Derme/patologia , Toxidermias/metabolismo , Toxidermias/patologia , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Metástase Neoplásica , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Osteossarcoma/tratamento farmacológico , Osteossarcoma/metabolismo , Osteossarcoma/patologiaRESUMO
BACKGROUND: Appropriate use criteria (AUC) provide physicians guidance in test selection, and can affect health care delivery, reimbursement policy, and physician decision-making. OBJECTIVES: The American Society of Dermatopathology, with input from the American Academy of Dermatology and the College of American Pathologists, sought to develop AUC in dermatopathology. METHODS: The RAND/UCLA appropriateness methodology, which combines evidence-based medicine, clinical experience, and expert judgment, was used to develop AUC in dermatopathology. RESULTS: With the number of ratings predetermined at 3, AUC were developed for 211 clinical scenarios involving 12 ancillary studies. Consensus was reached for 188 (89%) clinical scenarios, with 93 (44%) considered "usually appropriate" and 52 (25%) "rarely appropriate" and 43 (20%) having "uncertain appropriateness." LIMITATIONS: The methodology requires a focus on appropriateness without comparison between tests and irrespective of cost. CONCLUSIONS: The ultimate decision to order specific tests rests with the physician and is one where the expected benefit exceeds the negative consequences. This publication outlines the recommendations of appropriateness-the AUC for 12 tests used in dermatopathology. Importantly, these recommendations may change considering new evidence. Results deemed "uncertain appropriateness" and where consensus was not reached may benefit from further research.
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Uso Excessivo dos Serviços de Saúde/prevenção & controle , Dermatopatias/patologia , Dermatologia/normas , Humanos , Patologia Clínica/normasRESUMO
INTRODUCTION: Given the poor understanding of the pathophysiology of genital lichen sclerosus (GLS) and a lack of accepted definitive diagnostic criteria, we proposed to survey pathologists regarding their understanding of GLS. We hypothesized that significant disagreement about GLS will exist. MATERIALS AND METHODS: All urologists participating in the Trauma and Urologic Reconstruction Network of Surgeons identified genitourinary (GUP) and dermatopathologists (DP) at their respective institutions who were then invited to participate in an online survey regarding their experience with diagnosing GLS, GLS pathophysiology and its relationship to urethral stricture disease. RESULTS: There were 23 (12 DP, 11 GUP) pathologists that completed the survey. The most agreed upon criteria for diagnosis were dermal collagen homogenization (85.7%), loss of the normal rete pattern (33.3%) and atrophic epidermis (28.5%). No pathologists believed GLS had an infectious etiology (19% maybe, 42% unknown) and 19% believed GLS to be an autoimmune disorder (42% maybe, 38% unknown); 19% believed LS to be premalignant, but 52% believed it was associated with cancer; 80% believed that LS could involve the urethra (DP (92%) versus GUP (67%); p = 0.272). Of those diagnosing urethral GLS, 80% of DUP believed that GLS must first involve the glans/prepuce before involving the urethra, while all GUP believed that urethral disease could exist in isolation (p = 0.007). CONCLUSIONS: There was significant disagreement in this specialized cohort of pathologists when diagnosing GLS. A logical first step appears to be improving agreement on how to best describe and classify the disease. This may lead to improve treatments.
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Líquen Escleroso e Atrófico/patologia , Doenças Urogenitais Masculinas/patologia , Doenças Urogenitais Masculinas/cirurgia , Inquéritos e Questionários , Estreitamento Uretral/etiologia , Procedimentos Cirúrgicos Urológicos Masculinos/métodos , Atitude do Pessoal de Saúde , Biópsia por Agulha , Competência Clínica , Genitália Masculina/patologia , Pesquisas sobre Atenção à Saúde , Humanos , Imuno-Histoquímica , Líquen Escleroso e Atrófico/cirurgia , Masculino , Doenças Urogenitais Masculinas/diagnóstico , Patologistas/normas , Patologistas/tendências , Padrões de Prática Médica , Estudos Retrospectivos , Índice de Gravidade de Doença , Estados Unidos , Estreitamento Uretral/patologia , Estreitamento Uretral/cirurgiaRESUMO
BACKGROUND: Appropriate use criteria (AUC) provide physicians guidance in test selection, and can affect health care delivery, reimbursement policy and physician decision-making. OBJECTIVES: The American Society of Dermatopathology, with input from the American Academy of Dermatology and the College of American Pathologists, sought to develop AUC in dermatopathology. METHODS: The RAND/UCLA appropriateness methodology, which combines evidence-based medicine, clinical experience and expert judgment, was used to develop AUC in dermatopathology. RESULTS: With the number of ratings predetermined at 3, AUC were developed for 211 clinical scenarios involving 12 ancillary studies. Consensus was reached for 188 (89%) clinical scenarios, with 93 (44%) considered "usually appropriate," 52 (25%) "rarely appropriate" and 43 (20%) "uncertain appropriateness." LIMITATIONS: The methodology requires a focus on appropriateness without comparison between tests and irrespective of cost. CONCLUSIONS: The ultimate decision of when to order specific test rests with the physician and is one where the expected benefit exceeds the negative consequences. This publication outlines the recommendations of appropriateness-AUC for 12 tests used in dermatopathology. Importantly, these recommendations may change considering new evidence. Results deemed "uncertain appropriateness" and where consensus was not reached may benefit from further research.
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Dermatologia , Medicina Baseada em Evidências , Patologia , Testes Diagnósticos de Rotina , Humanos , Estados UnidosAssuntos
Hipotricose/diagnóstico , Alopecia , Criança , Diagnóstico Diferencial , Feminino , Humanos , Hipotricose/genética , Hipotricose/patologia , Linhagem , Couro CabeludoRESUMO
Importance: Patients with germline mutations in BAP1 may develop several flesh-colored melanocytic BAP1-mutated atypical intradermal tumors (MBAITs). These tumors generally develop earlier than other BAP1-associated tumors, highlighting an important role for dermatologists in identifying and screening patients with a history suggestive of a germline mutation. Objective: To describe 8 new families with germline mutations in BAP1 and provide a comprehensive review of reported cases. Design, Settings and Participants: Patients were identified in an outpatient dermatology clinical setting over a 6-month period (10 mutation carriers from 8 families) and through a literature review using PubMed (205 patients). Exposures: Mutations were identified through next-generation sequencing of saliva or blood samples, and RNA was extracted from fibroblasts cultured from a patient with an intronic variant to determine the impact of the mutation on the coding sequence. Main Outcomes and Measures: All 215 patients were assessed for personal and/or family history and genotype. These findings were compiled and assessed for any association between genotype and phenotype. Results: Overall, this study included 215 patients (108 women, 91 men, and 16 gender unspecified; median [range] age, 46.5 [10.0-79.0] years). Nine of the 10 patients who were identified in the outpatient dermatology setting were found to have MBAITs on clinical examination. Forty of 53 patients (75%) identified in the literature review who underwent total-body skin examinations (TBSE) were found to have MBAITs, suggesting a high penetrance in patients who have undergone TBSE. The most prevalent malignancies among BAP1 mutation carriers were uveal melanoma (n = 60 [28%]), mesothelioma (n = 48 [22%]), cutaneous melanoma (n = 38 [18%]), and renal cell carcinoma (n = 20 [9%]). A total of 71 unique mutations in BAP1 have been reported. Conclusions and Relevance: Our results indicate that germline mutations in both coding and noncoding regions throughout the BAP1 gene can impair protein function, leading to an increased risk for several associated malignancies. Four of the 8 probands we present had no history of BAP1-associated malignancies and were assessed for germline mutations when found to have MBAITs on dermatologic examination. Dermatologists can identify patients with a high likelihood of the BAP1 cancer syndrome through personal and family history and TBSE for the presence of possible MBAITs.
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Mutação em Linhagem Germinativa , Melanoma/patologia , Neoplasias Cutâneas/patologia , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética , Adolescente , Adulto , Idoso , Carcinoma de Células Renais/epidemiologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Criança , Feminino , Genótipo , Humanos , Neoplasias Renais/epidemiologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Melanoma/epidemiologia , Melanoma/genética , Mesotelioma/epidemiologia , Mesotelioma/genética , Mesotelioma/patologia , Pessoa de Meia-Idade , Fenótipo , Neoplasias Cutâneas/genética , Adulto JovemRESUMO
A 69-year-old male with granulomatosis with polyangiitis presented with new skin nodules. Skin biopsy showed metastatic poorly differentiated lung adenocarcinoma. The skin nodule was the initial presentation of his lung cancer. There is need for increased vigilance for cancer risk in ANCA-associated vasculitis patients.