RESUMO
ABSTRACT: The conventional morphological characteristics of Wnt-activated deep penetrating/plexiform melanocytomas/nevi (DPN) are those of large spindled or epithelioid melanocytes with distinctive voluminous amphophilic cytoplasm, fine pigmented granules, and surrounding melanophages. The central molecular hallmark is the activation of the Wnt-pathway predominantly driven by mutations in the beta-catenin (CTNNB1) gene. Although typically lacking a junctional component, a lesser-known superficial variant with a junctional component has been identified, which could potentially lead to diagnostic challenges. This study presents a cohort of 11 such cases displaying a junctional component of DPN from 10 patients (5 women and 5 men; age range: 27-78 years; median age: 51 years). The nevi were distributed as follows: 1 conjunctival, 1 scalp, 2 lower limb, and 6 truncal lesions. Eight cases were combined with a conventional nevus, 2 cases displayed pure DPN cytology exhibiting only a junctional element, and 9 cases exhibited some degree of lentiginous architecture. All cases demonstrated a low mitotic index (<1 mitosis/mm2). Immunohistochemistry revealed positive BRAF V600E staining in 8 cases (8/11), whereas all cases tested (11/11) were PRAME negative. Nuclear beta-catenin and LEF1 staining was consistently strong and diffuse with DPN cytology (11/11), along with robust cyclin D1 staining in all cases tested (11/11). By contrast, all 9 conventional nevi showed an absence of nuclear beta-catenin staining (0/9) and weaker, mosaic-type LEF1 and cyclin D1 staining was observed. This study emphasizes the diagnostic challenge these nevi can pose in the absence of a conventional, deeper DPN component, which can potentially be misdiagnosed as melanoma.
RESUMO
Next-generation sequencing (NGS) is increasingly being utilized as an ancillary tool for diagnostically challenging melanocytic neoplasms. It is incumbent upon the pathology community to perform studies assessing the benefits and limitations of these tools in specific diagnostic scenarios. One of the most challenging diagnostic scenarios faced by skin pathologists involves accurate diagnosis of desmoplastic melanocytic neoplasms (DMNs). In this study, 20 expert melanoma pathologists rendered a diagnosis on 47 DMNs based on hematoxylin and eosin sections with demographic information. After submitting their diagnosis, the experts were given the same cases, but this time with comprehensive genomic sequencing results, and asked to render a diagnosis again. Identification of desmoplastic melanoma (DM) improved by 7%, and this difference was statistically significant ( P <0.05). In addition, among the 15 melanoma cases, in the pregenomic assessment, only 12 were favored to be DM by the experts, while after genomics, this improved to 14 of the cases being favored to be DM. In fact, some cases resulting in metastatic disease had a substantial increase in the number of experts recognizing them as DM after genomics. The impact of the genomic findings was less dramatic among benign and intermediate-grade desmoplastic tumors (BIDTs). Interobserver agreement also improved, with the Fleiss multirater Kappa being 0.36 before genomics to 0.4 after genomics. NGS has the potential to improve diagnostic accuracy in the assessment of desmoplastic melanocytic tumors. The degree of improvement will be most substantial among pathologists with some background and experience in bioinformatics and melanoma genetics.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Melanoma , Variações Dependentes do Observador , Neoplasias Cutâneas , Humanos , Melanoma/genética , Melanoma/diagnóstico , Melanoma/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/diagnóstico , Feminino , Masculino , Reprodutibilidade dos Testes , Valor Preditivo dos Testes , Pessoa de Meia-Idade , Adulto , Idoso , Patologistas , Biomarcadores Tumorais/genéticaAssuntos
Dermatite , Linfoma Cutâneo de Células T , Neoplasias Cutâneas , Humanos , Imuno-Histoquímica , Estudos Retrospectivos , Linfoma Cutâneo de Células T/diagnóstico , Linfoma Cutâneo de Células T/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Dermatite/diagnóstico , Dermatite/etiologiaRESUMO
ABSTRACT: Preferentially expressed antigen in melanoma (PRAME) is a tumor-associated antigen first identified in a melanoma patient and found to be expressed in most melanomas as well as in variable levels in other malignant neoplasms of epithelial, mesenchymal, or hematolymphoid lineage. Detection of PRAME expression in formalin-fixed paraffin-embedded tissue is possible by immunohistochemistry (IHC) with commercially available monoclonal antibodies. In situ and invasive melanoma frequently show a diffuse pattern of nuclear PRAME immunoreactivity which contrasts with the infrequent and typically nondiffuse staining seen in nevi. In many challenging melanocytic tumors, results of PRAME IHC and other ancillary tests correlate well, but not always: The tests are not interchangeable. Most metastatic melanomas are positive for PRAME, whereas nodal nevi are not. Numerous studies on PRAME IHC have become available in the past few years with results supporting the value of PRAME IHC as an ancillary tool in the evaluation of melanocytic lesions and providing insights into limitations in sensitivity and specificity as well as possible pitfalls that need to be kept in mind by practicing pathologists.
Assuntos
Melanoma , Nevo , Neoplasias Cutâneas , Humanos , Antígenos de Neoplasias , Biomarcadores Tumorais/metabolismo , Imuno-Histoquímica , Melanoma/genética , Melanoma/metabolismo , Melanoma/patologia , Nevo/diagnóstico , Nevo/genética , Nevo/metabolismo , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Fatores de Transcrição , Melanoma Maligno CutâneoRESUMO
INTRODUCTION: We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids' quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium. METHODS: Following a pre-established protocol, participating centers ship formalin-fixed paraffin embedded (FFPE) tissue sections to Memorial Sloan Kettering Cancer Center for the centralized handling, dermatopathology review and histology-guided coextraction of RNA and DNA. Samples are distributed for evaluation of somatic mutations using next gen sequencing (NGS) with the MSK-IMPACTTM assay, methylation-profiling (Infinium MethylationEPIC arrays), and miRNA expression (Nanostring nCounter Human v3 miRNA Expression Assay). RESULTS: Sufficient material was obtained for screening of miRNA expression in 683/685 (99%) eligible melanomas, methylation in 467 (68%), and somatic mutations in 560 (82%). In 446/685 (65%) cases, aliquots of RNA/DNA were sufficient for testing with all three platforms. Among samples evaluated by the time of this analysis, the mean NGS coverage was 249x, 59 (18.6%) samples had coverage below 100x, and 41/414 (10%) failed methylation QC due to low intensity probes or insufficient Meta-Mixed Interquartile (BMIQ)- and single sample (ss)- Noob normalizations. Six of 683 RNAs (1%) failed Nanostring QC due to the low proportion of probes above the minimum threshold. Age of the FFPE tissue blocks (p<0.001) and time elapsed from sectioning to co-extraction (p = 0.002) were associated with methylation screening failures. Melanin reduced the ability to amplify fragments of 200bp or greater (absent/lightly pigmented vs heavily pigmented, p<0.003). Conversely, heavily pigmented tumors rendered greater amounts of RNA (p<0.001), and of RNA above 200 nucleotides (p<0.001). CONCLUSION: Our experience with many archival tissues demonstrates that with careful management of tissue processing and quality control it is possible to conduct multi-omic studies in a complex multi-institutional setting for investigations involving minute quantities of FFPE tumors, as in studies of early-stage melanoma. The study describes, for the first time, the optimal strategy for obtaining archival and limited tumor tissue, the characteristics of the nucleic acids co-extracted from a unique cell lysate, and success rate in downstream applications. In addition, our findings provide an estimate of the anticipated attrition that will guide other large multicenter research and consortia.
Assuntos
Melanoma , MicroRNAs , Ácidos Nucleicos , Humanos , Fixação de Tecidos/métodos , MicroRNAs/análise , Melanoma/genética , DNA/genética , Inclusão em Parafina/métodos , FormaldeídoRESUMO
The distinction between undifferentiated melanoma (UM) or dedifferentiated melanoma (DM) from undifferentiated or unclassifiable sarcoma can be difficult and requires the careful correlation of clinical, pathologic, and genomic findings. In this study, we examined the utility of mutational signatures to identify patients with UM/DM with particular attention as to whether this distinction matters for treatment because the survival of patients with metastatic melanoma has dramatically improved with immunologic therapy, whereas durable responses are less frequent in sarcomas. We identified 19 cases of UM/DM that were initially reported as unclassified or undifferentiated malignant neoplasm or sarcoma and submitted for targeted next-generation sequencing analysis. These cases were confirmed as UM/DM by harboring melanoma driver mutations, UV signature, and high tumor mutation burden. One case of DM showed melanoma in situ. Meanwhile, 18 cases represented metastatic UM/DM. Eleven patients had a prior history of melanoma. Thirteen of 19 (68%) of the tumors were immunohistochemically completely negative for 4 melanocytic markers (S100, SOX10, HMB45, and MELAN-A). All cases harbored a dominant UV signature. Frequent driver mutations involved BRAF (26%), NRAS (32%), and NF1 (42%). In contrast, the control cohort of undifferentiated pleomorphic sarcomas (UPS) of deep soft tissue exhibited a dominant aging signature in 46.6% (7/15) without evidence of UV signature. The median tumor mutation burden for DM/UM vs UPS was 31.5 vs 7.0 mutations/Mb (P < .001). A favorable response to immune checkpoint inhibitor therapy was observed in 66.6% (12/18) of patients with UM/DM. Eight patients exhibited a complete response and were alive with no evidence of disease at the last follow-up (median 45.5 months). Our findings support the usefulness of the UV signature in discriminating DM/UM vs UPS. Furthermore, we present evidence suggesting that patients with DM/UM and UV signatures can benefit from immune checkpoint inhibitor therapy.
Assuntos
Histiocitoma Fibroso Maligno , Melanoma , Segunda Neoplasia Primária , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Melanoma/genética , Melanoma/terapia , Melanoma/patologia , Sarcoma/genética , Sarcoma/terapia , Sarcoma/patologia , Biomarcadores Tumorais/genética , Imunoterapia , Mutação , Melanoma Maligno CutâneoRESUMO
Desmoplastic melanoma is a subtype of melanoma characterised by amelanotic fusiform melanocytes dispersed in a collagenous stroma. Cell-poor and fibrous stroma-rich 'pure' variants have been distinguished from 'mixed' variants with areas of higher cell density and/or less desmoplastic stroma. This distinction is relevant because patients whose tumours display a pure phenotype have a lower risk for regional lymph node metastasis and distant recurrence. However, little is known about interobserver agreement among pathologists in the subclassification of desmoplastic melanoma. To address this issue, we conducted a study in which eleven dermatopathologists independently evaluated whole slide scanned images of excisions from 30 desmoplastic melanomas. The participating pathologists were asked to classify the tumours as pure or mixed. They were also asked to record the presence or absence of neurotropism and angiotropism. We found substantial interobserver agreement between the 11 dermatopathologists in the classification of tumours as pure versus mixed desmoplastic melanoma (kappa=0.64; p<0.0001). There was fair agreement between the 11 dermatopathologists in the evaluation of presence versus absence of neurotropism (kappa=0.26; p<0.0001), and slight agreement in the assessment of angiotropism (kappa=0.13; p<0.0001). The level of concordance in the subclassification of desmoplastic melanomas is encouraging for the acceptance of this prognostic parameter in the real-world practice of melanoma pathology.
Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/patologia , Variações Dependentes do Observador , Melanoma/patologia , PrognósticoRESUMO
BACKGROUND: Lentigo maligna/lentigo maligna melanoma (LM/LMM) can present with subclinical extension that may be difficult to define preoperatively and lead to incomplete excision and potential recurrence. Preliminarily studies have used reflectance confocal microscopy (RCM) to assess LM/LMM margins. OBJECTIVE: To evaluate the correlation of LM/LMM subclinical extension defined by RCM compared with the gold standard histopathology. METHODS: Prospective study of LM/LMM patients referred for dermatologic surgery. RCM was performed at the clinically defined initial surgical margin followed by margin-controlled staged excision with paraffin-embedded tissue, and histopathology was correlated with RCM results. RESULTS: Seventy-two patients were included. Mean age was 66.8 years (standard deviation, 11.1; range, 38-89); 69.4% were men. Seventy of 72 lesions (97.2%) were located on the head and neck with mean largest clinical diameter of 1.3 cm (range, 0.3-5). Diagnostic accuracy for detection of residual melanoma in the tumor debulk (after biopsy) had a sensitivity of 96.7% and a specificity of 66.7% when compared with histopathology. RCM margin assessment revealed an overall agreement with final histopathology of 85.9% (κ = 0.71; P < .001). LIMITATIONS: No RCM imaging beyond initial planned margins was performed. CONCLUSION: RCM showed moderate to excellent overall agreement between RCM imaging of LM/LMM and histopathology of staged excision margins.
Assuntos
Sarda Melanótica de Hutchinson , Melanoma , Neoplasias Cutâneas , Masculino , Humanos , Idoso , Feminino , Sarda Melanótica de Hutchinson/diagnóstico por imagem , Sarda Melanótica de Hutchinson/cirurgia , Sarda Melanótica de Hutchinson/patologia , Estudos Prospectivos , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/patologia , Melanoma/diagnóstico por imagem , Melanoma/cirurgia , Melanoma/patologia , Margens de Excisão , Microscopia Confocal/métodosRESUMO
Multiple treatment modalities for Kaposi sarcoma (KS) have been reported, including chemotherapy, radiation therapy, surgical excision, electrochemotherapy, and cryotherapy. Common topical treatments include timolol, imiquimod, and alitretinoin. We searched our institutional database for patients with ICD-9 or 10 codes for KS seen by a dermatologist with experience in KS management from July 1, 2004 to January 1, 2022. We screened patient charts to include patients who received combination therapy of cryotherapy followed by topical imiquimod three times a week for 2 months (n = 9). Patients were followed in the clinic every 3 months. Time to resolution was assessed by photographic evidence of resolution as determined by a dermatologist and corroborated with clinical documentation in patient charts. Median age (IQR) at KS diagnosis was 58 (27.5) years. All patients were male (n = 9, 100%). Majority were white (n = 7, 78%) and non-Hispanic (n = 8, 89%). Five (56%) had classic KS, one (11%) had HIV-associated KS, and three (33%) were HIV-negative men who have sex with men. Median time to resolution was 30.5 weeks, with a median of two treatments. In our study, 93% (n = 42/45) of lesions and 89% (n = 8/9) of patients experienced complete resolution during a median (range) duration of follow-up of 58 (13-209) weeks. Side effects were limited to pain during cryotherapy, occasional blister formation after cryotherapy, and mild inflammation due to imiquimod. No infections were observed. Combination therapy of cryotherapy and topical imiquimod may be an efficacious and comparatively low-risk treatment for limited, cutaneous KS.
Assuntos
Infecções por HIV , Sarcoma de Kaposi , Minorias Sexuais e de Gênero , Neoplasias Cutâneas , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Imiquimode/uso terapêutico , Sarcoma de Kaposi/tratamento farmacológico , Homossexualidade Masculina , Crioterapia , Imunoterapia , Infecções por HIV/terapiaRESUMO
It is unclear why some melanomas aggressively metastasize while others remain indolent. Available studies employing multi-omic profiling of melanomas are based on large primary or metastatic tumors. We examine the genomic landscape of early-stage melanomas diagnosed prior to the modern era of immunological treatments. Untreated cases with Stage II/III cutaneous melanoma were identified from institutions throughout the United States, Australia and Spain. FFPE tumor sections were profiled for mutation, methylation and microRNAs. Preliminary results from mutation profiling and clinical pathologic correlates show the distribution of four driver mutation sub-types: 31% BRAF; 18% NRAS; 21% NF1; 26% Triple Wild Type. BRAF mutant tumors had younger age at diagnosis, more associated nevi, more tumor infiltrating lymphocytes, and fewer thick tumors although at generally more advanced stage. NF1 mutant tumors were frequent on the head/neck in older patients with severe solar elastosis, thicker tumors but in earlier stages. Triple Wild Type tumors were predominantly male, frequently on the leg, with more perineural invasion. Mutations in TERT, TP53, CDKN2A and ARID2 were observed often, with TP53 mutations occurring particularly frequently in the NF1 sub-type. The InterMEL study will provide the most extensive multi-omic profiling of early-stage melanoma to date. Initial results demonstrate a nuanced understanding of the mutational and clinicopathological landscape of these early-stage tumors.
Assuntos
Melanoma , MicroRNAs , Neoplasias Cutâneas , Humanos , Masculino , Idoso , Feminino , Melanoma/patologia , Neoplasias Cutâneas/tratamento farmacológico , Proteínas Proto-Oncogênicas B-raf/genética , Mutação/genética , Melanoma Maligno CutâneoAssuntos
Exantema , Mieloma Múltiplo , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/uso terapêutico , Exantema/tratamento farmacológico , Exantema/etiologia , Humanos , Lenalidomida/efeitos adversos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológicoRESUMO
Oncogenic alterations to DNA are not transforming in all cellular contexts1,2. This may be due to pre-existing transcriptional programmes in the cell of origin. Here we define anatomic position as a major determinant of why cells respond to specific oncogenes. Cutaneous melanoma arises throughout the body, whereas the acral subtype arises on the palms of the hands, soles of the feet or under the nails3. We sequenced the DNA of cutaneous and acral melanomas from a large cohort of human patients and found a specific enrichment for BRAF mutations in cutaneous melanoma and enrichment for CRKL amplifications in acral melanoma. We modelled these changes in transgenic zebrafish models and found that CRKL-driven tumours formed predominantly in the fins of the fish. The fins are the evolutionary precursors to tetrapod limbs, indicating that melanocytes in these acral locations may be uniquely susceptible to CRKL. RNA profiling of these fin and limb melanocytes, when compared with body melanocytes, revealed a positional identity gene programme typified by posterior HOX13 genes. This positional gene programme synergized with CRKL to amplify insulin-like growth factor (IGF) signalling and drive tumours at acral sites. Abrogation of this CRKL-driven programme eliminated the anatomic specificity of acral melanoma. These data suggest that the anatomic position of the cell of origin endows it with a unique transcriptional state that makes it susceptible to only certain oncogenic insults.
Assuntos
Melanoma , Neoplasias Cutâneas , Animais , Animais Geneticamente Modificados , Carcinogênese/genética , Pé , Mãos , Humanos , Melanoma/patologia , Unhas , Oncogenes/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Transcrição Gênica , Peixe-Zebra/genética , Melanoma Maligno CutâneoRESUMO
Importance: Severe pain on awakening (POA) and emergence delirium (ED) are common following pediatric adenotonsillectomy. Effective preventive interventions are lacking. Objective: To determine the effects of intraoperative auditory stimulation on reduction of POA and ED after pediatric adenotonsillectomy. Design, Setting, and Participants: Single-center, double-blinded, 4-armed, randomized clinical trial of children undergoing adenotonsillectomy from March 2018 to May 2019 at a tertiary care pediatric referral center. Interventions: Children were randomized to 1 of the following groups: auditory stimulation with music, auditory stimulation with noise, ambient noise insulation with masking earplugs, and a control group receiving no intervention. Ear inserts were placed in the operating room once general anesthesia was administered. Stimulation parameters were based on the preoperative audiological evaluation and the appropriate fitting of the transduction system, including ambient noise level monitoring. Main Outcomes and Measures: The primary outcome was POA levels measured on 10-point scales according to age-appropriate validated tools. The secondary outcome was ED levels assessed according to the Pediatric Anesthesia Emergence Delirium 20-point scale. Results: A total of 104 consecutive healthy children (median [interquartile range] age at surgery, 5.0 [3.8-6.4] years) were included in the analysis. Music had a large effect size on POA (0.63; 98% CI, 0.43-0.84) and a medium effect size on ED (0.47; 98% CI, 0.21-0.75), while noise had a medium effect size on POA (0.47; 98% CI, 0.22-0.73) and a large effect size on ED (0.63; 98% CI, 0.44-0.85) compared with controls. The earplugs group showed a small effect size on POA and ED. Considering a clinically meaningful threshold of greater than 4 for POA and 10 or greater for ED at dichotomized analysis, a large effect size was achieved by music (1.39; odds ratio [OR], 0.08; 98% CI, 0.02-0.29; and 0.84; OR, 0.22; 98% CI, 0.06-0.75, respectively) and noise (0.97; OR, 0.17; 98% CI, 0.05-0.6; and 1.48; OR, 0.07; 98% CI, 0.02-0.26, respectively), while earplugs resulted in a small effect size. Conclusions and Relevance: In this randomized clinical trial, children undergoing adenotonsillectomy who received intraoperative auditory stimulation demonstrated a clinically meaningful decrease in POA and ED in the immediate postoperative period. Further research is needed to assess whether intraoperative auditory stimulation may decrease POA and ED in children undergoing other types of surgical procedures. Trial Registration: ClinicalTrials.gov Identifier: NCT04112979.
Assuntos
Estimulação Acústica/métodos , Adenoidectomia , Cuidados Intraoperatórios/métodos , Manejo da Dor/métodos , Dor Pós-Operatória/prevenção & controle , Agitação Psicomotora/prevenção & controle , Tonsilectomia , Criança , Pré-Escolar , Dispositivos de Proteção das Orelhas , Feminino , Humanos , Masculino , Música , Ruído , Salas Cirúrgicas , Medição da DorRESUMO
PRAME (PReferentially expressed Antigen in MElanoma) is a melanoma-associated antigen expressed in cutaneous and ocular melanomas and some other malignant neoplasms, while its expression in normal tissue and benign tumors is limited. Detection of PRAME protein expression by immunohistochemistry in a cohort of 400 melanocytic tumors showed diffuse nuclear immunoreactivity for PRAME in most metastatic and primary melanomas. In contrast, most nevi were negative for PRAME or showed nondiffuse immunoreactivity. The difference in the extent of immunoreactivity for PRAME in unambiguous melanocytic tumors prompted the study of PRAME as an ancillary tool for evaluating melanocytic lesions in more challenging scenarios.
Assuntos
Melanoma , Neoplasias Cutâneas , Antígenos de Neoplasias , Humanos , Imuno-Histoquímica , Melanoma/diagnóstico , Neoplasias Cutâneas/diagnósticoRESUMO
Cancer-testis (CT) antigens were identified by their ability to elicit T- or B-cell immune responses in the autologous host. They are typically expressed in a wide variety of neoplasms and in normal adult tissues are restricted to testicular germ cells. PReferentially expressed Antigen of Melanoma (PRAME) is a member of the family of nonclassical CT antigens being expressed in a few other normal tissues besides testis. Interestingly, knowledge about the protein expression of many CT antigens is still incomplete due to the limited availability of reagents for their immunohistochemical detection. Here, we tested several commercially available serological reagents and identified a monoclonal antibody suitable for the immunohistochemical detection of PRAME in formalin-fixed paraffin-embedded specimens. We also tested a wide array of normal and neoplastic tissues. PRAME protein expression in normal tissues is congruent with original molecular data being present in the testis, and at low levels in the endometrium, adrenal cortex, and adult as well as fetal ovary. In tumors, there is diffuse PRAME immunoreactivity in most metastatic melanomas, myxoid liposarcomas, and synovial sarcomas. Other neoplasms such as seminomas and carcinomas of various origins including endometrial, serous ovarian, mammary ductal, lung, and renal showed an intermediate proportion of cases and variable extent of tumor cells positive for PRAME protein expression. As seen with other CT antigens, hepatocellular and colorectal carcinoma, Leydig cell tumors, mesothelioma, and leiomyosarcoma are poor expressers of PRAME.
Assuntos
Antígenos de Neoplasias/isolamento & purificação , Biomarcadores Tumorais/análise , Neoplasias/diagnóstico , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/metabolismo , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Imuno-Histoquímica/métodos , Masculino , Neoplasias/patologiaRESUMO
BACKGROUND: Extramammary Paget disease (EMPD) poses treatment challenges. Invasive and noninvasive treatment modalities exist with variable success reported. Reflectance confocal microscopy (RCM) is emerging as an adjuvant diagnostic tool. OBJECTIVE: To evaluate the treatment of EMPD patients and the role of RCM. METHODS: Prospective study. Demographic and tumor characteristics were recorded. Handheld-RCM was performed and correlated with histology. Treatment, clearance, pathology, and follow-up were all recorded. RESULTS: Thirty-six EMPD lesions in 33 patients were included. Mean age was 71.7 years, and 23 were men. Mean number of surgical stages needed to clear margins was 1.9 (SD, 0.9; 1.0-3.0 stages), and mean margin needed to clear was 1.8 cm. Reflectance confocal microscopy correlated well with scouting punch biopsies (kappa, 0.93; p < .001). Disruption of the dermoepidermal junction was associated with invasive EMPD versus in situ (83.3% vs 25.9%) on histology (p = .01). LIMITATIONS: Relatively small sample size. CONCLUSION: Extramammary Paget disease is challenging, and lesion demarcation is of the utmost importance. Using a staged surgical excision approach, the mean margins needed were 1.8 cm, less than previously reported. Nonsurgical modalities, including radiation therapy, imiquimod, or photodynamic therapy can be considered if surgery is not pursued. Reflectance confocal microscopy is a valuable noninvasive imaging modality for the management of EMPD.
Assuntos
Procedimentos Cirúrgicos Dermatológicos/métodos , Margens de Excisão , Microscopia Confocal/métodos , Doença de Paget Extramamária/cirurgia , Neoplasias Cutâneas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Paget Extramamária/diagnóstico , Estudos Prospectivos , Neoplasias Cutâneas/diagnósticoAssuntos
Infecções por Escherichia coli/imunologia , Hospedeiro Imunocomprometido , Malacoplasia/imunologia , Úlcera Cutânea/imunologia , Transplante de Células-Tronco/efeitos adversos , Idoso , Aloenxertos , Canal Anal/patologia , Infecções por Escherichia coli/patologia , Humanos , Malacoplasia/patologia , Masculino , Síndromes Mielodisplásicas/terapia , Úlcera Cutânea/patologia , TransplantadosRESUMO
A subset of Spitz tumors is associated with a copy number increase of chromosome 11p and activating mutations of HRAS. These aberrations have been reported to occur in association with desmoplastic Spitz nevi. Little is known to what extent 11p gains can also be found in nondesmoplastic tumors. To learn more about the spectrum of microscopic and cytogenetic changes that can be seen in Spitz lesions in association with 11p gains, we reviewed the clinical and pathologic features of 40 cases. Patient ages ranged from 3 to 75 years. The most common anatomic site was the head and neck region, followed by the upper extremities. Prominent desmoplasia was present in 10 cases. Seven tumors lacked significant stromal fibrosis. Twenty tumors were mitotically active. Novel microscopic features encountered in a few cases include a tumor with a polypoid silhouette and papillomatous surface and rare atypical tumors with a deep bulbous growth pattern. Among 36 cases analyzed by single-nucleotide polymorphism array or comparative genomic hybridization, 28 tumors had gains of the entire or near-entire p-arm of chromosome 11 with no other coexisting unbalanced genomic aberration. Eight cases had additional changes; 6 of these with 1 additional aberration per case, and 2 cases had several chromosomal aberrations. We also examined a subset of tumors by fluorescence in situ hybridization for the HRAS gene locus (11p15.5). All tumors were fluorescence in situ hybridization-positive. In conclusion, we expand the spectrum of pathologic findings associated with Spitz tumors with 11p gains. This cytogenetic aberration is not restricted to desmoplastic Spitz nevi. It can also be seen in nondesmoplastic and papillomatous lesions and atypical melanocytic tumors with a deep bulbous growth. We also document that in some Spitz tumors additional cytogenetic aberrations may be found, the significance of which remains to be determined.
Assuntos
Cromossomos Humanos Par 11/genética , Nevo de Células Epitelioides e Fusiformes/genética , Neoplasias Cutâneas/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Aberrações Cromossômicas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nevo de Células Epitelioides e Fusiformes/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Cutâneas/patologia , Adulto JovemRESUMO
To date, only twenty cases of cutaneous legionellosis have been reported. Cutaneous legionellosis has heterogeneous manifestations including abscesses, nodules, and cellulitis. The detection of most cutaneous Legionella species requires specific diagnostic cultures and assays. Herein, we report a case of cutaneous legionella in a hematopoietic cell transplantation recipient with culture-negative nodules unresponsive to empiric antibiotics. We also discuss the varied morphology of cutaneous legionellosis and important diagnostic considerations.