RESUMO
BACKGROUND: Although its clinical effect is reported to last up to 2 years, how long hyaluronic acid filler (HAF) histologically persists in the skin is unknown. OBJECTIVE: To determine the approximate persistence time of HAF in the skin and to correlate persistence time with HAF histological appearance, size, depth, and location. METHODS: Retrospective review of patient data and available frozen sections from 2003 to 2021 in which HAF was identified in 36 Mohs micrographic surgery patients. RESULTS: Incidental HAF histologically persisted in the skin for as long as 10.75 years in 1 patient and 3 years or more in 36.8% (7/19) of the patients who remembered the time of implantation. HAF is more apparent in frozen sections stained with toluidine blue than those stained with hematoxylin and eosin. Although HAF volume tended to be less with time, fragmentation was present both early at 3 months and at 3 years or more. There was no correlation of persistence time with anatomic location or depth. In 90.3% of the cases (28/31), HAF was located in the subcutaneous fat. There was no granulomatous or giant cell response at any time period. CONCLUSION: Hyaluronic acid filler may be seen histopathologically in the skin, usually in the subcutaneous fat, up to 10.75 years after implantation.
Assuntos
Ácido Hialurônico , Neoplasias Cutâneas , Secções Congeladas , Humanos , Cirurgia de Mohs , Pele/patologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgiaRESUMO
IMPORTANCE: Apart from the atypical mole phenotype, development of new melanocytic nevi in older individuals is uncommon and considered worrisome for melanoma. We performed a retrospective case series in a Veterans Affairs population from 1991 to 2013 to characterize blue nevi (BN) by patient age at biopsy, location, self-reported duration, and relation to prior or subsequent development of cutaneous melanoma. OBSERVATIONS: A total of 204 BN were identified in 194 predominantly male patients (90.7%) who had a mean (SD) age of 62.8 (14.4) years. Clinical duration of 10 years or less was reported by 90.3% of patients with available data (32.0%). Histopathologic examination classified 74.0% of BN as common, 1.5% as cellular, and 24.5% as combined type. No malignant BN were identified; however, 18 primary melanomas were diagnosed, most (72.2%) prior to blue nevus biopsy, including 38.9% in situ and 61.1% with mean (SD) Breslow thickness of 1.02 (0.99) mm. CONCLUSIONS AND RELEVANCE: The later patient-reported onset of BN suggests a potential alternative mechanism of nevogenesis compared with common acquired nevi and differs from prior reports of BN development in younger adults. The lack of association with melanoma in older individuals suggests that most benign-appearing BN may be safely observed, even in a cohort at higher risk for skin cancer.
Assuntos
Melanoma/patologia , Nevo Azul/patologia , Neoplasias Cutâneas/patologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Transformação Celular Neoplásica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Estados Unidos , United States Department of Veterans AffairsRESUMO
OBJECTIVE: To provide an updated and expanded analysis of clinical outcome and immunohistochemical (IHC) findings unique to primary dermal melanoma (PDM) that may be used to differentiate this entity from primary nodular melanoma (PNM) and cutaneous metastatic melanoma (MM). DESIGN: Cohort analysis and extensive IHC panel comparing PDM with PNM and cutaneous MM. SETTING: Melanoma clinics and pathology departments of academic and VA medical centers. PATIENTS: Thirteen patients with a solitary dermal or subcutaneous nodule of histologically proven melanoma, prospectively followed through April 30, 2007. INTERVENTIONS: Clinical, pathologic, and IHC assessment of patients diagnosed as having PDM. MAIN OUTCOME MEASURES: Long-term clinical outcome and determination of unique clinical and IHC features in the study cohort compared with other melanoma subtypes. RESULTS: Histologically, there was no evidence of an overlying in situ component, ulceration, or regression, and there was no associated nevus in any cases. Clinical history and findings from workup, including imaging studies, skin examination, and sentinel lymph node biopsy, were negative for evidence of melanoma elsewhere. The mean Breslow depth was 9.6 mm. Two patients developed satellite or in-transit recurrences, 1 developed pulmonary metastasis, and another died of liver metastases. Overall, the cohort showed a 92% melanoma-specific survival rate at a mean duration of follow-up of 44 months. The IHC findings showed that PDM exhibited lower levels of staining for the antigens p53 (P = .02), Ki-67 (Mib-1) (P = .002), cyclin D1 (P = .001), and podoplanin (recognized by D2-40 antibody) lymphovascular staining (P <.001) compared with MM and PNM. All other markers were comparable. CONCLUSIONS: Patients with PDM have remarkably prolonged survival compared with patients with MM or PNM of similar thickness. Preliminary results suggest that PDM may be characterized by lower levels of p53, Ki-67, cyclin D1, and D2-40 compared with histologically similar MM and PNM.
Assuntos
Derme/patologia , Melanoma/patologia , Melanoma/secundário , Neoplasias Cutâneas/patologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Masculino , Melanoma/mortalidade , Melanoma/terapia , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Medição de Risco , Distribuição por Sexo , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/terapia , Tela Subcutânea/patologia , Análise de SobrevidaRESUMO
BACKGROUND: Sebaceous carcinoma (SC) most commonly presents on the eyelid and is frequently misdiagnosed both clinically and pathologically. Only very rare cases of desmoplastic tricholemmoma (DTL) of the eyelid have been reported. METHODS: We present a case of DTL of the eyelid initially misdiagnosed as an invasive SC. RESULTS: A 55-year-old man presented with a rapidly growing 5 mm erythematous lesion on his upper eyelid. Histologic examination showed a lobular, folliculocentric proliferation of palely eosinophilic to clear cells surrounded by peripheral basal cells with palisading. The central portion of the lesion appeared infiltrative with clear cells surrounded by a thickened basement embedded in a dense, collagenous stroma. However, the cells showed mostly uniform cytoplasmic clearing, lacking the multivacuolization or nuclear scalloping of sebocytes. In addition, a periodic acid Schiff stain was positive with diastase sensitivity, indicating cytoplasmic glycogen, not lipid. CD34 immunohistochemical staining was also positive, which has been reported in DTL but not in SC. CONCLUSIONS: SC is often misdiagnosed as other entities, but misidentification of other neoplasms as SC is less common; however, this is an important diagnostic pitfall, as it may result in unnecessary and disfiguring surgical treatment and consequent medical-legal liability. Therefore, DTL should enter the differential diagnosis of clear-cell neoplasms on the eyelid.
Assuntos
Adenocarcinoma Sebáceo/diagnóstico , Neoplasias Palpebrais/diagnóstico , Doenças do Cabelo/diagnóstico , Folículo Piloso/patologia , Neoplasias Cutâneas/diagnóstico , Antígenos CD34/metabolismo , Biomarcadores Tumorais/metabolismo , Diagnóstico Diferencial , Neoplasias Palpebrais/metabolismo , Neoplasias Palpebrais/cirurgia , Glicogênio/metabolismo , Doenças do Cabelo/metabolismo , Doenças do Cabelo/cirurgia , Folículo Piloso/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/cirurgiaRESUMO
Relapsing fever (RF) is a multisystemic borrelial infection with frequent neurologic involvement referred to as neuroborreliosis. The absence of an effective antibody response results in persistent infection. To study the consequences to the brain of persistent infection with the RF spirochete Borrelia turicatae, we studied B cell (Igh6-/-) and B and T (Rag1-/-) cell-deficient mice inoculated with isogenic serotypes 1 (Bt1) or 2 (Bt2). We found that Bt1 was more tissue tropic than Bt2, not only for brain but also for heart. Igh6-/- mice developed more severe clinical disease than Rag1-/- mice. Bt1-infected brains had widespread microgliosis/brain macrophage activation despite localization of spirochetes in the leptomeninges rather than the brain parenchyma itself. Oligoarray analysis revealed that CXCL13 was the most upregulated gene in the brain of Bt1-infected Igh6-/- mice. CXCL13 was also the most abundant of the chemokines we measured in infected blood. Persistent infection did not result in injury to the brain. Treatment with exogenous interleukin-10 reduced microgliosis in the brain and production of CXCL13 in the blood. We concluded that brain involvement in B cell-deficient mice persistently infected with B. turicatae is characterized by prominent microgliosis and production of CXCL13 without detectable injury.
Assuntos
Infecções por Borrelia/metabolismo , Borrelia , Encéfalo/metabolismo , Quimiocinas CXC/metabolismo , Febre Recorrente/metabolismo , Febre Recorrente/patologia , Animais , Linfócitos B/fisiologia , Borrelia/classificação , Infecções por Borrelia/microbiologia , Infecções por Borrelia/patologia , Encéfalo/microbiologia , Quimiocina CXCL13 , Ensaio de Imunoadsorção Enzimática/métodos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Coração/microbiologia , Interleucina-10/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Análise de Sequência com Séries de Oligonucleotídeos/métodos , RNA Mensageiro/biossíntese , Febre Recorrente/microbiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Estatísticas não ParamétricasRESUMO
Sebaceous lesions, including sebaceous hyperplasia, sebaceomas, and sebaceous adenomas and carcinomas, are histologically distinctive adnexal proliferations with a spectrum of biological behavior ranging from benign to frankly malignant. The histologic distinction between sebaceous adenomas and carcinomas may be challenging, especially in cases showing atypical features and in small or partial biopsies. We studied multiple oncogenic and therapeutic related proteins by immunohistochemistry to identify differences in expression between benign and malignant sebaceous proliferations. A total of 27 cases, including 9 sebaceous adenomas, 4 sebaceomas, 8 sebaceous carcinomas, and 6 cases of sebaceous hyperplasia, were examined by immunohistochemistry, with antibodies directed against Ki-67 (MIB-1), bcl-2, p53, p21WAF1, p27Kip1, c-erbB-2 (Her-2/neu), CD117 (c-kit), cyclin D1, MDM2, CD99, MLH-1, and MSH-2. We found that sebaceous adenomas and sebaceomas stained like sebaceous hyperplasia did, whereas carcinomas had statistically significantly increased levels of p53 (50% versus 11%, respectively) and Ki-67 (30% versus 10%). The carcinomas also had significantly reduced levels of bcl-2 (7% versus 56%, respectively) and p21 (16% versus 34%) compared to the adenomas. Thus, a combination of several of these markers may be diagnostically useful in challenging cases. In addition, we found little or no Her-2/neu and CD117 staining, indicating that immunotherapy with Herceptin or Gleevac would likely not be useful for sebaceous carcinomas. Moreover, these results show that sebaceous adenomas and carcinomas are distinct neoplasms and provide no support for the theory that all sebaceous adenomas are truly malignant.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias Faciais/química , Neoplasias das Glândulas Sebáceas/química , Glândulas Sebáceas/química , Adenocarcinoma Sebáceo/química , Adenoma/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidor de Quinase Dependente de Ciclina p21/análise , Neoplasias Faciais/diagnóstico , Feminino , Humanos , Hiperplasia , Imuno-Histoquímica , Antígeno Ki-67/análise , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/análise , Receptor ErbB-2/análise , Neoplasias das Glândulas Sebáceas/diagnóstico , Glândulas Sebáceas/patologia , Proteína Supressora de Tumor p53/análiseRESUMO
The spirochete Borrelia burgdorferi is the agent of Lyme disease, which causes central nervous system manifestations in up to 20% of patients. We investigated the response of human brain microglial cells, glial progenitors, neurons, astrocytes, as well as peripheral blood monocytes to stimulation with B. burgdorferi. We used oligoarrays to detect changes in the expression of genes important for shaping adaptive and innate immune responses. We found that stimulation with B. burgdorferi lysate increased the expression of Toll-like receptors (TLRs) 1 and 2 in all cell types except neurons. However, despite similarities in global gene profiles of monocytes and microglia, only microglial cells responded to the stimulation with a robust increase in HLA-DR, HLA-DQ, and also coexpressed CD11-c, a dendritic cell marker. In contrast, a large number of HLA-related molecules were repressed at both the RNA and the protein levels in stimulated monocytes, whereas secretion of IL-10 and TNF-alpha was strongly induced. These results show that signaling through TLR1/2 in response to B. burgdorferi can elicit opposite immunoregulatory effects in blood and in brain immune cells, which could play a role in the different susceptibility of these compartments to infection.
Assuntos
Borrelia burgdorferi/fisiologia , Regulação da Expressão Gênica/fisiologia , Antígenos de Histocompatibilidade Classe II/metabolismo , Microglia/metabolismo , Monócitos/metabolismo , Receptor 1 Toll-Like/metabolismo , Receptor 2 Toll-Like/metabolismo , Encéfalo/citologia , Células Cultivadas , Citocinas/metabolismo , Feto , Citometria de Fluxo/métodos , Expressão Gênica/fisiologia , Antígenos de Histocompatibilidade Classe II/genética , Humanos , Microglia/microbiologia , Monócitos/microbiologia , Neurônios/metabolismo , Neurônios/microbiologia , Análise de Sequência com Séries de Oligonucleotídeos/métodos , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Receptor 1 Toll-Like/genética , Receptor 2 Toll-Like/genéticaRESUMO
Toll-like receptors (TLRs) trigger innate immune responses via the recognition of conserved pathogen-associated molecular patterns. Lipoproteins from Borrelia burgdorferi, the agent of Lyme disease, activate inflammatory cells through TLR2 and TLR1. We show that stimulation of human monocytes with B. burgdorferi lysate, lipidated outer surface protein A, and triacylated lipopeptide Pam3CysSerLys4 results in the up-regulation of both TLR2 and TLR1 but the down-regulation of TLR5, the receptor for bacterial flagellin, and that this effect is mediated via TLR2. TLR4 stimulation had no effect on TLR2, TLR1, and TLR5 expression. Human monocytes stimulated with TLR5 ligands (including p37 or flaA, the minor protein from B. burgdorferi flagella) up-regulated TLR5. In addition, TLR2 stimulation rendered cells hyporesponsive to a TLR5 agonist. These results indicate that diverse stimuli can cause differential TLR expression, and we hypothesize that these changes may be useful for either the pathogen and/or the host.