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1.
Dermatology ; 240(3): 487-493, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38228098

RESUMO

INTRODUCTION: Dermatofibrosarcoma protuberans (DFSP) is the most common sarcoma of the skin. Although distant metastases are infrequent, DFSP is highly aggressive locally with frequent local recurrences. It has been reported that the presence within the tumour of areas histopathologically mimicking fibrosarcoma may increase the risk of recurrence. OBJECTIVE: The objective of this study was to review the clinical features of our patients with DFSP and the factors associated with recurrence of the tumour, focussing on the presence of fibrosarcomatous areas. METHODS: Retrospective study of patients with DFSP diagnosed in 1990-2021 in a tertiary university hospital. The medical records were reviewed to obtain the following data: age, sex, tumour location, diameter, evolution time, presence of fibrosarcomatous areas, development of recurrence, and follow-up. Factors possibly associated with disease-free survival were analysed with Kaplan-Meier method and multivariate Cox regression. RESULTS: 148 patients (74 women/74 men, mean age 46.28 years, SD 14.431) were included in the study. Tumours involved the head and neck in 15 cases, thorax in 31, abdomen in 16, upper back in 43, lower back in 10, upper extremities in 10, and lower extremities in 23. Fibrosarcoma-like areas were observed in 16 tumours (10.81%). In 17 patients (11.49%), recurrences were observed (13 local recurrences, 3 lung metastasis, and 1 local recurrence with lung metastasis). Fibrosarcomatous DFSP recurred more frequently than classic DFSP (50% vs. 6.82%, respectively), and its disease-free survival was significantly lower (p < 0.001). In multivariate Cox regression, the presence of fibrosarcomatous areas was the only factor influencing disease-free survival. CONCLUSIONS: It is important to identify the fibrosarcomatous variant since it recurs more frequently and has lower recurrence-free survival. Distant metastases, mainly in the lung, are also more frequent in fibrosarcomatous DFSP.


Assuntos
Dermatofibrossarcoma , Recidiva Local de Neoplasia , Neoplasias Cutâneas , Humanos , Dermatofibrossarcoma/patologia , Dermatofibrossarcoma/mortalidade , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/terapia , Recidiva Local de Neoplasia/patologia , Idoso , Intervalo Livre de Doença , Adulto Jovem , Fibrossarcoma/patologia , Fibrossarcoma/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/mortalidade , Adolescente
2.
Dermatology ; 240(1): 164-169, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37918362

RESUMO

BACKGROUND: Subungual melanoma (SM) is an unusual type of melanocytic tumor affecting the nail apparatus. The mutational prevalence of the most prominently mutated genes in melanoma has been reported in small cohorts of SM, with unclear conclusions on whether SM is different from the rest of melanomas arising in acral locations or not. Hence, the molecular profile of a large series of SM is yet to be described. OBJECTIVES: The aim of this study was to describe the molecular characteristics of a large series of SM and their association with demographic and histopathological features. METHODS: Patients diagnosed with SM between 2001 and 2021 were identified from six Spanish and Italian healthcare centers. The mutational status for BRAF, NRAS, KIT, and the promoter region of TERT (TERTp) were determined either by Sanger sequencing or next-generation sequencing. Clinical data were retrieved from the hospital databases to elucidate potential associations. RESULTS: A total of 68 SM cases were included. Mutations were most common in BRAF (10.3%) and KIT (10%), followed by NRAS (7.6%), and TERTp (3.8%). Their prevalence was similar to that of non-subungual acral melanoma but higher in SM located on the hand than on the foot. CONCLUSIONS: To date, this study represents the largest cohort of SM patients with data on the known driver gene mutations. The low mutation rate supports a different etiopathogenic mechanism for SM in comparison of non-acral cutaneous melanoma, particularly for SM of the foot.


Assuntos
Melanoma , Doenças da Unha , Neoplasias Cutâneas , Telomerase , Humanos , Melanoma/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/diagnóstico , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-kit/genética , Regiões Promotoras Genéticas/genética , Mutação , Doenças da Unha/genética , Análise Mutacional de DNA , Telomerase/genética , Proteínas de Membrana/genética , GTP Fosfo-Hidrolases/genética
3.
Dermatology ; 238(3): 587-593, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34569484

RESUMO

BACKGROUND: Cutaneous leiomyoma (CL) is a benign smooth muscle tumour included in painful skin tumours. Multiple CLs are cutaneous markers of hereditary leiomyomatosis and renal cell cancer (HLRCC). OBJECTIVES: To retrospectively review our series of patients with CLs to analyse their clinical features and the association with HLRCC. METHODS: Cases coded as CL in the database of the pathology department between 2004 and 2019 were included in the study. Medical records were retrospectively reviewed to obtain the following data: age, sex, location, number of lesions, diameter, evolution time at diagnosis, suspected clinical diagnosis, tenderness, status of resection margins, development of recurrence, follow-up time, and association with HLRCC. RESULTS: 152 patients had CLs, 89 women and 63 men, mean age 56.26, SD 16.030 years. Subtypes were piloleiomyoma in 62 patients, angioleiomyoma in 80, and genital leiomyoma in 10. All of our 11 patients with multiple lesions corresponded to piloleiomyomas, and HLRCC was confirmed in 8 of them (73%). Patients with HLRCC were younger than patients with piloleiomyomas without HLRCC (34.88 vs. 56.17 years, p = 0.009). Vascular and genital leiomyomyomas were solitary and were not associated with HLRCC. CONCLUSION: In patients with multiple piloleiomyomas HLRCC must be ruled out as it is confirmed in a high proportion of cases. The probability of fumarate hydratase mutation is greater in multiple piloleiomyomas involving both the trunk and upper extremities in the same patient.


Assuntos
Neoplasias Renais , Leiomiomatose , Síndromes Neoplásicas Hereditárias , Neoplasias Cutâneas , Feminino , Fumarato Hidratase/genética , Humanos , Neoplasias Renais/genética , Leiomiomatose/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Neoplasias Uterinas
4.
Am J Dermatopathol ; 43(12): 980-983, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34783704

RESUMO

ABSTRACT: Sarcoidosis induced by anti-PD1 or anti-PDL1 agents such as atezolizumab has recently been reported. It has been suggested that the predilection of sarcoidosis to affect scars is due to the presence of antigens or foreign bodies that can serve as a stimulus for granuloma formation. However, to the best of our knowledge, sarcoidosis-specific skin lesions have not to date been reported involving xanthelasma. We report a patient who developed specific lesions of sarcoidosis infiltrating some xanthelasmata 6 months after starting treatment with atezolizumab. A 69-year-old woman was referred to the dermatology department for infiltration of xanthelasmata. The patient was being treated with atezolizumab for metastatic uterine carcinosarcoma. Cutaneous biopsy from an infiltrated xanthelasma and from still yellow, no infiltrated xanthelasma showed differing proportions of foamy histiocytes and sarcoid granulomas. On physical examination, erythemato-marronaceous papules clustered on both knees, and not previously detected by the patient, were observed. The biopsy showed sarcoid dermal granulomas with foreign bodies. A chest computerized tomography scan was consistent with intrathoracic involvement of sarcoidosis. Endobronchial ultrasound-guided transbronchial needle aspiration of a mediastinal lymphadenopathy showed epithelioid cell granulomas. Histopathologically, the foamy histiocytes of xanthelasma seem to be replaced by or evolve to epithelioid cells to form sarcoid granulomas. The possible pathogenic mechanism is discussed. Dermatologists and dermatopathologists should bear in mind that sarcoidosis can present as infiltration of pre-existing xanthelasmata.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/efeitos adversos , Sarcoidose/induzido quimicamente , Sarcoidose/patologia , Idoso , Carcinossarcoma/tratamento farmacológico , Feminino , Humanos , Neoplasias Uterinas/tratamento farmacológico , Xantomatose/patologia
5.
Am J Dermatopathol ; 42(4): 233-243, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32205511

RESUMO

Only a few series of patients with systemic sarcoidosis and specific subcutaneous lesions have been reported. We reviewed our patients with systemic sarcoidosis with specific subcutaneous lesions to analyze their histopathological features and their relationship with clinical features of the systemic disease. Patients with systemic sarcoidosis with predominantly subcutaneous sarcoid granulomas diagnosed between 1980 and 2016 in Bellvitge University Hospital were enrolled. We also analyzed patients with clinically and histopathologically identical lesions in whom a diagnosis of systemic sarcoidosis could not be made during follow-up. Twenty-eight patients with systemic sarcoidosis presented specific subcutaneous lesions (23 women and 5 men, mean age 55.64 SD 12.26 years). Dermal involvement was observed in 10 cases, always discrete and limited to deep reticular dermis. The distribution of the granulomatous infiltrate was lobular in 7 cases and lobular and septal in 21. Fibrosis was observed in 21 cases. There were no significant differences in persistence of lesions or persistence of systemic disease activity when comparing patients with and without fibrosis. In conclusion, fibrosis is a frequent finding in subcutaneous sarcoidosis, and although it may be intense, it is not associated with pulmonary fibrosis or with >2 years of persistence of systemic sarcoidosis activity.


Assuntos
Sarcoidose/patologia , Tela Subcutânea/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fibrose/patologia , Humanos , Masculino , Pessoa de Meia-Idade
6.
Am J Dermatopathol ; 40(5): 362-366, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28731867

RESUMO

It has been suggested that the predilection of sarcoidosis to affect scars is due to the presence of antigens or foreign bodies that can serve as a stimulus for granuloma formation. Several patients with sarcoidosis-specific skin lesions in venous puncture sites have been reported. However, in these patients the pathogenesis of the cutaneous lesions is not clear because the presence of foreign bodies is not to be expected. Our objective was to describe 3 patients who developed specific lesions of sarcoidosis in areas of venipuncture and to discuss their possible pathogenesis. The database of the Sarcoid Clinic of Bellvitge Hospital (an 800-bed university referral center providing tertiary care to approximately 1 million people in Barcelona, Spain) was reviewed to detect those patients with specific cutaneous lesions of systemic sarcoidosis in areas of venipuncture. Three patients with biopsy-proven specific cutaneous lesions of systemic sarcoidosis in areas of venipuncture for blood collection were detected (3 women, mean age 56 years). In one case, the histopathological image shows the hypothetical path of a needle through the skin. In 2 cases, an amorphous birefringent material was detected under polarized light. This material was consistent with silicone. In patients who are developing sarcoidosis, the smallest amount of oil used as lubricant in the needle for sample blood collection may induce the formation of granulomas. In addition to exploring scars, it is advisable to explore the cubital folds to detect specific cutaneous lesions of sarcoidosis.


Assuntos
Lubrificantes/efeitos adversos , Flebotomia/efeitos adversos , Sarcoidose/etiologia , Silicones/efeitos adversos , Dermatopatias/etiologia , Feminino , Granuloma/etiologia , Humanos , Pessoa de Meia-Idade
7.
Histopathology ; 69(6): 1077-1081, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27380612

RESUMO

AIMS: Many types of intravascular lymphohistiocytic proliferation have been described recently; this was previously an unnoticed or misinterpreted phenomenon. Intralymphatic lymphohistiocytic aggregates are relatively common, and include benign, malignant and indeterminate conditions. In contrast, all non-endothelial proliferations in the lumina of blood vessels have been interpreted so far as malignant. Herein, we present three cases of histiocytic proliferations in the lumen of blood vessels associated with intracytoplasmic granulocyte debris (haemophagocytosis), a previously undescribed entity. METHODS AND RESULTS: We identified three patients from two institutions with similar cutaneous lesions, both clinically and microscopically. Information regarding clinical history, histological features and immunoprofiles were obtained. The three cases presented intravascular histiocytosis with haemophagocytosis involving blood vessels of the dermis, a process that may be representative of a new entity. The patients were two women and one man who presented a symmetrical reticulated erythema with a tendency to involve the skin of the breasts. The lesions were indolent, did not ulcerate and followed a benign course. CONCLUSION: This seemingly novel condition is characterized by the presence of histiocytic cells inside blood vessels, where they have not been described previously as an entity. The most reasonable explanation for this process is an origin from the non-classical subset of monocytes that 'patrol' the inner face of blood vessels acting as macrophages. The existence of this entity should be kept in mind to avoid overdiagnosis of malignancy.


Assuntos
Vasos Sanguíneos/patologia , Linfo-Histiocitose Hemofagocítica/patologia , Adulto , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
8.
Am J Dermatopathol ; 38(3): 194-200, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26894770

RESUMO

Orofacial granulomatosis (OFG) is characterized by granulomatous inflammation in the orofacial region. Although several series have been reported, biopsy has not been performed in all cases and the histopathological features have not been extensively evaluated. Our purpose was to analyze the histopathological features of our patients with OFG. Twenty-two patients diagnosed with OFG at Bellvitge Hospital (Barcelona, Spain) from 1985 to 2010 were included in the study. All of our patients (14 men and 8 women; mean age 46.77 years, SD 13.61) presented with labial swelling, involving the upper lip in 13 cases and the lower lip in 9 at presentation. Fissured tongue was observed in 9 cases. Three patients suffered facial palsy. Granulomas were observed in 16 patients. All patients showed a perivascular, lymphohistiocytic inflammatory infiltrate with prominent plasma cells in 21 cases. In 5 cases, mast cells were easily observed. In 13 patients, an interstitial infiltrate was also present. All cases showed dilated lymphatic channels, and 19 edema of the lamina propria or the dermis. Perilymphatic granulomas were observed in 12 cases, intralymphatic granulomas in 2, and intralymphatic histiocytes in 2. In conclusion, loose epithelioid cells or lymphonodular granulomas were observed in 73% of our patients. Although none of our patients developed Crohn disease, OFG is histopathologically similar to cutaneous lesions of Crohn disease. The perilymphatic disposition of granulomas and the presence in some cases of intralymphatic histiocytes or intralymphatic granulomas may explain the dilatation of lymphatic vessels and the development of edema.


Assuntos
Granulomatose Orofacial/patologia , Adulto , Idoso , Feminino , Humanos , Lábio/patologia , Masculino , Pessoa de Meia-Idade , Língua/patologia , Adulto Jovem
9.
Lung ; 193(3): 335-43, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25794567

RESUMO

PURPOSE: Fibronectin (Fn) and tenascin-C (TnC) are two extracellular matrix proteins associated with remodeling changes. Fn and TnC gene and protein expression in lung tissue, including their predominant location in bronchial and pulmonary artery structures, have not yet been fully evaluated. The aim of the present study was to assess: (1) gene expression of Fn and TnC in lung samples from chronic obstructive pulmonary disease (COPD) and non-COPD subjects; and (2) protein content and location of Fn and TnC in both groups. METHODS: Consecutive subjects requiring lung resection due to lung cancer surgery were included. Lung specimens were examined for gene expression by quantitative real-time PCR (values expressed as fold change ratio). The analysis of their protein content and location was performed by western blot and immunohistochemical studies, respectively. Patients were divided into two cohorts according to COPD status. RESULTS: A total of 41 patients (20 with COPD and 21 without COPD) were included. An enhanced Fn gene expression was observed in the COPD group compared to the non-COPD group (4.73 ± 0.54 vs. 2.65 ± 0.57; P = 0.012), whereas no differences in gene TnC expression were observed (2.91 ± 0.44 vs. 2.60 ± 0.48; P = 0.633). No differences in lung protein content and location were found between groups. Immunohistochemical evaluation showed a predominantly vascular and bronchial location of Fn and TnC in both groups. CONCLUSIONS: An enhanced lung gene expression of Fn was observed in COPD subjects compared to non-COPD subjects. No differences were found in Fn protein expression or in TnC gene or protein expression among groups.


Assuntos
Fibronectinas/análise , Fibronectinas/genética , Pulmão/química , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/metabolismo , Tenascina/análise , Tenascina/genética , Idoso , Remodelação das Vias Aéreas , Western Blotting , Estudos de Casos e Controles , Feminino , Regulação da Expressão Gênica , Humanos , Imuno-Histoquímica , Pulmão/fisiopatologia , Pulmão/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/cirurgia , Reação em Cadeia da Polimerase em Tempo Real , Índice de Gravidade de Doença
10.
Dermatology ; 229(3): 205-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25278300

RESUMO

BACKGROUND: There are few studies focusing on the clinical characteristics of Merkel cell carcinoma (MCC). OBJECTIVE: To retrospectively analyze the clinical features of our patients and their relationship with sun exposure. METHODS: Thirty-six patients diagnosed with MCC (20 men and 16 women, mean age 72.08 years) were included in the study. RESULTS: 21 patients developed MCC in sun-exposed skin and 15 patients in non-sun-exposed areas. MCC was >2 cm in 19 cases. Six of the 7 patients who died as a result of MCC had non-sun-exposed tumors. Only tumor size >2 cm significantly influenced survival (p = 0.033). CONCLUSION: Sun-exposed lesions tended to be <2 cm in diameter and were more common in men, while non-sun-exposed tumors were larger, usually occurring in women and carrying a greater likelihood of death by MCC. Non-sun-exposed tumors usually present as fast-growing, multilobar nodular lesions with a smooth shiny surface.


Assuntos
Carcinoma de Célula de Merkel/mortalidade , Carcinoma de Célula de Merkel/patologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Luz Solar/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Carcinoma de Célula de Merkel/cirurgia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Hospitais Universitários , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Medição de Risco , Neoplasias Cutâneas/cirurgia , Espanha , Análise de Sobrevida , Resultado do Tratamento
11.
BMC Pulm Med ; 14: 120, 2014 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-25064447

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive parenchymal lung disease of unknown aetiology and poor prognosis, characterized by altered tissue repair and fibrosis. The extracellular matrix (ECM) is a critical component in regulating cellular homeostasis and appropriate wound healing. The aim of our study was to determine the expression profile of highlighted ECM proteins in IPF lungs. METHODS: ECM gene and protein expression was analyzed by cDNA microarrays, rt-PCR, immunohistochemistry and western-blot in lungs from idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP), categorized as chronic (cHP) and subacute (saHP), and healthy lung tissue. Primary fibroblast cultures from normal subjects and fibrotic patients were studied to evaluate tenascin-C (TNC) synthesis. RESULTS: A total of 20 ECM proteins were upregulated and 6 proteins downregulated in IPF. TNC was almost undetected in normal lungs and significantly upregulated in fibrotic lungs (IPF and cHP) compared to saHP. Furthermore, it was located specifically in the fibroblastic foci areas of the fibrotic lung with a subepithelial gradient pattern. TNC levels were correlated with fibroblastic foci content in cHP lungs. Versican and fibronectin glycoproteins were associated with TNC, mainly in fibroblastic foci of fibrotic lungs. Fibroblasts from IPF patients constitutively synthesized higher levels of TNC than normal fibroblasts. TNC and α-sma was induced by TGF-ß1 in both fibrotic and normal fibroblasts. TNC treatment of normal and fibrotic fibroblasts induced a non-significant increased α-sma mRNA. CONCLUSIONS: The difference in ECM glycoprotein content in interstitial lung diseases could contribute to the development of lung fibrosis. The increase of TNC in interstitial areas of fibrotic activity could play a key role in the altered wound healing.


Assuntos
Fibroblastos/metabolismo , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/metabolismo , Tenascina/biossíntese , Tenascina/genética , Actinas/genética , Actinas/metabolismo , Adulto , Idoso , Alveolite Alérgica Extrínseca/genética , Alveolite Alérgica Extrínseca/metabolismo , Células Cultivadas , Doença Crônica , Regulação para Baixo , Feminino , Fibronectinas/genética , Fibronectinas/metabolismo , Expressão Gênica , Humanos , Fibrose Pulmonar Idiopática/patologia , Pulmão/química , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/metabolismo , Tenascina/análise , Fator de Crescimento Transformador beta1/farmacologia , Regulação para Cima , Versicanas/genética , Versicanas/metabolismo
12.
Am J Dermatopathol ; 36(4): 344-6, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24562051

RESUMO

Cutaneous lesions in Whipple disease (WD) are infrequent, and the histological findings are usually nonspecific. Specific cutaneous lesions have rarely been described and usually involve the subcutaneous fat. We report a patient diagnosed with WD, who developed multiple small subcutaneous nodules after antibiotic treatment was administered. In addition to septal panniculitis, the cutaneous biopsy showed a mild granulomatous dermal reaction with PAS-positive macrophages characteristic of WD. A positive polymerase chain reaction in the cutaneous sample confirmed the presence of Tropheryma whipplei in the skin. Dermatopathologists should be aware that not only subcutaneous lesions but also dermal lesions may exhibit specific findings of WD.


Assuntos
Pele/patologia , Doença de Whipple/diagnóstico , Doença de Whipple/patologia , Antibacterianos/uso terapêutico , Biópsia , Humanos , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Resultado do Tratamento , Doença de Whipple/tratamento farmacológico
13.
J Exp Clin Cancer Res ; 43(1): 211, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39075581

RESUMO

BACKGROUND: Early cutaneous squamous cell carcinomas (cSCCs) generally show epithelial differentiation features and good prognosis, whereas advanced cSCCs present mesenchymal traits associated with tumor relapse, metastasis, and poor survival. Currently, the mechanisms involved in cSCC progression are unclear, and the established markers are suboptimal for accurately predicting the clinical course of the disease. METHODS: Using a mouse model of cSCC progression, expression microarray analysis, immunofluorescence and flow cytometry assays, we have identified a prognostic biomarker of tumor relapse, which has been evaluated in a cohort of cSCC patient samples. Phosphoproteomic analysis have revealed signaling pathways induced in epithelial plastic cancer cells that promote epithelial-mesenchymal plasticity (EMP) and tumor progression. These pathways have been validated by genetic and pharmacological inhibition assays. RESULTS: We show that the emergence of epithelial cancer cells expressing integrin αV (ITGAV) promotes cSCC progression to a mesenchymal state. Consistently, ITGAV expression allows the identification of patients at risk of cSCC relapse above the currently employed clinical histopathological parameters. We also demonstrate that activation of insulin-like growth factor-1 receptor (IGF1R) pathway in epithelial cancer cells is necessary to induce EMP and mesenchymal state acquisition in response to tumor microenvironment-derived factors, while promoting ITGAV expression. Likewise, ITGAV knockdown in epithelial plastic cancer cells also blocks EMP acquisition, generating epithelial tumors. CONCLUSIONS: Our results demonstrate that ITGAV is a prognostic biomarker of relapse in cSCCs that would allow improved patient stratification. ITGAV also collaborates with IGF1R to induce EMP in epithelial cancer cells and promotes cSCC progression, revealing a potential therapeutic strategy to block the generation of advanced mesenchymal cSCCs.


Assuntos
Transição Epitelial-Mesenquimal , Receptor IGF Tipo 1 , Transdução de Sinais , Neoplasias Cutâneas , Animais , Humanos , Camundongos , Receptor IGF Tipo 1/metabolismo , Receptor IGF Tipo 1/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/genética , Linhagem Celular Tumoral , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/genética , Prognóstico , Microambiente Tumoral , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética
14.
Nat Commun ; 15(1): 5352, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914547

RESUMO

Immune checkpoint blockade (ICB) approaches have changed the therapeutic landscape for many tumor types. However, half of cutaneous squamous cell carcinoma (cSCC) patients remain unresponsive or develop resistance. Here, we show that, during cSCC progression in male mice, cancer cells acquire epithelial/mesenchymal plasticity and change their immune checkpoint (IC) ligand profile according to their features, dictating the IC pathways involved in immune evasion. Epithelial cancer cells, through the PD-1/PD-L1 pathway, and mesenchymal cancer cells, through the CTLA-4/CD80 and TIGIT/CD155 pathways, differentially block antitumor immune responses and determine the response to ICB therapies. Accordingly, the anti-PD-L1/TIGIT combination is the most effective strategy for blocking the growth of cSCCs that contain both epithelial and mesenchymal cancer cells. The expression of E-cadherin/Vimentin/CD80/CD155 proteins in cSCC, HNSCC and melanoma patient samples predicts response to anti-PD-1/PD-L1 therapy. Collectively, our findings indicate that the selection of ICB therapies should take into account the epithelial/mesenchymal features of cancer cells.


Assuntos
Antígeno B7-H1 , Carcinoma de Células Escamosas , Plasticidade Celular , Transição Epitelial-Mesenquimal , Inibidores de Checkpoint Imunológico , Imunoterapia , Neoplasias Cutâneas , Animais , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/tratamento farmacológico , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Camundongos , Humanos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inibidores , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Masculino , Imunoterapia/métodos , Transição Epitelial-Mesenquimal/imunologia , Plasticidade Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/metabolismo , Antígeno CTLA-4/imunologia , Receptores Virais/metabolismo , Receptores Virais/genética , Antígeno B7-1/metabolismo , Receptores Imunológicos/metabolismo
15.
J Pathol ; 228(2): 230-40, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22374749

RESUMO

Little is known about the molecular events occurring in the metastases of human tumours. Epigenetic alterations are dynamic lesions that change over the natural course of the disease, and so they might play a role in the biology of cancer cells that have departed from the primary tumour. Herein, we have adopted an epigenomic approach to identify some of these changes. Using a DNA methylation microarray platform to compare paired primary tumour and lymph node metastatic cell lines from the same patient, we observed cadherin-11 promoter CpG island hypermethylation as a likely target of the process. We found that CDH11 DNA methylation-associated transcriptional silencing occurred in the corresponding lymph node metastases of melanoma and head and neck cancer cells but not in the primary tumours. Using in vitro and in vivo cellular and mouse models for depleted or enhanced CDH11 activity, we also demonstrated that CDH11 acts as an inhibitor of tumour growth, motility and dissemination. Most importantly, the study of CDH11 5'-CpG island hypermethylation in primary tumours and lymph node metastases of cancer patients showed this epigenetic alteration to be significantly confined to the disseminated cells. Overall, these results indicate the existence of metastasis-specific epigenetic events that might contribute to the progression of the disease.


Assuntos
Caderinas/genética , Metilação de DNA , Inativação Gênica , Neoplasias de Cabeça e Pescoço/genética , Melanoma/genética , Neoplasias Cutâneas/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células , Ilhas de CpG/genética , Epigênese Genética , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Linfonodos/patologia , Metástase Linfática/genética , Metástase Linfática/patologia , Melanoma/metabolismo , Melanoma/secundário , Camundongos , Camundongos Mutantes , Análise em Microsséries , Transplante de Neoplasias/métodos , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Australas J Dermatol ; 53(4): 288-90, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23157780

RESUMO

Lung carcinoma is one of the most frequent sources of skin metastases in male patients. Our objective was to analyse the clinical and pathological features of 30 patients with skin metastases from lung carcinoma. Cutaneous biopsies codified as 'skin metastasis from lung carcinoma' during 1988-2009 at Bellvitge Hospital (Barcelona, Spain) were reviewed. The histological types of 30 lung carcinomas (29 men, 1 woman) were squamous cell carcinoma (10 cases), undifferentiated carcinoma (7), adenocarcinoma (6), small cell carcinoma (5) and large cell carcinoma (2). The most frequent clinical presentation was as a solitary nodule (16 cases), and the most frequent site was the head (13 cases). Cutaneous metastases were present at the time of diagnosis of the lung primary tumour in 66% of cases. Skin biopsy might be helpful to establish the histological type of tumour, and thus help with therapeutic decision-making. Cutaneous metastases from lung cancer remain a poor prognostic feature.


Assuntos
Carcinoma/patologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias Pulmonares/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Carcinoma/secundário , Feminino , Neoplasias de Cabeça e Pescoço/secundário , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Cutâneas/secundário
17.
Med Clin (Barc) ; 158(5): 229-232, 2022 03 11.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34839941

RESUMO

BACKGROUND: Granulomatous mastitis (GM) is defined by the formation of granulomatous inflammation in breast tissue. Erythema nodosum (EN) is a reactive inflammatory panniculitis characterized by erythematous subcutaneous nodules in the lower limbs. The association of GM with EN has been rarely reported. Our aim was to retrospectively review our series of patients with GM to better characterize their features and their association with EN. METHODS: Cases histologically diagnosed as granulomatous inflammation in breast tissue between 1995 and 2020 were retrospectively reviewed. RESULTS: Forty-two women were diagnosed with GM. The average age at diagnosis was 41.619years, and 59.5% were of South-American ethnicity. EN was associated with GM in 11.9% of the patients. Patients with EN were diagnosed earlier than isolated GM (0.4months vs 6.81months; P<.05). Ulceration in the GM was more prevalent in patients with associated EN (60% vs 14.7%; P<.05). CONCLUSION: EN in patients with GM may reduce the evolution time and may help to diagnose this rare condition that mimics breast carcinoma.


Assuntos
Neoplasias da Mama , Eritema Nodoso , Mastite Granulomatosa , Eritema Nodoso/diagnóstico , Feminino , Mastite Granulomatosa/complicações , Mastite Granulomatosa/diagnóstico , Humanos , Pesquisa , Estudos Retrospectivos
18.
Dermatol Pract Concept ; 12(4): e2022173, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36534547

RESUMO

Introduction: Granuloma annulare (GA) has been reported as associated with multiple diseases, mainly diabetes mellitus (DM), thyroid diseases, and dyslipidemia. However, the high prevalence of some of these illnesses makes it difficult to assess whether the association is real or fortuitous. Objectives: Our objective was to analyze the clinical features of GA patients and the possible associations. Methods: This is a retrospective observational study of 225 patients with biopsy-proven GA diagnosed between 2009 and 2019 in a referral university hospital in Barcelona, Spain. Clinical charts were reviewed to obtain clinical data. As a control group we used a random list of 225 patients diagnosed in the hospital traumatology department in the same period, matched by age and sex. Results: Diabetes was diagnosed in 40 GA patients (18%) (34 in the control group, 15%) and hypothyroidism in 33 (15%) (22 in the control group 9.8%); the differences were not significant. We also did not detect any association with uveitis, sarcoidosis, necrobiosis lipoidica, Sweet syndrome, HIV infection, hepatitis B, or hematological malignancies. We only detected a possible association with hepatitis C (6 GA patients, 2.7%, versus 0 controls, P = 0.03), and hypercholesterolemia (108 GA patients, 48%, versus 79 controls, 35%, P = 0.007). Conclusions: The possible pathogenic explanations for the association with hepatitis C and hypercholesterolemia seem unlikely. We consider that the association of GA with other diseases, including hypercholesterolemia and hepatitis C, is doubtful and that it there is no justification rule out possible associated diseases in patients with GA.

19.
Cir Esp (Engl Ed) ; 100(4): 209-214, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35534138

RESUMO

BACKGROUND: Pleurodesis is a common technique for treating the accumulation of air or liquid in the pleural space caused by pneumothorax or pleural effusion, it is based on the bounding of pleural layers through induced inflammatory lesions. There are several pleurodesis procedures. OBJECTIVES: To test and describe the inflammatory effect of hyperthermia on the pleural and peritoneal mesothelia of rats, with the aim of testing the effectiveness of this process for inducing pleurodesis. METHODS: 35 Sprague-Dawley (male/female) rats were randomized into four treatment groups: Group A (Talc, 10 individuals); group B (control, 5 individuals); group C (hyperthermic isotonic saline, 10 individuals); and group D (filtrate air at 50°, 10 individuals). Inflammatory effect of hyperthermia was the primary outcome parameter. RESULTS: In the talc group, minimal adhesions between both pleural and peritoneal layers were observed in seven rats. Talc produced peritoneal mesothelium inflammation and fibrosis associated to foreign body giant cells in 80% (8/10) of the sample. Furthermore, clear evidence of a granulomatous foreign-body reaction was detected. No macroscopic and/or microscopic damage was registered in the remaining three groups (control, hyperthermic, and filtrate air). CONCLUSIONS: Talc is an excellent method for producing pleuro-peritoneal inflammatory lesions. On the contrary, hyperthermia apparently does not induce the macroscopic and microscopic damage that is required for efficient pleurodesis. Therefore, hyperthermia should not be used for pleurodesis procedures.


Assuntos
Hipertermia Induzida , Pleurodese , Animais , Feminino , Humanos , Masculino , Pleura/patologia , Pleurodese/métodos , Ratos , Ratos Sprague-Dawley , Talco
20.
Cir Esp (Engl Ed) ; 2021 Feb 16.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33608111

RESUMO

BACKGROUND: Pleurodesis is a common technique for treating the accumulation of air or liquid in the pleural space caused by pneumothorax or pleural effusion, it is based on the bounding of pleural layers through induced inflammatory lesions. There are several pleurodesis procedures. OBJECTIVES: To test and describe the inflammatory effect of hyperthermia on the pleural and peritoneal mesothelia of rats, with the aim of testing the effectiveness of this process for inducing pleurodesis. METHODS: 35 Sprague-Dawley (male/female) rats were randomized into four treatment groups: Group A (Talc, 10 individuals); group B (control, 5 individuals); group C (hyperthermic isotonic saline, 10 individuals); and group D (filtrate air at 50°, 10 individuals). Inflammatory effect of hyperthermia was the primary outcome parameter. RESULTS: In the talc group, minimal adhesions between both pleural and peritoneal layers were observed in seven rats. Talc produced peritoneal mesothelium inflammation and fibrosis associated to foreign body giant cells in 80% (8/10) of the sample. Furthermore, clear evidence of a granulomatous foreign-body reaction was detected. No macroscopic and/or microscopic damage was registered in the remaining three groups (control, hyperthermic, and filtrate air). CONCLUSIONS: Talc is an excellent method for producing pleuro-peritoneal inflammatory lesions. On the contrary, hyperthermia apparently does not induce the macroscopic and microscopic damage that is required for efficient pleurodesis. Therefore, hyperthermia should not be used for pleurodesis procedures.

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