RESUMEN
Fibromatosis, or desmoid tumour, is characterized by excessive and infiltrative proliferation of connective tissue originating from aponeurotic muscle structures. Mammary fibromatosis is rare in humans and animals and its precise aetiology is unknown. A 10-year-old mixed-breed female dog developed a mass in the right cranial thoracic mammary gland (M1) and underwent lumpectomy. The mass was firm, with an irregular surface and distinct limits. Microscopically, it was a neoplastic proliferation of fusiform cells with low atypia, interspersed with abundant dense collagenous tissue, confirmed by histochemical staining with Gomori's trichrome and Masson's trichrome and immunopositivity for vimentin and smooth muscle actin, confirming mammary fibromatosis. Mammary fibromatosis in dogs needs further studies to elucidate its clinical, epidemiological and aetiopathogenic aspects.
Asunto(s)
Enfermedades de los Perros , Fibroma , Fibromatosis Agresiva , Humanos , Femenino , Perros , Animales , Fibromatosis Agresiva/patología , Fibromatosis Agresiva/veterinaria , Fibroma/veterinaria , Músculos/patologíaRESUMEN
INTRODUCTION: Desmoid fibroma (DF) is a disorder characterized by strong clonal proliferation of myofibroblasts and fibroblasts. We describe a case of DF that mimicked a breast tumor, along with a review of the literature on the clinical manifestation, diagnostic process, and course of therapy for this combative disease. CASE REPORT: A 34-year-old female patient with breast lump at the junction of the upper quadrants of the left breast. After the diagnosis of DF, it was decided to perform a sectorectomy of the left breast associated with post-quadrant reconstruction, with immunohistochemistry and findings compatible with DF. DISCUSSION: Clinically manifests as a solid mass that is often painless and occasionally adherent to the chest wall. A treatment strategy should be idealized for each patient. Thus, there is the possibility of performing radical surgery for resection and/or radiotherapy, and surgery may be followed by radiotherapy.
Asunto(s)
Neoplasias de la Mama , Fibroma , Fibromatosis Agresiva , Pared Torácica , Femenino , Humanos , Adulto , Fibromatosis Agresiva/diagnóstico , Fibromatosis Agresiva/cirugía , Neoplasias de la Mama/diagnóstico , Fibroma/diagnóstico , Fibroma/cirugía , FibroblastosRESUMEN
Desmoid-type fibromatosis (DF) is a rare monoclonal, fibroblastic proliferation characterized by an unpredictable and variable clinical course. We present the case of a 56-year-old woman who underwent total thyroidectomy for papillary thyroid carcinoma in 2012 and who developed a cervical mass at the left laterocervical level during follow-up, raising the diagnosis of tumor recurrence. Computed tomography of the neck showed solid formations with heterogeneous contrast uptake in the right lateral region of the neck. At the level of the thoracic operculum, a second 26-mm formation was observed that medially contacted the left lateral wall of the trachea. Lateral lymphadenectomy was performed, which was incomplete. Histology showed findings consistent with desmoid-type fibromatosis. DF are slowly proliferating, non-metastatic tumors with a highly invasive capacity that are usually present in familial adenomatous polyposis (FAP)-Gardner syndrome. Our case had a history of massive colonic polyposis and first-degree relatives of colorectal cancer.
La fibromatosis de tipo desmoide (FD) es una rara proliferación fibroblástica monoclonal caracterizada por un curso clínico impredecible y variable. Presentamos el caso de una mujer de 56 años intervenida de tiroidectomía total por carcinoma papilar de tiroides en 2012 y que durante el seguimiento desarrolla una masa cervical a nivel laterocervical izquierdo, planteando el diagnóstico de recidiva tumoral. La tomografía computarizada de cuello demostró formaciones sólidas con captación heterogénea de contraste en la región lateral derecha del cuello. A nivel del opérculo torácico se observó una segunda formación de 26 mm que contactaba medialmente con la pared lateral izquierda de la tráquea. Se realizó una linfadenectomía lateral, que resultó incompleta. La histología mostró hallazgos compatibles con FD. La FD son tumores de proliferación lenta, no metastásicos y con una capacidad altamente invasiva que suelen estar presentes en la poliposis adenomatosa familiar (PAF)-síndrome de Gardner. Nuestro caso tenía antecedentes de poliposis colónica masiva y familiares de primer grado de cáncer colorrectal.
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Poliposis Adenomatosa del Colon , Fibromatosis Agresiva , Neoplasias de la Tiroides , Femenino , Humanos , Persona de Mediana Edad , Cáncer Papilar Tiroideo , Fibromatosis Agresiva/diagnóstico por imagen , Fibromatosis Agresiva/cirugía , Recurrencia Local de Neoplasia , Poliposis Adenomatosa del Colon/patología , Poliposis Adenomatosa del Colon/cirugía , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/cirugíaRESUMEN
BACKGROUND: The initial approach to the treatment of desmoid tumors has changed from surgical resection to watchful waiting. However, surgery is still sometimes considered for some patients, and it is likely that a few patients would benefit from tumor removal if the likelihood of local recurrence could be predicted. However, to our knowledge, there is no tool that can provide guidance on this for clinicians at the point of care. QUESTION/PURPOSE: We sought to explore whether a combined molecular and clinical prognostic model for relapse in patients with desmoid tumors treated with surgery would allow us to identify patients who might do well with surgical excision. METHODS: This was a retrospective, single-center study of 107 patients with desmoid tumors who were surgically treated between January 1980 and December 2015, with a median follow-up of 106 months (range 7 to 337 months). We correlated clinical variables (age, tumor size, and localization) and CTNNB1 gene mutations with recurrence-free survival. Recurrence-free survival was estimated using a Kaplan-Meier curve. Univariate and multivariable analyses of time to local recurrence were performed using Cox regression models. A final nomogram model was constructed according to the final fitted Cox model. The predictive performance of the model was evaluated using measures of calibration and discrimination: calibration plot and the Harrell C-statistic, also known as the concordance index, in which values near 0.5 represent a random prediction and values near 1 represent the best model predictions. RESULTS: The multivariable analysis showed that S45F mutations (hazard ratio 5.25 [95% confidence interval 2.27 to 12.15]; p < 0.001) and tumor in the extremities (HR 3.15 [95% CI 1.35 to 7.33]; p = 0.008) were associated with a higher risk of local recurrence. Based on these risk factors, we created a model; we observed that patients considered to be at high risk of local recurrence as defined by having one or two factors associated with recurrence (extremity tumors and S45F mutation) had an HR of 8.4 compared with patients who had no such factors (95% CI 2.84 to 24.6; p < 0.001). From these data and based on the multivariable Cox models, we also developed a nomogram to estimate the individual risk of relapse after surgical resection. The model had a concordance index of 0.75, or moderate discrimination. CONCLUSION: CTNNB1 S45F mutations combined with other clinical variables are a potential prognostic biomarker associated with the risk of relapse in patients with desmoid tumors. The developed nomogram is simple to use and, if validated, could be incorporated into clinical practice to identify patients at high risk of relapse among patients opting for surgical excision and thus help clinicians and patients in decision-making. A large multicenter study is necessary to validate our model and explore its applicability. LEVEL OF EVIDENCE: Level III, therapeutic study.
Asunto(s)
Fibromatosis Agresiva , Humanos , Fibromatosis Agresiva/genética , Fibromatosis Agresiva/cirugía , Estudios Retrospectivos , Recurrencia Local de Neoplasia/cirugía , Mutación , Pronóstico , beta Catenina/genéticaRESUMEN
OBJECTIVE: Familial Adenomatous Polyposis is a complex hereditary disease that exposes the carrier to a great risk of Colorectal Cancer (CRC). After prophylactic surgery, intra-abdominal desmoid tumors are known to be one the most important cause of death. Therefore, recognition of increased-risk patients and modification of operative strategy may be crucial. AIM: The objective of this study was to estimate the desmoid tumor risk in relation to various surgical and clinical variables. METHODS: Patients who had undergone polyposis since 1958 were included in the study. After exclusion criteria were met, those who had developed desmoid tumors were selected to undergo further evaluation. RESULTS: The study revealed that the risk of developing desmoid tumors was associated with various factors such as sex ratio, colectomy, and reoperations. On the other hand, the type of surgery, family history, and surgical approach did not affect the risk of developing desmoid tumors. The data collected from 146 polyposis patients revealed that 16% had desmoid polyps. The sex ratio was 7:1, and the median age at colectomy was 28.6 years. Family history, multiple abdominal operations, and reoperations were some of the characteristics that were common in desmoid patients. CONCLUSION: Recognition of clinical (female sex) and surgical (timing of surgery and previous reoperations) data as unfavorable variables associated with greater risk may be useful during the decision-making process.
Asunto(s)
Poliposis Adenomatosa del Colon , Fibromatosis Abdominal , Fibromatosis Agresiva , Humanos , Femenino , Adulto , Fibromatosis Agresiva/complicaciones , Fibromatosis Agresiva/cirugía , Poliposis Adenomatosa del Colon/complicaciones , Poliposis Adenomatosa del Colon/cirugía , Fibromatosis Abdominal/complicaciones , Fibromatosis Abdominal/patología , Fibromatosis Abdominal/cirugía , ColectomíaRESUMEN
Introdução: Tumores renais estão entre os 10 tipos de câncer mais frequentes na população, com o tumor de Wilms (TW) sendo o mais frequente em crianças e o carcinoma renal de células claras (ccRCC) o mais comum em adultos. O monitoramento de resposta a tratamento por biópsia líquida baseada na análise do DNA tumoral (tDNA) em pacientes com câncer renal usando plasma e urina vem sendo recentemente explorado. No entanto, sua relação na estratificação de prognóstico continua sendo uma área ainda pouco estudada. Ainda, o fator hereditário destes tumores é um campo de pouca investigação. Objetivos: Investigar a predisposição genética em pacientes com tumores renais e explorar o potencial do tDNA em urina e plasma como ferramenta para estratificação de prognóstico. Metodologia: Pacientes com TW e ccRCC foram recrutados de forma prospectiva para estratificação de prognóstico por tDNA. As coletas de amostras de fluidos corpóreos (plasma e urina) foram realizadas de forma seriada, sendo 3 coletas para TW: baseline, antes do tratamento, ou seja, antes da quimioterapia neoadjuvante; M1, após quimioterapia neoadjuvante e M2, após cirurgia; e 5 coletas para ccRCC: baseline, antes do tratamento, ou seja, no dia da cirurgia; M1, de 6 a 8 semanas após cirurgia; M2, 6 meses após cirurgia; M3, 18 meses após cirurgia e M4, 30 meses após cirurgia. Os tumores foram avaliados utilizando dois painéis: um contendo 35 genes para TW (PAINEL TW-35) e outro contendo 28 genes para ccRCC (PAINEL CCR-28). Tumores de pacientes com TW e com ccRCC que foram negativos para variante somática foram submetidos a sequenciamento de exoma ou ao painel comercial CCP (Thermo Fisher, USA) contendo 409 genes de câncer, respectivamente. As variantes somáticas específicas de cada tumor foram rastreadas no cfDNA das amostras de plasma e urina de forma personalizada através de PCR multiplex desenvolvida pelo grupo denominado PATS (personalized amplicon target sequencing). Para os casos de TW, o cfDNA do sobrenadante e do sedimento de urina foram avaliados isoladamente; para os casos de ccRCC, foram avaliados juntos de forma equimolar. Para o teste genético, foi utilizado um painel customizado de 126 genes de predisposição ao câncer tanto na série prospectiva de pacientes recrutados para esse estudo como retrospectiva utilizando amostras de nosso Biobanco. A perda de heteorizogose (LOH) foi avaliada nos casos de pacientes com variantes patogênicas ou de impacto clínico desconhecido e do quais havia DNA tumoral disponível. Sequenciamento de próxima geração (NGS) foi realizado na plataforma Ion GeneStudio S5 (Thermo Fisher, USA) para as análises somáticas e na plataforma NextSeq 500 (Illumina, USA) para as análises germinativas. Resultados: Um total de 10 casos de TW foram recrutados. Na análise somática dos TW foi possível detectar variantes específicas do tumor em 90% dos casos (9/10). WTX, SIX1 e CTNNB1 foram os genes mais mutados, sendo que cada um foi detectado em 2 casos (2/10, ii 20%). Dos 9 pacientes com variante somática específica do tumor, 100% apresenta ram tDNA positivo na coleta realizada antes do tratamento (baseline) em ao menos um fluido corpóreo, sendo 6 no plasma (6/8, 75%) e 4 na urina (4/7, 57%), com frequência alélica (FA) média de 26,48% no plasma e, na urina, 18,92% no sedimento e 17,12% no sobrenadante. Em relação às coletas de monitoramento após quimioterapia neoadjuvante (M1), 71% (5/7) foram tDNA positivos, sendo 5 no plasma (5/7, 71%) com FA média de 42,13% e 4 na urina (4/6, 67%), todos no sobrenadante, com FA média de 3,50%. No monitoramento após cirurgia (M2) 44% (4/9) foram tDNA positivos, sendo 1 no plasma (1/9, 11%) com FA média de 2,60% e 3 na urina (3/9, 33%) com FA média de 3,19% no sedimento e 5,16% no sobrenadante. Nenhuma associação com prognóstico pode ser estabelecida pelo fato da casuística ser pequena. Para os casos de ccRCC, 46 pacientes foram recrutados para o estudo. Foram identificadas variantes somáticas no DNA de tumor em 78,3% (36/46), sendo 35 pelo PAINEL CCR-28 (97%) confeccionado e analisado em um estudo anterior do grupo e a amostra negativa pelo PAINEL CCP no estudo atual. VHL foi o gene mais mutado, alterado em 67% amostras (24/36), seguido por PBRM1 em 36% (13/36). A análise do plasma e urina baseline, coletados antes da cirurgia, foi realizada no estudo anterior do grupo, sendo tDNA positivo detectado em 4 amostras de plasma e 4 de urina (4/32, 12,5% cada) com FA média de 1,83% e 2,66%, respectivamente. Para o monitoramento M1, o tDNA foi positivo no plasma em 10% (2/20) com FA média de 2,60%, e negativo nas 16 amostras de urina. No monitoramento M2, tanto o plasma quanto a urina foram negativos. No monitoramento M3, o tDNA foi positivo no plasma em 11.8% (2/17) e na urina em 7,1% (1/14), com FA média de 1,66% e 1,35%, respectivamente. No monitoramento M4, todas as amostras foram negativas. Foram detectadas associações entre tDNA positivo no plasma baseline (antes da cirurgia) com progressão da doença (p=.015), estadiamento tumoral ≥T3 (p=.002) e com menor sobrevida livre de progressão (p=.004). A análise germinativa em pacientes com TW resultou em uma taxa de detecção de variantes patogênicas (VP) em 10,2% deles (6/59) nos genes BRCA1, CHEK2, WT1 (2 casos), ERBB2 e SDHA. LOH foi avaliada em 7 casos e detectada somente em um caso com WT1. Em pacientes com CCR, 6,9% (5/72) foram portadores de VP nos genes MET, CASR, MITF e MUTYH (2 casos). Desses, 8 foram avaliados para LOH e nenhum foi positivo. Conclusões: Em pacientes com TW, para avaliação de tDNA com prognóstico, é necessário ampliar o número de casos. Em pacientes com ccRCC, a presença de tDNA no plasma coletado antes da cirurgia tem potencial de ser um biomarcador de prognóstico. A análise de genes de risco reforçou o papel de WT1 na predisposição ao TW.
Introduction: Desmoid Tumors (DT) are rare neoplasms with higher incidence in women. Active surveillance has replaced surgery in most of the cases due to rates of local relapses. Real world data are important to identify the barriers in the delivery of the best care for patients with rare tumors. The aim of the present study is to characterize the clinical and epidemiological aspects of DT and to evaluate the relapse rate. Methods: Retrospective, single-center analysis of patients with DT. Variables were age, sex, biopsy, familial adenomatous polypose (FAP) and trauma history, health care system, symptoms, tumor size and site, treatment and recurrence. The disease-free survival (DFS) was calculated with the Kaplan-Meier method. Results: 242 patients were evaluated, mean age was 34 years, 70,7% women, 74% had health insurance, 59.9% with symptom of growing lump, 37,6% originated in the abdomen and 34,3% had size > 5cm. Surgery was performed in 70,2%, 31% with negative margin and only 57% with previous biopsy. Recurrence rate was 38% in 1,2,5-year DFS was 75,3%, 64,2%, 57,8%, respectively. Size (p = 0.022) and tumor location in the dorsum (p = 0.001), extremities (p = 0.003) and pelvis (p = 0.003) were independent variable related to decrease in DFS in the cox regression model. Conclusion: our data reinforces the need to gather data from real world practice and the importance of awareness of DT and medical education about DT behavior and best approach due to the high rates of surgery and elevated number of patients treated without biopsy.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Fibromatosis Agresiva/epidemiología , Recurrencia , BrasilRESUMEN
El Tumor Desmoide, es un tumor raro de origen mesenquimal con una incidencia aproximada de 0.3% (1) que, si bien es considerado un tumor benigno por no presentar metástasis a distancia, se considera un tumor localmente agresivo con altas tasas de recidiva tras la extirpación quirúrgica de entre el 19 a 28% (2). Se presenta el caso clínico de una mujer de 21 años de edad, gestante de 7 semanas, que acudió a consulta a la Unidad de Mastología del Hospital de Clínicas por percatarse de nódulo en cuadrante superoexterno de mama derecha, que aumenta de tamaño. Se realizó exéresis tumoral con márgenes, cuyo diagnóstico fue un Tumor Desmoide y, posterior resección de márgenes para ampliación. El Tumor Desmoide es poco frecuente de localización mamaria, que fue tratada con cirugía con buena evolución en una mujer gestante, por lo que debe considerarse esta patología en pacientes jóvenes gestantes, como diagnóstico diferencial en nódulos mamarios.
Desmoid tumor is a rare tumor of mesenchymal origin with an approximate incidence of 0.3% (1). Although it is considered a benign tumor because it does not present distant metastases, it is considered a locally aggressive tumor with high rates of recurrence after surgical removal of between 19 to 28% (2). We present the clinical case of a 21-year-old woman, 7 weeks pregnant, who attended the Mastology Unit of the Hospital de Clínicas, after noticing a nodule in the upper outer quadrant of the right breast, which was increasing in size. Tumor excision with margins was performed, whose diagnosis was a Desmoid Tumor, and subsequent resection of margins for amplifying The Desmoid Tumor is rare in the breast and was treated with surgery with a good evolution in a pregnant woman, so this pathology should be considered in young pregnant patients, as a differential diagnosis in breast nodules.
Asunto(s)
Neoplasias de la Mama , Fibromatosis Agresiva , Neoplasias , Mama , Mujeres EmbarazadasRESUMEN
Introducción. Los tumores desmoides son lesiones de los tejidos blandos, histológicamente benignas, poco frecuentes y con gran agresividad local y carencia de potencial metastásico. Se relacionan estrechamente con antecedentes traumáticos o quirúrgicos, como la cesárea, y su tratamiento generalmente es quirúrgico. Métodos. Presentamos una serie de tres pacientes intervenidas en nuestro centro durante el año 2020. Se revisan sus antecedentes y se describe su tratamiento. Resultados. En todas nuestras pacientes se encontró algún antecedente quirúrgico, dos cesáreas y una resección de un disgerminoma. El tratamiento empleado fue la resección quirúrgica con márgenes libres y reparación del defecto mediante malla. Conclusiones. El tumor desmoide es una patología poco frecuente, su diagnóstico se realiza mediante exámenes imagenológicos y se confirma con el estudio histológico; es importante hacer el diagnóstico diferencial con el sarcoma. La cirugía radical sigue siendo el tratamiento de elección, aunque algunos autores proponen el tratamiento conservador.
Introduction. Desmoid tumors are soft tissue lesions, histologically benign, rare and with great local aggressiveness and lack of metastatic potential. They are closely related to traumatic or surgical history such as caesarean section. Their treatment is generally surgical. Methods. We present a case series of three patients operated on in our center during the year 2020. Their history is reviewed and their type of treatment is presented. Results. In all our patients, surgical history was found (two caesarean sections and one resection of a dysgerminoma). The treatment used was surgical resection with free margins and mesh repair of the defect. Conclusions. Desmoid tumor is a rare pathology; its diagnosis is made by imaging studies, and confirmed by histology. It is important to make a differential diagnosis with sarcoma. Radical surgery remains the treatment of choice, although some authors propose conservative treatment.
Asunto(s)
Humanos , Cesárea , Fibromatosis Agresiva , Cirugía General , Pared Abdominal , NeoplasiasRESUMEN
Introdução: O tumor desmoide (TD) é uma neoplasia rara com altas taxas de recorrência local, composto por células fibroblásticas que se caracterizam pela expressão de moléculas-chave, incluindo o filamento intermediário vimentina, ciclooxigenase-2 (COX-2) e ß-catenina nuclear. Células tumorais circulantes (CTCs) isoladas do sangue periférico de pacientes com sarcomas e outras neoplasias podem ser utilizadas como biomarcadores precoces de invasão e disseminação tumoral. A família dos Receptores do Fator de Crescimento Epidérmico (Epidermal Growth Factor Receptor, EGFR) também podem influenciar no processo de invasão das CTCs, na formação de metástases e na recolonização de seus tumores de origem por meio de um processo de "auto-semeadura do tumor". Objetivo: Nosso objetivo foi identificar CTCs no sangue periférico de pacientes com TD ou sarcomas e avaliar a expressão das proteínas ß-catenina, TGF-ßRI (do Inglês, Transforming Growth Factor-ß Receptor I), COX-2 (Cyclooxygenase2), vimentina, GLUT-1 (Glucose Transporter 1), LGR5 (G-Protein Coupled Receptor 5) e EGFR, e sua correlação com sobrevidas global (SG) e livre de progressão (SLP). Materiais e Métodos: Foi realizado um estudo prospectivo de pacientes com diagnóstico inicial ou TD recidivado com doença mensurável. Para sarcomas, utilizamos amostras coletadas de forma prospectiva e retrospectiva. As amostras de sangue de cada paciente foram processadas e filtradas pelo ISET® (Rarecells, França) para isolamento e quantificação de CTCs. A expressão das proteínas foi analisada por imunocitoquímica (ICC). Para análise molecular das CTCs provenientes de pacientes com TD foi padronizado o método de PCR digital. Resultados: Foram incluídos 18 pacientes com TD, todos com CTCs detectáveis, com níveis que variaram entre 0,513 CTCs/mL. Encontramos uma concordância da expressão de ß-catenina em CTCs e tumores primários de 42,8% (6/14) dos casos usando ICC e imunohistoquímica, respectivamente. Nos nossos testes prévios de PCR digital, encontramos cópias mutadas de S45Pro em 4 pacientes (40%) e de S45Phe em apenas um paciente (10%). Em contraste, não foram encontradas mutações Th41Ala. Nas amostras de sarcomas, analisamos 30 amostras e encontramos CTCs em 93% dos pacientes e os níveis variaram de 0-11,25 CTCs/mL. Observamos também que a SG dos pacientes positivos para EGFR (p=0,027) eram inferiores às sobrevidas dos pacientes negativos para as mesmas proteínas. Conclusões: Nosso estudo identificou alta prevalência de CTCs em pacientes com TD e sarcomas. A concordânciada expressão de ß-catenina entre tumor primário e CTCs traz novas perspectivas para avaliar a dinâmica das CTCs no compartimento sanguíneo, abrindo novos caminhos para o estudo da biologia e comportamento do TD. Este é o primeiro estudo a demonstrar a expressão da proteína LGR5 em CTCs de pacientes com diferentes tipos de sarcomas, o que pode abrir novas oportunidades para futuras investigações. O próximo passo é caracterizar CTCs em uma coorte maior de pacientes para entender melhor o papel do LGR5 e das demais proteínas no processo de metástases tumorais em sarcomas. Além disso, esses resultados abrem a possibilidade de usar CTCs para prever a dinâmica do TD no momento da progressão da doença e tratamento. Mais estudos com tamanhos de amostra maiores são necessários para validar nossos achados tanto em TD como em sarcomas
Introduction: Desmoid tumor (DT) is a rare neoplasm with high rates of local recurrence, composed of fibroblast cells that are characterized by the expression of key molecules, including the intermediate filament vimentin, cyclooxygenase-2 (COX-2) and ß-catenin. Circulating tumor cells (CTCs) isolated from the peripheral blood of patients with sarcomas and other neoplasms can be used as early biomarkers of tumor invasion and dissemination. The Epidermal Growth Factor Receptor (EGFR) family can also influence the process of CTC invasion, metastasis formation and recolonization of their tumors of origin through a process of "tumor selfseeding". Objective: Our objective was to identify CTCs in the peripheral blood of patients with TD or sarcomas and to evaluate the expression of ßcatenin proteins, transforming growth factor receptor beta I (TGF-ßRI), COX-2 (cyclooxygenase-2), vimentin, GLUT-1 (Glucose transporter 1), LGR5 (Gprotein coupled receptor 5) and EGFR and their relation with progression free (PFS) and overall suvival (OS). Methods: We performed a prospective study of patients with initial diagnosis or relapsed TD with measurable disease. For sarcomas, we used samples collected prospectively and retrospectively. Blood samples from each patient were processed and filtered by ISET® (Rarecells, France) for isolation and quantification of CTCs. Protein expression was analyzed by immunocytochemistry (ICC). For the molecular analysis of CTCs from patients with TD, the digital PCR method was standardized. Results: Eighteen TD patients were included, all with detectable CTCs, with levels ranging from 0.513 CTCs/mL. We found a concordance ofß-catenin expression in CTCs and primary tumors of 42.8% (6/14) of cases using ICC and immunohistochemistry, respectively. In our previous digital PCR tests, we found mutated copies of S45Pro in 4 patients (40%) and of S45Phe in only one patient (10%). In contrast, no Th41Ala mutations were found. In the sarcoma samples, we analyzed 30 samples and found CTCs in 93% of the patients and the levels ranged from 0-11.25 CTCs/mL. We also observed that the OS of EGFR positive patients (p=0.027) were lower than the survival of negative patients for the same proteins. Conclusions: Our study identified a high prevalence of CTCs in patients with TD and sarcomas. The agreement of ß-catenin expression between primary tumor and CTCs brings new perspectives to evaluate the dynamics of CTCs in the blood compartment, opening newavenues for the study of the biology and behavior of TD. This is the first study to demonstrate the expression of LGR5 protein in CTCs from patients with different types of sarcomas, which may open new opportunities for future investigations. The next step is to characterize CTCs in a larger cohort of patients to better understand the role of LGR5 and other proteins in the process of tumor metastases in sarcomas. Furthermore, these results open up the possibility of using CTCs to predict the dynamics of TD at the time of disease progression and treatment. More studies with larger sample sizes areneeded to validate our findings in both TD and sarcomas
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Sarcoma , Fibromatosis Agresiva , Células Neoplásicas Circulantes , Neoplasias de los Tejidos BlandosRESUMEN
Introducción. Los tumores desmoides o fibromatosis agresiva corresponden a neoplasias mesenquimales poco frecuentes. Son tumores localmente agresivos que ocurren especialmente en jóvenes, no desarrollan metástasis a distancia, pero se asocian con invasión locorregional y alta tasa de recurrencia después de la resección. Su etiología es desconocida, pero se ha asociado al síndrome de Gardner, trauma, embarazo, estados hiperestrogénicos y puerperio. El objetivo de este artículo fue hacer una revisión sobre el tema a propósito de un caso clínico. Caso clínico. Se presenta el caso de una paciente puérpera con progresivo y rápido aumento del volumen abdominal. Se realizó una tomografía computarizada de abdomen y pelvis que confirmó la presencia de una masa intraperitoneal bien definida. La paciente fue operada con escisión de la masa y confirmación histológica de tumor desmoide a partir de la muestra de patología. Discusión. Los tumores desmoides tienen una incidencia de 2 a 4 casos por millón de habitantes por año, con leve predominio en el sexo femenino y representan menos del 3 % de los tumores de partes blandas. Aunque el tumor se puede ubicar a nivel intraabdominal o en la pared, la ubicación más común es en las extremidades. Conclusiones. La sospecha y detección del tumor desmoide es fundamental, así como su adecuado estudio, para determinar el tratamiento quirúrgico como fue realizado en este caso
Introduction. Desmoid tumors or aggressive fibromatosis correspond to rare mesenchymal neoplasms. They are locally aggressive tumors that occur especially in young people, they do not develop distant metastases, but are associated with locoregional invasion and a high recurrence rate after resection. Its etiology is unknown, but it has been associated with Gardner syndrome, trauma, pregnancy, hyperestrogenic states, and puerperium. The objective of this article was to review the topic based on a clinical case. Clinical case. The case of a puerperal patient with progressive and rapid increase in abdominal volume is presented. An abdominal and pelvic CT scan was performed, which confirmed the presence of a well-defined intraperitoneal mass. The patient underwent surgery with excision of the mass and histological confirmation of a desmoid tumor from the pathology sample. Discussion. Desmoid tumors have an incidence of 2 to 4 cases per million inhabitants per year, with a slight predominance in females, and represent less than 3% of soft tissue tumors. Although the tumor can be located intra-abdominal or in the wall, the most common location is in the extremities. Conclusions. The suspicion and detection of the desmoid tumor is essential, as well as its adequate study to determine the surgical treatment as it was done in this case
Asunto(s)
Humanos , Síndrome de Gardner , Fibromatosis Agresiva , Periodo Posparto , Radiología , Cirugía General , Fibroma DesmoplásicoRESUMEN
Soft-tissue sarcomas constitute an uncommon and heterogeneous group of tumors of mesenchymal origin. Diagnosis, treatment, and management should be performed by an expert multidisciplinary team. MRI/CT of the primary tumor and biopsy is mandatory before any treatment. Wide surgical resection with tumor-free tissue margin is the mainstay for localized disease. Radiotherapy is indicated in large, deep, high-grade tumors, or after marginal resection not suitable for re-excision. Perioperative chemotherapy should be discussed for high-risk sarcomas of the extremities and trunk-wall. In the case of oligometastatic disease, patients should be considered for local therapies. First-line treatment with anthracyclines (or in combination with ifosfamide) is the treatment of choice. Other drugs have shown activity in second-line therapy and in specific histological subtypes but options are limited and thus, a clinical trial should always be discussed.
Asunto(s)
Sarcoma/diagnóstico , Sarcoma/terapia , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/terapia , Antraciclinas/uso terapéutico , Antineoplásicos/uso terapéutico , Lista de Verificación , Quimioterapia Adyuvante/métodos , Dermatofibrosarcoma/terapia , Femenino , Fibromatosis Agresiva/genética , Fibromatosis Agresiva/terapia , Humanos , Imagen por Resonancia Magnética , Masculino , Oncología Médica , Terapia Neoadyuvante/métodos , Radioterapia/métodos , Neoplasias Retroperitoneales/terapia , Sarcoma/diagnóstico por imagen , Sarcoma/patología , Sociedades Médicas , Neoplasias de los Tejidos Blandos/diagnóstico por imagen , Neoplasias de los Tejidos Blandos/patología , Tumores Fibrosos Solitarios/tratamiento farmacológico , España , Tomografía Computarizada por Rayos X , Neoplasias Uterinas/terapiaRESUMEN
A literature review on desmoid tumors was carried out, which are tumors that affect soft tissues with a locally aggressive behavior and are unable to metastasize. Sporadic cases are located on the extremities and chest wall; hereditary cases have an intra-abdominal predilection, and those associated with pregnancy occur on the abdominal wall. Imaging techniques assess disease extension. Trucut biopsy is the study of choice for diagnosis. Mutations in the CTNNB1 or APC genes cause an abnormal accumulation of b-catenin within the cell. In this review, an emphasis is made on therapeutic strategies' evolution and change, and current tools for decision making are analyzed, as well as clinical outcomes. Radiation therapy can play a therapeutic or adjuvant role. Advances in the understanding of the disease have allowed establishing better targeted treatments with lower morbidity; however, there are still unanswered questions regarding the choice of the ideal candidate for surveillance and/or early treatment. Data related to quality of life are also presented, as well as the uncertainty generated by this diagnosis for both doctor and patient.
Se realizó una revisión bibliográfica de los tumores desmoides, lo cuales afectan los tejidos blandos con un comportamiento localmente agresivo sin capacidad de producir metástasis. Los casos esporádicos se localizan en extremidades y pared torácica; los casos hereditarios tienen predilección intraabdominal y los asociados con el embarazo en la pared abdominal. Las técnicas de imagen evalúan la extensión de la enfermedad. La biopsia con aguja trucut es el estudio de elección para el diagnóstico. Las mutaciones en el gen CTNNB1 o en el gen de APC provocan acumulación anormal de betacatenina en la célula. En esta revisión se hace énfasis en la evolución y cambio de las estrategias terapéuticas y se analizan las actuales herramientas para la toma de decisiones, así como los resultados clínicos. La radioterapia puede tener un papel terapéutico o adyuvante. Los avances en la comprensión de la enfermedad han permitido establecer tratamientos mejor dirigidos y con menor morbilidad; sin embargo, aún existen interrogantes en cuanto a la elección del candidato ideal para la vigilancia o el tratamiento precoz. También se presentan datos relacionados con la calidad de vida y la incertidumbre que genera el diagnóstico en el médico y el paciente.
Asunto(s)
Fibromatosis Agresiva/diagnóstico , Fibromatosis Agresiva/terapia , Antiinflamatorios/uso terapéutico , Antineoplásicos/uso terapéutico , Biopsia/métodos , Toma de Decisiones Clínicas , Femenino , Fibromatosis Agresiva/patología , Humanos , Masculino , Calidad de Vida , Radioterapia , Incertidumbre , beta Catenina/metabolismoRESUMEN
Desmoid-type fibromatosis (DF) is a tumor with high local recurrence rate. Sixteen patients (18 desmoid tumors) were retrospectively evaluated. Initial surgery was performed in 13/18 tumors, with complete resection in 6 (one with free margin and five with microscopic residual disease); 10/13 had local relapse. Eleven patients with 13 tumors underwent treatment with methotrexate-vinblastine. The response rate to chemotherapy was 54%, and up to 81% if stable disease cases were included. The best response was partial remission. Only 2 had grade 4 toxicity. Twelve of 15 patients had sequelae. In 8 cases sequelae were directly related to the surgical intervention and 3 of them were severe. The 5-year progression-free survival and overall survival were 30% and 93.3%, respectively. DF has a high local relapse rate, regardless of surgical margin involvement. Low dose chemotherapy achieved stable disease and even remission of the lesions with low toxicity. The high rate of sequelae is probably related to the initial surgery performed in the majority of patients and may be avoided by the use of neoadjuvant low dose chemotherapy.
La fibromatosis tipo desmoide (FD) es un tumor con alta tasa de recurrencia local. Dieciséis pacientes (18 tumores desmoides) fueron evaluados retrospectivamente. La cirugía inicial se realizó en 13/18 tumores, con resección completa en 6 (uno con margen libr e y cinco con margen microscópicamente comprometido); 10/13 tuvieron recaída local. Once pacientes con 13 tumores recibieron tratamiento con metotrexato/ vinblastina. La tasa de respuesta a la quimioterapia fue del 54% y de hasta el 81% si se incluyen los casos que lograron enfermedad estable. La mejor respuesta fue remisión parcial. Solo 2 tuvieron toxicidad grado 4. Doce de 15 pacientes tuvieron secuelas. En 8 casos, las secuelas estuvieron directamente relacionadas con la intervención quirúrgica y 3 de ellas fueron graves. La sobrevida libre de progresión a 5 años y la supervivencia global fueron del 30% y del 93.3%, respectivamente. La FD tiene una alta tasa de recaída local, independientemente del margen quirúrgico. Dosis bajas de quimioterapia lograron una enfermedad estable e incluso la remisión de las lesiones, con baja toxicidad. La alta tasa de secuelas probablemente esté relacionada con la cirugía inicial realizada en la mayoría de los pacientes y podría evitarse mediante el uso de quimioterapia neoadyuvante en dosis bajas, como sugieren las estrategias actuales de tratamiento.
Asunto(s)
Enfermedad de Gaucher/diagnóstico , Niño , Fibromatosis Agresiva/tratamiento farmacológico , Fibromatosis Agresiva/cirugía , Estudios de Seguimiento , Humanos , Metotrexato , Recurrencia Local de Neoplasia , Estudios RetrospectivosRESUMEN
Resumen Se realizó una revisión bibliográfica de los tumores desmoides, lo cuales afectan los tejidos blandos con un comportamiento localmente agresivo sin capacidad de producir metástasis. Los casos esporádicos se localizan en extremidades y pared torácica; los casos hereditarios tienen predilección intraabdominal y los asociados con el embarazo en la pared abdominal. Las técnicas de imagen evalúan la extensión de la enfermedad. La biopsia con aguja trucut es el estudio de elección para el diagnóstico. Las mutaciones en el gen CTNNB1 o en el gen de APC provocan acumulación anormal de betacatenina en la célula. En esta revisión se hace énfasis en la evolución y cambio de las estrategias terapéuticas y se analizan las actuales herramientas para la toma de decisiones, así como los resultados clínicos. La radioterapia puede tener un papel terapéutico o adyuvante. Los avances en la comprensión de la enfermedad han permitido establecer tratamientos mejor dirigidos y con menor morbilidad; sin embargo, aún existen interrogantes en cuanto a la elección del candidato ideal para la vigilancia o el tratamiento precoz. También se presentan datos relacionados con la calidad de vida y la incertidumbre que genera el diagnóstico en el médico y el paciente.
Abstract A literature review on desmoid tumors was carried out, which are tumors that affect soft tissues with a locally aggressive behavior and are unable to metastasize. Sporadic cases are located on the extremities and chest wall; hereditary cases have an intra-abdominal predilection, and those associated with pregnancy occur on the abdominal wall. Imaging techniques assess disease extension. Trucut biopsy is the study of choice for diagnosis. Mutations in the CTNNB1 or APC genes cause an abnormal accumulation of b-catenin within the cell. In this review, an emphasis is made on therapeutic strategies evolution and change, and current tools for decision making are analyzed, as well as clinical outcomes. Radiation therapy can play a therapeutic or adjuvant role. Advances in the understanding of the disease have allowed establishing better targeted treatments with lower morbidity; however, there are still unanswered questions regarding the choice of the ideal candidate for surveillance and/or early treatment. Data related to quality of life are also presented, as well as the uncertainty generated by this diagnosis for both doctor and patient.
Asunto(s)
Humanos , Masculino , Femenino , Fibromatosis Agresiva/diagnóstico , Fibromatosis Agresiva/terapia , Calidad de Vida , Radioterapia , Biopsia/métodos , Fibromatosis Agresiva/patología , Incertidumbre , beta Catenina/metabolismo , Toma de Decisiones Clínicas , Antiinflamatorios/uso terapéutico , Antineoplásicos/uso terapéuticoRESUMEN
BACKGROUND: Desmoid type fibromatosis is a benign neoplastic process non-encapsulated locally invasive and aggressive, which arises from a proliferation of bland-looking fibroblasts and myofibroblasts. The most frequent location of fibromatosis is extraabdominal (60%), abdominal wall (25%) and intra-abdominal (8-15%), rarely can originate in the viscera (0.73%), such as the pancreas, gastroesophageal junction, diaphragm and appendix. The annual incidence of desmoid tumor is estimated at 2 to 5 cases per million. In this article, we report a case of unusual presentation, originated in the cecal appendix. CASE: A 41-year-old female patient with acute pelvic pain, admitted to surgical ward with a clinical and ultrasound diagnosis of probably ovarian pedicle tumor. An explorative laparotomy revealed a solid mass of 15 cm in diameter arising from the cecal appendix, with the anatomopathological study corresponding to a desmoid tumor of the cecal appendix. CONCLUSIONS: The desmoid tumor can arise from several extra and intra-abdominal locations, the latter being the rarest and most aggressive. Accurate preoperative diagnosis is very difficult and almost always patients enter to surgery with suspected diagnosis of intraabdominal tumor of unknown etiology. The risk factors associated to its appearance are not yet characterized. The complete surgical resection of the tumor -with free surgical margins (R0)- is the treatment of choice; however, the risk of recurrence is high even with optimal tumor removal.
Asunto(s)
Neoplasias del Apéndice/diagnóstico , Fibromatosis Agresiva/diagnóstico , Adulto , Femenino , HumanosRESUMEN
Abstract Desmoid-type fibromatosis (DF) is a tumor with high local recurrence rate. Sixteen patients (18 desmoid tumors) were retrospectively evaluated. Initial surgery was performed in 13/18 tumors, with complete resection in 6 (one with free margin and five with microscopic residual disease); 10/13 had local relapse. Eleven patients with 13 tumors underwent treatment with methotrexate-vinblastine. The response rate to chemotherapy was 54%, and up to 81% if stable disease cases were included. The best response was partial remission. Only 2 had grade 4 toxicity. Twelve of 15 patients had sequelae. In 8 cases sequelae were directly related to the surgical intervention and 3 of them were severe. The 5-year progression-free survival and overall survival were 30% and 93.3%, respectively. DF has a high local relapse rate, regardless of surgical margin involvement. Low dose chemotherapy achieved stable disease and even remission of the lesions with low toxicity. The high rate of sequelae is probably related to the initial surgery performed in the majority of patients and may be avoided by the use of neoadjuvant low dose chemotherapy.
Resumen La fibromatosis tipo desmoide (FD) es un tumor con alta tasa de recurrencia local. Dieciséis pacientes (18 tumores desmoides) fueron evaluados retrospectivamente. La cirugía inicial se realizó en 13/18 tumores, con resección completa en 6 (uno con margen libre y cinco con margen microscópicamente comprometido); 10/13 tuvieron recaída local. Once pacientes con 13 tumores recibieron tratamiento con metotrexato/vinblastina. La tasa de respuesta a la quimioterapia fue del 54% y de hasta el 81% si se incluyen los casos que lograron enfermedad estable. La mejor respuesta fue remisión parcial. Solo 2 tuvieron toxicidad grado 4. Doce de 15 pacientes tuvieron secuelas. En 8 casos, las secuelas estuvieron directamente relacionadas con la intervención quirúrgica y 3 de ellas fueron graves. La sobrevida libre de progresión a 5 años y la supervivencia global fueron del 30% y del 93.3%, respectivamente. La FD tiene una alta tasa de recaída local, independientemente del margen quirúrgico. Dosis bajas de quimioterapia lograron una enfermedad estable e incluso la remisión de las lesiones, con baja toxicidad. La alta tasa de secuelas probablemente esté relacionada con la cirugía inicial realizada en la mayoría de los pacientes y podría evitarse mediante el uso de quimioterapia neoadyuvante en dosis bajas, como sugieren las estrategias actuales de tratamiento.