Desmoid-type fibromatosis of the mesentery: a clinicopatho-logical and genetic analysis of 9 cases / 浙江大学学报·医学版

Nine cases of mesenteric desmoid-type fibromatosis were diagnosed and treated in Taizhou Hospital, Wenzhou Medical University between January 2010 and May 2022, including 2 females and 7 males, aged 16 to 59 years. The lesions were in the mesentery of small intestine with 7 cases, ileocecal junction with 1 cases and transverse colon with 1 case. The tumors had an unclear boundary and no envelope, the section was solid, gray and tough. The mean maximum diameter was (10.7±8.5) cm (range 3.5-33.0 cm). Microscopically, fusiform fibroblasts and myofibroblasts were parallel, bunched or staggered, buried in a large amount of extracellular collagen. The cell morphology was relatively consistent, without obvious atypia, and mitosis was rare. Immunohistochemistry showed that the tumor cells were positive for vimentin (9/9), β-catenin (9/9), while smooth muscle actin (5/9) stains were focally positive. Ki-67 proliferation index was 1%-10%. Cytokeratin Pan, S-100, STAT6, CD117, DOG1, CD34, desmin and anaplastic lymphoma kinase stains were negative. Genetic analysis showed that there were 7 cases of c.121G>A(p.Thr41Ala) mutation of CTNNB1 gene, 1 case of c.121G>A(p.Thr41Ala) and 1 case of c.134C>T(p.Ser45Phe) double mutation, and 1 case of wild type. Tumors were surgically resected in all 9 cases. Eight cases had no recurrence or metastasis, 1 case had recurrence 6 months later, and no recurrence or metastasis after additional surgical resection.

Avaliação clínica e epidemiológica de tumor desmoide no Brasil: estudo brasileiro / Clinical and epidemiological evaluation of desmoid tumor in Brazil: a Brazilian study

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.

Tumor Desmoide de mama en paciente gestante. A propósito de un caso / Desmoid Tumor in a pregnant pacient´s breast. Case report

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.

Tratamiento quirúrgico de la fibromatosis agresiva en relación con cesárea previa / Surgical treatment of aggressive fibromatosis in relation to previous cesarean section

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.

Análise de marcadores sanguíneos em pacientes com osteossarcoma, sarcomas de partes moles e tumor desmóide / Analysis of blood markers in patients with soft tissue sarcoma and desmoid tumor

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

Tumor desmoide abdominal gigante en puerperio: caso clínico y revisión de la literatura / Giant abdominal desmoid tumor during the puerperium: Case report and review of literature

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

Identification and inner relation between gastrointestinal stromal tumor and intra-abdominal desmoid tumor / 中华胃肠外科杂志

Intra-abdominal desmoid tumor (IADT) and gastrointestinal stromal tumor (GIST) are both mesenchymal tumors mostly found in gastrointestinal tracts and easily misdiagnosed, which would directly damage the survival prognosis and quality of life of patients. With the advent of the era of precision medicine, the understanding of the above two diseases is more in-depth, and the requirements for accurate diagnosis and individualized precision treatment are more stringent. Moreover, there seems to be some internal relationship between IADT and GIST, and the lack of systematic research and discussion makes clinical decision-making and patient management easy to fall into traps and misunderstandings. Therefore, this paper reviews the clinical characteristics, pathogenesis and treatments of the two, and explore their differences and internal relations, so as to provide research and practical reference for promoting more precise and individualized diagnosis and treatment regimens.

Tumores desmoides: consideraciones diagnóstico-terapéuticas / Desmoid tumors: diagnostic and therapeutic considerations

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.

Desmoid-type fibromatosis in children. Clinical features, treatment response, and long-term follow-up / Fibromatosis tipo desmoide en niños. Características, respuesta al tratamiento y seguimiento a largo plazo

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.

Fibromatosis tipo desmoide de apéndice cecal: reporte de caso inusual y revisión de la literatura / Appendicular desmoid tumor: unusual case and review of the literature

RESUMEN Antecedente : La fibromatosis tipo desmoide es un proceso neoplásico benigno no encapsulado localmente invasivo y agresivo, que se origina de la proliferación de fibroblastos y miofibroblastos aparentemente normales. La localización más frecuente de la fibromatosis es extra-abdominal (60%), pared abdominal (25%) e intra-abdominal (8-15%), en raras ocasiones puede originarse en las vísceras (0,73%), como el páncreas, unión gastroesofágica, diafragma y apéndice. La incidencia anual de tumor desmoide se estima de 2 a 5 casos por millón. En el presente artículo, reportamos un caso de presentación inusual, originado en el apéndice cecal. Caso : Paciente de sexo femenino de 41 años con dolor pélvico agudo, que ingresa a sala de operaciones con diagnóstico clínico y ecográfico de probable tumor de ovario a pedículo torcido. En el intraoperatorio se evidenció una tumoración sólida de 15 cm de diámetro que dependía del apéndice cecal, correspondiendo el estudio anatomopatológico a tumor desmoide de apéndice cecal. Conclusiones : El tumor desmoide puede originarse en diversas localizaciones extra e intra-abdominales, siendo esta última la más rara y agresiva. El diagnóstico preoperatorio exacto es muy difícil y casi siempre los pacientes ingresan al quirófano con sospecha diagnostica de tumoración intraabdominal de etiología desconocida. Los factores de riesgos asociados a su aparición aún no se encuentran caracterizados, siendo la resección quirúrgica completa del tumor -con márgenes quirúrgicos libres (R0)- el tratamiento de elección; sin embargo, el riesgo de recurrencia es alto incluso con la remoción óptima del tumor.

ABSTRACT 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 extra- abdominal (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.

Factors Associated with Disease Stabilization of Desmoid-Type Fibromatosis

BACKGROUND: Spontaneous disease stabilization of desmoid-type fibromatosis (DF) has been demonstrated in many reports, and the watchful waiting approach without any frontline treatment is becoming popular as an initial management strategy. In this study, we aimed to assess the disease stabilization rate and identify predictive factors for disease stabilization of DF in patients with conservative treatment.METHODS: We reviewed 76 patients with sporadic extra-abdominal DF who were managed with frontline conservative treatment in our institute. The minimum follow-up was 12 months. Stabilization was defined as radiological evidence of no change or continuous decrease in size of the tumor for six months or more. The primary endpoint was stabilization of DF. Possible patient-, disease-, and treatment-related factors predictive of disease stabilization were analyzed with multivariate analysis.RESULTS: At final follow-up, 54 of the 76 tumors (71%) were stable, and mean time to stabilization was 30.4 months (range, 7 to 112 months). On Kaplan-Meier survival analysis, the spontaneous stabilization rate was 25.4% at one year, 52.7% at two years, and 70.9% at three years. The mean time to spontaneous stabilization was longer in patients with ≤ 40 years of age (p = 0.022) or recurrence (p = 0.041). On multivariate analysis with the Cox proportional hazard method, recurrence (hazard ratio [HR], 1.79; p = 0.041) and younger age (HR, 2.04; p = 0.022) were identified as independent prognostic factors for longer time to disease stabilization.CONCLUSIONS: Frontline conservative treatment seems to be the optimal treatment for most patients with DF. Younger patients or those with recurrence may require longer time to spontaneous disease stabilization.

Mesenteric desmoid tumor after Roux-en-Y gastric bypass: a case report

We report the case of a 37-year-old woman investigated for left flank pain 1 year after bariatric surgery (Roux-en-Y gastric bypass). Abdominal computed tomography (CT) revealed a solid intra-abdominal lesion measuring 9.3 × 9.4 × 10.4 cm, compressing adjacent structures with no signs of invasion. Ileocolectomy with partial mesenteric resection was performed. A histopathological and immunohistochemical analysis confirmed the diagnosis of mesenteric desmoid tumor.(AU)

Fibromatosis mamaria. Reporte de dos casos clínicos y revisión bibliogáfica / Mammary fibromatosis. Two case report and review of literatura

RESUMEN Introducción y objetivos: La fibromatosis produce tumores benignos pero localmente agresivos, que afectan a los tejidos blandos. A nivel mamario, representa tan sólo el 0.2% de las neoplasias de la mama. Nuestro objetivo con el presente artículo es profundizar en el conocimiento de la fibromatosis mamaria, a través del estudio de dos casos clínicos, mostrando sus características clínico-radiológicas e histológicas, e intentar establecer un protocolo de actuación adecuado. Métodos: Estudio retrospectivo de dos casos clínicos de fibromatosis mamaria diagnosticados en el Hospital Universitario La Paz entre los años 2018 y 2019. Resultados: Presentaremos dos pacientes con diagnóstico de fibromatosis mamaria, ambas debutaron con la autopalpación de un nódulo mamario. Al realizarles una ecografía, se visualizó un nódulo sólido, mal definido y axila ecográficamente negativa, que precisó de biopsia-aspiración con aguja gruesa. En los dos casos, se decidió resección quirúrgica de la lesión. Seguimiento mediante exploración mamaria y pruebas de imagen periódicas. Conclusiones: Aunque se trata de una entidad benigna, la fibromatosis mamaria puede simular un proceso maligno, tanto clínica como radiológicamente, por lo que precisa de un estudio histológico. A pesar de que la diseminación metastásica es muy poco frecuente, no se debe olvidar el carácter agresivo a nivel local de esta patología, y sus altas tasas de recurrencia. Como tratamiento, se debe realizar una resección quirúrgica, aunque recientemente se ha contemplado la opción de vigilancia estrecha sin tratamiento. No existe evidencia científica que justifique la utilización de otros tratamientos como la radioterapia o el tratamiento hormonal.

ABSTRACT Introduction and objectives: Fibromatosis produces benign but locally aggressive tumours that affect soft tissues. At breast level, it represents only 0.2% of breast neoplasms. Our goal with this article is to increase knowledge on breast fibromatosis, through the study of two clinical cases; explaining their clinical-radiologic and histological characteristics. Additionally, try to establish an adequate protocol, for the management of the disease and for its subsequent monitoring. Methods: A retrospective study about two clinical cases of breast fibromatosis diagnosed in La Paz Hospital between 2018-2019. Results: both patients presented with clinical manifestations, autopalpation of a breast nodule. A breast ultrasound was performed and a solid nodule was visualized, with poorly defined edges and ecographically negative armpit. A core needle biopsy was performed to confirm the histological diagnosis. In both clinical cases, the treatment was surgical resection of the lesion. Periodic revisions are being performed in order to exclude recurrence. Conclusions: Although it is a benign disease, breast fibromatosis can simulate a malignancy, both in a clinical and radiological way, so histological study is mandatory in order to achieve an accurate diagnosis. Even metastatic dissemination is extremely rare, the local aggressive nature and high rates of recurrence for fibromatosis makes surgical excision, with wide free margins, the most important tool in treatment, although the possibility of close surveillance without treatment is recently being contemplated. There is no scientific evidence to justify the use of other treatments such as radiotherapy or hormonal treatment.

Postoperative developed intra-abdominal desmoid tumor after surgical resection of gastrointestinal malignancy: A review of 10 cases

PURPOSE: Desmoid tumors are locally aggressive tumors with no known potential for metastasis. They tend to recur even after complete excision. Sometimes it is not easy to differentiate between intra-abdominal desmoid and tumor recurrence, especially after gastrointestinal (GI) tumor resection. The current study aims to review the characteristics, management, and outcomes of patients with intra-abdominal desmoid tumor post GI resection.METHODS: During the period between 2007 and 2018, after a retrospective review of patients' clinical data, 10 patients were finally included. Medical records were screened for demographic, clinical, pathological data, management strategy, postoperative morbidity, mortality, recurrence rate and follow-up.RESULTS: The study comprised 10 patients (8 males). The median age was 53.5 years (range, 35–68 years). Two patients diagnosed as familial adenomatous polyposis (FAP). All the patients underwent previous GI resection: three (30%) for colon cancer, three (30%) gastrectomy, two (20%) total proctocolectomy with ileal pouch-anal anastomosis (TPC+IPAA) for FAP, one (10%) low anterior resection (three rectal cancers) and one (10%) distal pancreatectomy. The tumor was found to be in bowel mesentery in eight cases (80%). The median tumor size was 5.3 cm (range, 2.6–19.0 cm). Six patients (60%) underwent open resection, while four patients (40%) underwent laparoscopic surgery. Complications occurred in five cases (50%) and ranged from Clavien-Dindo (II-III). The median follow-up period was 16.5 months (1.5–136.0 months) with recurrence in one case (10%). Pathology came out to be desmoid tumor fibromatosis in all cases.CONCLUSION: When a mass develops after surgical resection for abdominal GI malignancy and tends to be large in size, located in the bowel mesentery and away from previous primary tumor site, most probably it is desmoid rather than tumor recurrence.

Avaliação das mutações nos códons 41 e 45 do gene codificante da betacatenina em pacientes portadores de tumor desmoide esporádico e sua associação com o prognóstico / Evaluation of mutations in codons 41 and 45 of the Beta-Catenin encoding gene in patients with sporadic desmoid tumors and its association with prognosis

O tumor desmoide (TD) é uma proliferação fibroblástica clonal rara, caracterizada por crescimento infiltrativo e tendência à recidiva local, embora incapaz de metastatizar. A maioria desses tumores é esporádica e contém mutações no gene que codifica a proteína betacatenina. Três mutações em dois códons do gene CTNNB1 foram identificadas como mais frequentes. O tratamento cirúrgico dessa doença tem se mostrado um verdadeiro desafio, e a identificação de fatores prognósticos poderia ajudar na caracterização de grupos com maior ou menor risco para desenvolver recidiva local após esse tratamento. O objetivo deste estudo foi avaliar mutações nos códons 41 e 45 do gene CTNNB1 em pacientes portadores de tumores desmoides esporádicos tratados com cirurgia, bem como avaliar a possível influência de variáveis clínicas, demográficas e moleculares na sobrevida livre de recidiva. Materiais e Métodos: Foi conduzido estudo retrospectivo, unicêntrico, transversal. Foram incluídos pacientes com diagnóstico de tumor desmoide submetidos à ressecção cirúrgica, que tinham dados clínicos e material biológico disponíveis. A correlação entre as variáveis qualitativas foi feita pelo teste qui-quadrado ou teste exato de Fisher; a comparação das variáveis quantitativas pelo teste U de Mann-Whitney ou pelo teste de Kruskal-Wallis; a análise de sobrevida livre de recidiva pela técnica de Kaplan-Meier; e os riscos relativos pela técnica de regressão de Cox uni ou multivariada. Resultados: No período de 1980 a 2015, foram identificados 107 pacientes. A maioria era do sexo feminino (58,9%), de etnia branca (78,9%), tinha idade entre 25 e 50 anos (58,9%), com lesões que se localizavam fora das extremidades (63,4%), apresentando tamanho menor que 10 centímetros (76,4%) e todos foram tratados cirurgicamente. O tempo de seguimento médio foi de 134 meses, a taxa global de sobrevida livre de recidiva (SLR) foi de 74,5% em 2 anos, 65,1% em 5 anos, 63,7% em 10 anos e 59,5% em 20 anos. Dos 107 pacientes que possuíam informações clínicas, foram obtidas 71 amostras tumorais para análise molecular que foi realizada utilizando NGS. Destes, 61 pacientes (85,9%) apresentavam alguma mutação nos códons 41 ou 45 do éxon 3 do gene CTNNB1 e 10 espécimes (14,1%) não tinham qualquer mutação nesses códons. Trinta e três (46,5%) pacientes apresentaram mutação T41A 16 (22,5%) S45F, 6 (8,5%) S45P, 5 (7%) T41A e S45F e 1 (1,4%) T41A e S45F, o valor médio da frequência alélica foi de 16,54%. Os pacientes com mutação S45F apresentaram taxa de sobrevida livre de recidiva em dois, cinco e dez anos menor do que os demais pacientes não mutados ou com outro tipo de mutação (26,7% 13,3% e 13,3% versus 78,4%, 68,1% e 65,4%, respectivamente). Na análise multivariada, tipo de mutação (RR = 5,25 IC [ 2,27­12,15]; p < 0,0001) e topografia (RR = 3,15 IC [1,35­ 7,33]; p = 0,008) foram fatores independentes para o risco de recidiva e o modelo prognóstico proposto evidenciou que os pacientes com alto risco (um ou dois fatores) podem apresentar até 8,36 vezes mais risco de recidiva local após o tratamento cirúrgico que os demais pacientes (IC [2,87­24,6]; p = 0,0001). Os resultados do presente estudo permitem concluir que o sequenciamento de segunda geração é um método adequado para detectar as mutações nos pacientes com tumores desmoides, e a mutação S45F esteve associada com maior risco de recidiva local. Em conjunto com outros fatores clínicos, a presença dessa mutação pode identificar um subgrupo de pacientes com elevado risco de recidiva. Esse achado pode auxiliar na indicação de cirurgias extensas e mutilantes, evitando a morbidade para um grupo específico de pacientes. Todavia, tais achados devem ser validados em uma coorte mais ampla de pacientes

The desmoid tumor (DT) is a rare (mono)clonal fibroblastic proliferation characterized by infiltrative growth with tendency to local recurrence although unable to metastasize. Most of these tumors are sporadic and contain mutations in the gene encoding Beta-Catenin. Three mutations in two codons of the CTNNB1 gene were identified as being more frequent. Surgical treatment of this disease has been revealed to be a real challenge and the identification of prognostic factors would help in the identification of groups with higher or lower risk to develop local recurrence after this treatment. The objective of this study was to evaluate mutations in codons 41 and 45 of the CTNNB1 gene in patients whose tumors were treated with surgery as well as to assess clinical and demographic variables and correlate them with relapse-free survival. Materials and Methods: a retrospective, unicentric, cross-sectional study was conducted. Patients diagnosed with desmoid tumor who were submitted to surgery, had clinical data and biological material available were included. The correlation between the qualitative variables was made by the chi-square test or Fisher exact test; the quantitative variables comparison by the Mann-Whitney U test or Kruskal-Wallis test; the relapse-free survival by Kaplan-Meier; and relative risks by the univariate or multivariate Cox regression technique. Results: 107 patients were identified from 1980 to 2015. The majority were female (58.9%), white (78.9%) 25-50 years old (58.9%), their lesions were located outside the extremities (63.4%), measured less than 10 centimeters (76.4%) and they were all surgically treated. Mean follow up period was 134 months, overall relapse-free survival rate (RFS) was 74.5% in 2 years, 65.1% in 5 years, 63.7% in 10 years and 59.5% in 20 years. From 107 patients who had clinical information, 71 samples were obtained for molecular analysis. Among these, 61 patients (85.9%) had mutations at codons 41 or 45 of exon 3 of the CTNNB1 gene and 10 specimens (14.1%) had no mutations at these codons. Thirty-three (46.5%) patients had mutation T41A 16 (22.5%) S45F, 6 (8,5%) S45P, 5 (7%) T41A and S45F and 1 (1,4%) T41A and S45F, the mean of allele frequency was 16.54%. Patients with mutation S45F had a relapse-free survival rate of two, five and 10 years smaller than the patients with no mutations or with a different mutation (26.7% 13.3% and 13.3% versus 78.4%, 68.1% and 65.4%, respectively). In the multivariate analysis, type of mutation (RR = 5,5 IC[2.27 ­ 12.15]; p < 0.0001) and topography (RR = 3.15 IC [1.35 ­ 7.33]; p = 0.008) correlated with risk of relapse and the proposed prognostic model demonstrated that high risk patients (one or two factors) may present a greater risk (up to 8.36 times) of local recurrence after surgical treatment than other patients (IC[2.87 ­ 24.6]; p = 0.0001). The results of the present study allow us to conclude that second generation sequencing is a suitable method to detect mutations in patients with desmoid tumors and the S45F mutation has been associated with an increased risk of local recurrence. Combined with other clinical factors, the presence of this mutation may identify a subgroup of patients with a high risk of relapse. This finding may support the indication of extensive and mutilating surgeries, avoiding morbidity for a specific group of patients. Nevertheless, such findings should be validated in a broader cohort of patients

Survival outcomes after adjuvant radiotherapy for aggressive fibromatosis depend on time frame and nuclear β-catenin

PURPOSE: To identify prognostic factors influencing progression-free survival (PFS) of aggressive fibromatosis (AF) after postoperative radiotherapy (PORT) and assess correlations between immunohistochemistry (IHC) features of β-catenin/smooth muscle actin (SMA) and PFS. MATERIALS AND METHODS: Records of 37 patients with AF treated by PORT from 1984 to 2015 were retrospectively reviewed. Fifteen patients underwent wide excision for AF and 22 patients received debulking operation. The median total dose of PORT was 59.4 Gy. IHC staining results of β-catenin and SMA were available for 11 and 12 patients, respectively. RESULTS: The median follow-up duration was 105.9 months. Five-year PFS rate was 70.9%. Tumor size or margin status was not related to PFS in univariate analysis (p = 0.197 and p = 0.716, respectively). Multivariate analysis showed that increased interval from surgery to PORT (>5.7 weeks) was a marginal risk factor for PFS (p = 0.054). Administration of PORT at the initial diagnosis resulted in significantly improved PFS compared to deferring PORT after recurrence (p = 0.045). Patient with both risk factors of deferring PORT after recurrence and interval from surgery to PORT >5.7 weeks had significantly lower 5-year PFS than patients without risk factor (34.1% vs. 100.0%; p = 0.012). Nuclear β-catenin intensity tended to inversely correlate with 5-year PFS, although it did not reach statistical significance (62.5% at low vs. 100.0% at high; p = 0.260). SMA intensity was not related to PFS (p = 0.700). CONCLUSION: PORT should be performed immediately after surgery irrespective of margin status or tumor size especially in recurrent case. Nuclear β-catenin staining intensity of IHC might correlate with local recurrence.

Colonic fibromatosis - a case report and review of the literature / Fibromatose colônica - relato de caso e revisão da literatura

ABSTRACT Intra-abdominal desmoids tumours are very rare and usually occur in patients with familiar adenomatous polyposis and previous surgery. They represent fibroepithelial growths with varied biologic behavior and therefore different prognosis. We report a case of a 60-year-old patient with a large right colonic mass who underwent right hemicolectomy. Histology proved morphological and immuno-histochemical features indicating fibromatosis. This desmoid tumour appeared growing from the colonic wall rather than the mesocolon, confirming a true colonic wall fibromatosis, a deep isolated form of intra-abdominal fibromatosis. Surgical resection is the treatment of choice in isolated well confirmed lesions. Multidisciplinary team approach is crucial for treatment and prognosis.

RESUMO Os tumores desmoides intra-abdominais são muito raros e geralmente ocorrem em pacientes com polipose adenomatosa familiar e cirurgia prévia. Eles representam crescimentos fibroepiteliais com comportamento biológico variado e, portanto, prognóstico diferente. Relatamos o caso de um paciente de 60 anos com grande massa colônica à direita, submetido a hemicolectomia direita. A histologia demonstrou características morfológicas e imuno-histoquímicas que indicavam fibromatose. Este tumor desmoide surgiu crescendo a partir da parede do cólon, e não do mesocólon, confirmando uma verdadeira fibromatose da parede do cólon, uma forma isolada profunda de fibromatose intra-abdominal. A ressecção cirúrgica é o tratamento de escolha em lesões isoladas bem confirmadas. A abordagem multidisciplinar é crucial para o tratamento e prognóstico.

Large desmoid tumors in familial adenomatous polyposis: a successful outcome

Desmoid tumors develop from connective tissue, fasciae, and aponeuroses, and may occur in the context of familial adenomatous polyposis or may arise sporadically; also, they may be extra-abdominal, intra-abdominal, or located in the abdominal wall. These benign tumors have a great aggressiveness with a high rate of local recurrence. Familial adenomatous polyposis is an inherited condition with autosomal dominant transmission, and is characterized by the development of multiple colonic and rectal adenomatous polyps, as well as desmoid tumors. We present the case of a 54-year-old woman with germline APC gene mutation, who underwent a total colectomy, subsequently developing two large infiltrative solid intra-abdominal lesions consistent with desmoid tumors. Medical treatment with Cox-2 inhibitors was initiated without result. She was submitted to resection for intestinal obstruction, but developed local recurrence. The lesions were also unresponsive to tamoxifen, and chemotherapy was initiated with dacarbazine plus doxorubicin, switching to vinorelbine plus methotrexate, achieving a good response in all lesions after 12 months. The approach to these intra-abdominal lesions should be progressive, beginning with observation, then a medical approach with non-steroidal anti-inflammatory drugs or with an anti-hormonal agent. Afterwards, if progression is still evident, chemotherapy should be started. Surgery should be reserved for resistance to medical treatment, in palliative situations, or for extra-abdominal or abdominal wall desmoids tumors.