Large Multicentric Synchronous Extra-Abdominal Fibromatosis of the Leg and Foot: A Case Report.

Extra-abdominal fibromatosis is an uncommon, benign locally aggressive fibrous soft-tissue tumor that usually occurs in the shoulders, chest wall, back, thigh, and head and neck affecting the young adult population. It is commonly located in the subcutaneous tissue and may infiltrate the adjacent skeletal muscles. We hereby report a rare case of a large extra-abdominal fibromatosis of the leg and foot in a 38-year-old woman. The patient presented with a large voluminous lesion clinically and on imaging, which was difficult to diagnose. Magnetic resonance imaging (MRI) was very helpful in diagnosing the lesion. It revealed a large relatively well-defined, lobulated hypointense mass in the posterior compartment of the leg with extension into the lower thigh and foot with local infiltration into the gastrocnemius and soleus muscles. An incisional biopsy was performed, and the mass was diagnosed on pathological examination as a spindle-shaped fibroblast proliferation suggesting extra-abdominal fibromatosis.

Primary intra­abdominal desmoid fibromatosis associated with familial adenomatous polyposis: A case report.

Desmoid fibromatosis (DF) is a clonal proliferative disorder of myofibroblasts, which arises, with a low incidence, in soft tissue, including within the abdomen. The incidence of DF is associated with familial adenomatous polyposis (FAP), and is more common following FAP surgery. It is rare for a patient to make his/her first visit to hospital due to DF symptoms associated with FAP. In the present report, a case of mesenteric DF associated with FAP is described. This case also had incomplete intestinal obstruction due to DF. By summarizing previous studies examining DF and FAP treatment, combined with the disease characteristics of this patient, the clinical treatment strategy for DF associated with FAP was explored.

Aggressive fibromatosis in the submandibular region of a child.

Aggressive fibromatosis is proliferation of well-differentiated fibroblasts. Submandibular region is rare location for fibromatosis. We report a case of a rapidly growing mass in submandibular region of 5-year-old girl, excised surgically and ascertained to be aggressive fibromatosis on histological examination. Recovery was uneventful, and she was disease-free in 6-month follow-up.

Sporadic Desmoid Tumours: Systematic Review with Reflection on the Role of Cryoablation.

Desmoid tumours (DT) are rare locally infiltrative soft-tissue tumours which do not metastasise. DT arise sporadically or are associated with familial syndromes, with different clinical and genetic patterns. In recent years there has been an increasing therapeutic role of cryoablation for the treatment of sporadic DT. Therefore, in this present review, we: (a) summarize all the main epidemiological, clinical, and therapeutic aspects of sporadic DT that are relevant to an interventional radiologists' practice; (b) present the results of a systematic review that has been conducted with the intent of highlighting the main clinical outcomes available thus far with cryoablation; and (c) discuss the current and future potential applications of cryoablation in this field. Five studies were included in the systematic review accounting for 146 patients. Only 18.5% patients received cryoablation as a first-line treatment. Overall, the volume of the DT undergoing cryoablation was very large (mean total DT volume of 237 cm3). Major complications were noted for 13.3-30% patients and following 2.4-6.7% interventional sessions. The rates of complete tumour response ranged between 0 and 43.3%. 1- and 3-year local progression-free survival rates were 85.1-85.8%, and 77.3-82.9%, respectively. Complete pain relief was reported in 40-66.7% symptomatic patients. In conclusion, cryoablation is currently proposed as a therapeutic strategy to very large DT, which is recognized to be associated with an increased procedure-related morbidity and reduced rates of complete tumour response. Proposing cryoablation as the first-line treatment may improve these clinical outcomes.

The epidemiology of desmoid tumors in Denmark.

INTRODUCTION/AIM: The epidemiology, demographic, clinical, treatment, and healthcare resource utilization (HRU) characteristics of desmoid tumor (DT) patients treated at two sarcoma centers in Denmark is described. METHODS: Using Danish health registers, we studied DT patients treated at two sarcoma centers between 2009 and 2018. For each patient, ten persons from the general population were randomly matched on birth year, sex, and region of residence. RESULTS: Of the 179 DT patients identified, 76% were female and the median patient age was 38 years at diagnosis (interquartile range: 31-50). An average annual incidence of DTs over the study period was 3.2 per 1000,000 individuals with the observed annual incidence of DTs ranging from 2.2 (2011) to 4.3 (2017) per 1000,000 individuals. No notable linear time trend in incidence was observed. Anatomical DT sites included extra-abdominal (49%), abdominal wall (40%), and intra-abdominal or retroperitoneal areas (8%). In total, 56% of patients were initially treated surgically. However, while 75% of patients diagnosed with DT between 2009 and 2014 were initially treated surgically, this was true for only 32% of patients diagnosed with DT between 2015 and 2018. A total of 56% of DT patients used chemotherapeutic agents, tyrosine kinase inhibitors, NSAIDs, opioids, antidepressants, or steroids at some point during the three years before their DT diagnoses. In contrast, 70% of surgically treated and 63% of non-surgically treated patients used one of these drugs in the subsequent three years, including NSAIDs (45% surgical vs. 33% non-surgical), opioids (39% surgical vs. 27% non-surgical), and steroids (22% surgical vs. 18% non-surgical). The average number of inpatient and outpatient visits, days of hospitalization, and additional surgical procedures were higher among DT patients than the comparison cohort. CONCLUSION: DTs are rare but have a large impact on patients' health, HRU, and medication utilization.

APC mosaicism in a young woman with desmoid type fibromatosis and familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is usually caused by germline mutations in the adenomatous polyposis coli (APC) gene. The classic form is characterized by hundreds to thousands of adenomas in the colorectum and early onset colorectal cancer (CRC) if left untreated. FAP is also associated with multiple extra-colonic manifestations such as gastroduodenal polyps, osteomas, epidermoid cysts, fibromas and desmoids. Most desmoid tumours in FAP patients occur intra-abdominally. Approximately 15-20% of the APC mutations are de novo mutations. Somatic mosaicism has been reported in some sporadic cases of polyposis but is probably an underestimated cause of the disease. This case report presents the detection of a mosaic APC mutation in a 26-year-old woman who as a child had been diagnosed with desmoid type fibromatosis. FAP was suggested when she presented with extensive extra abdominal fibromatosis. Our findings indicate that APC mutations may be suspected in patients presenting with a desmoid regardless of its location. If there is clinical evidence that the patient has FAP, adenomas and colonic mucosa in addition to leukocyte DNA should be included in the screening, preferably using methods that are more sensitive than Sanger sequencing.

A Patient With Desmoid Tumors and Familial FAP Having Frame Shift Mutation of the APC Gene.

Desmoids tumors, characterized by monoclonal proliferation of myofibroblasts, could occur in 5-10% of patients with familial adenomatous polyposis (FAP) as an extra-colonic manifestation of the disease. FAP can develop when there is a germ-line mutation in the adenomatous polyposis coli gene. Although mild or attenuated FAP may follow mutations in 5΄ extreme of the gene, it is more likely that 3΄ extreme mutations haveamore severe manifestation of thedisease. A 28-year-old woman was admitted to the Cancer Institute of Iran with an abdominal painful mass. She had strong family history of FAP and underwent prophylactic total colectomy. Pre-operative CT scans revealed a large mass. Microscopic observation showed diffuse fibroblast cell infiltration of the adjacent tissue structures. Peripheral blood DNA extraction followed by adenomatous polyposis coli gene exon by exon sequencing was performed to investigate the mutation in adenomatous polyposis coli gene. Analysis of DNA sequencing demonstrated a mutation of 4 bpdeletions at codon 1309-1310 of the exon 16 of adenomatous polyposis coli gene sequence which was repeated in 3 members of the family. Some of them had desmoid tumor without classical FAP history. Even when there is no familial history of adenomatous polyposis, the adenomatous polyposis coli gene mutation should be investigated in cases of familial desmoids tumors for a suitable prevention. The 3΄ extreme of the adenomatous polyposis coli gene is still the best likely location in such families.

The role of S100a4 (Mts1) in Apc- and Smad4-driven tumour onset and progression.

INTRODUCTION: S100a4 is a calcium-binding protein belonging to the family of S100-proteins, highly expressed in different stromal cell types. S100A4 has been reported as a prognostic marker in colorectal cancer in association with tumour progression and metastasis. METHODS: In this study, we analysed the in vivo role of S100a4 in intestinal tumour initiation and progression using different transgenic and knockout mouse models. RESULTS: We found that genetic ablation or overexpression of S100a4 in both Apc- and Smad4-mutant mice do not affect tumour initiation in the intestinal tract. In contrast, S100a4 epithelial overexpression in Apc1638N/+/KRASV12G mice increases the dissemination of intestinal tumour cells to the liver, in agreement with its role in tumour metastasis. Moreover, we report a novel role for S100a4 in desmoid formation where S100a4 deficiency results in a significant reduction of the tumour burden characteristic of the Apc1638N model. In agreement with these results, S100a4 appears to be co-expressed together with mesenchymal stem cell (MSC) markers in desmoid tumours from Apc1638N/+ mice, as well as from sporadic and hereditary human desmoids. CONCLUSION: Our data provide the first report on the in vivo role of S100a4 in intestinal tumourigenesis and describe a new role for S100a4 in the aetiology of desmoids formation.

Fibromatosis agresiva en la infancia en el servicio de Oncopediatría / Aggresive fibromatosis in childhood at the oncologic pediatric service

Introducción: la fibromatosis abarca un amplio espectro de lesiones fibrosas proliferativas con apariencia microscópica similar, que afectan a diferentes localizaciones anatómicas. Se agrupan dentro de los tumores fibrosos benignos en niños, y poseen un potencial intermedio entre las lesiones benignas y malignas.Objetivo: describir las características clínicas y el tratamiento de los pacientes con diagnóstico de fibromatosis agresiva tratados en el servicio de Oncopediatría en el Instituto Nacional de Oncología y Radiobiología.Métodos: se realizó un estudio descriptivo, longitudinal y retrospectivo desde el 1º de enero de 2003 al 31 de diciembre de 2013, según variables demográficas, clínicas y terapéuticas. Se identificaron los pacientes a partir de las bases de datos del registro hospitalario del Instituto Nacional de Oncología y Radiobiología. Se seleccionaron todos los pacientes con diagnóstico histológico de esta enfermedad.Resultados: se identificaron 9 pacientes con predominio del sexo masculino (56 por ciento), con un rango de edades entre 0 y 9 años; y la localización más frecuente fue cabeza y cuello. Las modalidades de tratamiento utilizadas fueron: cirugía en 100 por ciento de los casos, y quimioterapia y radioterapia concurrente (33 por ciento). En estos momentos se cuenta con 100 por ciento de supervivencia.Conclusiones: la fibromatosis agresiva son lesiones benignas muy raras, agresivas localmente y sin potencial metastásico. Su tratamiento fundamental es la cirugía, sin embargo, deben incluirse otras modalidades terapéuticas para lograr el control local de la enfermedad(AU)

Fibromatosis agresiva en la infancia en el servicio de oncopediatría / Aggresive fibromatosis in childhood at the oncologic pediatric service

INTRODUCCIÓN: la fibromatosis abarca un amplio espectro de lesiones fibrosas proliferativas con apariencia microscópica similar, que afectan a diferentes localizaciones anatómicas. Se agrupan dentro de los tumores fibrosos benignos en niños, y poseen un potencial intermedio entre las lesiones benignas y malignas. OBJETIVO: describir las características clínicas y el tratamiento de los pacientes con diagnóstico de fibromatosis agresiva tratados en el servicio de Oncopediatría en el Instituto Nacional de Oncología y Radiobiología. MÉTODOS: se realizó un estudio descriptivo, longitudinal y retrospectivo desde el 1º de enero de 2003 al 31 de diciembre de 2013, según variables demográficas, clínicas y terapéuticas. Se identificaron los pacientes a partir de las bases de datos del registro hospitalario del Instituto Nacional de Oncología y Radiobiología. Se seleccionaron todos los pacientes con diagnóstico histológico de esta enfermedad. RESULTADOS: se identificaron 9 pacientes con predominio del sexo masculino (56 %), con un rango de edades entre 0 y 9 años; y la localización más frecuente fue cabeza y cuello. Las modalidades de tratamiento utilizadas fueron: cirugía en 100 % de los casos, y quimioterapia y radioterapia concurrente (33 %). En estos momentos se cuenta con 100 % de supervivencia. CONCLUSIONES: la fibromatosis agresiva son lesiones benignas muy raras, agresivas localmente y sin potencial metastásico. Su tratamiento fundamental es la cirugía, sin embargo, deben incluirse otras modalidades terapéuticas para lograr el control local de la enfermedad.

INTRODUCTION: fibromatosis covers a wide spectrum of proliferative fiber lesions with similar microscopic appearance that affect various anatomical locations. These lesions are grouped into the benign fiber tumors in children and have an intermediate potential between the benign and the malignant lesions. OBJECTIVE: to describe the clinical characteristics of and the treatment prescribed for patients with diagnosis of aggressive fibromatosis, who were treated at the oncologic pediatrics service of the National Institute of Oncology and Radiobiology. METHODS: retrospective, longitudinal and descriptive study conducted from January 1st, 2003 through December 31st 2013 based on demographic, clinical and therapeutic variables. The patients were identified according to databases from the hospital register of the National Institute of Oncology and Radiobiology. All the patients with histological diagnosis for the disease participated in the study. RESULTS: nine patients were detected with predominance of males (56 %), age ranging from 0 to 9 years and the most common location were head and neck. The treatment modalities included surgery in 100 % of cases and concurrent chemotherapy and radiotherapy (33 %). Currently, the survival rate is 100 %. CONCLUSIONS: aggressive fibromatosis are benign lesions that are very unusual, locally aggressive and with no metastatic potential. The main treatment is surgery; but other therapeutic variants should be included to achieve the local management of disease.

Optimal therapy for desmoid tumors: current options and challenges for the future.

Desmoid tumors, or aggressive fibromatosis, are rare, locally infiltrative neoplasms caused by mutations that activate ß-catenin. Although these tumors do not metastasize, they are difficult to manage due to variability in tumor presentation and behavior. A variety of treatment options exist, including surgery, radiotherapy, chemotherapy, hormone therapy, isolated limb perfusion, cryoablation and tyrosine kinase inhibitors. Treatment-induced morbidity and poor local control rates, combined with spontaneous stabilization of some desmoid tumors, have allowed watchful waiting to recently emerge as a front-line management option. This has emphasized the need to better understand tumor behavior in order to differentiate between tumors that may stabilize and those that may progress. Here, we review the most recent findings in desmoid tumor biology and treatment options for this enigmatic disease.

Aggressive fibromatosis of the mandible in a two-month old infant.

Aggressive fibromatosis is a benign spindle cell tumor with locally infiltrative behavior and tendency to recur. It has overlapping features with other spindle cell lesions and hence it is pertinent to be distinguished from them as they have different treatment modalities. We report a rare case involving the mandible of a two-month old infant with histopathological, immunohistochemical and imaging features.

Giant omental fibromatosis presenting as pelvic mass.

Omental fibromatosis (abdominal desmoids) is a rare benign but locally aggressive neoplasm characterized by mass like or infiltrative growth of fibrous tissue. It usually arises from the abdominal wall or the extremities, however rarely it may also arise in the omentum, ileocolic mesentery, transverse or sigmoid mesocolon and ligamentum teres. Here, we present an 18-year-old male, who presented with lower abdominal pain and palpable lump in hypogastric region. Computed tomography of the abdomen showed large heterogeneous mass in lower abdomen, possibly arising from mesentery with regional adenopathy. Patient underwent exploratory laparotomy with a preoperative diagnosis of mesenteric tumour possibly gastrointestinal stromal tumour (GIST). Histopathological examination revealed the lesion as omental fibromatosis. To the best of our knowledge, very few cases of omental fibromatosis are noted in literature. Here, we describe a rare case of giant omental fibromatosis which resembled mesenteric GIST clinically but finally diagnosed as fibromatosis by histomorphology and immunohistochemistry (IHC). The present article describes fibromatosis of greater omentum and the difficulty in preoperative diagnosis, as it is frequently misdiagnosed as GIST.

Desmoid tumours: our experience of six cases and review of literature.

Desmoid tumours represent aggressive fibroblastic proliferation of the musculoaponeurotic structures commonly from the anterior abdominal wall. These tumours infiltrate locally, recur frequently but do not metastasize. Antecedent trauma, pregnancy and estrogens play a role in the etiopathogenesis of these tumours. In familial adenomatous polyposis (FAP) genetic history associated with chromosomal abnormality and familial incidence as in Gardner's syndrome is reported and most of these tumours are intraperitoneal either in the mesentery or pelvis and may be multiple and they carry poor prognosis. Surgery is the most preferred treatment and requires wide excision with 1 cm margin followed by reconstruction of the defect in the anterior abdominal wall either with local musculoaponeurotic layers or with synthetic mesh. In intra-abdominal cases associated with FAP in addition to surgery, hormonal treatment, chemotherapy and Radiotherapy are also advised depending upon the particular condition but usually prognosis is not encouraging. In this article we present our personal experience in the successful treatment of six cases of sporadic desmoids, five in females of child bearing age, and all in the anterior abdominal wall and one extra abdominal in a child aged 13 y in the gluteal region (Case 6). It is very interesting and unique to see two desmoid tumours developing in the same patient (Case2)one in each of the Rectus abdominal muscles (Right & Left).

Expression of FAP, ADAM12, WISP1, and SOX11 is heterogeneous in aggressive fibromatosis and spatially relates to the histologic features of tumor activity.

Aggressive fibromatosis (AF) represents a group of tumors with a variable and unpredictable clinical course, characterized by a monoclonal proliferation of myofibroblastic cells. The optimal treatment for AF remains unclear. Identification and validation of genes whose expression patterns are associated with AF may elucidate biological mechanisms in AF, and aid treatment selection. This study was designed to examine the protein expression by immunohistochemistry (IHC) of four genes, ADAM12, FAP, SOX11, and WISP1, that were found in an earlier study to be uniquely overexpressed in AF compared with normal tissues. Digital image analysis was performed to evaluate inter- and intratumor heterogeneity, and correlate protein expression with histologic features, including a histopathologic assessment of tumor activity, defined by nuclear chromatin density ratio (CDR). AF tumors exhibited marked inter- and intratumor histologic heterogeneity. Pathologic assessment of tumor activity and digital assessment of average nuclear size and CDR were all significantly correlated. IHC revealed protein expression of all four genes. IHC staining for ADAM12, FAP, and WISP1 correlated with CDR and was higher, whereas SOX11 staining was lower in tumors with earlier recurrence following excision. All four proteins were expressed, and the regional variation in tumor activity within and among AF cases was demonstrated. A spatial correlation between protein expression and nuclear morphology was observed. IHC also correlated with the probability of recurrence following excision. These proteins may be involved in AF pathogenesis and the corresponding pathways could serve as potential targets of therapy.

[Fibromatosis breast in the male. Case study]. / Fibromatosis mamaria en el varón. A propósito de un caso.

BACKGROUND: mammary fibromatosis is a rare pathology. It constitutes 0.2% of breast cancers, and case in men are exceptional. The definitive diagnosis is histological. CLINICAL CASE: we report the case of a male of 52 years, diagnosed with breast fibromatosis after pathologic study of tumor in the right breast. Programmed surgery for excision with wide margins was done. We performed a mastectomy of the subcutaneous fibromatosis with a pathologic study with clear margins. The postoperative course was uncomplicated and did not require adjuvant therapy. At 6 months follow-up he remains free of disease. The treatment of choice is surgical excision with wide margins. Adjuvant treatment is controversial. CONCLUSIONS: the fibromatosis in the breast is very rare and an exceptional occurrence in men. Surgery is the definitive treatment; few results exist for adjuvant therapy.

Antecedentes: la fibromatosis mamaria es una enfermedad rara; sus casos son 0.2% de las neoplasias de mama, y en los varones es aún más rara. El diagnóstico definitivo es anatomopatológico. Caso clínico: se comunica el caso de un varón de 52 años, con diagnóstico anatomopatológico de fibromatosis mamaria posterior al estudio de un tumor en la mama derecha. Se le practicó exéresis con amplios márgenes, luego mastectomía subcutánea, con estudio histológico de fibromatosis con márgenes libres. El postoperatorio transcurrió sin complicaciones y no requirió tratamiento coadyuvante. En el seguimiento a seis meses continuaba libre de enfermedad. El tratamiento de elección es la escisión con amplios márgenes y el oncológico coadyuvante es motivo de controversia. Conclusiones: la fibromatosis en la mama es poco frecuente y su aparición en el varón excepcional. El tratamiento quirúrgico es el definitivo, no así la terapia oncológica neoadyuvante que sigue suscitando controversia.

Fibromatosis agresiva de la pared torácica asociada a implante mamario: a propósito de un caso / Aggressive fibromatosis of the chest wall associated to mammary implant: a case report

La fibromatosis agresiva es una lesión benigna, que comprende el 0,3% de todos los tumores sólidos. A pesar que la pared torácica es un lugar común, este tipo de tumor raramente se ha asociado con los implantes o tejido mamarios. Pocos casos se han descrito en conjunción con un implante de seno. Se presenta el caso de una paciente femenina de 27 años, quien le aparece esta patología dos años después de la colocación de implante mamario

The aggressive fibromatoses is a benign lesion, is not frequent, represent the 0.3% of the all solid tumors. The chest wall was considered a common place for tumors, but this type is rarely associated with the mammary implants. There are few cases reported in conjunction with a mammary implant. We presented a rare clinical case of a feminine patient of 27 years old, to whom apparition of this pathology two years after the collocation of mammary implant

Colonic adenomatous polyposis syndromes: clinical management.

Colorectal cancer is one of the major causes of cancer deaths in both men and women. It is estimated that 5 to 10% of patients with colorectal cancer have an inherited germline mutation that predisposes them to cancer. Hereditary colorectal cancer syndromes can be divided into those associated with colonic polyposis - familial adenomatous polyposis (FAP), attenuated familial adenomatous polyposis (aFAP), and MYH associated polyposis (MAP), and those not associated with colonic polyposis - hereditary nonpolyposis colon cancer (HNPCC). The hereditary polyposes are usually easier to diagnose than HNPCC, but their higher penetrance and variable phenotype pose some difficult problems in management and surveillance. The timing and type of surgical intervention, the management of desmoid risk, the treatment of rectal or pouch neoplasia, and the management of duodenal neoplasia are all questions that must be addressed in patients with FAP or MAP.

A rare case of nasal desmoid tumor.

Desmoid tumor or Aggressive Fibromatosis is rarely seen in the nasal cavity and are prone to recurrences. A patient with earlier history of excision was treated with repeat ergery employing the Weber-Ferguson incision followed by post-op radiotherapy.