Desmoid Fibromatosis Research Articles

Imaging criteria for measuring the response of desmoid fibromatosis to systemic therapy are not well established. We evaluated a series of patients with desmoids who underwent systemic therapy to document magnetic resonance imaging (MRI) features associated with a positive clinical response. This Institutional Review Board-approved retrospective study included 23 patients (mean age 40.5) with 29 extra-abdominal tumors. Therapeutic regimens included cytotoxic chemotherapy (n = 19), targeted therapy (n = 3), and nonsteroid anti-inflammatory drugs (NSAIDS; n = 1). Clinical effects were categorized as progressive disease, stable, or partial response. Maximum tumor dimension (Dmax), approximate tumor volume (VTumor), and quantitative tumor T2 hyperintensity and contrast enhancement (relative to muscle) for pre- and post-treatment MRIs were compared. Three lesions progressed, 5 lesions were stable, whereas 21 showed a clinical response. Dmax decreased more in responders (mean -11.0%) than in stable/progressive lesions (mean -3.6 and 0% respectively, p = 0.28, ANOVA); by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) 27 out of 29 lesions were "stable," including the 3 progressive lesions. In responders, VTumor change averaged -29.4%, but -19.2% and +32.5% in stable and progressive lesions respectively (p = 0.002, ANOVA); by 3D criteria 14 out of 29 lesions showed a partial response. T2 hyperintensity decreased by 50-54% in partial response/stable disease, but only by 10% in progressive lesions (p = 0.049, t test). Changes in contrast enhancement ranged from -23% to 0%, but were not statistically significant among response groups (p = 0.37). Change in T2 hyperintensity showed a positive correlation with volumetric change (r = 0.40). Decreases in volume and T2 hyperintensity reflect the positive response of desmoid fibromatosis to systemic therapy; RECIST 1.1 criteria are not sensitive to clinically determined tumor response.

Pediatric fibroblastic and myofibroblastic tumors are a relatively common group of soft-tissue proliferations that are associated with a wide spectrum of clinical behavior. These tumors have been divided into the following categories on the basis of their biologic behavior: benign (eg, myositis ossificans, myofibroma, fibromatosis colli), intermediate-locally aggressive (eg, lipofibromatosis, desmoid fibroma), intermediate-rarely metastasizing (eg, inflammatory myofibroblastic tumors, infantile fibrosarcoma, low-grade myofibroblastic sarcoma), and malignant (eg, fibromyxoid sarcoma, adult fibrosarcoma). Imaging has a key role in the evaluation of lesion origin, extent, and involvement with adjacent structures, and in the treatment management and postresection surveillance of these tumors. The imaging findings of these tumors are often nonspecific. However, certain imaging features, such as low or intermediate signal intensity on T2-weighted magnetic resonance images and extension along fascial planes, support the diagnosis of a fibroblastic or myofibroblastic tumor. In addition, certain tumors have characteristic imaging findings (eg, multiple subcutaneous or intramuscular lesions in infantile myofibromatosis, plaquelike growth pattern of Gardner fibroma, presence of adipose tissue in lipofibromatosis) or characteristic clinical manifestations (eg, great toe malformations in fibrodysplasia ossificans fibroma, neonatal torticollis in fibromatosis colli) that suggest the correct diagnosis. Knowledge of the syndrome associations of some of these tumors-for example, the association between familial adenomatous polyposis syndrome and both Gardner fibroma and desmoid fibromatosis, and that between nevoid basal cell carcinoma syndrome and cardiac fibroma-further facilitate a diagnosis. The recognition of key imaging findings can help guide treatment management and help avoid unnecessary intervention in cases of benign lesions such as myositis ossificans and fibromatosis colli. In this article, we describe the various types of fibroblastic and myofibroblastic tumors in children and the characteristic clinical manifestations, imaging features, and growth patterns of these neoplasms-all of which aid in the appropriate radiologic assessment and management of these lesions. (©)RSNA, 2016.

To assess the feasibility, safety and preliminary efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of extra-abdominal desmoid tumours. Fifteen patients with desmoid fibromatosis (six males, nine females; age range, 7-66years) were treated with MRgFUS, with seven patients requiring multiple treatments (25 total treatments). Changes in viable and total tumour volumes were measured after treatment. Efficacy was evaluated using an exact one-sided Wilcoxon test to determine if the median reduction in viable tumour measured immediately after initial treatment exceeded a threshold of 50% of the targeted volume. Median decrease after treatment of at least two points in numerical rating scale (NRS) worst and average pain scores was tested with an exact one-sided Wilcoxon test. Adverse events were recorded. After initial MRgFUS treatment, median viable targeted tumour volume decreased 63%, significantly beyond our efficacy threshold (P = 0.0013). Median viable total tumour volume decreased (105mL [interquartile range {IQR}, 217mL] to 54mL [IQR, 92mL]) and pain improved (worst scores, 7.5 ± 1.9 vs 2.7 ± 2.6, P = 0.027; average scores, 6 ± 2.3 vs 1.3 ± 2, P = 0.021). Skin burn was the most common complication. MRgFUS significantly and durably reduced viable tumour volume and pain in this series of 15 patients with extra-abdominal desmoid fibromatosis. • Retrospective four-centre study shows MRgFUS safely and effectively treats extra-abdominal desmoid tumours • This non-invasive procedure can eradicate viable tumour in some cases • Alternatively, MRgFUS can provide durable control of tumour growth through repeated treatments • Compared to surgery or radiation, MRgFUS has relatively mild side effects.

The management strategy for retrorectal tumours is complex. Due to their rarity, few surgeons have expertise in management. A systematic literature review was conducted using the PubMed database. English language publications in the years 2011-2015 that assessed preoperative management, surgical strategies and chemoradiotherapy for presacral tumours were included. Two hundred and fifty-one abstracts were screened of which 88 met the inclusion criteria. After review of the full text, this resulted in a final list of 42 studies eligible for review. In all, 932 patients (63.2% female, 36.8% male; P < 0.01) with a retrorectal tumour were identified. Most were benign (65.9% vs. 33.7%, P < 0.01). Imaging distinguished benign from malignant lesions in 88.1% of cases; preoperative biopsy was superior to imaging in providing an accurate definitive diagnosis (91.3% vs. 61.4%, P < 0.05) with negligible seeding risk. Biopsy should be performed in solid tumours. It is useful in guiding neoadjuvant therapy for gastrointestinal stromal tumours, sarcomas and desmoid type fibromatosis and may alter the management strategy in cases of diffuse large B-cell lymphoma and metastases. Biopsies for cystic lesions are not recommended. The gold standard in imaging is MRI. The posterior Kraske procedure is the most common surgical approach. Overall, the reported recurrence rate was 19.7%. This review evaluated the management strategies for retrorectal tumours. A preoperative biopsy should be performed for solid tumours. MRI is the most useful imaging modality. Surgery is the mainstay of treatment. There is limited information on robotic surgery, single-port surgery, transanal endoscopic microsurgery, chemoradiotherapy and reconstruction.

Pediatric desmoid fibromatosis of the parapharyngeal space: A case report and review of literature

Desmoid fibromatosis is a rare but locally aggressive tumor comprised of myofibroblasts. Desmoids do not have the ability to metastasize but can cause significant morbidity and mortality by local invasion. These tumors may occur throughout the body, but are commonly found on the abdominal wall and within the intestinal mesentery. Desmoids in these areas may cause unique clinical problems for physicians and patients. Mutations in either the β-catenin or the APC genes are usually the cause for the development of these tumors with the former comprising the sporadic development of tumors and the latter being associated with familial adenomatous polyposis syndrome. Surgical resection with histologically negative margins has been the cornerstone of therapy for this disease, but this paradigm has begun to shift. It is now common to accept a microscopically positive margin after resection as recurrence rates may not be significantly affected. An even more radical evolution in management has been the recent movement towards “watchful waiting” when new desmoids are diagnosed. As the natural history of desmoids has become better understood, it is evident that some tumors will not grow and may even spontaneously regress sparing patients the morbidity of more aggressive therapy. Other modalities of treatment for desmoids include radiation and systemic therapy which both can be used adjuvantly or as definitive therapy and have shown durable response rates as single therapy regimens. The decision to use radiation and/or systemic therapies is often based on tumor biology, tumor location, surgical morbidity, and patient preference. Systemic therapy options have increased to include hormonal therapies, non-steroidal anti-inflammatory drugs and chemotherapy, as well as targeted therapies. Unfortunately, the rarity of this disease has resulted in a scarcity of randomized trials to evaluate any of these therapies emphasizing the need for this disease to be treated at high volume multidisciplinary institutions.Electronic supplementary materialThe online version of this article (doi:10.1007/s40487-016-0017-z) contains supplementary material, which is available to authorized users.

Melanotic neuroectodermal tumour of infancy and Aggressive desmoid fibromatosis are histologically benign tumors but with aggressive behavior, it’s occurring during the little infancy and are caracterised by Fast-growing, osteolysis and recurrence. The treatment is essentially surgical. Melanotic neuroectodermal tumour of infancy is a rare tumour which affects young children arising from neural crest with a black coloring. It grows rapidly and first touches the maxilla. We related the case of a three-month age male who presents a tumor in the right maxilla. The case have CT scan and histology feature. Aggressive desmoid fibromatosis is a benign tumor with locally infiltrative behavior and tendency to recur. We report a rare case involving the mandible arch of three years old girl with histopathological, immunohistochemical and imaging features. She underwent a large surgically resection of the arch of the mandible, there has been no recurrence three years after.

Noninflammatory masses in the ischiorectal fossa are rare. This study aimed to review our experience with ischiorectal fossa tumors and to address the question of whether percutaneous biopsy should be undertaken. This is a retrospective study. This study was conducted at a tertiary institution. From April 2007 to November 2014, all consecutive ischiorectal fossa masses treated in a referral center were retrospectively reviewed. They were all presented and discussed in a multidisciplinary team meeting. Magnetic resonance imaging was performed in all the patients. Inflammatory pathologies, such as abscess, were excluded from the analysis. Percutaneous biopsy and surgical excision of ischiorectal fossa tumors were reviewed. Perioperative, pathological, and oncological outcomes were measured. Eleven patients were identified (8 female; median age, 50 years; range, 25-90). Percutaneous biopsy was undertaken in 8 patients. All biopsies were diagnostic and altered preoperative management in 3 cases (aggressive angiomyxoma (n = 2), desmoid fibromatosis (n = 1)). Overall final diagnosis was benign in 3 patients, locally aggressive neoplasm in 3, and malignant in 5 cases (leiomyosarcomas (n = 2), liposarcomas (n = 2), and angiomyosarcoma (n = 1)). Surgical approaches were perineal in 8 patients, abdominoperineal in 1 patient, and totally abdominal in 1 patient. One patient (age 90 years) was managed nonsurgically. After resection, 2 positive margins were observed (R1 rate, 20%). After a mean follow-up of 24.3 months, 3 patients have experienced local recurrence, which required further surgery in 2 cases. This study is limited by the small number of patients. Noninflammatory masses in the ischiorectal fossa are rare, but they are commonly malignant and should be imaged by MRI. Unless the radiological appearances are diagnostic, percutaneous biopsy is recommended and alters management in about one-third of cases.

Abstract BACKGROUND Desmoid tumor (DT) is known as a locally aggressive tumor caused by altered Wnt/b-catenin signaling pathway. Although high frequency of mutations are observed in APC and CTNNB1, its values as a predictive marker of local recurrence is controversial and only serine to phenyalanie substitution at codone 45 (S45F) in CTNNB1 is reported. We designed a study to investigate candidate mutations which affect the local recurrence in DT. METHODS Tissues from 25 patients, treated with mass excision, were acquired and targeted gene sequencing (TGS) were performed for the 45 genes in COSMIC data set. Patients were divided into 2 groups, subjects with recurred DT and subjects without disease recurrence. Locus, previous reported in COSMIC data set, with altered frequency &amp;gt; 0.01 was considered as a significant alteration. Statistical significance of each altered locus and candidate genes were tested by Cox-regression analysis and fisher's exact test. Time to recurrence is used in survival analysis and P under 0.05 is considered as a significant result. Primary endpoint of this study is evaluating a hazard ratio (HR) for each alteration. RESULTS Out of 25 patients, 13 patients (52.0%) have recurred after initial treatment. APC mutation is observed in 13 patients (52.0%) and CTNNB1 mutation in 21 patients (84.0%) with no CTNNB1 S45F mutation observed. Median follow up duration was 72.3 months. More subjects were recurred with HRAS mutation (38.5% vs 0%, P = 0.039) and HR was increased (HR = 3.65, 95% confidential interval [CI] 1.09-12.15, P = 0.035). However, other genes, including CTNNB1 and APC, did not satisfied statistical significance. Among the 575 alterations detected by TGS, 9 missense mutation in 5 genes showed increased HR by Cox-proportional analysis and values are followed: (1) CTNNB1 S45G (HR 27.6, P = 0.007) (2) FGFR3 V266M (HR 14.8, P = 0.008); (3) CDKN2A P81L (HR 5.1, P = 0.020), D105E (HR 11.1, P = 0.049), R107C (HR 23.5, P = 0.026); (4) PTPN11 S502L (HR 23.5, P = 0.026); (5) TP53 A189V (HR 23.5, P = 0.026), C182Y (HR 23.5, P = 0.026), S96G (HR 23.5, P = 0.026). Out of 5 subjects with above alterations, 4 subjects recurred within 15.0 months and median time to relapse was shorter compared to the subjects without alteration (10.5 months vs 18 months, P = 0.057). CONCLUSIONS In this study, we identified 6 genes and 9 specific locus which are related with recurrence of desmoid tumor. Our result is coincidence with previous result that an alteration in codon 45 of CTNNB1 is related with desmoid tumor recurrence. Values of other significant alteration in our report should be validated with confirmatory studies. Citation Format: Sehhoon Park, Youngil Koh, Se-Hoon Lee, Chan-Young Ock, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Dae Seog Heo. Investigating candidate genomic alteration which affects the local recurrence in patients with desmoid fibromatosis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4946. doi:10.1158/1538-7445.AM2015-4946

Soft tissue tumors are a heterogeneous group of tumors arising from connective tissues. These tumors may be benign, benign but locally aggressive, or malignant. Surgery either alone or in combination with adjuvant therapies such as radiation or chemotherapy can potentially cure a patient with a soft tissue tumor. The morbidity and complications associated with treatment can have significant and lasting adverse effects on limb function and quality of life. In some situations, patients develop local recurrence of disease and require further surgery, which can result in further treatment-associated morbidity. We have adapted MR guided focused ultrasound (MRgFUS) techniques to the treatment of benign and malignant soft tissue tumors of the extremities with the goal of safely and effectively performing MRgFUS ablation on human subjects. This presentation describes the use of MRgFUS for the treatment of desmoid fibromatosis, arteriovenous malformations, and malignant sarcomas.

Nationwide Trends in the Current Management of Desmoid (Aggressive) Fibromatosis

Background and purpose: Desmoid tumors or aggressive fibromatosis are infrequent conditions, with a large clinical variability, and preferencial location on abdominal wall, extra-abdominal soft tissue, and mesentery. Histologically benign but locally aggressive, they have a marked tendency to recurrence. There are two known variants: sporadic and associated to familial adenomatous polyposis. Its etiology remains unknown, but it appears to be related to estrogenic estimulation, surgical aggression and mutations of the short arm of chromosome 5. Diagnosis is usually difficult, and must combine medical history, semiology and imaging, though only histological analysis of the specimen will provide a definitive diagnosis after surgical resection, which is potentially curative. Gastric location has not been reported so far. Case report: 37-year-old woman with recent delivery, presenting abdominal lump with non specific clinical semiology and rapid growth rate. After diagnostic tests, a hypervascular mass of about 15 centimeter of diameter, depending on gastric wall is found. She underwent an elective distal gastrectomy and Billroth I reconstruction. Histology confirms a mesenchymal desmoid gastric tumor. Discussion: The differential diagnosis for abdominal oligosymptomatic lumps which respect the mucosa of the gastrointestinal tract lead clinical suspicion to mesenchymal tumors such as sarcomas, desmoids, or GIST. Radiologic tests are useful to confirm resectability and detect complications. When facing unresectable disease, planning a biopsy and systemic treatment with chemotherapy and/or radical radiotherapy should be considered. Diagnosis is reached after histological and inmunohistochemical analysis of the specimen, which in case of a desmoid, will show negative expression to markers of sarcoma (actin, desmin, S100) or GIST (CD117, DOG1, PDGFRA), and positive staining with anti-beta-catenin. Conclusion: Desmoid tumors should be considered in the differential diagnosis of abdominal oligosymptomatic masses, specially in fertile women or if history of surgical trauma. Patients with desmoid tumors should undergo colonic polyposis screening, as well as patients with adenomatous polyposis and an abdominal lump should lead suspected diagnosis to the possibility of a desmoid tumor.

99. Nationwide trends in the current management of desmoid (aggressive) fibromatosis

Desmoid fibromatosis is a benign fibroblastic neoplasm with high recurrence rates predominantly observed in pediatric and adolescent patients. The use of wide resection margins has been discussed controversially in literature. In addition, data on non-surgical treatment is limited as phase III studies are still missing. Nineteen patients under the age of 18 years were identified. Tumor location, surgical treatment for primary or recurrent tumors, resection margins, medical neo-/adjuvant treatment, time to recurrence as well as immunohistochemical markers (estrogen receptor, ER α and β, progesterone and androgen receptors, somatostatin, Ki-67, c-kit, platelet-derived growth factor receptors, PDGFRs, α and β, β-catenin) were evaluated. The mean age at diagnosis was 6.6 years, with a mean follow-up of 114 months. Recurrences were detected in four out of nineteen patients. Surprisingly, the recurrence rate was not influenced by type of resection used (R0, R1/2). All samples were tested negative for ER α, somatostatin, and progesterone receptor. In contrast, a majority of tumors showed positive results for PDGFR α and β and β-catenin. No correlation between positive immunohistochemical markers and tumor recurrences was detectable. In conclusion, recurrence rates are not depending on resection type and immunohistochemical markers seem to behave differently in children and adolescents in contrast to adult patients.

Peritoneal disease can be caused by a wide spectrum of pathologies. While peritoneal disease is usually caused by primary or secondary malignancies, benign diseases can occur and mimic malignancies. This article begins with an overview of peritoneal embryology and anatomy followed by a detailed description of the multimodality imaging appearance of peritoneal diseases. Common diseases include peritoneal carcinomatosis, pseudomyxoma peritonei, lymphomatosis, sarcomatosis, and tuberculous peritonitis. The uncommon diseases which cause peritoneal disease include desmoid fibromatosis, desmoplastic small round cell tumor, malignant mesothelioma, well-differentiated mesothelioma, multicystic mesothelioma, papillary serous carcinoma, leiomyomatosis, extramedullary hematopoiesis, inflammatory pseudotumor and amyloidosis. This manuscript will help the radiologist become familiar with the different peritoneal spaces, pathways of spread, multimodality imaging appearance and differential diagnoses of peritoneal diseases in order to report the essential information for surgeons and oncologists to plan treatment.

Introduction: The desmoid fibromatosis is a very rare connective tissue disease which is recognized as semimalignant. The aim of this work is to review the relevant literature and to analyze the management of our patient collective. Material and Method: Surgery was performed on 7 patients with extraabdominal desmoid fibromatosis between August 1998 and May 2007. MRI examination as well as biopsy was carried out in all cases. All patients were operated on; the mean follow up was 4 years (1–7). Upon follow up, every patient has undergone clinical and MRI examination. Results: The results show that we have achieved R0 resection in 4 cases and R1 in two cases and Rx in one case. In 4 patients, no recurrence was observed after the single surgery performed in our hospital. In 2 patients a single revision surgery was performed in each case and yielded no further recurrence. In only one case, multiple surgeries (one primary and two revision surgeries) were necessary, after which no recurrence was reported.Conclusion: The early diagnosis of the disease is of utmost importance to the success of the outcome. MRI examination and biopsy are mandatory. Surgery is the therapy of choice. The recurrence rate is high and is linked to the difficulty of recognition of the exact infiltrative extent of the tumour. This necessitates a close follow-up.

Extra-abdominal desmoid fibromatosis – A sarcoma unit review of practice, long term recurrence rates and survival

Insulin-like growth factor II messenger RNA–binding protein 3 expression in gastrointestinal mesenchymal tumors

Study Design Case report. Objective The objective of the article is to illustrate a case of desmoid tumor (DT) formation after posterior instrumentation of the thoracic spine. Methods A 57-year-old woman presented with lower extremity clumsiness, balance, and ambulation difficulty resulting from spinal cord compression due to an upper thoracic atypical vertebral hemangioma. Ten months after undergoing embolization, resection, and placement of instrumentation for this lesion, the patient developed a growing mass at the rostral end of the incision. Biopsy revealed desmoid fibromatosis. The mass was removed via an en bloc resection. Histology revealed an infiltrative DT above the laminectomy site abutting the instrumentation. Results At 2-year follow-up, there was no evidence of recurrence of the tumor. Conclusion Paraspinal DTs have been reported in the literature to develop after surgical procedures of the spine. Often times, patients attribute swelling or fullness at the site of their surgery to scar tissue formation or instrumentation. One must consider the possibility of a DT in the setting of reported surgical site fullness or mass after spine surgery. It is thought that postoperative inflammation present in the surgical bed may promote formation of DTs. Instrumentation may also contribute to inflammation and increase the likelihood of developing a DT. Generous margins must be taken to prevent recurrence.

An abdominal mass is a common clinical presentation, and a small percentage of such patients will have an abdominal wall tumour with the two most common pathologies being fibromatosis and soft tissue sarcoma. Here we present the available literature on the diagnosis and management of both fibromatosis and soft tissue sarcoma, in the context of our experience in a tertiary referral centre for sarcoma. Appropriate cross-sectional imaging and a pre-operative tissue diagnosis by percutaneous core biopsy are necessary to define management. Desmoid fibromatosis can be managed initially by observation with serial imaging, with surgery being reserved for those patients who demonstrate progression. Soft tissue sarcoma can display a range of pathologies from relatively indolent tumours to locally aggressive sarcomas that can readily metastasise. An accurate pre-operative histological diagnosis and staging enables a multidisciplinary approach to management. This may include chemotherapy and radiotherapy, but the mainstay of treatment remains wide surgical resection and abdominal wall reconstruction. Patient outcomes are worse if referral is delayed or if the sarcoma is incompletely resected without an initial tissue diagnosis.