Desmoid Tumors: Current Perspective and Treatment.

OPINION STATEMENT: Desmoid tumors are rare tumors with a tendency to infiltrate locally. The lack of a standard treatment approach makes choosing the most appropriate treatment for patients challenging. Most experts recommend watchful observation for asymptomatic patients as spontaneous regression of tumor is observed in up to 20% of patients. Upfront resection of the desmoid tumor has fallen out of favor due to high morbidity and high relapse rates associated with the tumor. Systemic therapy has evolved over several decades. Where chemotherapy, hormonal therapy, and non-steroidal anti-inflammatory drugs were used over the last several decades, tyrosine kinase inhibitors came to the forefront within the last decade. Most recently, gamma-secretase inhibitors have shown significant clinical benefit in patients with desmoid tumors, bringing forth an entirely new mechanistic approach. Several Wnt pathway inhibitors are also under development. Invasive approaches like cryoablation have also shown clinical benefit in patients with extra-abdominal desmoid tumors in recent years. The recent approval of nirogacestat has ushered in a new era of treatment for patients diagnosed with desmoid tumors. Several new molecules are expected to be approved over the coming years.

Rare solid tumors in a patient with Wiskott-Aldrich syndrome after hematopoietic stem cell transplantation: case report and review of literature.

Background and aims: Wiskott-Aldrich syndrome (WAS) is an X-linked recessive primary immunodeficiency disorder characterized by severe eczema, recurrent infections, and micro-thrombocytopenia. Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapeutic option for patients with classic form. The risk of developing post-transplant tumors appears to be higher in patients with WAS than in other inborn errors of immunity (IEIs), but the actual incidence is not well defined, due to the scarcity of published data. Methods: Herein, we describe a 10-year-old patient diagnosed with WAS, treated with HSCT in the first year of life, who subsequently developed two rare solid tumors, kaposiform hemangioendothelioma and desmoid tumor. A review of the literature on post-HSCT tumors in WAS patients has been performed. Results: The patient received diagnosis of classic WAS at the age of 2 months (Zhu score = 3), confirmed by WAS gene sequencing, which detected the nonsense hemizygous c.37C>T (Arg13X) mutation. At 9 months, patient underwent HSCT from a matched unrelated donor with an adequate immune reconstitution, characterized by normal lymphocyte subpopulations and mitogen proliferation tests. Platelet count significantly increased, even though platelet count never reached reference values. A mixed chimerism was also detected, with a residual WASP- population on monocytes (27.3%). The patient developed a kaposiform hemangioendothelioma at the age of 5. A second abdominal tumor was identified, histologically classified as a desmoid tumor when he reached the age of 10 years. Both hematopoietic and solid tumors were identified in long-term WAS survivors after HSCT. Conclusion: Here, we describe the case of a patient with WAS who developed two rare solid tumors after HSCT. An active surveillance program for the risk of tumors is necessary in the long-term follow-up of post-HSCT WAS patients.

Radiation-induced Desmoid Tumor Development in the Radiotherapy Field in a Child With Pineoblastoma: A Case Report.

Although treatment-related secondary malignancies are rare, they are important problems after the treatment of childhood malignant diseases. Irradiation-induced sarcomas are the development of sarcoma different from the primary tumor after a latent period of ≥3 years or more in the radiotherapy field. Desmoid tumor is extremely rare as irradiation-induced tumor. A 7.5-year-old girl was referred to our hospital after a subtotal mass excision for a solid lesion with a cystic component located in the pineal gland. Pathologic examination revealed pineoblastoma. After surgery, craniospinal radiotherapy, and chemotherapy consisting of vincristine, cisplatin, and etoposide were performed. Painless swelling in the left parieto-occipital region ~75 months after the end of the treatment developed in the patient. A mass was detected in the intracranial but extra-axial region by radiologic imaging methods. Due to the total removal of the mass and the absence of a tumor in the surgical margins, she was followed up without additional treatment. The pathologic diagnosis was a desmoid tumor. She was followed up disease free for ~7 years after the primary tumor and ~7 months after the secondary tumor. Treatment-related desmoid tumor development after treatment for a central nervous system tumor in a child is extremely rare.

Colectomy and desmoid tumours in familial adenomatous polyposis: a systematic review and meta-analysis.

Desmoid tumours (DT) are one of the main causes of death in patients with familial adenomatous polyposis (FAP). Surgical trauma is a risk factor for DT, yet a colectomy is inevitable in FAP to prevent colorectal cancer. This systematic review and meta-analysis aimed to synthesize the available evidence on DT risk related to type, approach and timing of colectomy. A search was performed in MEDLINE, EMBASE and the Cochrane Library. Studies were considered eligible when DT incidence was reported after different types, approaches and timing of colectomy. Twenty studies including 6452 FAP patients were selected, all observational. No significant difference in DT incidence was observed after IRA versus IPAA (OR 0.99, 95% CI 0.69-1.42) and after open versus laparoscopic colectomy (OR 0.88, 95% CI 0.42-1.86). Conflicting DT incidences were seen after early versus late colectomy and when analysing open versus laparoscopic colectomy according to colectomy type. Three studies reported a (non-significantly) higher DT incidence after laparoscopic IPAA compared to laparoscopic IRA, with OR varying between 1.77 and 4.09. A significantly higher DT incidence was observed in patients with a history of abdominal surgery (OR 3.40, 95% CI 1.64-7.03, p = 0.001). Current literature does not allow to state firmly whether type, approach, or timing of colectomy affects DT risk in FAP patients. Fewer DT were observed after laparoscopic IRA compared to laparoscopic IPAA, suggesting laparoscopic IRA as the preferred choice if appropriate considering rectal polyp burden. PROSPERO REGISTRATION NUMBER: CRD42020161424.

Percutaneous ultrasound-guided radiofrequency ablation for giant desmoid tumors of the intra-abdominal cavity in a patient with Gardner syndrome.

Gardner syndrome (GS) is a rare variant of familial adenomatous polyposis, leading to numerous intra- and extracolonic lesions. Extracolonic lesions of GS are most common with desmoid tumors (DTs) in the abdominal wall, intra-abdominal cavity, and mesentery. Surgery remains the primary treatment for DTs; however, the patients are challenged with the high recurrence rate after surgical resection, and wide resection often results in debilitating loss of function. This study presents a case of a 47-year-old female with GS who had undergone total colectomy and ultra-low anastomosis of the ileal anal canal, and she developed giant DTs in the intra-abdominal cavity. The patient underwent ultrasound-guided percutaneous radiofrequency ablation (RFA) for intra-abdominal DTs in September 2014, October 2015, and January 2016. Palliative RFA significantly slowed the progression of the tumor and improved the symptoms of abdominal compression; thus, it is a possible therapeutic option for intra-abdominal unresectable DTs in patients with GS.

The Role of Radiation Therapy for Symptomatic Desmoid Tumors.

OPINION STATEMENT: Desmoid tumors have a variable clinical course that ranges from indolence or spontaneous regression to an aggressive pattern marked by local invasion. Up to half may remain stable or regress; watchful waiting is the preferred approach in the initial management of desmoid tumors. Symptomatic or progressive tumors or those that may affect adjacent critical structures require surgery, radiotherapy, or systemic therapy. Although radiotherapy effectively controls desmoid tumors in most cases, concerns regarding late toxicity exist. Definitive radiotherapy for macroscopic disease is indicated when a non-morbid complete surgical resection cannot be accomplished and provides similar control rates to surgery plus radiotherapy but avoids toxicity from combined-modality treatment (surgery and radiotherapy). Adjuvant radiotherapy can be considered for microscopically involved margins, particularly for recurrent cases or when a future recurrence may be challenging to treat. Large size, extremity site, and younger age are poor prognostic factors after radiotherapy. In the extremity, radiotherapy may have superior outcomes to surgery. Younger patients, especially children, are challenging to manage as they are at particular risk for late toxicity due to the number of potential years at risk. For patients under 20 years old, for whom a non-morbid complete resection is not possible, we recommend systemic therapy as the first line of treatment. Although the long-term efficacy of systemic therapy is unproven, this strategy allows additional time for growth and development prior to radiotherapy. In younger patients and those with axial desmoid tumors adjacent to critical organs, consideration should be given to using proton therapy as the dosimetric advantages may mitigate some of the toxicity associated with conventional radiotherapy.

Does ileoanal pouch surgery increase the risk of desmoid in patients with familial adenomatous polyposis?

PURPOSE: Patients with familial adenomatous polyposis (FAP) may undergo either ileorectal anastomosis (IRA) or ileal pouch anal anastomosis (IPAA) depending on the degree of rectal involvement. Desmoid tumors (DTs) may arise postoperatively. Whether IPAA is associated with a higher risk of DTs as compared with IRA remains controversial. The purpose of this study was to determine whether IPAA increased the risk of DTs by analyzing the published data that compared IRA and IPAA as the primary treatment for FAP. METHODS: A metaanalysis was performed to analyze the published data between 1989 and 2019. IRA and IPAA were compared with respect to the incidence of DTs. RESULTS: Eight retrospective studies with a total of 1072 patients were identified: 491 underwent IPAA and 581 IRA. There was no significant difference in the incidence of DTs between IPAA and IRA (11.81% vs. 9.47%, OR 0.95, P = 0.85). Meanwhile, the overall complication (42.97% vs. 36.76%, OR 1.32, P = 0.11), incidence of cancer (4.88% vs. 8.37%, OR 0.28, P = 0.26), and overall mortality (0.33% vs. 5.20%, OR 0.49, P = 0.53) were comparable too. CONCLUSION: Ileoanal pouch surgery is associated with similar risk of desmoid in patients with FAP after surgery.

[Complex morphological (cytological, histological) diagnostics of desmoid fibroma associated with a breast implant (case report from practice).]

A rare clinical observation of desmoid fibroma associated with a breast implant is presented. When making a morphological (cytological, histological) diagnosis at the light-optical level before surgery, a differential morphological diagnosis was performed between cicatricial changes, the stromal component of the phyloid tumor and desmoid fibroma. Only immunohistochemistry allowed us to establish a diagnosis of desmoid fibroma, since tumor cells expressed diffusely SMA, focally desmin, and most importantly, ß-catenin expression was observed in some cells.

[Biology and signaling pathways involved in the oncogenesis of desmoid tumors]. / Biologie et voies de signalisations impliquées dans l'oncogenèse des tumeurs desmoïdes.

Desmoid tumors (TDs) are derived from mesenchymal stem cells and their pathogenesis is strongly linked to the Wingless/Wnt cascade where the deregulation of ß-catenin plays a major role. A mutation of the CTNNB1 encoding ß-catenin is found in the majority of sporadic TD cases and constitutional mutations of APC have been described in heritable forms in patients with familial adenomatous polyposis (FAP). Estrogens could also play a role in pathogenesis and this is the basis for the use of hormone therapy. Other signaling pathways have been involved in the development of TDs such as Notch, Hedgehog, JAK/STAT, PI3 Kinase/AKT and mTOR. Metalloproteases are expressed in TDs and play a role in invasiveness. TGF-ß, as a growth factor, stimulates the transcriptional activity of ß-catenin. Future studies will need to focus on better describing and understanding the immune environment of TDs. One of the major difficulties for the experimental study of TDs is the virtual absence of a preclinical model, either in vitro or in vivo. This is partly why the interactions between the different signaling pathways presented here and their consequences for the development of TDs are still poorly understood.

Neuromuscular choristoma-associated desmoid-type fibromatosis: Establishing a nerve territory concept.

INTRODUCTION: Desmoid-type fibromatosis (DTF) frequently arises in patients with neuromuscular choristoma (NMC). We hypothesize that NMC-associated DTF occurs in soft tissues innervated by the NMC-affected nerve, and arises from CTNNB1-mutated (myo) fibroblasts within or directly adjacent to the NMC. MATERIALS AND METHODS: A retrospective review of patients treated at our institution was performed for patients with biopsy-confirmed diagnosis of NMC-DTF. Clinical presentation, physical examination, electrodiagnostic findings and radiological features (MR and FDG PET/CT images for each NMC-DTF) and pathologic re-review of available materials were analyzed. A literature review was also performed. RESULTS: Eight patients from our institution met the inclusion criteria. All patients presented with neuropathic symptoms and soft tissue or bone changes in the nerve territory innervated by the NMC. All MR images (N=8 cases) showed the characteristic features of NMC, and also showed direct contact between unifocal (N=5) or multifocal (N=3) DTF(s) and the NMC-affected nerve NMC. FDG PET/CT (N=2 cases) showed diffuse, increased FDG uptake along the entire affected nerve segment, contiguous with the FDG-avid DTF. In all cases, the DTFs arose in the soft tissues of the NMC-affected nerve's territory. No patient developed DTF at any other anatomic site. CONCLUSIONS: These data demonstrate that NMC-DTF arises solely within the NMC-affected nerve territory, and has direct contact with the NMC itself. Based on all these findings and the multifocality of NMC in several cases, we recommend imaging and surveillance of the entire NMC-affected nerve (from spine to distal extremity) to identify clinically-occult DTF in patients with NMC.

[A Case of Intra-Abdominal Desmoid Tumors Occuring Four Years after Open Radical Prostatectomy].

Desmoid tumor is one kind of fibromatosis, and much occurs the abdominal wall and outside the abdominal wall. Intra- abdominal desmoid tumor is rare at about 8%. We experienced a case of intra-abdominal desmoid tumors occurring 4 years after open radical prostatectomy with some literature review. A 72-year-old man had undergone open radical prostatectomy for prostate cancer. Four years after that resection, multiple intra-abdominal tumors measuring 56 mm in maximum diameter was identified on follow-up computed tomography, and he was referred to our department for management. We performed laparotomy and investigation of the biopsy. Immunohistochemistry of the resected specimen indicated the tumor cells were positive for vimentin and ß-catenin, and the diagnosis was desmoid. We performed partial resection of the small intestine and ileocecal resection. His postoperative course was uneventful and he was discharged on the 12th postoperative day. He has shown no sign of recurrence in the 4 months follow-up since surgery. In the past, an operation was the best treatment for intra-abdominal desmoid tumor. But it is reported that watchful waiting is also possible by the case which has no symptom and dysfunction in NCCN guidelines 2019. Further research is needed.

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)

An Intra-abdominal Solid-cystic Desmoid That Emerged after Distal Gastrectomy.

Desmoid is a locally aggressive fibroblastic neoplasm, typically showing a heterogeneous solid mass, and its pathogenesis is multifactorial, including surgical scars. We herein report a rare case of an intra-abdominal desmoid, consisting of solid and cystic components covered with epithelial linings, that emerged after distal gastrectomy. The preoperative diagnosis was inconclusive, so laparotomy was performed. Histopathology of the solid component showed proliferating spindle cells, which were positive for beta-catenin in their nuclei. Clinicians need to bear in mind that desmoids can appear in a solid-cystic form, and immunostaining of beta-catenin should be applied for tumors that emerge around postoperative wounds.

Yield of Colonoscopy in Identification of Newly Diagnosed Desmoid-Type Fibromatosis with Underlying Familial Adenomatous Polyposis.

BACKGROUND: Desmoid-type fibromatosis can arise in patients with familial adenomatous polyposis (FAP), therefore patients with desmoids often undergo colonoscopy to rule out FAP. Because finding FAP is uncommon, we sought to define subsets of desmoid patients in whom colonoscopy frequently identified FAP. METHODS: Patients with desmoid-type fibromatosis were identified from surgery and pathology databases at a single institution, and information on colonoscopy and FAP diagnosis was collected retrospectively. CTNNB1 mutation status was defined by Sanger sequencing and digital polymerase chain reaction of archived specimens. RESULTS: Among 626 patients with desmoids, 26 were diagnosed with FAP. In 20 patients, FAP diagnosis predated the desmoid diagnosis. Among patients without prior FAP diagnosis, 161 underwent colonoscopy, which identified only six cases of FAP (diagnostic yield 3.7%). Yields were substantially higher among patients with four characteristics: age < 40 years (11% yield), intra-abdominal or retroperitoneal tumors (5.4%), multifocal disease (29%), and family history (8%) (all p < 0.001). All cases of FAP were detected in patients younger than 40 years of age and with at least one of the other three characteristics. CTNNB1 mutation status was available in 82 patients with known FAP status. None of the 61 patients with CTNNB1 mutations were diagnosed with FAP, while 7 of the 21 patients with no CTNNB1 mutation detected (24%) were FAP patients. CONCLUSIONS: Patients with desmoid-type fibromatosis and undiagnosed FAP generally have multiple risk factors, which may be used to selectively recommend colonoscopic screening. Routine CTNNB1 sequencing may also rule out FAP and allow for deferral of colonoscopy.

Abnormal Presentation of Aggressive Fibromatosis After Radiotherapy for Keloids: Case Report and Brief Literature Review.

RATIONALE: Keloids, dermal fibroproliferative lesions, often occur secondary to skin injury and extend beyond the margins of the original lesion. Aggressive fibromatosis (AF) is a rare condition arising from fibroblasts and is characterized clinically as a nonmetastasizing but locally invasive tumor. In this work, we present the case of a patient who developed AF in the chest 3 years after surgery and postoperative radiotherapy for keloids. PATIENT CONCERNS: A 15-year-old female patient who underwent surgery and postoperative radiotherapy for keloids presented with AF in the chest 3 years after intervention. DIAGNOSES AND OUTCOMES: Physical examination revealed a fan-shaped scar on the manubrium sterni with a radius of 7 cm, as well as a 9 (L) × 2-cm (W) longitudinal reddish and irregularly surfaced scar arising from previous incisions. By comparing this case with similar cases reported previously, we infer that a history of exposure to radiation is the main factor that contributes to the development of AF in patients suffering from keloid scars. We also discussed the clinical characteristics of AF and treatment options and suggest factors that should be considered when using radiotherapy in patients with keloids. LESSONS: To our knowledge, this is the first reported case of AF developing in a patient after radiotherapy for keloids. Radiotherapy may be a causal factor of AF.

Urological sequelae of desmoids associated with familial adenomatous polyposis.

The aim of this retrospective cohort study was to review urological complication rates arising from familial adenomatous polyposis associated desmoid tumours and their management. All patients over a 35-year period were identified from a prospectively maintained polyposis registry database and had an intra-abdominal desmoid tumour. Those without ureteric complications (n = 118, group A) were compared to those that developed ureteric obstruction (n = 40, group B) for demographics, treatment interventions and survival outcomes. 158 (56% female) patients were identified. Median age at diagnosis was 31 years and desmoids typically occurred 3.6 years after colectomy for familial adenomatous polyposis. Ureteric obstruction secondary to tumour growth occurred in 25% of cases. There was no significant difference in gender distribution or overall age at desmoid diagnosis between the two groups. In group B, the median age at desmoid diagnosis was significantly younger in women compared to men (25 and 43 years, respectively) (p = 0.01). Thirty-eight percent of patients already had ureteric obstruction at desmoid diagnosis, the remainder occurred after 48.6 months, but 20 years in two cases. Seventy-three percent (29/40) had ureteric stenting, a long-term requirement for most. Permanent renal injury occurred in six cases but survival between the two groups was not significantly different. Ureteric obstruction occurs frequently in patients with familial adenomatous polyposis and an intra-abdominal desmoid tumour. Those most at risk are the young following colectomy. Clinicians should actively survey the renal tract at regular intervals after a diagnosis of an intra-abdominal desmoid tumour as complications can arise insidiously, at any stage.

Treatment of extensive post tonsillectomy oropharyngeal stenosis secondary to fibromatosis.

Aggressive fibromatosis is an uncommon, benign tumor of fibroblastic origin with high potential for local invasion. Less than a quarter of these lesions are located in the head and neck, and although extremely rare, associations have been demonstrated with physical trauma. We describe a unique case of oropharyngeal fibromatosis with traumaticetiology, managed successfully with surgical excision of the lesion with negative surgical margins. A 5-year old patient was found to have an aggressive fibromatosis causing oropharyngeal stenosis following tonsillectomy. We demonstrate that surgical resection with a clear margin allowed for alleviation of stenosis without recurrences reported since the procedure.