Analysis of germline variants in pediatric patients diagnosed with desmoid tumors and nuchal-type fibromas

Desmoid tumor (DT) is a fibroblastic proliferation arising in soft tissue characterized by localized infiltrative growth with an inability to metastasize but with a tendency to recurrence. Nuchal-type fibromas are benign soft tissue lesions that are usually developed in the posterior neck. The development of these neoplasms can be associated with a hereditary cancer predisposition syndrome, mainly familial adenomatous polyposis (F.A.P.) syndrome caused by APC germline mutations. Gardner syndrome is a variant of FAP characterized by the presence of extracolonic manifestations including soft tissue tumors as DTs and nuchal-type fibromas. However, the development of these tumors could be associated with germline alterations in other genes related to colorectal cancer development. The objective of this study was to analyze germline variants in APC, MUTYH, POLD1 and POLE genes in five pediatric patients diagnosed with DTs or nuchal-type fibromas. We identified two pathogenic variants in the APC gene in two different patients diagnosed with nuchal-type fibroma and DTs and two variants of uncertain significance in POLD1 in two patients diagnosed with nuchal-type fibroma. Two patients had family history of colorectal cancer, however, only one of them showed an APC germline pathogenic variant. The analysis of germline variants and genetic counseling is essential for pediatric patients diagnosed with DTs or nuchal-type fibromas and their relatives.

Aggressive fibromatosis is a rare clonal proliferative tumor arising from mesenchymal cells in the fascia and musculoaponeurotic structures. The aim of the present study was to describe several cases of extra-abdominal recurrent aggressive fibromatosis. The present study was a single-center retrospective case series of patients with recurrent aggressive fibromatosis. The cases were managed at a single private facility. A total of 9 patients with recurrent fibromatosis were included. The mean and median ages of the patients were 29 and 30 years, respectively. In total, two thirds (66.67%) of the cases were female. A negative previous medical history was reported in 7 cases (77.7%), and diabetes and hypertension were reported in 1 case (11.1%). Overall, only 1 case (11.1%) had a family history of breast fibromatosis. The time interval between primary tumor resection and recurrent presentation was 28 months. In 6 cases (66.7%), the tumor was located in the extremities. Pain was the most common presenting symptom in 6 cases (66.7%). All patients had their recurring tumor surgically removed, followed by radiation in 5 cases. The resection margin was positive in 4 cases (44.4%). Each patient was subjected to a careful three-month follow-up for recurrences. On the whole, the present study demonstrates that despite the fact that several therapeutic approaches for extra-abdominal recurrent aggressive fibromatosis have been described in the literature, there is a significant likelihood of recurrence following resection.

Mesenteric desmoid-type fibromatosis (DTF) is a rare benign yet aggressive neoplasm that has an unpredictable biological behavior ranging from spontaneous regression to extensive local infiltration and has a high tendency for recurrence. The presenting symptoms are usually nonspecific and mostly related to the large size of the tumor compressing adjacent organs. Imaging studies can be suggestive of the diagnosis, but confirmation is based on histopathological and immunohistochemical examination. The lack of knowledge on the etiology and pathogenetic behavior of this tumor leads to therapeutic and prognostic challenges. Future genetic studies may help in advancing our understanding of this neoplasm and in formulating the proper management and follow-up plan. Here we present a case of a 14-year-old female who presented to the emergency room complaining of diffuse abdominal pain and distention. A computed tomography (CT) scan showed a large mass occupying most of the abdominal cavity and compressing adjacent organs. Exploratory laparotomy with resection and anastomosis was performed, and the histopathological and immunohistochemical examination of the resected mass was consistent with mesenteric DTF.

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.

Purpose: Although the treatment of abdominal wall desmoid-type fibromatosis (DF) has evolved over the past decades, surgical treatment remains an important approach. Previously, surgeries for abdominal DF were mostly performed by laparotomy, which involves massive dissection and significant trauma. Here, we report our single-center experience of the laparoscopic management of abdominal wall DF in young female patients.

Methods: The clinical data of nine patients diagnosed with abdominal wall DF during January 2020-April 2022 at the Qilu Hospital of Shandong University were retrospectively analyzed. All patients underwent laparoscopic resection of abdominal wall DF and immediate abdominal wall reconstruction (AWR) with mesh augmentation via the intraperitoneal onlay mesh (IPOM) technique.

Results: Laparoscopic DF resection and AWR were successfully performed in all patients. The mean operation time was 175.56 ± 46.20 min. The width of abdominal wall defect was 8.61 ± 3.30 cm. Full- and partial-thickness myofascial closure and reapproximation were performed in five, two, and two patients, respectively. The average mesh size was 253.33 ± 71.01 cm2. The total and postoperative lengths of hospital stay were 11.00 ± 3.46 and 4.89 ± 2.03 days, respectively. Tumor recurred in one patient after 20 months of the resection. Nonetheless, death, herniation, or bulging were not observed in any patient during a mean follow-up of 16.11 ± 8.43 months.

Conclusion: Laparoscopic resection of abdominal wall DF and immediate AWR with IPOM mesh reinforcement is safe and reliable for young female patients. Management of such patients should be decided according to the biological behavior, size, and location of tumors.

Locally aggressive mesenchymal tumors comprise a heterogeneous group of soft tissue and bone tumors with intermediate histology, incompletely understood biology, and highly variable natural history. Despite having a limited to absent ability to metastasize and excellent survival prognosis, locally aggressive mesenchymal tumors can be symptomatic, require prolonged and repeat treatments including surgery and chemotherapy, and can severely impact patients’ quality of life. The management of locally aggressive tumors has evolved over the years with a focus on minimizing morbid treatments. Extensive oncologic surgeries and radiation are pillars of care for high grade sarcomas, however, play a more limited role in management of locally aggressive mesenchymal tumors, due to propensity for local recurrence despite resection, and the risk of transformation to a higher-grade entity following radiation. Patients should ideally be evaluated in specialized sarcoma centers that can coordinate complex multimodal decision-making, taking into consideration the individual patient’s clinical presentation and history, as well as any available prognostic factors into customizing therapy. In this review, we aim to discuss the biology, clinical management, and future treatment frontiers for three representative locally aggressive mesenchymal tumors: desmoid-type fibromatosis (DF), tenosynovial giant cell tumor (TSGCT) and giant cell tumor of bone (GCTB). These entities challenge clinicians with their unpredictable behavior and responses to treatment, and still lack a well-defined standard of care despite recent progress with newly approved or promising experimental drugs.