RAD51C and MYST3 Mutations in a Case of Desmoid-Type Fibromatosis With No Mutation in CTNNB1 or APC

Most cases of desmoid-type fibromatosis (DTF) exhibit a mutation in APC or CTNNB1. We report a case of mesenteric DTF in which no mutation in APC or CTNNB1 was found, but a germline variant of uncertain significance (VUS) in RAD51C and a subclonal mutation in MYST3 were identified. Whether these genetic changes are important in DTF in this case, or whether genetically conventional DTF cells were present at a density below detection is unknown; it will be of interest to see results in further studies of wild-type APC/CTNNB1 cases.

Lipoma, the most common mesenchymal tumor, often appears as a slow-growing mass in the musculoskeletal system (MSK). While generally non-invasive, their location can cause symptoms. Desmoid fibromatosis (DF), a rare and locally aggressive neoplasm, poses challenges in MSK system diagnosis and management due to its infiltrative nature. Despite lacking metastatic potential, DF has a high recurrence rate, classifying it as “intermediate, locally aggressive” in the WHO classification. Collaborative efforts among orthopedic surgeons, radiologists, and pathologists are crucial for accurate diagnosis and treatment planning for all tumors of the MSK system. This case report presents the first documented example of a DF within a lipoma, highlighting the challenges of diagnosing and treating musculoskeletal tumors.

Desmoid fibromatosis is an uncommon soft tissue tumor that is locally aggressive and can result in both pain and limited range of motion (ROM). The rehabilitation protocol is designed to promote optimal recovery and functional outcomes by following a phased approach. Initially, the focus is on managing pain and performing passive ROM exercises immediately after surgery. As the weeks progress, the exercises transition to active-assisted and then active ROM exercises. Additionally, strengthening exercises, manual therapy techniques, and functional training are incorporated to improve muscle strength, flexibility, and coordination. The goal of the rehabilitation journey is to ensure a safe return to daily activities while closely monitoring for any signs of recurrence or functional deficits. This comprehensive approach highlights the importance of collaboration between surgical teams, rehabilitation specialists, and patients in order to achieve successful outcomes.

Article in German

A desmoid tumour, also known as aggressive fibrous tumour or desmoid fibromatosis, is a rare, benign tumour originating from connective tissue cells. Desmoid tumours account for approximately 0.03+% of all neoplasms and less than 3+% of all soft tissue tumours. The estimated incidence in the general population is 2 to 4 cases per million people per year [1]. Desmoid tumours are characterised by aggressive growth but typically do not metastasize. They often occur in young adults and preferably affect specific body regions such as the abdomen, shoulder, chest, or extremities. The exact cause of the condition is not fully understood, but genetic changes and hormonal factors may play a role. Symptoms of a desmoid tumour depend on its location and size, with pain, swelling, or restricted movement commonly occurring. A diagnosis is typically made through a tissue sample (biopsy) and imaging techniques such as MRI or CT [2]. To our knowledge, this is the first documented case of recurrence of a desmoid tumour in the scar at the donor site of a latissimus dorsi flap previously used for the reconstruction of desmoid resection in the lower leg.

Introduction and importance: Desmoid tumors (DT), rare benign neoplasms of soft tissues, exhibit local aggressiveness and high recurrence rates. Originating from myofibroblast proliferation, complete surgical intervention is the preferred treatment. Despite their benign nature, these tumors are infrequent, predominantly affecting women between 15 and 60, with a higher incidence in adolescence.

Case presentation: A 44-year-old woman with a DT in the leg mimicking external popliteal sciatic neuropathy. Diagnosis confirmed by biopsy, surgery performed with preservation of the external popliteal nerve, ensuring optimal nerve function. Two-year follow-up with no recurrence, demonstrating the success of the surgical intervention.

Clinical discussion: DTs, although rare, exhibit three distinct genomic mutations, with the 45F genotype associated with the highest risk of recurrence. Generally sporadic, these tumors can be linked to familial adenomatous polyposis (F.A.P.) and influenced by states of hyperestrogenism. DTs typically present as deep-seated masses, with frequent local recurrence despite complete resection.

Conclusion: DTs pose diagnostic and therapeutic challenges, often requiring complete surgical intervention. Management depends on symptomatology, with careful monitoring for small asymptomatic tumors and adjuvant radiotherapy in case of incomplete resection. Despite surgical success, frequent recurrence underscores the need for in-depth research to enhance therapeutic approaches.