Desmoid tumour: a rare cause of congenital unilateral calf enlargement mimicking calf hypertrophy

Desmoid tumours, also known as aggressive fibromatosis, are rare tumours derived from mesenchymal stem cells, accounting for only 0.03 % of all tumours. While 85-90 % of cases are sporadic, desmoid tumours can occasionally be associated with Gardner syndrome (or Familial Adenomatous Polyposis), which is linked to variants in the tumour suppressor gene, APC (adenomatous polyposis coli) gene on chromosome 5. We describe a paediatric patient with congenital unilateral calf enlargement who was diagnosed as fibromatosis confirmed by muscle biopsy. Genetic workup was unrevealing, and muscle biopsy confirmed the diagnosis of fibromatosis. APC gene mutations were negative in this patient. Fibromatosis is a rare diagnosis which may have implications for the whole family and may present with congenital calf enlargement.

Background: Desmoid-type fibromatosis of the breast is a rare, benign, but locally aggressive tumor that typically affects women. Its presentation in male patients is exceedingly rare, and even more so following a cosmetic procedure such as liposuction. This case report describes a unique presentation of breast fibromatosis in a male patient, who developed the condition after undergoing liposuction for cosmetic purposes to define the pectoral area. The case highlights the diagnostic challenges it poses due to its malignancy-like appearance on imaging. Materials and methods: A 28-year-old male patient presented with a right palpable mass in the breast following a liposuction procedure aimed at enhancing pectoral definition. Imaging studies, including ultrasound and MRI, raised suspicion of a malignancy. However, histopathological analysis from a core needle biopsy revealed fibromatosis. The patient underwent surgical excision of the tumor, and histological evaluation confirmed the diagnosis of benign desmoid-type breast fibromatosis. Results: Histopathological examination revealed benign fibromatosis with no evidence of malignancy. The tumor was completely excised with clear margins, and the patient has had no signs of recurrence during the follow-up period. Conclusions: This case highlights the rare occurrence of breast fibromatosis in a male patient following liposuction for cosmetic purposes. Given its ability to mimic malignancy on imaging, early diagnosis and complete surgical excision are essential for effective management and to prevent recurrence.

Background/aim: Desmoid tumors (DTs), also referred to as aggressive fibromatosis, originate from connective tissues and typically manifest with a propensity for local invasion. Despite extensive research efforts aimed at exploring novel anti-tumor agents for DTs, the development of effective clinical management strategies remains an ongoing challenge due to the limited success of current treatments, which frequently lead to inconsistent outcomes and a high recurrence rate of DTs. To overcome these limitations, we focused our research aim on a drug repositioning approach to identify existing medications that could be effective against DTs.

Materials and methods: Mouse models with Apc mutations, specifically Apc1638N/+ and Apc1638N/+/Trp53-/-, were generated to study DTs. Primary desmoid cells were isolated from these models for experimental analysis. Idarubicin hydrochloride (IDH), a topoisomerase II (TOPO II) inhibitor, was tested on these primary cells, colorectal cancer (CRC) cell lines, and tumor organoids derived from Apc1638N/+ mice. Cell viability was determined with the WST reagent and colony formation assay was evaluated. The anti-tumor efficacy of IDH was tested in an in vivo CRC xenograft model using HCT-116 cells.

Results: The TOPO II inhibitor IDH showed significant growth inhibition effects on Apc1638N/+ and Apc1638N/+/Trp53-/- cells. IDH also showed remarkable anti-tumor effects on CRC cell lines and tumor organoids derived from intestinal tumor cells of the Apc1638N/+ mouse model. Furthermore, IDH exerted dramatic anti-tumor effects on an HCT-116 cell line xenograft mouse model.

Conclusion: IDH could be a promising therapeutic agent for inhibiting DTs and CRC by targeting TOPO II.

Background: Familial adenomatous polyposis is a cancer-predisposing syndrome caused by germline pathogenic variants of the adenomatous polyposis coli gene, leading to numerous colorectal polyps and a high risk of colorectal cancer. Desmoid tumours have become significant in the management of familial adenomatous polyposis after a colectomy, yet the exact incidence remains undetermined due to a lack of dedicated surveillance.

Methods: This retrospective study accessed data from the prospectively maintained Hereditary Digestive Tumours Registry from 2000 to 2023. Desmoid-free survival was analysed using Cox regression and Kaplan-Meier curves.

Results: A total of 202 patients with familial adenomatous polyposis who underwent colorectal surgery were enrolled. Of the patients, 21 (10.4%) developed intra-abdominal desmoid tumours after surgery. Desmoid tumours were associated with surgical procedure, histology of cancer at the time of surgery, and family history of intra-abdominal desmoid tumours. The overall desmoid-free survival probability at a median follow-up of 84 months was 90%. Histology of cancer at the time of surgery (HR 0.25 (95% c.i. 0.10 to 0.59)), family history of intra-abdominal desmoid tumours (HR 2.92 (95% c.i. 1.22 to 6.97)), an open approach compared with a laparoscopic approach (HR 2.43 (95% c.i. 1.03 to 5.73)), and a proctocolectomy compared with a rectal-sparing total colectomy (HR 3.01 (95% c.i. 1.28 to 7.10)) emerged as significant prognostic factors affecting desmoid-free survival.

Conclusion: A minimally invasive rectal-sparing total colectomy appears protective against the development of desmoid tumours. Early surgery does not seem to increase desmoid tumour risk. A dedicated surveillance regimen for desmoid tumours in patients with familial adenomatous polyposis is needed to improve outcomes and quality of life.

esmoid tumours are rare benign tumours that show locally aggressive and invasive features leading to potential complications. They can be quite challenging for the treating surgeon if they occur adjacent to neurovascular structures. The aetiology of these tumours is still unclear, but the incidence is higher in females and in patients with a history of trauma or surgical procedures, raising the possibility of genetic and hormonal factors as well as post-traumatic or post-operative inflammatory changes promoting the formation of desmoid fibromatosis. We report a case of a 34-year-old Asian female who presented to our hospital with a history of difficulty in swallowing due to an enlarging lump on the left side of her neck. Patient had a past medical history of previous cervical spinal disc surgery due to a herniated disc. Diagnostic imaging showed a large soft tissue mass centred between the left common carotid artery and the cervical vertebrae displacing the trachea and oesophagus to the right side. A biopsy was obtained, and histopathological examination was suggestive of a desmoid tumour. The patient underwent surgical resection of the tumour but returned later with recurrence and had to undergo the surgery again to achieve full cure.

There has been noteworthy progress in molecular characterisation and therapeutics in soft tissue sarcomas. Novel agents have gained regulatory approval by the FDA. Examples are the tyrosine kinase inhibitors avapritinib and ripretinib in gastrointestinal stromal tumours (GIST), the immune check point inhibitor atezolizumab in alveolar soft part tissue sarcoma, the γ-secretase inhibitor nirogacestat in desmoid tumours, the NTRK inhibitors larotrectinib and entrectinib in tumours with NTRK fusions, the mTOR inhibitor nab-sirolimus in PEComa, and the EZH-2 inhibitor tazemetostat in epithelioid sarcoma. The FDA has also recently granted accelerated approval for autologous T-cell therapy with afami-cel in patients with HLA-A*02 and MAGE-A4-expressing synovial sarcoma. There are other promising treatments that are still investigational, such as MDM2 and CDK4/6 inhibitors in well-/dedifferentiated liposarcoma, immune checkpoint inhibitors in the head and neck angiosarcoma and a subset of patients with undifferentiated pleomorphic sarcoma, and PARP inhibitors in leiomyosarcoma. The challenges in drug development in soft tissue sarcoma are due to the rarity and the molecular heterogeneity of the disease and the fact that many subtypes are associated with complex karyotypes or non-targetable molecular alterations. We believe that progress maybe possible with a better understanding of the complex biology, the development of novel compounds for difficult targets such as proteolysis targeting chimeras (Protacs), the utilisation of modern clinical trial designs, and enhanced collaboration of academia with industry to develop treatments with a strong biologic rationale.