Clinical application of next-generation sequencing for the management of desmoid tumors: A case report and literature review [Full Article]

A 42-year-old man visited our clinic for routine follow-up 1 year after left upper lobe lingular segmentectomy for lung adenocarcinoma. Chest computed tomography showed a pleural mass adherent to the thoracotomy site. Positron emission tomography revealed mildly increased metabolism with a maximal standardized uptake value of 2.7 within the tumor, suggesting local recurrence of the previous neoplasm. Exploratory thoracotomy and en bloc resection of the tumor revealed spindle cells in a massive collagenous tissue consistent with a desmoid tumor. Next-generation sequencing (NGS) was performed to confirm the diagnosis and to identify any genetic alterations that might be relevant to the prognosis of this tumor. The tumor harbored an S45F mutation in CTNNB1, which has been correlated with a high recurrence rate. Therefore, we performed adjuvant radiotherapy on the resection bed at a dose of 56 Gy. The patient experienced no postoperative or radiotherapy-related complications. Periodic follow-up examinations using computed tomography were performed every 3 months, and no evidence of recurrence of either tumor was observed during the 38 months after the last surgery. To the best of our knowledge, this is the first case reporting the clinical application of NGS and aggressive treatment based on the genotyping results for the management of a desmoid tumor.

Desmoid tumours which present to CoRSU rehabilitation hospital in Kampala are frequently managed surgically. This study compares the demographics and management of patients presenting to CoRSU hospital with that of other centres against best practice. The CoRSU database was searched for any patients diagnosed with “desmoid tumour” or “fibromatosis”. Fourteen patients with suitable histology were found. There were six males in the cohort and eight females. The median age at diagnosis was 12 (range 5-35). The most common tumour sites were the extremities, limb girdles and chest wall. Four patients had at least one recurrence, and of these all of them had a primary tumour in the extremities or limb girdles. The patient demographics at CoRSU are similar to those demonstrated in the literature. The study supported the idea that younger patients are more likely to develop extra-abdominal tumours, and older patients may present with abdominal tumours. Most patients were managed surgically, in line with current recommendations.

A 15-year-old boy presented with a painless, progressively growing swelling of his right arm. The swelling was firm, non-tender and with restricted mobility. MRI imaging revealed a well-defined, heterogenous, lobulated swelling extending beneath arm and shoulder muscles. Wide local excision of the swelling was done under general anesthesia and pathologic examination revealed aggressive fibromatosis of the arm. Adjuvant radiotherapy was provided to the patient to reduce the risk of local recurrence of the tumor. Aggressive fibromatosis of the upper limb presents as a painless, progressively growing swelling. Assessment with MRI is imperative for making a preliminary diagnosis. Wide local excision with safety margin with adjuvant radiotherapy is the main line of treatment to minimize the incidence of recurrence and preserve the limb.

The goal of this meta-analysis was to evaluate the association between CTNNB1 mutation and recurrence in surgically treated desmoid tumor (DT) patients. PubMed, Embase and Cochrane library were systematically searched. The outcome of interest was the risk of recurrence. The number of patients with CTNNB1 mutation and the number of recurrences they developed were recorded and compared. The quality of these studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Odds ratios and variances were calculated and pooled. A total of eight studies were identified including 637 patients. S45F-mutated DTs were more likely to recur compared with wild type, T41A and other mutated DTs. However, there were no statistically significant differences in the rate of recurrence between wild type and T41A mutation or other mutation. Among CTNNB1 mutations, the mutation S45F is a high-risk factor for recurrence of DT and may be a predictive marker for the recurrence of sporadic DT.

Desmoid-type fibromatosis represents a challenge in the landscape of surgical oncology, for several reasons. The tumors can be infiltrative and locally aggressive, surgery may be morbid, and patients are usually young, and thus treatment sequelae must be managed for decades. Desmoids do not have metastatic potential, therefore management strategies for desmoids have evolved to employ frontline treatments that are largely non-operative. In fact, with unpredictable and benign behavior, we now recognize that desmoids can also stabilize and regress, making active observation an option for many patients. Moreover, many medical therapies are active in the disease. We reviewed landmark studies describing contemporary issues that affect treatment recommendations for desmoid patients: prognostic factors, indication to active surveillance, role of surgical margins, postoperative radiotherapy, and the most recent expert consensus papers.

Hereby, we report a case of fibromatosis arising in the left popliteal fossa, proven by histopathology and immunohistochemistry. Local excision of the mass was performed. The patient was asymptomatic for 6 months, after which she complained of difficulty in walking. Clinical evaluation elicited recurrence in the surgical bed. In spite of the surgical excision with tumor-free margins, recurrence was seen within a span of 6 months. 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) was done to rule out multifocal disease and to define the extent of relapse. Although magnetic resonance imaging provides an excellent soft-tissue resolution to delineate the disease, 18F-FDG PET/CT is an important and supplementary tool which aids in the management of fibromatosis.