Droplet Digital PCR (ddPCR) as a Novel Technology in Detecting CTNNB1 Mutations in Desmoid Fibromatosis

Desmoid fibromatosis (DF) is a locally aggressive soft tissue neoplasm with frequent recurrences. DF is characterized by alterations in the Wnt/β-catenin pathway, with the majority showing sporadic mutations in CTNNB1, whereas others have germline mutations in APC. Immunohistochemical staining for β-catenin is often difficult to interpret and can be negative in up to 30% of cases. Prior studies have shown that some DFs lacking nuclear expression of β-catenin may carry activating CTNNB1 mutations. Droplet digital polymerase chain reaction (ddPCR) has been used effectively in detecting mutations in formalin-fixed, paraffin-embedded (FFPE) samples of various cancer types. In this study, we assess the diagnostic utility of ddPCR to detect CTNNB1 mutations in DF with β-catenin expression on immunohistochemistry (IHC), as well as in diagnostically challenging cases. Of the 28 DFs with nuclear β-catenin expression by IHC, 24 cases showed a CTNNB1 mutation by ddPCR using primers against the most common point mutations in CTNNB1. The most frequent mutation was T41A (n=14; 50%), followed by S45F (n=8; 33%) and S45P (n=3;12%). We identified 8 additional (myo)fibroblastic lesions of uncertain classification, which were negative for nuclear β-catenin expression by IHC. We detected CTNNB1 mutations in 3 unknown lesions, including S45F (n=2) and S45P (n=1). ddPCR is a sensitive, rapid and cost-efficient methodology to detect common CTNNB1 mutations in DF, especially in diagnostically challenging cases.

Desmoid fibromatosis is a rare connective tissue malignancy. It can occur in a variety of locations, including the abdominal wall, extremities and abdominal cavity. There has been an association with development in a prior surgical scar. Common symptoms can vary depending on the location and can include being painless to having pain at the site, functional impairment and bowel obstruction from intra-abdominal masses. In the following report, we discuss a case in which a patient’s abdominal pain was attributed to a postoperative haematoma based on CT radiographic features; however, further work-up and biopsy yielded desmoid fibromatosis, a rare locally aggressive malignancy.

Despite being distinct lesions, gastrointestinal stromal tumours (GISTs) and desmoid fibromatosis may appear similar on imaging when they involve the stomach wall or bowel. As a result, they may be confused with one another when initially diagnosed. This report aims to present a case where a desmoid tumour was mistaken for a gastric GIST in a 27-year-old gentleman despite extensive investigation prior to exploratory laparotomy, and why differentiation through pathology, with a focus on the immunohistochemistry profile, is key for proper prognostication and appropriate management, including timely investigation for associated diseases such as Familial Adenomatous Polyposis in patients with desmoid tumours.

Background: The active surveillance (AS) has been suggested for the initial treatment of extra-abdominal desmoid fibromatosis (EADF), the percentage of patients who shifted to invasive secondary treatments was significant. Tranilast, an anti-keloid medication, is frequently used in Japan, but there is no detailed report on its efficacy. Methods: We retrospectively analyzed the medical records of EADF patients treated with tranilast between January 2009 and March 2021. Since EADF has been reported to shrink spontaneously, the effects of all drugs should be compared to AS. Therefore, we compared its clinical course with that under AS (determined by a systematic review) to assess the effect of tranilast. A systematic literature review of AS outcomes was conducted on July 22, 2021, according to PRISMA guidelines. The primary endpoint was the rate of conversion to secondary treatment. Secondary endpoints were progression-free survival, objective response rate (ORR), disease control rate (DCR), and adverse events. The rates of conversion to secondary treatment, ORRs, and DCRs were compared between the two groups using the Fisher’s exact test.ResultsEighteen patients who received tranilast as the initial treatment for EADF were included. Two patients (11.1%) underwent surgical resection due to tumor growth and continuous pain. Compared to the secondary treatment conversion rate from the pure AS approach (40.1%), tranilast was shown to significantly reduce the rate (p = 0.01). The ORR and DCR did not different between the two groups. Conclusions: As initial treatment for EADF, tranilast is preferred over AS.

Introduction: The development of desmoid fibromatosis (DF) is associated with pregnancy. The current treatment consensus recommends active surveillance (AS). However, data in pregnancy-associated DF is scarce and it is uncertain whether AS is the best management strategy for this DF-subgroup. The aim of this study was to describe demographic, tumor, obstetric, treatment characteristics and treatment outcome in pregnancy-associated DF. Methods: Female DF patients who were 18-50 years old at time of diagnosis (2000-2020) and had a history (≤5 years) of pregnancy at time of diagnosis were included. Results: Overall, 62 patients were included. The most common locations were abdominal wall (74%), pelvis (10%) and extremities (10%). Mutational analysis was conducted in 31 patients of which 94% had CTNNB1-mutations. Ten patients (16%) were diagnosed during pregnancy, while the remainder were diagnosed after pregnancy with a median time from delivery to diagnosis of 19 months (1-60). The frontline management was AS in 38 patients (61%) of whom 12 (33%) developed progressive disease and surgery in 23 patients (37%). In total, 30 patients underwent surgery and five had local recurrence (17%). Positive resection margins were no prognostic factor. Nine patients received systemic treatment in second- or third-line. Conclusions: Pregnancy-associated DF generally has an indolent behavior, where our results underscore the difficulty of establishing a clear definition of this entity. This study shows that AS should be the frontline management strategy for pregnancy-associated DF. When active treatment is indicated, surgery is a good option with low recurrence rates, even with positive (R1) resection margins.

Background: Desmoid tumors are extremely rare borderline benign and malignant tumors that do not exhibit accumulation on fluorodeoxyglucose positron emission tomography-computed tomography. In the present study, we report a rare case of a desmoid tumor with fluorodeoxyglucose accumulation at the anastomotic postoperative gastric cancer site. Case presentation: A 68-year-old Japanese man underwent robot-assisted laparoscopic distal gastrectomy for early-stage gastric cancer in 2019. The pathological diagnosis was stage IA cancer, and no adjuvant chemotherapy was administered. Two years after surgery, a soft mass appeared on the greater curvature side of the anastomosis on computed tomography. Fluorodeoxyglucose positron emission tomography-computed tomography revealed fluorodeoxyglucose accumulation, which suggested a malignancy; therefore, surgery was performed for diagnostic treatment. The histopathological findings led to the diagnosis of a desmoid tumor. The patient has not experienced recurrence to date. Conclusions: In the present study, we encountered a desmoid tumor arising from the anastomotic site of a postoperative gastric cancer. This case is rare as fluorodeoxyglucose positron emission tomography-computed tomography showed fluorodeoxyglucose accumulation in the desmoid tumor, and a preoperative diagnosis could not be reached. We hope that further studies will improve the accuracy of preoperative diagnosis.