Beta-Catenin Mutation with Complex Chromosomal Changes in Desmoid Tumor of the Scalp: A Case Report

Gain-of-function mutations in the beta-catenin gene (CTNNB1) drive genomic instability within different cancers. However, it is unclear whether alterations in beta-catenin signaling can still lead to chromosomal rearrangements in neoplasms without metastatic potential. Here, we report a unique case, whereby a desmoid tumor of the scalp contains a missense mutation in CTNNB1. This mutation is located at the T41 phosphorylation site—previously reported to be necessary for proper beta-catenin degradation. Online database analysis then revealed that our mutation is likely causative of many different cancers and also absent in the healthy public. Karyotyping of the desmoid tumor cells then showed complex chromosomal changes in 16 out of 20 cells examined. To treat this patient, we surgically removed both the neoplasm and underlying calvarium and then successfully reconstructed the skull and scalp. Taken together, our data suggest that increased beta-catenin signaling can lead to genomic instability in the absence of metastatic potential.

Three distinct mutations involving the CTNNB1 (beta-catenin) gene have been identified in the vast majority of desmoid-type fibromatosis tumors, which cause activation of the Wnt signaling pathway and impact prognosis. This study examines whether the different CTNNB1 mutants (T41A, S45F) occurring in DTF tumors differentially affect Wnt signaling activity, which might explain the different disease course between DTF patients harboring different CTNNB1 mutations. Real-time polymerase chain reaction (RT-PCR) on 61 formalin fixed paraffin embedded DTF samples with known CTNNB1 status was used to measure the relative mRNA expression level of Wnt target genes AXIN2, DKK1 and CCND1. Additionally, publicly available mRNA expression data retrieved from the Gene Expression Omnibus of 128 DTF samples were used for an unsupervised cluster analyses based on the expression of a selection of Wnt targets. No statistically significant difference in relative expression levels of Wnt target genes AXIN2, DKK1 and CCND1 was identified between either CTNNB1 wild-type, S45F or T41A mutated DTF samples. Moreover, the hierarchical cluster analyses using selected Wnt targets did not discriminate between different CTNNB1 mutation types. No differences in the expression levels of Wnt target genes were observed between the different CTNNB1 mutation types in DTF tumors. Further studies are needed to decipher the mechanism accounting for the diverse disease courses between DTF patients with different CTNNB1 variants.

In this article, we reported a 28-year-old female with a desmoid tumor of the anterior abdominal wall who underwent surgical resection. Preoperative evaluation was done using abdominal ultrasound, computed tomography, and magnetic resonance imaging. The histopathological examination of the resected specimen revealed a desmoid tumor. Because of the heterogeneity of the desmoid tumors, treatment needs to be individualized. However, complete surgical resection with negative margins seems to be the treatment of choice for this tumor entity and postoperative radiotherapy can help reduces the local recurrence rate.

Desmoid tumors can be safely managed with watchful waiting, including either observation alone or tamoxifen/NSAIDs. Surgery at first presentation can be associated with significant treatment burden. All diagnoses of desmoid tumor within the Alberta Cancer Registry from August 2004 to September 2015 were identified. Patients with FAP were excluded. Demographics, tumor characteristics and treatment and outcome data were collected. Outcomes were compared between immediate surgery and watchful waiting. The effect of abdominal wall site on progression and recurrence and the effect of microscopic margin on recurrence were assessed with Fisher’s exact test. Watchful waiting was successful in 58% of patients, and a further 28% only required one aggressive treatment thereafter, for a total of 86%. Surgery had a favorable recurrence rate (15%), but some recurrences were associated with significant treatment burden. Treatment should be tailored to individual patients in a multidisciplinary setting. A trial of observation appears warranted in most patients. Recurrence rate was not affected by positive margins.

Desmoid tumors (DTs) of the head and neck have typically been classified as extra-abdominal, although the anatomic challenges of the head and neck warrant consideration of these DTs as a special entity. We present a review of DTs and describe our series of five patients with DTs of the head and neck treated within 2 decades. In our series of 5 patients with head and neck DTs, no patient experienced a recurrence during a median follow-up of 47.5 months (range 13 to 150), although all had positive histologic margins. The functional integrity of vital structures over meticulous radicality of the tumor resection must be considered, especially in the head and neck.

This case series is focused to determine the treatment outcomes for pediatric patients of aggressive fibromatosis. It is a retrospective case series conducted on 7 patients presented to section of Orthopedics, department of surgery of our institute in Karachi. Out of 7 pediatric patients, there were 6 (85.7%) males and 1 (14.3%) female patient. The median age was 6 years IQR (5-11) years. Gluteal region was the most common site of disease. Four patients (57.1%) had positive tumor margins while three (42.9%) had negative margins. Out of 7 patients, 4 patients (57.1%) had recurrent disease and they had positive margins. The median Disease Free survival time was 14 months and there was no expiry of patients. The conclusion of our study was that aggressive fibromatosis is more prevalent in children below 15 years of age and disease burden is higher in male gender. Positive margins after surgery indicate a high risk for disease recurrence therefore; primary surgery with negative margins is the treatment of choice for children with AF. However, we recommend that multicenter trials should be conducted in the future to clarify the role of adjuvant treatment for patients with pediatric AF.