Cutaneous desmoid-type fibromatosis: a rare case with molecular profiling

Here we present a 78-year-old male with desmoid-type fibromatosis arising in the dermis of the right medial calf with a pathogenic mutation in CTNNB1 and a variant of unknown significance in APC.

We made a pathological diagnosis gross total tumor resection by the international collaboration with Myanmar, Cambodia, and Japan. The case was a 5-year-old Burmese boy. A recurrent growing tumor was found in his right buttock, which caused gait disturbance and aesthetic problems. In order to remove this giant desmoid fibromatosis (DF), the oncologist consulted our department. Because DF had localized outside the pelvic ring, it could be resected with the embolization of the branch of the internal iliac artery. In operation, the sciatic nerve was preserved and a gross total resection was performed with R1 surgery. The patient is alive without any functional disorders and recurrences and is maintaining a good QOL. This is the first report on treating DF in Myanmar by an international collaboration team.

This paper aimed to (1) to compare the outcomes of extra-abdominal desmoid tumor fibromatosis (DTF) after different treatment modalities, (2) to assess prognostic factors for recurrence following surgical excision, and (3) to assess prognostic factors for progression during observation. This was a retrospective multicenter study under the patronage of the European Musculoskeletal Oncology Society (EMSOS). Three hundred eighty-eight patients (240 female, 140 male) with a mean age of 37.6 (±18.8 SD, range: 3-85) were included in the study. Two hundred fifty-seven patients (66%) underwent surgical excision of ADF, 70 patients (18%) were observed without therapy, the residual patients had different conservative treatments. There were no significant differences in terms of tumour recurrence or progression between the different treatment groups. After surgical excision, younger age, recurrent disease and larger tumour size were risk factors for recurrence, while tumours around the shoulder girdle and painful lesions were at risk of progression in the observational group. Local recurrence rate after surgery was similar to progression rates under observation. Hence, observation in DTF seems to be justified, considering surgery in case of dimensional progression in 2 consecutive controls (3 and 6 months) and in painful lesions, with particular attention to lesions around the shoulder girdle.

We reviewed 85 cases of desmoid-type fibromatosis (DF) and performed Sanger sequencing for detecting mutations in CTNNB1 and immunostaining for detecting beta-catenin localization. We included 70 DF samples, of which 56 cases demonstrated nuclear beta-catenin localization and 43 cases harboured CTNNB1 mutations. CTNNB1-mutant DF samples consistently displayed nuclear beta-catenin expression and were derived from larger-sized tumours compared to samples with wild-type CTNNB1. When we further classified DF cases into 2 subgroups based on the type of specimen, excised specimens with nuclear beta-catenin expression frequently displayed CTNNB1 mutation and no statistical correlation between nuclear beta-catenin expression and CTNNB1 mutation was observed in biopsies. When we classified CTNNB1 mutation cases into 2 subgroups (DF with T41A or T41I, and DF with S45F or S45P), T41A or T41I mutations were observed more frequently in males than in females. Additionally, DF tumours harbouring S45F or S45P mutations were located more frequently in the abdominal wall than tumours with T41A or T41I mutations. In conclusion, CTNNB1 mutation correlates with nuclear beta-catenin expression in larger or excised DF tumours, and DF harbouring CTNNB1 mutations manifest variable clinical presentations.

To investigate the efficiency of pre-therapy magnetic resonance imaging (MRI) features in predicting the prognosis of desmoid-type fibromatosis patients treated with imatinib. A total of 38 desmoid-type fibromatosis patients treated with imatinib were collected in this retrospective study. The high signal intensity on pre-therapy MRI was evaluated on axial T2 and T1 contrast-enhanced sequences with fat suppression. Hyperintense T1 contrast enhancement (CE) proportion (? 75%) was identified as an independent predictor for PFS. Patients with hyperintense T1 CE proportion <75% demonstrated no progression, while patients with hyperintense T1 CE proportion ?75% demonstrated a progression rate of 78.4%. Hyperintense T1 CE proportion in the tumor is a potential predictor of disease progression in patients with desmoid-type fibromatosis treated with imatinib. Hyperintense T1 CE proportion <75% indicates progression-free during treatment.

Desmoid-type fibromatosis (DF) is a locally aggressive but non-metastatic (myo)fibroblastic neoplasm. A hallmark of the tumor is nuclear positivity for beta-catenin in immunohistochemistry due mostly to CTNNB1 mutations. However, a recent study has reported that even beta-catenin ‘nuclear-negative’ DFs can harbor CTNNB1 mutations and that the positive ratio of nuclear beta-catenin in DF is different among antibodies. Here, we reviewed soft tissue lesions for which the possibility of DF was considered and compared the sensitivity and specificity of nuclear beta-catenin for the diagnosis of DF among commonly used anti-beta-catenin antibodies, i.e., clone beta-catenin 1, 17C2 and 14. We analyzed 26 cases of DF, 28 cases of benign fibroblastic lesions, and 27 cases of other soft tissue tumors. The sensitivity and specificity of nuclear beta-catenin for the diagnosis of DF were different among antibodies; 54% and 98% in clone beta-catenin 1, 85% and 84% in 17C2, and 96% and 62% in 14. IHC of LEF1 showed comparable results with IHC of beta-catenin, with a sensitivity of 88% and specificity of 76%. Additionally, when beta-catenin 1 was used, DFs showed characteristic dotted cytoplasmic staining, often appearing as rings. Our results might be helpful for making a correct diagnosis of DF.