Immunohistochemical and Molecular Analyses Focusing on Mesenchymal Cells in Papillary Thyroid Carcinoma with Desmoid-Type Fibromatosis

This study was designed to evaluate the prevalence of CTNNB1 (beta-catenin) mutations in cases of papillary thyroid carcinoma with desmoid-type fibromatosis (PTC-DTF) expressing aberrant nuclear and cytoplasmic immunoreactivity for beta-catenin. Eight cases of PTC-DTF were available for this study. Immunohistochemistry for beta-catenin and BRAFV600E was performed. CTNNB1 and BRAFV600E mutations were also evaluated by direct sequencing. For beta-catenin, although we could demonstrate aberrant nuclear and cytoplasmic immunoreactivity in DTF components in all cases, suggesting activated Wnt signaling, direct sequencing revealed a missense mutation, c.121A>G (p.T41A), in exon 3 in only one case, and no mutations in exons 3, 4, and 5 in the other cases. In the BRAFV600E analyses, immunohistochemistry revealed positive staining in the carcinoma cells but not DTF components of all cases. These findings were subsequently validated by direct sequencing. This study suggests the significance of the BRAFV600E mutation and activation of Wnt signaling pathway in the carcinoma cells and DTF components, respectively. We believe that the CTNNB1 mutations are not the major factor behind beta-catenin translocation indicating Wnt pathway activation. Further study is required to evaluate whether molecular abnormalities other than the CTNNB1 mutation cause activation of Wnt signaling in DTF components of PTC-DTF.

Mesenteric fibromatosis (MF) is a locally aggressive proliferative spindle cell lesion of the mesentery. A 34-year-old male presented with increasing abdominal pain and constipation. On workup, patient was found to have a large pelvic mass on CT A/P concerning for cancer. The patient underwent surgical excision of >15 cm intra-abdominal tumor along with adherent small bowel section. Histology of the tumor showed a spindle cell lesion consistent with MF. Previous reports have shown association of MF with Gardner syndrome and familial adenomatous polyposis. We present the first reported case of MF in a patient with previous neuroblastoma.

The aim of this study was to investigate the response of DF cells to microenvironmental factors such as inflammatory and growth factors or hormones. We observed that the inflammatory cytokine, transforming growth factor-beta (TGF-beta1) stimulated cell growth and myofibroblast differentiation of DF cells regardless of the presence of a beta-catenin mutation. The role of TGF-beta1 in cell growth and myogenic differentiation of in vitro cultures of primary DF cells and normal fibroblasts was investigated by gene and protein expression analyses. We demonstrated that TGF-beta1 exerted its role via the canonical Smad pathway with the phosphorylation of Smad3 being crucial for TGF-beta1 dependent DF cell growth and myofibroblastic differentiation. Furthermore we demonstrated that cell confluence is a critical determinant of TGF-beta1 inducing the DF myofibroblast differentiation, implying that the intercellular communications have an important role on the DF myofibroblast behavior. We observed the formation of an increased stress-fiber pattern in DF cells with increased projected cell area and stronger cell-cell contacts in presence of TGF-beta1. These results demonstrated that TGF-?1 plays a crucial role in the DF cells growth and, together with cell-cell interactions, in DF myofibroblast conversion; we also highlighted that the cellular sensitivity to this cytokine was an intrinsic feature of the DF cells.

We present a case of a 51-year lady who presented with a 6.2 x 4.5 x 3.3 cm neoplasm in the anatomic area of the greater gastric curvature, the splenic hilum and the tail of the pancreas that was diagnosed as GIST on the CT scan. The patient was submitted to laparoscopic excision of the tumor and histopathological examination revealed desmoid type fibromatosis of the splenic hilum infiltrating the spleen, pancreatic tale and greater gastric curvature. According to the authors’ knowledge, this is the first reported case of a sporadic splenic desmoid tumor, which has been treated successfully by laparoscopic en block resection.

Laparoscopy is used increasingly in prophylactic surgery for patients with familial adenomatous polyposis (FAP) undergoing colectomy with ileorectal anastomosis (IRA). Little is known about the impact of laparoscopy on subsequent desmoid risk. This study documented the risk of desmoid in patients undergoing laparoscopic and open IRA. Some 112 patients (61 female) underwent colectomy and IRA. Patients who underwent laparoscopic IRA had a reduced risk of desmoid formation (3 of 69 (4 per cent) versus 7 of 43 (16 per cent) in the open group; P = 0.043). Laparoscopic IRA may reduce risk of subsequent desmoid formation in patients with FAP.

Here, we describe a case where an extra-abdominal DT mimicked a schwannoma in the posterior cervical spine. A 67-year-old female patient presented with acute neck and bilateral shoulder pain. After attempting conservative treatments with no symptomatic relief, a magnetic resonance imaging of the cervical spine was obtained, showing a paraspinal mass in the posterior elements from C2 to C4. The computed tomography guided needle biopsy showed rare spindle cells, suggestive of a spindle cell neoplasm, and complete surgical resection was performed. The pathology report was consistent with fibromatosis, leading to a final diagnosis of the extra-abdominal desmoid. This case demonstrates a rare presentation of an unusual tumor that often manifests with nonspecific symptoms or no symptoms at all.