Venous malformations (VMs) are among the most common slow-flow vascular malformations characterized by irregular venous channels, luminal thrombi, and phleboliths. To systematically manifest the disorganized vascular structures in sporadic VMs, we initially evaluated histopathological characteristics, perivascular cell coverage, adhesion molecules expression and vascular ultrastructures. Then, the expression of Tie2 and TGF-β in VMs was detected. Meanwhile, the in vitro studies were performed for mechanism investigation. Our data showed that the perivascular α-SMA+ cell coverage and expression of adhesion molecules in VMs were significantly decreased compared with those in the normal skin tissues. We also found that the expression and phosphorylation levels of Tie2 were upregulated, whereas TGF-β was downregulated in VMs, and they were negatively correlated. Moreover, the in vitro results also revealed a possible balancing effect between Tie2 and TGF-β, as demonstrated by the findings that Ang-1 (agonist of Tie2) treatment significantly downregulated TGF-β expression, and treatment with recombinant TGF-β could also suppress Tie2 expression and phosphorylation. This study provided strong evidence supporting the disorganized vascular structures and dysregulation of related molecules in sporadic VMs, and demonstrated a possible balancing effect between Tie2 and TGF-β, which might help to develop novel therapeutics for vascular disorganization-related disorders.

Background To describe epidemiological features of 565 Chinese patients with odontogenic keratocysts (OKC), to investigate possible prognostic factors related to recurrence, and to analyse features of recurrent OKC (rOKC). Material and Methods A retrospective chart review of 565 cases of OKC treated between 2003 and 2015 was undertaken. The probability of recurrence related to prognostic factors including large size, cortical perforation combined with involved teeth in the lumen of the cyst, inflammation, sites of the involved lesion, sex, and daughter cyst variables were analysed. The subsequent relapse of each OKC was compared. Results Patients ranged in age from 7 to 81 years (mean age, 28.4 years) and, of those affected, 66.9% were male and 33.1% were female. Mandibular OKC occurred in 63.01% and 36.99% occurred in the maxilla, 80.53% of patients had non-rOKC, 10.44% rOKC, and 9.03% had multiple OKC lesions. Enucleation with preservation of the involved teeth in the cystic lesion combined with cortical perforation was statistically associated with high recurrence rate, as were daughter cysts, and multilocular lesions. The number of recurrences and the average time (in years) to relapse decreased from the first relapse of OKC to the third relapse, and the difference was significant ( P <.05). Conclusions Preservation of the involved teeth combined with cortical perforation appeared to be a potential prognostic factor associated with high recurrence. The follow-up evaluation period for rOKC with ≥ 2 previous treatments should be shorter than for first-time rOKC. The decreasing average duration (years postoperatively) to relapse was related to the number of rOKCs, timing of relapse, and rOKC type. Key words: Keratocystic odontogenic tumor, risk of recurrence, involved teeth and cortical perforation, relapse, epidemiological features.

This study unmasks the downregulation of the TGF-β/CCN2 pathway in VMs, and indicates its target potential for sclerotherapy.

Rationale:Only 4.5% of brown tumors involve facial bones; of these, solitary bone involvement is usual. Brown tumors of multiple facial bones are extremely rare. Here, we report the case of a brown tumor of multiple facial bones initially misdiagnosed as an odontogenic cyst.Patient concerns:A pregnant 26-year-old woman was referred to our hospital with painful swelling of multiple facial bones, anemia, urinary calculi, marasmus, and a history of multiple bone fractures. Laboratory examination revealed an elevated serum calcium level of 3.09 mmol/L (normal range: 2.0–2.8 mmol/L) and a low phosphorus level of 0.62 mmol/L (normal range: 0.81–1.65 mmol/L). The serum alkaline phosphatase concentration was 397 IU/L (normal range: 24–82 IU/L) and parathyroid hormone level was 267 pg/mL (normal range: 14–72 pg/mL). Cone beam computed tomography revealed multiple ossifying fibromas of the maxilla and mandible. Incisional biopsy revealed abundant spindle cells with areas of hemorrhage and haphazardly arranged diffuse multinucleated giant cells.Diagnoses:The patient was diagnosed with primary hyperparathyroidism (HPT).Interventions:She was treated by parathyroidectomy.Outcomes:The multiple osteitis fibrosa cystica gradually resolved as bone re-mineralized. The patient has been followed up for 2 years without evidence of tumor recurrence.Lessons:As multiple osteolytic lesions of facial bones can be caused by primary HPT, serum calcium and parathyroid hormone assays should be performed routinely when investigating these lesions.

M2-polarized macrophages that may be recruited through TLOs in infected LMs may contribute to the progression of the disease by secreting VEGF-C, and therefore accelerating the proliferation of lymphatic endothelial cells.