Blandine Ruhin-Poncet

Histological features and management of a mandibular Gorham disease: a case report and review of maxillofacial cases in the literature

Gorham disease (GD) is a rare osteolysis without sex, race, or age predilection, affecting bones in different regions. Based on clinical, histological, and molecular features, diagnosis is difficult and required exclusion of neoplastic, inflammatory, infectious, and endocrinologic disease. Etiology is still unknown. We report the case of a 36-year-old man suffering from severe progressive osteolysis located at the mandible. Histology showed massive osteolysis without malignant cells. Immunohistochemistry revealed thin-walled vessels and lymphatic ducts. These investigations lead to diagnosis of GD. Radical surgical treatment was followed by bisphophonate therapy. Recurrence occurred 4 months after surgery and alphaa-interferon therapy permitted remission. To support this case report, we reviewed the 41 maxillofacial cases published in the literature since 1928. Jaw is the main location; histology mostly shows hemangioma-like proliferation. Immune disorders are usually advanced as a cause although physiopathology is unknown. Therefore, appropriate treatment is controversial. Antiosteoclastic drugs are usually proposed in addition to surgery, but immunomodulating drugs and radiation therapy should also be considered in the treatment.

A treatment algorithm for managing giant mandibular ameloblastoma: 5-year experiences in a Paris university hospital

AIMS To review our experiences with giant mandibular ameloblastoma (GMA) over a 5-year period, and to formulate a treatment algorithm for managing this tumour. METHODS We retrospectively reviewed all GMA patients who underwent segmental mandibulectomy and immediate free fibular osteoseptocutaneous flap reconstruction (SM-IFFOFR) by a single reconstructive team from 2002 to 2006. All treatment methods and outcomes were analysed. FINDINGS Forty-four ameloblastoma patients were operated upon during this study period. Sixteen cases had GMA, of which 9 patients were included in this series (mean age: 35 years). The defects in the mandible ranged from 7 to 16 cm in length (mean: 12 cm). The average length of the harvested fibula was 11 cm, and the number of osteotomies ranged from 1 to 2. The mean ischemic time was 137 min (range: 90-180 min). Neck recipient vessels were used for flap perfusion in all cases. All but one flaps were viable without any complications, whilst partial skin-island necrosis occurred in 2 patients. Hospital stay was 2 weeks in most of the patients. No tumour recurrence was found during the follow-up period (range: 26-73 months). Dental implants were placed in 2 patients. CONCLUSIONS Despite several limitations of this study, we suggest that a radical approach with the SM-IFFOFR is an effective treatment for GMA. Further well-designed, larger series with longer follow-up periods are still encouraged.

Msx and Dlx Homeogene Expression in Epithelial Odontogenic Tumors

Epithelial odontogenic tumors are rare jaw pathologies that raise clinical diagnosis and prognosis dilemmas notably between ameloblastomas and clear cell odontogenic carcinomas (CCOCs). In line with previous studies, the molecular determinants of tooth development—amelogenin, Msx1, Msx2, Dlx2, Dlx3, Bmp2, and Bmp4—were analyzed by RT-PCR, ISH, and immunolabeling in 12 recurrent ameloblastomas and in one case of CCOC. Although Msx1 expression imitates normal cell differentiation in these tumors, other genes showed a distinct pattern depending on the type of tumor and the tissue involved. In benign ameloblastomas, ISH localized Dlx3 transcripts and inconstantly detected Msx2 transcripts in epithelial cells. In the CCOC, ISH established a lack of both Dlx3 and Msx2 transcripts but allowed identification of the antisense transcript of Msx1, which imitates the same scheme of distribution between mesenchyme and epithelium as in the cup stage of tooth development. Furthermore, while exploring the expression pattern of signal molecules by RT-PCR, Bmp2 was shown to be completely inactivated in the CCOC and irregularly noticeable in ameloblastomas. Bmp4 was always expressed in all the tumors. Based on the established roles of Msx and Dlx transcription factors in dental cell fates, these data suggest that their altered expression is a proposed trail to explain the genesis and/or the progression of odontogenic tumors.

Mandibular cuniculatum carcinoma: Apropos of 3 cases and literature review

Cuniculatum carcinoma is a well‐differentiated form of squamous cell carcinoma that shares histologic characteristics with papillary squamous cell carcinoma and verrucous carcinoma. Cuniculatum carcinoma usually occurs on the plantar region, and only 16 cases involving the oral cavity have been described in the literature.

The Effect of Etidronate on the Periodontium of Ovariectomized Rats

BACKGROUND Bisphosphonates are indicated for the treatment of osteoporosis. However, they could have an adverse effect on specific sites, such as the bisphosphonate-related osteonecrosis of the jaw. The aim of this study is to investigate the effect of etidronate on the resorption and apposition sides of the periodontium in ovariectomized rats. METHODS Twenty-four female Wistar rats were randomly subjected to either ovariectomy or sham operation. After 8 weeks, six animals of each group were sacrificed. The other 12 rats received 5 mg/kg/day etidronate subcutaneously during 4 weeks. Tartrate-resistant acid phosphatase reaction and immunohistochemical staining for receptor activator of nuclear factor-κB (RANK), RANK-ligand (RANKL), osteoprotegerin (OPG), and osteocalcin was performed. Immunoreactivity was evaluated using a semiquantitative analysis. RESULTS In ovariectomized rats, osteoclasts were noticed in the root socket of molars, including the apposition side of the periodontium, in which RANKL expression was significantly evidenced. In the etidronate-treated group, OPG expression was significantly expressed and osteoclasts that were noticed in the resorption side remained undetected in the apposition side even under ovariectomy. RANK was significantly expressed in ovariectomized rats treated with etidronate. Osteoid formation and osteocalcin expression were described on the alveolar bone surfaces in etidronate-treated rats, with or without ovariectomy. CONCLUSIONS Etidronate has specific site and bone cell actions in the periodontium. It inhibits the osteoclast differentiation induced by ovariectomy in the apposition side of the periodontium but maintains bone formation over all the socket surfaces. Such specificity may be related to the pathogenesis of the bisphosphonate-induced osteonecrosis of the jaw.

Kératokystes (ou tumeurs odontogéniques kératokystiques)

The aim of this study was to describe the management of keratocysts based on our own experience and on a large literature review. Keratocysts are benign odontogenic epithelial tumors. The main aspects of this lesion are described (definition, epidemiology, clinic, radiology, histology, treatment, and prognosis). In small intra-osseous tumors, surgical procedure must be as conservative as possible, most often enucleation. In large tumors with destruction of the cortical bone, or with destruction of coronoid process or notch, extensive resection can be indicated, with sometimes a transfacial approach for an accurate control, especially in soft tissues. Strict follow-up is mandatory because of the high risk of recurrence.

Specificity of paediatric jawbone lesions: tumours and pseudotumours.

INTRODUCTION Characteristics and epidemiology of jaw tumours have been described mostly in adults. Compared with their adult counterparts, childhood jaw tumours show considerable differences. The aim of this study was to describe the different jaw tumours in children, define diagnostic tools to determine their specificity and describe optimal treatment. METHODS All children patients with jaw lesions, excluding cysts, apical granuloma and osteitis were included in our study between 1999 and 2009. The medical records were analyzed for clinical, radiological, and pathological findings, treatments and recurrences. RESULTS Mean patient age was 10.9 years old, ranging from 2 months to 18 years old. Of the 63 lesions, 18 were odontogenic and 45 non-odontogenic lesions. 6% of all cases were malignant tumours; the mean age of presentation was 7.25 years old, [ranging from 0.2 to 18 years old]. Approximately 80% of the tumours developed after 6 years of age. Odontogenic tumours occurred more often after the age of 6. CONCLUSION Compared with their adult counterpart, childhood jaw tumours show considerable differences in their clinical behaviour and radiological and pathological characteristics. Clinical features of some tumours can be specific to children. Tumourigenesis is related to dental development and facial growth. Conservative treatment should be considered.

Tumeurs kératokystiques odontogènes de l’enfant et syndrome de Gorlin. Comment expliquer les récidives et l’agressivité des lésions ?

INTRODUCTION Keratocystic odontogenic tumors (KOT), as complications in Nevoid Basal Cell Carcinoma Syndrome (NBCCS), occur early (before 20 years of age) and are usually more aggressive. The aim of this retrospective study was to determine the clinical, histological, and genetic phenotype, of these lesions and to define predictive features of aggressiveness. PATIENTS AND METHODS We retrospectively studied five patients presenting with one or several KOT with NBCCS. We collected their clinical, radiological, and therapeutic data, rate of recurrence or new localization. Anatomopathological examinations were reviewed systematically. Somatic PTCH, SMO and SMAD 4 sequencing were completed. RESULTS The average age at diagnosis was 11.2 years. The average number of KOT was 3.2 most often located in the molar region. All the cysts were enucleated. Anatomopathological examination revealed the presence of satellite cysts and daughter cysts and epithelial expansion in more than 80% of cases. No somatic mutation was observed among KOT. DISCUSSION KOT develop in the first 10 years, in patients presenting with NBCCS, and recurrence is observed in the second and third decade. KOT are typically aggressive and have a tendency to recur, especially in patients with NBCCS. Anatomopathological examination may be predictive of the lesions aggressiveness. Understanding the genetic and immunological mechanisms should open the way for new medical treatment.

PTCH1 mutation and local aggressiveness of odontogenic keratocystic tumors in children: is there a relationship?

Keratocystic odontogenic tumors (KCOTs) are locally aggressive jaw lesions that may be related to PTCH1 mutations in isolation or in association with nevoid basal cell carcinoma syndrome. We sought to clarify the role of PTCH1 mutation in KCOT aggressiveness. We assessed cyst pathological characteristics, Ki-67 immunostaining, and somatic and germinal PTCH1 mutation in 16 KCOTs from 10 unrelated patients. Ten PTCH1 mutations were identified in 16 tumors. All tumors with PTCH1 mutations presented the criteria of pathological aggressiveness. We also noted the presence of a chorionic epithelial structure apparently acting as a secondary germinal center in these same tumors. Ki-67 immunostaining was not associated with PTCH1 mutation. KCOTs harboring the mutation display a chorionic epithelial structure that acts as a secondary germinal center. Genetic and microenvironmental factors might interact to propel tumor development.

Article originalTumeurs kératokystiques odontogènes de l’enfant et syndrome de Gorlin. Comment expliquer les récidives et l’agressivité des lésions ?Pediatric keratocystic odontogenic tumor and nevoid basal cell carcinoma syndrome. Predictive factors for recurrence and aggressiveness

INTRODUCTION Keratocystic odontogenic tumors (KOT), as complications in Nevoid Basal Cell Carcinoma Syndrome (NBCCS), occur early (before 20 years of age) and are usually more aggressive. The aim of this retrospective study was to determine the clinical, histological, and genetic phenotype, of these lesions and to define predictive features of aggressiveness. PATIENTS AND METHODS We retrospectively studied five patients presenting with one or several KOT with NBCCS. We collected their clinical, radiological, and therapeutic data, rate of recurrence or new localization. Anatomopathological examinations were reviewed systematically. Somatic PTCH, SMO and SMAD 4 sequencing were completed. RESULTS The average age at diagnosis was 11.2 years. The average number of KOT was 3.2 most often located in the molar region. All the cysts were enucleated. Anatomopathological examination revealed the presence of satellite cysts and daughter cysts and epithelial expansion in more than 80% of cases. No somatic mutation was observed among KOT. DISCUSSION KOT develop in the first 10 years, in patients presenting with NBCCS, and recurrence is observed in the second and third decade. KOT are typically aggressive and have a tendency to recur, especially in patients with NBCCS. Anatomopathological examination may be predictive of the lesions aggressiveness. Understanding the genetic and immunological mechanisms should open the way for new medical treatment.