Clinical and Radiologic Response of Central Giant Cell Granuloma to Denosumab: A 6-Year Prospective Observational Study.

Central giant cell granuloma (CGCG) is a rare lesion of the jaw occurring in young adults and adolescents. Surgery, the traditional mainstay of therapy, is associated with significant morbidity. Denosumab, a humanised monoclonal antibody to RANKL, is effective in a related entity, giant cell tumour of bone (GCTB), but experience in the more indolent CGCG is limited. This prospective observational study of all denosumab-treated CGCG at a tertiary referral centre (2015-2021) aimed to evaluate the safety, efficacy and recurrence risk using denosumab in CGCG at lower-frequency dosing than used for GCTB. All received standardised, time-limited courses of denosumab 120 mg with stepwise increase in dosing interval based on response. They were followed for up to 75 months using a radiation-minimising protocol: 3-monthly clinical, biochemical and radiological assessment (orthopantomograms, cone beam CT). Eight patients, median age 20.5 years [IQR 6], received 13 initial doses [IQR 10] of denosumab 120 mg. Radiologic response was seen after 5.5 doses [IQR 4.5]: ossification in all and size reduction in three. Recurrence occurred in four of seven completing therapy, observed 12 months post-cessation [IQR 6.5]. Larger baseline size, aggressive subtype and fewer than 12 initial doses were more common in the recurrence group. There was no osteonecrosis of the jaw. Hypocalcaemia occurred in one receiving modified dosing. This study represents the largest, most diverse cohort of denosumab-treated CGCG with the longest follow-up in literature. It demonstrates the efficacy of lower-frequency, time-restricted course of denosumab but highlights the risk of recurrence. Long-term follow-up is critical.

Membrane and cytoplasmic marker exchange between malignant neoplastic cells and fibroblasts via intermittent contact: increased tumour cell diversity independent of genetic change.

We previously demonstrated that human osteosarcoma cells (SAOS-2) induce contact-dependent apoptosis in endothelium, and expected similar apoptosis in human gingival fibroblasts (h-GF) using SAOS-2 alkaline phosphatase (AP) to identify cells. However, h-GF apoptosis did not occur, despite reduction in AP-negative h-GF number (p < 0.01) and enhancement of this by h-GF TNFα pretreatment (p < 0.01). We suggest that TNFα-enhanced transfer of membrane AP from SAOS-2 to h-GF would explain these data. This idea was investigated using fluorescence prelabelled cells and confocal laser scanning microscopy. Co-cultures of membrane-labelled h-GF (marker-DiO) and SAOS-2 (marker-DiD) generated dual-labelled cells, primarily at the expense of single labelled h-GF (p < 0.001), suggesting predominant membrane transfer from SAOS-2 to h-GF. However, opposite directional transfer predominated when membrane labels were reversed; SAOS-2 further expressed green fluorescent protein (GFP) in cytoplasm and nuclei, and h-GF additionally bore nuclear label (Syto59) (p < 0.001). Cytoplasmic exchange was investigated using h-GF prelabelled with cytoplasmic DDAO-SE and nuclear Syto59, co-cultured with SAOS-2 expressing GFP in cytoplasm and nuclei, and predominant cytoplasmic marker transferred from h-GF to SAOS-2 (p < 0.05). Pretreating h-GF with TNFα increased exchange of membrane markers (p < 0.04) but did not affect either cell surface area profile or circularity. Dual-labelled cells had a morphological phenotype differing from SAOS-2 and h-GF (p < 0.001). Time-lapse microscopy revealed extensive migration of SAOS-2 and cell process contact with h-GF, with the appearance of SAOS-2 indulging in 'cellular sipping' from h-GF. Similar exchange of membrane was seen between h-GF and with other cell lines (melanoma MeIRMu, NM39, WMM175, MM200-B12; osteosarcoma U20S; ovarian carcinoma cells PE01, PE04 and COLO316), while cytoplasmic sharing was also seen in all cell lines other than U20S. We suggest that in some neoplasms, cellular sipping may contribute to phenotypic change and the generation of diverse tumour cell populations independent of genetic change, raising the possibility of a role in tumour progression.

Maxillary sinus pathology in 119 patients--a histopathologic study.

INTRODUCTION: Information on histopathological changes within sinus mucosa is lacking, both in the general population, and in subjects with specific facial morphology and chronic respiratory obstruction. AIMS AND OBJECTIVES: To provide baseline data of the frequency and nature of pathological changes in the maxillary sinus in a specified group of patients. METHODS: 119 patients undergoing elective maxillary osteotomies were selected. These included patients with (70) and without (49) vertical maxillary excess (VME), and mouth and nasal breathers. The frequency and nature of the histopathological changes within the maxillary antral lining were recorded. RESULTS: Patients ranged from 13 to 47 years, with a M:F ratio of 1:2.4. The findings included congestion (95%), submucosal oedema (90%), retention cysts (26%), true polyps (4.6%) and inflammation. There was eosinophilia (68%), basement membrane thickening (28%), goblet cell hyperplasia (95%) and dystrophic calcification (59%). CONCLUSIONS: A significant degree of sinus pathology was found in this specified group of patients. This was probably due to their living in a polluted urban environment. In the presence of such widespread pathological changes and the virtual impossibility of obtaining "normal" control tissue, investigators may find it impossible to correlate maxillary sinus pathology with either facial form or breathing pattern.

Ameloblastic Carcinoma.

BACKGROUND: Ameloblastic carcinoma secondary type is an extremely rare and aggressive odontogenic neoplasm that exhibits histological features of malignancy in primary and metastatic sites. It arises through carcinomatous de-differentiation of a pre-existing ameloblastoma or odontogenic cyst, typically following repeated treatments and recurrences of the benign precursor neoplasm. Identification of an ameloblastic carcinoma, secondary type presenting with histologic features of malignant transformation from an earlier untreated benign lesion remains a rarity. Herein, we report 1 such case. CASE REPORT: A 66-year-old man was referred for management of a newly diagnosed ameloblastic carcinoma. He underwent radical surgical intervention comprising hemimandibulectomy, supraomohyoid neck dissection, and free-flap reconstruction. Final histologic analysis demonstrated features suggestive of carcinomatous de-differentiation for a consensus diagnosis of ameloblastic carcinoma, secondary type (de-differentiated) intraosseous. CONCLUSIONS: Ameloblastic carcinoma, secondary type represents a rare and challenging histologic diagnosis. Radical surgical resection with adequate hard and soft tissue margins is essential for curative management of localized disease.

A novel approach to the management of a central giant cell granuloma with denosumab: A case report and review of current treatments.

PURPOSE: To describe the efficacy of denosumab in the treatment of an aggressive giant cell granuloma of the mandible. METHODS: Denosumab was administered to a patient with a large aggressive giant cell granuloma of the mandible resistant to standard medical therapy. The effectiveness and response was measured on the basis of patient symptoms and radiological parameters. RESULTS: A significant reduction in patient symptoms was reported in association with tumour regression on follow up radiographs. CONCLUSION: This report demonstrates potential use of denosumab in aggressive giant cell granulomas of the jaws that have been resistant to medical therapy.

Oral synovial sarcoma: a report of 2 cases and a review of the literature.

The head and neck region constitutes the second most common site of involvement for synovial sarcoma, accounting for up to 10% of all cases. Intraoral synovial sarcoma is rare; in fact, only 29 cases have been reported. We describe 2 additional cases occurring in the floor of the mouth and the retromolar area. In addition, we have reviewed the clinicopathologic features of the previously reported cases. Our findings indicate that intraoral lesions differ from lesions occurring in other sites only in that intraoral cases show a greater male predilection and a generally painless initial presentation. In the oral cavity, the possible earlier detection, easy accessibility, and small size render these tumors more likely to be amenable to surgical excision, but their biologic behavior remains aggressive, with a poor long-term prognosis. Awareness of the potential for the occurrence of this neoplasm in the oral cavity is important for effective histopathologic diagnosis of intraoral spindle cell malignancies.

Oral Kaposi's sarcoma: a clinicopathologic study from South Africa.

OBJECTIVES: In this retrospective study, we defined the clinicopathologic characteristics of oral Kaposi's sarcoma (KS) and determined the presence of human herpesvirus 8 in the oral lesions in a group of South African patients. These results were compared with similar data from patients in developed countries. STUDY DESIGN: Eighty-one cases of oral KS were retrieved from the departmental archives. Fourteen patients with oral pyogenic granuloma served as control subjects. DNA was extracted by using a modified phenol chloroform extraction method and amplified by using polymerase chain reaction. If beta-globin DNA sequences could not be demonstrated, the patient was excluded from the study. RESULTS: Of the 81 patients included in the study, 68 (84%) had been diagnosed since 1997. Oral KS was often the first presenting sign of human immunodeficiency virus infection. Some of the lesions exceeded 4 cm in diameter. The most commonly affected site was the palate (37 patients), followed by the tongue and gingiva. Multiple oral sites were frequently involved. The mean age of the patients was 34.7 years (range, 2-58 years). The male-to-female ratio was 1.31 to 1. Most of the patients (94%) were black. Human herpesvirus 8 DNA sequences were detected in 44 of the 45 cases of oral KS in which the DNA was analyzed, and in 1 case of pyogenic granuloma. CONCLUSIONS: The only significant clinicopathologic differences in findings between our study and previous studies in developed countries were (1) the male-to-female ratio, (2) the preponderance of black patients, and (3) the more frequent involvement of the tongue. There are no studies reporting the clinicopathologic characteristics of oral KS in populations of developing countries.

A rare case of ameloblastic carcinoma.

Ameloblastic carcinoma is a rare type of ameloblastoma that has received little mention in the literature. While a number of cases have been published over many years, no institution has been able to produce a substantial case series. Ameloblastic carcinoma originates in the embryonic tooth components. It is believed to be an aggressive tumor that can metastasize; once metastasis occurs, the prognosis tends to be poor. Ameloblastic carcinoma is primarily a surgical condition that is best treated with resection; there has been little indication that other modalities are helpful. We present the case of a 40-year-old woman who was found to have a mandibular lesion by a dentist. After surgical resection, the tumor was found to be an ameloblastic carcinoma. The patient recovered without complication, and she was recurrence-free 18 months postoperatively. We also briefly review the available literature on the natural history of and management options for this rare tumor.

Mandibular osteomyelitis and tooth exfoliation following zoster-CMV co-infection.

Herpes zoster is a common viral infection, the oral soft tissue manifestations of which are widely known and recognized. Reports of spontaneous tooth exfoliation and jaw osteonecrosis following herpes zoster infection in the distribution of the trigeminal nerve are extremely infrequent and sporadic, with only 39 cases being reported in the literature. We report an additional case of mandibular osteomyelitis and spontaneous tooth exfoliation following herpes zoster infection, which occurred in the left mandible of a 70-year-old diabetic man; however, our case also showed CMV co-infection. The role of CMV in the pathogenesis of the osteonecrosis remains uncertain. Awareness of the possibility of CMV co-infection in various oral diseases including oral ulcers, Kaposi's sarcoma, and herpes zoster infections especially in immunocompromised patients is important, since spread of the CMV can easily occur to other sites with potentially fatal consequences. Early diagnosis can lead to effective treatment and prevention of complications.

Central granular cell odontogenic tumor: immunohistochemistry and ultrastructure.

Central granular cell odontogenic tumors are rare, with only 30 cases having been reported. The tumors usually occur in the mandibular molar area and are seen as localized painless swellings in patients older than 40 years. We report an additional case that occurred in the posterior mandible of an elderly black woman. All reported cases of this tumor are benign, and cure is effected by localized surgical excision. Ultrastructurally, the cells contain numerous lysosomes and phagocytic vacuoles. Immunohistochemically, the granular cells were positive for vimentin, CD68, muramidase, carcinogenic embryonic antigen, and bcl-2. These features support a mesenchymal origin with a possible histiocytic lineage for the granular cells. Awareness of the occurrence of this neoplasm is important to promote detection and differentiation from other intraoral granular cell lesions.