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.

Treatment of Early Glottic cancer with Transoral Laser Microsurgery: An Australian Experience.

Introduction: Early laryngeal carcinomas may be treated by transoral laser microsurgery (TLM) or external beam radiotherapy. We review our experience of surgical treatment of laryngeal pre-malignant and malignant lesions over the past 15 years in a high-volume head neck unit. Methods: A review of a prospective patient database of patients with laryngeal SCC, who were treated with CO2 TLM between 2004 and 2019 was carried out. Results: 83 patients with a mean age of 67.7 (SD: 10.6) years underwent primary curative TLM for T1a/b SCC. 5-year overall survival was 93.2% (95%CI 86.9-100%), disease free survival was 86.0% (95%CI 78.1-94.6%), locoregional control was 91.2% (95%CI: 85.1-97.7%) and larynx preservation rate of 95.1% at 5 years. Conclusion: TLM is an excellent treatment modality for T1 early glottic SCC, with excellent locoregional control and disease-free survival. It is minimally invasive, outpatient-based, and cost-effective procedure preserving upper aerodigestive tract dysfunction for all activities of daily living.

Tumor depth of invasion versus tumor thickness in guiding regional nodal treatment in early oral tongue squamous cell carcinoma.

OBJECTIVES: Tumor thickness (TT) and tumor depth of invasion (DOI) correlate with the risk of regional lymph node metastases in early oral tongue squamous cell carcinoma (OTSCC). We aimed to determine optimal cutoff points to guide elective nodal treatment in early OTSCC. STUDY DESIGN: This retrospective study included 145 patients treated between 1995 and 2012 for histologically proven OTSCC (<4 cm). The minimum P value method was used to calculate the cut-point values of TT and DOI that predicted for nodal disease. The utility of the DOI cut-point value and the 5-mm DOI currently used for staging were then compared. RESULTS: Logistic regression analysis demonstrated that DOI (P = .00036) and TT (P = .0001) were highly correlated with nodal disease and each other. The cut-points that best predicted for nodal disease were 4.5 mm for DOI and 8 mm for TT. There was no difference in utility between DOIs of 4.5 mm and 5 mm. CONCLUSIONS: TT and DOI were highly correlated with nodal risk but had different cut-points for prediction. Our findings highlight the need to recognize these parameters as discrete entities and to report them appropriately. This study's findings support the use of the 5-mm DOI, currently used for staging, as also the threshold value to guide elective nodal treatment.

Diagnostic utility of microsurgical carbon dioxide laser excision of oral potentially malignant lesions vs incisional biopsy: a retrospective histopathological review.

OBJECTIVE: Complete excision of oral potentially malignant lesions (OPMLs) could result in improved and earlier detection of more severe grades of oral epithelial dysplasia and/or frank malignancy. Transoral microsurgical carbon dioxide laser techniques allow for resection of OPMLs, even those that are extensive. The advantages are improved diagnostic yield, improved viability of the specimen for pathologic evaluation, reduced postoperative morbidity, and easier postoperative clinical surveillance. STUDY DESIGN: Retrospective review of the histopathology slide material and attendant clinical notes of 31 sequential patients with OPMLs demonstrated the following histopathologic diagnoses on conventional incisional biopsy (CIB): verrucous hyperplasia (2 patients); mild dysplasia (11 patients), moderate dysplasia (3 patients) or severe dysplasia (15 patients); and subsequently, these patients went on to have laser excision biopsy (LEB) of their OPMLs. RESULTS: Histologic diagnosis was upgraded after LEB in 14 (45%) patients (P < .001), with unexpected findings of cancer in 9 cases (29%) and more severe dysplasia in 5 cases (16%). CONCLUSIONS: Use of LEB to supplement CIB appears superior in the detection of severe dysplasia and frank malignancy in OPMLs compared with use of CIB alone. Prospective trials are indicated to determine if the superior diagnostic utility of LEB improves patient outcomes with regard to earlier detection of oral squamous cell and/or verrucous carcinoma.

Data Set for the Reporting of Carcinomas of the Nasal Cavity and Paranasal Sinuses: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting.

The International Collaboration on Cancer Reporting was established to internationally unify and standardize the pathologic reporting of cancers based on collected evidence, as well as to allow systematic multi-institutional intercountry data collection to guide cancer care in the future. This data set has been developed by the collaborative efforts of an international multidisciplinary panel of experts involved in the care of patients with carcinomas of the nasal cavity and paranasal sinuses (sinonasal tract). The nasal cavity and paranasal sinuses (including frontal, sphenoid, ethmoid, and maxillary sinuses) comprise a very complex anatomic area of the head and neck, affected by a sometimes bewildering array of neoplasms. Management of malignancies in this anatomic region involves complex surgery because of the anatomic confines and close proximity to many vital structures. Given a multidisciplinary approach, the standardized reporting of the carcinomas that develop in this anatomic region include both required (core) and recommended (noncore) elements in pathology reporting in order to be able to identify critical prognostic factors, often requiring clinical and radiologic correlation. A summary of the International Collaboration on Cancer Reporting guidelines and clinically relevant elements, along with additional explanatory notes, are provided, based on evidentiary support from the literature, set in the context of practical application.

Sentinel lymph node biopsy for early oral cancers: Westmead Hospital experience.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has become an alternative option to elective neck dissection (END) for early oral cavity squamous cell carcinoma (OCSCC) outside of Australia. We sought to assess the technical feasibility of SLNB and validate its accuracy against that of END in an Australian setting. METHODS: We performed a prospective cohort study consisting of 30 consecutive patients with cT1-2 N0 OCSCC referred to the Head and Neck Cancer Service, Westmead Hospital, Sydney, between 2011 and 2014. All patients underwent SLNB followed by immediate selective neck dissection (levels I-III). RESULTS: A total of 30 patients were diagnosed with an early clinically node-negative OCSCC (seven cT1 and 23 cT2), with the majority located on the oral tongue. A median of three (range: 1-14) sentinel nodes were identified on lymphoscintigraphy, and all sentinel nodes were successfully retrieved, with 50% having a pathologically positive sentinel node. No false-negative sentinel nodes were identified using selective neck dissection as the gold standard. The negative predictive value (NPV) of SLNB was 100%, with 40% having a sentinel node identified outside the field of planned neck dissection on lymphoscintigraphy. Of these, one patient had a positive sentinel node outside of the ipsilateral supraomohyoid neck dissection template. CONCLUSION: SLNB for early OCSCC is technically feasible in an Australian setting. It has a high NPV and can potentially identify at-risk lymphatic basins outside the traditional selective neck dissection levels even in well-lateralized lesions.

Relationship between CO2 laser-induced artifact and glottic cancer surgical margins at variable power doses.

BACKGROUND: The carbon dioxide laser can induce thermal cytologic artifacts at the margin of early glottic squamous cell carcinoma histologic specimens, which makes assessment of the margin difficult. This study assesses and correlates the depth of laser-induced thermal artifact with laser power rating. METHODS: The surgical margins of 30 patients with early glottic squamous cell carcinomas who underwent laser resection were reanalyzed retrospectively. RESULTS: Thermal damage consisted of collagen denaturation within the vocal cord lamina propria and vocalis muscle, and epithelial structural changes. There was a decrease in depth of tissue artifact with increased power rating (p > .05). The average depth of thermal damage was 380.83 ± 178.79 µm. CONCLUSION: The laser causes less thermal damage at higher power, presumably because of the increased speed of cutting and reduced contact time with surrounding cells. Knowledge of the depth of thermal artifact is important surgically when ensuring the cancer is excised with sufficient oncologic margin. © 2015 Wiley Periodicals, Inc. Head Neck 38: E712-E716, 2016.

Neuroendocrine Adenoma of the Middle Ear: A Rare Histopathological Diagnosis.

Neuroendocrine tumours occur throughout the body but are rare in the head and neck region and particularly rare in the middle ear. Clinical findings are often nonspecific and therefore pose a diagnostic challenge. Furthermore, the nomenclature of neuroendocrine tumours of the middle ear is historically controversial. Herein a case is presented of a middle ear adenoma in a 33-year-old patient who presented with otalgia, hearing loss, and facial nerve palsy. A brief discussion is included regarding the histopathological features of middle ear adenomas and seeks to clarify the correct nomenclature for these tumours.

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.

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.

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.

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.

Proliferating cell nuclear antigen and Ki67 immunoreactivity in ameloblastomas.

OBJECTIVE: This study used proliferating cell nuclear antigen (PCNA) and Ki67 to evaluate and compare the in situ proliferative activity of (1) solid and multicystic and (2) unicystic ameloblastomas in an attempt to provide a scientific basis for any differences in biologic behavior that exists between these 2 groups of lesions. STUDY DESIGN: Twenty archival tissue sections, 10 of primary unicystic and 10 of solid and multicystic ameloblastomas, were immunohistochemically stained with PCNA and Ki67 antisera. Immunoreactivity was evaluated by the counting of cells, and the data obtained were statistically analyzed. RESULTS: The results showed that cellular proliferative activity varied within the ameloblastoma types. The unicystic ameloblastomas showed statistically significantly higher PCNA and Ki67 labeling indices than the solid and multicystic variant. CONCLUSION: There appears, therefore, to be no correlation between proliferative activity as shown by these proteins and reported biologic behavior.

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.

Desmoplastic fibroblastoma presenting as a parotid tumour: a case report and review of the literature.

Desmoplastic fibroblastomas (DFs) are rare fibrous soft tissue tumours that usually arise in subcutaneous tissue or skeletal muscle in a variety of anatomical sites. These lesions most frequently present as painless, slow-growing mobile masses. A case of DF is described in a 47-year-old man who presented with a painless right parotid mass of 2 months duration. At surgery, the lesion was attached to the tail of the right parotid gland. Histopathological examination demonstrated a fibrous lesion comprising spindled and stellate shaped fibroblasts with focal myxoid stromal change. The features were consistent with a DF. This report documents a rare parotid lesion which may mimic other more common parotid gland neoplasms.

Synovial chondrosarcoma arising in synovial chondromatosis of the temporomandibular joint.

Synovial chondromatosis of the temporomandibular joint is rare. Even less commonly documented is the progression of synovial chondromatosis to a synovial chondrosarcoma. The aim of this paper is to present only the third case of synovial chondrosarcoma of the temporomandibular joint. Distinction between these two entities by histology alone is extremely difficult and even though it is advised that the definitive diagnosis should be based on clinical, radiographic and histological evidence, this has proved not to be so simple. The patient, a 63 year old female presented with a swelling associated with her left temporomandibular joint. CT and MRI scans confirmed the presence of a periauricular chondroid mass. Fine needle aspiration biopsy revealed an atypical chondroid lesion that was supicious for a chondrosarcoma. The left temporomandibular joint and surrounding tissues were resected after further imaging and extensive clinical, radiological and cytologic consultations. A diagnosis of synovial chondrosarcoma arising in synovial chondromatosis was made.