Background Central giant cell granuloma (CGCG) presents as a locally invasive, intraosseous lesion characterized by the accumulation of multinucleated giant cells amidst a matrix of hemorrhage and reactive fibrous tissue that infiltrates bone trabeculae. This idiopathic non-neoplastic proliferative lesion primarily affects the mandible, typically presenting as either unilocular or multilocular radiolucencies on X-rays. Although trauma or intraosseous hemorrhages are potential triggers, the precise histogenesis and etiology remain unclear. CGCG predominantly occurs in children and young adults, with a slight female predilection. Methods and materials A retrospective analysis of 21 cases of CGCG diagnosed at the Oral Pathology/Pathology department of Temple University Hospital between 2015 and 2022 was conducted. Each case was evaluated based on various parameters, including age, gender, presenting symptoms, radiographic findings, clinical differential diagnosis, and histological confirmation. The primary radiographic technique employed for diagnosis was X-ray imaging of the mandible and maxilla. The histological examination involved cutting paraffin-embedded tissue into 5-micrometer-thick sections, which were then stained using routine hematoxylin and eosin (H&E) stain. Notably, no specialized histochemical or immunohistochemical stains were utilized in the evaluation process. Results In our study, we reviewed 21 cases; 9 were male, 11 were female, and one had no available gender data. The age range was 15-76 years, with a mean of 50 years. The mandible was the most commonly affected location (17 cases; 81%) while the maxilla was less commonly involved (4 cases; 19%). Many CGCG lesions were asymptomatic (13 cases; 62%); eight cases (38%) were symptomatic, with pain and fullness of the affected dental region being the main manifestations. In a few cases, conditions such as brown tumor (severe hyperparathyroidism) and odontogenic neoplasms, such as ameloblastoma, were suspected clinically and radiographically. The diagnosis of CGCG with associated acute and chronic inflammation was confirmed in all the cases. Histological evaluation of routinely stained slides was the main diagnostic tool utilized. No special stains or molecular studies were required to establish the final diagnosis. Conclusions Our investigation has determined that CGCG exhibits a non-neoplastic nature, displaying a spectrum of behaviors ranging from non-aggressive to aggressive tendencies. While CGCG is predominantly observed in the mandible, rare instances of involvement in the maxilla have also been documented. Importantly, no confirmed association with neoplastic lesions was identified during our analysis. The clinical course of CGCG tends to be indolent, with some cases presenting in association with impacted teeth. It\'s noteworthy that CGCG can present features mimicking neoplastic conditions, such as ameloblastoma, or localized lesions linked to systemic disorders such as hyperparathyroidism (brown tumor).

OBJECTIVE: The advent of denosumab has rendered giant cell tumors (GCT) of the bone amenable. It makes sense to evaluate its effect on the patient\'s symptoms and the histopathological outcomes. The aim of the study is to ascertain the effect of 24-week neoadjuvant denosumab therapy on the following parameters: visual analogue scale (VAS), musculoskeletal tumor society (MSTS) scores, tumor size, and the number of giant and stromal cells.
METHODS: This observational study was conducted from February 2022 to April 2023 at SCB Medical College and Hospital, India. Fifty-four GCT participants had their VAS and MSTS scores assessed at baseline and then every four weeks for the next 24 weeks. At 24 weeks, changes in their tumor size and the number of giant and stromal cells per high-power field (hpf) were also evaluated.
RESULTS: Fifty-four (82%) out of the 66 enrolled participants completed the study. Among those 54, 29 (54%) participants were female. The study population had a mean age of 39.0 ± 4.7 years. The median VAS scores were (female: 7.0, male: 7.0; p = 0.51) at baseline and (female: 2.0, male: 2.0; p = 0.39) at 24 weeks. The median MSTS scores at baseline and 24 weeks were (female: 8.0, male: 8.0; p = 0.41) and (female: 15.0, male: 16.0; p = 0.66), respectively. The median reductions in tumor size, the number of giant, and stromal cells (per hpf) were (female: 6.0 mm, male: 5.0 mm; p = 0.11), (female: 25, male: 27; p = 0.07), and (female: 1200, male: 2100; p < 0.001), respectively.
CONCLUSIONS: After receiving neoadjuvant denosumab for 24 weeks, the study participants\' clinical symptoms and histological indicators improved. With the exception of the stromal cells, there was no statistically significant difference between the male and female participants.

The presence of syncytial-type multinucleated giant tumor cells with emperipolesis in clear cell renal cell carcinoma (RCC) is uncommon, with only 31 cumulative published cases to date. After a rereview of 125 clear cell RCC of World Health Organization/International Society of Urological Pathology grade 3 or 4, 14 clear cell RCCs with admixed syncytial-type giant cells (to our knowledge, the largest series to date) were found with a mean patient age of 67 years and with no sex difference (M = 7, F = 7). Mean tumor size was 7.3 cm. The syncytial-type giant cells comprised between 2% and 20% of the tumor and were present mainly around areas of necrosis. Five tumors were staged as pT1 or pT2, 8 as pT3, and 1 as pT4. Other findings included sarcomatoid differentiation (3/14), rhabdoid differentiation (4/14), and emperipolesis (12/14). Positive immunostains included keratin AE1/AE3 (13/13), carbonic anhydrase 9 and CD10 (12/14 each), vimentin (8/14), EMA (5/12), and alpha-methyacyl-CoA racemase (3/12). Keratin 7, keratin 20, human melanoma black 45, KIT, TFE3, cathepsin K, CD68, CD61, and beta human chorionic gonadotropin were negative. Six of 13 patients had recurrence or metastases during a mean follow-up time of 56 months. Four of 13 patients died of disease, 2 of 13 patients were alive with the disease, and 7 of 13 patients had no evidence of disease. Although the incidence of finding syncytial-type multinucleated giant tumor cells in clear cell RCC is low (approximately 1.2%), given that a subset of the patients showed poor outcomes while lacking other poor histologic parameters (eg, sarcomatoid or rhabdoid differentiation), it may be prudent to recognize and report this feature when encountered.

UNASSIGNED: Hashimoto thyroiditis is an autoimmune disease which is diagnosed based on well-defined clinical and cytological criteria.
UNASSIGNED: The objective of this research is to study cytomorphological features in patients of Hashimoto thyroiditis and compare the findings with other studies. Literature on morphology of multinucleated giant cells was found to be lacking, and this study has focused on the number and morphology of these cells in this study.
UNASSIGNED: FNAC was done in patients who met the clinical diagnostic criteria of Hashimoto thyroiditis formulated by \"Japan Thyroid Association\" and smears were analyzed by light microscopy. Data analysis was done by XLSTAT in Microsoft Excel 2010. The Wilcoxon Signed Rank Test was done to analyze the data on multinucleated giant cells. The null hypothesis was that the median of the population of differences between the paired data of small and large giant cells is zero.
UNASSIGNED: A total of 26 patients were included in a period of one year. Contrary to observations in other studies, multinucleated giant cells were found in most participants. The Wilcoxon Signed Rank Test proved that small multinucleated giant cells were significantly more common than large multinucleated giant cells in Hashimoto thyroiditis; P value (two-tailed) being <0.0001 at significance alpha of 0.05. This study has also revealed that a few patients with Hashimoto thyroiditis can have large and very large multinucleated giant cells in a small number. Data on other cytomorphological features were no different than in other studies.
UNASSIGNED: The presence of multinucleated giant cells in 92.3% of patients in this study is far higher than in other studies which can have important diagnostic implications. Few large multinucleated giant cells can be present in a small number in a few patients as in Hashimoto thyroiditis.

BACKGROUND: Since giant cell tumors of bone (GCTB) and other giant cell rich tumors of bone (GCRTB) share the histological presence of osteoclastic giant cells and expression of RANK/RANKL, we hypothesized that GCRTB will respond similarly to denosumab as GCTB. The primary objective of this study was to determine the efficacy of denosumab in patients with GCRTB that have recurred or require morbid surgery.
METHODS: In this open-label, multicenter, phase II trial, patients with GCRTB were included (June 2018-March 2020). Recruitment was stopped because of low accrual. Patients received denosumab (120 mg) subcutaneously (SC) on day 1 of every 4-week cycle with a loading dose of 120 mg SC on days 8 and 15.
RESULTS: Three patients were enrolled. One withdrew consent before start of study. The remaining patients had central giant cell granuloma of the jawbone (CGCG). Median treatment duration was 15 cycles (range 12-18). In both subjects, improvement in ossification of lesions was seen. Median follow-up was 28.5 months (range 20-37). One patient developed a recurrence for which surgery was performed.
CONCLUSIONS: Due to critical emerging real-world data of denosumab in GCRTBs, the study was prematurely stopped and not supportive of use of denosumab for this indication. (ClinicalTrials.gov Identifier: NCT03605199).

Denosumab is recommended for advanced giant cell tumor of bone (GCTB) that is unresectable or resectable with unacceptable morbidity. But the effect of preoperative denosumab treatment on the local control GCTB remains controversial.
We conducted a study of 49 patients with GCTB in the limbs treated with denosumab before surgery and 125 patients without in our hospital from 2010 to 2017. Propensity-score matching (PSM) at a 1:1 ratio between the denosumab and control groups was performed to minimize possible selection bias, and compared the recurrence rate, limb function, and surgical degradation between the two groups.
The 3-year recurrence rates in the denosumab group and the control group were 20.4% and 22.9% after PSM, respectively (p = 0.702). In the denosumab group, 75.5% (n = 37/49) of patients experienced surgical downgrading. Limb joint preservation rates were 92.1% (35) for 38 patients treated with denosumab and 60.2% (71) for 118 control subjects. (p ≺ 0.001). Postoperative MSTS were higher in patients in the denosumab group than in the control group (24.1 vs. 22.6, p = 0.034).
Preoperative denosumab treatment did not result in an increased risk of local recurrence of GCTB. Patients with advanced GCTB may benefit from preoperative denosumab treatment for surgical downgrading and the preservation of the joint.

SARS-CoV-2 was reported to induce cell fusions to form multinuclear syncytia that might facilitate viral replication, dissemination, immune evasion, and inflammatory responses. In this study, we have reported the types of cells involved in syncytia formation at different stages of COVID-19 disease through electron microscopy.
Bronchoalveolar fluids from the mild (n = 8, SpO2 > 95%, no hypoxia, within 2-8 days of infection), moderate (n = 8, SpO2 90% to ≤ 93% on room air, respiratory rate ≥ 24/min, breathlessness, within 9-16 days of infection), and severe (n = 8, SpO2 < 90%, respiratory rate > 30/min, external oxygen support, after 17th days of infection) COVID-19 patients were examined by PAP (cell type identification), immunofluorescence (for the level of viral infection), scanning (SEM), and transmission (TEM) electron microscopy to identify the syncytia.
Immunofluorescence studies (S protein-specific antibodies) from each syncytium indicate a very high infection level. We could not find any syncytial cells in mildly infected patients. However, identical (neutrophils or type 2 pneumocytes) and heterotypic (neutrophils-monocytes) plasma membrane initial fusion (indicating initiation of fusion) was observed under TEM in moderately infected patients. Fully matured large-size (20-100 μm) syncytial cells were found in severe acute respiratory distress syndrome (ARDS-like) patients of neutrophils, monocytes, and macrophage origin under SEM.
This ultrastructural study on the syncytial cells from COVID-19 patients sheds light on the disease\'s stages and types of cells involved in the syncytia formations. Syncytia formation was first induced in type II pneumocytes by homotypic fusion and later with haematopoetic cells (monocyte and neutrophils) by heterotypic fusion in the moderate stage (9-16 days) of the disease. Matured syncytia were reported in the late phase of the disease and formed large giant cells of 20 to 100 μm.

Giant cell sarcomas (GCS) are rare head and neck neoplasms.
The Surveillance, Epidemiology, and End Results (SEER) database was analyzed for all patients who have been diagnosed with GCS from 1973 to 2014.
Four hundred and forty cases of GCS of the head and neck were identified. The average age at diagnosis was 74.4 years, 86.8% were white, 82.5% were male, 70.7% were insured, and 88.2% lived in an urban metropolitan region. Connective tissue was the most frequent primary site (42.5%). The 5Y-DSS rate was 91.1%, while the 5Y-OS was 54.6% for all cases. Patients treated with surgery alone had the highest 5Y-DSS rate of 94.5. T-classification odds ratio was a significant predictor of survival accounting for confounding variables on multivariate analysis.
GCS presents most frequently in connective tissue of the head and neck with overall high probability of survival. The treatment of choice is surgery alone.

The purpose of this study was to compare the immunohistochemical expression of tenascin-C (Tn-C) regarding clinicopathological variables and its association with the clinical behavior of central giant cell lesions (CGCLs). Forty-eight paraffin-embedded samples of CGCLs were selected. Based on clinical and radiographic features, the lesions were classified as aggressive (A-CGCLs) and non-aggressive (NA-CGCLs) subtypes. Histological assessment included the microvessel count (MVC), multinucleated giant cell (MGC) count, and the proportion of tissue area involved by mononuclear stromal cells/interstitial fibrosis. Immunoreactivity, immunolocalization, and distribution patterns of Tn-C were studied immunohistochemically. The association between Tn-C expression and clinicopathological characteristics was analyzed separately and adjusted for confounders using logistic regression models. A significantly greater proportion of cases with moderate-to-intense, intracellular, and diffuse staining of Tn-C was observed in A-CGCLs. CGCLs with a size ≥3.3 cm, fast growth, cortical disruption, high MVC/MGC counts, and low interstitial fibrosis showed a significantly greater frequency of moderate-to-intense, intracellular, and diffuse staining. Logistic regression analysis indicated a strong/independent association of these three immunohistochemical parameters with the aggressiveness of lesions. These data appear to suggest a possible role for Tn-C in the etiopathogenesis of CGCLs of the jaws, where its upregulation might favor the destructive behavior of A-CGCLs.

To evaluate the occurrence, abundance, distribution, nature and clinical significance of multinucleated giant cell (MGC) in esophageal cancer.
MGCs were examined with conventional pathology, immunohistochemistry and immunofluorescence in 107 esophageal cancer tissues. The findings were correlated to pathological diagnosis and clinical behavior of the cancers.
MGCs were identified in 31.7% (34/107) of the cases. MGCs were positive for CD11c, CD11b, CD32, CD16, HLA-DR and MMP9, and negative for CD163, CD206 and CD64 giving a molecular profile of proinflammatory M1 but not immunosuppressive M2. MGCs were significantly related to decreased lymph node metastasis (p = 0.011), low pTNM stage (p = 0.044), favorable survival (p = 0.04), squamous cell cancer type rather than other histopathological subtypes (p = 0.020) and associated to better differentiation (p = 0.063).
MGCs belong to M1 macrophage and perform phagocytosis and scavenging of cancer cells that would benefit patients\' survival and could serve as a prognostic marker.