Numerous Multinucleated Giant Cells Research Articles

Central giant cell granuloma in the posterior region of mandible mimicking a fibro-osseous lesion and hemangioma: a case report

BackgroundA central giant cell granuloma (CGCG) is a benign, proliferative, intraosseous, and non-odontogenic lesion occurring primarily in children and young adults. On the histological level, it is characterized by numerous multinucleated giant cells scattered randomly throughout a sea of spindle-shaped mesenchymal stromal cells which are dispersed throughout the fibrovascular connective tissue stroma containing areas of haemorrhage. When it comes to radiographic features, CGCG can have an array of variations, ranging from well-defined expansile lesions to ill-defined and destructive lesions, with or without expansion.Case presentationThis case report reviews an 11-year-old Caucasian patient with a chief complaint of slow-growing swelling involving the right posterior mandibular region. The cone beam computed tomography (CBCT) revealed an ill-defined mixed lesion mimicking both fibro-osseous lesion and hemangioma. However, microscopic examination revealed multinucleated giant cells in a fibrous stroma suggestive of central giant cell granuloma.ConclusionOur intent in reporting this case is to highlight the importance of thorough clinical, radiographical and histopathological examination for accurate diagnosis and therapeutic interventions as well as to emphasize the importance of taking different possibilities into consideration when examining bony swellings in the head and neck region.

Granulomatous Slack Skin With Lung and Esophagus Involvement: A Case Report and Molecular Analysis.

Granulomatous slack skin (GSS) is a rare subtype of mycosis fungoides, and few cases have been known to spread to the blood, lymph nodes, or viscera. We present a case with early dissemination to the lung. A 27-year-old woman, previously healthy, presented with scattered disseminated scaly patches, associated with vulvar and intergluteal firm swelling and groin-skin induration for 1 year. She also reported mild fatigue and breathlessness on moderate exertion. The patient underwent blood tests, skin biopsies, and computed tomography scan. The skin biopsy showed a mildly atypical T-cell lymphoid infiltrate involving the dermis/hypodermis, with focal epidermotropism, associated with a granulomatous infiltrate and elastophagocytosis. The computed tomography scan revealed bilateral ground-glass lung nodular opacities. Positron emission tomography showed an increased signal in the skin and subcutis around the buttocks, inguinal and mediastinal lymph nodes, and lungs. The lung biopsy confirmed a dense T-cell infiltrate with numerous multinucleated giant cells. Subsequently, esophageal involvement was also observed following biopsy. Molecular analyses demonstrated identical T-cell clones in the skin and lung. After 6 cycles of chemotherapy/localized external radiotherapy, the patient had a partial skin response and stable lung disease. A preferred diagnosis of GSS with systemic spread was made based on clinical/histologic/molecular findings, after considering granulomatous mycosis fungoides and peripheral T-cell lymphoma, not otherwise specified. This case highlights the frequent diagnostic difficulty in distinguishing GSS from an inflammatory granulomatous dermatitis. Pulmonary and esophageal involvements are rare in GSS, and the simultaneous presentation of characteristic cutaneous GSS with systemic disease poses an additional classification challenge.

Case of Ray Fungus Presenting with Abdominal Distension

Actinomycosis is a rare infection caused by filamentous, non acid fast staining and gram positive bacteria. The diagnosis is rarely made preoperatively, and only histopathological examination can confirm it, as the condition presents with varied clinical manifestations, often resembling a malignant lesion on radiographic images. Hereby, the authors present a case of a 67-year-old female, who was admitted for evaluation of an abdominal mass. Radiologically, the mass resembled a desmoplastic fibroma, and clinically, it was suspected to be the same. The mass was excised and sent for histopathological examination. Grossly, two specimens were received. The first consisted of adherent bowel loops, including the ileum, appendix, caecum and descending colon, with the mass arising from mesentery involving the bowel, measuring 11.5x9.5x6 cm. The second specimen was a partial cystectomy specimen, with the abdominal wall mass infiltrating the bladder anteroposteriorly, measuring 11x10x8 cm. Microscopic examination revealed extensive areas of inflammation with actinomycotic organisms exhibiting the Splendore-Hoeppli phenomenon, along with numerous multinucleated giant cells and acute on chronic inflammatory infiltrate. Surrounding areas showed dense collagen bundles. The prognosis after complete surgical resection is good, along with the administration of broad spectrum intravenous antibiotics.

Cutaneous Atypical Fibroxanthoma With Osteoclast-Like Giant Cell: A Rare but Diagnostic Pitfall.

Atypical fibroxanthoma (AFX) is a dermal-based, low-grade neoplasm with no specific lineage of differentiation. The occurrence of AFX with osteoclast-like giant cells is exceptionally rare. Less than 20 cases have been reported in the literature. A 77-year-old man with a medical history of multiple basal and squamous cell carcinomas of the skin, presented with a progressively growing erythematous nodule on the sun-damaged right central parietal scalp. A shave biopsy showed a dermal spindle cell proliferation accompanied by numerous osteoclast-like multinucleated giant cells and predominant atypical mitotic figures. The immunohistochemical staining showed a diffuse positive staining for CD68 and SMA, patchy staining for CD10, and negative staining for SOX-10, pan-cytokeratin, CK5/6, S100, CD34, and desmin. The tumor was completely excised with negative margins. A subsequent follow-up over a period of 13 months showed no recurrence. Distinguishing AFX with osteoclast-like giant cells from both malignant and benign skin lesions with osteoclast-like giant cells is crucial. Although AFX tumors display worrisome malignant histologic features, most cases have a favorable prognosis with a local recurrence rate below 5% and exceedingly rare metastasis.

An Unusual Entity: Giant Cell Tumour of Soft Tissue in the Nasal Cavity

Giant cell tumour of soft tissue (GCT-ST) are rare soft tissue tumours, with the first case reported in the 1970s. Involvement of the head and neck region, particularly in the nasal cavity is extremely uncommon. GCT-ST are considered the bone counterpart given the striking histological and immunohistochemical resemblance. Despite that, GCT-ST and GCT of bones are genetically distinct. Microscopically, GCT-ST exhibit numerous osteoclast-type multinucleated giant cells within a background of mononuclear stromal cells. They are locally aggressive and can potentially recur. It is important to distinguish GCT-ST from giant cell reparative granuloma (GCRG) as they both share similar clinical and morphological characteristics, however, they have different treatment modalities. We report a case of GCT-ST occurring in the nasal cavity, an unusual site of presentation.

ODP095 HYPERCALCEMIA FROM SILICONE BUTTOCK INJECTION INDUCED GRANULOMA.

Abstract Granulomatous disease is an infrequent cause of non-PTH mediated hypercalcemia. Hypercalcemia from granulomas due to cosmetic silicone injections are not commonly recognized. A 57 year old woman with rheumatoid arthritis was incidentally discovered to have hypercalcemia. Laboratory studies reported elevated calcium 11.0 mg/dL (RR: 8.6-10.2), suppressed PTH 12.7 pg/mL (RR: 15-65), low 25 OH - vitamin D 13ng/mL (RR 30-100), normal 1-25 dihydroxyvitamin D 78 pg/mL (RR 18-72), SPEP Kappa/Lambda Ratio 2.12 (RR 0.26-1.65), but no M spike, normal UPEP, an eleavted 24hr Urine Calcium 451.5 (RR: 100-300). PTHrp 20 pg/mL (RR: 14-27). Quantiferon test negative. ACE level 76 (RR: 9-67). X-ray of the chest showed no hilar adenopathy. Patient had a non-FDA approved silicone buttocks injection 20 years earlier. Patient's main complaint consisted of buttocks pain and tenderness as well as discomfort upon sitting. PET/CT showed "heterogeneous density in the bilateral gluteal region from silicon implants". "The thickness of the implant is about 6 cm in the soft tissues metabolically active diffusely with a maximum SUV of 2.84. This is consistent with silicone granulomas". A biopsy showed "Clear annular histiocytic inclusions consistent with macrophage ingestion of foreign substance. Abundant surrounding inflammatory reaction with numerous multi-nucleated giant cells consistent with granulomatous response." Plastic surgery was consulted and were unable to surgically remove the silicone. Patient was offered medical treatment for hypercalcemia, but deferred due to concern for side effects. Cosmetic enhancement is a growing industry and cosmetic fillers including silicone have been used throughout the 20th century. Previously considered inert silicon may have inflammatory reactions attributed to denatured silicon, incorrect injection and large injection volumes. Silicon induced granulomas frequency ranges from 0.01–5% and may appear 2–25 years after the injections. Histologic diagnosis is critical and is similar to those found in sarcoidosis. Treatment of silicon induced hypercalcemia is similar to treatment of other granulomatous disease utilizing glucocorticoids. Bisphosphonates are considered in cases resistant to glucocorticoid treatment. Surgical treatment is rarely considered. The patient was receiving abatacept therapy (750 mg IV monthly) for rheumatoid arthritis. Abatacept is a monocolonal antibody which binds to CD80 and CD86 on antigen presenting cells (APCs) blocking T-cell activity. Since starting Abatacept treatment the patient's hypercalcemia has improved. There are currently ongoing clinical trials of abatacept to treat sarcoidosis and granulomatosis with polyangiitis that may shed light on the efficacy of this drug to treat granulomatous disease. Due to the rise in the use of cosmetic fillers, complications are also likely to be on the rise. Soft tissue fillers injections have increased in the United States and it is likely that complications from these non-FDA approved treatments will increase. It is important that endocrinologists are familiar with the physiology and treatments. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

TRABECULAR JUVENILE OSSIFYING FIBROMA OF THE MANDIBLE: A CASE REPORT

This report aims to describe an extensive fibro-osseous lesion in a 24-year-old woman with an enlargement in the left mandible. Computed tomography showed a large multiloculated hypodense area between teeth 36 and 42, with thinning and expansion of cortical bone. Under the clinical hypothesis of central giant cell lesion, preoperative exams and incisional biopsy were performed, which was conclusive for a fibro-osseous lesion. The lesion was resected, and the mandibular reconstruction was performed with a titanium plate. Histopathologic analysis of the excised specimen showed fusocellular proliferation with trabecular deposition of immature bone and osteoid, among numerous multinucleated giant cells. Additionally, cavities filled with red blood cells and supported by cellularized fibrous connective tissue were observed. The anatomopathologic conclusion of the surgical specimen was a benign fibro-osseous lesion, leading to the diagnosis of trabecular juvenile ossifying fibroma associated with aneurysmal bone cyst. The patient is in follow-up. This report aims to describe an extensive fibro-osseous lesion in a 24-year-old woman with an enlargement in the left mandible. Computed tomography showed a large multiloculated hypodense area between teeth 36 and 42, with thinning and expansion of cortical bone. Under the clinical hypothesis of central giant cell lesion, preoperative exams and incisional biopsy were performed, which was conclusive for a fibro-osseous lesion. The lesion was resected, and the mandibular reconstruction was performed with a titanium plate. Histopathologic analysis of the excised specimen showed fusocellular proliferation with trabecular deposition of immature bone and osteoid, among numerous multinucleated giant cells. Additionally, cavities filled with red blood cells and supported by cellularized fibrous connective tissue were observed. The anatomopathologic conclusion of the surgical specimen was a benign fibro-osseous lesion, leading to the diagnosis of trabecular juvenile ossifying fibroma associated with aneurysmal bone cyst. The patient is in follow-up.

EXTENSIVE PERIPHERAL GIANT CELLS LESION: CASE REPORT

Peripheral giant cells lesion is a reactive injury caused by local irritation or trauma. Most injuries are small, although extensive injuries are seen occasionally. A 33-year-old woman sought care because of a volume increase in the right jaw that caused discomfort and facial asymmetry. The intraoral physical examination revealed an 8 cm nodular lesion in the inserted lower right gingiva with a purplish color, smooth surface, and hardened consistency. Computed tomography scan showed bone rarefaction in the region of teeth 45 and 47. An incisional biopsy was performed, and the histopathologic examination revealed a proliferation of cells, sometimes spindle-shaped, sometimes ovoid, permeated by numerous multinucleated giant cells. After diagnosis, a peripheral giant cell lesion was excised with safety margins and extraction of the teeth associated with the lesion was performed. The patient is being followed up, with no signs of recurrence of the lesion.

Central giant cell granuloma: A case report with review of literature

Central Giant Cell Granuloma is a rare, benign, proliferative non-neoplastic lesion of the jaw. This lesion constitutes about 10% of all the lesions of the jawbones. The aim of this article is to review a case report of central giant cell granuloma of the mandible in 44 year-old female patient with the chief complaint of pain and swelling in the left side of the mandible since1.5 months. The diagnosis was made using histopathological examination which revealed numerous multinucleated giant cells distributed in a highly cellular stroma.

IDH-wild type glioblastomas featuring at least 30% giant cells are characterized by frequent RB1 and NF1 alterations and hypermutation

Giant cell glioblastoma (GC-GBM) is a rare variant of IDH-wt GBM histologically characterized by the presence of numerous multinucleated giant cells and molecularly considered a hybrid between IDH-wt and IDH-mutant GBM. The lack of an objective definition, specifying the percentage of giant cells required for this diagnosis, may account for the absence of a definite molecular profile of this variant. This study aimed to clarify the molecular landscape of GC-GBM, exploring the mutations and copy number variations of 458 cancer-related genes, tumor mutational burden (TMB), and microsatellite instability (MSI) in 39 GBMs dichotomized into having 30–49% (15 cases) or ≥ 50% (24 cases) GCs. The type and prevalence of the genetic alterations in this series was not associated with the GCs content (< 50% or ≥ 50%). Most cases (82% and 51.2%) had impairment in TP53/MDM2 and PTEN/PI3K pathways, but a high proportion also featured TERT promoter mutations (61.5%) and RB1 (25.6%) or NF1 (25.6%) alterations. EGFR amplification was detected in 18% cases in association with a shorter overall survival (P = 0.004). Sixteen (41%) cases had a TMB > 10 mut/Mb, including two (5%) that harbored MSI and one with a POLE mutation. The frequency of RB1 and NF1 alterations and TMB counts were significantly higher compared to 567 IDH wild type (P < 0.0001; P = 0.0003; P < 0.0001) and 26 IDH-mutant (P < 0.0001; P = 0.0227; P < 0.0001) GBMs in the TCGA PanCancer Atlas cohort. These findings demonstrate that the molecular landscape of GBMs with at least 30% giant cells is dominated by the impairment of TP53/MDM2 and PTEN/PI3K pathways, and additionally characterized by frequent RB1 alterations and hypermutation and by EGFR amplification in more aggressive cases. The high frequency of hypermutated cases suggests that GC-GBMs might be candidates for immune check-point inhibitors clinical trials.

CUTANEOUS AND PULMONARY BLASTOMYCOSIS INFECTION: A CASE REPORT

<h3>Introduction</h3> Blastomycosis is a chronic granulomatous disease caused by <i>Blastomyces dermatitidis</i>. More frequently, it presents as a respiratory disease. However, extrapulmonary disease occurs in 25% to 30% of patients after hematogenous dissemination from the lungs. The most common site is the skin; bone, the genitourinary system, and the central nervous system can also be affected. <h3>Case Report</h3> A 34-year-old female patient from Oaxaca, México, presented with an asymptomatic ulcer, verrucous and eroded plaques, and scab areas of unknown evolution on the low and medium third of the face and the nose. The histopathologic staining with hematoxylin and eosin revealed a squamous epithelium with a pseudoepitheliomatous hyperplasia and granulomatous inflammation, containing numerous Langhans multinucleated giant cells and spherical microorganisms of approximately 12 µm characterized by a double-contoured yeast and thick birefringent wall. Periodic acid-Schiff and Grocott's methenamine silver special staining showed positive results for fungal organisms. The thoracic imaging revealed lung involvement. The histopathologic final diagnosis was blastomycosis. <h3>Discussion</h3> In Mexico from 1898 to 2017, only 6 cases were reported. Blastomycosis infections can clinically be easily mistaken for malignant neoplasms or other cutaneous infections more prevalent in Mexico, such as leishmaniasis, coccidioidomycosis, leprosy, or adiaspiromycosis. <h3>Conclusions</h3> The treatment of choice for all forms of the disease includes itraconazole 600 mg, oral 3 days, followed by 200 to 400 mg every day for 6 to 12 months. Spontaneous remissions have been reported in patients with a mild form of blastomycosis. Our patient had 6 months of follow-up with remission of the lesion

Internal Resorption of Multiple Posterior Teeth in a Patient Diagnosed with Hyperparathyroidism: A Case Report

This case reports a 46-year-old man with end-stage renal disease and internal resorption (IR) affecting multiple posterior teeth. IR involves odontoclast’s removal of dentin within pulp chambers and root canal space. Typically, asymptomatic until detected on radiographs, IR is relatively rare, so the etiology and pathogenesis are poorly understood. Patients’ radiographs with cone-beam computed tomography revealed extensive IR in multiple premolars and all remaining molar teeth. Blood tests and hormonal assay measured elevated phosphorus and parathyroid hormone levels consistent with secondary hyperparathyroidism. Histopathology showed highly vascularized and inflamed pulp tissues with numerous odontoclast-like multinucleated giant cells along dentinal walls and in resorption lacunae. Immunohistochemistry showed that multinucleated giant cells and adjacent mononuclear precursors stained strongly for tartrate-resistant acid phosphatase like osteoclasts. Extraction of crown-root fractures and endodontic treatment with crown restorations for all IR teeth effectively arrested disease progression at 9 months’ follow-up. Elevated parathyroid hormone from secondary hyperparathyroidism that promotes bone osteoclast activity may also stimulate odontoclasts causing IR.

Intestinal Mycobacterium avium Infection in Pet Dwarf Rabbits (Oryctolagus cuniculus)

Mycobacteriosis has been rarely described in pet rabbits (Oryctolagus cuniculus). Here we present two cases of intestinal mycobacteriosis from north-eastern Germany. The first adult rabbit was euthanized due to severe cardiovascular failure, hypothermia and chronic weight loss. Necropsy revealed cachexia and a focal, fibrinonecrotic lesion in the caecum. Histologically, severe granulomatous inflammation, with numerous multinucleated giant cells and abundant acid-fast bacilli, was detected under the fibrinonecrotic material in the abdominal wall adjacent to the caecal lesion, caecal lymph nodes, spleen, liver and lungs. Microbiological culture detected Mycobacterium avium subspecies hominissuis, Escherichia coli, Clostridium disporicum and Bacteroides ovatus. A retrospective assessment of 2,013 other pet rabbit necropsies, performed between 1995 and 2019, revealed one additional case of intestinal mycobacteriosis. This animal had been euthanized due to persistent hindlimb lameness and necropsy revealed comminuted fractures of the pelvic bones and multiple large liquefied abscess-like lesions in the caecal and colonic walls. Histology revealed granulomatous inflammation with acid-fast bacilli. Polymerase chain reaction on formalin-fixed, paraffin-embedded tissue identified the presence of M. avium spp. In contrast to European wild rabbits (Oryctolagus cuniculus) from Scotland, these findings indicate that intestinal mycobacteriosis is rare in pet rabbits from north-eastern Germany. Zoonotic potential should be considered due to the close contact between pets and their owners and the chronic course of the disease with an initial lack of clinical signs.

NON-NEOPLASIC TUMOROUS PROLIFERATION IN A 9-YEAR-OLD CHILD AND 2 YEARS’ FOLLOW-UP: A CASE REPORT

Peripheral giant cell granuloma (PGCG) is a non-neoplastic tumorous proliferation that occurs in all age groups. The frequency in children up to 10 years old is around 9%. The objective of this study was to report a purplish nodular lesion of 4 mm × 4 mm × 5 mm, painless, pediculated, in a 9-year-old child who attended the dental office reporting discomfort and increased volume in the lower jaw left gingival region. The patient had good oral hygiene and no biofilm. The diagnostic hypothesis was pyogenic granuloma, PGCG, and gingival hyperplasia. An excisional biopsy was performed, and histopathologic examination revealed a proliferative lesion composed of oval, fusiform, and numerous multinucleated giant cells. The diagnosis was PGCG. The patient was followed up for 2 years, and there was no recurrence of the lesion. Peripheral giant cell granuloma (PGCG) is a non-neoplastic tumorous proliferation that occurs in all age groups. The frequency in children up to 10 years old is around 9%. The objective of this study was to report a purplish nodular lesion of 4 mm × 4 mm × 5 mm, painless, pediculated, in a 9-year-old child who attended the dental office reporting discomfort and increased volume in the lower jaw left gingival region. The patient had good oral hygiene and no biofilm. The diagnostic hypothesis was pyogenic granuloma, PGCG, and gingival hyperplasia. An excisional biopsy was performed, and histopathologic examination revealed a proliferative lesion composed of oval, fusiform, and numerous multinucleated giant cells. The diagnosis was PGCG. The patient was followed up for 2 years, and there was no recurrence of the lesion.

The essential role of intraflagellar transport protein IFT81 in male mice spermiogenesis and fertility.

Intraflagellar transport (IFT) is an evolutionarily conserved mechanism that is indispensable for the formation and maintenance of cilia and flagella; however, the implications and functions of IFT81 remain unknown. In this study, we disrupted IFT81 expression in male germ cells starting from the spermatocyte stage. As a result, homozygous mutant males were completely infertile and displayed abnormal sperm parameters. In addition to oligozoospermia, spermatozoa presented dysmorphic and nonfunctional flagella. Histological examination of testes from homozygous mutant mice revealed abnormal spermiogenesis associated with sloughing of germ cells and the presence of numerous multinucleated giant germ cells (symblasts) in the lumen of seminiferous tubules and epididymis. Moreover, only few elongated spermatids and spermatozoa were seen in analyzed cross sections. Transmission electron microscopy showed a complete disorganization of the axoneme and para-axonemal structures such as the mitochondrial sheath, fibrous sheath, and outer dense fibers. In addition, numerous vesicles that contain unassembled microtubules were observed within developing spermatids. Acrosome structure analysis showed normal appearance, thus excluding a crucial role of IFT81 in acrosome biogenesis. These observations showed that IFT81 is an important member of the IFT process during spermatogenesis and that its absence is associated with abnormal flagellum formation leading to male infertility. The expression levels of several IFT components in testes, including IFT20, IFT25, IFT27, IFT57, IFT74, and IFT88, but not IFT140, were significantly reduced in homozygous mutant mice. Overall, our study demonstrates that IFT81 plays an essential role during spermatogenesis by modulating the assembly and elongation of the sperm flagella.

SAT-434 RENAL TUBERCULOSIS: A CASE REPORT FROM UNIVERSITY TEACHING HOSPITAL OF KIGALI (CHUK)

Urogenital tuberculosis constitutes a current public health problem especially in endemic areas. Renal tuberculosis is among rare form of extra pulmonary tuberculosis (EPTB) and the clinical presentation of this form of the disease may be misleading. The pseudotumoral type of renal tuberculosis is extremely uncommon and differential diagnosis may include even malignant tumors like renal cell carcinoma. Diagnosis require renal biopsy which is a specialized procedure. Prompt treatment of the underlying TB focus can prevent progression to end-stage renal disease. Treatment of renal TB includes surgery followed by anti- tuberculosis treatment. We report a case of renal TB, presented as kidney tumor. On histology TB was suspected and confirmed by Auramine stain at University Teaching Hospital of Kigali (CHUK). We report a 49 years old male, consulted with left kidney mass who underwent left nephrectomy. Histological findings were suggestive of renal tuberculosis, confirmed by auramaine stain. This is a 49 years old male presented with left kidney mass invading vena cava, left nephrectomy was performed and vena cava thrombus was sampled. The nephrectomy specimen was weighing 1792g and measuring (17x14x11) cm. The kidney outer surface was multinodulated, cystic and firm with intact capsule. The renal parenchyma was almost entirely involved by multiple small cysts like lesions, firm and grey. The hilum was also involved by cystic lesions. The so called vena cava thrombus were two fragments of (2x1.7x1) cm, firm and grey. Histology showed extensive caseous necrosis creating pseudocyst cavities, numerous Langhans-type multinucleated giant cells. Fragments of tissue labeled ‘thrombus from vena cava’ showed granulomatous inflammation with frequent Langhans-type multinucleated giant cells. Auramine stain was positive for acid fast bacilli (AFB). Figure legend Photomicrographs of Renal tuberculosis: A: Pseudoyst (H&E, X40). B: Necrosis (H&E, X100). C: Multinucleated giant cells (H&E, X100). D: Chronic inflammatory cells (H&E, X100). Dour text here Cour text here Bour text here Aour text here Renal tuberculosis is very rare and pseudotumoral presentation of urogenital tuberculosis is extremely rare. Renal tuberculosis should be suspected when atypical renal masses are seen in patients from tuberculosis endemic areas.

Near haploidization is a genomic hallmark which defines a molecular subgroup of giant cell glioblastoma.

BackgroundGiant cell glioblastoma (gcGBM) is a rare histologic subtype of glioblastoma characterized by numerous bizarre multinucleate giant cells and increased reticulin deposition. Compared with conventional isocitrate dehydrogenase (IDH)-wildtype glioblastomas, gcGBMs typically occur in younger patients and are generally associated with an improved prognosis. Although prior studies of gcGBMs have shown enrichment of genetic events, such as TP53 alterations, no defining aberrations have been identified. The aim of this study was to evaluate the genomic profile of gcGBMs to facilitate more accurate diagnosis and prognostication for this entity.MethodsThrough a multi-institutional collaborative effort, we characterized 10 gcGBMs by chromosome studies, single nucleotide polymorphism microarray analysis, and targeted next-generation sequencing. These tumors were subsequently compared to the genomic and epigenomic profile of glioblastomas described in The Cancer Genome Atlas (TCGA) dataset.ResultsOur analysis identified a specific pattern of genome-wide massive loss of heterozygosity (LOH) driven by near haploidization in a subset of glioblastomas with giant cell histology. We compared the genomic signature of these tumors against that of all glioblastomas in the TCGA dataset (n = 367) and confirmed that our cohort of gcGBMs demonstrated a significantly different genomic profile. Integrated genomic and histologic review of the TCGA cohort identified 3 additional gcGBMs with a near haploid genomic profile.ConclusionsMassive LOH driven by haploidization represents a defining molecular hallmark of a subtype of gcGBM. This unusual mechanism of tumorigenesis provides a diagnostic genomic hallmark to evaluate in future cases, may explain reported differences in survival, and suggests new therapeutic vulnerabilities.

AGGRESSIVE BEHAVIOR AND PUZZLING MANAGEMENT OF MULTIPLE BROWN TUMORS RELATED TO PRIMARY HYPERPARATHYROIDISM

A 16-year-old female patient complaining of a maxillary mass with 6-month duration, causing asymmetry, spontaneous bleeding, and feeding difficulty presented at intraoral examination a large erythematous and ulcerated pedunculated mass arising from the expanded maxilla. The anterior mandible was also enlarged but covered by normal oral mucosa. Anamnesis included primary hyperparathyroidism with parathyroidectomy in the past 6 months. Panoramic x-ray showed a radiolucent and mixed area in the maxilla and anterior mandible associated with tooth displacement and resorption. Incisional biopsy of the pedunculated mass in maxilla was performed to improve the patient´s quality of life, and histologic examination revealed a proliferation of ovoid to fusiform cells accompanied by numerous multinucleated giant cells, confirming the hypothesis of central giant cell granuloma, precisely, brown tumor. Brown tumors rarely involve maxilla and can behave aggressively, and the excision of parathyroid lesions results in controlled serum levels leading to a gradual decrease in the maxillary tumors.

Hybrid Central Odontogenic Fibroma with Central Giant Cell Granuloma Like Lesion ; A Case Report and Review of the Literature

The combination of central odontogenic fibroma and central giant cell granuloma is extremely rare and has been reported in only 46 cases worldwide in previous articles. The lesion is called a hybrid central odontogenic fibroma with central giant cell granuloma like lesion (HCOF-CGCG) due to a histopathological characteristics of multinucleated giant cell and odontogenic epithelium in fibro-cellular background. We report a case of HCOF-CGCG in a 27-year old Thai male patient who was identified as the first case in Thailand. Radiographic examination showed a well-defined radiolucency lesion at posterior mandibular area. Enucleation and curettage were done and microscopic study revealed a fibro-cellular proliferating tissue containing numerous strands, cord of odontogenic epithelium, and numerous multinucleated giant cells. This report also included a literature review of the previous 45 cases.

WITHDRAWN: An exceptional case of giant cell interstitial pneumonia with multi-organ involvement and review of the literature

Abstract Giant cell interstitial pneumonia (GIP) is an exceedingly rare lung disease, usually due to occupational exposure to hard-metal compounds (tungsten, carbide, cobalt). Diagnosis of GIP is mainly based on the presence of multinucleated giant cell (MNGC) in alveolar spaces by histologic examination. Here, we present a case of GIP with multi-organ involvement. A 63-year-old man was diagnosed with tuberculosis firstly, but conventional treatment did not relieve the symptoms. In addition, the patient had a contact history with copper for more than 40 years, and the lesions in this patient invaded into lymph node of hilus pulmonis and spread from the primary lung lesion through the blood stream to other organs. And in previous reported cases, the lesions were restricted to the lungs. Finally, numerous prominent multi-nucleated giant cells were noticed by histological examination, the patient eventually diagnosed with GIP. We believe this special case of GIP would provide new perspectives and knowledge of GIP because of the multiorgan involvement.