Giant Cell Research Articles

Inflammation of the temporalis muscle and adjacent nerve tissue in giant cell arteritis: expanding the spectrum of inflammatory lesions.

To investigate the histopathological features of the temporalis muscle (TM) and adjacent nerve tissue in active cranial giant cell arteritis (C-GCA). Temporal artery biopsy (TAB) specimens containing fragments of the TM from patients with active C-GCA fulfilling the 2022 ACR/EULAR classification criteria (n = 11) were assessed by conventional histology and immunohistochemistry in comparison with non-GCA controls (n = 3). Clinical, laboratory and imaging features based on patient charts at time of biopsy were retrospectively recorded. The majority of the studied TAB specimens showed inflammation of the TM (10/11) and adjacent nerve fascicles (7/11) that was characterized by prominent endomysial lymphomonocytic infiltrates, whereas controls showed no inflammatory lesions and no disruption of the local architecture. Association of active C-GCA with sarcolemmal MHC class I (8/8) and MHC class II (6/11) upregulation suggests primary inflammation of the TM in a subset of patients. αB-Crystallin positivity (10/11) highlights areas of pre-necrotic myofibres within the TM. The presence of endomysial fibrosis, signs of atrophy and variations of muscle fibre size suggest a rather longstanding and potentially subclinical process of myoinflammation. Our results expand the spectrum of inflammatory lesions known to be associated with active C-GCA. Specifically, inflammatory infiltration of the TM and adjacent nerve structures could contribute to localized symptoms of the temporomandibular region and may be included in future concepts of pathophysiology.

Polymyalgia rheumatica and giant cell arteritis: diagnosis and management.

There have been advances in the diagnosis and treatment of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). Themes in PMR and GCA include classification criteria, ultrasound imaging of temporal and axillary arteries replacing biopsies for diagnosis of GCA, faster diagnosis and treatment with rapid access clinics for suspected GCA, and expanding treatment options with the goal of rapid suppression of inflammation and sparing steroids. Treatment is aimed at suppressing inflammation quickly in both GCA and PMR. Randomized trials have demonstrated success in reducing glucocorticoids when adding advanced therapies such as interleukin 6 (IL6) inhibitors. Other treatments including Janus kinase (JAK) inhibitors (especially a phase 3 trial of upadacitinib at 15 mg daily and secukinumab (an IL17 inhibitor) are being tested. Some uncontrolled GCA protocols are limiting glucocorticoids to initial IV pulse therapy only or rapid tapering of oral glucocorticoids with upfront treatment with tocilizumab. There is uncertainty of who should have an advanced therapy and how long to use it for and what order to consider advanced therapies when treatment fails. In PMR, studies are performed when patients cannot taper glucocorticoids effectively, whereas in GCA, advanced therapies are started with disease onset or with recurrent GCA.

Rectal Schistosomiasis and Adenocarcinoma

Abstract Introduction/Objective Schistosoma infestation has been implicated by the International Agency for Research on Cancer as an etiology for several cancers such as colon, liver, and bladder. S. japonicum is classified as a probable carcinogen in humans (class 2B). These trematodes may cause chronic infection in the affected organ leading to the trend of “inflammation-adenoma-carcinoma”. There is rising evidence that infection with Schistosoma japonicum is correlated with the liver and colorectal carcinoma in endemic Asian countries. We herein present a case of rectal adenocarcinoma associated with Schistosoma as a possible causal factor. Methods/Case Report An 88-year-old-woman from China, currently living in United States for past six years, presented with rectal bleeding. Colonoscopy showed evidence of a rectosigmoid mass 2.2 x 1.0 x 0.3 cm. She underwent trans-anal excision of the tumor. Microscopic examination showed moderately differentiated adenocarcinoma with tumor invading the muscularis propria (pT2). There were numerous oval / round calcified eggs (30 - 46 microns) with minute subterminal or no spine morphologically consistent with Schistosoma japonicum associated with granulomatous and foreign body giant cell reaction, fibrosis, and tissue eosinophilia. She was treated with Praziquantel and is currently undergoing endoscopic surveillance for recurrence. Results (if a Case Study enter NA) N/A Conclusion Patients with chronic Schistosoma japonicum infection have 3 times increased risk of developing colorectal cancer than those with no previous exposure to schistosomal infection. We believe that chronic S. japonicum infection is the likely etiology of rectal cancer in our patient. Physicians should be aware of such associations, especially for immigrants from endemic areas, to facilitate accurate diagnosis and management.

SWI/SNF Altered Gastric Carcinoma with Squamous Differentiation in a young patient with aggressive clinical course

Abstract Introduction/Objective Inactivation of SMARCA4 (BRG1) protein subunit of the SWI/SNF complex has been reported in various malignancies affecting multiple organs, often associated with a poor prognosis. We report a rare case of gastric SMARCA4-deficient carcinoma in a young patient, showing squamous differentiation and an aggressive clinical course. Methods/Case Report A 28-year-old male presented with epigastric pain and 15-lb weight loss over 3 months. Evaluation revealed a gastric cardia mass, liver lesion, and gastro-hepatic lymph-node. Biopsy of gastric and liver lesions revealed a poorly differentiated carcinoma. Following a course of neoadjuvant chemotherapy, and immunotherapy, total gastrectomy and distal esophagectomy were performed. Grossly, there was a 13 cm mass involving his gastric cardia and body, extending into his distal esophagus. On microscopy, the transmural tumor was arranged as solid sheets, syncytial aggregates, and nests with a focal pseudoglandular pattern in a lymphoplasmacytic rich stroma. Scattered bizarre giant cells were noted, along with brisk mitosis and focal necrosis. Focally, the tumor showed abundant glassy eosinophilic cytoplasm reminiscent of squamoid cells. Two of forty-two lymph nodes were positive for metastatic carcinoma. IHC showed focal positivity for AE1/3, OSCAR, CAM5.2, along with areas staining for p40 and p63; negative for CK7, CK20, CDX2, SATB2, synaptophysin, INSM1, SOX-10, LCA ERG, and SALL4. Nuclear expression for mismatch repair proteins was retained. HER2 was negative (score 0), and PDL-1 CPS score was 40. EBER in-situ hybridization was negative, with retention of INI-1. There was complete loss of SMARCA4 by IHC and next generation sequencing confirmed frameshift alteration of SMARCA4. Final pathologic diagnosis was SMARCA4 deficient poorly differentiated carcinoma with squamous differentiation (ypT3pN1). The patient received adjuvant therapy with Paclitaxel and Ramucirumab. However, his disease progressed, and he succumbed to his illness five months after surgery. Results (if a Case Study enter NA) N/A Conclusion Our case illustrates that SMARCA4 deficient gastric carcinomas can have heterogeneous morphology, with an aggressive clinical course in young patients. This highlights the importance of early diagnosis and consideration of alternative therapeutic approaches, as these tumors typically do not respond to standard treatments.

Multisystem ALK-Positive Histiocytosis With DCTN1::ALKFusion in an Adult, Responsive to Alectinib: Case Report and Literature Review.

Anaplastic lymphoma kinase (ALK)-positive histiocytosis has emerged as a clinically relevant diagnosis featuring a wide span of clinical presentations, which are unified by the presence of ALK-positive histiocytes on histopathology and molecular drivers involving the ALK kinase gene. This report presents an adult case of multisystem ALK-positive histiocytosis with xanthogranuloma-like features on histopathology that was responsive to ALK inhibition, and includes a review of ALK-positive histiocytoses with cutaneous involvement reported in the literature. A 56-year-old male developed a widespread eruption of red-brown papules on the face, trunk, and upper extremities. Histopathological evaluation revealed a well-circumscribed, nodular dermal infiltrate of epithelioid histiocytes with Touton giant cells, rare bizarre multinucleated cells, and focal emperipolesis. The lesional cells were positive for CD68 and ALK1 immunohistochemical stains, and negative for CD1a. Next-generation sequencing identified a DCTN1::ALK fusion. On imaging, he was found to have bone, lung, soft tissue, and salivary gland involvement. ALK inhibition was initiated with alectinib, resulting in rapid improvement of cutaneous lesions and eventual complete resolution of abnormal imaging findings, which was sustained at 24 months of follow-up. This case adds to the spectrum of ALK-positive histiocytoses and further demonstrates the positive response with targeted therapy.

Surgical Management of 2,350 Pediatric Dermoid Cysts.

We examined operative and pathologic findings of a large series of dermoid cysts at a high-volume pediatric hospital over 23 years. A retrospective review was performed of all dermoid cysts excised from 2000 to 2023 at the Children's Hospital of Philadelphia. Lesions were classified by location. Depth was stratified into Type 1, superficial; Type 2, subperiosteal or containing a stalk to a cranial suture; Type 3, intraosseous or intracartilaginous; Type 4, intracranial extradural; and Type 5, intracranial intradural. Of 2,350 lesions, 2,237 (95.2%) were in the head and neck. Most common locations were lateral brow and orbit, 892 (38%); anterior neck, 303 (12.9%); and frontal, 253 (10.8%). Among the series, 67.9% were Type 1, 10.1% were Type 2, 16.5% were Type 3, 2.3% were Type 4, and 3.2% were Type 5. Older age at surgery correlated with depth among locations demonstrating intracranial extension (r=.061, p=.016). Anterior fontanelle (59.1%), nasal (16.2%), occipital (5.6%), and temporal (4.7%) lesions had the highest intracranial extension rates. Temporal (49.4%), frontal (32.8%), nasal (29.9%), and occipital (22.2%) lesions had higher rates of osseous/cartilaginous involvement. On histopathologic examination, 403 (17.1%) were ruptured. Ruptured lesions were associated with giant cell reaction (46.4 versus 5.7%, p<.001). Anterior fontanelle, nasal, occipital, and temporal lesions are at higher risk of intracranial extension and may require preoperative imaging. Frontal and parietal lesions have a lower risk of intracranial involvement. Lateral brow and orbit, periauricular, and anterior neck lesions demonstrate a higher rate of osseous involvement without intracranial tracking.

Serial assessment of ultrasound sensitivity and scores in patients with giant cell arteritis before and 3 and 10 days after treatment.

To evaluate sensitivity and scores of vascular ultrasound (US) before and after initiating glucocorticoid (GC) treatment in patients with new-onset giant cell arteritis (GCA). Treatment-naïve patients with GCA were prospectively included. 18F-FDG PET/CT, US and temporal artery (TA) biopsy were performed in all patients. US was repeated 3 and 10 days after GC commencement. Intima-media thickness and presence of halo signs were assessed. Sonographers were unblinded to clinical data. The OMERACT GCA Ultrasonography score (OGUS) and halo count (HC) were calculated. Forty-eight patients were included. Before GC exposure, US sensitivity was 94% (95% CI: 83-99), 73% (95% CI: 58-85) and 71% (95% CI: 56-83) when assessing all vessels, TAs, and large vessels (LVs), respectively. At day 3 and 10, overall US sensitivity was 92% (95% CI: 78-98, p= 0.16) and 83% (95% CI: 69-92, p= 0.10), respectively. At day 10, TA-US and LV-US sensitivity was 53% (95% CI: 38-68, p< 0.01), and 60% (95% CI: 44-74, p= 0.13), respectively. Median OGUS decreased from 1.06 (IQR 0.83-1.24)-0.95 (IQR 0.78-1.14, p< 0.01), and 0.90 (IQR 0.73-1.01, p< 0.001) after 3 and 10 days, respectively. Median HC decreased from 3 (IQR 2-5)-2 (IQR 1-4, p< 0.01) after 10 days. The vasculitic US findings expressed by OGUS diminish after 3 days of GC treatment. TA-US sensitivity decreased after 10 days, whereas LV-US was less likely to change, highlighting the importance of LV-assessment. Consistent with the EULAR recommendations, these findings encourage prompt US assessment, preferably within 3 days, to ensure an accurate diagnosis.

An overview of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in giant cell arteritis.

PET/CT is an imaging modality that is increasingly being used to diagnose large-vessel vasculitis. In the case of giant cell arteritis, it was first used to demonstrate inflammation of the walls of large arterial trunks such as the aorta and its main branches, showing that aortic involvement is common in this vasculitis and associated with the occurrence of aortic complications such as aneurysms. More recently, with the advent of digital PET/CT, study of the cranial arteries (i.e., temporal, occipital, maxillary and vertebral arteries) has become possible, further increasing the diagnostic interest of this examination for the diagnosis of GCA. Despite these advantages, there are still limitations and questions regarding the use of PET/CT for the diagnosis and especially the follow-up of GCA. The aim of this review is to take stock of currently available data on the use of PET/CT for GCA diagnosis and follow-up.

Surgical Treatment of Primary Spinal Tumors

Primary spinal tumors appear to be much less common than metastatic lesions, but their surgical treatment comprises a complex and multifaceted task. Numerous factors influence indications and timing of surgical intervention, including neurological status of the patient, histological characteristics of the tumor, its localization, stability of the spinal column, and comorbidities. Significant spinal cord compression, rapid progression of neurologic deficits, or pronounced instability of the spinal column may require urgent surgical intervention. When the spinal canal is not affected, treatment should start with a biopsy to accurately determine the histology of the tumor. Some tumor types, such as giant cell tumors, osteoblastomas, chordomas, and chondrosarcomas, require complete removal of the tumor. However, performing a wide resection in a single block is often found difficult due to compression of vascular and nerve structures. Current approaches to surgical management of primary spinal tumors involve minimally invasive techniques that significantly improve postoperative recovery and reduce the risk of complications. These techniques were originally used to treat degenerative spinal diseases and trauma; however, they have also demonstrated their effectiveness in tumor surgery. Adapting surgical strategy based on histology and tumor location, as well as integrating minimally invasive techniques, can improve patient survival and quality of life. The present paper describes the latest advances in the surgical treatment of primary spinal tumors, discusses current techniques and strategies, and prospects for further research in this area.

Deep Fungal Infections of Skin and Role of Histopathology in Diagnosis

Abstract Introduction: Deep mycoses acquired by penetrating trauma to the skin can have varied and sometimes atypical morphological presentations resulting in diagnostic dilemmas and delay in treatment onset. Histopathology can be a useful tool in not only diagnosing but also differentiating various deep mycoses. Aims and Objectives: To observe various morphological presentations and histopathological features of deep fungal infections. Materials and Methods: A retrospective multi-centric study was conducted from 2010 to 2020 at 16 centres. The cases with diagnoses of various deep mycoses were included in the study. The patients presenting with cutaneous manifestations were included in the study. Their demographic details, history, presenting signs and symptoms, morphological presentations, histopathological features and treatment details were collected from the case sheets. Results: A total of 124 cases were found from the case records. The most common type was chromoblastomycosis (42) followed by mycetoma (28) and rhinosporidiosis (17). The mean age was 43.76 ± 5.44 years. The average duration of symptoms before presentation was between 2 months to 10 years (average 2.5 ± 1.33 years). Male to female ratio was 1:0.7. Prior history of trauma was recorded in 36% of cases. Chromoblastomycosis cases presented with verrucous to atrophic plaques with black dots on the surface and histopathology findings included pesudoepitheliomatous hyperplasia, epithelioid cell granulomas, copper penny bodies within granulomas and abscesses. Rhinosporidiosis cases had polypoid grape-like lesions in the nose and eyes most commonly with histopathology findings of abundant thick-walled sporangia in dermis packed with thousands of spores. Eumycetoma patients had pigmented, indurated swelling with multiple sinuses discharging black granules and histopathology showed dermal abscesses and foreign body granulomatous reaction with PAS-positive hyphae. Histoplasmosis patients presented with few to multiple nodulo-pustular lesions on skin and palatal ulcers while small basophilic bodies packed in the cytoplasm of histiocytes were noted in histopathology. Phaeohyphomycosis cases presented as deep-seated cystic lesions and biopsy revealed deepithelialized cysts in the dermis or hypodermis with lumen showing necro inflammatory debris and fungal hyphae. Sporotrichosis cases had erythematous, tender nodules and papules either as single lesions or as multiple lesions arranged in a linear fashion and histopathology showed pseudoepitheliomatous hyperplasia of epidermis, loose to well-defined epithelioid cell granulomas and microabscesses. Spores were found in two cases. Cryptococcosis patient had multiple umbilicated lesions resembling giant molluscum contagiosum loose epithelioid cell granulomas and medium-sized spores lying in both intra and extracellularly on histopathology. Penicilliosis patients had nodulo-pustular lesions and histopathology showed an admixture of histiocytes, epithelioid cells, plasma cells, lymphocytes and polymorphs in the dermis with the presence of yeast-like spores in the cytoplasm of histiocytes and epithelioid cells. Entomophthoromycosis cases presented with asymptomatic subcutaneous firm swelling with loss of skin pinchability. Conclusion: Though clinical findings of deep fungal infections are characteristic similar morphology and atypical presentations can be sometimes confusing. Histopathology is useful for confirming the diagnosis.

Treatment Modalities for Refractory-Recurrent Tenosynovial Giant Cell Tumor (TGCT): An Update

Background and Objectives: Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive, benign neoplasm arising from the synovium of joints, tendon sheaths, and bursa. There are two main subtypes of TGCT: localized-type TGCT(L-TGCT) and diffuse-type TGCT (D-TGCT). While surgical excision is still considered the gold standard of treatment, the high recurrence rate, especially for D-TGCT, may suggest the need for other treatment modalities. Materials and Methods: This study reviews current literature on the current treatment modalities for refractory-relapsed TGCT disease. Results: The gold standard of treatment modality in TGCT remains surgical excision of the tumor nevertheless, the elevated recurrence rate and refractory disease, particularly in D-TGCT indicates and underscores the necessity for additional treatment alternatives. Conclusions: TGCT is a benign tumor with inflammatory features and a potential destructive and aggressive course that can lead to significant morbidity and functional impairment with a high impact on quality of life. Surgical resection remains the gold standard current treatment and the optimal surgical approach depends on the location and extent of the tumor. Systemic therapies have been recently used for relapsed mainly cases.

A Novel Ultrasound Finding for the Diagnosis of GiantCellArteritis: Comparison With Temporal ArteryBiopsy Findings.

Hypoechoic halo is a typical ultrasound finding in giant cell arteritis (GCA), but it may be a false positive due to arteriosclerosis. Therefore, we focused on the segmental distribution of GCA lesions, defined the luminal irregularity in long-axis images as the string of beads sign, and examined its diagnostic ability. As a result, the C-statistic of hypoechoic halo and string of beads sign was better than that of hypoechoic halo alone (1.00 vs. 0.89). Based on the above, the diagnostic ability of GCA can be improved by adding the string of beads sign to the conventional hypoechoic halo.

Vasculitis associated with VEXAS syndrome.

To define the prevalence, distribution, and characteristics of patients with VEXAS who have confirmed vasculitis. Patients with VEXAS syndrome, verified by positive UBA1 mutation, were included. Chart review was performed to identify. characteristics and outcomes. Vasculitis diagnosis was based on either histopathology showing vascular inflammation or non-invasive angiography findings. Summary statistics were calculated. Eighty-nine patients met inclusion criteria. All were male with a median age of onset of 66.9 years (IQR 60.1, 72.7). Median (IQR) follow up was 3.8(2.2-5.5) years during which 21 patients (23.6%) had evidence of vasculitis. Vasculitis subtypes included small vessel vasculitis (19.1%), cutaneous medium vessel vasculitis (2.2%), and large vessel vasculitis (2.2%). No patient had more than one vessel size involved. Histopathology in small vessel vasculitis patients was consistent with cutaneous leukocytoclastic vasculitis in the majority, though one patient had leukocytoclastic peritubular capillaritis on renal biopsy. Cranial symptoms (headache, vision changes, or jaw pain) were noted in 18.0%. Two additional patients not experiencing cranial symptoms exhibited large vessel involvement with confirmed carotid thickening on non-invasive angiography; one of these had a positive temporal artery biopsy. VEXAS syndrome manifests as a variable vessel vasculitis in a quarter of patients, with cutaneous small and medium vessel involvement being particularly common. Some patients may have positive ANCA serologies or even renal vasculitis leading to misdiagnosis. Cranial symptoms are common and may mimic giant cell arteritis, though documented large vessel inflammation is rare.

Versatility of patient specific implants in reconstruction of maxillofacial defect: a case report of central giant cell granuloma

Reconstructing maxillofacial defects is challenging due to its complex anatomy and cosmetic and functional effects on patients. From a functional and esthetic view, it is imperative for surgeons to accurately restore the defect in a way that will ensure patient satisfaction and well-being. Here, a case of large lytic lesion of anterior mandible, causing extensive bony resorption, in a young female patient is reported. Incisional biopsy was performed and the histopathological features were suggestive of Central giant cell granuloma (CGCG). Surgical treatment by en-bloc resection of the lesion was done. Several reconstruction options are available in the literature are available for the residual bony defect including iliac crest graft, costochondral graft, submental island flaps and more. However, the advent of additive manufacturing, 3–dimensional (3D) printing, and the recent advances in those technologies has positively influenced the biomedical field, leading to the utilization of patient-specific implants (PSIs) in the surgical repair of maxillofacial defects. This report highlights the advantages of using Patient Specific Implant and describes our experience with it.

LONG-TERM NATURAL HISTORY OF GIANT NULL CELL PITUITARY ADENOMA.

Pituitary adenomas that extend to the ventricular system are extremely rare. We present a 5-year natural history of a giant null cell pituitary adenoma with invasion into the cavernous sinus extending to the third ventricle. MRI series that were available could be useful for neurosurgeons, ophthalmologists, and endocrinologists as well as radiologists. Patients with the diagnosis of pituitary adenoma that are certain according to the radiological and clinical examination should be consulted by a neurosurgeon experienced in endoscopic endonasal surgery, a neuroendocrinologist, and an ophthalmologist. The surgery postponement in such cases results in disability and quality of life worsening. At that time, the surgery of giant pituitary adenomas demands high skills, and the risk of postoperative complications is high. The proper treatment modality including earlier surgery seems to be favorable for patient outcome.

Targeting Bone Tumours with 45S5 Bioactive Glass.

Despite advances in treatment modalities, bone tumour therapies still face significant challenges. Severe side effects of conventional approaches, such as chemo- and radiation therapy, result in poor survival rates and high tumour recurrence rates, which are the most common issues that need to be improved upon. The aim of this study was to evaluate the therapeutic properties of 45S5 bioactive glass (BG) for targeting bone tumours. The viability of the cells derived from osteosarcoma, chondrosarcoma, and giant cell tumours was significantly reduced in the presence of 45S5-BG. In contrast, the viability of non-malignant osteoblast-like cells, chondrocytes, and bone marrow-derived stromal cells was not or only slightly affected. While alterations to the particle surface induced by heat treatment, acid etching, or incubation in a simulated body fluid had only minor effects on cytotoxicity, reducing the particle size or sintering the material significantly improved the cytotoxic effect of 45S5-BG. Further, using a chicken chorioallantoic membrane assay, the co-transplantation of 45S5-BG resulted in a significant reduction in tumour formation in vivo. Given the known positive effects of BGs on bone regeneration, our findings suggest that 45S5-BG holds great potential for the development of new and effective bone tumour therapies, with minimal side effects on non-malignant cells and simultaneous contribution to bone healing.

Giant cell arteritis (GCA) as a risk factor for seizures: a cohort study

ABSTRACT Objectives The objective of this study was to assess the risk of seizures in Giant Cell Arteritis (GCA) patients in a large cohort of Israeli subjects, in comparison to matched controls. Methods Patients diagnosed with GCA between 2002 and 2017 were included. Controls were matched based on sex, age, socioeconomic status, country of birth, diabetes mellitus, and hypertension in a 4:1 ratio. Patients with seizure records prior to the study period were excluded. Hazard ratios for seizures was obtained by cox regression models. Results The study cohort was composed by 8,103 GCA patients and 32,412 matched controls. The GCA group included 5,535 women (68%), 2,644 patients born in Israel (33%), and 2,888 patients with low socioeconomic status (36%). The median age of this group was 71. During the followed cumulative person-years of 54,641 and 222,537 in the GCA and control group, respectively, 15.92 cases per 10,000 person-years was found in the GCA group, compared to 9.62 per 10,000 person-years in the controls. GCA was associated with seizures in the unadjusted (HR = 1.66, 95% CI [1.29 to 2.13]) and adjusted (HR = 1.67, 95% CI [1.3 to 2.14]) models. GCA was also associated with seizures after controlling for strokes (HR = 1.55, 95% CI [1.16 to 2.07]). Conclusion According to this study, individuals with GCA are at a higher risk of developing seizures when compared to the general population. This increased risk is independent of their predisposition for stroke. One proposed mechanism is that the GCA pro-inflammatory state may decrease the neuronal threshold for depolarization.

ALTERNATIVAS NÃO INVASIVAS NO MANEJO DO GRANULOMA CENTRAL DE CÉLULAS GIGANTES DOS MAXILARES: UMA REVISÃO NARRATIVA DA LITERATURA

Introduction: The Central Giant Cell Granuloma of the jaws is described as an uncommon intraosseous lesion that can exhibit different clinical and imaging characteristics. It can present in an aggressive or non-aggressive manner. When aggressive, the lesion is typically expansive, painful, and associated with bone tissue destruction. The standard treatment is surgical removal, but the choice of the ideal therapeutic approach depends on factors such as the patient’s age, lesion behavior, and its extent. Objective: To explore the main conservative treatment options for the management of Central Giant Cell Granuloma of the jaws. Methods: This is a narrative literature review based on research in databases such as PubMed and Google Scholar, conducted between July and August 2024, using DeCS/MeSH descriptors in English, “calcitonin” OR “interferon” OR “denosumab” AND “central granuloma of giant cells in jaws” AND “central giant-cell lesion” OR “corticosteroids injections” AND “intralesional triamcinolone.” Literature Review: The drug class used for the treatment of Central Giant Cell Granuloma is corticosteroids, which show high rates of therapeutic success, followed by calcitonin, denosumab, and interferon. However, despite promising results, additional clinical trials are necessary to establish the true efficacy of these treatments. Conclusion: All non-invasive treatment modalities have been shown to be effective in reducing or achieving complete regression of Central Giant Cell Granuloma of the jaws, either alone or in combination. However, there are limitations, such as the risk of adverse effects and the limited number of published studies to date.

Vimseltinib versus a placebo in patients with tenosynovial giant cell tumor: a plain language summary of the MOTION phase 3 trial.

This article presents a patient-friendly summary of the MOTION phase 3 clinical trial results, which were published in The Lancet in June 2024.The primary goal of the MOTION trial was to understand if treatment with a drug called vimseltinib shrank tumors more than a placebo in participants with symptomatic tenosynovial giant cell tumor, also known as TGCT, for which surgery was unlikely to provide benefit. A placebo is something that looks like the treatment being studied but does not contain any medicine.The MOTION trial compared the effects of vimseltinib versus a placebo using several different outcomes associated with TGCT. These outcomes included tumor size, active range of motion of the affected joint, and several patient-reported quality-of-life measures including physical function, stiffness, overall health, and pain. The trial showed that more participants treated with vimseltinib experienced significant tumor shrinkage, as defined by a 30% or greater reduction in tumor size, compared with those receiving a placebo. Participants receiving vimseltinib had improved active range of motion, and they reported improved physical function, stiffness, overall health, and pain, regardless of the amount of tumor shrinkage, compared with participants receiving a placebo. Most side effects in participants treated with vimseltinib were not severe and were manageable. Vimseltinib was better at shrinking tumors and improving active range of motion, stiffness, pain, and other health measures than the placebo for participants with TGCT. Vimseltinib has the potential to become a new treatment option for patients with TGCT for whom surgery may not provide benefit.

Genome-wide analysis of anterior-posterior mRNA regionalization in Stentor coeruleus reveals a role for the microtubule cytoskeleton.

Cells have complex and beautiful structures that are important for their function. However, understanding the molecular mechanisms that produce these structures is a challenging problem due to the gap in size scales between molecular interactions and cellular structures. The giant ciliate Stentor coeruleus is a unicellular model organism whose large size, reproducible structure, and ability to heal wounds and regenerate have historically allowed the formation of structure in a single cell to be addressed using methods of experimental embryology. Such studies have shown that specific cellular structures, such as the membranellar band, always form in particular regions of the cell, which raises the question: what is the source of positional information within this organism? By analogy with embryonic development, in which regionalized mRNA is often used to mark position, we asked whether specific regionalized mRNAs might mark position along the anterior-posterior axis of Stentor . By physically bisecting cells and conducting bulk RNA sequencing, we were able to identify sets of messages enriched in either the anterior or posterior half. We then conducted half-cell RNA-sequencing in paired anteriors and posteriors of cells in which the microtubule cytoskeleton was disrupted by RNAi of β-tubulin or dynein intermediate chains. We found that many messages either lost their regionalized distribution or switched to an opposite distribution, such that anterior-enriched messages in control became posterior-enriched in the RNAi cells, or vice versa. This study indicates that mRNA can be regionalized within a single giant cell and that microtubules may play a role, possibly by serving as tracks for the movement of the messages.