Dysgerminoma with Syncytiotrophoblastic Giant Cells Associated with a Concurrent Ectopic Pregnancy.

Background: Dysgerminomas constitute around 1-2% of all germ cell tumours. It is very very rare to have dysgerminoma with concurrent pregnancy with an incidence of 0.2-1 per 100,000 pregnancies. It is extremely difficult to conceive with no assisted reproductive interventions and carry it till completion with no complications in a concurrent dysgerminoma. Dysgerminoma has a characteristic specific histomorphology and is easy to diagnose. However, occasionally, syncytiotrophoblastic differentiation can be seen in dysgerminoma although it is a rare histopathological finding. Also, the raised serum B-HCG levels due to the syncytiotrophoblast giant cells seen can lead to a diagnostic dilemma. Clinical presentation: Here we report a case of a 27-year-old 8-week pregnant female who came to the hospital with chief complaints of left-sided abdominal pain and a lump abdomen. Clinical and radiological examination revealed a left ovarian tumour of malignant aetiology with the presence of right ectopic pregnancy. A staging laparotomy with left salpingoophorectomy was performed and sent for histopathological examination. It was reported as dysgerminoma with syncytiotrophoblastic giant cells. The right fallopian tube showed products of conception. Finally, she was planned for adjuvant chemotherapy and serial B-HCG levels. Summary: This case is reported not only just for its rare histopathological finding but also for the diagnostic dilemma it causes both to the surgeon as well as the pathologist. There are various factors which can act as prognosticators such as early suspicion of a tumor, radiological findings, surgery, histopathological examination, and oncology team.

Free Osteoarticular Metatarsal Autograft in the Reconstruction of Giant Cell Tumor of Metacarpal: Report of Two Cases and Description of a Technique.

Giant cell tumors are benign but locally aggressive bone neoplasms containing many multinucleated giant cells similar to osteoclasts. The author reports the case of two patients with giant cell tumor in the metacarpals, one of whom was multicentric. Giant cell tumor in the hand is a rare condition, and, at this location, it commonly presents at an advanced stage, with extensive bone destruction. Thus, its safe resection, associated with a large resulting bone failure, represents a great challenge to the orthopedist. The various treatment options described in the literature cause severe cosmetic and/or functional impairment to the hand. Thinking about it, the author describes the treatment technique through the transfer of metatarsus-free osteoarticular graft to the metacarpal with good functional and cosmetic results.

Giant-cell arteritis on photon-counting detector CT: A case report.

A 77-year-old woman presented to our hospital with a 2-week history of fever, headache, and induration along the bilateral superficial temporal arteries (STAs). The color Doppler ultrasonography of the STA showed a hypoechoic mural thickening surrounding a residual color flow. A contrast-enhanced photon-counting detector (PCD) CT demonstrated mural thickening and stenosis of the bilateral STAs. The patient underwent a biopsy of the right STA. Histopathological findings were consistent with giant cell arteritis (GCA). The patient's symptoms were temporarily relieved after initiation of steroid treatment, but jaw claudication occurred 2 months later. Contrast-enhanced CT showed improved vascular abnormalities of the STAs but new mural thickening and stenosis of the bilateral maxillary artery. Due to its higher resolution, image contrast, and lower noise, PCD-CT may have great potential in detecting, diagnosing, and monitoring GCA.

Adverse Tissue Reactions to Orise Gel During Endoscopic Mucosal Resection and Dissection.

BACKGROUND: To facilitate endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD), submucosal injection of lifting agents (LAs) is frequently used. ORISE™ gel, approved in 2018 by the US Food and Drug Administration (FDA), has been commonly utilized until recently. Its use grew rapidly due to its practical pre-filled syringe, prolonged lift effect, and ideal coloration. However, it has been noted to cause unexpected tissue reactions, described as "giant cell reaction" (GCR), which can obscure both macroscopic and microscopic views, potentially interfering with pathological evaluation. This study aims to describe the adverse effects of ORISE™ gel. METHODS: This retrospective study analyzed pathology specimens from all consecutive patients who received ORISE™ injections for attempted polyp removal and subsequently underwent segmental colon resection at our center between 2019 and 2022. Descriptive analysis was performed. RESULTS: A total of 45 patients were included, with 38% (n=17) being female and a median age of 66 years. The indications for surgery included adenocarcinoma in 14 patients (31%), suspected malignancy in 3 patients (7%) who had benign GCR-induced masses, and other indications in 28 patients, such as large polyps or recurrent polyps after initial endoscopic treatment. Surgical procedures included right hemicolectomy (44%), low anterior resection (13%), left colectomy (11%), sigmoidectomy (7%), and abdominoperineal resection (4%). Histologic evidence of prior LA injection was seen in 31 patients (69%), with 24 of these exhibiting GCR. At final pathology, no residual neoplasm was found in 9 patients (18%), while 14 patients (31%) had adenocarcinoma [T1 (7), T2 (3), T3 (3), T4 (1)]. CONCLUSION: ORISE™ Gel interacts with various tissue layers of the colon, frequently resulting in GCR. This reaction and the potential subsequent mass effect formation can impact decision-making in the management of complex colorectal lesions. Further study into the cause and consequences of LA tissue reactions is warranted.

Giant cell tumor of bone of temporal bone and skull base: report of 6 cases.

OBJECTIVE: Five cases of giant cell tumor of bone (GCTB) in the head and neck region were reported, with a main focus on the radiological findings to identify common characteristics for the diagnosis of GCTB in these sites. MATERIALS AND METHODS: Five consecutive patients diagnosed with GCTB were retrospectively selected. Radiological features on conventional and advanced MR sequences and CT were analyzed. HE staining and immunohistochemical examination were performed using antibodies against p63 and CD68. RESULTS: The common clinical features were local mass (3/5), tinnitus (3/5) and headache (2/5). Radiologically, all the cases were well-circumscribed osteolytic lesion, majority of cases demonstrated an expansile growth pattern and "soap bubble" appearance on CT (4/5). On MRI, the tumors showed predominantly hypointensity both on T1WI and T2WI, and no evidence of restricted diffusion on DWI. Intratumoral hemorrhage (2/5), cystic alternation (2/5) and very low signal on T2WI in the periphery region of the tumor (4/5) was found. Fluid-fluid level was noted in one case, which was eventually verified to be GCTB with secondary aneurysmal bone cyst (ABC). With contrast agent, all the cases showed striking (3/5) or mild to intermediate (2/5) enhancement. CONCLUSIONS: Although the above described radiological findings are not specific for GCTB in head and neck region, a well-defined osteolytic lesion in the bones of head and neck region with "soap bubble" appearance on CT and hypointensity on T2WI with very low signal in the peripheral region of the tumor on MRI highly suggest GCTB for patient ages 20 to 40.

The role of 18FDG-PET imaging in VEXAS syndrome: a multicentric case series and a systematic review of the literature.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic) syndrome is characterized by heterogeneous clinical manifestations. Due to the inflammatory nature of this condition, 18-FDG-PET (18-fluorodeoxyglucose-positron emission tomography) might be used to diagnose and monitor the disease. However, no data are available about the most common findings of PET imaging in this disease. For this reason, we summarised all the available reports of patients with VEXAS who underwent at least one PET scan and described 8 additional patients' PET from our centres. Overall, we described 35 patients' PET findings. All patients were male, with a median age of 70 years. The most frequent hypermetabolic sites on PET scans were the bone marrow (77.1%), lymph nodes (35.3%), lungs (28.6%), spleen and large vessels (22.9%), and cartilage (20%). Six patients underwent a PET scan 2.7 ± 1.5 years before VEXAS diagnosis, showing nonspecific uptake in the bone marrow. Four patients had a follow-up PET scan, showing a decrease or a disappearance of the previously identified hypermetabolic areas. In conclusion, although no specific uptake site has been found for VEXAS syndrome, PET imaging could help detect inflammatory foci that are not clinically evident. In addition, high metabolic activity in bone marrow might precede the clinical onset of the disease, shedding light on the pathogenesis of VEXAS.

Giant Cell Tumor of First Metatarsal: A Rare Case Report with Literature Review.

Introduction: Giant cell tumor (GCT) is a benign locally aggressive tumor with features of frequent recurrence and metastatic potential. GCT of small bones of hand and feet is rare with high recurrence and potential to metastasis. This study aims to provide a case report of GCT of the first metatarsal treated with wide excision, autologous fibular grafting, and fixation with locking plate. Case Report: An 18-year-old male patient presented with progressive swelling over the dorsomedial aspect of foot for 1 year. Upon clinical examination, the swelling was firm with local signs suggestive of a benign bony tumor arising from the base of first metatarsal of the left foot. Radiology reveals an expansile osteolytic lesion arising from the base of 1st metatarsal with coarse septations and features suggestive of a benign bone lesion. A core biopsy was obtained under local anesthesia and histopathology report suggested a GCT. Surgical intervention by en bloc excision and reconstruction by fibular autograft and stabilized with a locking plate was done. The patient was given a below-knee cast for 6 weeks postoperatively. Full weight bearing was started after 6 weeks. At 12 months of follow-up, the graft was well taken up and there were no signs of recurrence both clinically and radiologically. Conclusion: GCT of 1st metatarsal is a rare entity with higher recurrence rate compared to conventional GCT. En bloc excision and autologous fibular graft with plate fixation are preferred treatment options.

Unusual Histopathological Challenges in Diagnosis of Giant Cell Tumor Cases Treated with Neoadjuvant Denosumab Chemotherapy: A Rare Case Report.

Introduction: Giant cell tumor of bone (GCTB) is a rare yet locally aggressive neoplasm primarily affecting young adults. Its hallmark features include multinucleated osteoclast-type giant cells and mononuclear tumor cells. Treatment with denosumab, an anti-RANK ligand antibody, has shown efficacy, but it alters histomorphology, posing diagnostic challenges. Co-occurrence with achondroplasia, though rare, warrants consideration in bone lesion evaluations. Case Report: A 30-year-old male with achondroplasia presented with a proximal femur GCT, a rare association. Neoadjuvant denosumab was administered due to thin tumor cortex and cortical breech. Surgical excision with bone cement filling and Philo's plate supplementation was performed. Histopathological examination post-treatment revealed the absence of osteoclast-type giant cells, extensive necrosis, hyalinization, and mononuclear infiltrates. Discussion: Denosumab induces a reduction in osteoclast numbers, causing tumor shrinkage and sclerosis, while altering typical GCT histology. Similar findings were noted in the literature, including stromal changes like spindle-shaped cells, inflammation, vascular proliferation, and hemosiderin-laden foamy macrophages. Recognition of these alterations is crucial for accurate diagnosis. Conclusion: GCT, though rare, presents distinct histopathological features aiding diagnosis. Denosumab treatment modifies tumor morphology, necessitating thorough clinical evaluation for accurate diagnosis post-treatment. Understanding, these challenges is essential for optimal management of GCT cases.

Giant Cell Tumor as a Rare Cause of Loose Bodies in the Knee Joint - A Case Report.

Introduction: Loose bodies in the knee joint are relatively common and the common causes are transchondral fractures, synovial chondromatosis, osteochondritis dissecans, meniscal injury, and osteoarthritis. Neoplastic growths from synovium have been reported to have presentations mimicking loose bodies or meniscus tears. Case Report: We report the case of an unusual cause of loose body in the knee joint of a 35-year-old male who reported for follow-up 3 years after the surgical management of giant cell tumor (GCT) of the distal femur. He had symptoms of loose bodies in the joint without any complaint specific to the operative site. Imaging revealed loose bodies within the joint which were removed arthroscopically. Histopathology showed the loose bodies as GCT. The patient had relief of symptoms after removal and the patient has no evidence of recurrence at the primary site or in the knee joint. Conclusion: GCTs should be considered a cause of loose bodies in the joint when there is a neighboring bone affected by GCT and all such loose bodies removed should undergo histopathological examination.

Functional Outcomes of Limb Salvage Surgery in Patients with Giant Cell Tumor of Bone of the Lower Extremities: A Cross-sectional Comparative Study.

Background and Objectives: Giant cell tumor of bone (GCTB) is a benign aggressive tumor primarily treated with surgery. Neoadjuvant treatment with denosumab or zoledronic acid is a common adjunct given to down-stage tumors and facilitate limb sparing surgery. This study sought to determine the characteristics, outcomes, and occurrence of complications following resection (RS) or extended curettage (EC) for GCTB of the lower extremities. Correlation of neoadjuvant therapy with the occurrence of complications was also investigated. Methods: This is an analytical cross-sectional study of 30 patients diagnosed with GCTB of the lower extremity treated between 2015 to 2022 in a single tertiary hospital. Functional outcomes were determined using the 1993 version of the Musculoskeletal Tumor Society (MSTS) score. Mean follow-up for all patients was 2.6 years (SD 1.8). Twenty-two patients (73%) underwent resection, while eight (27%) patients underwent extended curettage. Of the 30 patients, 26 (87%) patients received neoadjuvant therapy, with 21 (81%) given denosumab and five (19%) given zoledronic acid. Results: Functional outcomes were excellent for 23 patients (77%), with no significant difference between RS and EC groups. Nine complications occurred in the RS group, including dehiscence (n=3), superficial infection (n=2), implant failure (n=1), nonunion (n=1), palsy (n=1), and implant irritation (n=1). Five complications occurred in the EC group, four of which were noted to be recurrences, with one case of deep infection. Recurrence was noted to be significantly higher (p=0.0004) in the EC group. Separate correlation analysis showed no significant difference in incidence of complications but found that duration of surgery was significantly longer (p=0.0001), and intraoperative blood loss was significantly higher (p=0.0072) in the RS group. No significant difference (p=0.78) was noted in complication rate between patients given denosumab versus zoledronic acid. Conclusions: Functional outcomes of EC and RS appear to be comparable, including the incidence of complications. However, recurrence was noted to be significantly higher in EC. There appears to be no clear advantage between denosumab or zoledronic acid for GCTB. As a neoadjuvant medication and/or to control tumor progression, zoledronic acid may be the more economic option especially for patients in developing countries.

Clinicopathologic and prognostic characteristics of tumor budding-like in giant cell tumor of bone.

BACKGROUND: Currently, tumor budding (TB) is defined as an important factor for a poor prognosis in various types of cancers. The authors identified a significant presence of TB-like structures at the tumor invasive front in giant cell tumor of bone (GCTB), which may have the same biologic function as TB. The objective of this report was to describe the distribution of TB in GCTB and investigate its correlation with clinicopathologic characteristics, the immune microenvironment, survival prognosis, and response to denosumab treatment. METHODS: This multicenter cohort study included 426 patients with GCTB who received treatment between 2012 and 2021 at four centers. Two independent pathologists performed visual assessments of TBL structures in hematoxylin-and-eosin-stained tumor sections. Immunohistochemistry was used to evaluate tumor-infiltrating lymphocyte subtypes (CD3-positive, CD4-positive, CD8-positive, CD20-positive, programmed cell death protein-1-positive, programmed cell death-ligand 1positive, and FoxP3-positive) as well as Ki-67 expression levels in 426 tissue samples. These parameters were then analyzed for associations with patient outcomes (local recurrence-free survival [LRFS] and overall survival [OS]), clinicopathologic characteristics, and response to denosumab treatment. RESULTS: High-grade TB was associated with poorer LRFS and OS in both patient groups. In addition, TB was correlated with various clinicopathologic features, tumor-infiltrating lymphocyte expression, and response to denosumab treatment. TB outperformed the traditional Enneking and Campanacci staging systems in predicting patient LRFS and OS. CONCLUSIONS: The current data support the assessment of TBL structures as a reliable prognostic tool in GCTB, potentially aiding in the development of personalized treatment strategies for patients.

The impact of histopathological criteria for definite vasculitis in giant cell arteritis: retrospective analysis of temporal artery biopsies.

Histopathological findings associated with definite vasculitis in temporal artery biopsy (TAB) defined in 2022 ACR/EULAR classification criteria for Giant Cell Arteritis (GCA) was published in 2022. We aimed to evaluate the TAB of our GCA patients for histopathological findings associated with definite vasculitis. Patients who were diagnosed with GCA by clinicians and underwent TAB between January 2012 and May 2022 were included. Hospital electronic records and patients' files were reviewed retrospectively. A total of 90 patients' pathology reports were evaluated by a pathologist and a rheumatologist. In cases where microscopic findings were not specified in the pathology reports, histopathologic specimens were re-evaluated (n = 36). A standard checklist was used for histopathological findings of definite vasculitis. Patients were divided into two groups; (i) definite vasculitis-GCA and (ii) non-definite-GCA group, and the clinical and demographic characteristics for all patients were compared. The mean age of patients was 69.8 (± 8.5) years and 52.2% were female. In the first evaluation, 66 (73.3%) patients had a diagnosis of vasculitis according to pathology reports. In the re-evaluation of biopsy specimens, at least one definite finding of vasculitis was observed in TAB of 10/24 (41.6%) patients whose microscopic findings were not specified in the pathology reports. The ROC analysis showed that biopsy length had diagnostic value in predicting the diagnosis of definite vasculitis (AUC: 0.778, 95% CI: 0.65-0.89, p < 0.001). In those with a biopsy length of ≥ 1 cm, sensitivity was 76.5%, specificity was 64.3%, and PPV value was 92. In multivariate analysis, the most significant factor associated with definite vasculitis was biopsy length (OR: 1.18 (1.06-1.31), p = 0.002). Microscopic findings were reported in over 70% of patients. Reinterpretation of results according to a standard check-list improved the impact of TAB in the diagnosis of GCA. A biopsy length ≥ 1 cm was found to contribute towards a definitive histopathological vasculitis diagnosis.

Retrospective Analysis of Specimen Quality in Temporal Artery Biopsies for Giant Cell Arteritis and Disease Association in North Midlands, England.

Background Temporal artery biopsy (TAB) is the recommended index diagnostic method for giant cell arteritis (GCA). Per the British Society for Rheumatology (BSR) guidelines, we assessed our procedural performance. Additionally, we evaluated the occurrence of GCA diagnosis in immunosuppressed patients and other comorbidities. Methods Following the audit registration, a retrospective analysis of prospectively collected data was conducted from 2017 to 2022 at a large university hospital in North Midlands, England. Data on demographics and comorbidities were gathered. The study's primary outcome was adherence to BSR guidelines and our service provisions. Secondary outcomes included examining the relationship between biopsy-confirmed GCA and other comorbidities. Statistical analysis was carried out using SPSS version 29 (IBM Corporation, Armonk, New York, United States of America). Two-sample t-test and Chi-square/Fisher exact test were used for continuous and categorical variables, respectively. Holm-Bonferroni method was incorporated to adjust for multiple comparisons. Results A total of 156 patients who underwent temporal artery biopsy (TAB) were included in the study, with a male-to-female ratio of 0.44:1. The median age was 73. Among the patients, 19% were smokers. The procedures were performed by either a vascular surgeon (119, 76%) or by an ophthalmologist (37, 24%). Two-thirds of the patients underwent TAB within seven days of referral. In 73, 47% of cases, the post-fixation biopsy sample size exceeded 10 mm. Positive biopsy results were found in 45 patients (29%). GCA was confirmed in 39% of patients with polymyalgia rheumatica (PMR), 24% with diabetics, 20% with hypothyroidism, 29% with hypertension, 32% with hyperlipidaemia, and 26% with other inflammatory diseases. However, the p-value was below the statistically significant threshold. The biopsy outcome was also not dependent on the speciality, time from referral to biopsy, nor on the length of the post-fixation specimen. Conclusions Temporal artery biopsy remains a valuable and crucial diagnostic tool in challenging equivocal cases of giant cell arteritis (GCA), although it is limited by its sensitivity, but there is also room for improvement. There is still uncertainty regarding the relationship between biopsy positivity, post-fixation sample size, and the interval between referral and procedure. Additionally, the speciality of the clinician performing the biopsy does not appear to significantly influence the likelihood of a positive result. We still do not fully understand why this is, but the association of the GCA with other comorbidities was unpredictably insignificant.

Locking plate augmentation of polymethylmethacrylate-filled distal femoral defects: A biomechanical study.

Benign, locally aggressive tumors of the distal femur are typically treated with intralesional curettage and polymethylmethacrylate (PMMA) cementation. However, it is not known whether plate fixation should be added to biomechanically augment these PMMA-filled defects. The purpose of this study was to evaluate the performance of two competing techniques for reconstruction of a distal femoral defect. For this biomechanical study, we used 12 composite femurs with properties comparable to bone. In nine femurs, identical contained medial distal femoral defects were created using a robotic arm. Group A contained three intact femurs, Group B three femurs with an unfilled defect, Group C three femurs reconstructed with PMMA alone, and Group D three femurs reconstructed with PMMA plus a medial locking plate. Locations of greatest stress concentration were determined by PhotoStress analysis, then three strain gauges were applied to each specimen at these high-stress locations. Specimens were loaded within a physiologic range followed by loading to failure. Outcome measures included construct stiffness, strain along the distal femur, and load at failure. Results showed that stiffness and strain were not significantly different between reconstructive techniques; however, both techniques reduced tensile strain along the popliteal surface by approximately 40% compared to non-reconstructed specimens. All specimens failed at the femoral neck before failing at the distal femur. These findings suggest that plate augmentation of PMMA-filled distal femoral defects like the one in this study offers insignificant biomechanical benefit within physiologic loads and therefore may be unnecessary.

Combined preoperative denosumab and adjuvant microwave ablation for high-risk giant cell tumor of bone: a retrospective study in a single center.

BACKGROUND: Giant cell tumor of bone (GCTB) is a locally aggressive neoplasm with a high propensity for recurrence following intralesional curettage. The introduction of denosumab, a RANKL inhibitor, has shown potential in facilitating joint-sparing surgery. However, concerns exist regarding its impact on local recurrence rates. This study aimed to evaluate the efficacy and safety of combined preoperative denosumab with adjuvant microwave ablation (MWA) for the treatment of high-risk GCTB. METHODS: We conducted a retrospective review of 19 patients with high-risk GCTB who underwent preoperative denosumab treatment followed by curettage and adjuvant MWA. The primary outcome measure was the local recurrence rate, with secondary outcomes including functional status assessed by the Musculoskeletal Tumor Society (MSTS) score and safety profile of the treatment. RESULTS: In this retrospective analysis, we evaluated the outcomes of 19 patients with high-risk GCTB treated with preoperative denosumab and adjuvant MWA. The median follow-up duration was 33.1 months, 3 patients (15.8%) experienced local recurrence at a median of 21.6 months postoperatively and the local recurrence-free survival was 81.2% at two years. Notably, no patient developed lung metastasis, and all recurrences were successfully managed with repeat curettage and MWA, with a mean MSTS score of 27.3. No patient required joint replacement due to tumor recurrence, resulting in a 100% joint preservation rate. CONCLUSION: The combination of preoperative denosumab and adjuvant MWA is a feasible and effective strategy for the management of high-risk GCTB, providing effective local control with preserved joint function. This approach may offer a surgical alternative for young patients where joint preservation is paramount.

Juvenile trabecular ossifying fibroma associated with central giant cell granuloma and aneurysmal bone cyst like changes - A triple hybrid tumour? Or a pathologic sequelae?

Hybrid tumours encompass lesions containing two or more pathologic entities. The pathogenesis of these lesions is barely understood and described. Juvenile trabecular ossifying fibroma (JTOF) is a benign but locally aggressive fibro-osseous neoplasm commonly affecting the maxilla of the adolescent age group. Hybrid lesions of JTOF have been reported along with central giant cell granuloma (CGCG), aneurysmal bone cyst (ABC) and traumatic bone cyst, respectively. However, the co-occurrence of JTOF with CGCG and ABC in a single patient has not yet been reported in the literature, hence, making ours the first case report of this kind. Theories describing the pathogenesis of this rare phenomenon have also been proposed and elaborated.

Paediatric oral hyaline ring granuloma associated with an impacted tooth and its management preserving the tooth germ: A case report.

Oral hyaline ring granuloma is an unusual granulomatous lesion affecting the jaws characterized by the presence of numerous eosinophilic rings with multinucleated giant cells. The lesion can be of central or peripheral variety, caused by the impaction of foreign particles in the oral cavity. While literature describes this lesion in association with dentures, carious teeth and extraction socket, this paper reports the first case of an oral hyaline ring granuloma associated with an impacted premolar tooth and its surgical management.

Helminth derivative tuftsin-phopshorylcholine, to treat autoimmunity.

Autoimmune diseases (AIDs) affect 5-10% of the population . There are more than ~100 different autoimmune diseases. The AIDs are one of the top 10 causes of death in women under 65; 2nd highest cause of chronic illness; top cause of morbidity in women in the US. The NIH estimates annual direct healthcare costs for autoimmune diseases about $100 billion, in comparison, with cancers investment of $57 billion, heart and stroke cost of $200 billion. The current treatments for autoimmune diseases encompasses: steroids, chemotherapy, immunosuppressants, biological drugs, disease specific drugs (like acethylcholine-estherase for myasthenia gravis). The treatments for autooimmune diseases supress the patient immune network, which leads the patients to be more susceptible to infections. Hence, there is a need to develop immunomodulatory small molecules with minimal side effects to treat autoimmune diseases. The helminths developed secreting compounds which modulate the human defense pathways in order to develop tolerance and survive in the host environment. We have imitated the immunomodulatory activity of the helminth by using a derivative of the helminth secretory molecule. A bi-functional small molecule -tuftsin (T)-phosphorylcholine (PC), coined as TPC, was constructed . This chimeric molecule showed its immunomodulatory activity in 4 murine models of autoimmune diseases, attenuating the clinical score and the inflammatory response by immunomodutating the host immune system. Ex-vivo in human peripheral blood mononuclear cells (PBMCs) and biopsies originated from arteries of patients with giant cell arteritis. This paper decipher the mode of action of TPC immunomodulatory activity. Our data propose the potential for this small molecule to be a novel therapy for patients with autoimmune diseases.

Pexidartinib Upfront in a Case of Tenosynovial Giant Cell Tumor: Proof of Concept for a Treatment Paradigm Shift.

BACKGROUND: Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive tumor of the joints, bursa, and tendon sheath that can cause considerable pain and substantial morbidity. Although surgery is the primary treatment for patients with TGCT, surgical resection is associated with high rates of recurrence, particularly for patients with diffuse TGCT. Pexidartinib, a colony-stimulating factor 1 receptor inhibitor, is approved by the US Food and Drug Administration for the treatment of adult patients with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery. CASE DESCRIPTION: A 32-year-old man presented with intra-articular diffuse TGCT with pain and received noncurative treatment for 5 years (2014-2019). In 2019, the patient was found to have extensive disease accompanied by pain and limited range of motion. The patient's case was presented to a sarcoma multidisciplinary tumor board, who determined that surgery would cause significant morbidity and macroscopic residual tumor. As a result of the extent of disease, young age, and otherwise good health, treatment with pexidartinib was started through a compassionate use program at 800 mg/day. After dose reductions to pexidartinib at 400 mg/day and then 200 mg/day as a result of creatine phosphokinase elevations, the patient achieved a complete response after 2 years of treatment; pain was reduced and mobility was restored. The patient reported no side effects related to pexidartinib treatment. Treatment was stopped in 2022 for future family planning. After pexidartinib therapy was interrupted, the patient's wife had a successful pregnancy and delivery; however, the disease showed a slow but constant clinical deterioration, with a reduction in the range of movement of the affected knee and an apparent increase in widespread TGCT nodules. CONCLUSION: Our case is unique because it provides support for pexidartinib use as upfront therapy for TGCT, instead of surgery, in selected cases.