Foreign Body Giant Cells Research Articles

Foreign body giant cell reaction due to Durolane (hyaluronic acid derivative) injection - A case report.

Osteoarthritis can be treated with hyaluronic acid derivatives, such as Durolane manufactured by Bioventus (Hill, 2017), particularly when conventional treatments prove ineffective. In osteoarthritic joints, the synovial fluid has a lower concentration of hyaluronic acid compared to healthy joints. Intra-articular therapy with exogenous hyaluronic acid can improve viscoelastic properties, enhance chondrocyte synthesis, reduce cartilage degradation, and alleviate pain associated with osteoarthritis (Migliore and Procopio in Clin Cases Miner Bone Metab. 12:31-3, 2015). This report describes a unique case where a patient, following Durolane administration, presented with an intraosseous foreign body giant cell reaction. A 2.5-cm lesion was identified on MRI, initially raising concerns for metastatic disease or multiple myeloma. Subsequent IR CT-guided biopsy confirmed a diagnosis of "foreign body giant cell reaction to gel," linked to the Durolane injection. This case presents a contribution to the literature due to the scarcity of documented instances where Durolane injection leads to an intraosseous foreign body giant cell reaction resembling metastatic disease. While a solitary intraosseous pseudotumor, reportedly due to viscosupplement injection, has been published, it differs in both location (hip vs. knee) and imaging characteristics from the presented case. The manifestation of a foreign body giant cell reaction after Durolane injection, mimicking malignant osseous lesions, merits attention among practitioners. This case underscores the necessity for further research into potential adverse reactions associated with hyaluronic acid derivatives.

PERITONEAL KERATIN GRANULOMAS MIMICKING PERITONEAL CARCINOMATOSIS: A POTENTIAL DIAGNOSTIC PITFALL

Abstract Introduction/Objective Keratin granulomas from a primary uterine cancer can present as peritoneal tumor nodules, mimicking peritoneal carcinomatosis. Endometrial adenocarcinomas with viable peritoneal tumor implants and/or involvement of bladder or bowel mucosa are categorized as stage IV disease. We present a rare case of endometrial adenocarcinoma of the uterus with squamous differentiation and multiple peritoneal nodules of keratin granulomas, masquerading as peritoneal carcinomatosis. Methods/Case Report A 68-year-old female with insignificant past medical history presented with complaints of postmenopausal bleeding for the past four months. Physical examination was unremarkable. Transvaginal ultrasound showed a 4.9 cm echogenic mass in the uterus. The endometrial biopsy showed squamous debris with atypical cells suspicious of malignancy. Endometrial curettings revealed endometrial adenocarcinoma, endometrioid type with squamous differentiation, FIGO Grade 1. Subsequently, she underwent hysterectomy with bilateral salpingo- oophorectomy. Intraoperatively, multiple suspicious nodules on the sigmoid colon and in the pelvis were identified, of which excisional biopsies and pelvic peritoneal washing were taken. Microscopic examination of the resection confirmed endometrial adenocarcinoma, FIGO Grade 1, nuclear grade 1, with extensive foreign body giant cell reaction to dead squamous cells (ghost cells). Cytologic examination of the peritoneal washing was unremarkable and excisions of the sigmoid serosal and peritoneal nodules showed pink eosinophilic laminated nodules surrounded by inflammatory cells including plasma cells, lymphocytes and multinucleated giant cells without any viable tumor cells. Results (if a Case Study enter NA) NA Conclusion Keratin granulomas are a foreign body reaction to keratin deposition from the squamous component of endometrioid adenocarcinoma. The pathogenesis of this foreign body response to keratin is considered to be a trans- tubal spread of keratin through retrograde shedding from the fallopian tubes. In the absence of viable tumor cells, it appears to have no negative prognostic significance. Careful microscopic examination of peritoneal keratin granulomas is imperative to avoid erroneous upstaging of the tumor and the subsequent advanced treatment.

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.

An idiosyncratic reaction to the synthetic biologic membrane on a surgical wound

Abstract Introduction/Objective Biodegradable temporizing matrix (BTM) is a synthetic polymer used to temporarily close wounds and aid the body in generating new tissue. BTM is applied to a debrided wound.BTM acts as a scaffold aiding the migration of granulation tissue into the matrix. Once the tissue is fully integrated throughout the BTM, the sealing membrane is removed. The matrix slowly deteriorates until fully absorbed at approximately 18 weeks. Methods/Case Report An 80-year-old woman with a past medical history of eczema, rheumatoid arthritis and gout presented with swelling of the left third metatarsal. Imaging showed an abscess which was eventually drained and cultured to show mycobacterium chelone. The patient was started on antibiotics for mycobacterium. On follow up she reported a nodule on left forearm recently increased in size. MRI on 9/28 showed abscess of the dorsal aspect of phalanx. She underwent surgical debridement 10/31 on her finger and the forearm nodule. After debridement a polynovo BTM graft was placed. Histopathology showed skin and subcutaneous tissue with necrotizing granulomas of the finger and the forearm. Cultures and stains for mycobacterium returned negative.The patient was subsequently followed up for wound healing. She reported nodules on the left forearm at the scar from previous surgical site which were biopsied. Histopathology showed granulomatous inflammation, rare foreign body giant cells, and birefringent material. The stains for Ziehl-Neelsen, Fite and Gomori’s Methenamine Silver for Urate Crystals were all negative excluding the possibility of gouty tophi or mycobacterium. Results (if a Case Study enter NA) NA Conclusion The complex history of the patient with mycobacterium, gout, the giant cell reaction and the unique appearing birefringent crystals presented a puzzling problem. Given the negative stain results for mycobacteria and the presence of birefringent (foreign) material, we deem these granulomas most likely an idiosyncratic reaction to the synthetic biologic membrane applied during her prior procedure. There are no known cases of giant cell reaction and similar morphology of birefringent (foreign) material in literature.

Comparative In Vivo Biocompatibility of Cellulose-Derived and Synthetic Meshes in Subcutaneous Transplantation Models.

Despite the increasing interest in cellulose-derived materials in biomedical research, there remains a significant gap in comprehensive in vivo analyses of cellulosic materials obtained from various sources and processing methods. To explore durable alternatives to synthetic medical meshes, we evaluated the in vivo biocompatibility of bacterial nanocellulose, regenerated cellulose, and cellulose nanofibrils in a subcutaneous transplantation model, alongside incumbent polypropylene and polydioxanone. Notably, this study demonstrates the in vivo biocompatibility of regenerated cellulose obtained through alkali dissolution and subsequent regeneration. All cellulose-derived implants triggered the expected foreign body response in the host tissue, characterized predominantly by macrophages and foreign body giant cells. Porous materials promoted cell ingrowth and biointegration. Our results highlight the potential of bacterial nanocellulose and regenerated cellulose as safe alternatives to commercial polypropylene meshes. However, the in vivo fragmentation observed for cellulose nanofibril meshes suggests the need for measures to optimize their processing and preparation.

Granulomas without foreign body giant cells in perianal fistula tissue suggest Crohn's disease.

Histopathological characteristics of granulomas in perianal fistula of patients with Crohn's disease (CD) remain unexplored. We aimed to assess the histopathological features of granulomas in perianal fistula in CD. A retrospective analysis was conducted by reviewing the medical and pathological records of 4430 cases who underwent perianal fistulectomy at our hospital between June 2015 and June 2023. The patients were divided into the CD group, tuberculosis (TB), and non-CD group, respectively, based on their final diangosis. The detection rate of granulomas and differential histopathological features were investigated. Among the 4430 patients, granulomas were identified in 41 cases, including 25 had CD, 2 had pulmonary TB, and 14 only exhibiting perianal lesions with no other comorbidities. Additionally, there were altogether 93 CD cases, resulting in a detection rate of granuloma of 26.9%, which was considerably higher than that in the non-CD group (26.9% vs 0.3%, p < 0.001). The majority (85.7%) of the perianal fistula tissues in the non-CD group contained foreign body giant cells, while this was observed in only 1 (4.0%) out of the 25 cases with CD. We proposed that granulomas in the perianal fistula in the non-CD group were mostly foreign body granulomas. Moreover, granulomas in the non-CD group were larger than that of the CD group (1135 μm vs 519 μm, p < 0.001). Most CD cases have less granulomas (≤3) and no foreign body giant cells. Ribbon-like granulomas can be seen only in CD cases.

Macrophage microRNA-146a is a central regulator of the foreign body response to biomaterial implants

Host recognition and immune-mediated foreign body response (FBR) to biomaterials can adversely affect the functionality of implanted materials. FBR presents a complex bioengineering and medical challenge due to the lack of current treatments, making the detailed exploration of its molecular mechanisms crucial for developing new and effective therapies. To identify key molecular targets underlying the generation of FBR, here we perform analysis of microRNAs (miR) and mRNAs responses to implanted biomaterials. We found that (a) miR-146a levels inversely affect macrophage accumulation, foreign body giant cell (FBGC) formation, and fibrosis in a murine implant model; (b) macrophage-derived miR-146a is a crucial regulator of the FBR and FBGC formation, as confirmed by global and cell-specific knockout of miR-146a; (c) miR-146a modulates genes related to inflammation, fibrosis, and mechanosensing; (d) miR-146a modulates tissue stiffness near the implant during FBR as assessed by atomic force microscopy; and (e) miR-146a is linked to F-actin production and cellular traction force induction as determined by traction force microscopy, which are vital for FBGC formation. These novel findings suggest that targeting macrophage miR-146a could be a selective strategy to inhibit FBR, potentially improving the biocompatibility of biomaterials.

Cholesterol granuloma of the maxillary sinus: a case report

BackgroundCholesterol granuloma is not a common entity in the paranasal sinuses. It is a foreign body reaction to the cholesterol crystal deposition. Mostly associated with chronic middle ear diseases.Case presentationThis article reports a case of cholesterol granuloma in the maxillary sinus. A 23-year-old Asian man presented with cough, nasal obstruction, and postnasal discharge. On endoscopy, there was a mass protruding from the right maxillary ostium. On computed tomograpy imaging, there was a polypoidal mass in the right maxillary sinus. Endoscopic sinus surgery was performed, the cholesterol granuloma was removed from the right maxillary sinus, and the tissue was submitted for histopathological examination, which showed foreign body giant cell reaction to cholesterol crystals.ConclusionCholesterol granuloma of maxillary sinus is not common and often missed by clinicians. It is necessary to consider the cholesterol granuloma of maxillary sinus in the differential diagnosis sinonasal lesions. Histopathological analysis is required for confirmation and should be removed surgically. This case may help as a reference for clinician to approach these kinds of cases.

A report on five cases of cholesterol granulomas in the thymus

BackgroundCholesterol granuloma (CG) is a benign entity characterized by the presence of cholesterol crystals and foreign body giant cells. This condition can be attributed to cholesterol crystals that are deposited in the tissues and react with foreign body giant cells, resulting in granuloma formation. Lesions commonly develop in the otolaryngeal region, such as the middle ear. However, crystals rarely form in the thymus, accounting for 1% of all mediastinal tumors. Herein, we present five cases of mediastinal CG.Case presentationThe patients were aged 49–61 (mean, 55.4) years. Among them, three were men and two women. One patient had fever, and four patients were asymptomatic. The patients’ lesions were detected during follow-up of other diseases or medical examinations showing the presence of abnormal chest shadows. The patients did not have a history of trauma or surgery. All lesions were located within the thymus gland. Three patients presented with multifocal lesions and two with a single lesion. Four patients had contrast effect on computed tomography scan. Four patients had abnormal fluorodeoxyglucose accumulation (mean maximum standardized uptake value, 4.67) on positron emission tomography-computed tomography. Four patients underwent complete surgical resection. The size of the resected lesions ranged from 1.8 to 5.1 (mean, 3.24) cm. Histologically, all patients presented with small nodules with cholesterol clefts and foreign body giant cells and histiocyte infiltration within the thymic tissue. The postoperative course was excellent. None of the patients who underwent complete resection presented with recurrence. Moreover, the patient who underwent partial resection did not have lesion enlargement.ConclusionsCG in the thymus is clinically challenging to differentiate from malignant lesions, and histologic diagnosis via surgical resection is required.

Prompt Cytopathological Diagnosis of Multiple Xanthomatous Skin Nodules in an Adolescent Girl Opening the Doors to Detection of Familial Hypercholesterolemia

Background Xanthomas are papulo-nodular, yellow, soft, painless, dermal-based non-neoplastic cutaneous lesions that comprise of localized aggregates of lipid-laden histiocytes. Case report A thirteen-year-old adolescent girl presented with multiple, large, bilateral, nodules present over elbows, posterior aspect of heel, and knees for five years. Fine needle aspiration cytology was performed, and the smears showed numerous foamy histiocytes, a few benign spindle cells, and foreign-body giant cells against a lipidaceous background. Her maternal aunt and grandmother also had xanthelasma palpebrarum. Serum lipid levels were advised and were markedly deranged in all three of them. Based on the corroborative clinical, biochemical, and cytopathological findings, a final diagnosis of familial hypercholesterolemia (FH) was rendered. Conclusion The present case sheds light on the importance of prompt cytopathological diagnosis of xanthomatous lesions, especially in children and adolescents, as it can help prevent morbidity and mortality due to associated premature adverse cardiovascular and cerebrovascular events if left undiagnosed.

Diagnostic dilemma: axillary cysticercosis masquerading as breast mass

Cysticercosis, caused by the tapeworm Taenia solium, is a significant public health concern, particularly prevalent in developing nations. We present a case of isolated cysticercosis in the axillary region, mimicking a breast mass, in a 47-year-old woman who presented with a gradually enlarging mass in her right axilla and was initially diagnosed with fibroadenoma. However, further investigations revealed cysticercosis in the larvae, including ultrasonography and fine-needle aspiration cytology (FNAC). The patient underwent surgical excision of the cysts following a two-week course of albendazole therapy. Histopathological examination confirmed cysticercosis with a foreign body giant cell reaction. Cysticercosis typically involves muscular and subcutaneous tissues, posing diagnostic challenges due to its resemblance to other conditions. Ultrasonography, FNAC, and MRI play crucial roles in accurate diagnosis. Treatment involves a combination of surgical removal and antiparasitic medications such as albendazole. This case highlights the importance of considering cysticercosis in differential diagnosis, especially in endemic regions, and underscores the effectiveness of a comprehensive treatment approach integrating medical therapy and surgical intervention. Effective management ensures the eradication of parasitic infection and the alleviation of associated symptoms, exemplifying patient-cantered care for optimal outcomes. Increased awareness, preventive measures, and early diagnosis are essential for mitigating the burden of cysticercosis, particularly in regions with poor sanitation and high prevalence rates.

Lentil aspiration pneumonitis

This patient has a complex medical history that includes intellectual disability, blindness, deafness, seizure disorder, tracheomalacia, and recurrent aspiration. He had a percutaneous endoscopic gastrostomy in place for tube feeding. He again presented with acute respiratory distress, hypoxemia, fever, and leukocytosis. Chest computed tomography (CT) revealed bilateral infiltrates and nodular densities. A previous chest CT done 6 years prior to admission revealed multiple micronodules scattered throughout both lung fields. The patient had had a previous lung biopsy 20 years prior to admission which revealed lentil starch material in bronchioles and multifocal foreign body giant cell reactions. The patient was treated with an empiric antibiotic regimen and improved. This case demonstrates the radiographic and histologic changes associated with lentil pneumonia which is an unusual type of aspiration pneumonia. Keywords: Lentil pneumonia, granulomas, aspiration, nodules

Poster 141: In Vitro Inflammatory Response to Surgical Scaffolds for Rotator Cuff Repair

Objectives: Surgical scaffolds are used to augment rotator cuff tendon repairs. Interactions between recruited immune cells and tendon-resident stromal cells influence whether the scaffold is integrated or rejected by the body. The primary aim of this in vitro study was to compare the inflammatory response of human monocytes to different surgical scaffolds. The secondary aim was to determine how this monocyte response affects the behavior of human rotator cuff tendon-derived stromal cells in vitro. Methods: Primary human monocytes were cultured on four commercially available scaffolds: LARS ligament (synthetic); GraftJacket (allograft), Permacol (xenograft, cross-linked), and Conexa (xenograft, noncross-linked). Secreted inflammatory proteins were measured after 1 and 10 days. Foreign body giant cell formation was assessed after 10 days. Proliferation and gene expression of tendon stromal cells were assessed after being grown in a conditioned medium from monocyte-scaffold cultures. Results: After 10 days, monocytes cultured on the Conexa scaffold secreted the highest levels of the pro-inflammatory markers GM-CSF, IL-8, and IL-10 (fig. 1). After 1 day, tendon stromal cells incubated in conditioned media from Conexa-monocyte cultures expressed lower Collagen Type VI and increased MMP3 and MMP6 mRNA (fig. 2). Foreign Body Giant Cell formation was most prominent in monocytes cultured on the Permacol scaffold (Figure 3). Conclusions: In vitro experiments demonstrated that xenograft scaffolds elicited a more pronounced pro-inflammatory response in human monocytes compared to synthetic and allograft scaffolds. Inflammatory cytokines secreted by monocytes in response to xenografts may modulate scaffold integration through paracrine signaling to tendon stromal cells. These findings may help explain the clinical performance of xenograft scaffolds for tendon repair and inform future scaffold design.

Electrospun Composites of Chitosan with Cerium Oxide Nanoparticles for Wound Healing Applications: Characterization and Biocompatibility Evaluation In Vitro and In Vivo.

Cerium oxide nanoparticles (CeONPs), as part of tissue regeneration matrices, can protect cells from reactive oxygen species and oxidative stress. In addition, they can influence the properties of the scaffold, including its electrospinnability and mechanical strength. In this work, we prepared electrospun fiber mats from a chitosan and polyethylene oxide blend (CS-PEO) with the addition of ceria nanoparticles (CS-PEO-CeONP). The addition of CeONPs resulted in a smaller fiber diameter and higher swelling compared to CS-PEO fiber mats. CeONP-modified fiber mats also had a higher Young's modulus due to the reinforcing effect of the nanoparticles. Both mats had comparable adhesion and cytocompatibility to mesenchymal stem cells, which had a more rounded morphology on CS-PEO-CeONP compared to elongated cells on the CS-PEO mats. Biocompatibility in an in vivo rat model showed no acute toxicity, no septic or allergic inflammation, and no rough scar tissue formation. The degradation of both mats passed the stage of matrix swelling. CS-PEO-CeONP showed significantly slower biodegradation, with most of the matrix remaining in the tissue after 90 days. The reactive inflammation was aseptic in nature with the involvement of multinucleated foreign-body type giant cells and was significantly reduced by day 90. CeONPs induced the formation of the implant's connective tissue capsule. Thus, the introduction of CeONPs influenced the physicochemical properties and biological activity of CS-PEO nanofiber mats.

Mir-146a is required for foreign body response and giant cell formation

The implantation of biomaterials or medical devices often leads to the development of a foreign body response (FBR), an inflammatory condition that can lead to implant failure, which may cause harm to or death of the patient. Hallmarks of the FBR include accumulation of macrophages and destructive foreign body giant cells (FBGCs), and development of fibrous scar tissue encompassing the implant. There are no effective medical treatments for FBR, although improved fundamental understanding of the molecular mechanisms underlying the development of FBR may lead to novel strategies for the amelioration of FBR. MicroRNAs (miRs) are endogenous, small, non-coding RNAs that have emerged as powerful regulators of gene expression in numerous cellular processes including macrophage activation, inflammation, and fibrosis. In this research, we tested the hypothesis that specific miRs play a crucial role in regulating the FBR to biomaterials. In our subcutaneous implantation mouse model, we found that: 1) miR-146a expression levels decreased in the implant-adhered tissues, and the decrease correlated with increased macrophage accumulation, FBGC formation, and collagen accumulation; and 2) miR-146a deletion in mice exacerbated in vivo macrophage accumulation, FBGC formation, and collagen accumulation. In our in vitro model, we found that deficiency of miR-146a function exacerbated key macrophage functions including adhesion on stiff matrix, and FBGC formation in primary mouse macrophages. In essence, our findings suggest that miR-146a might act as a suppressor of FBR. We expect that the results of this study may provide invaluable information and insight regarding the molecular mechanisms mediating the FBR to biomaterials, which may lead to the development of a novel microRNA-based therapeutic strategy for the amelioration of the poorly understood FBR to biomaterials. NIH (R01 AI172086) grant to Shaik O. Rahaman. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Biocompatible adipose extracellular matrix and reduced graphene oxide nanocomposite for tissue engineering applications

Despite the immense need for effective treatment of spinal cord injury (SCI), no successful repair strategy has yet been clinically implemented. Multifunctional biomaterials, based on porcine adipose tissue-derived extracellular matrix (adECM) and reduced graphene oxide (rGO), were recently shown to stimulate in vitro neural stem cell growth and differentiation. Nevertheless, their functional performance in clinically more relevant in vivo conditions remains largely unknown. Before clinical application of these adECM-rGO nanocomposites can be considered, a rigorous assessment of the cytotoxicity and biocompatibility of these biomaterials is required. For instance, xenogeneic adECM scaffolds could still harbour potential immunogenicity following decellularization. In addition, the toxicity of rGO has been studied before, yet often in experimental settings that do not bear relevance to regenerative medicine. Therefore, the present study aimed to assess both the in vitro as well as in vivo safety of adECM and adECM-rGO scaffolds. First, pulmonary, renal and hepato-cytotoxicity as well as macrophage polarization studies showed that scaffolds were benign invitro. Then, a laminectomy was performed at the 10th thoracic vertebra, and scaffolds were implanted directly contacting the spinal cord. For a total duration of 6 weeks, animal welfare was not negatively affected. Histological analysis demonstrated the degradation of adECM scaffolds and subsequent tissue remodeling. Graphene-based scaffolds showed a very limited fibrous encapsulation, while rGO sheets were engulfed by foreign body giant cells. Furthermore, all scaffolds were infiltrated by macrophages, which were largely polarized towards a pro-regenerative phenotype. Lastly, organ-specific histopathology and biochemical analysis of blood did not reveal any adverse effects. In summary, both adECM and adECM-rGO implants were biocompatible upon laminectomy while establishing a pro-regenerative microenvironment, which justifies further research on their therapeutic potential for treatment of SCI.

Histological, Clinical Assessment, and Treatment of a Permanent Filler Complication in the Upper Lip: A Case Report with 16-Year Follow-Up

There is a considerable increase in the use of substances and medical procedures aimed at changing the esthetics of the face, particularly the appearance of the lips. Permanent fillers such as polydimethylsiloxane, also called liquid silicone, are widely used, but their application for facial esthetics is currently obsolete. Silicone belongs to this polymer family; its viscosity is determined by its degree of polymerization. Liquid injectable silicone is odorless, colorless, non-volatile, and oily to the touch. The substance is not altered by storage at room temperature and is not carcinogenic or teratogenic. However, the long-term complications remain a reality, as they can occur decades after the application. Thus, the goal of this case report was to present a complication after 16 years of treatment using liquid silicone. This case report involved a 52-year-old male with a complication of bilateral permanent filler in the upper lip performed 16 years ago, its surgical removal, and histological analysis. The patient had the first appointment at the University Dental Clinic—Universidade Católica Portuguesa (Viseu, Portugal) in April 2022, dissatisfied with his upper lip’s esthetic appearance and shape. He was not a smoker or diabetic but had hypertension and hypercholesterolemia and was medicated with Losartan, Hydrochlorothiazide, and Pitavastatin. No relevant findings were observed in the extraoral examination; he had bruxism and a good periodontal condition. The patient had an asymptomatic bilateral mass, hard to palpation, located on the upper lip due to permanent lip filling performed to increase its volume in 2006 associated with non-related generalized granules of Fordyce. The treatment options presented just observation or complete material removal in two surgical steps, which was the patient’s choice. Then, the first surgical procedure was performed under local anesthesia on the right side of the lip, one carpule of Lidocaine 2% with adrenaline 1:100,000, with a chalazion clamp, a diode laser for hemorrhagic control, and a simple suture. In this procedure, three fragments were biopsied: a cuboid measuring 1 × 1 × 0.8 cm and an irregular one consisting of two fragments that at one end of the piece were in continuity with each other, one measuring 1.6 × 0.5 × 0.4 cm and the other 2.5 × 0.6 × 0.5 cm. A similar macroscopic appearance in all the material, white in color, irregular surface, elastic, white section surface, or slightly fasciculate. The patient was medicated with Tylenol 500 mg thrice a day for two days. With 20-day intervals, the sutures from the first surgery were removed, as well as the foreign body from the upper lip on the left side, following the same surgical technique and medication. Histologically, it was possible to identify a chronic inflammatory, lymphoplasmacytic, and granulomatous reaction, with foreign body giant cells’ reaction, in relation to non-polarizable exogenous material due to the reaction to silicone. The most common complications are granulomas’ appearance and material displacement. The case report shows these granulomas are characterized as chronic low-caliber inflammation around the silicone. They have an unknown etiology but are probably multifactorial, from continuous trauma, friction or irritation, iatrogenic factors, infection, immunological mechanisms, and genetic and molecular variations, and can be highly related to the impurity of the injected material. This case brings the opportunity for health professionals to increase awareness of the long-term adverse effects of the silicone material used to fill the lip in order to make its application more predictable and conscious.

Cellular Immunity of Drosophila willistoni Reveals Novel Complexity in Insect Anti-Parasitoid Defense.

Coevolution of hosts and their parasites has shaped heterogeneity of effector hemocyte types, providing immune defense reactions with variable effectiveness. In this work, we characterize hemocytes of Drosophila willistoni, a species that has evolved a cellular immune system with extensive variation and a high degree of plasticity. Monoclonal antibodies were raised and used in indirect immunofluorescence experiments to characterize hemocyte subpopulations, follow their functional features and differentiation. Pagocytosis and parasitization assays were used to determine the functional characteristics of hemocyte types. Samples were visualized using confocal and epifluorescence microscopy. We identified a new multinucleated giant hemocyte (MGH) type, which differentiates in the course of the cellular immune response to parasitoids. These cells differentiate in the circulation through nuclear division and cell fusion, and can also be derived from the central hematopoietic organ, the lymph gland. They have a binary function as they take up bacteria by phagocytosis and are involved in the encapsulation and elimination of the parasitoid. Here, we show that, in response to large foreign particles, such as parasitoids, MGHs differentiate, have a binary function and contribute to a highly effective cellular immune response, similar to the foreign body giant cells of vertebrates.

Abstract 2830: Intravital multiphoton microscopy of bone metastatic renal cell carcinoma

Abstract Clear cell renal carcinoma (ccRCC) represents 80% of renal neoplasms, with bone as a major site for distant spread (35-40% of patients). These secondary lesions cause a variety of skeletal-related complications, including pain, spinal cord compression, hypercalcemia, mobility issues and fractures, posing a significant negative impact on patient quality of life and survival. Furthermore, bone is well-known as a site of therapy resistance, which confers to patients treated with systemic therapies significantly worse time-to-treatment failure and progression-free and overall survival compared to those without bone metastases. Because of the complexity of the bone microenvironment and the paucity of suitable models, preclinical investigation of bone metastasis and therapy response is challenging. Preclinical models of bone metastasis that integrate tissue engineering and advanced imaging techniques can facilitate the study of the mechanism of tumor progression and therapy response. We recently developed a window model amenable to intravital multiphoton microscopy (MPM) to longitudinally monitor human ccRCC lesions in tissue engineered bone constructs (TEBCs) in immunodeficient mice. TEBCs were generated by functionalizing polymeric polycaprolactone scaffolds with bone morphogenetic protein 7. Human ccRCC lesions, after implantation into the bone cavity, were longitudinally monitored for growth and niche development, using multi-parameter recording of collagen/bone matrix (SHG), bone surface (THG), blood vessels/stromal phagocytes (fluorescent dextran), and tumor cells (GFP). However, this model lacked key components of the immune system (including B and T-cells), which are of major interest in the study of tumor progression and (immune) therapy response. Therefore, we developed a tissue-engineered preclinical model that incorporate species-specific interactions between cancer and bone stromal cells, and account for an intact immune system. To this purpose, we optimized TEBC formation in C57BL/6 fluorescent reporter mice (Sp7-mCherry, osteoblasts; Trap-td-Tomato, osteoclasts; GFP, immune cells, αSMA-RFP fibroblasts; and Flk1-GFP, blood vessels), coupled to detection by intravital or ex vivo multiphoton microscopy analysis, to monitor the evolution and fate of the TEBC. Interestingly, the bone marrow in the core of the TEBC was replaced by a desmoplastic tissue with features like the foreign body response, including foreign body giant cells, which was not present in immunodeficient mice. By applying dual color GFP/αSMA-RFP mice, which expressed red fluorescence in activated fibroblasts, we confirmed the fibrotic nature of this core. To avoid its formation, we generated scaffold-free ossicle, by direct implantation of BMP7 and VEGF in the subcutaneous tissue. To conclude, we established a protocol for generating ectopic ossicles in immunocompetent mice. Citation Format: Stefan Maksimovic, Nina Constanza Boscolo, Sergio Barrios, Antonios Mikos, Matthew T. Campbell, Eleonora Dondossola. Intravital multiphoton microscopy of bone metastatic renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2830.

Distinctive Pathology Associated With Focal Stenosis of the Main Pancreatic Duct Secondary to Remote Trauma: A Long-term Complication of Seat Belt Pancreatitis.

The radiologic finding of focal stenosis of the main pancreatic duct is highly suggestive of pancreatic cancer. Even in the absence of a mass lesion, focal duct stenosis can lead to surgical resection of the affected portion of the pancreas. We present four patients with distinctive pathology associated with non-neoplastic focal stenosis of the main pancreatic duct. The pathology included stenosis of the pancreatic duct accompanied by wavy, acellular, serpentine-like fibrosis, chronic inflammation with foreign body-type giant cell reaction, and calcifications. In all cases, the pancreas toward the tail of the gland had obstructive changes including acinar drop-out and interlobular and intralobular fibrosis. Three of the four patients had a remote history of major motor vehicle accidents associated with severe abdominal trauma. These results emphasize that blunt trauma can injure the pancreas and that this injury can result in long-term complications, including focal stenosis of the main pancreatic duct. Pathologists should be aware of the distinct pathology associated with remote trauma and, when the pathology is present, should elicit the appropriate clinical history.