Monocyte-Macrophage Lineage Cell Fusion.

Cell fusion (fusogenesis) occurs in natural and pathological conditions in prokaryotes and eukaryotes. Cells of monocyte-macrophage lineage are highly fusogenic. They create syncytial multinucleated giant cells (MGCs) such as osteoclasts (OCs), MGCs associated with the areas of infection/inflammation, and foreign body-induced giant cells (FBGCs). The fusion of monocytes/macrophages with tumor cells may promote cancer metastasis. We describe types and examples of monocyte-macrophage lineage cell fusion and the role of actin-based structures in cell fusion.

Foreign body reaction toward hydrophilic polymer at the site of endovascular procedure: A report of two cases.

Hydrophilic polymer-coated devices have been increasingly utilized for various endovascular procedures, however not been without adverse effects. We report two cases of subacute cutaneous lesions on the neck encountered in our dermatology clinic. Histopathologic findings were significant for a nodular aggregate of epithelioid histiocytes and lymphocytes with numerous foreign body giant cells in the dermis. The granulomatous infiltrate was associated with an amorphous basophilic non-polarizable material. Further chart review reveals both patients receiving a central venous procedure in the past, thus attributing the hydrophilic polymers as the likely source of the foreign material found at the insertion site. Our cases contrast to the more commonly reported distal embolization by these hydrophilic polymer layers. We suspect the incidence of retained hydrophilic polymer at the site of prior endovascular procedures may be underreported in the literature with the more inconspicuous presentations. Therefore, retained foreign material should be considered by both treating physicians and dermatopathologists in presenting cases of lesions that occur at common sites of endovascular procedures.

Mechanotransduction via a TRPV4-Rac1 signaling axis plays a role in multinucleated giant cell formation.

Multinucleated giant cells are formed by the fusion of macrophages and are a characteristic feature in numerous pathophysiological conditions including the foreign body response (FBR). Foreign body giant cells (FBGCs) are inflammatory and destructive multinucleated macrophages and may cause damage and/or rejection of implants. However, while these features of FBGCs are well established, the molecular mechanisms underlying their formation remain elusive. Improved understanding of the molecular mechanisms underlying the formation of FBGCs may permit the development of novel implants that eliminate or reduce the FBR. Our previous study showed that transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive ion channel/receptor, is required for FBGC formation and FBR to biomaterials. Here, we have determined that (a) TRPV4 is directly involved in fusogenic cytokine (interleukin-4 plus granulocyte macrophage-colony stimulating factor)-induced activation of Rac1, in bone marrow-derived macrophages; (b) TRPV4 directly interacts with Rac1, and their interaction is further augmented in the presence of fusogenic cytokines; (c) TRPV4-dependent activation of Rac1 is essential for the augmentation of intracellular stiffness and regulation of cytoskeletal remodeling; and (d) TRPV4-Rac1 signaling axis is critical in fusogenic cytokine-induced FBGC formation. Together, these data suggest a novel mechanism whereby a functional interaction between TRPV4 and Rac1 leads to cytoskeletal remodeling and intracellular stiffness generation to modulate FBGC formation.

Giant cells lepromatous leprosy. Diffuse dermatitis with exuberant foreign body giant cells in treated lepromatous leprosy / Células gigantes en lepra lepromatosa. Dermatitis difusa con células gigantes tipo cuerpo extraño exuberantes en lepra lepromatosa tratada

Patients with lepromatous leprosy that have received treatment for many years usually get follow up biopsies for persistent skin lesions or positive bacilloscopy even if the values are lower than in the initial bacilloscopy. We report the case of a 48-year old woman with long-standing lepromatous leprosy of 15 years of evolution, with a bacterial index of 4 in the direct smear and the initial skin biopsy. The patient was treated with multidrug therapy for 32 months although the treatment recommended by the World Health Organization (WHO) is only for 12 months. A skin biopsy was taken to determine if there was an active disease. We observed a diffuse dermal inflammation with numerous foreign body giant cells and vacuolated macrophages (Virchow´s cells). These cells contained granular acid-fast material that was also positive with immunohistochemistry for BCG. There were fragmented bacilli and the BI was 2. These cells were also strongly positive for CD68. The biopsy was interpreted as a residual form of lepromatous leprosy that did not require further multidrug therapy. We have observed similar histological profiles in several cases. The lack of clinical data makes it a histological challenge. The accumulation of lipids in these giant cells is due to bacillary destruction and fusion of vacuolated macrophages. We discuss here the role of bacillary and host lipids in the pathogenesis of lepromatous leprosy. We concluded that there was no need to extend the 12-month multidrug therapy recommended by WHO.

Los pacientes con lepra lepromatosa (LL) que han recibido tratamiento durante años, usualmente tienen seguimiento con biopsias de piel para lesiones persistentes o con baciloscopia positiva, con valores menores a los iniciales. Presentamos una mujer de 48 años con LL de 15 años de evolución, con índice bacilar (IB) 4 en el extendido directo y en la biopsia, que recibió terapia multidroga durante 32 meses, aunque el tratamiento recomendado por la Organización mundial de la salud (OMS) es de 12 meses. Se tomó una biopsia de piel para determinar si la enfermedad estaba activa. Se observó inflamación dérmica difusa con numerosas células gigantes tipo cuerpo extraño y macrófagos vacuolados (células de Virchow). Estas células, CD68 positivas, contenían material granular ácido-alcohol resistente, positivo con inmunohistoquímica para BCG. Se encontraron bacilos fragmentados y el IB fue de 2. Se interpretó como una forma residual de LL y que la paciente no requería MDT adicional. Este perfil histológico lo hemos observado en casos similares. Sin datos clínicos estas biopsias son un reto diagnóstico. La acumulación de lípidos en estas células gigantes se debe a la destrucción bacilar y a la fusión de macrófagos vacuolados. Revisamos el papel de los lípidos del bacilo y del huésped en la patogénesis de la LL. En estos casos no es necesario extender los 12 meses de MDT recomendados por la OMS. En el seguimiento de los pacientes se recomienda contar con los hallazgos clínicos, la baciloscopia, la biopsia anual de piel y los títulos IgM anti-glicolípido fenólico.

Solochrome cyanine: A histological stain for cobalt-chromium wear particles in metal-on-metal periprosthetic tissues.

Metal-on-metal (MoM) hip arthroplasties produce abundant implant-derived wear debris composed mainly of cobalt (Co) and chromium (Cr). Cobalt-chromium (Co-Cr) wear particles are difficult to identify histologically and need to be distinguished from other wear particle types and endogenous components (e.g., haemosiderin, fibrin) which may be present in MoM periprosthetic tissues. In this study we sought to determine whether histological stains that have an affinity for metals are useful in identifying Co-Cr wear debris in MoM periprosthetic tissues. Histological sections of periprosthetic tissue from 30 failed MoM hip arthroplasties were stained with haematoxylin-eosin (HE), Solochrome Cyanine (SC), Solochrome Azurine (SA) and Perls' Prussian Blue (PB). Sections of periprosthetic tissue from 10 cases of non-MoM arthroplasties using other implant biomaterials, including titanium, ceramic, polymethylmethacrylate (PMMA) and ultra-high molecular weight polyethylene (UHMWP) were similarly analysed. Sections of 10 cases of haemosiderin-containing knee tenosynovial giant cell tumour (TSGCT) were also stained with HE, SC, SA and PB. In MoM periprosthetic tissues, SC stained metal debris in phagocytic macrophages and in the superficial necrotic zone which exhibited little or no trichrome staining for fibrin. In non-MoM periprosthetic tissues, UHMWP, PMMA, ceramic and titanium particles were not stained by SC. Prussian Blue, but not SC or SA, stained haemosiderin deposits in MoM periprosthetic tissues and TSGT. Our findings show that SC staining (most likely Cr-associated) is useful in distinguishing Co-Cr wear particles from other metal/non-metal wear particles types in histological preparations of periprosthetic tissue and that SC reliably distinguishes haemosiderin from Co-Cr wear debris.

Células gigantes en lepra lepromatosa: dermatitis difusa con células gigantes exuberantes de tipo cuerpo extraño en lepra lepromatosa tratada / Giant cells lepromatous leprosy: Diffuse dermatitis with exuberant foreign body giant cells in treated lepromatous leprosy

Resumen Los pacientes con lepra lepromatosa que han recibido tratamiento durante años, usualmente requieren seguimiento con biopsias de piel para detectar lesiones persistentes o si la baciloscopia es positiva, incluso si los valores son menores que los iniciales. Se presenta el caso de una mujer de 48 años de edad con lepra lepromatosa de 15 años de evolución, índice bacilar de 4 en el extendido directo y en la biopsia, que recibió tratamiento con múltiples medicamentos durante 32 meses, aunque lo recomendado por la Organización Mundial de la Salud (OMS) es una duración de 12 meses. Se tomó una biopsia de piel para determinar si la enfermedad estaba activa. Se observó inflamación dérmica difusa con numerosas células gigantes de tipo cuerpo extraño y macrófagos vacuolados (células de Virchow). Estas células, CD68 positivas, contenían material granular ácido-alcohol resistente positivo con inmunohistoquímica para BCG. Se encontraron bacilos fragmentados y el índice bacilar fue de 2. Se interpretó como una forma residual de lepra lepromatosa y se concluyó que la paciente no requería prolongar el tratamiento con múltiples medicamentos. Este perfil histológico se ha observado en casos similares, pero sin datos clínicos estas biopsias representan un reto diagnóstico. La acumulación de lípidos en estas células gigantes se debe a la destrucción bacilar y a la fusión de macrófagos vacuolados. Se revisó el papel de los lípidos del bacilo y del huésped en la patogenia de la lepra lepromatosa. En estos casos, no es necesario extender los 12 meses de tratamiento con múltiples medicamentos recomendados por la OMS. En el seguimiento de los pacientes, se recomienda contar con los hallazgos clínicos, la baciloscopia, la biopsia anual de piel y los títulos IgM antiglucolípido fenólico.

Abstract Patients with lepromatous leprosy that have received treatment for many years usually get follow up biopsies for persistent skin lesions or positive bacilloscopy even if the values are lower than in the initial bacilloscopy. We report the case of a 48-year old woman with long-standing lepromatous leprosy of 15 years of evolution, with a bacterial index of 4 in the direct smear and the initial skin biopsy. The patient was treated with multidrug therapy for 32 months although the treatment recommended by the World Health Organization (WHO) is only for 12 months. A skin biopsy was taken to determine if there was an active disease. We observed a diffuse dermal inflammation with numerous foreign body giant cells and vacuolated macrophages (Virchow´s cells). These cells contained granular acid-fast material that was also positive with immunohistochemistry for BCG. There were fragmented bacilli and the BI was 2. These cells were also strongly positive for CD68. The biopsy was interpreted as a residual form of lepromatous leprosy that did not require further multidrug therapy. We have observed similar histological profiles in several cases. The lack of clinical data makes it a histological challenge. The accumulation of lipids in these giant cells is due to bacillary destruction and fusion of vacuolated macrophages. We discuss here the role of bacillary and host lipids in the pathogenesis of lepromatous leprosy. We concluded that there was no need to extend the 12-month multidrug therapy recommended by WHO. Clinical findings, bacilloscopy, annual skin biopsy, and anti-phenolic glycolipid-I IgM titers are recommended procedures for the follow-up of these patients.

Granulomatosis with polyangiitis: potentially lethal gingival lesions presenting to the dentist.

Gingival pathology is a daily presentation, however a small number of systemic conditions can manifest similar to a common gingival condition and have fatal results. Dentist referred 56-year-old woman to Oral and Maxillofacial Surgery department with a 2-week medical history of gingival bleeding not responding to local measures. Biopsy showed eosinophilic infiltrate and vasculitis, and blood tests showed positive markers including cytoplasmic antineutrophil cytoplasmatic antibodies. Granulomatosis with polyangiitis is a rare disease affecting the respiratory tract, blood vessels and kidneys. Oral lesions are rarely the primary presenting feature. When left untreated, most cases are fatal within a year of diagnosis. The diagnosis can only be made when certain criteria are found, including granular oral lesions exhibiting an eosinophilic inflammatory infiltrate on biopsy. With 5% of cases showing intraoral lesions as the primary feature, it is essential that dentists have the knowledge of this rare disease to refer and not to treat as a common gingival condition.

Biomaterial-induced multinucleated giant cells express proinflammatory signaling molecules: A histological study in humans.

The biomaterials physicochemical characteristics influence their cellular reaction, degradation and regenerative capacities. Macrophages and multinucleated giant cells (MNGCs) are observed in the augmentation area of biomaterials. This study, for the first time, evaluated the polarization pattern of macrophages and MNGCs in response to two different bone substitute materials (synthetic bone substitute material [SBSM] = NanoBone vs. xenogeneic bone substitute material [XBSM] = Bio-Oss) in human bone biopsies compared to non-augmented bone (control). Histomorphometrical analysis of the polarization in proinflammatory (M1) and anti-inflammatory (M2) cells was performed using different immunohistochemical markers: CD-68 = macrophages; CCR-7 and Cox-2 (M1) and CD-206 and CD-163 (M2) and tartrate-resistant acid phosphatase (TRAP). The macrophage polarization pattern in SBSM showed a significantly higher number of M1 cells than did XBSM and non-augmented bone. XBSM induced a significantly higher number of CD-206-positive macrophages than SBSM did. No significant difference was found between XBSM and the non-augmented bone. MNGCs expressed CD-68 and TRAP. In both test-groups, MNGCs showed a high proinflammatory character (CCR-7 and Cox-2-positive) and their number in the SBSM group was significantly higher than that of XBSM. The tissue distribution showed a significantly low percentage of the remaining biomaterial in SBSM compared to XBSM. Within the limitations of this study, these findings show that MNGCs exhibit a rather proinflammatory character and lead to biomaterial degradation, once they are induced in a high number. The premature degradation of bone substitute materials is compensated with a high percentage of connective tissue and not new bone formation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 780-790, 2019.

The in vivo inflammatory and foreign body giant cell response against different poly(l-lactide-co-d/l-lactide) implants is primarily determined by material morphology rather than surface chemistry.

Biomaterials can cause a chronic local inflammation called foreign body reaction, with formation of foreign body giant cells (FBGC) by monocyte/macrophage fusion. However, FBGC appearance and role for biomaterials with different physicochemical properties are not yet fully understood. This study aimed at examining FBGC and inflammatory cells after intramuscular implantation of poly(l-lactide-co-d/l-lactide) (PLA) as membranes and uncoated electro-spun fiber meshes or meshes with a positively charged plasma-polymer coating into rats. After 7, 14 and 56 days, CD68+ and CD163+ macrophages, T lymphocytes, MHC-II+ cells, FBGC, and nestin-stained tissue area as regeneration marker were morphometrically analyzed. FBGC occurrence was primarily determined by material morphology, as their numbers for meshes were 10-fold higher during acute and 50-fold higher during chronic inflammation than for membranes but comparable between uncoated and coated meshes. CD68+ macrophages decreased around and within meshes, while CD163+ macrophages and MHC-II+ cells increased within meshes. T lymphocytes within meshes were higher for coated meshes, suggesting that the peri-implant tissue immunological response is also influenced by surface chemistry. FBGC were predominantly CD68+ and CD163- , and nestin-stained tissue area was negatively correlated with CD68+ monocytes/macrophages numbers and positively correlated with CD163+ macrophages numbers, highlighting differing roles in FBGC formation and tissue regeneration. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2726-2734, 2018.

Granuloma formation associated with patellar tendon necrosis in response to Ethibond confirmed by histopathological examination.

The aim of this study is to describe a case of delayed granuloma formation associated with tendon necrosis in response to Ethibond confirmed by histopathological examination and to review and discuss the related literature. A 40-year-old woman underwent a patellar tendon repair with Krakow-like #5 Ethibond sutures. Four years after the repair, she noticed progressive soreness with knee extension and swelling. An ultrasound examination revealed a proximal partial patellar tendon rupture. Based on these findings, the patient was advised to undergo surgical intervention due to a diagnosis of re-rupture. Tendinosis, fibrosis and necrosis scar tissue surrounding the previous suture were observed and excised, and samples were sent for histopathological and microbiological examination. Stripping of the patellar paratenon was performed. Surprisingly, a giant cell foreign body reaction surrounding the synthetic refringent material, as well as polymorphonuclear cells surrounding the necrotic tendon, was reported.

Peritoneal Pulse Granulomas With Spiral Bodies Mimicking Peritoneal Carcinomatosis: A Case Report.

Pulse (hyaline ring) granuloma, a rare entity first described in lung and oral cavity, has been reported under various names before the identification of hyaline rings as fragments of pulses (the edible seeds of legumes). Similar lesions were thereafter described in extra-oral localizations, mainly the gastrointestinal tract, or localizations having potential communication with the gastrointestinal tract. Recently, 2 reports described "spiral bodies" surrounded by foreign body-type multinucleated giant cell reaction in pulse granulomas, corresponding to remnant plant vascular structures (helical xylem elements). In this article, we report a case of a 70-year-old male patient presenting to our hospital for an incisional hernia repair. He had a history of antrectomy 2 years previously for perforated duodenal ulcer complicated with fecal peritonitis. During the hernia repair procedure, multiple peritoneal whitish nodules and one subserosal appendiceal nodule were found. Appendectomy and biopsy of a peritoneal nodule were performed. Microscopic examination showed nodular lesions located in the subserosa to be pulse granulomas. Also surrounded by histiocytes, spiraled thin and rigid foreign bodies were identified. In this article, we report a case of pulse granuloma with spiral bodies complicating perforated duodenal ulcer and mimicking a peritoneal carcinomatosis. We also provide a discussion on the origin of spiral bodies in light of relevant literature.

Tumor necrosis factor receptor-associated factor 6 is required to inhibit foreign body giant cell formation and activate osteoclasts under inflammatory and infectious conditions.

Osteoclasts and foreign body giant cells (FBGCs) are derived from common progenitors and share properties such as multi-nucleation capacity induced by cell-cell fusion; however, mechanisms underlying lineage determination between these cells remain unclear. Here we show that, under inflammatory conditions, osteoclasts are stimulated in a manner similar to M1 macrophages, while formation of FBGCs, which exhibit M2-like phenotypes, is inhibited in a manner similar to that seen in M1/M2 macrophage polarization. FBGC/osteoclast polarization was inhibited by conditional knockout of tumor necrosis factor receptor associated factor 6 (Traf6) in adults in vivo and in vitro. Traf6-null mice were previously reported to die soon after birth, but we found that Traf6 deletion in adults did not cause lethality but rather inhibited osteoclast activation and prevented FBGC inhibition under inflammatory conditions. Accordingly, basal osteoclastogenesis was significantly inhibited by Traf6 deletion in vivo and in vitro and accompanied by increased bone mass. Lipopolysaccharide-induced osteoclast formation and osteolysis were significantly inhibited in Traf6 conditional knockout mice. Our results suggest that Traf6 plays a crucial role in regulating M1 osteoclast and M2 FBGC polarization and is a potential therapeutic target in blocking FBGC inhibition, antagonizing osteolysis in inflammatory conditions, and increasing bone mass without adverse effects in adults.

Intraconal gauze mass: An unusual complication of orbital fracture repair - a case report.

Gossypiboma and textiloma are terms used to describe tumor-like masses caused by retained gauze or surgical sponges after any operation. It is a rare surgical complication, usually difficult to diagnose due to its variable clinical presentation and nonstandard radiological appearance. We describe here a rare case of orbital gossypiboma in a child after surgical correction of an orbital blowout fracture.

Histological Evaluation of a Self-Expanding Stent-Graft 23 Months After Implantation in the Superficial Femoral Artery.

PURPOSE: To report histological examination of a Viabahn stent-graft implanted in the superficial femoral artery (SFA) for nearly 2 years. CASE REPORT: A 78-year-old man with peripheral artery disease was treated successfully with a 6.0×250-mm Viabahn self-expanding stent-graft in the right SFA, relieving his lower limb claudication. The patient died suddenly due to acute myocardial infarction 23 months later. Histological evaluation of the stent-graft implantation site revealed moderate neointimal proliferation at both proximal and distal edges of the device. In the middle part of the stent, significant macrophages and multinucleated foreign body giant cells had accumulated, although the stent was entirely patent. Furthermore, no endothelial cell coverage was found. CONCLUSION: Judging from these features, it might be necessary to continue dual antiplatelet therapy after stent-graft implantation over the long term to prevent thrombosis and subsequent restenosis or reocclusion.

Tumefactive foreign body giant cell reaction following high-pressure paint injection injury: A case report and review of literature.

High-pressure paint injection injury is an uncommon but well-described injury. The histologic features of long-term paint injection injury with retained material are less recognized. A 46-year-old male presented clinically as "recurrent giant cell tumor of tendon sheath." The right index finger demonstrated fusiform enlargement by a pigmented mass with diffuse infiltration into the soft tissue of the hand. Histologically the tumor showed multiple giant cells in a fibrotic stroma extending into the dermis. There were multiple types of foreign material including diffuse brown black pigment, weakly optically polarizing foreign material and white inclusions with a "train track" appearance. The cells were positive for CD68 and negative for S100 antigen. Further investigation revealed that the patient had a history of high-pressure paint injection injury to his digit 6 years prior. Foreign material injected under high pressure into tissues may result in a pseudo-neoplastic foreign body granulomatous reaction that can mimic giant cell tumor of tendon sheath. Our case demonstrates that this reaction can be florid and can have slow growth over years. A high index of suspicion, a good clinical history and careful examination can distinguish these 2 entities.

Histological Findings in Six Failed Metal-on-Metal Implants.

Although joint replacement surgery to relieve pain due to osteoarthritis is generally a successful operation, adverse local tissue reactions can occur in hip arthroplasty in patients who receive metal-on-metal (MoM) implants and lead to early failure. This has led to revisions, lawsuits, and manufacturing recalls. An understanding of the pathological process initiated by metal wear debris is essential in clinical surveillance of cases. We retrospectively reviewed six cases of patients who underwent MoM hip arthroplasties and required early revision. Tissue removed at revision surgery was analyzed histologically by two independent reviewers. All six patients (four males, two females) underwent revision hip arthroplasty after early failure. Revision occurred between 18 and 56 months after the index procedure. Four patients received MoM implants from Depuy, one from Stryker, and one from Wright Medical. A consistent array of pathological findings was associated with these failed MoM implants. Beginning with the development of metal debris, a histiocytic response and proliferation occurred with subsequent corrosion product formation. Membranes were formed, many with cellular infiltrates and pseudosynovial linings and often with ulceration and bleeding. The tissue also demonstrated lymphocytosis and perivascular infiltrates with atypical changes of the endothelial lining cells. Our findings document a predictable cascade of harmful local tissue changes initiated by metal debris in failed MoM hip arthroplasties.

Treatment of abdominal wall hernia with suture, or polypropylene, or collagen prosthesis.

PURPOSE: To develop an experimental model for incisional hernias and to compare morphological and functional aspects of hernia repairs by suture, polypropylene mesh and collagen mesh. METHODS: A defect measuring 7cm x 2cm was created in the anterior abdominal of 28 New Zealand male rabbits, divided into four groups (n = 7): (1) control, (2) suture of the anterior sheath of the rectus abdominal muscle, (3) setting of polypropylene mesh, and (4) setting of collagen mesh. On the 90th postoperative day, the animals were examined to verify the presence of incisional hernia. Samples of abdominal wall and scar were collected for histological study. RESULTS: Incisional hernia was identified in 85.7% of the control group, 57.1% of the suture group, 42.9% of the collagen mesh group, and none in the polypropylene mesh group (p = 0.015). Mesh exposure could be identified in 71.4% of the animals in group 3 and in no animal in group 4 (p = 0.021). The polypropylene mesh is effective in the treatment of abdominal wall defects, causing an intense inflammatory reaction. CONCLUSION: The collagen mesh is biocompatible, producing a minimal inflammatory reaction, but fails in the treatment of abdominal wall defects.