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.

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.

Biomimetic coatings for bone tissue engineering of critical-sized defects.

The repair of critical-sized bone defects is still challenging in the fields of implantology, maxillofacial surgery and orthopaedics. Current therapies such as autografts and allografts are associated with various limitations. Cytokine-based bone tissue engineering has been attracting increasing attention. Bone-inducing agents have been locally injected to stimulate the native bone-formation activity, but without much success. The reason is that these drugs must be delivered slowly and at a low concentration to be effective. This then mimics the natural method of cytokine release. For this purpose, a suitable vehicle was developed, the so-called biomimetic coating, which can be deposited on metal implants as well as on biomaterials. Materials that are currently used to fill bony defects cannot by themselves trigger bone formation. Therefore, biological functionalization of such materials by the biomimetic method resulted in a novel biomimetic coating onto different biomaterials. Bone morphogenetic protein 2 (BMP-2)-incorporated biomimetic coating can be a solution for a large bone defect repair in the fields of dental implantology, maxillofacial surgery and orthopaedics. Here, we review the performance of the biomimetic coating both in vitro and in vivo.

Effects of adsorbed proteins and surface chemistry on foreign body giant cell formation, tumor necrosis factor alpha release and procoagulant activity of monocytes.

The adhesion and activation of monocytes and macrophages are thought to affect the foreign body response to implanted medical devices. However, these cells interact with devices indirectly, because of the prior adsorption of proteins. Therefore, we preadsorbed several "model" biomaterial surfaces with proteins and then measured foreign body giant cell (FBGC) formation, tumor necrosis factor alpha (TNFalpha) release, and procoagulant activity. The model surfaces were tissue culture polystyrene (TCPS), untreated polystyrene (PS), and Primaria, whereas the proteins used were albumin, fibronectin, fibrinogen, and immunoglobulin. FBGC formation, TNFalpha release, and procoagulant activity of monocytes were the highest for surfaces preadsorbed with IgG. FBGC formation was lower on surfaces with adsorbed fibrinogen and fibronectin than on uncoated surfaces. TNFalpha release and procoagulant activity of monocytes were similar on surface adsorbed with fibrinogen, fibronectin, or albumin. Monocyte activation was also affected by the surface chemistry of the substrates, because FBGC formation was the highest on PS and the lowest on TCPS. Monocyte procoagulant activity was the highest on Primaria. Adsorbed proteins and surface chemistry were found to have strong effects on FBGC formation, monocyte TNFalpha release, and procoagulant activity in vitro, providing support for the idea that these same variables could affect macrophage-mediated foreign body response to biomaterials in vivo.

Cytokine receptor profile of arthroplasty macrophages, foreign body giant cells and mature osteoclasts.

In the arthroplasty pseudomembrane surrounding a loose prosthesis there is a marked macrophage and foreign body giant cell (FBGC) response to implant-derived wear particles. These cells contribute to the osteolysis of loosening by releasing cytokines and growth factors which influence the formation and activity of osteoclasts. Using a panel of monoclonal antibodies directed against known cytokine/growth factor receptors, we have determined by immunohistochemistry whether arthroplasty macrophages, FB-GCs and osteoclasts express receptors for cytokines and growth factors that are known to modulate osteolysis. All these cell types reacted with antibodies directed against the following cytokine/growth factor receptors: gp130, IL-1R type 1, IL-2R, IL-4R, IL-6R, TNFR, M-CSFR, GM-CSFR and SCFR but not with antibodies directed against IL-3R and IL-8R. Arthroplasty macrophages, FBGCs and osteoclasts thus show a similar pattern of cytokine/growth factor receptor expression. This reflects the fact that arthroplasty macrophages are capable of osteoclast differentiation and that these cell types form part of the mononuclear phagocyte system. As regards the osteolysis of aseptic loosening, it also indicates that these cells are targets for numerous cytokines and growth factors which influence osteoclast formation and bone resorption.

Multinucleated giant cells in thyroid neoplasms. A cytologic, histologic and immunohistochemical study.

OBJECTIVE: To evaluate the presence of multinucleated foreign body-type giant cells (MGCs) in papillary carcinoma (PC), follicular variant of papillary carcinoma (FV) and follicular adenomas (FA) and to investigate their origin by immunoperoxidase studies. STUDY DESIGN: The cytologic and histologic material of 10 PCs, 8 FVs, and 11 FAs were evaluated for the presence of MGCs. The immunohistochemical staining pattern of MGCs in paraffin-embedded tissue was studied using cytokeratin, epithelial membrane antigen, thyroglobulin, vimentin, A-1 antichymotrypsin, lysozyme and CD68. RESULTS: MGCs were demonstrated in 10/10 PCs, 5/8 FVs and 0/11 FAs. In the immunostained sections, MGCs were negative for epithelial markers and positive for histiocytic markers. CONCLUSION: These results indicate that MGCs are histiocytic and frequently present in PCs and FVs and usually absent from FAs.

Ultrastructure of multinucleated giant cell apoptosis in foreign-body granuloma.

To elucidate the role of apoptosis in the disappearance of multinucleated giant cells from the granulation tissue in cases of foreign-body granuloma, we induced a foreign-body reaction by implanting a collagen sponge into the dorsum of the rat and observed apoptotic changes within the multinucleated giant cells using electron microscopy. Two types of multinucleated giant cells were identified presenting apoptotic characteristics morphologically. One was characterized by apoptosis of only one nucleus, followed by cytoplasmic changes, rupture of the plasma membrane and necrosis evoking an inflammatory reaction. The other showed typical apoptotic changes in the majority or in all of the nuclei, followed by phagocytosis of the apoptotic syncytia. The results of the present study suggest that apoptosis occurring within only one nucleus might be triggered by overexpression of the p53 protein, because DNA abnormalities are confined to this single nucleus. In contrast apoptosis occurring simultaneously in the majority or all of the nuclei is most probably due to cell death caused by senescence.

Paramyxovirus-like nuclear inclusions identical to those of Paget's disease of bone detected in giant cells of primary oxalosis.

Nuclear inclusions, identical to those characteristic of Paget's disease of bone, were observed in giant cells in four of eight cases of primary oxalosis. The giant cells containing nuclear inclusions were directly involved in phagocytosis of large oxalate crystals in the context of typical foreign body granulomas in the bone marrow. Cytochemically, all of them exhibited strong tartrate-resistant acid phosphatase activity, and a proportion of them also tartrate-resistant acid ATPase. The inclusions consisted of typical arrays of filamentous material as described in Paget's disease, admixed with variable proportions of electron-dense material closely reminiscent of nucleolar pars fibrillaris and fibrillary centres. These data indicate: (a) the occurrence of Paget-like inclusions in a bone disease unrelated to Paget's disease, not causally related to viral infection, and resulting from an inborn metabolic derangement; and (b) the occurrence of Paget-like inclusions in foreign body giant cells as opposed to osteoclasts. We suggest that the occurrence of paramyxovirus-like nuclear inclusions in either osteoclasts or giant cells may represent an epiphenomenon of cell fusion and giant cell formation whenever appropriate stimuli act on latently infected precursor cells. Furthermore, our data suggest that nucleoli may represent the specific site of virus-like inclusion formation.