Molluscum contagiosum surrounded by a white halo and Sezary syndrome.

BACKGROUND: Molluscum contagiosum (MC) is caused by a DNA virus of the poxvirus group. It is common in children, and is also found in sexually active adults and HIV-seropositive patients. Cellular immunity is essential to controlling MC virus infection. We report the first observation of a patient with stage IV Sezary syndrome, who presented multiple molluscum contagiosum, spread and surrounded by a pale halo. CASE REPORT: A woman aged 70 presented with aggravation of Sezary syndrome diagnosed in 2009 and treated with topical corticosteroids. The examination showed a generalized pruritic exanthem and multiple flesh-coloured papules from 1 to 3 mm, spread over the entire skin surface and surrounded by a white halo. Histological examination of a lesion showed the presence of infected cells with intracytoplasmic inclusions infected in an acanthotic epidermis, surrounded by a melaninopenic hypomelanosis with a normal melanocyte density. There was no inflammatory character. The diagnosis of multiple molluscum contagiosum was given, the application of clobetasol propionate was suspended and treatment with chlorambucil 4 mg/day and prednisone 0.5 mg/kg/day was started. The evolution of the rash and pruritus was rapidly favourable. After 3 months, the rash and pruritus had regressed. There was no molluscum contagiosum or clear halo. CONCLUSION: We report the original observation of a patient with stage IV Sezary syndrome, who presented multiple molluscum contagiosum, spread and surrounded by a pale halo, without inflammation, eczema or disappearance of melanocytes. This halo could be due to the secretion of a protein by molluscum contagiosum inhibiting inflammation around this MC. To our knowledge, this phenomenon reported in a patient with severe atopic dermatitis associated with Sezary syndrome has not previously been described.

Molecular diagnosis of disseminated adiaspiromycosis due to Emmonsia crescens.

Emmonsia crescens is a saprophytic fungus that is distributed worldwide, causing diseases mostly in rodents. It has also been described, though rarely, as an etiologic agent of pulmonary pathology in humans, potentially leading to death. A case of pulmonary adiaspiromycosis is reported in a 30-year-old immunocompetent man. The patient presented with a history of several weeks of weakness, cough, fever, and weight loss of 10 kg. Clinical and radiographic findings showed pulmonary lesions consistent with tuberculosis or histoplasmosis, but no pathogen was found with classical microbiological procedures. The diagnosis of adiaspiromycosis due to Emmonsia crescens was initially made using molecular biology techniques. Histological observations subsequently confirmed the presence of adiaspores in granulomas. To our knowledge, this is the first case of adiaspiromycosis diagnosed by PCR and sequencing. The patient was treated with itraconazole and was seen at 1 month with symptomatic improvement. Here we will discuss this rare fungal infection and its difficult treatment and diagnosis. As represented in this case, molecular biology is a powerful method to optimize diagnostic tests and therefore improve the care of the infected patient.

Reactive nodular fibrous pseudotumor: a first report of gastric localization and clinicopathologic review.

Reactive nodular fibrous pseudotumor (RNFP) of the gastrointestinal tract is a distinct benign lesion, which could originate from a reactive proliferation of multipotential subserosal cells. This is the first case to be reported in the stomach. It was fortuitously discovered in a 60-year-old man with history of bulbar ulcer and gastritis. Gross examination revealed three lesions in the gastric wall and an adjacent lesion in the lesser omentum. Histologically, lesions were composed of a proliferation of spindle and stellate cells in a dense collagenic hyalinized background containing a mononuclear cell inflammatory infiltrate with numerous lymphoid aggregates and plasma cells with perivascular disposition. Immunohistochemistry showed staining for cytokeratins (AE1/AE3), vimentin and smooth muscle actin, without staining for the neurofilament and S100 proteins, synaptophysin, calretinin, CD117 (c-kit), CD34, desmin, caldesmon or anaplastic lymphoma kinase (ALK-1). Complete excision was performed, and no evidence of disease was found 4 months later. After analysing clinical, morphological and immunohistochemical features of this entity, the main differential diagnoses will be discussed, including calcifying fibrous pseudotumor, which shares morphological characteristics with RNFP, but which immunohistochemistry and the ultrastructural study suggest that it may be a result of another reactive process.

[A marginal zone-B cell lymphoma revealed by platelet satellitism and lympho-agglutination phenomenon around atypical lymphocytes]. / Satellitisme plaquettaire et lympho-agglutination exclusivement aux lymphocytes atypiques révélant un lymphome B de la zone marginale.

A 48-year-old man, with persistent pyrexia, presented with thrombocytopenia and lymphocytosis. The peripheral blood smears showed atypical lymphocytes and a platelet satellitism phenomenon around atypical lymphocytes associated to lympho-agglutination. Platelet satellitism was exclusively observed with atypical lymphocytes in EDTA-treated blood and at room temperature. This phenomenon was not observed when adding normal plasma and could be reproduced several times. Flow cytometry analysis of the peripheral blood, cytological and histological studies revealed a marginal zone-B cell lymphoma. The mechanism underlying platelet satellitism is not fully understood, but is likely to involve an immunologic binding of EDTA-dependent antiplatelet autoantibodies directed against the platelets glycoprotein IIb/IIIa complex. The association between platelet satellitism and lymphoma could also involve a monoclonal Ig secreted by lymphoma cells.

[Granuloma at the injection site of leuprorelin acetate: foreign body reaction to polylactic acid]. / Granulome sur le site d'injection de leuproréline retard: réaction à corps étranger à l'excipient?

BACKGROUND: Gonadorelin (LH-RH) analogues are used in urology, gynaecology and paediatrics. Sterile abscesses sometimes occur at the injection site although the underlying mechanism is poorly understood. CASE REPORT: A 72 year-old man presented weeping ulceration of the right buttock several days after the 9th intramuscular injection of an LH-RH analogue (leuprorelin SR 11.25 mg) for prostate cancer. There was no local reaction following the 10th injection but an abscess was observed at the injection site after the 11th injection. Screening for an infectious aetiology was negative. Histological examination of a skin biopsy specimen demonstrated granulomatous inflammation with a necrotic centre. Intradermal reaction to triptorelin, an LH-RH analogue containing no excipient, was negative. Intradermal reaction to leuprorelin SR, which contains lactic acid polymer, was positive with the appearance of an erythematous papule after 20 minutes, as well as demonstration of granulomatous reaction upon histological examination of a biopsy specimen obtained 10 days later. DISCUSSION: This case suggests a foreign body reaction to leuprorelin SR, or more probably to the lactic acid polymer excipient, as seen with Newfill (L-polylactic acid) used to treat lipoatrophy.

Quantitative analysis of the elastic fibres in the human temporomandibular articular disc and its attachments.

A quantitative study of the elastic fibres found in the human temporomandibular disc and its attachments was performed. Seven left discs from 57- to 82-year-old subjects, without macroscopic evidence of a TMJ disorder, were analysed and prepared in parasagittal sections. The surface amount was measured, thresholded and expressed from 0 to 1, using microscopic digitized views after Weigert's resorcin-fuchsin staining of elastic fibres. Fibre density rates ranged from 0 to 0.687. The mean density was 0.1532 (sigma=0.1150) in the upper bilaminary zone, 0.1097 (sigma=0.1159) in the lower bilaminary zone, 0.0474 (sigma=0.0782) in the anterior band, 0.0180 (sigma=0.0603) in the posterior band and null in the intermediate zone. The difference in density rate between the structures was significant, except for the posterior band and the intermediate zone. The elastic fibre density rates in central and medial locations of the upper and lower bilaminary zones were twice as big as in the lateral locations. In the anterior band, the elastic fibre density was less abundant medially than in its lateral part. These quantitative results support the current elastic fibre distribution scheme, and confirm the necessity of studying their orientation, taking into account age and temporomandibular joint health parameters.

The role of platelet-derived growth factor production by tumor-associated macrophages in tumor stroma formation in lung cancer.

Lung cancer is the most common cause of death by cancer in developed countries. Since a tumor cannot develop without the parallel expansion of a tumor stroma, a better understanding of its formation could lead to new therapeutical approaches. In this respect, since platelet-derived growth-factor (PDGF) is a chemotactic and growth factor for mesenchymal and endothelial cells, lung tumors of patients undergoing surgery for non-small cell lung cancer were evaluated for their replication rate using iododeoxyuridine incorporation, and for the expression of PDGF genes and the presence of PDGF A and B chains and of PDGF receptor alpha and beta subunits. This observation demonstrates that: (a) tumor cells and stroma mesenchymal cells, but not tumor-associated macrophages, display a high replication rate; (b) 1 of 3 tumors are characterized by cancer cells expressing the genes for PDGF A and/or B chains, while 1 of 2 tumors are composed of tumor cells presenting PDGF receptors alpha and beta subunits on their surface, and in only 1 of 6 tumors, tumor cells coexpress PDGF and its receptor; (c) in almost all tumors, tumor-associated macrophages express PDGF A and/or B chain genes; (d) mesenchymal cells, as well as endothelial cells, do not express PDGF A and B chain genes but do express PDGF receptor alpha and beta subunits; and (e) an ongoing active process was suggested in the periphery of the tumor by the simultaneous strong expression of PDGF A and B chain genes by tumor-associated macrophages and the high replication rate of mesenchymal and endothelial cells in the same area. Thus, PDGF is likely to have a limited autocrine role in tumor cell replication but is a potential player, in a paracrine fashion, in tumor stroma development.

Increased expression of the vascular endothelial growth factor is a pejorative prognosis marker in papillary thyroid carcinoma.

Vascular endothelial growth factor (VEGF) is a potent stimulator of endothelial cell proliferation. It has been implicated in tumor growth of human thyroid carcinomas. Using the VEGF immunohistochemistry staining score, we correlated the level of VEGF expression with the metastatic spread of 19 cases of thyroid papillary carcinoma. The VEGF immunostaining score, ranging from 0-9, was determined as the multiplication of a percentage of labeled thyrocytes score (0, no labeling; 1, <30%; 2, 31--60%; 3, >61% of labeled thyrocytes) and an intensity score (0, no staining; 1, weak; 2, mild; 3, strong staining). The mean score +/- SD was 5.74 +/- 2.59 for all carcinomas. The mean score for metastatic papillary carcinoma was 8.25 +/- 1.13 vs. 3.91 +/- 1.5 for nonmetastatic papillary cancers (P < 0.001). By discriminant analysis, we found a threshold value of 6.0, with a sensitivity of 100% and a specificity of 87.5%. There were no statistical differences between metastatic and nonmetastatic carcinomas when age, tumor size, or thyroglobulin levels were considered. The VEGF immunostaining score seems to be a helpful marker for metastasis spread in differentiated thyroid cancers. An increased production of VEGF could assess an aggressive disease and be the hallmark of a trend to produce metastasis. We propose the VEGF immunostaining score as a marker for the prognosis in differentiated thyroid cancers. A value of 6 or more, should be considered as at high risk for metastasis threat, prompting the physician to institute a tight follow up of the patient.

Blood monocyte chemotaxis.

Migration is a prerequisite for blood monocytes to exert their biological activities, since they have to migrate from blood into the tissues where they transform into macrophages. In vivo chemotaxis of blood monocytes is seldom evaluated, while their in vitro ability to migrate is frequently tested. The most frequently used test relies on BM migration through filters using modified Boyden chemotactic chambers. Using checkerboard analysis it is possible to define chemotactic and chemokinetic factors.

In situ hybridization for localization of mRNAs in mononuclear phagocytes in cell culture and tissue sections.

We report an in situ hybridization procedure to detect in cell preparations and tissue sections messenger RNAs coding for mononuclear phagocyte proteins. The multistep procedure is described for use in conjunction with isotopic and non-isotopic probes.

Host-donor interactions in healing of human split-thickness skin grafts onto nude mice: in situ hybridization, immunohistochemical, and histochemical studies.

The behavior of host and donor cell lines in human split-thickness skin grafts onto nude mice was studied by in situ hybridization (ISH) using genomic DNAs as probes, and immunohistochemically with species-specific or cross-species specific antibodies, at different stages ranging from day 3 to more than 1 year following grafting. Changes in the graft vascular and interstitial extracellular matrix were also assessed using species-specific or cross-species specific antibodies to human or murine type I, III, and IV collagens. Finally, transplant reinnervation was investigated using antibodies to various nerve cytoplasmic antigens and the thiocholine method to demonstrate acetylcholinesterase. Using these methods we were able to show the following: (1) the graft epidermis that is not replaced by mouse keratinocytes is progressively colonized by recipient Langerhans cells (LCs); (2) revascularization of the grafts begins soon by inoculation of the graft vessels with the host microcirculatory bed, and mouse endothelial cells growing into preexisting human capillary tubes produce a new basement membrane, prior to the replacement of the original one; (3) within 3-5 days following grafting, mouse fibroblasts migrate into the graft dermis. The density of the human and murine fibroblast populations then progressively increases. Characterization of the interstitial collagens identifies both human and murine type I and III collagens. Production of type III collagens decreases during the progression of fibrogenesis while human type I collagen becomes the predominant matrix protein; (4) transplant reinnervation is deficient, and neurites growing into severed graft nerve trunks were never detected.

Analysis of tissue chimerism in nude mouse brain and abdominal xenograft models of human glioblastoma multiforme: what does it tell us about the models and about glioblastoma biology and therapy?

In situ hybridization coupled to immunohistochemistry for antigens of interest allows unequivocal identification of tumor cells from reactive stroma cells and normal adjacent structures in human glioblastoma multiforme grafts transplanted into nude mice. With this methodology, we have explored the development of glioblastoma multiforme solid grafts transplanted into nude mouse brains or flanks. The brain transplants closely resembled the human situation, particularly in relation to differentiation and growth patterns. The morphological features of peritumoral reactive gliosis were similar to those observed in humans. A mouse glial stroma within the main tumor masses was also demonstrated. Kinetic studies showed that the compartment of isolated tumor cells that infiltrated host brains and the reactive gliosis constituted two cycling cell populations. Despite VEGF protein expression by tumor cells and some reactive astrocytes, the abnormally permeable microvascular beds were not hyperplastic. The observation of a non-infiltrative pattern of growth when grafts were established in host flanks demonstrated that the organ-specific environment plays a determining role in the growth and invasive properties of glioblastoma. The phylogenetic distance between man and mouse and the recipient immunoincompetence should not impose serious limitations on the use of this model for studying malignant glioma biology and therapy in vivo.

Successful reinfection of chronically infected mice by a different Toxoplasma gondii genotype.

It is generally assumed that primary infection by Toxoplasma gondii protects from reinfection. A recent study using a murine model has questioned this dogma using indirect procedures to detect the reinfecting strain. We have reinvestigated this issue using a transfected strain of T. gondii (Prugniaud beta galactosidase: Pru beta gal) which expresses Escherichia coli beta-galactosidase. Detection of enzyme activity on fixed parasites allows a direct distinction between transfected and untransfected strains. We have found that in OF1 mice primary infection with the 76 K strain of T. gondii fully protects mice against tissue cyst production upon reinfection with the Pru beta gal T. gondii strain whereas primary infection with the Pru beta gal T. gondii strain does not impair tissue cyst formation upon reinfection with the Ned strain of T. gondii, which belongs to another T. gondii genotype. These results suggest that the immune protection conferred by one strain of T. gondii can be breached by reinfection with a strain belonging to another genotype; which can have significant consequences in human or veterinary medicine.

Osteochondroma after pediatric hematopoietic stem cell transplantation: report of eight cases.

Eight children developed osteochondroma (OS) at a mean of 88 months after hematopoietic stem cell transplantation (HSCT). The mean age at HSCT was 56 months (12-84). This represents a cumulative incidence of 20% among patients less than 18 years of age transplanted from 1981 to 1997. These eight patients underwent allogeneic (n = 2) or autologous (n = 6) transplantation for either acute leukemia (n = 6) or neuroblastoma (n = 2) after a conditioning regimen including TBI (n = 7) or a combination of Bu and CY. OS was multiple in seven patients and solitary in one. Eight lesions were resected and all were benign. Four children received growth hormone before diagnosis of OS, but there was no clinical, radiological or histological difference between those who did not. Univariate analysis showed an increased rate associated only with autologous HSCT, with a 31.7% probability of a new OS at 12 years after HSCT. Osteochondroma should be added to the other adverse effects of HSCT in children.

Role of iron in lymphoma-induction by ATP.

Iron complexed by ATP induces lymphomas in mouse organs other than the specific targets of the lympho-adenitis provoked by sodium ATP: lymph nodes, spleen and liver. The reduction of life spans and the production of substantial volumes of ascites, that are lacking in the case of sodium ATP, are an index of the degree of malignancy of the induced lymphomas. On the basis of the known characteristics of iron-ATP complex of cellular calcium homeostasis alteration, the mechanism of these phenomena is discussed.

Iron- and aluminum-induced carcinogenesis.

Ferric and aluminum complexes with ATP have shown the induction of tumors in the site of subcutaneous injection, whereas sodium ATP has not. A concomitant but apparently independent phenomenon was a severe lymphoadenitis. The tumor calcium concentration showed an inverse relationship with the tumor growth rate. Carcinogenesis and lymphoadenitis are discussed considering well known effects of ferric and aluminum complexes with ATP on the cellular calcium homeostasis and of ATP on lymphatic tissue proliferation.

Resection followed by vascularized bone autograft in patients with possible recurrence of malignant bone tumors after conservative treatment.

In conservative treatment of malignant bone tumors, assessment of the local condition is difficult. The radiological changes seen in the irradiated tumor and the frequent occurrence of pathological fractures at this site may give rise to the fear that the tumor has relapsed. Resection of the whole of the involved bone is the best way to assure adequate local control but the extent of the bone defect and the bad local conditions secondary to irradiation make reconstruction hazardous. In two patients (one with Ewing's sarcoma of the femur and one with osteogenic sarcoma of the humerus) the authors used a free, vascularized fibular graft for the reconstruction having obtained consolidation of the limb after resection of the irradiated tumor, with preservation of its function. The encouraging results obtained have suggested a conservative attitude as primary treatment of specific malignant bone tumors.

[Ebstein's malformation in newborn infants. Apropos of 8 cases]. / La malformation d'Ebstein chez le nouveau-né. A propos de 8 observations

In relation with 8 cases, the features of Ebstein's malformation were studied in the neonatal form. In spite of its rarity, it should be recognized because of its peculiar prognosis, as it is liable to be permanently improved by medical treatment, after a difficult adaptation period. Besides, it is essential to distinguish it from other neonatal heart diseases which ressemble to it, but require an urgent surgical treatment.

[Neonatal aortic valvular stenosis. Apropos of 8 cases]. / La sténose aortique valvulaire à expression néonatale. A propos de 8 observations

Congenital aortic stenosis presenting in the neonate must be distinguished from the commoner hypoplastic left heart-syndrome, which is beyond surgical correction. It is certainly a serious problem, but early diagnosis and supporting angiography to rule out the presence of an associated left ventricular malformation and to check the volume of the left ventricular cavity should lead to a decision to operate. Out a 4 neonates from this series who were presented for surgery, the 2 survivors had good long-term results.

[Amplification of immunologic reactions using catalytic deposition at the reaction sites of tyramine derivatives. A decisive gain in sensitivity in immunohistochemistry and in situ hybridization]. / L'amplification des réactions immunologiques par dépôt catalytique aux sites de réaction de dérivés de la tyramine. Un gain décisif de sensibilité en immunohistochimie et en hybridation in situ.

In the catalyzed reporter deposition technique, horseradish peroxidase catalyzes the activation of conjugated phenolic compounds resulting in the covalent binding of the radicalized intermediates to electron rich moieties in the protein molecules present at the site of reaction. Comparing the biotinyl-, digoxigeninyl-, and fluoresceinyl-derivatives of tyramine and four immunohistochemical formats, we showed that the most sensitive detection system was that using biotinyl-tyramide and an immunohistochemical technique using a biotinylated secondary antibody followed by a streptavidin peroxidase. Amplification without background staining was obtained in most biotin rich tissues with digoxigeninyl-tyramide. With fluoresceinyl-tyramide, clear signal amplification was observed in the fluorescent microscope. Finally, when compared with standard methods, increased sensitivity was obtained with the fluorescent derivative for detection of hybridized sequences in interphase chromosomes.