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.

Disseminated Scopulariopsis brevicaulis infection in an allogeneic stem cell recipient: case report and review of the literature.

A fatal case of disseminated Scopulariopsis brevicaulis infection in an allogeneic stem cell transplant recipient is described. The patient was initially thought to have pulmonary aspergillosis, on the basis of clinical signs and antigenaemia, but Aspergillus was not isolated by culture. Scopulariopsis brevicaulis was subsequently isolated from skin and then from sputum and stool. Further investigation revealed that the infection had spread from a primary pulmonary site to the skin. A review of the literature underscores the difficulty of diagnosing infections caused by such emerging fungal pathogens and the poor outcome of immunocompromised patients with non-Aspergillus mould infections.

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.

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.

[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.

[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.

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.

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.

Morphologic and functional development of whole human fetal stomachs grafted into nude mice.

To study in vivo the cellular differentiation and secretion of human developing fetal stomach, ethically and technically impossible to perform in utero, 256 fetal stomachs were xenografted. Human stomachs from 6- to 10-week-old fetuses were grafted for 1-273 days into nude mice. Biopsies for immunohistochemistry, hybridization and electron microscopy were taken and a catheter introduced into the human stomach. Macroscopic growth was fast and cells in S phase were numerous during the first 9 weeks, then the stomach size was stable and the gastric mucosa, of adult type, remained normal. In situ hybridization detected only a minute mouse mesenchymal chimerism in the graft. Chromogranin A, intrinsic factor and H+/K+ adenosine triphosphatase were immunohistolocally detected in epithelial cells 20 days after grafting, gastrin was detected after 30 days and pepsinogen after 60 days. The pH in gastric juice, which was at 8.0 +/- 0.1 from days 10-25, dropped from 4.39 +/- 1.80 at 30 days to 1.58 +/- 0.29 at 90 days. Intrinsic factor was stable and pepsin ranged from 6.8 +/- 7.8 to 134 +/- 51 units at 90 days. The differentiation of the epithelial cells in xenografts was very accelerated in comparison to that in utero.

[Sinobronchial syndrome]. / Le syndrome sinobronchique.

The sinobronchial syndrome consists of chronic sinusitis and chronic nonspecific inflammation of the lower airways, typically chronic bronchitis, bronchiectasis and diffuse panbronchiolitis. This airway disease of unknown etiology is not related to smoking. It is common in Japan and is poorly described in western countries. We report a case in a non-Asian patient. The known efficacy of long-term low-dose erythromycin therapy justifies careful diagnosis of sinobronchial syndrome in patients of non-Asian ethnic origin.

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.

[Formaldehyde fixation in the third millennium]. / La fixation formolée à l'aube du troisième millénaire.

This review deals with the general principles and problems of formaldehyde fixation. After a short description of 1) formaldehyde methods of production, 2) chemical properties of formaldehyde solution, and 3) kinetic of formaldehyde binding in tissue, formaldehyde reactivity with the tissue biopolymers, proteins and cucleic acids mainly, are described. How formaldehyde fixation of tissues adversely affects the reactivity of cellular proteins with their respective specific antibody and the ways the most commonly used retrieval techniques in immunohistochemistry act are, thereafter, discussed. Finally, concerns that need to be dealt with when formalin-fixed specimens are used for genomic analysis and studies of DNA expression are highlighted.

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.

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.

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.

Pathological fracture in non-ossifying fibroma with histological features simulating aneurysmal bone cyst.

A 12-year-old-girl presented with a fracture of an osteolytic lesion of the distal radius. A 7-year-old girl presented with a fracture of an osteolytic lesion of the femoral shaft. In both cases it was a non-ossifying fibroma with fracture misdiagnosed at pathology as aneurysmal bone cyst. Fractures through non-ossifying fibromas may alter the histological pattern of the initial lesion in two ways: firstly, by the presence of blood pigments due to the fracture, and secondly, by formation of new bone. Radiological-pathological correlation is essential to avoid histological errors after pathological fracture in a non-ossifying fibroma.