Expression of the beta chemokines CCL3, CCL4, CCL5 and their receptors in idiopathic inflammatory myopathies.

The idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases characterized by chronic lymphocytic and macrophagic infiltration in muscle. Because the mechanism for recruitment of these cells probably involves chemokines, we focused on the study of the expression pattern of some beta chemokines and receptors because it may provide a basis for selective immunotherapy. The expression of CCL3 (MIP-1alpha), CCL4 (MIP-1beta), CCL5 (RANTES) and their main receptors (CCR1 and CCR5) was studied by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry in a series of 16 IIM and five controls (four normal muscles and one tonsil). Except for CCL5, strong expression was observed by RT-PCR with all molecules in all IIM subtypes in comparison to control muscle. Immunohistochemistry revealed diffuse CCL4 expression in all vessels in dermatomyositis. In both polymyositis and sporadic inclusion body myositis (s-IBM) it was restricted to vessels in the vicinity of inflammatory exudates. CCL5 expression was low, restricted to a few inflammatory cells in all IIM; CCR1 expression was mainly restricted to macrophages and s-IBM endothelial cells, whereas CCR5 was localized in inflammatory cells invading non-necrotic muscle fibres. Expressions of both receptors were also recorded in few muscle fibres. In conclusion, the upregulation of beta chemokines and receptors in IIM and their differential expression by various cells may contribute to chronic inflammation and to the peculiar distribution of inflammatory exudates in these diseases.

Class I MHC detection as a diagnostic tool in noninformative muscle biopsies of patients suffering from dermatomyositis (DM).

This study is to further confirm the diagnostic value of class I MHC detection in muscle biopsies of adult patients presenting with clinical features of dermatomyositis (DM) and to address its diagnostic value in the case of nonspecific biopsies. A retrospective study was performed on muscle biopsies in 22 patients presenting with clinical features of DM. Immunohistochemical detection of class I MHC was performed in all cases. On pathological features two groups of patients were recorded: group I (14 patients) with typical features of DM and group II (eight patients) with almost normal muscle biopsies (no inflammatory exudates, no perifascicular atrophy). Abnormal sarcolemmal class I MHC expression was recorded in all cases. In all muscle biopsies of group I patients, class I MHC expression was observed in almost all fibres but was stronger in perifascicular areas (eight patients) or was restricted to perifascicular atrophic fibres (six patients). In all muscle biopsies of group II patients, only some perifascicular fibres expressed class I MHC. According to Bohan and Peter criteria, patients were classified as definite DM (nine group I and three group II patients), probable DM (five group I and two group II patients) and possible DM (three group II patients). Abnormal perifascicular class I MHC expression is of diagnostic value in patients presenting with clinical features of DM especially when muscle biopsy fails to show typical features such as inflammatory infiltrates and/or perifascicular atrophy.

[Dermatomyositis and polymyositis]. / La dermatomyosite et la polymyosite.

Dermatomyositis (DM) and polymyositis (PM) are the two main forms of idiopathic inflammatory myopathies. They have in common a proximal muscle weakness, but skin manifestations, juvenile forms and increased incidence of malignancies are clinical characteristics of DM. The follow up of creatine-kinases is the best biological test in spite of their possible normality. The significance of antibodies titers is uncertain, except the association Jo-1 interstitial and lung disease indicating a poor prognosis. The association with HLA haplotypes expresses a genetic predisposition of a dysimmunity to develop DM or PM. Pathological changes are well known with a humoral immune effector mechanism in DM, and a muscle fibre aggression by CD8 + T cells in PM. Non inflammatory forms of DM and PM and rhabdomyolytic forms of PM are not very rare, they are recognized by the HLA class 1 immunoreactivity. Pathophysiological processes involve muscle fibers, inflammatory cells and endothelial cells of capillaries, with a complex intervention of cytokines, adhesion molecules, MHC classe 1, membrane attack complex, anti endothelial cells antibodies, perforin secretion and sometimes apoptotic Fas-mediated mechanisms. Despite these recent advances, causal antigens and activator processes of endothelial cell lysis and autoinvasive cytotoxicity of muscle fibers remain to be identified.

[American pulmonary histoplasmosis. Prospective study with 232 soldiers after a 2-year assignment in Guiana]. / Histoplasmose pulmonaire americaine. Etude prospective chez 232 militaires ayant effectue un sejour de 2 ans en Guyane.

The purpose of this report is to describe the results of a prospective study on pulmonary histoplasmosis in French Guiana. Chest radiographs were performed in 232 French legionnaires returning from a two-year assignment in French Guiana. Further examinations were performed in a total of 8 subjects in whom chest radiographs demonstrated the presence of nodules in the lungs. No evidence of cancer or tuberculosis was found. Findings confirmed histoplasmomas in two cases and demonstrated probable histoplasmosis nodules in 6 cases including three involving calcified lesions. Five of these eight patients had been in high-risk rain forest environments. Pulmonary histoplasmosis should be considered as a possible diagnosis in subjects returning from endemic zones. Confirmation depends on a spectrum of findings. Calcified nodules require only radiographic surveillance with follow-up at six months. Non-calcified nodules require further investigation including CT-scan, bronchoscopy, and serological tests. Surgical biopsy may be necessary to achieve exact histological and mycological identification of the lesion and is recommended in smokers.

[Atypical acral hyperkeratosis in a black woman]. / Hyperkeratose acrale atypique sur peau noire.

This report describes the case of a 33-year-old black woman who presented atypical hyperkeratosis. Atypical features included location on the dorsum of the foot and presence of punctate pits. The lesion was classified as intermediate between keratosis punctata of the palmar creases and focal acral hyperkeratosis. The main elements of differential diagnosis are Hyperkeratosis lenticularis perstans and punctuated porokeratosis. The clinical and histological features of these lesions are discussed based on a review of the literature. Therapy including application of topical emollients is problematic.

CCR2A and CCR2B, the two isoforms of the monocyte chemoattractant protein-1 receptor are up-regulated and expressed by different cell subsets in idiopathic inflammatory myopathies.

The idiopathic inflammatory myopathies (IIM), including dermatomyositis (DM), polymyosititis (PM) and inclusion body myositis (IBM), are a group of autoimmune diseases characterized by chronic lymphocytic and macrophagic infiltration in muscle. The mechanism for recruitment of these cells probably involves chemokines. We have previously reported that monocyte chemoattractant protein-1 (MCP-1), a beta chemokine, seems to play a major role in mononuclear cell recruitment especially in DM. Here we have investigated the distribution of the main MCP-1 receptors CCR2A and CCR2B in IIM by polymerase chain reaction (PCR), immunohistochemistry and in situ hybridization. We have shown by reverse transcription-PCR that both CCR2A and CCR2B were expressed at low level in normal muscle and that CCR2A was up-regulated in IIM (P=0.02) and was higher in PM and IBM than in DM (P=0.04). By immunohistochemistry and in situ hybridization we have observed that CCR2 isoforms were expressed by different cell subsets in both normal and IIM muscle. CCR2A was expressed in vessel walls and by some mononuclear cells, especially in cells involved in partial invasion in PM and IBM. CCR2B expression was observed in all satellite cells, in the muscular domain of neuromuscular junctions and in some regenerative fibers of IIM, but not in inflammatory exudates. In conclusion, the present study highlights the major role played by MCP-1 and its counter-receptor CCR2 in the pathophysiology of IIM, and shows that the CCR2 receptors are cell specific. The variation of the total amount of CCR2A and its local distribution according to the type of IIM might be a new path towards the understanding of the constitution of mononuclear infiltrates in IIM.

Prognostic factors in intracranial ependymomas in children.

OBJECT: The occurrence of intracranial ependymomas in children is relatively infrequent, and their prognostic factors are still controversial, especially regarding histological composition. METHODS: A retrospective study was conducted of 37 children treated during the last 20 years for intracranial ependymomas at the Hôpital de la Timone. Both univariate and multivariate statistical analyses were performed to assess the prognostic relevance of patient age and sex, extent of tumor removal, location of the tumor (supratentorial compared with infratentorial, median compared with lateral), tumor histological composition, and adjuvant therapies in affecting the 5-year progression-free survival (PFS) rate and overall survival (OS) rate. The following histopathological features, either alone or in combination, were analyzed: endothelial proliferation, necrosis, loss of differentiating structures (present compared with absent), the number of mitotic figures per 10 hpf, and cellularity (number of nuclei/5 hpf). In addition, immunohistochemical detection of Ki-67 antigen was performed and the Ki-67 labeling index (LI) evaluated in all cases. The 5-year OS and PFS rates were 45% and 25%, respectively (median follow up 34 months). Four patients died of disease without remission (median 163 days) and disease in 21 patients relapsed: 18 in situ and three both in situ and distantly. On univariate analysis total surgical resection and median infratentorial location were associated with a better outcome (p < 0.002) for both OS and PFS. Loss of differentiating structures was associated with poor prognosis (p < 0.008) and the combination of necrosis, endothelial proliferation, and mitotic index greater than 5 was also a negative predictive factor for both OS (p < 0.002) and PFS (p = 0.02). The PFS time was shorter in patients younger than 4 years of age and in patients in whom a Ki-67 LI greater than 1 was found (p = 0.03 and 0.006, respectively). Adjuvant radiotherapy and chemotherapy were not relevant to prognosis. Moreover, among the 15 patients in whom total excision was achieved, OS was better in those who did not receive adjuvant therapies. In contrast, adjuvant therapies significantly enhanced PFS time in patients in whom tumor excision was incomplete. CONCLUSIONS: This study and analysis of the literature further highlight that total tumor removal is the treatment of choice for ependymomas in children. Postoperative measurement of residual tumor is required, especially because a subgroup of patients might be treated by surgery alone. Median infratentorial ependymomas have to be distinguished from the lateral type. Appropriate and reproducible histological parameters and Ki-67 LI are of interest as predictors of outcome.

p16INK4a and p19INK4d mRNA expression in neuroglial tumours: correlation with Ki67 proliferation index.

The INK4a-ARF locus encodes two unrelated proteins that both function in tumour suppression: p16INK4a and p19INK4d. Although p19INK4d expression has not been studied in central nervous system (CNS) tumours, it has been reported that p16INK4a inactivation is involved in the growth of glioblastomas. This observation has not been reported in relation to other CNS tumours. To understand further the role of p16INK4a and p19INK4d in neuroglial tumour growth, expression of both p16INK4a and p19INK4d mRNAs was studied by reverse transcription polymerase chain reaction RT-PCR in 59 neuroglial tumours, in which Ki67 labelling indices (LI) were also determined. P16INK4a mRNA was found in all pilocytic astrocytomas (7/7), in all grade II and III astrocytomas (7/7 and 4/4, respectively), in 4/12 glioblastomas, 8/8 oligodendrogliomas, 10/11 anaplastic oligodendrogliomas, 4/7 ependymomas and 3/3 anaplastic ependymomas but not in normal brain. In contrast, p19INK4d mRNA was detected in all tumours and control tissues. p16INK4a expression was associated with a low Ki67 LI in glioblastomas but not in other tumours. P16INK4a expression was not related to anaplasia in oligodendrogliomas and ependymomas. In tumours expressing p16INK4a, in situ hybridization showed a widespread expression of p16INK4a mRNA in tumour cells and in foci of microvascular proliferation. These results strongly support the concept that p16INK4a is involved in the regulation of proliferation in glioblastomas. Other cell cycle regulators which are yet unknown may also play a role in the control of oligodendrogliomas or ependymomas outgrowth. Further studies are required to evaluate the role of p19INK4d in neuroglial tumours.

[Ewing's sarcoma of the soft tissues: apropos of 3 cases and review of the literature]. / Sarcome d'Ewing des parties molles: à propos de 3 cas et revue de la littérature.

Three cases of extraosseous Ewing sarcoma are reported. This pathology of the young adult is very rare as shown by the review of the literature. Clinical or imaging (CT or MRI) findings are non-specific and diagnosis is based on histology. Nonetheless, this diagnosis should be considered in all patients with primary soft tissue tumors.

[Hamartomatous adiposity of the thyroid]. / Adipose hamartomateuse de la thyroïde.

Report of one case of hamartomatous adiposity of the thyroid gland. Only eight cases have been reported. The lesion is composed of thyroid tissue and mature adipose elements. Previously reported cases are reviewed and the pathogenesis is discussed.

[Helminth diagnosis in pathologic anatomy]. / Le diagnostic des helminthes en anatomie pathologique.

Most publications devoted to diagnosis of helminths emphasize characteristic parasitological features. Histological feature are seldom described in detail. The purpose of this study was to propose a diagnostic method suitable for use by histologists who, unlike parasitologists, do not visualize the whole worm but rather pieces randomly scattered over a slide. It is relatively easy to distinguish helminths which have smooth muscle, no respiratory or circulatory system, and no coelom from arthropods which have striated muscle, both respiratory and circulatory systems, and coelom. At the adult stage, roundworms or nemathelminths present an external cuticle that may have patterned markings. The visceral cavity is empty. Adults can dwell either in the intestine in which case they are oviparous (oxyuris, ascaris, Ancylostoma, Strongyloides stercoralis, Trichuris...) or in tissue in which case they are viviparous (filaria). Larva of some species can be found in tissues. Adult tape-worms are devoid of cuticle and have a mesenchymatous visceral cavity. Cestodes which are segmented and have no digestive tract (taenias) are readily distinguishable from trematodes which are not segmented and have a digestive tract (faciolasis) Some cestodes unable thrive in man can cause cyst formation (hydatidosis, sparganosis, cysticercosis, coenurosis). On the basis of symptoms and histological features, it is usually possible to diagnose the genus and even the species of the offending helminth provided that the parasite has not been excessively damaged and that a sufficient number of sections are available.