Intravenous infusion of donor apoptotic leukocytes before transplantation delays allogeneic islet graft rejection through regulatory T cells.

AIM: This study describes the ability of intravenous donor apoptotic leukocyte infusion before islet transplantation to delay allogeneic graft rejection and implicates regulatory T cells (T(reg)) in the effect. METHODS: Allogeneic FVB (Friend virus B-type) islet transplants were placed under the kidney capsule of BALB/c recipient mice rendered diabetic by streptozotocin. Apoptotic donor leukocytes were infused intravenously 7 days before transplantation. Foxp3/DTR/GFP transgenic C57BL/6 mice were used as recipients to show depletion of T(reg) after apoptotic cell infusion. Control mice received islet transplants without apoptotic cells. RESULTS: The graft median survival time (MST) in recipient mice was 15±1.5 days when apoptotic cells were infused 7 days prior to transplantation of a 1000-islet-containing allograft and 6±0.5 days in the control mice (P<0.01). The same effect was observed using a 500-islet allograft, with an MST of 9±1.1 days vs. 3±0.8 days with and without (controls) apoptotic cells, respectively (P<0.01). This immunomodulatory effect was not observed when apoptotic cell administration was performed on the day of transplantation. Specific T(reg) depletion in Foxp3/DTR/GFP recipient mice inhibited the beneficial effect of apoptotic cell infusion with an MST of 8±1.5 days after apoptotic cell infusion vs. 2±0.2 days when T(reg) were depleted (P<0.01). Furthermore, T(reg) were specifically detected in the islet grafts of mice infused with apoptotic cells prior to islet transplantation. CONCLUSION: Infusion of donor apoptotic cells 7 days before allogeneic transplantation delays islet allograft rejection through a process involving T(reg).

Spinal cord compression complicating aseptic spondylodiscitis in ankylosing spondylitis.

Aseptic spondylodiscitis is a well recognized complication of ankylosing spondylitis. Neurological complications of such discovertebral lesions are uncommon. We report a new case with a diagnosis of T12-L1 spondylodiscitis which developed ten years after a spinal cord compression. Such neurological complications of aseptic spondylodiscitis may be explained by proliferative epidural tissue without predominant inflammatory infiltrates and also the development of new bone reaction, suggesting the contribution of mechanical factors.

[Kappa light chain deposition disease, presenting as Sjögren's syndrome, successfully treated by high-dose melphalan and autologous blood stem transplantation]. / Maladie de Randall, simulant une maladie de Gougerot-Sjögren, traitée avec succès par chimiothérapie et autogreffe de moelle osseuse.

INTRODUCTION: Light chain deposition disease is a systemic disorder characterised by tissue deposition of monoclonal immunoglobulin light chains without tinctorial properties. It has been exceptionally reported with salivary involvement mimicking Sjögren's syndrome and peripheral neuropathy. CASE REPORT: We report a case of light chain deposition disease associated with plasma cell dyscrasia presenting as sicca syndrome with salivary glands hypertrophy and polyneuropathy successfully treated by high dose melphalan and autologous blood stem transplantation. CONCLUSION: Light chain deposition disease should be recognized as an aetiology of sicca syndrome and peripheral neuropathy. Further studies should assess the prevalence of sicca syndrome in light chain deposition disease and better characterise the neurological manifestations.

Sarcoidosis occuring during anti-TNF-alpha treatment for inflammatory rheumatic diseases: report of two cases.

Anti-TNF-alpha agents have been tried in cases of refractory sarcoidosis, giving favourable results. Thus, the occurrence of a granulomatous disease in a patient receiving such drug seems paradoxical. We describe 2 patients with inflammatory rheumatic disease, the first with ankylosing spondylitis, the second with rheumatoid arthritis, under anti-TNF-alpha treatment (infliximab and etanercept respectively) who developed non-caseating granulomas of the lungs and lymph nodes consistent with the diagnosis of sarcoidosis. Limited and various similar cases have been reported. It is generally considered that these granulomatous diseases are related to the anti-TNF-alpha agent.

[Importance of human papillomavirus (HPV) screening in the follow-up after CIN2-3 treatment]. / Intérêt de la recherche du papillomavirus humain (HPV) dans le suivi post-conisation des CIN2-3. A propos de 386 cas.

INTRODUCTION: Cervical intraepithelial neoplasia (CIN) 2 and CIN3 lesions clearly represent precancerous states even if some of them would heal spontaneously. Management is based on surgical excision of part of the uterine cervix because such lesions can potentially progress into carcinomas. In most cases, this treatment leads to the cure of intraepithelial lesions. However, even after such an efficient treatment, theses patients are still at a higher risk of developing an invasive cervical cancer. That is why guidelines recommend a specific follow-up in order to screen for residual disease (incomplete excision) or for recurrences (after a complete excision). The actual problem in the follow-up strategy lies in the screening tools in use - cervical smears and colposcopy - whose sensitivities are low and hence, not quite sufficient when applied to a high risk population. These intraepithelial lesions are due to high risk human papillomaviruses (HPV) and there cannot be any lesion progression without HPV. Consequently, a viral testing would help in identifying a high risk subpopulation of women after cone loop cervical excision. MATERIAL AND METHODS: We studied, retrospectively, the contribution of HPV testing (Hybrid Capture 2((R))) in the follow-up after CIN2-3 treatment in 386 cone loop cervical excisions performed at a single centre during 80 months. RESULTS: Between three to six months follow-up after surgery, HPV remained present in 22.5% cases. The sensitivity of HPV testing in the screening for residual lesions or for recurrences was 100%, that of cervical smears cytology was 72%, whereas that of the pathological analysis of margins reached only 67%. The negative predictive value of a negative HPV detection associated with a normal cytology was 100%. DISCUSSION: Owing to its clinical relevance, HPV testing optimises postoperative follow-up and leads to the rapid and efficient selection of a subgroup, representing less than one upon three patients who are really at risk of an invasive lesion and to wholly reassure the others. Indeed, a negative HPV testing, associated with a normal cervical cytology, obtained after surgery correspond to a negative predictive value of almost 100% and this allows us to increase the time-interval between two screenings and to rapidly place the patient in a routine follow-up.

[Primary non-Hodgkin lymphoma of the uterine corpus. Case report and review of the literature]. / Lymphome malin non Hodgkinien primitif du corps utérin. A propos d'un cas et revue de la littérature.

We report a case of primary nonHodgkin lymphoma (NHL) of the uterine corpus, diagnosed by endometrial biopsy, in a 60-year-old patient suffering from uterine bleeding. Pathological analysis had concluded to diffuse large B-cell lymphoma. Further staging had not revealed other nodal or extranodal localization (Ann Arbor stage IE) and there were no signs of recurrence during follow-up. Therefore, the diagnostic criteria for true primary NHL of the uterine corpus were met. This localization is extremely rare since only six cases have previously been published. The patient was successfully treated by an immunochemotherapy combining rituximab-CHOP and rituximab-VCAP. After 28 months of follow-up, she is free from the disease. A review of the literature regarding these exceptional tumors is undertaken.

Incidence of amyloidosis over 3 years: the AMYPRO study.

OBJECTIVES: There is a lack of epidemiological information concerning amyloidosis, particularly in France. We started a 3-year prospective study (AMPYRO) to analyze the epidemiological features of amyloidosis in the eastern part of France. METHODS: From 2003 to 2005, all patients with a tissue sample showing amyloid deposits, were included in this study. Immunohistochemistry using anti-P component, anti-SAA, anti-light chains immunoglobulins and anti-transthyretin was applied for each tissue sample. For each patient, past and present medical histories along with biological features were recorded. RESULTS: Seventy-six patients with amyloid were identified over 3 years. The age-standardized incidence rate of amyloidosis was estimated at 14 cases per million person-years. The final entire population included in the AMYPRO study was composed of 66 patients with a mean age of 71.7+/-11.5 years old. The amyloid typing after clinical, biological and immunohistochemistry revealed senile amyloid in 40 cases (60.6%), AL amyloid in 13 (19.7%) and AA amyloid in 9 (13.6%). Neither clinical nor biological features differed significantly between the transthyretin-positive and transthyretin-negative populations. CONCLUSION: Regarding only tissue samples, senile amyloid was the most prominent amyloid type identified. Therefore, the clinician needs to be aware that in most of the amyloid cases identified on the pathologic examination there is no need for additional examination unless there are clinical or biological signs of a primary or secondary amyloidosis.

Comparison of AMPLICOR and Hybrid Capture II assays for high risk HPV detection in normal and abnormal liquid-based cytology: use of INNO-LiPA Genotyping assay to screen the discordant results.

The study was aimed to evaluate the feasibility of detecting human papillomavirus (HPV) in women with normal or abnormal cervical smears using the Roche Amplicor MWP HPV Test. We compared by AMPLICOR Test and Hybrid Capture II (HCII) Test, the prevalence of HR-HPV in 470 cervical samples including 55 samples with WNL cytology, 208 ASC-US, 193 LGSIL and 14 HGSIL. Samples with discordant results were retested with INNO-LiPA Genotyping HPV Test v2. The HR-HPV positivity in WNL cytology samples was similar (21.8%) by AMPLICOR and HCII. In ASC-US, the HPV positivity was 42.3% by both tests. In LGSIL, HPV positivity was 66.3% and 66.8% by AMPLICOR and HCII, respectively. In HGSIL, 92.8% of samples were positive by AMPLICOR and 85.7% by HCII. The agreement of both tests was 96.2% with a Kappa value of 0.92. Eighteen cases were discordant: 9 HCII positive/AMPLICOR negative and 9 HCII negative/AMPLICOR positive. The INNO-LiPA test revealed HPV positivity in every case. Interestingly, all HCII+/AMPLICOR- samples were found to harbour HPV53. As for the HCII-/AMPLICOR+ samples, 8 demonstrated a multiple infection with HR 16- and/or 18- and/or 56-phylogenetically related HPV types. Moreover, two of these samples were co-infected with HPV6 and two other with HPV54. By using consensus HR-HPV as our reference HPV positivity, the sensitivity (96.6%) and specificity (100%) of AMPLICOR was similar to that of HCII Test. The AMPLICOR HPV Test is sensitive, specific, feasible and appropriate for routine HPV detection.

[Orbitotemporal segmental neurofibromatosis]. / Neurofibromatose de type I segmentaire: à propos d'une localisation orbito-temporale.

INTRODUCTION: Neurofibromatosis is a rare pathology with heterogeneous clinical presentation. OBSERVATION: We report a case of a right orbitotemporal plexiform neurofibroma in a 64-year-old woman with von Recklinghausen's neurofibromatosis. A craniofacial CT scan, with injection, showed a heterogeneous tumor in front of the skull base and the temporoparietal bone with no intracranial extension but an extension into the maxillary sinus and nasal cavity. In summery, she presented orbitotemporal segmental neurofibromatosis type 1 because of the unilateral lesion. She had a first surgery to remove her jugal and preauricular tumor with an exenteration, which provided an eye histology. The histology found no Lisch nodules but a cellular proliferation causing choroidal hyperplasia. We noted neurofibromin on choroidal cells and normal cells in addition to pathologic cells (Schwann cells and melanocytes), meaning that two cell populations were obtained in the same tissue: a somatic mosaicism. DISCUSSION/CONCLUSION: We advance the hypothesis that there was a regulation of cellular growth in a particular microenvironment because of the absence of tumor. To identify and confirm the somatic mosaicism, we would need a FISH analysis (probes containing sequences of the NF1 gene with a probe specific for the chromosome 17 centromere).

Primary lymphoma of the lacrimal sac: an EORTC ophthalmic oncology task force study.

AIM: To define the clinical and histopathological characteristics of primary lacrimal sac lymphoma in a predominantly white population. METHODS: Specimens of lacrimal sac lymphoma and follow up data were solicited from members of the Ophthalmic Oncology Task Force of the European Organization for Research and Treatment of Cancer (EORTC) and the European Ophthalmic Pathology Society (EOPS). Specimens were stained with haematoxylin and eosin and an immunohistochemical panel against leucocyte antigens was applied. Diagnosis was reached by consensus of five experienced pathologists according to the World Health Organization classification system. The histopathological findings were correlated with the clinical data. RESULTS: Of 15 primary lacrimal sac lymphomas, five (33%) were diffuse large B cell lymphoma (DLBCL), five (33%) were extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT lymphoma), three were classified as "transitional MALT lymphoma," being in transition from MALT lymphoma to DLBCL, and two were unclassified B cell lymphomas. Nine of the patients were female, and the median age at the time of diagnosis was 71 years (range 45-95 years). The most frequent presenting symptoms were epiphora (85%), swelling in the region of the lacrimal sac (79%), and dacryocystitis (21%). All but one patient presented in stage I. Systemic spread occurred in three of nine patients (33%). The 5 year overall survival was 65%. CONCLUSIONS: DLBCL and MALT lymphoma are equally common in the lacrimal sac in contrast with the remaining periorbital and/or orbital region where MALT lymphoma predominates.

[Involvement of thyroid gland at non-Hodgkin lymphoma initial diagnosis: 2 pediatric cases]. / Goitre thyroïdien révélateur d'un lymphome non hodgkinien: à propos de 2 cas.

Extranodal thyroid lymphomatous involvement is rare in childhood. We report here 2 children, 1 with vertical transmission-acquired human immunodeficiency virus (HIV), presenting with lymphomatous infiltration of the thyroid gland at diagnosis. One child had infra-clinical endocrine impairment and both responded well to chemotherapy. Although the cases are too scarce to be affirmative, thyroid gland involvement doesn't seem to alter the good prognosis of childhood Burkitt's lymphoma. The third child's cancer in frequency is Non-Hodgkin Lymphomas. Presenting as the initial AIDS event in 1 patient, this case report also highlights the need to systematically propose antiretroviral therapy in vertically HIV infected children.

[Oncogenic osteomalacia: the role of the phosphatonins. Diagnostic usefulness of the Fibroblast Growth Factor 23 measurement in one patient]. / L'ostéomalacie oncogène : rôle des phosphatonines. Intérêt du dosage du fibroblast growth factor 23 démontré chez un malade.

INTRODUCTION: Oncogenic osteomalacia (OO) is a rare paraneoplastic syndrome characterized by severe hypophosphatemia induced by phosphaturic factors which are secreted by some tumors of mesenchymal origin. Fibroblast Growth Factor 23 (FGF-23) belongs to this family. Measurement of FGF-23 might improve the diagnosis of OO. EXEGESIS: We report the case of 71-year-old Caucasian man who had a history of severe osteomalacia with multiples fractures and extreme hypophosphatemia with hyperphosphaturia and normal serum calcium level. Serum FGF-23 was 199 RU/ml (N < 100 RU/ml). The tumor, detected by F-18 FDG PET/CT SCAN was localized in the mandible. Surgical removal of the tumor relieved all symptoms with normalization of serum phosphate levels within 3 days after surgery. CONCLUSION: We conclude that FGF-23 measurement is likely to be of considerable importance for facilitating early diagnosis of OO.

Oncogenic osteomalacia: diagnostic importance of fibroblast growth factor 23 and F-18 fluorodeoxyglucose PET/CT scan for the diagnosis and follow-up in one case.

A case of oncogenic osteomalacia is reported in a 71-year-old man who presented with bone pain, muscle weakness, and severe hypophosphatemia. The tumor which was localized in the left lower mandible was not detected by tomodensitometry, resonance magnetic imaging, and (111)IN-octreotide scintigraphy, but was easily localized by F-18 fluorodeoxyglucose PET/CT SCAN (F-18 FDG PET/CT SCAN). To our knowledge, the value of this technique for detecting tumors in oncogenic osteomalacia has never been reported. Secondly, this case provided an opportunity for confirming the usefulness of serum fibroblast growth factor 23 (FGF23) measurement for the diagnosis and follow-up. We conclude that FGF23 measurements combined with F-18 FDG PET/CT SCAN were decisive tools in a case of oncogenic osteomalacia and are likely to be of considerable importance for facilitating early diagnosis and follow-up in the future.

Detection of cervical precancer and cancer in a hospital population; benefits of testing for human papillomavirus.

The aim was to determine the relevance of human papillomavirus (HPV) testing in identifying high-grade cervical intraepithelial neoplasia or worse (CIN2/3+) in a hospital population (n=3574) characterised by a high rate of cytological abnormalities and high-risk HPV infections. According to the results of the initial Papanicolaou and HPV test, women were directly referred for colposcopy/biopsy or recalled for a control visit. Sensitivity and specificity were corrected for verification bias. HPV-testing sensitivity was 94.3%, higher than that of cytological testing at any cut-off point (65.1%-86.8%), while specificity was greater for cytology than for HPV testing (99.3% or 91.8% versus 83.4%). The combination of both tests allowed 100% sensitivity and negative predictive value. We conclude that HPV testing is a relevant tool for the detection of cervical disease. The best way of combining cytology and HPV detection in screening programmes should be evaluated in large-scale studies.

[Involvement of thoracic aorta revealing temporal arteritis. Three cases]. / Atteinte de l'aorte thoracique inaugurale de la maladie de Horton. A propos de trois cas.

INTRODUCTION: Temporal arteritis involves large vessels in 15% of cases. Their discovery is usually late, commonly several years after the diagnosis. EXEGESIS: We describe three cases of temporal arteritis with thoracic aorta involvement: two patients presented with aorta aneurysm which revealed temporal arteritis, one patient had aortic insufficiency. Clinical features of temporal arteritis were absent in two patients. Temporal artery biopsy, performed in two cases, was positive. Two patients were treated with corticosteroids, associated in one case with immunosuppressive agent. Surgery was necessary in all patients. CONCLUSION: Thoracic aorta involvement in Horton's disease is most often discovered when corticotherapy is decreased. Aneurysm rupture or aortic dissection in aortic affection are the major complication. Patient with thoracic aorta involvement need a clinical and radiological follow up over long period.

[Small intestinal stromal tumors with skenoid fibers. Clinicopathological study of three cases]. / Trois observations de tumeurs stromales de l'intestin grêle à fibres en écheveau.

Gastrointestinal stromal tumours (Gist) are mesenchymal tumour with uncertain prognosis occurring in the gastrointestinal tract wall. For clinicians, these tumours raise two problems: to establish the diagnosis and to determinate the future behaviour for the choice officient therapeutics. For the diagnosis the new marker c-KIT is useful. A new treatment with an inhibitor of c-KIT has given encouraging results. currently there is no consensus on specific cut-points to distinguish as low or high risk (i.e., malignant) Gist. For metastases-free Gist, the prominent histopronostic markers are size, mitotic index and localization of the tumour. The small intestine Gist have the reputation to be more aggressive than in other localization. Skenoid fibers in small intestine Gist could be a marker of good prognostic. The authors reported three cases of small intestine Gist with skenoid fibers. The discussion point out the significance of this particular morphological aspect.

Intracerebral alveolar echinococcosis.

There are two species of the genus Echinococcus, Echinococcus multilocularis (also called alveolar hydatid) and Echinococcus granulosus, characterized by distinct growth features in humans. The main endemic regions for human alveolar echinococcosis (AE) caused by E. multilocularis are Central Europe, Russia, Turkey, Japan, China, eastern France and North America. Human echinococcosis is usually caused by an intrahepatic growth of parasitic larvae. Cerebral occurrence of E. multilocularis disease is rare, accounting for only 1% of cases, and is generally considered to be fatal. This report presents two cases of intracerebral E. multilocularis disease which occurred in two infected patients with AE pulmonary metastases. The anatomical and clinical features are discussed. Our retrospective survey would indicate that surgical treatment should be envisaged whenever possible.