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Biomedical subjects

J Hassoun

Publications and source records attributed to J Hassoun.

At least 19 recordsLinked to original sources

[Standards, Options and Recommendations 2004: good practice guidelines for second opinion in anatomic and surgical pathology in oncology (integral report)].

CONTEXT: The " Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the French Federation of Cancer Centres (FNCLCC), the 20 French Regional Cancer Centres, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. OBJECTIVE: To develop good practice guidelines for second opinion in anatomic and surgical pathology in oncology, in collaboration with the French Society for Anatomic and Surgical Pathology. METHOD: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs using the definitions of the Standards, Options and Recommendations project. Once the guideline has been defined, the document is submitted to independent reviewers for review. RESULTS: The working group defined four types of second opinions in anatomic and surgical pathology: personal consultation, inter-institutional consultation, peer review consultation for a scientific survey, intra-departmental consultation in the context of quality control. The main recommendation is that second opinion should respect the patients' rights and the medical ethics code. For each of the four situations defined recommendations have been developed, taking this principle into consideration.

Ethics, Medical↗

Expression of a model gene in prostate cancer cells lentivirally transduced in vitro and in vivo.

In a preclinical model for prostate cancer gene therapy, we have tested lentiviral vectors as a practical possibility for the transfer and long-term expression of the EGFP gene both in vitro and in vivo. The human prostate cancer cell lines DU145 and PC3 were transduced using experimental conditions which permitted analysis of the expression from a single proviral vector per cell. The transduced cells stably expressed the EGFP transgene for 4 months. After injection of the transduced cell populations into Nod-SCID mice a decrease in EGFP was only observed in a minority of cases, while the majority of tumors maintained transgene expression at in vitro levels. In vivo injection of viral vector preparations directly into pre-established subcutaneous or orthotopic tumor masses, obtained by implantation of untransduced PC3 and DU145 cells led to a high transduction efficiency. While the efficiency of direct intratumoral transduction was proportional to the dose of virus injected, the results indicated some technical limitations inherent in these approaches to prostate cancer gene therapy.

Animals↗

Characterization of Hodgkin's lymphoma-like undifferentiated carcinoma of the nasopharyngeal type as a particular UCNT subtype mimicking Hodgkin's lymphoma.

Undifferentiated carcinoma of the nasopharyngeal type (UCNT) that histologically mimics Hodgkin's lymphoma (HL) ("Hodgkin's lymphoma-like UCNT"--HL-like UCNT) is known as a diagnostic pitfall. Using immunohistochemistry, Western blot and cDNA array technology, we wanted to document its phenotypical and molecular characteristics. We report herein 5 cases of UCNT that morphologically mimic HL and 3 classical UCNT cases. We compared the expression profiles of a thousand selected genes in HL-like UCNT and in classical UCNT cases. No difference in the profile of EBV infection was noted between the HL-like UCNT and control cases. Significant differences were detected in the expression of genes involved in the matrix modelling, angiogenesis, apoptosis and regulation of the Th-2 interleukins. The eosinophil chemoattractant eotaxin was expressed in the stroma of HL-like UCNT, but not in the control cases. The eotaxin receptor CCR3 was expressed in both stromal and carcinoma cell populations of HL-like UCNT, this pattern being similar to the one observed in HL. These results show that UCNT morphologically resembling HL share also some specific phenotypical and molecular features with HL, and might deserve to be isolated as a particular UCNT subtype.

Apoptosis↗

[Juvenile aponeurotic fibroma. A case report with a review of the literature].

Juvenile aponeurotic fibroma is a rare benign tumour which occurs mainly in young patients under 20 years of age and especially during childhood. Clinical presentation is a unique, hard and painless tumour of the palm or sole. The treatment commonly accepted for this locally recurrent tumour is complete excision with function preservation. In this paper, we report on a case of juvenile aponeurotic fibroma of the thenar area with a thickening of the first metacarpal bone shaft. Bone involvement in juvenile aponeurotic fibroma is a very rare condition. We only found one report of a comparable case in literature.

Adolescent↗

A Nod Scid mouse model to study human prostate cancer.

Prostate cancer is the second cause of cancer mortality in men in Western countries. To study new therapeutic approaches such as gene therapy, animal models of human prostate cancer with metastatic behavior are mandatory. We used the Nod Scid mouse strain to develop an orthotopic animal model. Two androgen-independent cell lines (PC-3 and DU 145) were used. Local tumor growth and metastases were analyzed. The tumor take rates were close to those reported in the literature. However, a high frequency of various metastatic sites has been observed (liver, lung, spleen, adrenal, kidney, lymph node, and diaphragm). It can be concluded that the Nod Scid mouse is a relevant preclinical animal model to study human prostate cancer. Metastatic sites seem more numerous in comparison to other orthotopic mice models described.

Adenocarcinoma↗

Caspases: conductors of the cell death machinery in lymphoma cells.

The present review focuses on recent insights into the regulation of caspases by other components of the apoptotic pathway, including the mechanisms by which caspase activation influence the death of lymphoma cells. In the light of our recent findings and similar observations of other investigators, it is likely that lymphoma cells possess the complete caspase machinery required for the apoptotic process. Inhibition of caspases activation appears as a potential mechanism to explain apoptotic defects of malignant B-cells, and thus may constitute the basis for new cancer therapies.

Apoptosis↗

Vertebral metastases from pineoblastoma.

Two male patients aged 26 and 18 years presented with vertebral metastases originating from pineoblastomas on which surgery had been performed 8 years and 5 months earlier, respectively. In the first case in which the metastasis developed in the T8 corpus, the disease is presently under control after high-dose chemotherapy and autologous blood stem cell transplantation. The second patient (sacral metastasis), despite aggressive adjuvant therapy, died 2 years after the last operation because of spinal seeding. These uncommon cases are discussed with reference to the literature on extraneural metastases that originate from neuroepithelial tumors of the central nervous system.

Adolescent↗

[Medical demography: the portrait of pathologic anatomy and cytology].

Assessment of care supply in terms of medical labor force is difficult because of the disparity of available data. Using the medical specialty of pathology as an example, we present for the first time a demographic analysis based on the confrontation of main data sources. This study underlines some of the structural and dynamic problems which threaten the demographic stability of the specialty. The public service suffers from a lack of practitioners, especially in regional hospitals. Whereas one third of French pathologists work in the larger hospitals around Paris, in some other regions private services constitute the main component of the supply. Projections based on the aging phenomenon and a reduction in entry indicate a future problem in the renewal of generations of pathologists. The consequences of this programmed decrease in the number of French pathologists will be further exacerbated by the movement of the sex ratio in favor of women.

Demography↗

Pelvic ependymoma arising from the small bowel.

A 37-year-old woman underwent resection of an abdominal tumour which was adherent to the wall of the ileum. The diagnosis of an ependymoma was supported by evidence of typical perivascular pseudorosettes which stained positive for glial fibrillary acidic protein and contained abundant intermediate filaments within the elongated processes by electron microscopy. Flow cytometric study showed a diploid population of tumour cells. This is the first case of an ependymoma arising from the small bowel without any connection to the genital tract, the omentum or with the sacroccygeal area. As is the case with other unusual and ectopic localisations of ependymomas, prognosis of this tumour is difficult to evaluate.

Adult↗

[DNA-array analysis of the expression profile of apoptosis gene regulators in malignant lymphoma].

Microarray technology has recently led to the identification of molecular prognostic subgroups in non Hodgkin's lymphomas. In order to determine the usefulness of ready-made macroarrays as routine diagnosis tools in haemato-pathology, we have analysed lymph node biopsies using a cDNA macroarray containing genes involved in apoptosis, including caspases. Nine biopsy specimens were analysed on total frozen tissues: 4 samples of B-cell follicular lymphoma (FL), two of B-cell diffuse large cell lymphoma (DLCL), and three of non-neoplastic lymph nodes from benign lymphadenitis. Eight cell populations were sorted from fresh tissues: malignant B-cells from 2 FL cases and 2 DLCL cases, reactive B-cells from 1 benign lymph nodes, reactive T-cells from 1 benign lymph node, virgin (mantle zone) B-cells and germinal center (GC) B-cells from benign tonsils. Immunohistochemistry (IHC) on paraffin sections was performed for localization of caspases 2, 3, 4, 7, 8, and 9. In the clustered array data, sorted cells from samples sharing common histological lesions grouped together, whereas the array/histology correlation was less satisfactory for tissues. The expression profiles of both array and IHC methods were correlated for most caspases and samples. Variations in array profiles of sorted cell populations can be statistically associated with specific histological features, suggesting a possible diagnostic application of ready-made "Apoptosis macroarrays" in haematopathology.

Apoptosis↗

[Mammary carcinoma arising in microglandular adenosis: a case report].

Microglandular adenosis is an uncommon benign breast entity considered as a variant form of adenosis. The diagnosis is frequently made by the pathologist as it is often clinically asymptomatic. Carcinoma arising in microglandular adenosis is very uncommon. We report a case of carcinoma arising in microglandular adenosis in a 54-year-old woman. The immunohistochemical profile, especially S100 protein expression and absence of epithelial membrane antigen, was useful to recognize the microglandular adenosis and the carcinoma of alveolar architecture, while invasion was suggested by the basement membrane disruption highlighted with anti-collagen IV immunostaining. The good prognosis of carcinoma associated with microglandular adenosis points out the importance of distinguishing this lesion from other breast carcinomas.

Basement Membrane↗

Prognosis of breast-carcinoma lymphagenesis evaluated by immunohistochemical investigation of vascular-endothelial-growth-factor receptor 3.

Very few studies have yet addressed the question of the existence and role of lymphagenesis in tumor growth; it is generally overshadowed by the greater emphasis placed on the blood vascular system. Monoclonal antibodies against vascular endothelial-growth-factor receptor 3 (VEGFR3) have been shown to provide a specific antigenic marker for lymphatic endothelium. By comparison with the microvascular count (MVC), we investigated the prognostic value of the microlymphatic count (MLC) in a series of 60 cases of 2-cm-diameter breast carcinomas. The mean value of MVC was 72.5 and of MLC, 40.5. There was no quantitative correlation between these 2 parameters. The MVC but not the MLC had a prognostic value in overall survival. Neither the MLC nor the MVC had any correlation with axillary-lymph-node invasion.

Biomarkers↗

Frequent nuclear localization of ICAD and cytoplasmic co-expression of caspase-8 and caspase-3 in human lymphomas.

Lymphoma cells often display in vitro resistance to FAS-induced apoptosis, in which caspases act as crucial cell death effectors. Following FAS stimulation, caspase-8 activates caspase-3, which in turn activates the caspase-activated DNAse (CAD) by proteolysis of its inhibitor (ICAD). To investigate the mechanism of FAS resistance, the expression of caspase-8 was analysed by immunohistochemistry, together with that of the substrates caspase-3 and ICAD, in 52 representative samples from non Hodgkin's lymphoma (NHL), 12 from Hodgkin's disease (HD), and eight benign lymphoid tissues. In benign tissues, caspase-8 was co-expressed with caspase-3 in the cytoplasm in germinal centre (GC) cells and was co-expressed with ICAD in the nuclei of the mantle and marginal zone cells. ICAD expression was weak or absent in GC cells. Cytoplasmic staining for both caspase-8 and caspase-3 was present in 11/12 cases of diffuse large cell B-NHL. Caspase-8 positivity was nuclear and cytoplasmic in 9/9 follicular NHLs, in 5/5 mantle cell NHLs and in 6/6 marginal zone NHLs. Five out of six peripheral T-cell NHLs expressed cytoplasmic caspase-8. Ten out of the 12 HD cases lacked significant cytoplasmic staining for caspase-3 and caspase-8 in the majority of Reed-Sternberg cells. All lymphoma cases exhibited predominant nuclear ICAD positivity. Subcellular fractionation analysis of three lymphoma samples and normal mantle zone cells confirmed that ICAD and caspase-8 were at least partly localized in the nucleus. These results show that the profile of caspase-8 expression is correlated with histological lymphoma subtypes; that caspase-8 is co-expressed with caspase-3 in GC cells and their neoplastic counterparts; that ICAD has an immunohistochemical nuclear localization in vivo; and that caspase-8 and ICAD can be co-expressed in the nuclei of mantle zone and marginal zone cells; their unexpected nuclear localization allows a reappraisal of the biochemical cascade of caspase activation.

Apoptosis Regulatory Proteins↗

Central neurocytoma: 2 case reports and review of the literature.

Central neurocytoma is a rare benign tumor of the central nervous system occuring in young adults and typically located in the ventricles. The tumor is composed of small round cells with neuronal differentiation and has a favourable prognosis. We report two cases of giant central neurocytomas with a triventricular extension in two young women. The first case concerned a 26 years old righthanded woman in whom an intraventricular mass was discovered, after a car accident with head trauma. Skull radiography showed an enlargment of the sella turcica. A CT scan performed in order to examine the pituitary gland revealed a voluminous and heterogenous intraventricular tumor with calcification. The second case concerned a 26 years old righthanded woman, presenting with a 4 Glasgow Coma Scale Score preceded by an acute onset of headache with projectile vomiting. A CT scan performed in emergency revealed a voluminous intraventricular mass with significant hydrocephalus. We review the different pathological and topographical patterns of previously published neurocytomas and discuss surgical management, effectiveness of radiation therapy and biological behavior.

Adult↗

So-called malignant and extra-ventricular neurocytomas: reality or wrong diagnosis? A critical review about two overdiagnosed cases.

Central neurocytoma (CN) is described as a rare intra-ventricular benign neuronal tumor of the brain. Two primary tumors first diagnosed as malignant and extra-ventricular neurocytomas are reported here. Histologically, the tumor of the first patient, a forty-one-year-old man, consisted of monotonous cells with round nuclei, but no fibrillar background. The second tumor, in a nineteen-year-old girl, showed areas of moderately pleomorphic round cells, with numerous rosettes and ganglion cell differentiation, in an abundant fibrillary network. Both presented calcifications. Mitoses were more frequent in recurrences and spinal locations than in the primaries. All tumors stained strongly for synaptophysin, and GFAP was partly positive in the first case only. Patients received post-surgical radiotherapy and were still alive eight and six years, respectively, after initial surgery. The interpretation of atypical cases, such as ours is not easy: the diagnoses finally retained were oligodendroglioma in the first case and ganglioneuroblastoma in the second case. Furthermore, neurocytomas atypical either by their unusual topographical or histological presentation or by their poor prognosis, have been frequently entitled in this way on synaptophysin positivity. So, we were prompted to reassess the entity of CN, seventeen years after the first description, to re-appreciate the reality of anatomo-clinical variants and to discuss the value of synaptophysin positivity in these tumors. In conclusion, it seems preferable to individualize true classical CN, which has a favorable outcome, from so-called extra-ventricular, atypical and anaplastic, clinically malignant neurocytomas for which complementary treatment is required.

Adolescent↗

Variation in the histological pattern of nodal involvement by gamma/delta T-cell lymphoma.

AIMS: Gamma-delta (gammadelta) T-cell non-Hodgkin's lymphomas (NHLs) usually present with liver, spleen and marrow infiltration. Lymph node involvement by gammadelta T-cell NHL has been rarely documented so far; its histological pattern needs to be further defined. METHODS AND RESULTS: Two cases of nodal gammadelta T-cell NHL are reported: case 1, a 44-year-old man, presented with cytomegalovirus retinitis and superficial lymphadenopathies. Histological analysis of an inguinal lymph node showed complete destruction by a diffuse pleomorphic lymphoid proliferation, which was positive for CD2, CD3, CD43, CD45, TIA-1 and granzyme B, and displayed a gammadelta phenotype (deltaTCR1+, Vdelta1+, Vdelta2-, Vdelta3-, betaF1-). Bone marrow was normal. Case 2, a male 24-year-old patient with a history of renal transplantation, presented with hepatosplenomegaly and supraclavicular lymph node enlargement. Lymph node architecture was globally preserved. Peripheral sinuses contained scattered nests of medium-sized irregular lymphoid cells. Bone-marrow was infiltrated. Phenotype showed positivity for CD2, CD3, CD45 and TIA1 and expression of gammadelta TCR (deltaTCR1+, deltaV1+, deltaV2-, deltaV3-, betaF1-). Both patients died a short time after diagnosis. CONCLUSIONS: These observations suggest that at least two forms of nodal gammadelta T-cell NHL may be encountered: one mimicking classical alphabeta T-cell NHL, with diffuse pleomorphic cell proliferation, and one displaying sinusoidal neoplastic infiltration suggesting a close relationship with hepatosplenic gammadelta T-cell NHL.

Adult↗

[Hepatic MALT lymphoma disclosing a nodal extension].

We report a case of a 50-year-old man with chronic viral hepatitis B presenting with a primary hepatic lymphoma of mucosa-associated lymphoid tissue, revealed clinically by a pedicular nodal mass. The liver biopsy showed an active chronic hepatitis and a dense portal lymphoid infiltrate with centrocyte-like cells inducing typical biliary lympho-epithelial lesions. The lymph-node biopsy revealed a marginal zone lymphoma pattern. A monoclonal rearrangement of the immunoglobulin heavy chain gene was detected in the lymph node by polymerase chain reaction. This case of primary hepatic mucosa-associated lymphoid tissue lymphoma confirms that the liver also contains mucosa-associated lymphoid tissue, in which low grade lymphoma can arise.

Antineoplastic Combined Chemotherapy Protocols↗