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J P Merlio

Publications and source records attributed to J P Merlio.

At least 55 records · Page 3Linked to original sources

CD30-positive cutaneous large cell lymphomas. A comparative study of clinicopathologic and molecular features of 16 cases.

The authors have analyzed and compared the clinicopathologic and molecular features of 16 cases of large cell cutaneous lymphomas expressing CD30 antigen. Three main clinical groups were defined: (1) a group of localized skin disease (7 cases); (2) a group of multicentric skin disease (5 cases); and (3) a group of concomitant skin and extracutaneous disease. Good prognosis was associated with localized skin disease and no history of lymphoma. Interestingly, a majority of Reed Sternberg-like cells was only observed in this group (5 of 6 cases). The two other groups did not show distinctive evolutive nor morphologic features. Southern blot and/or polymerase chain reaction (PCR) technique showed clonality and a T-cell genotype in respectively 13 of 14 and 12 of 12 analyzed cases. Viral infection of tumoral cells was investigated by PCR, in situ hybridization (ISH) or electron microscopy. Epstein-Barr virus (EBV) sequences were detected by PCR and ISH in tumoral cells of cutaneous lesions in one case of skin lymphoma with extracutaneous spreading. No EBV sequence was detected by ISH in the localized lymphomas, whereas HIV particles were visible in tumoral cells in one of these cases. No human T-cell lymphotropic virus (HTLV) tax sequence was amplified by PCR in any case of our series. Our results confirm that CD30-positive cutaneous large cell lymphomas are different clinical and molecular entities. However, a combined clinical and morphologic analysis may help to identify a subset of CD30 cutaneous lymphomas with favorable prognosis.

Adolescent↗

Cystic smooth-muscle tumor of the liver and spleen associated with Epstein-Barr virus after renal transplantation.

Immunosuppression is known to favor the development of various types of tumors. After organ transplantation, the risk of lymphoproliferative disease, whether clonal or not, is particularly increased and clearly associated with Epstein-Barr virus infection. We report a case of an unusual large cystic tumor of the liver with satellite hepatic and splenic nodules occurring 4 years after renal transplantation. Radiologic examination showed a rich vascularization of the tumor. Light and electron microscopy of a surgical liver biopsy, completed by an immunohistochemical study, demonstrated a well-differentiated tumor of smooth-muscle origin. Using in situ hybridization, we showed large amounts of Epstein-Barr virus messenger RNAs within the tumor cells. In addition, Southern blot analysis revealed that viral DNA was present in the form of a single monoclonal episome within the tumor. The polymerase chain reaction analysis of the genomic DNA of tumoral cells also indicated a monoclonal pattern. At last, the tumor was shown to be of host origin. Six months later, and despite three courses of chemotherapy, the tumoral lesions were unchanged. This case underlines the role of Epstein-Barr virus infection in the development of unusual and clonal smooth-muscle tumors after organ transplantation. The evolution of these rare tumors is uncertain.

Female↗

Detection of t(2;5)(p23;q35) translocation by reverse transcriptase polymerase chain reaction and in situ hybridization in CD30-positive primary cutaneous lymphoma and lymphomatoid papulosis.

The t(2;5) generates a chimeric NPM-ALK transcript encoded by the nucleophosmin NPM gene fused to the anaplastic lymphoma kinase gene ALK. Using a reverse transcriptase nested polymerase chain reaction assay we have detected NPM-ALK transcripts within CD30+ primary cutaneous lymphoma and lymphomatoid papulosis (LP). The t(2;5) was identified in 4 out of 9 CD30+ anaplastic lymphomas and in 1 out of 4 CD30+ pleomorphic lymphomas. Moreover, the t(2;5) was detected in 3 out of 10 LPs. All NPM-ALK-positive lymphomas and 1 NPM-ALK-positive LP exhibited a clonal rearrangement of the T cell receptor gamma-chain gene. The t(2;5) was detected in 2 cases of LP without other evidence for a clonal lymphoid population. To identify cells carrying the t(2;5) translocation, we used immunohistochemistry to detect the ALK-encoded p80 protein and in situ hybridization for the specific detection of NPM-ALK transcripts. Both p80 protein and NPM-ALK transcripts were expressed by anaplastic or large CD30+ lymphoma cells with positive NPM-ALK amplification. The presence of t(2;5) in a subset of CD30+ cutaneous lymphoma and LP may indicate a common pathogenesis with a subset of anaplastic nodal lymphoma.

Adult↗

Contribution of histopathologic and molecular analyses to the diagnosis of cutaneous B-cell infiltrates.

To evaluate the value of morphologic, immunohistochemical and molecular analyses, we studied 21 skin biopsy specimens from 19 patients with primary cutaneous B-cell infiltrates. Morphologic review by two independent dermatopathologists confirmed the consensus diagnoses of lymphoma (n = 6) or benign lymphoid hyperplasia (n = 6). A discordant diagnosis was made for the other samples (n = 9), which were thereafter considered as unclassified lymphoid infiltrates. Immunohistochemical analysis showed either a monotypic expression of immunoglobulin light chain or a positive staining with anti-bcl-2 antibodies in three and four samples, respectively, of lymphoma. Polymerase chain reaction was used to analyze immunoglobulin heavy chain and T-cell receptor gamma chain gene rearrangement and to amplify t(14;18) and t(11;14) break points. A clonal molecular marker was detected in 12 of 19 patients. Among these 12 patients, a final diagnosis of lymphoma was confirmed in 8 patients, including the 6 with a morphologic diagnosis of lymphoma. Two patients with clonal benign lymphoid hyperplasia and two with clonal unclassified lymphoid infiltrate presented a benign clinical outcome; one patient was lost to follow-up. Alternatively, no clonal molecular marker was found in two of the patients with lymphoma. The morphologic and molecular criteria, therefore, provided complementary and partially overlapping information for the diagnosis of cutaneous B-cell infiltrates. We proposed a practical use for these data.

Adolescent↗

[Splenic lymphoma with villous lymphocytes: morphologic, immunologic and molecular study. Report of three cases].

Splenic lymphoma with villous lymphocytes (SLVL) is a low grade lymphoproliferation characterized by a massive splenomegaly, an absence of lymphadenopathy and the presence in the peripheral blood of atypical B-lymphocytes with hairy-cell appearance. We have studied the morphological, immunological and molecular characteristics of 3 cases of SLVL. SLVL presented on blood smears characteristic irregularities of the plasma membrane consisting in thin and short villi unevenly distributed. The main phenotype was CD5-, CD11c+, and CD25-, but individual SLVL cases can not be identified by using immunohistochemical criteria alone. Clonal rearrangements of the immunoglobulin heavy chain gene were found in all 3 cases and in one case presented a bcl2-JH rearrangement. SLVL are clonal B-cell lymphoproliferations and can be associated with t(14; 18) translocation.

Aged↗

[Pseudolymphoma induced by carbamazepine. Apropos of 2 cases].

We present two pseudolymphoma occurring 8 days and 1 month after carbamazepine introduction. Both patients present fever, rash, generalized lymphadenopathy and hepatosplenomegaly in the second case. Hematologic abnormalities included anemia, eosinophilia, hepatic cytolysis. Histologic evaluation of a lymph node biopsy specimen demonstrated near-total effacement of the nodal architecture mimicking a lymphoma. Gene rearrangement studies proved the benign nature of the proliferation. Carbamazepine-induced lymphoproliferative disorders are relatively rare with only 38 observations published. The pathogenesis is uncertain. Immune dysregulation is probable. Morphologic and immunophenotypic data must be completed by gene rearrangement studies. Corticoid therapy is useless. The evolution is favorable after the cessation of carbamazepine.

Adult↗

[Lymphomatoid papulosis in a child].

BACKGROUND: Lymphomatoid papulosis (LyP), uncommon in children, has a benign clinical course in contrast with a malignant histology. CASE REPORT: A 9-year old boy developed nodular skin lesions for 6 months on the scalp and penis and a papule skin on his trunk. Surgical excision of scalp nodules was performed to prevent necrosis and ulceration of the ear. The biopsy showed a dense mixed cellular infiltrate including histiocytes, lymphocytes and numerous atypical large cells of which a minority expressed the CD30 antigen. PCR showed an oligoclonal rearrangement of the TCR gamma chain gene. Physical examination, bone marrow aspirate and thoracoabdominal CT scans were normal. Three years after surgery, no other lesions occurred. DISCUSSION: Differential diagnosis of LyP is difficult with non Hodgkin's lymphoma, especially CD30+ lymphoma. Prognosis remains the major problem in LyP. Ten to 20% of cases are associated with lymphomas in adults.

Child↗

Peripheral T-cell lymphoma in a chronically immunosuppressed renal transplant patient.

Non-Hodgkin large cell lymphomas occurs more commonly in organ-transplanted patients than in the general population. They are usually of B-cell origin whereas T-cell lymphomas are rare. We report a new case of peripheral T-cell lymphoma in an immunosuppressed renal transplanted patient. The patient presented a hepatosplenic mass with a widespread extension causing serious pancytopenia. It was classified as a pleomorphic medium and large cell type and corresponded to the "common" alpha beta-TCR type lymphoma. Lymphomatous cells exhibited an incomplete mature T-cell phenotype. T-cell receptor gene clonal rearrangement associated with a germline configuration of the immunoglobulin heavy chain gene confirmed a clonal T-cell genotype. By using both Southern blot analysis and polymerase chain reaction, we failed to demonstrate any association with Epstein-Barr virus or human T-cell lymphotropic virus type I or type II.

Adult↗

Primary extramedullary plasmacytoma of the liver. A case report.

We report the first case of primary extramedullary plasmacytoma of the liver. The tumor was situated in segment VIII of the liver without extrahepatic extension. Histologically, the tumor was composed of sheets of mature plasma cells with slight atypia in association with proplasmacytes invading the hepatic parenchyma. Neither plasmoblasts nor lymphoplasmacytes were present. Immunohistochemistry demonstrated monoclonal IgG and kappa light-chain expression. In situ hybridization confirmed the monotypic expression of kappa light-chain mRNA. Bone marrow examination revealed no abnormality. After surgery, the IgG kappa spike detected in preoperative plasma samples decreased. The patient is disease free 31 months postoperatively.

Aged↗

p53 oncoprotein expression in cutaneous lymphoproliferations.

BACKGROUND AND DESIGN: p53 overexpression has been reported in systemic lymphoproliferations, but our study is the first large series, to our knowledge, dealing with p53 expression in primary cutaneous lymphomas. p53 immunohistochemical detection using DO7 monoclonal antibody was performed in 54 cutaneous lymphoproliferative disorders, including 37 primary cutaneous T- or B-cell lymphomas. RESULTS: No expression of p53 was found in 14 mycosis fungoides and seven pleomorphic T-cell lymphomas of either low or high grade of malignancy. Furthermore, no p53-positive cells were shown in low-grade B-cell lymphomas and in benign chronic dermatoses. p53 overexpression was seen over lymphomatous cells in 10 cutaneous lymphomas of high grade of T- or B-cell origin with two immunoblastic, three centroblastic, and five anaplastic lymphomas. Five of them occurred in human immunodeficiency virus-infected individuals, suggesting a possible interaction between p53 and viral proteins. p53 immunoreactivity was found over Reed-Sternberg-like cells in two cases of lymphomatoid papulosis. A labeling of keratinocytes located mainly in basal cell layers of the epidermis was observed in only five cases regardless of the lymphoma histologic subtype. CONCLUSIONS: p53 overexpression was not found in the most frequent primary cutaneous lymphomas, epidermotropic T-cell lymphomas. Alternatively, p53 immunoreactivity was observed in most primary cutaneous lymphomas of high grade of malignancy occurring in individuals either infected or not infected by human immunodeficiency virus. Molecular studies will determine if p53 overexpression is associated with p53 gene alteration and help to understand the role of p53 in primary cutaneous lymphoma genesis.

Humans↗

Simultaneous development of two different B-cell lymphomas in a patient with acquired immune deficiency syndrome evidenced by molecular analysis.

We report a case of a man positive for the human immunodeficiency virus who rapidly died of lymphoma with cerebral, lung, and pericardic involvement. After autopsy, histopathological study of the different tumor sites showed the same morphological feature of immunoblastic lymphoma, with large areas of necrosis. In situ hybridization showed monotypic kappa light chain mRNA within lung lymphoma cells and monotypic lambda light chain mRNA within cerebral lymphoma cells. Polymerase chain reaction analysis showed two different immunoglobulin heavy chain gene rearrangements for lung and cerebral lymphoma. Here the simultaneous association of two malignant lymphomas derived from different B-cell clones indicates that molecular analysis of different tumor sites can distinguish between dissemination of the same lymphoma and simultaneous proliferation of different malignant B-cell clones.

Acquired Immunodeficiency Syndrome↗

Expression of polyadenylated and non-polyadenylated trkC transcripts in the rodent central nervous system.

We have previously isolated a full-length cDNA clone encoding rat TrkC, a member of the Trk family of tyrosine kinase receptors, that specifically mediates biological responses to neurotrophin-3. Here, we report the identification of five major trkC transcripts in the adult and developing rat and mouse brain suggesting the presence of several TrkC receptors. Northern blot hybridizations revealed that three of these trkC transcripts (of 14, 3.9 and 4.8 kb) were poly(A)+ messenger RNAs, while the two others, of shorter size (1.1 and 0.7 kb), were poly(A)- messenger RNAs. All transcripts were expressed in 11 brain regions but poly(A)- messenger RNAs were found at much higher levels than poly(A)+ messenger RNAs in the cerebellum. Hybridization with five oligonucleotide and two complementary DNA probes, corresponding to different parts of the full-length trkC complementary DNA, revealed that the two poly(A)- transcripts may encode for receptors truncated in their extracellular and kinase intracellular domains. During ontogeny, poly(A)- trkC messenger RNAs were found at low amounts at prenatal and early postnatal ages with a drastic increase in the cerebellum at postnatal day 30. No poly(A)- transcript was identified for the trk B gene. In situ hybridization revealed that trkC messenger RNAs are expressed both in granular and Purkinje cells in the cerebellum. Northern blot on RNA extracted from mice mutant strains with degeneration of either granular or both granular and Purkinje cells suggested that poly(A)- and poly(A)+ trkC messenger RNAs are expressed within the same cells. We have demonstrated the existence of several trkC transcripts that differ both by their size and polyadenylation. This phenomenon could be of physiological relevance in regulating TrkC functions. To the best of our knowledge, this is an original feature for a mammalian gene expression. Studies focused on poly(A)- messenger RNAs could give rise to the identification of other genes expressed in a similar fashion.

Animals↗

[Study of B-lymphocyte clonality using in vitro gene amplification (PCR) in paraffin embedded samples].

Family-specific primers were used in polymerase chain reaction (PCR) to analyse clonality of immunoglobulin heavy chain (IgH) gene rearrangement. DNA templates were extracted from formalin-fixed paraffin-embedded biopsies from B-cell lymphomas (n = 19), T-cell lymphomas (n = 3), reactive lymphadenopathies (n = 20) and negative controls (n = 2). PCR was also performed on DNA extracted from fragments of the same biopsies that were either fixed in Bouin's solution (n = 24) or snap-frozen (n = 22). The latter were also studied for IgH gene rearrangement by the Southern blot technique. Polyclonal or clonal fragments were obtained from all frozen biopsies. No amplification was observed in 3 out of 44 formalin fixed specimens and 18 out of 24 Bouin fixed specimens. A clonal amplification was only observed in 16 out of 19 formalin-fixed B-cell lymphoma specimens. Therefore this technique allows to study B-cell clonality from formalin-fixed, embedded material.

Acetates↗

Expression of mRNAs for neurotrophin receptors in the dorsal root ganglion and spinal cord during development and following peripheral or central axotomy.

Expression of mRNAs for the protein tyrosine kinases trk, trkB and trkC, encoding essential components of high-affinity neurotrophin receptors, was studied in the spinal cord and dorsal root ganglion during normal development and in the adult rat following peripheral and central axon injury. Northern blots revealed multiple trkB transcripts in the embryonic, early postnatal and adult spinal cord with different patterns of expression during development. The levels of 9.0 kb and 4.8 kb trkB transcripts, encoding a full-length trkB receptor, increased progressively during embryonic development with maximal levels around birth, followed by a decline at adulthood. In contrast, the level of 7.5/7.0 kb trkB transcripts, encoding a truncated trkB receptor, reached maximal levels shortly after birth and similar levels remained in the adult animal. In the spinal cord a 4.7kb trkC transcript was detected with maximal levels shortly after birth. In situ hybridization revealed a uniform labeling throughout the spinal cord for both trkB and trkC mRNAs with maximal intensities of labeling shortly after birth. The level of the 2.4 kb trkB transcript in the spinal cord increased 5-fold 8 days after a crush lesion of the sciatic nerve or the dorsal root, while no change was seen in the levels of the other trkB transcripts. No change in the 4.7 kb trkC mRNA was seen following these two injuries, although increased levels of several smaller size trkC transcripts were observed. For both trkB and trkC, similar size transcripts as seen in the spinal cord were also detected in adult rat dorsal root ganglia. Consistent with previous observations of decreased levels of cytoskeletal proteins after peripheral and central axotomy, the level of neurofilment light chain mRNA decreased markedly in the dorsal root ganglia following a crush lesion of the sciatic nerve or of the dorsal root. A small decrease was also seen in the level of preprotachykinin-A mRNA encoding the protein precursor of substance P. In the same animals, the levels of all five trkB transcripts increased 3-fold in the dorsal root ganglia in response to these two injuries. A small increase was also seen in the level of trkC mRNA. The level of brain-derived neurotrophic factor (BDNF) mRNA increased two-fold in the dorsal root ganglia following either of the two lesions, while no change was detected in trk mRNA following these two injuries.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Increased production of the TrkB protein tyrosine kinase receptor after brain insults.

The protein-tyrosine kinases Trk, TrkB, and TrkC are signal-transducing receptors for a family of neurotrophic factors known as the neurotrophins. Here we show that seizures induced by hippocampal kindling lead to a rapid, transient increase of trkB mRNA and protein in the hippocampus. TrkB is a component of a high affinity receptor for brain-derived neurotrophic factor (BDNF). No change was detected in mRNAs for Trk or TrkC, components of the high affinity nerve growth factor or neurotrophin-3 receptors, respectively. trkB mRNA was also transiently increased in the dentate gyrus following cerebral ischemia and hypoglycemic coma; these treatments had no effect on trk and trkC mRNAs. The increase in trkB mRNA and protein showed the same time course and distribution as the increase in BDNF mRNA. These data suggest that BDNF and its receptor may play a local role within the hippocampus in kindling-associated neural plasticity and in neuronal protection following epileptic, ischemic, and hypoglycemic insults.

Animals↗

Human immunodeficiency virus type 1 replication within cystic lymphoepithelial lesion of the salivary gland.

Cystic lymphoepithelial lesions of salivary glands (CLLSG) are nodular or diffuse salivary gland enlargements that are observed in patients who tested positive for human immunodeficiency virus type 1 (HIV-1). Two cases of CLLSG are reported. Particular emphasis is placed on the presence of HIV-1 major-core protein (P24), HIV-1 RNA sequences, Epstein-Barr virus (EBV) DNA sequences, and lymphocyte receptor gene rearrangement. Lymphoid alterations consisted of explosive hyperplasia with a prominent follicular reticular dendritic cell (DRC) network and numerous intrafollicular CD8+ lymphocytes. Intrafollicular DRC strongly expressed HIV-1 major-core protein and HIV-1 RNA, indicating that most DRCs actively replicated the HIV-1 virus. The presence of active HIV-1 replication within DRC and the absence of clonal EBV infected lymphoid population strongly suggest that CLLSG pathogenesis is primarily induced by HIV-1. The presence of oligoclonal immunoglobulin gene rearrangements in our cases, however, suggest the need of long-term follow-up of such patients to determine whether CLLSG could be a benign prelymphomatous disease.

Adult↗