Frequency and prognostic value of cutaneous molecular residual disease in mycosis fungoides: a prospective multicentre trial of the Cutaneous Lymphoma French Study Group.

BACKGROUND: Monoclonal T-cell receptor (TCR) rearrangement is detected in 57-75% of early-stage mycosis fungoides (MF) at diagnosis. A retrospective study showed molecular residual disease (MRD) in 31% of patients in complete clinical remission (CR) after 1 year of treatment. OBJECTIVES: To confirm the frequency of MRD at 1 year and to determine its prognostic value for further relapse. METHODS: Patients with T1-, T2- or T4-stage MF were prospectively included in this multicentre study. At diagnosis, clinical lesions and healthy skin were biopsied. After 1 year of topical treatment, previously involved skin of patients in CR was biopsied for histology and analysis of TCR-γ gene rearrangement. The results were compared with the clinical status each year for 4 years. RESULTS: We included 214 patients, 133 at T1, 78 at T2 and three at T4 stage. At diagnosis, 126 of 204 cases (61·8%) showed TCR clonality in lesional skin. After 1 year, 83 of 178 patients (46·6%) still being followed up were in CR and 13 of 63 (21%) showed MRD. At 4 years, 55 of 109 patients (50·5%) still being followed up were in CR and 44 of 109 (40·4%) were in T1 stage. MRD did not affect clinical status at 4 years (CR vs. T1/T2, P = 1·0; positive predictive value 36·4%; negative predictive value 67·6%). CONCLUSIONS: T-cell clonality at diagnosis and MRD at 1 year are not prognostic factors of clinical status at 4 years.

The isotype of the BCR as a surrogate for the GCB and ABC molecular subtypes in diffuse large B-cell lymphoma.

Gene expression profiling has identified two major molecular subtypes of diffuse large B-cell lymphoma (DLBCL) that are histologically indistinguishable but differ in cure rates. Here, we investigated whether the isotype of the B-cell receptor (BCR) expressed by the tumoral cells correlated with the molecular subtype and survival. Gene expression analysis clustered the 53 patients included in this study into three subgroups, 17 germinal center B-cell-like (GCB) cases, 26 activated B-cell-like (ABC) cases and 10 intermediate cases. The molecular subtype was correlated with the isotype, as 15/17 GCB cases expressed a secondary isotype (immunoglobulin (Ig)G or IgA), whereas 24/26 ABC cases expressed a primary isotype (IgM or IgD) (P<0.0001). There was a trend toward a worse outcome for patients with an ABC DLBCL and a shorter overall survival for patients with IgM+ tumor (P=0.21 and 0.014, respectively). Finally, fluorescence in situ hybridization (FISH) analysis revealed a striking asymmetric pattern, as the IGHM gene is conserved only on the productive IGH allele in most IgM+ tumors. Taken together, these data indicate that the isotype of the BCR is a reliable indicator for the GCB and ABC subtypes in DLBCL, and suggest that the conservation of an IgM is required for ABC DLBCL lymphomagenesis to occur.

The new haematology analyzer DxH 800: an evaluation of the analytical performances and leucocyte flags, comparison with the LH 755.

INTRODUCTION: The analytical performance and the abnormality messages on differential (flags) of the new analyzer Beckman Coulter DxH 800 were compared with those of the LH 755. METHODS: First, we evaluated the accuracy of the results of the DxH 800, in comparison with the LH 755, in 125 samples without alarm using unflagged sample results on both analyzers. Second, flagged samples on the LH 755 but not flagged by the DxH 800 were evaluated by flow cytometry for accuracy of the DxH 800 results. Finally, we evaluated the sensitivity and specificity of abnormality messages on differential given by the analyzers, in comparison with manual blood smears. RESULTS: The correlation coefficients (R) for complete blood count parameters and differential demonstrated that the DxH 800 results were similar to that of LH 755. Excellent correlation coefficients between DxH 800 and flow cytometry results were found for white blood cell count (R = 0.985, n = 31), platelet count (R = 0.976, n = 51) and nucleated red blood cells (R = 0.966, n = 37). The overall performance showed an increased sensitivity (0.892) and specificity (0.864) of the flags on DxH 800 when compared to the LH 755 (0.846 and 0.733, respectively). CONCLUSION: The DxH 800 provides reliable results and increases laboratory efficiency by reducing working time and costs associated with the optical validation of the results.

Lymphocyte volume and conductivity indices of the haematology analyser Coulter GEN.S in lymphoproliferative disorders and viral diseases.

The haematology analyser Coulter GEN.S gives a set of data -'positional parameters'- defining white blood cell (WBC) populations by mean of index values (mean and standard deviation of volume, conductivity and scatter, used to identify the WBC populations). The volume and conductivity parameters related to the lymphocytes were analysed at diagnosis in patients suffering from chronic B-lymphocytic leukaemia (B-CLL), other non-CLL lymphoproliferative disorders (OLPD) and viral diseases. The standard deviation of volume index (SDVI) is significantly higher in the three groups, whereas the mean volume index (MVI) is significantly lower in B-CLL, and increased in OLPD and viral diseases. These two groups could be distinguished by their mean conductivity index (MCI), which is significantly lower in viral disease group. Cut-offs were calculated for each parameter by the mean of Receiver Operating Characteristic (ROC) analysis. The study of the detection performances showed that the combination of lymphocyte count with SDVI, MVI and MCI could be used with a good sensitivity and specificity to discriminate between the most frequent lymphocyte pathologies, even in patients with normal lymphocyte count.

[Protein Z: a new regulator of coagulation in arterial vessels?]. / La protéine Z: une protéine régulatrice de la coagulation au niveau artériel?

Protein Z (PZ) is a vitamin K dependent factor identified in human plasma in 1984 whose physiological function was poorly understood. It was recently shown that protein Z is implicated in the down-regulation of coagulation by forming a complex with a plasma proteinase inhibitor called protein Z-dependent protease inhibitor (ZPI) which inhibits activated factor Xa on phospholipid surfaces. In the absence of an additional challenge, the disruption of PZ gene in mice is asymptomatic, but the association with the factor VLeiden mutation leads to a near complete mortality during the neonatal period with microvascular thrombosis. Unexpectedly, in humans, a relationship between protein Z deficiency and ischemic strokes, was firstly evidenced, but not confirmed by all the epidemiological study. Additional studies suggest that protein Z deficiency could be also a risk factor for acute coronary syndromes, early fetal losses, and increased the arterial risk in antiphospholipid syndrome. This review analyzes the different studies so far published and discusses the different results obtained in order to understand whether or not protein Z deficiency could be considered as an arterial ischemic risk factor.

[Miescher's cheilitis and lymphocytic clonal expansion: 2 cases]. / Macrochéilite de Miescher et expansion lymphocytaire monoclonale. Deux cas.

INTRODUCTION: Melkersson Rosenthal's syndrome is a rare disease that classically combines: orofacial edema, peripheral facial paralysis and a plicated tongue. Miescher's cheilitis represents the monosymptomatic form of the disease. Its etiopathogenesis is unknown. We report 2 cases of Miescher's cheilitis during which the discovery of a monoclonal lymphocyte expansion raised the question of an eventual link between these two diseases. CASE REPORTS: CASE No 1. A 30 Year-old man, without medical past history, had been followed up for 3 Years for Miescher's cheilitis. The supplementary examinations permitted elimination of an infectious cause, Crohn's disease, sarcoidosis or a contact allergy. A serum monoclonal IgG kappa was discovered fortuitously. An X-ray of the skeleton and the myelogram were normal. There was no detectable monoclonal rearrangement of the genes of the blood or bone marrow T or B-cell lymphocyte receptor. In the absence of progression towards a malignant blood disease three Years later, we concluded in a benign monoclonal gammapathy. CASE No 2. A 36 Year-old Algerian man, without past medical history, had been followed-up for 8 Years for a granulomatous macrocheilitis. The search for Crohn's disease, sarcoidosis or a contact allergy was negative and the diagnosis of an incomplete Melkersson Rosenthal syndrome was retained. The blood count revealed persisting hyperlymphocytosis in the blood. The etiological search for a hyperlymphocytosis showed a monoclonal rearrangement of the T-cell lymphocyte receptor genes in the blood lymphocytes. The myelogram was normal. COMMENTS: Melkersson Rosenthal's syndrome is a rare granulomatous disease of the mucosa of the mouth. The etiopathogenesis of this affection is unknown and controversial, several case reports suggest that it could be a disease of immunological origin. A clonal T-cell lymphocyte population was revealed in the labial lesions of a 12 Year-old patient presenting with Melkersson Rosenthal's syndrome during a control visit, without the role of this lymphocyte population having been determined. We report two other cases associating blood lymphocyte proliferation and Melkersson Rosenthal' syndrome. This association is not necessarily fortuitous because of the rarity of the syndrome on the one hand and the uncommon nature of the detection of lymphocyte clones in young patients on the other. The presence of a clonal population can be interpreted in two manners: it can demonstrate chronic antigen stimulation, which with a super-antigenic effect leads to the expansion of a lymphocyte population making it detectable. The other hypothesis would be an increased secretion of cytokines by the lymphocyte clone provoking a granulomatous organization, as during granulomatous lymphomas.

Evaluation of the coulter LH 750 haematology analyzer compared with flow cytometry as the reference method for WBC, platelet and nucleated RBC count.

The Coulter LH 750 is a new haematology analyser with several new features: a count of nucleated red blood cells (NRBCs), automated WBC correction in presence of a flag indicating a cellular interference and a lower incidence of platelet or WBC interference flags when compared with the GEN.S, our current instrument. We had three main goals in our study: evaluating the LH 750 WBC counts when a GEN.S flag suggests a risk of WBC interference, ascertaining whether the platelet counts not flagged by the LH 750 were accurately assessed in samples flagged by the GEN.S and evaluating the NRBC assay provided by the LH 750. Flow cytometry, using CD45 and CD41, respectively for WBC and platelet labelling, was used as a reference method to assess the accuracy of the LH 750 counts. NRBC were identified by double labelling with propidium iodide (PI) and CD45, NRBCs being CD45-/PI+. A significant relationship was found between LH 750 and flow cytometric WBC counts, whether a WBC correction was made by the LH 750 (r = 0.9809, n = 54) or not (r = 0.9901, n = 23). A highly significant relationship was observed for platelets not only in the range from 0 to 450 x 10(9)/l (r = 0.981, n = 108) but also in cases of thrombocytopenia (range: 0-80 x 10(9)/l; r = 0.956, n = 51). In samples with NRBCs, the NRBC percentages given by the LH 750 and by flow cytometry were highly correlated (r = 0.977, n = 60) and WBC counts were accurate. In conclusion, the reduction in flagging by the LH 750, the accuracy of the results, and the availability of a NRBC count, constitute major advantages.

[Study of the clonality of cutaneous and blood lymphocytes during drug-induced hypersensitivity in 6 patients]. / Etude de la clonalité des lymphocytes cutanés et sanguins au cours du syndrome d'hypersensibilité médicamenteuse chez 6 malades.

INTRODUCTION: The drug-induced hypersensitivity syndrome or DRESS (drug reaction with eosinophilia and systemic symptoms) is a severe toxiderma because it is accompanied by lethal visceral involvement in 6 to 10% cases. Its physiopathology remains unclear. In order to specify the immunological characteristics of this toxiderma we analyzed, prospectively, the rearrangement of the blood and cutaneous T-cell lymphocyte receptor (TCR) genes of patients exhibiting a drug-induced hypersensitivity syndrome between April 1998 and April 2000. PATIENTS AND METHODS: The inclusion criteria were: age over 18 years, occurrence of a drug-induced generalized eruption, existence of associated systemic involvement (lymph node or visceral), and presence of hypereosinophilia greater than 0.5 G/l and/or circulating atypical lymphocytes. Six patients (3 men and 3 women), with a mean age of 54 years were included. The imputable drug was an anti-seizure in 3 cases, allopurinol in 2 and oxazepam in one. Remission occurred within a delay of 10 to 30 days after the acute phase. Two patients presented several flares. RESULTS: No clonal rearrangement in TCR genes was detected in the cutaneous samples. A clonal rearrangement of TCR genes was initially detected in the blood lymphocytes of 3 out of the 6 patients (allopurinol: n=2 and oxazepam: n=1). The latter remained detectable during the evolution, during the second or third flare of the drug-induced hypersensitivity in 2 patients (allopurinol: n=1 and oxazepam: n=1). DISCUSSION: The presence of circulating T-cell clones detectable for several months after the occurrence of a drug-induced hypersensitivity shows the mono or oligoclonal expansion of activated T-cells, induced by the drug imputed. Their persistence over several months corresponds to a remnant activation of the immune system that can explain the prolonged and/or recurrent evolution of the drug-induced hypersensitivity syndrome in some patients.

Increase of high fluorescence reticulocytes indicates mobilization of peripheral stem cells in children recovering from aplasia after chemotherapy or bone marrow transplantation.

Enumeration of CD34 + cells is the standard assay procedure for optimization of peripheral blood stem cell harvesting. High fluorescence reticulocytes (HFR) have been shown to signal a rebound in haematopoiesis after chemotherapy. The aim of this study was to evaluate HFR determination, as compared to CD34 + cell counts and CFU-GM, as a potential predictor of PBSC counts after recovery from chemotherapy and/or bone marrow transplantation. Twenty-five paediatric patients undergoing intensive courses of chemotherapy and 9 undergoing bone marrow auto or allografts were investigated. In most of our cases, HFR recovered at the same time or earlier than CD34 + cells. Similarly, the rise in HFR preceeded the CFU-GM peak in most of these cases. In no case did we observe a CFU-GM peak without a rise in HFR%. In our experience, the daily relative HFR increase may be used to predict the optimal time for mobilization of stem cells and was therefore of value clinically to confirm the timing of apheresis.

Fibronectin increases the migration induced by stromal cell-derived factor-1 alpha (SDF-1 alpha) in pre-B acute lymphoblastic leukemia cells.

The chemokine, stromal cell-derived factor-1 alpha (SDF-1 alpha) and its receptor CXCR-4 (fusin, LESTR) are thought to be involved in the trafficking of hematopoietic progenitors and stem cells, as suggested by the chemotactic effect of SDF-1 alpha on these cells. Gene inactivation studies have shown that both SDF-1 alpha and CXCR-4 are essential for B lymphopoiesis. Migration of leukemic cells may also be dependent on SDF-1 alpha and CXCR-4. Fibronectin (FN) is a component of the extracellular matrix (ECM), and one of the natural supports for cell movement in their bone hematopoietic environment. In the present study, we examined the influence of FN on the chemotactic effect of SDF-1 alpha and on the CXCR-4 expression and function on human precursor-B acute lymphoblastic leukemia (pre-B ALL) cells at sequential stages of development. Fourteen children with pre-B ALL were studied. Their immunophenotypes belonged to the first three stages of B cell differentiation. Despite relatively high levels of CXCR-4 expression at all stages, the responsiveness to SDF-1 alpha, measured as the percentage of migrating cells in the transwell culture system, varied with patients and seems to be less significant for pre-B3 (and pre-B1) than for pre-B2. There was no correlation (r = 0.2) between the SDF-1 alpha induced migration (range: 2.5-39%) and the cell surface density of CXCR-4 (range: 46.5-97.5%). The extracellular matrix protein FN, either coated on the filter (for more than 18 hours) or in soluble form, enhanced the SDF-1 alpha induced migration of pre-B ALL respectively (2 fold and 1.6 fold) without influencing CXCR-4 expression in short term cultures. Therefore, we analyzed the expression of the FN receptors, VLA-4 (CD49d) and VLA-5 (CD49e), by direct immunofluorescence, on these leukemic cells. VLA-4 was strongly expressed in all stages of pre-B ALL (range: 77-97%) while VLA-5 expression was more variable (range: 14-94%), but no correlation with the FN-dependent increased SDF-1 alpha chemotactic effect was noted. In conclusion, the migratory behavior of pre-B leukemic cells in response to SDF-1 alpha partly depends upon the stage of differentiation, and partly upon unexplained patient variability. Our results suggest that several molecules from the extracellular matrix, such as FN, may be implicated in this phenomenon.

[Detection of clonal T-cell receptor gamma gene rearrangement with the use of PCR-DGGE for diagnosis of erythroderma]. / Réarrangement des gènes du récepteur des lymphocytes T cutanés par la technique de PCR-DGGE pour le diagnostic étiologique des érythrodermies.

BACKGROUND: It is often difficult to establish the etiological diagnosis of erythroderma because clinical findings and immunohistology cannot always distinguish between lymphomatous erythroderma and inflammatory erythroderma. The purpose of this work was to assess the contribution of PCR-DGGE for detecting clonal T-cell receptor gamma gene rearrangement to the etiological diagnosis of erythroderma. PATIENTS AND METHODS: The following inclusion criteria were used: patient with erythroderma; skin biopsy for histologic study, immunophenotyping and molecular biology; minimal follow-up of 12 months after initial diagnosis. Thirty patients were included from May 1, 1995 to November 30, 1998. Histology slides were reread by one of the authors blinded to other data who classed them in three categories: probable lymphoma, probable inflammatory disease, uncertain diagnosis. Molecular data were also analyzed in the same blinded manner. Immunohistology diagnosis was compared with the molecular data and the final diagnosis retained from clinical, histological and molecular findings as well as the disease course to last follow-up (November 1, 1999) after a mean 12 +/- 18 months follow-up. RESULTS: Eight biopsies were classed as probable lymphomas; a T-cell clonal rearrangement of the TCR genes was detected in 7/8 cases. The one sample with no detectable T clone was a drug-induced Sézary pseudolymphoma. The histologial classification identified 16 cases of probable inflammatory disease; no clonal rearrangement of the TCR genes was found in these cases. One of these patients had fungoid mycosis treated with caryolysin for three months and developed treatment intolerance at the time of the skin biopsy. For six biopsies the histological diagnosis was "uncertain"; a clonal rearrangement of the TCR genes was found in 2/3 of the fungoid mycosis cases and in none of the three cases of toxic dermal reactions. DISCUSSION: This study demonstrated the contribution of genotypic analysis with PCR-DGGE to the diagnosis of erythroderma. Monoclonal TCR gene rearrangement was detected in 9/11 (82 p. 100) of the patients with lymphoma and in 0/19 of the patients with an inflammatory dermatosis. The etiological diagnosis of erythroderma is an excellent indication for molecular stud of skin biopsies with PCR-DGGE.

De novo acute B cell leukemia/lymphoma with t(14;18).

The t(14;18)(q32;q21) translocation is the most common translocation in B cell malignancies being found in 80% of follicular lymphomas and about 20% of diffuse large B cell lymphomas. Only rare cases of de novo acute B cell lymphoblastic leukemia with t(14;18) have been described. We describe five cases of this entity which appears to have very homogeneous clinical, phenotypic and genotypic features. None of these patients had prior history of follicular lymphoma. The disease was characterized by acute clinical features with nodal and/or extranodal disease, massive bone marrow infiltration and rapid increase of circulating blast cells of mature B cell phenotype. All patients disclosed complex chromosomal and molecular abnormalities involving at least the BCL-2 and c-MYC genes. Furthermore, three patients had evidence of BCL-6 involvement and one patient had a p53 mutation. Despite intensive chemotherapy, including for two patients allogeneic bone marrow transplantation in first complete remission, all patients died within a few months. Neuro-meningeal relapse occurred in three of the five patients in spite of neuro-meningeal prophylaxis. De novo leukemia/lymphoma with t(14;18) is a rare entity with a very poor prognosis. Whether early bone marrow transplant could modify the natural history of the disease remains to be determined. An intensive neuro-meningeal prophylaxis appears to be mandatory in these patients.

Cutaneous involvement in patients with angioimmunoblastic lymphadenopathy with dysproteinemia: a clinical, immunohistological, and molecular analysis.

OBJECTIVE: To determine whether cutaneous involvement in patients with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is related to a clonal T-cell proliferation. DESIGN: Retrospective study. SETTING: University hospitals. PATIENTS: Ten patients with AILD and cutaneous involvement. MAIN OUTCOME MEASURE: The T-cell receptor-gamma (TCRG)gene rearrangement was studied with the use of polymerase chain reaction and denaturing gradient gel electrophoresis in blood, nodal, and skin samples. Skin and nodal samples were investigated also for the presence of Epstein-Barr virus (EBV) RNA by in situ hybridization. RESULTS: A transient morbilliform eruption of the trunk was seen most often. Other cutaneous features were infiltrated plaques and purpuric or urticarial lesions. A clonal TCRG gene rearrangement was detected in 7 skin samples, corresponding to a maculopapular eruption with a histological pattern of nonspecific mild lymphoid dermal infiltrate in 6 patients, and to erythematous plaques with histological findings of typical cutaneous lymphoma in 1 patient. In the 5 patients in whom a TCRG gene rearrangement was evidenced in skin and lymph node samples, identical clones were detected in both. Five patients died by the end of the study, with a mean survival of 33.2 months. Four of these 5 patients had a clonal infiltrate in skin and lymph nodes. The EBV RNA was detected in only 1 of 10 skin biopsy specimens and in 5 of 8 lymph nodes tested. CONCLUSIONS: Cutaneous involvement is often related to a clonal T-cell proliferation in AILD, even when clinical and histological features are nonspecific. Cutaneous infiltrate seems to be clonally related to the nodal T-cell proliferation. The role of EBV infection in skin lesions was not evidenced.

[Hemophagocytic syndrome and metastatic melanoma: 3 cases]. / Syndrome d'activation macrophagique et mélanome métastatique : 3 cas.

BACKGROUND: Macrophage activation syndrome was initially described during viral infections in immunocompromised patients. Since the original report, many diseases have been found to be associated with macrophage activation syndrome. Lymphoproliferative disorders have been more frequently reported to be associated with macrophage activation syndrome than solid tumors. We herein report three cases of macrophage activation syndrome in patients with metastatic malignant melanoma. CASE-REPORTS: Two young 32 and 40 year-old men with a liver metastatic malignant melanoma and a 62 year-old woman with a polymetastatic malignant melanoma presented a sudden deterioration of general health with hyperthermia and biological abnormalities: liver cytolysis, leucocytosis, thrombocytopenia, hypertriglyceridaemia. A fatal clinical outcome occurred rapidly despite corticotherapy and/or chemotherapy. For the first two patients the macrophage activation syndrome diagnosis was delayed because of the similarities of macrophage activation syndrome and metastatic malignant melanoma symptoms. DISCUSSION: The diagnosis of macrophage activation syndrome in patients with metastatic malignant melanoma may be difficult because of the similarities between clinical features of macrophage activation syndrome and those of metastatic malignant melanoma. Hypertriglyceridaemia is present in 60 p. 100 of macrophage activation syndrome and should lead to process a bone marrow aspirate. The search for a triggering infection should be systematically carry out because it is implicated in more than half of macrophage activation syndrome whatever the associated disease may be: neoplasia, autoimmune disease. The pathogenesis of macrophage activation syndromes occurring in patients with metastatic cancer remains unexplained. Treatment of macrophage activation syndrome is not unanimously established and usually consists in the treatment of the associated condition as well as a corticosteroid and/or an immunosuppressive treatment regimens. Prognosis of macrophage activation syndrome is usually poor especially when it is associated with a neoplasia since a fatal outcome occurs in 40 to 60 p. 100 of cases.

Increased expression of u-PA and u-PAR on monocytes by LDL and Lp(a) lipoproteins--consequences for plasmin generation and monocyte adhesion.

Monocyte-derived foam cells figure prominently in rupture-prone regions of atherosclerotic plaque. As urokinase/urokinase-receptor (u-PA/u-PAR) is the trigger of a proteolytic cascade responsible for ECM degradation, we have examined the effect of atherogenic lipoproteins on monocyte surface expression of u-PAR and u-PA. Peripheral blood monocytes, isolated from 10 healthy volunteers, were incubated with 10 to 200 microg/ml of native or oxidised (ox-) atherogenous lipoproteins for 18 h and cell surface expression of u-PA and u-PAR was analysed by flow cytometry. Both LDL and Lp(a) induced a dose-dependent increase in u-PA (1.6-fold increase with 200 microg/ml of ox-LDL) and u-PAR [1.7-fold increase with 200 microg/ml of ox-Lp(a)]. There is a great variability of the response among the donors, some of them remaining non-responders (absence of increase of u-PA or u-PAR) even at 200 microg/ml of lipoproteins. In positive responders, enhanced u-PA/u-PAR is associated with a significant increase of plasmin generation ( .9-fold increase with 200 microg/ml of ox-LDL), as determined by an amidolytic assay. Furthermore, monocyte adhesion to vitronectin and fibrinogen was significantly enhanced by the lipoproteins [respectively 2-fold and 1.7-fold increase with 200 microg/ml of ox-Lp(a)], due to the increase of micro-PAR and ICAM-1, which are receptors for vitronectin and fibrinogen. These data suggest that atherogenous lipoproteins could contribute to the development of atheromatous plaque by increasing monocyte adhesion and trigger plaque weakening by inducing ECM degradation.

Polymerase chain reaction analysis of immunoglobulin gene rearrangement in cutaneous lymphoid hyperplasias. French Study Group for Cutaneous Lymphomas.

UNLABELLED: The differential diagnosis of cutaneous lymphoid hyperplasia and B-cell lymphoma may be difficult. Whether the detection of clonal immunoglobulin gene rearrangement in the cutaneous lesion is predictive of a malignant outcome remains controversial. We therefore studied cases of cutaneous lymphoid hyperplasia by polymerase chain reaction analysis. DESIGN: Retrospective study of patients seen between 1988 and 1996. SETTING: Two dermatology university departments. PATIENTS: Twenty-four patients with cutaneous lymphoid hyperplasias were included according to clinical, histopathological, and immunophenotypic criteria. MAIN OUTCOME MEASURES: Clinical, histopathological, and laboratory findings. RESULTS: There were 13 men and 11 women (mean age, 49 years) who presented with erythematous or violaceous papules or nodules. The lesions were unique in 13 cases and multiple in 11 cases. All patients had immunochemical evidence of a mixed T- and B-cell infiltrate with polytypic B cells. Polyclonality was demonstrated in 23 patients, whereas a dominant B-cell clone was detected in 1 patient. No lymphoma developed during the follow-up (median, 4 years). In the same period, we studied 53 cases of B-cell lymphomas. Thirty-five (66%) of the 53 cases had a detectable clonal immunoglobulin gene rearrangement. CONCLUSIONS: In the majority of our cases, polyclonality demonstrated by polymerase chain reaction analysis was in accordance with the diagnosis of cutaneous lymphoid hyperplasia. In 1 of the 24 patients, the presence of a B-cell clone could be evidenced. This fact did not modify the treatment as there were no histological or immunophenotypic signs suggestive of a lymphoma.