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Biomedical subjects

F Delacrétaz

Publications and source records attributed to F Delacrétaz.

At least 19 recordsLinked to original sources

Pitfalls in TRAP assay in routine detection of malignancy in effusions.

Telomerase has been found to be reactivated in a majority of cancers but is inactive in most somatic cells. Our principal goal was to determine the potential use of the telomeric repeat amplification protocol (TRAP) assay as marker for malignancy in cytological effusions. The simple selection criterion was the cytological diagnosis, and routine samples were classified into malignant (58 samples) and nonmalignant (233 samples). Of the malignant samples, 44/58 (76%) were positive by TRAP assay. Of the 14 telomerase-negative cytology-positive samples, RNA integrity was poor in 9, indicating suboptimal sample conservation for molecular analysis. In 3 of the remaining 5 samples with a negative TRAP assay, a high number of malignant cells was observed, and these cells might have been telomerase-negative. Thus, the sensitivity of TRAP assay for the presence of malignant cells was about 76%. In the cytologically nonmalignant effusions, the presence of telomerase activity was observed in 24% (55/233). Of these, 6% were highly suspicious for malignancy, 9% were doubtful, and 9% were cytologically nonmalignant effusions confirmed by a follow-up of 12 mo or more. According to these data, the specificity of the TRAP assay to detect tumor cells in effusions ranged only between 82-91%. Our results indicate that, although the TRAP assay is positive in 6-15% of putative malignant effusions, the relatively high number of TRAP false-negative and false-positive cases renders this test unsuitable for routine diagnostic purposes.

Adolescent↗

Polymerase chain reaction in the diagnosis of T-cell lymphoma in paraffin-embedded bone marrow biopsies: a comparative study.

AIMS: In routine histological analysis of bone marrow biopsies, the distinction between reactive T-cell infiltrates and T-cell lymphoma can be difficult, even with the use of extensive immunohistochemistry. The aim of this study was to evaluate the diagnostic contribution of TCR-gamma gene rearrangement analysed by PCR. METHODS AND RESULTS: The samples studied consisted of 46 paraffin-embedded bone marrow biopsies (diagnosis, staging and follow-up) from 26 patients with T-cell lymphoma. The bone marrow biopsies were categorized into three groups according to the morphological and immunohistochemical results. Group 1, positive for T-cell lymphoma (24 bone marrow biopsies), group 2, suspicion of T-cell lymphoma (15 bone marrow biopsies) and group 3, negative for T-cell lymphoma (seven bone marrow biopsies). DNA could be amplified in 45/46 bone marrow biopsies (98%). Clonal rearrangement was detected in 30/45 bone marrow biopsies tested (67%) including 15/24 bone marrow biopsies (62.5%) of group 1, 11/14 (78.5%) of group 2 and 4/7 (57%) of group 3. In total, PCR analysis supported a diagnosis of T-cell lymphoma in 15/45 bone marrow biopsies (33%), in which histological and/or immunohistochemical examination provided inconclusive evidence of malignancy. CONCLUSIONS: TCR-gamma PCR is a complementary tool for the assessment of T-cell lymphoma in bone marrow biopsies. Optimal evaluation of bone marrow biopsies requires an integrative approach of all available results from morphology, immunohistochemistry, molecular biology and clinical data.

Biopsy↗

[Primary bilateral adrenal lymphoma].

When abdominal imaging reveals the existence of unsuspected adrenal masses, a diagnostic strategy is necessary. We report the case of a woman presenting with pulmonary embolism, in whom abdominal ultrasound revealed voluminous masses in both adrenals without clinical or biological signs of hormone hypersecretion, but with mild primary adrenal failure. From a CT scan-directed needle biopsy of the right adrenal mass and subsequent staging we were able to diagnose a primary bilateral adrenal lymphoma, diffuse large B-cell type (REAL/WHO). On CHOP chemotherapy both adrenal masses decreased dramatically and the patient is in remission 18 months later. Primary adrenal lymphoma is a rare condition, since 65 cases have been reported to date. Histological diagnosis is nevertheless important, in view of the excellent response to specific therapy observed in some cases.

Adrenal Gland Neoplasms↗

CD34/QBEND10 immunostaining in bone marrow biopsies: an additional parameter for the diagnosis and classification of myelodysplastic syndromes.

CD34/QBEND10 immunostaining has been assessed in 150 bone marrow biopsies (BMB) including 91 myelodysplastic syndromes (MDS), 16 MDS-related AML, 25 reactive BMB, and 18 cases where RA could neither be established nor ruled out. All cases were reviewed and classified according to the clinical and morphological FAB criteria. The percentage of CD34-positive (CD34 +) hematopoietic cells and the number of clusters of CD34+ cells in 10 HPF were determined. In most cases the CD34+ cell count was similar to the blast percentage determined morphologically. In RA, however, not only typical blasts but also less immature hemopoietic cells lying morphologically between blasts and promyelocytes were stained with CD34. The CD34+ cell count and cluster values were significantly higher in RA than in BMB with reactive changes (p<0.0001 for both), in RAEB than in RA (p=0.0006 and p=0.0189, respectively), in RAEBt than in RAEB (p=0.0001 and p=0.0038), and in MDS-AML than in RAEBt (p<0.0001 and p=0.0007). Presence of CD34+ cell clusters in RA correlated with increased risk of progression of the disease. We conclude that CD34 immunostaining in BMB is a useful tool for distinguishing RA from other anemias, assessing blast percentage in MDS cases, classifying them according to FAB, and following their evolution.

Adolescent↗

Frequent methylation silencing of p15(INK4b) (MTS2) and p16(INK4a) (MTS1) in B-cell and T-cell lymphomas.

The methylation status of p15(INK4b) (MTS2), p16(INK4a) (MTS1) and p14(ARF) (p16beta) was analyzed in 56 lymphomas by restriction-enzyme related polymerase chain reaction (PCR) (REP), methylation-specific PCR (MSP), and bisulfite genomic sequencing (BGS). Methylation of the p15 and p16 genes was detected, respectively, in 64% and 32% of the B-cell lymphomas, in 44% and 22% of the T-cell lymphomas, and in none of the 5 reactive lymph nodes analyzed. Both p15 and p16 genes were methylated more often in the high-grade (78% and 50%, respectively) than in the low-grade B-cell lymphomas (55% and 21%, respectively). For 5 cases, mapping of the methylated CpGs of the p16 promoter region confirmed the results of REP and MSP. In addition, a large variation in the methylation patterns of p16 exon 1 was observed, not only from one lymphoma to another, but also within a given tumor. Methylation of p15 and p16 was associated with an absence of gene expression, as assessed by reverse transcription-PCR. The p14 gene was unmethylated and normally expressed in all 56 tumors. We found no mutations of p15, p16, or p14 in any of the 56 lymphomas. Our results suggest a role for p15 and p16 gene methylation during lymphomagenesis and a possible association between p15 and p16 inactivation and aggressive transformation in B-cell and T-cell lymphomas.

Carrier Proteins↗

Prognostic value of follicular dendritic cells in nodular sclerosing Hodgkin's disease.

AIMS: In nodular sclerosing Hodgkin's disease (NSHD), the prognostic relevance of the histopathological grading in two subtypes NSI (low-grade) and NSII (high-grade) remains controversial. Analysis of follicular dendritic cells (FDC) may provide new prognostic parameters. METHODS AND RESULTS: Tumours from 59 patients with NSHD were studied. Mean follow-up time was 8 years. Forty-one cases were classified as NSI and 18 as NSII. FDC were immunostained with the paraffin-resistant monoclonal antibodies CD21 and CNA.42. We distinguished three patterns in the neoplastic tissue: FDC1, the presence of well-defined follicle-like structures (n = 20); FDC2, the presence of largely destroyed FDC networks (n = 25); and FDC3, no or a few isolated FDC (n = 14). The three groups differed clearly regarding the frequency of relapse and the survival. The longest survival was seen in the FDC1 group, the shortest in the FDC3 group, the FDC2 group being intermediate (P = 0.0025). FDC status was a discriminating prognostic factor for all patients, and within various age and stage categories. Combining the FDC status and the NSI-NSII grading defined the best survival group as FDC1-NSI. CONCLUSIONS: Assessment of FDC pattern, associated with histological subtyping, brings valuable data for predicting survival and outcome in NSHD.

Adolescent↗

Systemic mastocytosis following a malignant ovarian germ cell tumour.

Cases of mediastinal germ cell tumours associated with haematological disorders (two cases of systemic mastocytosis included) have been reported previously. This combination is more frequent than would be expected by chance alone. We report the case of a 30-year-old woman, who presented with a systemic mastocytosis following a malignant ovarian germ cell tumour which was treated by chemo- and radiotherapy. The patient predominantly complained of skeletal pains, which led to an erroneous radiological diagnosis of fibrous dysplasia for years. An aggressive variant of systemic mastocytosis was diagnosed on bone marrow examination. Systemic mastocytosis was confirmed by splenectomy, liver biopsy and finally autopsy. The present case is unique because of the ovarian location of the germ cell tumour. We suggest our observation could be related to the broad group of haematological malignancies associated with germ cell tumours.

Adolescent↗

[Polyarthralgia, fever and purpura in a patient known to have splenomegaly].

A 43-year-old patient was admitted for swollen and painful ankles, knees and elbows, palpable purpura of the lower extremities and fever. Splenomegaly had been diagnosed 5 years previously. At clinical workup, spleen and liver size were increased and purplish papular skin lesions were noted above the ankles. Erythrocyte sedimentation rate was 2 mm/h. ASAT and ALAT as well as rheumatoid factor were moderately elevated. Serology was positive for hepatitis C. Differential diagnosis of palpable purpura and complementary diagnostic procedures are discussed.

Adult↗

Distribution and localization of Epstein-Barr virus subtypes A and B in AIDS-related lymphomas and lymphatic tissue of HIV-positive patients.

Tissue samples of 21 HIV-positive patients have been studied for the presence and distribution of Epstein-Barr virus (EBV) subtypes A and B. This was done by PCR, EBER in situ hybridization, and immunohistochemical detection of EBV latent membrane protein (LMP) in AIDS-associated malignant lymphomas (16 cases) and lymphatic organs of patients without lymphoma (5 cases). Eleven cases were considered to be EBV-positive, with type A in four, and type B virus in four other cases. In patients with malignant lymphoma, EBV was localized in tumour tissue exclusively. One patient without lymphoma presented with multiple EBV genome type B-positive cells in all the lymphoid tissue samples examined. In HIV-positive patients, both subtypes of EBV, A and B, may play a role in the pathogenesis of lymphoproliferative lesions.

Adult↗

Current concepts in pediatric burn care: management of burn wounds with cultured epidermal autografts.

Our experience with CEA is based on 21 patients operated on from 1986 to 1991. The areas covered with CEA measured 500 cm2 to 3160 cm2. At one setting no more than 40 sheets of 40 cm2 CEA have been transplanted. The take of CEA is over 75% when applied to dermis. The same holds true when covering "deepithelialised" skin homografts on immunosuppressed patients. Scar formation has not been a problem, and the overall results have been good.

Adolescent↗

Sinus histiocytosis with massive lymphadenopathy (Rosai Dorfman disease) in an HIV-positive patient.

We report a case of a 31-year-old HIV infected black female, who presented with asymptomatic generalized lymphadenopathy. Three particularly enlarged lymph nodes were biopsied (2 cervical and 1 axillary). The histological picture was consistent with a diagnosis of sinus histiocytosis with massive lymphadenopathy (SHML) or Rosai-Dorfman disease. Large histiocytes, positive for a variety of macrophage markers and for the S-100 protein, were observed in the distended sinuses. A few hyperplastic follicles, such as usually seen in HIV-infection-associated lymphadenopathy, were present at the periphery of one lymph node. No infections agent besides HIV could be detected by histological or microbiological analysis or by in situ hybridization. This is the first reported case of SHML associated with HIV infection. The possible relationship between the two diseases is discussed.

Adult↗

Dysmegakaryopoiesis predicting response to therapy in acute myeloid leukaemia. A histologic and clinical study.

With standard induction therapy between 50 to 85% of patients with Acute Myeloid Leukaemia (AML) achieve Complete Remission (CR). We investigated whether any morphological feature of bone marrow (BM) plastic embedded biopsies could predict failure of therapy. We reviewed BM plastic embedded biopsies from 54 adult patients presenting with untreated AML. The main histologic parameters analysed were cellularity, dysmegakaryopoiesis (DysM), percentage of marrow blasts and fibrosis. CR was obtained in 34 of 49 treated patients (69%). The rate of CR was significantly lower in the group of patients presenting with DysM: CR was achieved in 54% of the 28 treated patients with DysM and in 90% of the 21 treated patients without DysM (p less than 0.02). Patients with DysM had a significantly lower blood count and bone marrow blasts at presentation. Median age was not significantly different in the 2 groups. Cellularity and fibrosis were not predictive. DysM may be the hallmark of an AML subgroup with distinct clinical behaviour and lower rate of CR with conventional therapy. DysM should be carefully looked for on BM marrow biopsies and aspirate from AML patients at diagnosis.

Acute Disease↗

Genotypic and phenotypic evidence of T-cell leukemia in a patient successfully treated by interferon-alpha for typical hairy cell leukemia.

A 53-year-old man was diagnosed to have typical hairy cell leukemia. Immunophenotyping of frozen splenic tissue showed clonality of hairy cells for mu lambda, confirmed by the corresponding immunoglobulin gene rearrangements. The patient was successfully treated with interferon-alpha (IF-alpha). In the fifth year of treatment with IF-alpha the morphology of peripheral blood mononuclear cells (PBMC) and of bone marrow infiltration changed with the appearance of numerous small to intermediate shaped lymphocytes of a T-helper phenotype. Frank leukemia, resistant to IF-alpha treatment and ultimately aggressive chemotherapy, developed. Emergence of this second clonal disease was confirmed by rearrangement studies performed on PBMC; rearrangements of both alleles of the TCR beta were identified, whereas the JH and lambda IVS genes were in germline configuration. The outgrowth of a second, malignant T-cell clone paralleled by the disappearance (down-regulation?) of the initial B-cell clone while under cytokine treatment is consistent with the possibility that IF-alpha favoured the emergence of this second clone.

Bone Marrow↗

[Refractory anasarca].

In a 68-year-old male hospitalized for a traffic accident physical examination revealed a left tibial fracture and an asymptomatic left pleural effusion. The evolution was characterized essentially by the appearance of oedema of the legs, ascites, and aggravation of the left pleural effusion with concomitant right effusion. Immediate therapy consisted of digitalis and diuretics. Several days later the patient suddenly complained of epigastric pain irradiating to his arms, followed by vomiting. ECG showed transitory elevation of ST segment in V3 to V5. Blood levels of CK and CK-MB were normal. An electrocardiogram showed extensive antero-septal-apical akinesis and a very small cardiac effusion. Pleural and abdominal tap revealed the presence of a milky liquid containing 40 g/l proteins, 8.6 mmol/l triglycerides and 2.5 mmol/l cholesterol, with no atypical or tumorous cells. CAT scan revealed the presence of a retroperitoneal mass extending from the diaphragm to the iliac crests and apparently enclosing the aorta and the vena cava and causing bilateral hydronephrosis. The development of chylous ascites and/or chylothorax indicates the presence of an extrinsic or intrinsic obstruction of lymphatic drainage or the existence of a laceration or rupture of the thoracic canal. Chylous ascites is not a frequent finding, since only 28 cases have been diagnosed in 20 years at the Massachusetts General Hospital and 71 in 30 years at the Mayo Clinic. In these 2 series a tumoral etiology was found in more than 85% of the cases. The most frequently encountered tumor was lymphoma followed by cancer of the pancreas, stomach, or other tumors. CLINICAL DIAGNOSIS: Retroperitoneal tumor, most probably lymphoma; inferior vena cava compression syndrome; subacute antero-septal infarction. In spite of the poor general condition of the patient exploratory laparotomy was performed, and several specimens were taken from the lymphatic nodes located at the angle of Treitz, in the mesentery and the mesocolon and along the celiac axis. HISTOPATHOLOGICAL DIAGNOSIS: Non-Hodgkin B-cell malignant lymphoma, low-grade, lymphoplasmacytoid (immunocytoma) according to the Kiel classification, or small lymphocytic, plasmacytoid according to the International Working Formulation (abdominal lymph nodes, liver, epiploon, peritoneum, rectus abdominis muscle). EVOLUTION: Chemotherapy was instored consisting of a combination of prednisone, vincristine, and cyclophosphamide. The patient's condition was complicated by peritonitis. Laparotomy revealed phlegmonous cholecystitis and a perforated colon. The post-operative course was characterized by septic shock, cardiac and respiratory insufficiency which resulted in the death of the patient. Autopsy confirmed the presence of a low-grade lymphoma stage IV (retroperitoneum, mesentery, cervical, axillary and abdominal lymph nodes, liver, spleen, pancreas, colon, rectum, kidneys, adrenal glands, bronchi, epicardium). No evidence of an infarctus or oth

Aged↗

[Therapy of thrombocytosis in myeloproliferative syndromes using recombinant interferon-alpha-2a].

In a prospective open study 16 consecutive patients with a myeloproliferative syndrome and thrombocytosis were treated with interferon (IFN) alpha-2a. 4 patients had polycythemia vera, 4 essential thrombocythemia, 3 myeloid metaplasia and 5 chronic granulocytic leukemia. Platelet counts decreased in all treated patients within 2 to 12 weeks from a median value of 1010 x 10(9)/l to 350 x 10(9)/l. No primary or secondary resistance was observed. The initial dose of IFN was 9 m U per day. After correction of the thrombocytosis, it was progressively reduced to a minimum dose of 3 m U per week. Despite the good platelet response to IFN, leukocytosis persisted in 3 patients and polycythemia in a further 3. Side effects and poor compliance required discontinuation of therapy in 6 patients. Special attention is focused on the follow-up in 6 patients who have been treated for more than 15 months.

Adult↗