Chronic lymphocytic leukemia associated with myelodysplastic syndrome and/or chronic myeloid leukemia: evidence for independent clonal chromosomal evolution.

We describe the cytogenetic findings of three cases with simultaneous or sequential development of a B-chronic lymphocytic leukemia (B-CLL) and either a myelodysplastic syndrome (MDS) in 2 cases or a chronic myeloid leukemia (CML) in one case. The coexistence of these two hematologic malignancies leads to questions about their cell of origin. Through analysis of the cytogenetic abnormalities, we studied the derivation of both malignancies. The cytogenetic analyses of these three patients were simultaneously studied from both peripheral blood and bone marrow. Furthermore unstimulated short-time (USSTC) and long-time (72-96 hours) stimulated cultures (LTSC) were systematically performed. In all cases, we have demonstrated the independent bi-clonal evolution. This is the first report ever described for patients with CLPD and MDS and/or MPD shown to arise from distinct chromosomal abnormalities.

Acute myeloid leukemias, multiple myelomas, and chronic leukemias in the setting of HIV infection.

B-cell lineage-derived high-grade malignant lymphomas are a well-recognized complication of HIV infection. However, isolated cases of unusual hematologic malignancies such as acute myeloid leukemias (AML), multiple myeloma (MM) or plasmacytomas, and chronic leukemias have been reported. This review focuses on these uncommon malignancies supervening in the setting of HIV infection. Eighteen cases of AML have been reported. Extramedullary localizations are frequently noticed. Nontreated patients have a survival of 2.7 weeks, compared with 9.8 months for patients treated with chemotherapy; being HIV-positive is not a contraindication to the treatment of AML. Based on the observed 72% incidence of AML M4 and M5 in an HIV-infected population versus 19% to 36% expected in a non-HIV-infected population, we postulate that the association of AML and HIV is not coincidental. The monocytotropism of HIV, the chronic cytokine-mediated activation of monocytes/macrophages, and the immunodeficiency may explain this association. Twenty-two cases of MM or plasmacytomas have been described, most of them in young patients. Again, extramedullary plasma cell tumors are recorded in many patients. Physiopathologic studies suggest that MM may develop because of an antigen-driven response to the circulating viral antigens. A role for Epstein-Barr virus (EBV) in the pathogenesis, as previously described in high-grade non-Hodgkin's lymphomas, is suggested by the presence of EBV genomes in plasma cell tumors. Finally, a broad spectrum of chronic leukemias derived from B- or T-cell lymphocyte lineage has been reported. These associations seem coincidental.

[Acute myelocytic leukemia in immunodeficiency virus infection]. / Les leucémies aiguës myéloïdes au cours de l'infection par le virus de l'immunodéficience humaine.

B lineage-derived malignant proliferation is a well recognized complication of HIV infection. Acute myeloid leukemias have been reported but no complete review of these cases has been performed. The Medline database was reviewed for the years 1980-1997. Eighteen cases of AML have been reported. When previously known, HIV infection was present for 40 months. In 7 patients HIV infection and AML were diagnosed simultaneously. According to the FAB classification, 5 cases were M2, 8 M4, 5 M5. Extramedullary localizations (skin, testis, spleen) were noticed in 10 patients. Non-treated patients had a survival of 2.7 weeks versus 9.8 months in patients treated with chemotherapy. Pathophysiologic studies were performed in 3 cases: reverse transcriptase activity and p24 antigen were noted in tumoral cultured cells in 1 case; absence of viral particules in culture in another one; absence of cloned DNA provirus integration in blasts cells in a third patient. Based on the observed high rate of M4/M5 (72%) versus 19-36% expected in a non HIV-infected population, we postulate that the association of AML and HIV is not coincidental. The monocytotropism of HIV, the chronic cytokines-mediated activation of monocyte/macrophages, the immunodeficiency may explain this association.

CD3+ CD8+ CD56- clonal large granular lymphocyte leukaemia and HIV infection.

High-grade malignant lymphomas associated with HIV infection are usually derived from B lymphocytes. Although a broad spectrum of T-cell-derived malignancies has been described, no case of monoclonal T large granular lymphocyte leukaemia has been reported to date. We report a case of clonal T-LGL (CD3+, CD4-, CD8+, CD56-, CD57+) in an HIV-infected. HTLV1/2-negative individual. Large granular lymphocytes are thought to represent activated cytotoxic T lymphocytes. HIV infection, as previously reported for HTLV1/2, may represent a pathway of antigen activation and lead to clonal expansion of T large granular lymphocytes.

The 17p-syndrome: a distinct myelodysplastic syndrome entity?

The 17p- syndrome is a subset of myelodysplastic syndrome characterized by "typical" dysgranulopoïesis, combining a pseudo-Pelger-Hüet and a deletion of the short arm of chromosome 17. We describe two patients; one with de novo myelodysplastic syndrome (RAEB), one with secondary MDS (RAEB-T). Both showed a 17p- deletion resulting from tanslocations involving 17p associated with an additional complex cytogenetics, and both of them had a particular type of dysgranulopoiesis, combining pseudo-Pelger-Hüet anomaly.

Longitudinal melanonychia induced by hydroxyurea: four case reports and review of the literature.

Although the occurrence of skin lesions during long-term hydroxyurea therapy is well known, longitudinal melanonychia (LM) are more rarely described. In the present paper, we report four cases of LM associated with skin lesions induced by long-term daily hydroxyurea therapy (4 to 10 years), characterized by two uncommon aspects: late onset (2.5 to 5 years) and predominance of toenail involvement in three cases.

Cardiac localization of non-Hodgkin's lymphoma: two case reports and review of the literature.

Secondary non-Hodgkin's lymphoma of the heart (SNHLH) are more frequent than primitive non-Hodgkin's lymphoma and represent the third most common malignant tumour of the heart in autopsy studies. Cardiac involvement usually occurs as a late manifestation in patients with disseminated disease. Initial cardiac lymphoma, defined as cardiac involvement at initial diagnosis with concomitant extracardiac localizations, have nevertheless been reported in approximately 42 cases. The present paper concerns two patients with non-Hodgkin's B-cell lymphoma where cardiac involvement occurring 3 and 6 years after initial diagnosis constituted the unique site of relapse. These cases differ from previous reports of the literature by the predominance of extranodal localizations at initial diagnosis and the late onset of cardiac involvement. Clinical and radiological findings were otherwise in accordance with those usually described in such patients. Transthoracic echocardiography revealed the cardiac tumour in the first case, but in the second case transoesophageal echocardiography and magnetic resonance imaging (MRI) were required to demonstrate its presence. As in most reports, the site of tumour involvement was the right cardiac cavity and histology showed high grade B-cell non-Hodgkin's lymphoma. Polychemotherapy, associated with radiotherapy in the second case, led to partial or complete remission of the cardiac tumour without recurrence within the months of follow-up, although both patients died of their disease within one year.