Frédéric Charlotte

Bone marrow involvement in lymphomas with hemophagocytic syndrome at presentation: a clinicopathologic study of 11 patients in a Western institution.

Hemophagocytic syndrome (HPS) is a clinicopathologic syndrome that can reveal a non-Hodgkins lymphoma. The pathologic features of lymphoma associated with HPS remain ill defined. We studied 11 lymphomas associated with HPS on initial bone marrow biopsies, consecutively diagnosed during a 6-year period in a Western institution. There were seven diffuse large B-cell lymphomas (DLBCLs), three T-cell lymphomas (one peripheral T-cell lymphoma unspecified, two hepatosplenic &ggr;&dgr; T-cell lymphomas [HS &ggr;&dgr;TLs]), and one aggressive NK-cell lymphoma/leukemia (NKL). These lymphomas shared common clinicopathologic features with a systemic presentation, a poor outcome (nine patients died within 2 years), and a mild interstitial lymphoid infiltrate of the bone marrow at presentation in nine patients. This equivocal lymphoma infiltrate was blending with normal hematopoietic cells, and CD20 and CD3 immunolabelings were essential for its detection. A high number of reactive T (CD3+) cells, most often with a predominant cytotoxic (CD8+ TiA1+) phenotype, was present in all DLBCLs. By in situ hybridization, Epstein-Barr virus was detected in neoplastic cells of three cases (one DLBCL, one HS &ggr;&dgr;TL, and one NKL), which also showed serum viral DNA. Polymerase chain reaction studies disclosed HHV6 DNA sequences in tumor tissues of two DLBCLs, whereas HHV8 DNA was not detected. Because tumor mass indicative of lymphoma was not striking in most patients, bone marrow biopsy appears to be of great value for the diagnosis of an HPS-associated lymphoma, which may be, in Western patients, of B- as well as T- or NK-cell type. Immunostaining for CD3 and CD20 is essential to identify the common subtle lymphoma involvement. Together with a better understanding of the pathogenic processes, an early diagnosis may improve the prognosis of HPS-associated lymphoma.

HHV-8-Associated T-Cell Lymphoma in a Lymph Node With Concurrent Peritoneal Effusion in an HIV-Positive Man

Primary effusion lymphoma (PEL) is an uncommon large cell lymphoma, usually seen in human immunodeficiency virus (HIV)-infected patients. PEL is characterized by various clinical, histomorphologic, and immunophenotypical features, and is associated with the human herpes virus 8 (HHV-8). PEL may present as either a body cavity-based lymphomatous effusion or a solid tumor mass. Most so-called “solid PEL” usually have an extranodal location; exceptionally rarely, they occur in lymph nodes. The majority of PEL consist of malignant cells of B-cell genotype; seldom they are of T-cell origin. We report a rare case of HHV-8-associated “solid PEL” of T-cell type in a 41-year-old HIV-seropositive man with a concomitant peritoneal effusion. The T-cell lymphoma was diagnosed on the basis of morphologic, immunophenotypic, and molecular findings of a lymph node biopsy. The tumor cells strongly expressed CD45R0, CD7, CD43, MUM1/IRF4, CD30, HHV-8, and EBER, and demonstrated a clonal rearrangement of T-cell receptor-γ chain gene. The following case provides another example of a lymph node-based “solid” PEL, demonstrating the variety within the spectrum of HHV-8-associated lymphoma.

Intensive chemotherapy with hematopoietic cell transplantation after ESHAP therapy for relapsed or refractory non-Hodgkin's lymphoma. Results of a single-centre study of 65 patients.

This study was designed to assess the results of protracted courses of ESHAP (etoposide, cytarabine, cisplatin, methylprednisolone) therapy followed by intensive chemotherapy and hematopoietic cell transplantation (IC+HCT) for relapsed or refractory non-Hodgkins lymphoma (NHL). Treatment consisted of 3 cycles of ESHAP; responsive patients (pts) then received 3 more cycles, and IC+HCT was used for pts in maintained partial (PR) or complete (CR) remission after the sixth ESHAP. Sixty-five pts entered the study. At enrollment, 27 pts had bone marrow (BM) and/or central nervous system (CNS) lymphomatous infiltration. Disease status was primary refractory lymphoma in 41 pts (63 %), and relapse in 24 pts (37 %). Results showed that two pts were not evaluable for the therapeutic response because of early treatment-related death. Thirty-nine (62 %) pts entered PR or CR after 3 cycles of ESHAP. Eleven pts subsequently had disease progression. Twenty-eight pts were in persistent CR or PR after 6 cycles of ESHAP. Refractory pts did not show a different response rate to relapsing pts (chi2= 1.73). Five pts were excluded from IC+HCT because of an inadequate graft or treatment-related toxicity. Twenty-three (35 %) pts completed the procedure. Five pts (22 %) relapsed after IC+HCT. The overall survival rate of the 39 responsive pts is 45 % at 60 months, with a median survival time of 30 months. Median survival among the 35 pts in whom second-line chemotherapy failed is 7.1 months, with a 4-year survival rate of 3 %. Despite the poor prognostic features of this group, 45% of pts responding to the first 3 cycles of chemotherapy are in prolonged remission, suggesting that rather than to transplant after just 2 cycles of salvage therapy, pursuing second-line chemotherapy may better discriminate between patients more likely to benefit from a subsequent transplant.

AIDS-related primary lymphoma of the pleural cavity. A case report.

BACKGROUNDnPleural effusions are common in patients with the acquired immunodeficiency syndrome (AIDS). Their most frequent causes are Kaposis sarcoma and mycobacterial infections. We report cytologic, immunophenotypic and molecular features of a primary pleural non-Hodgkins lymphoma (NHL) that represent an uncommon cause of isolated pleural effusion in patients with AIDS.nnnCASEnA 66-year-old, human immunodeficiency virus-positive male presented with chest pain and dyspnea. He had no history of opportunistic infections or Kaposis sarcoma. A chest radiography displayed a right-sided pleural effusion. Cytology of pleural fluid revealed lymphomatous cells with markedly irregular nuclei. Their immunophenotype was indeterminate. Computed tomography of the thorax and abdomen did not show any tumor mass. Molecular analysis demonstrated that the lymphomatous cells had a B-cell genotype and contained Kaposis sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) DNA sequences.nnnCONCLUSIONnThis case belongs to a new subgroup of AIDS-related NHL that is characterized by unusual morphology, null immunophenotype, B-cell genotype and association with both KSHV and EBV.

Pulmonary Infiltration in Anaplastic T-Cell Lymphoma

Respiratory distress with pulmonary parenchymal infiltration is common during the course of lymphoma or other lymphoproliferative disorders. This event may be related to a variety of causes, as discussed here based on the case of a woman with remission of anaplastic large T-cell lymphoma (ALCL), respiratory distress, lung infiltrates, and CD8+ lymphocytes in bronchoalveolar lavage (BAL) fluid samples.