Classification and clinical behavior of blastic plasmacytoid dendritic cell neoplasms according to their maturation-associated immunophenotypic profile.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare subtype of leukemia/lymphoma, whose diagnosis can be difficult to achieve due to its clinical and biological heterogeneity, as well as its overlapping features with other hematologic malignancies. In this study we investigated whether the association between the maturational stage of tumor cells and the clinico-biological and prognostic features of the disease, based on the analysis of 46 BPDCN cases classified into three maturation-associated subgroups on immunophenotypic grounds. Our results show that blasts from cases with an immature plasmacytoid dendritic cell (pDC) phenotype exhibit an uncommon CD56- phenotype, coexisting with CD34+ non-pDC tumor cells, typically in the absence of extramedullary (e.g. skin) disease at presentation. Conversely, patients with a more mature blast cell phenotype more frequently displayed skin/extramedullary involvement and spread into secondary lymphoid tissues. Despite the dismal outcome, acute lymphoblastic leukemia-type therapy (with central nervous system prophylaxis) and/or allogeneic stem cell transplantation appeared to be the only effective therapies. Overall, our findings indicate that the maturational profile of pDC blasts in BPDCN is highly heterogeneous and translates into a wide clinical spectrum -from acute leukemia to mature lymphoma-like behavior-, which may also lead to variable diagnosis and treatment.

Fine needle aspiration cytology diagnosis, flow cytometry immunophenotyping and histology in clinically suspected lymphoproliferative disorder: a comparative study.

OBJECTIVE: To evaluate advantages and drawbacks of fine needle aspiration cytology (FNAC) with flow cytometry (FC) in our routine, using, whenever possible, histology as the gold standard. STUDY DESIGN: From November 2003 to April 2005, we studied, by FNAC and FC, 113 patients with a tentative clinical diagnosis of lymphoproliferative disorder. Excision was performed in 43 patients. RESULTS: Excluding the 7 cases in which FNAC/FC made the diagnosis of metastatic carcinoma, a conclusive diagnosis was obtained with FNAC/FC in 87.7% (93 of 106) of patients. Most of these (n = 48) corresponded to reactive processes. Histologic study of 8 cases confirmed FNAC/FC diagnosis of reactive process. Insufficient material was obtained in 8 (7.1%) patients, and discordance between FNAC and FC occurred in 5 (4.4%), leading to inconclusive diagnosis. There was concordance in benign and malignant diagnoses between FNAC/FC and histology in every case in which conclusive diagnosis of FNAC/FC was advanced. CONCLUSION: FNAC and FC together provide a reliable, definitive diagnosis in most cases, obviating, whenever a reactive process is found, unnecessary surgery or follow-up. Histology was useful in the few cases in which FNAC/FC could not reach conclusive diagnosis and in subclassification of specific lymphomas.

Intraclonal diversity in a Sezary syndrome with a differential response to 2-deoxycoformycin of the two lymphoma cell populations.

We report a case of Sezary syndrome with two abnormal CD4+ T-cell populations detected in the peripheral blood by flow cytometry immunophenotyping and DNA cell content, suggesting a biclonal T-cell lymphoproliferative disorder. Despite these findings, molecular analysis of the T-cell receptor genes was consistent with a monoclonal T-cell proliferation, supporting the existence of intraclonal diversity rather than a true biclonal disease. The patient achieved a transient response with 2-deoxycoformycin, with a selective decrease of the larger/hyperploid T-cell population; later on, an increased representation of this T-cell population was observed concomitantly with clinical relapse.

Abnormal NK cell lymphocytosis detected after splenectomy: association with repeated infections, relapsing neutropenia, and persistent polyclonal B-cell proliferation.

We report the case of a boy with hereditary spherocytosis who presented with mild microcytic hypochromic anemia and recurrent leg ulcers that had been present since childhood. Chronic natural killer (NK) cell and B-cell lymphocytosis was detected 1 year after therapeutic splenectomy during investigation of recurrent episodes of neutropenia and persistent lymphocytosis. NK cells proved to be abnormal at immunophenotyping studies, and B-cells were polyclonal and displayed a normal immunophenotype. Genotypic analysis of T-cell receptor (TCR)-beta and TCR-gamma genes showed a germ-line pattern. The clinical course of this patient was characterized by multiple pulmonary infections and amygdalitis. We discuss the potential roles of persistent immune stimulation due to chronic hemolysis and severe leg ulcers and of splenectomy in the origin of NK cell lymphocytosis and the relationship between NK cells and recurrent infections, relapsing neutropenia, and polyclonal B-cell response.