De-novo CD5 + B- prolymphocytic leukemia (PLL) presenting at younger age with favourable outcome/Kucuk yasta olumlu prognoz ile seyreden de-novo CD5 + B- prolenfositik losemi (PLL).
Prolymphocytic leukemia (PLL) was first described in 1974 as a rare variant of chronic lymphocytic leukemia (CLL) . By definition, prolymphocytes must exceed 55%, and cases with 11-54% prolymphocytes are designated CLL/PLL [1,2]. In 60-70% of cases, PLL is of B-cell lineage, and the rest constitute T-PLL. De novo B-PLL is a rare and progressive disease comprising 1% of CLLs  with a median survival of 65 months . It has an older age of presentation, with median age at 70 years  and poor outcome. The usual immunophenotype is strong surface IgM, FMC 7 and B-cell antigen CD19, CD20, CD22, and CD79a and b. CD5 is present in one-third of cases and CD23 is typically absent . Herein, we report a case of B-PLL with younger age of presentation, indolent clinical course and strong CD5 positivity.
This 48-year-old male presented to us with weight loss for 4 months and fever, headache and easy fatigability for 1 month. On examination, he had pallor, nontender lymphadenopathy (B/L axillary and right inguinal 0.5-1 cm), hepatomegaly palpable 3 cm and massive splenomegaly palpable 10 cm below respective costal margins. Routine hemogram showed low hemoglobin ranging from 74-83 g/L, persistent high total leukocyte counts (TLC) ranging from 55-75 x [10.sup.9]/L and sustained platelet counts ranging from 214-244 x [10.sup.9]/L.
Peripheral smear and bone marrow aspirate showed a predominant population (90%) of medium-sized cells with moderate amount of light basophilic agranular cytoplasm with occasional cytoplasmic blebs, and slightly eccentric nucleus with relatively regular nuclear margins, less condensed chromatin and a single centrally placed nucleolus (Figure 1). Cytochemically, these cells were negative for myeloperoxidase, Sudan black, acid phosphatase and periodic acid Schiff, while few cells showed granular and dot positivity with non-specific esterase as described in an older literature . The bone marrow trephine biopsy was cellular and showed diffuse as well as nodular pattern of infiltration by immature cells. With this morphology, a diagnosis of chronic lymphoproliferative disorder with possibilities of PLL and hairy cell leukemia (HCL)-variant was made and immunophenotyping was advised. Immunophenotyping was strongly positive for CD5, CD45, CD19, CD22, FMC-7, S-Ig and CD38, moderately positive for CD11c, weakly positive for CD23, and negative for CD-103 and ZAP 70. Cyclin D1 staining was not available. With this phenotype, a diagnosis of CD5+ B-cell PLL was made.
[FIGURE 1 OMITTED]
During hospitalization, the patient received supportive care and a first cycle of chemotherapy with fludarabine and cyclophosphamide for 3 days, which he tolerated well with reduction in total blood counts from 63 x [10.sup.9]/L (pre-chemotherapy) to 43 x [10.sup.9]/l (post-chemotherapy). He was subsequently discharged and developed fever after a few days of discharge, for which he was re-admitted and received antibiotics. His TLC had declined to 6 x [10.sup.9]/l with 29% prolymphocytes. He subsequently underwent all six cycles of chemotherapy uneventfully. At 6 months post-chemotherapy, he had one episode of community-acquired pneumonia of the left lower lobe requiring hospitalization, which was treated successfully. Now at 14 months postchemotherapy, he has no pallor or organomegaly and his counts have normalized with Hb 130 g/L, TLC 6.3 x [10.sup.9]/L and platelet count 142 x [10.sup.9]/L, and with bone marrow showing remission.
Patients with B-PLL typically have massive splenomegaly, minimal lymphadenopathy, very high TLC with distinct morphology, resistance to chemotherapy, and poor prognosis [1,5]. The treatment in PLL has progressed from splenectomy, splenic irradiation, leukapheresis and alkylating agents to purine nucleoside analogs (fludarabine, cladribine and pentostatin) with prolonged progression-free survival with fludarabine . More recently, the monoclonal antibodies alemtuzumab  and rituximab  have proved useful in treating B-PLL.
Aberrant CD5 expression is a characteristic feature of small lymphocytic lymphoma/CLL (SLL/CLL) and mantle cell lymphoma (MCL), which can be distinguished reliably by CD23, being positive in the former and negative in the latter . In BPLL, CD5 expression is variable and seen in up to one-third of cases. Thus, B-cell PLL may be divided into CD5+ PLL (arising in CLL) and CD5- PLL (de novo PLL). CD5+ PLL has a longer median survival than CD5- PLL . In contrast, our case represents a de novo B-PLL with CD5 positivity rather than CLL in transformation, who had a short duration of illness, younger age at presentation and good response to chemotherapy. In another study , no significant difference between de novo PLL and prolymphocytoid transformation of CLL was found, but patients with p53 mutations had worse prognosis irrespective of the presentation. B-PLL has also been sub-classified into two groups based on cytogenetic findings, namely t (11; 14) positive group and t (11; 14) negative group. CD5 expression was more frequent in the former . The authors have retrospectively re-classified these cases as MCL. Although leukemic phase of blastoid MCL can be a difficult differential diagnosis of B-PLL, in the index case, the monomorphic population of atypical lymphocytes with characteristic morphology and immunophenotyping characteristics tilted our diagnosis in favor of B-PLL short of cyclin D1 staining and cytogenetics.
The other differential diagnosis entertained was HCL-variant. The immunophenotype differs somewhat from classical HCL in that there is variable expression of CD103 and lack of CD25 . Since HCL is typically CD5- and 23- negative, we ruled it out as a possibility in this case. A study  evaluating CD11c+ CD5+ chronic B-cell leukemias found that these represent forms of either CLL or PLL rather than HCL.
In conclusion, this case illustrates the importance of immunophenotyping as an adjunct to morphology in the diagnosis of chronic lymphoproliferative disorders. It also underscores the fact that de novo cases of B-PLL may have aberrant CD5 positivity may not be as aggressive as previously believed.
Received: February 22, 2007 Accepted: October 11, 2007
Gelis tarihi: 22 Subat 2007 Kabul tarihi: 11 Ekim 2007
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Rakhee Kar, Rajat Kumar, Seema Tyagi
Department of Hematology, All India Institute of Medical Sciences, New Delhi, India
Address for Correspondence: Dr. Rakhee Kar, Department of Haematology, AIIMS 110029 New Delhi, India
Phone: +91-11-26594670 E-mail: email@example.com
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|Title Annotation:||cluster of differentiation|
|Author:||Kar, Rakhee; Kumar, Rajat; Tyagi, Seema|
|Publication:||Turkish Journal of Hematology|
|Article Type:||Case study|
|Date:||Sep 1, 2008|
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