B Cell Prolymphocytic Leukemia

11/10/2014
B cell prolymphocytic leukemia
Official reprint from UpToDate

www.uptodate.com 2014 UpToDate
Authors
Arnold S Freedman, MD
Jon C Aster, MD
Claire Dearden, MD, BSc,
FRCP, FRCPath
Section Editor
Andrew Lister, MD, FRCP,
FRCPath, FRCR
Deputy Editor
Rebecca F Connor, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Sep 2014. | This topic last updated: Sep 03, 2014.
INTRODUCTION B cell prolymphocytic leukemia (B-PLL) is a very rare B cell neoplasm comprised of socalled prolymphocytes, typically with involvement of the peripheral blood, bone marrow, and spleen. The name
"prolymphocyte" is actually a misnomer, as the tumor cells in this disease are mature activated B cells. By
definition, these prolymphocytes comprise greater than 55 percent of the cells in the blood and bone marrow.
The epidemiology, clinical presentation, pathology, diagnosis, and treatment of B-PLL are discussed here.
EPIDEMIOLOGY B-PLL is an extremely rare disease, comprising far less than 1 percent of B cell leukemias
[1]. Since the diagnosis was changed to exclude cases of mantle cell lymphoma, atypical chronic lymphocytic
leukemia (CLL), and CLL/PLL (defined as between 15 and 55 percent prolymphocytes), B-PLL has become
increasingly rare.
B-PLL mainly affects the elderly with a mean age at presentation of between 65 and 70 years [2]. Men and
women appear to be equally affected [1]. The vast majority of patients are Caucasian.
CLINICAL FEATURES Patients typically present with a rapidly rising white blood cell count >100,000/microL
and massive splenomegaly; anemia and thrombocytopenia are present in approximately 65 and 35 percent,
respectively [3,4]. Systemic B symptoms (ie, fevers, night sweats, weight loss) are common. If present,
peripheral lymphadenopathy is not prominent. (See "Clinical presentation and diagnosis of non-Hodgkin
lymphoma", section on 'Systemic complaints (B symptoms)'.)
PATHOLOGY
Morphology
Peripheral blood and bone marrow By definition, more than 55 percent of the circulating cells in the
peripheral blood are prolymphocytes; more typically, the percentage of prolymphocytes is greater than 90
percent. Peripheral blood prolymphocytes are medium-sized cells (approximately twice the size of a small
lymphocyte), with moderately condensed chromatin and a single, prominent vesicular nucleolus (picture 1). The
nucleus is typically round or oval, and the cytoplasm is usually moderately abundant and slightly basophilic
[5,6]. The bone marrow is infiltrated in an interstitial or nodular pattern by similar cells (picture 2).
Other tissues B-PLL is only rarely diagnosed in tissues other than the blood and bone marrow [4].
The spleen shows extensive white and red pulp infiltration by prolymphocytes [2,7-9] morphologically
similar to those seen in the blood and bone marrow (picture 3).
Involved lymph nodes may show vague nodularity, but the proliferation centers (pseudofollicles) seen in
CLL are absent [2,7-9].
Immunophenotype B-PLL is a tumor of monoclonal B cells that typically express bright surface IgM +/- IgD,
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bright surface Ig kappa or lambda light chain, bright CD20, and CD19, CD22, CD79a, and FMC7. This is in
contrast to chronic lymphocytic leukemia (CLL) which generally has dim expression of surface Ig and CD20.
ZAP-70 and CD38 are expressed in about 50 percent of cases, while CD5 and CD23 are expressed in about
one-third of cases.
CD38 and ZAP-70 do not have prognostic significance [10]. Helping to distinguish B-PLL from other
lymphoproliferative disorders is the absence of expression of CD11c, CD103, CD10, CD25, and cyclin D1 [3].
Genetic features The genetic lesions underlying B-PLL are largely unknown. Deletions of 17p (the
chromosomal arm that carries the TP53 gene) and TP53 mutations are found in more than half of cases [11].
Deletions of 13q14, the site of the retinoblastoma gene, occur in about 25 percent of cases [12,13]. Prior to the
current World Health Organization (WHO) classification system, translocations involving 14q32 were reported in
two-thirds of patients with B-PLL, the most common being the t(11;14)(q13;q32) involving the cyclin D1 gene.
However, patients with this translocation are now considered to have a leukemic variant of mantle cell
lymphoma [14]. As such, it is important to exclude this translocation, either by cytogenetic testing or by
immunohistochemical staining for cyclin D1, in cases of suspected B-PLL. (See "Clinical manifestations,
pathologic features, and diagnosis of mantle cell lymphoma".)
Immunoglobulin genes are clonally rearranged, and in approximately half of cases demonstrate somatic
hypermutation [4]. Although not used in routine practice, the gene expression profile of B-PLL is different from
that of CLL and displays over-expression of c-MYC and AKT, and downregulation of TP53 [15].
DIAGNOSIS The diagnosis of B-PLL is usually made based on the results of immunophenotypic and genetic
analysis of the peripheral blood. Results of bone marrow biopsy and aspirate can confirm these findings, but are
often available after the peripheral blood analysis. When the white blood cell count is elevated and an
evaluation of the peripheral blood and bone marrow is consistent with B-PLL, lymph node biopsy rarely adds
additional information and is not necessary. Splenectomy can be diagnostic in patients with an unclear
presentation and a massively enlarged spleen.
By definition, prolymphocytes must exceed 55 percent of lymphoid cells in the peripheral blood. These cells can
be confirmed by flow cytometry demonstrating a characteristic immunophenotype with light chain restriction,
bright surface immunoglobulin, and the expression of B cell antigens (eg, CD20, CD22, FMC7, CD79a). CD5
and CD23 expression is usually weak or absent. CD11c, CD103, CD10, and CD25 are not expressed. (See
'Immunophenotype' above.)
Tumors demonstrating t(11;14)(q13;q32) must be excluded by either conventional cytogenetics, fluorescence in
situ hybridization (FISH), or by immunohistochemical stains for cyclin D1. (See 'Genetic features' above.)
DIFFERENTIAL DIAGNOSIS The differential diagnosis of B-PLL includes other chronic lymphoid neoplasms
with a leukemic presentation (table 1). They are described in more detail below.
T cell prolymphocytic leukemia T cell prolymphocytic leukemia (T-PLL) has a similar clinical presentation
and morphologic appearance to B-PLL however differs in its immunophenotype. Unlike B-PLL, T-PLL expresses
one or more T cell antigens (CD2, CD3, CD7, CD53). (See "Clinical manifestations, pathologic features, and
diagnosis of T cell prolymphocytic leukemia".)
Chronic lymphocytic leukemia Both B-PLL and chronic lymphocytic leukemia (CLL) can present with
lymphocytosis, splenomegaly, and circulating prolymphocytes in the blood, but in CLL prolymphocytes comprise
less than 55 percent of the cells, whereas in most cases of B-PLL greater than 90 percent of the cells are prolymphocytes. Compared with typical CLL cells, prolymphocytes are larger cells with somewhat immatureappearing nuclear chromatin, a prominent nucleolus, and a moderate amount of cytoplasm (picture 1). While
prolymphocytes are seen in variable numbers in CLL, they typically comprise over 90 percent of the neoplastic
cells in B-PLL and usually comprise fewer than 10 percent of the circulating cells in CLL. In addition, in twothirds of cases of B-PLL the prolymphocytes are CD5 negative, whereas as a rule the prolymphocytes of CLL
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are CD5 positive. (See "Clinical presentation, pathologic features, diagnosis, and differential diagnosis of
chronic lymphocytic leukemia".)
Patients with peripheral blood prolymphocyte counts between 10 and 55 percent have been designated as
having chronic lymphocytic leukemia/prolymphocytic leukemia in the past, but this entity has been eliminated in
the latest WHO classification of lymphoid neoplasms [4]. Rarely, cases of CLL can undergo prolymphocytoid
transformation. In such cases, the peripheral blood will contain a mixture of small mature CLL cells and
prolymphocytes. The prolymphocytes in such cases usually have an immunophenotype similar to that seen with
typical CLL, although sometimes with higher levels of surface Ig. In contrast, circulating cells in de novo B-PLL
are monomorphic prolymphocytes with an immunophenotype characteristic of B-PLL as described above. In
addition, histologic findings on bone marrow biopsy in cases of CLL with prolymphocytoid transformation are
consistent with those found in CLL (eg, proliferation centers). (See 'Immunophenotype' above and "Staging and
prognosis of chronic lymphocytic leukemia", section on 'Prolymphocytoid transformation'.)
Mantle cell lymphoma Mantle cell lymphoma (MCL) can have a leukemic phase that mimics B-PLL and
gene expression profiling suggests that B-PLL and leukemia MCL have similar patterns of gene expression [16].
As in a subset of B-PLLs, MCL cells co-express CD5 and CD20. However, the neoplastic cells of MCL express
cyclin D1, which is dysregulated by a (11;14) translocation involving the cyclin D1 gene. SOX11 expression is
usually present in the rare cases of MCL that do not express cyclin D1. In contrast, the malignant cells in PLL
are negative for cyclin D1 and do not demonstrate t(11;14). (See "Clinical manifestations, pathologic features,
and diagnosis of mantle cell lymphoma".)
Follicular lymphoma On rare occasions, patients with follicular lymphoma can have a leukemic phase, but
this usually does not present a diagnostic dilemma, as the circulating tumor cells in typical cases are
centrocytes with highly irregular or cleaved nuclear contours that by flow cytometry express CD10. (See
"Clinical manifestations, pathologic features, diagnosis, and prognosis of follicular lymphoma".)
Lymphoplasmacytic lymphoma Lymphoplasmacytic lymphoma (LPL), a tumor that is commonly
associated with Waldenstrom macroglobulinemia, occasionally involves the peripheral blood. However, the
circulating malignant cells of LPL often have a plasmacytoid appearance and are usually few in number,
whereas B-PLL is usually associated with WBCs of over 100,000 cells/microL. Moreover, B-PLL is never
associated with a significant level of paraproteinemia, whereas this is typical of patients with LPL. (See "Clinical
manifestations, pathologic features, and diagnosis of lymphoplasmacytic lymphoma".)
Hairy cell leukemia There is a variant of hairy cell leukemia (HCL-variant) that exhibits morphologic features
intermediate between hairy cells and prolymphocytes. Such cases may also have extreme leukocytosis and
expression of the interleukin-2 receptor beta chain, but not the alpha chain (CD25). Unlike B-PLL, most cases of
HCL-variant express some combination of CD11c, CD103, CD123, cyclin D1, and annexin A1, none of which
are typically expressed on B-PLL cells. (See "Clinical features and diagnosis of hairy cell leukemia".)
Splenic marginal zone lymphoma Both splenic marginal zone lymphoma (MZL) and B-PLL can present
with splenomegaly and peripheral blood lymphocytosis. When compared with splenic MZL, B-PLL is more likely
to present with clinically aggressive disease, B symptoms, and extreme leukocytosis (>100,000/microL). While
the circulating lymphocytes in B-PLL usually have a regular, smooth cytoplasmic outline, splenic MZL cells
usually have short polar villi, although this may be masked by poor slide preparation. Both B-PLL and splenic
MZL express CD20 and bright surface Ig. Neither typically expresses CD5. Expression of CD22 is usually
strong in B-PLL and variable in MZL. Both MZL and B-PLL involve both the splenic white pulp and red pulp, but
in MZL marginal zones are usually prominent due to expansion by cells with abundant pale cytoplasm, and
plasmacytic differentiation may also be observed, features that are absent in B-PLL. Bone marrow morphology
in MZL may take the form of reactive-appearing follicles surrounded by marginal zone B cells, features that are
not seen in B-PLL. In difficult cases, pathologic evaluation of the bone marrow, spleen, and hilar lymph nodes
may be used in concert to determine the most likely diagnosis. (See "Clinical manifestations, pathologic
features, and diagnosis of splenic marginal zone lymphoma".)
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TREATMENT The clinical course of B-PLL is variable, and therapy may not be indicated initially in
asymptomatic patients [17]. Most patients, however, do require treatment, and the most appropriate choice is
unclear due to lack of clinical data. B-PLL is most commonly treated with combination regimens used for chronic
lymphocytic leukemia (CLL) such as fludarabine, cyclophosphamide, rituximab (FCR) or bendamustine
rituximab (BR). (See "Selection of initial therapy for symptomatic or advanced chronic lymphocytic leukemia",
section on 'Fludarabine, cyclophosphamide, and rituximab'.)
Responses to various regimens have been reported, although they are most frequently partial responses, and
rarely durable. Individual chemotherapy regimens have not been directly compared, and a choice among
regimens is made largely based upon the side effect profile and the clinician's experience with the regimen.
Chlorambucil alone is not very effective, and combination regimens such as cyclophosphamide, doxorubicin,
vincristine, and prednisolone (CHOP) have resulted in partial responses in up to one-third of cases [17]. Case
reports and small series have been reported for the use of purine analogs such as cladribine [18], fludarabine
[19], and pentostatin, used alone and in combinations, with some improvement in response. The major advance
appears to have been the addition of rituximab [20]. Combinations of rituximab with fludarabine or
bendamustine together with an anthracycline (mitoxantrone or epirubicin) (FMR, FER, and BMR) have been
reported to have significant activity in B-PLL [21-23].
B-PLL patients with TP53 deletions or mutations should be treated with regimens that incorporate alemtuzumab
[24,25], since TP53 deletions and mutations are associated with primary resistance to purine analog/alkylator
based-therapy. Splenectomy [26] or splenic irradiation [27] may provide effective palliation in selected cases.
Allogeneic hematopoietic cell transplantation (HCT) should be considered in younger, fit patients who have
responded to their initial therapy, as prognosis in B-PLL is not as favorable as in CLL [28]. In addition, patients
who have abnormalities of TP53 or who have poor or short-lived responses to chemo-immunotherapy may also
be eligible for allogeneic HCT.
New therapies, such as novel anti-CD20 monoclonal antibodies (eg, ofatumumab and obinutumumab) and
small molecule inhibitors of BCR signaling (eg, ibrutinib, idelalisib), have not been specifically evaluated in BPLL. However, it is likely that activity will be similar to that seen in CLL, including in patients unable to tolerate
intensive therapies and/or who have TP53 abnormalities. (See "Selection of initial therapy for symptomatic or
advanced chronic lymphocytic leukemia", section on 'High-risk disease: del(17p) or TP53 mutations'.)
PROGNOSIS Survival of patients with B-PLL is usually three to five years despite therapy. It has been
difficult to determine prognostic markers for patients with B-PLL because it is such a rare tumor and because
previous reports contained not only patients with B-PLL but also patients with T cell prolymphocytic leukemia
and mantle cell lymphoma.
Among patients with B-PLL, prognostic features that suggest a poor outcome include anemia,
thrombocytopenia, advanced age, and the presence of TP53 mutations [3,29]. Unlike in patients with chronic
lymphocytic leukemia, neither ZAP-70 expression, nor immunoglobulin heavy chain gene mutations, nor CD38
expression, appears to act as prognostic markers [10].
SUMMARY
B cell prolymphocytic leukemia (B-PLL) is a rare B cell neoplasm comprised of prolymphocytes, typically
with involvement of the peripheral blood, bone marrow, and spleen. It is most common in elderly
Caucasians. (See 'Epidemiology' above.)
Patients typically present with a rapidly rising white blood count >100,000/microL and massive
splenomegaly with or without B symptoms (ie, fevers, night sweats, weight loss). If present, peripheral
lymphadenopathy is not prominent. (See 'Clinical features' above.)
The diagnosis is usually made by bone marrow biopsy and aspirate with flow cytometry and genetic
studies. By definition, prolymphocytes must exceed 55 percent of lymphoid cells in the peripheral blood.
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These cells express pan-B cell markers and high levels of surface immunoglobulin, and are CD5 negative
in two-thirds of cases and almost always negative for CD10. Cases of mantle cell lymphoma
masquerading as B-PLL must be excluded, particularly in suspected B-PLL cases that express CD5. (See
'Diagnosis' above.)
The differential diagnosis of B-PLL includes other chronic lymphoid neoplasms with a leukemic
presentation. (See 'Differential diagnosis' above.)
B-PLL is commonly treated with combination regimens used for chronic lymphocytic leukemia. Individual
chemotherapy regimens have not been directly compared, and a choice among regimens is made largely
based upon the side effect profile and the clinician's experience with the regimen. (See 'Treatment' above.)
Survival is usually three to five years despite therapy. Prognostic markers have been difficult to determine,
but anemia, thrombocytopenia, advanced age, and the presence of TP53 mutations appear to predict a
poor outcome. (See 'Prognosis' above.)
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REFERENCES
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demographic characteristics, 1997-2002. Cancer Causes Control 2008; 19:379.
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4. Swerdlow SH, Campo E, Harris NL, et al. (Eds). World Health Organization Classification of Tumours of
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8. Galton DA, Goldman JM, Wiltshaw E, et al. Prolymphocytic leukaemia. Br J Haematol 1974; 27:7.
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reference to the spleen: a comparison with chronic lymphocytic leukaemia. Histopathology 1980; 4:3.
10. Del Giudice I, Davis Z, Matutes E, et al. IgVH genes mutation and usage, ZAP-70 and CD38 expression
provide new insights on B-cell prolymphocytic leukemia (B-PLL). Leukemia 2006; 20:1231.
11. Lens D, De Schouwer PJ, Hamoudi RA, et al. p53 abnormalities in B-cell prolymphocytic leukemia. Blood
1997; 89:2015.
12. Lens D, Coignet LJ, Brito-Babapulle V, et al. B cell prolymphocytic leukaemia (B-PLL) with complex
karyotype and concurrent abnormalities of the p53 and c-MYC gene. Leukemia 1999; 13:873.
13. Sol F, Woessner S, Espinet B, et al. Cytogenetic abnormalities in three patients with B-cell
prolymphocytic leukemia. Cancer Genet Cytogenet 1998; 103:43.
14. Ruchlemer R, Parry-Jones N, Brito-Babapulle V, et al. B-prolymphocytic leukaemia with t(11;14) revisited:
a splenomegalic form of mantle cell lymphoma evolving with leukaemia. Br J Haematol 2004; 125:330.
15. Del Giudice I, Osuji N, Dexter T, et al. B-cell prolymphocytic leukemia and chronic lymphocytic leukemia
have distinctive gene expression signatures. Leukemia 2009; 23:2160.
16. van der Velden VH, Hoogeveen PG, de Ridder D, et al. B-cell prolymphocytic leukemia: a specific
subgroup of mantle cell lymphoma. Blood 2014; 124:412.
17. Shvidel L, Shtalrid M, Bassous L, et al. B-cell prolymphocytic leukemia: a survey of 35 patients
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emphasizing heterogeneity, prognostic factors and evidence for a group with an indolent course. Leuk
Lymphoma 1999; 33:169.
18. Saven A, Lee T, Schlutz M, et al. Major activity of cladribine in patients with de novo B-cell prolymphocytic
leukemia. J Clin Oncol 1997; 15:37.
19. Doorduijn JK, Michiels JJ. Effectiveness of fludarabine in end-stage prolymphocytic leukemia. Leukemia
1994; 8:1439.
20. Mourad YA, Taher A, Chehal A, Shamseddine A. Successful treatment of B-cell prolymphocytic leukemia
with monoclonal anti-CD20 antibody. Ann Hematol 2004; 83:319.
21. Tempescul A, Feuerbach J, Ianotto JC, et al. A combination therapy with fludarabine, mitoxantrone and
rituximab induces complete immunophenotypical remission in B-cell prolymphocytic leukaemia. Ann
Hematol 2009; 88:85.
22. Chow KU, Kim SZ, von Neuhoff N, et al. Clinical efficacy of immunochemotherapy with fludarabine,
epirubicin and rituximab in the treatment for chronic lymphocytic leukaemia and prolymphocytic
leukaemia. Eur J Haematol 2011; 87:426.
23. Weide R, Pandorf A, Heymanns J, Kppler H. Bendamustine/Mitoxantrone/Rituximab (BMR): a very
effective, well tolerated outpatient chemoimmunotherapy for relapsed and refractory CD20-positive
indolent malignancies. Final results of a pilot study. Leuk Lymphoma 2004; 45:2445.
24. McCune SL, Gockerman JP, Moore JO, et al. Alemtuzumab in relapsed or refractory chronic lymphocytic
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25. Chaar BT, Petruska PJ. Complete response to alemtuzumab in a patient with B prolymphocytic leukemia.
Am J Hematol 2007; 82:417.
26. Absi A, Hsi E, Kalaycio M. Prolymphocytic leukemia. Curr Treat Options Oncol 2005; 6:197.
27. Oscier DG, Catovsky D, Errington RD, et al. Splenic irradiation in B-prolymphocytic leukaemia. Br J
Haematol 1981; 48:577.
28. Castagna L, Sarina B, Todisco E, et al. Allogeneic peripheral stem-cell transplantation with reducedintensity conditioning regimen in refractory primary B-cell prolymphocytic leukemia: a long-term follow-up.
Bone Marrow Transplant 2005; 35:1225.
29. Hercher C, Robain M, Davi F, et al. A multicentric study of 41 cases of B-prolymphocytic leukemia: two
evolutive forms. Leuk Lymphoma 2001; 42:981.
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GRAPHICS
Peripheral blood morphology of four different B cell
leukemias
(A) B-cell prolymphocytic leukemia, showing monomorphic prolymphocytes with

condensed chromatin, prominent nucleolus, and scanty basophilic cytoplasm.
(B) Chronic lymphocytic leukemia with increased prolymphocytes, showing a
single prolymphocyte, and several typical CLL cells, which are half the size of the
prolymphocyte, have less cytoplasm and no nucleolus.
(C) Variant form of hairy cell leukemia, showing cells with condensed chromatin
and a conspicuous single nucleolus, but with more abundant pale cytoplasm with
cytoplasmic projections.
(D) Splenic marginal zone lymphoma showing lymphocytes with short polar villi
and basophilic cytoplasm.
This research was originally published in Blood. Dearden C. How I treat prolymphocytic
leukemia. Blood 2012; 120:538. Copyright 2012 American Society of Hematology.
Graphic 85966 Version 1.0
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Prolymphocytic leukemia bone marrow
Low power view (16X) of a bone marrow aspirate from a patient with
prolymphocytic leukemia, showing monotonous infiltration with small,
round mononuclear cells.
Courtesy of Carola von Kapff, SH (ASCP).
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Histology of the spleen in B cell prolymphocytic

leukemia
(A) Low power view (original magnification x20) showing replacement of

the white pulp and infiltration of the red pulp.
(B) High power view (original magnification x100) of the white pulp
showing the typical prolymphocyte morphology with abundant
cytoplasm, round nuclei, and a central eosinophilic nucleolus.
This research was originally published in Blood. Dearden C. How I treat
prolymphocytic leukemia. Blood 2012; 120:538. Copyright 2012 American
Society of Hematology.
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Differential diagnosis of B cell prolymphocytic leukemia

Entity
Histology
Immunophenotype
Genetic
features/Other
B cell
>55 percent (and
Express bright surface
t(11;14) must be
prolymphocytic
leukemia
usually >90 percent) of

circulating white cells
are "prolymphocytes":
IgM +/- IgD and bright

CD20 as well as other Bcell antigens (CD19,
excluded.
medium-sized cells
with moderately
CD22, CD79a, FMC7).
abundant, slightly
basophilic cytoplasm; a
round or oval nucleus
with moderately
condensed chromatin;
and a single, prominent
No associated
paraproteinemia.
CD5 and CD23 expression

is usually weak or absent.
CD11c, CD103, CD10,
CD25, and cyclin D1 are
not expressed.
nucleolus.
The bone marrow is
infiltrated in an
interstitial or nodular
pattern by similar cells.
Chronic
"Typical" CLL cells are
Typically express CD5
Trisomy 12,
lymphocytic
leukemia/Small
lymphocytic
small mature appearing

lymphocytes with a
dense nucleus, partially
and CD23. Expression of

CD20 and surface
immunoglobulin is dim.
deletions of 6q, 11q,

13q, and 17p
lymphoma
aggregated chromatin,
no discernible nucleoli,
and a narrow border of
clear to slightly
basophilic cytoplasm.
"Prolymphocytes" may
be present, but are
<55 percent of
circulating cells.
T cell
prolymphocytic
leukemia
Similar morphologic
appearance to B-PLL.
Expresses pan-T cell

antigens (CD2, CD3,
CD5, CD7).
inv(14q)
Mantle cell
Can have a leukemic
Typically CD20 and CD5
t(11;14)
lymphoma
phase that mimics BPLL morphologically.
positive and CD23

negative.
Express cyclin D1.
Follicular
Circulating centrocytes
Typically expresses CD10.
t(14;18)
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lymphoma
have highly irregular or

cleaved nuclear
contours.
Lymphoplasmacytic
Occasionally associated
Often associated
lymphoma
with circulating
malignant cells with a
plasmacytoid
with a
paraproteinemia.
appearance.
Hairy cell leukemia
Variant has circulating

tumor cells with
morphology
Unlike B-PLL, most cases

of HCL express CD11c,
CD103, CD123, cyclin D1,
intermediate between
hairy cells and
prolymphocytes.
and/or annexin A1.

Express the interleukin-2
receptor beta chain, but
not the alpha chain
(CD25).
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Disclosures
Disclosures: Arnold S Freedman, MD Nothing to disclose. Jon C Aster, MD Nothing to disclose.
Claire Dearden, MD, BSc, FRCP, FRCPath Consultant/Advisory Boards: Genzyme/Sanofi [T-PLL
(Alemtuzumab)]; Roche [B-PLL (Rituximab)]. Andrew Lister, MD, FRCP, FRCPath, FRCR
Consultant/Advisory Boards: Celgene [malignant lymphoma]. Equity Ownership/Stock Options (Spouse
also): GSK; Johnson & Johnson; AstraZeneca; Novartis; Pfizer. Other Financial Interest: Roche
[honorarium for lectures; follicular lymphoma]; Gilead [data monitoring committee - CLL, indolent
lymphoma (idelalisib (CAL 101))]; Roche [data monitoring committee - indolent lymphoma (obinutuzumab
(GA101))]; Millennium [data monitoring committee - Hodgkin lymphoma (brentuxumab vedotan)];
Spectrum/Allos [data monitoring committee - PTCL (pralatrexate)]. Rebecca F Connor, MD Employee of
UpToDate, Inc. Equity Ownership/Stock Options (Spouse previously owned): Pharmacyclics [B cell
lymphomas (Ibrutinib)].
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through requirements for references
to be provided to support the content. Appropriately referenced content is required of all authors and
must conform to UpToDate standards of evidence.
Conflict of interest policy
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B cell prolymphocytic leukemia

Official reprint from UpToDate

B cell prolymphocytic leukemia

B cell prolymphocytic leukemia

B cell prolymphocytic leukemia

B cell prolymphocytic leukemia

B cell prolymphocytic leukemia

B cell prolymphocytic leukemia

(A) B-cell prolymphocytic leukemia, showing monomorphic prolymphocytes with

B cell prolymphocytic leukemia

Prolymphocytic leukemia bone marrow

B cell prolymphocytic leukemia

Histology of the spleen in B cell prolymphocytic

(A) Low power view (original magnification x20) showing replacement of

B cell prolymphocytic leukemia

Differential diagnosis of B cell prolymphocytic leukemia

>55 percent (and

Express bright surface

usually >90 percent) of

IgM +/- IgD and bright

CD22, CD79a, FMC7).

CD5 and CD23 expression

"Typical" CLL cells are

Typically express CD5

small mature appearing

and CD23. Expression of

deletions of 6q, 11q,

Expresses pan-T cell

Can have a leukemic

Typically CD20 and CD5

phase that mimics BPLL morphologically.

positive and CD23

Typically expresses CD10.

B cell prolymphocytic leukemia

have highly irregular or

Variant has circulating

Unlike B-PLL, most cases

and/or annexin A1.

Graphic 54944 Version 1.0

B cell prolymphocytic leukemia

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