b cell prolymphocytic leukemia

11/10/2014 B cell prolymphocytic leukemia

http://www.uptodate.com/contents/b-cell-prolymphocytic-leukemia?topicKey=HEME%2F4747&elapsedTimeMs=2&source=search_result&searchTer 1/12

Official reprint from UpToDate www.uptodate.com 2014 UpToDate

AuthorsArnold S Freedman, MDJon C Aster, MDClaire Dearden, MD, BSc,FRCP, FRCPath

Section EditorAndrew Lister, MD, FRCP,FRCPath, FRCR

Deputy EditorRebecca F Connor, MD

B cell prolymphocytic leukemia

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 so-called 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. Bydefinition, 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 lymphocyticleukemia (CLL), and CLL/PLL (defined as between 15 and 55 percent prolymphocytes), B-PLL has becomeincreasingly rare.

B-PLL mainly affects the elderly with a mean age at presentation of between 65 and 70 years [2]. Men andwomen 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/microLand 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-Hodgkinlymphoma", section on 'Systemic complaints (B symptoms)'.)

PATHOLOGY

Morphology

Peripheral blood and bone marrow By definition, more than 55 percent of the circulating cells in theperipheral blood are prolymphocytes; more typically, the percentage of prolymphocytes is greater than 90percent. Peripheral blood prolymphocytes are medium-sized cells (approximately twice the size of a smalllymphocyte), with moderately condensed chromatin and a single, prominent vesicular nucleolus (picture 1). Thenucleus 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].

Immunophenotype B-PLL is a tumor of monoclonal B cells that typically express bright surface IgM +/- IgD,

The spleen shows extensive white and red pulp infiltration by prolymphocytes [2,7-9] morphologicallysimilar to those seen in the blood and bone marrow (picture 3).

Involved lymph nodes may show vague nodularity, but the proliferation centers (pseudofollicles) seen inCLL are absent [2,7-9].



bright surface Ig kappa or lambda light chain, bright CD20, and CD19, CD22, CD79a, and FMC7. This is incontrast 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 aboutone-third of cases.

CD38 and ZAP-70 do not have prognostic significance [10]. Helping to distinguish B-PLL from otherlymphoproliferative 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 (thechromosomal 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 thecurrent World Health Organization (WHO) classification system, translocations involving 14q32 were reported intwo-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 celllymphoma [14]. As such, it is important to exclude this translocation, either by cytogenetic testing or byimmunohistochemical 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 somatichypermutation [4]. Although not used in routine practice, the gene expression profile of B-PLL is different fromthat 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 geneticanalysis of the peripheral blood. Results of bone marrow biopsy and aspirate can confirm these findings, but areoften available after the peripheral blood analysis. When the white blood cell count is elevated and anevaluation of the peripheral blood and bone marrow is consistent with B-PLL, lymph node biopsy rarely addsadditional information and is not necessary. Splenectomy can be diagnostic in patients with an unclearpresentation and a massively enlarged spleen.

By definition, prolymphocytes must exceed 55 percent of lymphoid cells in the peripheral blood. These cells canbe 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). CD5and 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 insitu 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 neoplasmswith 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 presentationand morphologic appearance to B-PLL however differs in its immunophenotype. Unlike B-PLL, T-PLL expressesone or more T cell antigens (CD2, CD3, CD7, CD53). (See "Clinical manifestations, pathologic features, anddiagnosis of T cell prolymphocytic leukemia".)

Chronic lymphocytic leukemia Both B-PLL and chronic lymphocytic leukemia (CLL) can present withlymphocytosis, splenomegaly, and circulating prolymphocytes in the blood, but in CLL prolymphocytes compriseless than 55 percent of the cells, whereas in most cases of B-PLL greater than 90 percent of the cells are pro-lymphocytes. Compared with typical CLL cells, prolymphocytes are larger cells with somewhat immature-appearing nuclear chromatin, a prominent nucleolus, and a moderate amount of cytoplasm (picture 1). Whileprolymphocytes are seen in variable numbers in CLL, they typically comprise over 90 percent of the neoplasticcells in B-PLL and usually comprise fewer than 10 percent of the circulating cells in CLL. In addition, in two-thirds of cases of B-PLL the prolymphocytes are CD5 negative, whereas as a rule the prolymphocytes of CLL



are CD5 positive. (See "Clinical presentation, pathologic features, diagnosis, and differential diagnosis ofchronic lymphocytic leukemia".)

Patients with peripheral blood prolymphocyte counts between 10 and 55 percent have been designated ashaving chronic lymphocytic leukemia/prolymphocytic leukemia in the past, but this entity has been eliminated inthe latest WHO classification of lymphoid neoplasms [4]. Rarely, cases of CLL can undergo prolymphocytoidtransformation. In such cases, the peripheral blood will contain a mixture of small mature CLL cells andprolymphocytes. The prolymphocytes in such cases usually have an immunophenotype similar to that seen withtypical CLL, although sometimes with higher levels of surface Ig. In contrast, circulating cells in de novo B-PLLare monomorphic prolymphocytes with an immunophenotype characteristic of B-PLL as described above. Inaddition, histologic findings on bone marrow biopsy in cases of CLL with prolymphocytoid transformation areconsistent with those found in CLL (eg, proliferation centers). (See 'Immunophenotype' above and "Staging andprognosis of chronic lymphocytic leukemia", section on 'Prolymphocytoid transformation'.)

Mantle cell lymphoma Mantle cell lymphoma (MCL) can have a leukemic phase that mimics B-PLL andgene 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 expresscyclin D1, which is dysregulated by a (11;14) translocation involving the cyclin D1 gene. SOX11 expression isusually present in the rare cases of MCL that do not express cyclin D1. In contrast, the malignant cells in PLLare 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, butthis usually does not present a diagnostic dilemma, as the circulating tumor cells in typical cases arecentrocytes 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 commonlyassociated with Waldenstrom macroglobulinemia, occasionally involves the peripheral blood. However, thecirculating 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 neverassociated with a significant level of paraproteinemia, whereas this is typical of patients with LPL. (See "Clinicalmanifestations, pathologic features, and diagnosis of lymphoplasmacytic lymphoma".)

Hairy cell leukemia There is a variant of hairy cell leukemia (HCL-variant) that exhibits morphologic featuresintermediate between hairy cells and prolymphocytes. Such cases may also have extreme leukocytosis andexpression of the interleukin-2 receptor beta chain, but not the alpha chain (CD25). Unlike B-PLL, most cases ofHCL-variant express some combination of CD11c, CD103, CD123, cyclin D1, and annexin A1, none of whichare 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 presentwith splenomegaly and peripheral blood lymphocytosis. When compared with splenic MZL, B-PLL is more likelyto present with clinically aggressive disease, B symptoms, and extreme leukocytosis (>100,000/microL). Whilethe circulating lymphocytes in B-PLL usually have a regular, smooth cytoplasmic outline, splenic MZL cellsusually have short polar villi, although this may be masked by poor slide preparation. Both B-PLL and splenicMZL express CD20 and bright surface Ig. Neither typically expresses CD5. Expression of CD22 is usuallystrong in B-PLL and variable in MZL. Both MZL and B-PLL involve both the splenic white pulp and red pulp, butin MZL marginal zones are usually prominent due to expansion by cells with abundant pale cytoplasm, andplasmacytic differentiation may also be observed, features that are absent in B-PLL. Bone marrow morphologyin MZL may take the form of reactive-appearing follicles surrounded by marginal zone B cells, features that arenot seen in B-PLL. In difficult cases, pathologic evaluation of the bone marrow, spleen, and hilar lymph nodesmay be used in concert to determine the most likely diagnosis. (See "Clinical manifestations, pathologicfeatures, and diagnosis of splenic marginal zone lymphoma".)



TREATMENT The clinical course of B-PLL is variable, and therapy may not be indicated initially inasymptomatic patients [17]. Most patients, however, do require treatment, and the most appropriate choice isunclear due to lack of clinical data. B-PLL is most commonly treated with combination regimens used for chroniclymphocytic leukemia (CLL) such as fludarabine, cyclophosphamide, rituximab (FCR) or bendamustinerituximab (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, andrarely durable. Individual chemotherapy regimens have not been directly compared, and a choice amongregimens 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]. Casereports 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 advanceappears to have been the addition of rituximab [20]. Combinations of rituximab with fludarabine orbendamustine together with an anthracycline (mitoxantrone or epirubicin) (FMR, FER, and BMR) have beenreported 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/alkylatorbased-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 haveresponded to their initial therapy, as prognosis in B-PLL is not as favorable as in CLL [28]. In addition, patientswho have abnormalities of TP53 or who have poor or short-lived responses to chemo-immunotherapy may alsobe eligible for allogeneic HCT.

New therapies, such as novel anti-CD20 monoclonal antibodies (eg, ofatumumab and obinutumumab) andsmall molecule inhibitors of BCR signaling (eg, ibrutinib, idelalisib), have not been specifically evaluated in B-PLL. However, it is likely that activity will be similar to that seen in CLL, including in patients unable to tolerateintensive therapies and/or who have TP53 abnormalities. (See "Selection of initial therapy for symptomatic oradvanced 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 beendifficult to determine prognostic markers for patients with B-PLL because it is such a rare tumor and becauseprevious reports contained not only patients with B-PLL but also patients with T cell prolymphocytic leukemiaand 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 chroniclymphocytic leukemia, neither ZAP-70 expression, nor immunoglobulin heavy chain gene mutations, nor CD38expression, appears to act as prognostic markers [10].

SUMMARY

B cell prolymphocytic leukemia (B-PLL) is a rare B cell neoplasm comprised of prolymphocytes, typicallywith involvement of the peripheral blood, bone marrow, and spleen. It is most common in elderlyCaucasians. (See 'Epidemiology' above.)

Patients typically present with a rapidly rising white blood count >100,000/microL and massivesplenomegaly with or without B symptoms (ie, fevers, night sweats, weight loss). If present, peripherallymphadenopathy is not prominent. (See 'Clinical features' above.)

The diagnosis is usually made by bone marrow biopsy and aspirate with flow cytometry and geneticstudies. By definition, prolymphocytes must exceed 55 percent of lymphoid cells in the peripheral blood.



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REFERENCES

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2. Melo JV, Catovsky D, Galton DA. The relationship between chronic lymphocytic leukaemia andprolymphocytic leukaemia. I. Clinical and laboratory features of 300 patients and characterization of anintermediate group. Br J Haematol 1986; 63:377.

3. Ravandi F, O'Brien S. Chronic lymphoid leukemias other than chronic lymphocytic leukemia: diagnosisand treatment. Mayo Clin Proc 2005; 80:1660.

4. Swerdlow SH, Campo E, Harris NL, et al. (Eds). World Health Organization Classification of Tumours ofHaematopoietic and Lymphoid Tissues, IARC Press, Lyon 2008.

5. Catovsky D, Foa R. The Lymphoid Leukaemias, Butterworths, London 1990.6. Stone RM. Prolymphocytic leukemia. Hematol Oncol Clin North Am 1990; 4:457.7. Bearman RM, Pangalis GA, Rappaport H. Prolymphocytic leukemia: clinical, histopathological, and

cytochemical observations. Cancer 1978; 42:2360.8. Galton DA, Goldman JM, Wiltshaw E, et al. Prolymphocytic leukaemia. Br J Haematol 1974; 27:7.9. Lampert I, Catovsky D, Marsh GW, et al. The histopathology of prolymphocytic leukaemia with particular

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

These cells express pan-B cell markers and high levels of surface immunoglobulin, and are CD5 negativein two-thirds of cases and almost always negative for CD10. Cases of mantle cell lymphomamasquerading 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 leukemicpresentation. (See 'Differential diagnosis' above.)

B-PLL is commonly treated with combination regimens used for chronic lymphocytic leukemia. Individualchemotherapy regimens have not been directly compared, and a choice among regimens is made largelybased 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 apoor outcome. (See 'Prognosis' above.)



emphasizing heterogeneity, prognostic factors and evidence for a group with an indolent course. LeukLymphoma 1999; 33:169.

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20. Mourad YA, Taher A, Chehal A, Shamseddine A. Successful treatment of B-cell prolymphocytic leukemiawith monoclonal anti-CD20 antibody. Ann Hematol 2004; 83:319.

21. Tempescul A, Feuerbach J, Ianotto JC, et al. A combination therapy with fludarabine, mitoxantrone andrituximab induces complete immunophenotypical remission in B-cell prolymphocytic leukaemia. AnnHematol 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 prolymphocyticleukaemia. Eur J Haematol 2011; 87:426.

23. Weide R, Pandorf A, Heymanns J, Kppler H. Bendamustine/Mitoxantrone/Rituximab (BMR): a veryeffective, well tolerated outpatient chemoimmunotherapy for relapsed and refractory CD20-positiveindolent malignancies. Final results of a pilot study. Leuk Lymphoma 2004; 45:2445.

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Haematol 1981; 48:577.28. Castagna L, Sarina B, Todisco E, et al. Allogeneic peripheral stem-cell transplantation with reduced-

intensity 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: twoevolutive forms. Leuk Lymphoma 2001; 42:981.

Topic 4747 Version 9.0



GRAPHICS

Peripheral blood morphology of four different B cellleukemias

(A) B-cell prolymphocytic leukemia, showing monomorphic prolymphocytes withcondensed chromatin, prominent nucleolus, and scanty basophilic cytoplasm.(B) Chronic lymphocytic leukemia with increased prolymphocytes, showing asingle prolymphocyte, and several typical CLL cells, which are half the size of theprolymphocyte, have less cytoplasm and no nucleolus.(C) Variant form of hairy cell leukemia, showing cells with condensed chromatinand a conspicuous single nucleolus, but with more abundant pale cytoplasm withcytoplasmic projections.(D) Splenic marginal zone lymphoma showing lymphocytes with short polar villiand basophilic cytoplasm.

This research was originally published in Blood. Dearden C. How I treat prolymphocyticleukemia. Blood 2012; 120:538. Copyright 2012 American Society of Hematology.

Graphic 85966 Version 1.0



Prolymphocytic leukemia bone marrow

Low power view (16X) of a bone marrow aspirate from a patient withprolymphocytic leukemia, showing monotonous infiltration with small,round mononuclear cells.

Courtesy of Carola von Kapff, SH (ASCP).




Histology of the spleen in B cell prolymphocyticleukemia

(A) Low power view (original magnification x20) showing replacement ofthe white pulp and infiltration of the red pulp. (B) High power view (original magnification x100) of the white pulpshowing the typical prolymphocyte morphology with abundantcytoplasm, round nuclei, and a central eosinophilic nucleolus.

This research was originally published in Blood. Dearden C. How I treatprolymphocytic leukemia. Blood 2012; 120:538. Copyright 2012 AmericanSociety of Hematology.



http://www.uptodate.com/contents/b-cell-prolymphocytic-leukemia?topicKey=HEME%2F4747&elapsedTimeMs=2&source=search_result&searchTe 10/12

Differential diagnosis of B cell prolymphocytic leukemia

Entity Histology Immunophenotype Geneticfeatures/Other

B cellprolymphocyticleukemia

>55 percent (andusually >90 percent) ofcirculating white cellsare "prolymphocytes":medium-sized cellswith moderatelyabundant, slightlybasophilic cytoplasm; around or oval nucleuswith moderatelycondensed chromatin;and a single, prominentnucleolus.

The bone marrow isinfiltrated in aninterstitial or nodularpattern by similar cells.

Express bright surfaceIgM +/- IgD and brightCD20 as well as other B-cell antigens (CD19,CD22, CD79a, FMC7).

CD5 and CD23 expressionis usually weak or absent.CD11c, CD103, CD10,CD25, and cyclin D1 arenot expressed.

t(11;14) must beexcluded.

No associatedparaproteinemia.

Chroniclymphocyticleukemia/Smalllymphocyticlymphoma

"Typical" CLL cells aresmall mature appearinglymphocytes with adense nucleus, partiallyaggregated chromatin,no discernible nucleoli,and a narrow border ofclear to slightlybasophilic cytoplasm.

"Prolymphocytes" maybe present, but are



lymphoma have highly irregular orcleaved nuclearcontours.

Lymphoplasmacyticlymphoma

Occasionally associatedwith circulatingmalignant cells with aplasmacytoidappearance.

Often associatedwith aparaproteinemia.

Hairy cell leukemia Variant has circulatingtumor cells withmorphologyintermediate betweenhairy cells andprolymphocytes.

Unlike B-PLL, most casesof HCL express CD11c,CD103, CD123, cyclin D1,and/or annexin A1.Express the interleukin-2receptor beta chain, butnot the alpha chain(CD25).




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, FRCRConsultant/Advisory Boards: Celgene [malignant lymphoma]. Equity Ownership/Stock Options (Spousealso): GSK; Johnson & Johnson; AstraZeneca; Novartis; Pfizer. Other Financial Interest: Roche[honorarium for lectures; follicular lymphoma]; Gilead [data monitoring committee - CLL, indolentlymphoma (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 ofUpToDate, Inc. Equity Ownership/Stock Options (Spouse previously owned): Pharmacyclics [B celllymphomas (Ibrutinib)].Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, theseare addressed by vetting through a multi-level review process, and through requirements for referencesto be provided to support the content. Appropriately referenced content is required of all authors andmust conform to UpToDate standards of evidence.Conflict of interest policy

Disclosures

b cell prolymphocytic leukemia

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