CASE REPORT

Development of hairy cell leukemia in a patient aftercardiac transplantation

LAWRENCE TSAO, KIMBERLY E. CHU, GOVIND BHAGAT, & BACHIR ALOBEID

Department of Pathology, Columbia University, New York, NY, USA

AbstractPost-transplant lymphoproliferative disorders (PTLDs) are well-recognized complications of bone marrow and solid organtransplantation, comprising a heterogenous group of lymphoproliferations with a spectrum of morphologic, phenotypic andmolecular features. Although PTLDs are usually Epstein–Barr virus-driven B-cell lymphoproliferations, T/natural killer-celllymphoproliferations, multiple myeloma, and Hodgkin’s lymphoma are also recognized as part of the PTLD spectrum. Hairycell leukemia, a low-grade B-cell lymphoproliferation, has not been recognized as part of the PTLD spectrum. We report thefirst case of hairy cell leukemia occurring after cardiac transplantation. It is unclear whether this case, similar to other cases oflow-grade B-cell lymphoproliferations reported after transplantation, is related to immunosuppression and therefore part ofthe spectrum of PTLDs, or merely represents coincidental event occurring in an immunocompromised patient.

Keywords: Hairy cell leukemia, post-transplant lymphoproliferative disorders

Introduction

Post-transplant lymphoproliferative disorders

(PTLDs) are well-recognized complications of bone

marrow and solid organ transplants generally believed

to arise secondary to long-term immunosuppressive

therapy. The risk of developing PTLDs varies

depending on the type of transplant and the degree

of immunosuppression. The majority of PTLDs are

Epstein–Barr virus (EBV)-associated B-cell lympho-

proliferations [1]. Under the World Health

Organization (WHO) classification system, PTLDs

are classified into early lesions, polymorphic PTLDs,

monomorphic PTLDs, Hodgkin’s lymphoma and

Hodgkin’s lymphoma-like PTLD. The mono-

morphic PTLDs are further sub-classified according

to the WHO classification system of lymphomas in

immunocompetent patients.

Hairy cell leukemia (HCL) is a rare low-grade B-

cell lymphoproliferation usually occurring in elderly

patients with distinct clinical, morphologic and

immunophenotypic features. In general, low-grade

B-cell lymphoproliferative disorders with the excep-

tion of mucosa associated lymphoid tissue (MALT)

lymphomas [2 – 5] have not been reported after

transplantation, and these lymphoproliferations are

not recognized as part of the spectrum of PTLDs in

the WHO classification system. To the best of our

knowledge, we report the first case of HCL occurring

in the post-transplant setting.

Case report

The patient was a 63-year-old male who underwent

cardiac transplantation for ischemic cardiomyopathy.

Before transplant, peripheral blood counts with

differential were unremarkable. The post-transplant

course was unremarkable with only mild anemia,

thrombocytopenia, and one episode of acute

rejection (ISHLT Grade 3A). Maintenance immu-

nosuppressive therapy included cyclosporine,

azathioprine and prednisone. Four years later, the

patient presented with leukopenia, thrombocytope-

nia (white blood cell count of 2.26 109/l, platelets

386 109/l), and mild splenomegaly.

Azathioprine was withdrawn but peripheral blood

counts did not improve. Bone marrow aspirate

biopsy was performed and hairy cell leukemia was

diagnosed. Immunosuppressive therapy was further

reduced to include only cyclosporine. However, after

4 months with no response, the patient received

chemotherapy in the form of a 1-week course of

Correspondence: Lawrence Tsao, 14 – 329 Vanderbilt Clinic, New York, NY 10032, USA. E-mail: lt2016@columbia.edu

Received for publication 20 June 2005.

Leukemia & Lymphoma, February 2006; 47(2): 361 – 363

ISSN 1042-8194 print/ISSN 1029-2403 online � 2006 Taylor & Francis

DOI: 10.1080/10428190500254505

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2-chlorodeoxyadenosine (2-CdA). Complete remis-

sion was achieved with resolution of splenomegaly

and normalization of peripheral blood counts. At

4 years follow-up, the patient has remained in clinical

remission with no evidence of splenomegaly or

abnormal peripheral blood findings.

Wright – Giemsa stained bone marrow aspirate and

peripheral blood smears showed atypical lymphoid

cells with round to oval nuclei, homogeneous,

spongy chromatin and moderate cytoplasm, some

with circumferential ‘hairy’ cytoplasmic projections

(Figure 1a). The bone marrow trephine biopsy on

conventional hemotoxylin and eosin-stained sections

showed a hypocellular bone marrow with a diffuse

interstitial infiltrate of small to medium-sized lym-

phoid cells with round to oval nuclei, inconspicuous

nucleoli and moderate clear cytoplasm. These cells

expressed CD20 (Figure 1b), CD79a, DBA.44 and

CD10 by immunohistochemistry (Dako Envision

plus system, Carpinteria, CA, USA). EBV-LMP-1

expression was not seen by immunohistochemistry.

Epstein-Barr-encoded RNA (EBER) in situ hybridi-

zation was not performed. Reticulin staining of the

bone marrow showed moderate reticulin fibrosis.

Flow cytometric analysis (FACSCalibur flow cyto-

meter and CellQuest software, Becton Dickinson,

San Diego, CA, USA) of peripheral blood showed a

kappa restricted B-cell population expressing CD19,

CD20, CD10 (weak), CD25, CD11c and sIgG

(Figure 2a – f). CD5 (Figure 2a) and CD23 were

not expressed. Conventional karyotyping showed a

normal 46XY karyotype. The clinical, morphologic

and phenotypic features were consistent with a

diagnosis of hairy cell leukemia developing after

cardiac transplantation.

Discussion

We report a case of HCL diagnosed 4 years after

cardiac transplant with no evidence of leukemia on

peripheral counts before transplant. Although HCL

has been previously reported in a renal transplant

patient [6], this particular patient was diagnosed with

HCL as early as 21 days after transplantation with

pre-transplant blood counts showing neutropenia

and lymphocytosis, suggesting the presence of HCL

before transplant. To the best of our knowledge, our

case is the first reported case of HCL developing after

transplantation.

In general, low-grade B-cell lymphoproliferative

disorders as a group, except for MALT lymphoma,

have not been reported after solid organ transplanta-

tion. There have been several case series reporting

the development of MALT lymphoma post-trans-

plantation [2 – 5]. The most recent case series with

review of the literature identified 16 cases of MALT

lymphoma occurring after solid organ transplanta-

tion [2]. These cases characteristically presented late

in the post-transplant course (mean 72 months,

range 14 – 132 months), were EBER negative [3 – 5],

and showed good response to conservative manage-

ment (Helicobacter pylori therapy, immunosup-

pression reduction) with only occasional need for

radiation (19%) and chemotherapy (6%) [2].

HCL is currently not considered part of the

spectrum of PTLDs. Our case is the first case of

Figure 1. (a) Atypical lymphocyte with hairy cytoplasmic projections seen in peripheral blood characteristic of hairy cell leukemia. (b) CD20

immunohistochemical staining showing hypocellular marrow with diffuse interstitial infiltration of CD20 positive cells.

362 L. Tsao et al.

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HCL described after transplantation. Although

extremely rare, HCL has been reported in immuno-

compromised patients secondary to human

immunodeficiency virus infection [7]. It is unclear

whether these cases merely represent coincidental

events in immunocompromised patients or neo-

plasms arising secondary to decreased immuno-

surveillance. Because HCL is rare [8], it is difficult

to compare the incidences between immunocompro-

mised and immunocompetent patients. EBER status

by in situ hybridization is also not quite helpful

because late arising PTLDs are more frequently EBV

negative [9]. In our case, EBER by in situ hybridiza-

tion was not performed but EBV-LMP-1 was

negative by immunohistochemistry, consistent with

an EBV-independent process. The lack of response

to reduction of immunosuppression and good

response to HCL treatment can be seen as evidence

against a PTLD; however, only approximately

one-third of all EBV-negative PTLDs arising late

after transplantation will respond to reduction of

immunosuppression [9].

We report the first case of HCL developing after

transplantation. The case did not respond to reduc-

tion of immunosuppression but responded with

complete remission to a 1-week course of 2-CdA.

There was no evidence of EBV association. Because

this is the first case of HCL developing in a post-

transplant setting, it is unclear whether this case

represents a PTLD in the form of HCL or HCL

coincidentally developing in a transplant patient.

Additional cases are needed for further clarification.

References

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et al. MALToma: a Helicobacter pylori-associated malignancy in

transplant patients: a report from the Israel Penn International

Transplant Tumor Registry with a review of published

literature. Transplantation 2003;75:225 – 228.

3. Hsi ED, Singleton TP, Swinnen L, Dunphy CH, Alkan S.

Mucosa-associated lymphoid tissue-type lymphomas occurring

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7. Arruda VR, Bizzacchi JM, Metze IL. Hairy cell leukemia and

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Figure 2. Flow cytometric scattergrams showing (a) CD20 bright,

CD5 negative, (b) kappa light chain restricted population of cells.

These cells also show a typical hairy cell leukemia phenotype with

(c) FMC-7, (d) sIgG, (e) CD25 and (f) bright CD11c expression.

Hairy cell leukemia after cardiac transplant 363

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