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1554 Part XI: Malignant Lymphoid Diseases Chapter 93: Hairy Cell Leukemia 1555

has been estimated that 48 percent of infections are caused by pyogenic acid phosphatase (TRAP) was routinely performed since hairy cells are
organisms including Staphylococcus aureus, Pseudomonas aeruginosa, positive for this enzyme. However, this stain is technically difficult and
Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumonia, and was therefore replaced by immunohistochemical stains (IHC) for this
Legionella pneumophilia. Multiple other organisms have been identi- enzyme. Moreover, a more definitive diagnosis can be made by flow
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fied as a source of infection including Aspergillus, Candida, Blastomyces, cytometry identifying the characteristic immunophenotypic profile.
Histoplasma, Cryptococcus, Toxoplasmosis, Pneumocystis jiroveci, and HCL cells are strongly positive for CD20, and are positive for CD11c+,
atypical mycobacteria. CD25+, CD103+, and CD123+. The leukemic cells are usually negative
While the majority of infections occur before effective treatment for CD5−, CD10−, CD27−, and CD43−. Consequently, it is essential
has been initiated, the additional risk of infection as a complication to secure a comprehensive immunophenotypic profile of the leukemic
of treatment exists both immediately following therapy and for many cells, as even small monoclonal populations can be identified by multi-
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months thereafter. The purine nucleoside analogues that are used as channel flow cytometry in the blood (see Fig. 93–1).
a backbone of induction therapy can produce profound and prolonged
myelosuppression. Because of the extensive marrow involvement with MARROW BIOPSY
leukemia, the myeloid reserve is severely compromised at the initia-
tion of therapy. Following effective therapy, the granulocytes gradually In establishing the diagnosis, a marrow biopsy should be obtained to
recover, but the purine nucleoside analogues usually induce a prolonged evaluate the degree of marrow cellularity and the percentage of leuke-
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period of reduction in lymphoid cells, thus opportunistic infections mic cell infiltration (Fig. 93–2). In addition, marrow fibrosis is char-
resulting from compromised lymphocyte function may also emerge in acteristic of this disease. The marrow cellularity can be quite variable.
the posttreatment period. Once the patient has achieved a complete Some patients with this diagnosis have a severely hypocellular marrow,
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remission, the risks for infection become progressively less as the hema- and this pattern could be misread as hypocellular or aplastic anemia.
tologic parameters improve. Full recovery of lymphocyte function fol- More often, there is either infiltrative disease or diffuse marrow replace-
lowing purine analogue therapy, however, may require several years. 46,47 ment with the characteristic mononuclear cells with nonoverlapping
Unusual symptoms related to HCL may include bone pain and cellular borders. These cells have resembled a “fried egg–like” appear-
autoimmune complications. 48,49 Bone pain may be the result of lytic dis- ance. Immunohistochemical stains can be used to definitively identify
ease that can involve the spine, the femur, and other skeletal sites. Lytic the leukemic cells within the biopsy. Immunohistochemical staining of
bone disease can occur at any time during the course of the disease. the marrow with anti-CD20 is most useful, followed by staining with
Both magnetic resonance imaging (MRI) and computed tomography annexin and DBA.44 monoclonal antibody to further narrow the differ-
(CT) scans have been helpful in identifying these lesions even when ential diagnosis. The demonstration that the mutation BRAF V600E is
plain films of involved areas are normal. Biopsies of bone lesions have found in the overwhelming majority of cells from patients with HCL-c
confirmed the presence of hairy cells, and these manifestations may has provided yet another confirmatory stain for this disease. 58
respond to effective treatment of the leukemia. Many of the patients Additional baseline laboratory tests to obtain before treatment
with bone lesions respond to systemic treatment of the disease, but oth- include an assessment of renal function as both of the commonly used
ers require additional localized irradiation. purine nucleoside analogues are excreted by a renal route. It is important
Diverse autoimmune findings in patients represent other unusual to screen for evidence of previous hepatitis B as serious complications
complications. 49,50 Patients may complain of migratory inflammatory including acute liver injury have resulted from the use of immunosup-
episodes involving the joints and tenosynovial tissues. These painful pressive agents (e.g., rituximab). 59
inflammatory episodes are usually self-limited and resolve sponta-
neously but may be recurrent. Vasculitic skin lesions and erythema LABORATORY VALUES USEFUL IN PATIENT
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nodosum have been reported. Autoimmune hemolytic anemia and MONITORING
thrombocytopenia have also been observed. 52–54 The autoimmune phe-
nomena are not related to tumor burden, and may be present at ini- Serial complete blood count monitoring with attention to the absolute
tial diagnosis or occur anytime throughout the course of the disease. neutrophil count, the platelet count, and the hemoglobin is the most
Finally, patients have also presented with paraneoplastic neurological useful approach to follow the progress of HCL patients. As the expres-
syndromes. 55 sion of soluble interleukin-2 (IL-2) receptor correlates with tumor
burden a baseline determination of the soluble IL-2 receptor may be
LABORATORY FEATURES important for following the course of the disease and its response to
treatment. Soluble CD22 also can be followed in a similar manner as a
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Patients with HCL reviewed in a large Italian series had pancytopenia correlate of leukemic cell burden. 61,62
(77 percent) reflecting impaired hematopoiesis due to marrow infil-
tration and splenic sequestration. 21,43 Approximately 28.4 percent of DIFFERENTIAL DIAGNOSIS
patients had a hemoglobin less than 8.5 g/dL with 14.9 percent requiring
a blood transfusion, 39 percent of patients had an absolute neutropenia Several B-cell clinical entities can be considered when establishing a
(neutrophils <500/μL), and 72.6 percent had a platelet count less than diagnosis of HCL-c. The World Health Organization (WHO) defined
100,000. Jansen earlier developed prognostic criteria for HCL relating an HCL-v that is completely separate from the classic form of this dis-
the degree of anemia and splenomegaly to survival. The Jansen staging ease. 19,39,58,64 The frequency of HCL-v is approximately 10 percent of
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system was developed before the age of effective therapy. Nevertheless, HCL-c. This rare chronic B-cell lymphoproliferative disorder is char-
a later study also showed that the degree of anemia in younger patients acterized by leukocytosis, lack of monocytopenia and neoplastic B cells
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correlated with overall survival following therapy with pentostatin. with nucleoli and convoluted nuclei. The cytoplasm may have a shaggy
Most patients have monocytopenia. Many patients have morphologic edge, but the ruffled border is usually not circumferential as in HCL-c.
evidence of “hairy cells” on blood films characterized by pale blue or The immunophenotype is characterized as CD25− and CD123− nega-
gray cytoplasm with a serrated/ruffled border (Fig. 93–1). The nucleus tive, annexin-1 negative, and negative for TRAP, both by cytochemical
is oval and often reniform in shape with spongy chromatin and indis- and by immunohistochemical methods. The BRAF V600E mutation is
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tinct nucleoli. In the past, cytochemical staining with tartrate-resistant not present in this entity. The clinical course of the disease is initially

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