Hairy Cell Leukemia, Symptoms And Life Expectancy

What Is Hairy Cell Leukemia?

Hairy cell leukemia (HCL) is a mature B-cell neoplasm that involves primarily the blood, bone marrow, and splenic red pulp. Hairy cell leukemia is rare, with only about 600 to 1000 cases per year diagnosed in the United States and accounting for only 2% of all leukemias.5 It affects predominantly middle-aged men and does not occur in children.

Etiology Of Hairy Cell Leukemia?

Hairy cell leukemia is not associated with the Epstein-Barr virus or other infectious pathogens. Several reports of hairy cell leukemia occurring in family members have raised the possibility of a genetic predisposition for the disease. In many families, the cases were linked to an HLA A1, B7 haplotype, and association with other HLA haplotypes has also been reported. Some studies have suggested exposure to organic solvents and petroleum products as risk factors. Nevertheless, the vast majority of hairy cell leukemia cases appear to be sporadic.

Hair Cell Leukemia Signs?

Patients with hairy cell leukemia present most often with clinical sequelae related to one or more cytopenias. In one large series, infections (29%) and weakness or fatigue (27%) were the most common initial symptoms.

Diagnosis Of Hairy Cell Leukemia

Abnormalities found on physical examination and in laboratory studies in hairy cell leukemia patients at presentation are summarized.  Hairy cell leukemia is characterized by a leukopenic rather than a leukemic presentation: about half of patients are markedly neutropenic at diagnosis (absolute neutrophil count <0.5 ×109 /L), and half are pancytopenia. An elevated white blood cell count (>10 × 109 /L) characterizes only 10% to 15% of cases. Marked leukocytosis with numerous circulating neoplastic cells is rare in hairy cell leukemia and, if present, raises the possibility of the so-called hairy cell leukemia variant or another lymphoma subtype.

Hair Cell Leukemia Symptoms?

Monocytopenia is seen in almost all hairy cell leukemia cases and is considered to be one of the most sensitive markers of disease. Leukoerythroblastosis is usually not seen, despite the common presence of bone marrow fibrosis. Palpable splenomegaly is present at diagnosis in 72% to 90% of patients, whereas peripheral lymphadenopathy is uncommon. Infections represent a major cause of morbidity in hairy cell leukemia patients and include both bacterial infections as well as infections by opportunistic organisms such as Pneumocystis species and fungi. 

This striking susceptibility to infections likely reflects both the reduced number of circulating granulocytes and monocytes as well as the disrupted function of immune effector cells, including defective interferon-gamma production. Uncommon disease manifestations include lytic bone lesions; involvement of extranodal organs such as lung, stomach, and esophagus; and bulky abdominal lymphadenopathy.

Computed Tomography (CT) Of Hair Cell Leukemia?

Retroperitoneal lymphadenopathy is detected by computed tomography (CT) in about 15% of patients at presentation and in up to 56% of patients later during the course of the disease. Massive abdominal lymphadenopathy has been associated with a poorer response to therapy, leading some to suggest the use of abdominal CT scans to stage hairy cell leukemia. However, CT imaging to stage hairy cell leukemia is not common practice in the current era. 

Diagnostic Procedures Of Hair Cell Leukemia?

Although a diagnosis of hairy cell leukemia can be based on peripheral blood morphology and immunophenotype, examination of bone marrow is recommended in all newly diagnosed cases to assess the extent of marrow involvement and provide the baseline for assessing response to treatment.

The pattern of hairy cell leukemia in bone marrow is highly characteristic and is distinct from other small B-cell lymphomas. The key diagnostic features of hairy cell leukemia are summarized. A good bone marrow core biopsy is essential because the bone marrow aspirate is often poorly cellular or unobtainable due to marrow fibrosis.

Hair Cell Leukemia Morphology on Smear Preparations?

Hairy cell leukemia morphology is ideally represented on well-prepared Wright-Giemsa-stained peripheral blood smears. Hairy cells are 1.5 to 2 times the size of small lymphocytes and are characterized by oval to bean-shaped nuclei, dispersed granular chromatin with features intermediate between a mature lymphocyte and a blast, and absent or inconspicuous, small nucleoli. Hairy cell cytoplasm is moderately abundant, pale blue, and often flocculent, with ill-defined or ruffled borders exhibiting thin surface projections. Occasional cytoplasmic granules or small rod-shaped structures may be evident. These correspond to the ribosome-lamellar complexes frequently seen in hairy cells by electron microscopy.

Smear Preparation For Hairy Cell Leukemia

Hairy projections are best seen in thin areas of the smears and, when well-demonstrated, are present all around the cell membrane. Poorly prepared or thick smears (particularly from bone marrow aspirations) may cause artifactual hairlike projections or cytoplasmic ruffling in other cell types, mimicking hairy cells. Moreover, the cell trauma associated with preparing the bone marrow aspirate renders the characteristic hairy cell cytomorphology more difficult to appreciate in aspirate smears or touch preparations than in peripheral smears.

Hair Cell Leukemia Morphology In Bone Marrow Sections?

At low power, the bone marrow infiltrate in hairy cell leukemia is interstitial or diffuse and does not form well-defined nodular aggregates that characterize most other small B-cell lymphomas. At diagnosis, the bone marrow is hypercellular in most cases, with diffuse sheets of hairy cells. However, in the early stages of the disease, the bone marrow may be hypocellular or may have a subtle interstitial infiltrate that is not readily apparent on routine histologic stains.

At higher power, the hairy cells appear round and monotonous, with oval to indented and occasionally convoluted nuclei set in an abundant clear cytoplasm that holds the nuclei equidistant and imparts the characteristic “fried egg” appearance; large lymphoid cells are virtually absent. Depending on the fixation and processing method, the cytoplasm may appear clear, uniformly pale pink, or flocculent on the hematoxylin-eosin stain. The spaced appearance of hairy cells in tissue sections appears to be due to the pericellular deposition of fibronectin.

The hairy projections are usually not evident on routine histologic stains, although these may be visualized with DBA44 immunohistochemistry. Immunohistochemical stains for CD20 or DBA44 may also reveal an intrasinusoidal component to the infiltrate in up to 70% of cases. In some cases, particularly when there is extensive involvement, the neoplastic cell infiltrate may appear spindle.


Hair Cell Leukemia In Spleen and Other Organs?

Hairy cell leukemia almost always involves the spleen. In contrast to most other B-cell lymphomas (including splenic marginal-zone lymphoma, hairy cell leukemia preferentially involves the splenic red pulp rather than the white pulp. Microscopically, the hairy cells in the spleen appear similar to those in involved bone marrow sections. Microscopic areas of hemorrhage (so-called pseudoviruses or blood lakes) are characteristic but not specific for hairy cell leukemia and result from hairy cell adhesion and damage to sinus endothelial cells.


Causes Of Hairy Cell Leukemia?

Owing to advances in hairy cell leukemia diagnosis and therapy, pathologists now rarely encounter splenectomy specimens from hairy cell leukemia patients. Hairy cell leukemia almost always involves the liver at presentation and commonly causes modest hepatomegaly, although the liver is usually not biopsied. In liver biopsies, the hairy cells are located in small clusters in the sinuses and portal tracts.

Immunohistochemistry And Cytochemistry Of Hair Cell Leukemia?

If the characteristic hairy cell leukemia immunophenotype can be demonstrated by flow cytometry of peripheral blood or bone marrow aspirate, paraffin section immunohistochemistry on biopsy samples is usually unnecessary except to help quantify involvement in morphologically subtle or treated cases. Hairy cells can be readily identified in tissue sections by routine B-cell markers such as CD20 and CD79a, and these markers often reveal far more hairy cells than are evident on routine stains. 

Variants Of Hair Cell Leukemia?

About 10% of patients with otherwise typical hairy cell leukemia have immunoglobulin gene rearrangement using the VH4-34 region. These cases tend to have more advanced disease at presentation, poorer response to purine analog therapy, and shorter survival compared with other hairy cell leukemia cases.

The nature of these hairy cell leukemia cases and their relationship to hairy cell leukemia-v and splenic diffuse red pulp small B-cell lymphoma still remains controversial. The disease known as hairy cell variant (hairy cell leukemia-v) is rare, and it is only about 10% as frequent as hairy cell leukemia. These cases display significant morphologic, immunophenotypic, and clinical differences from hairy cell leukemia and also show a profile of genetic aberrations that is distinct from hairy cell leukemia. 

Hairy Cell Leukemia In Bone Marrow

The leukemic cells resemble hairy cells in terms of having abundant cytoplasm and surface projections, but also have prominent central nucleoli that are not typically seen in hairy cell leukemia and are reminiscent of prolymphocytes. Unlike in classical hairy cell leukemia, monocytopenia is not seen. The pattern of bone marrow and splenic red pulp infiltration is similar to that in hairy cell leukemia, although bone marrow fibrosis is usually not seen in hairy cell leukemia-v.81 Immunophenotypically, hairy cell leukemia-v shares some similarities with hairy cell leukemia in that it expresses CD11c, DBA44 (by immunohistochemistry), and often CD103, but it is negative for CD123, cyclin D1, and annexin A1 and is usually negative for CD25.

Treatment Of  Hair Cell Leukemia?

About 90% of hairy cell leukemia patients will require treatment for symptoms related to recurrent infections, splenomegaly, or progressive cytopenia. The clinical course of hairy cell leukemia has changed dramatically over the past several decades owing to major advances in therapy. The purine analogs 2 chlorodeoxyadenosine (2-CdA) and deoxycoformycin (pentostatin, DCF) represent highly effective therapies for hairy cell leukemia and have replaced interferon-α and splenectomy as the first-line therapy.

Hairy Cell Leukemia Life Expectancy?

The long-term survival of hairy cell leukemia treated with 2-CdA is excellent (96% at 13 years), and death due to hairy cell leukemia is now uncommon; patients can be expected to experience a normal or near-normal life expectancy. Although late relapses are relatively common (ranging from 24% at 5 years to nearly 50% at 10 years), the relapsed disease usually responds to retreatment with purine analogs.

Monoclonal antibodies such as rituximab and anti-CD22 immunotoxin have proved effective in purine analogue–resistant hairy cell leukemia; rituximab also may be used in combination with purine analogs as first-line therapy. Vemurafenib, a low–molecular-weight inhibitor of BRAF has been used effectively to treat hairy cell leukemia cases that are resistant to other therapies.
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