Figure 73-10. A massively enlarged, 2.2-kg spleen from a patient with chronic lymphocytic leukemia. Superficial areas of

infarction are indicated by thin arrows and splenic infarction by the thick arrow.

Patients by definition in stage II or greater CLL will have splenomegaly and anemia and

thrombocytopenia secondary to hypersplenism. Splenomegaly often reaches very large sizes and

patients may have symptoms secondary to the compressive effects of the large spleen on the stomach

with early satiety and pain (Fig. 73-10). Treatment of early stage disease is either observation or

treatment with nontoxic doses of alkylating agents such as chlorambucil or cyclophosphamide. There

are many treatment options for higher-risk patients, including fludarabine, cyclophosphamide

(Cytoxan), rituximab in varied combination, and other chemotherapeutic agents. Many patients will

eventually develop hypersplenism and splenomegaly. One strategy that has been employed in particular

for patients who are nonoperative candidates is splenic radiation.87 The splenic radiation has decreased

the size of the spleen improving symptoms due to mass effect, but it may have complications of further

thrombocytopenia and leukopenia.

Splenectomy is a highly successful treatment for both the pressure effects due to splenomegaly and

the cytopenias.88,89 Reports of 85% resolution of thrombocytopenia and 100% resolution of anemia have

been published.90 The negative feature of splenectomy in this patient population is that they are

typically elderly and are typically debilitated from having gone through years of having CLL and

potentially prior chemotherapy treatment. In one series in which a prospective comparison was made

between splenectomy and fludarabine for later stage CLL, there was a 9% perioperative mortality in the

splenectomy group primarily due to sepsis in this patient population.91 However, in this same study,

there were highly significant improvements in thrombocytopenia and anemia. The patients who are

younger and have larger spleen sizes tend to do better. In this comparative study of patients with Rai

stage IV CLL, the 2-year actuarial survival rate was 51% in the splenectomy arm and a 28% survival

rate in the fludarabine arm.91 At present, splenectomy is recommended for patients who have failed

medical therapy and have anemia with transfusion requirements or thrombocytopenia with bleeding or

compressive symptoms such as splenomegaly.

Chronic Myelogenous Leukemia

Chronic myelogenous leukemia (CML) is a leukemia with the cell of origin, a primitive hematopoietic

cell. This primordial cell can differentiate into myeloid cell lines, erythroid cell lines, platelet cell lines,

and possibly B lymphoid and T lymphoid cells. CML occurs preferentially in men to women at a 1.5:1

ratio, and like CLL typically occurs in the sixth decade of life or older. This disease varies from CLL in

that it invariably progresses from a chronic stage to an accelerated and blastic stage whereas CLL

remains more indolent. The initial chronic phase may last anywhere between 1 and 5 years and is

characterized by splenomegaly, constitutional symptoms of fatigue, abdominal fullness, and weight

loss.92 The accelerated phase is apparent with 15% of circulating cells being more immature blast cells

and then within 3 to 6 months this generally converts to the terminal blast phase in which the blastic

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cells fill the bone marrow and the circulating blood at >30% of leukocytes and may cause destruction

of other organs. Death due to infection or bleeding invariably results after the blast crisis begins.

The diagnosis of CML is made by the leukocytosis with myeloid differentiation and presence of

granulocytes filling the bone marrow space. Ninety percent of patients have the classic Philadelphia

chromosome that is a reciprocal translation between chromosomes 9 and 22. On the basis of randomized

trials, there is no benefit in terms of delaying the accelerated and blast phases of the disease by doing a

splenectomy during the chronic phase of the disease. Certain select patients who have significant

hypersplenism or splenomegaly may benefit with symptomatic improvement during the chronic

phase.93,94

A recent study from MD Anderson reports their experience of splenectomy during the accelerated or

blast phase of disease.95 Patients were referred for this procedure with symptoms of splenomegaly in

42% of cases, thrombocytopenia in 30% of cases, to potentially improve administration of

chemotherapy by reducing the hypersplenism in 19% of cases, and because of symptoms with both

hypersplenism and thrombocytopenia in 9% of cases. The perioperative mortality rate in this series of

53 patients was 1.9% with one patient death. There was universal benefit of symptoms related to

splenomegaly and there was a marked improvement of platelet count and requirement for platelet

transfusions in patients with preoperative thrombocytopenia. The median 6-month transfusion

requirements decreased from 21 down to 1, combining both platelet and red cell transfusions. The

median postsplenectomy survival was 19 months for patients in the accelerated phase and 6.5 months

for patients in the blastic phase of their disease. This report concludes that for select patients who have

severe transfusion requirements and/or severe symptoms of splenomegaly, there is objective benefit

with relatively low morbidity in patients with this later stage of CML.

Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma is the most common cause of lymphoma outnumbering Hodgkin disease by a

ratio of almost 6:1 in the United States. Non-Hodgkin lymphoma is a much more heterogeneous disease

with a large range of histologic cell types defined by morphology and immunohistochemistry studies to

differentiate subgroups of the disease. The clinical course of these different subgroups correlates with

these microscopic findings. In general, diffuse or infiltrative non-Hodgkin lymphoma tends to have a

worse prognosis than nodular NHL. The diffuse high-grade type occurs most commonly in the younger

patient population (age <35 years) or the very elderly. More aggressive non-Hodgkin lymphomas tend

to be T-cell lymphomas with the low grade tending to be B cell. Non-Hodgkin lymphoma as opposed to

Hodgkin disease occurs at presentation in approximately one-third of cases in extranodal sites while

two-thirds are limited to lymphadenopathy.96,97 In general, the disease is more diffuse at the time of

presentation mandating treatment by combination chemotherapy. It is for this reason that the staging

laparotomy classically using Hodgkin disease (see below) is not applicable in NHL.

In patients dying of NHL, up to 80% of patients will have significant splenic involvement with

splenomegaly due to lymphatic infiltration.98,99 As is true with other infiltrative neoplastic diseases,

symptoms of pancytopenia and splenomegaly are common in patients with NHL. Patients who are

operative candidates have significant benefit with up to 80% of patients having decreased transfusion

requirements and the majority of patients having relief of gastric oppression and pain symptoms due to

splenomegaly.100 In terms of the response of the pancytopenias, it is somewhat dependent on the bone

marrow reserve that may have been heavily pretreated with prior chemotherapy and/or radiation

therapy. There is no differential test to identify adequate marrow reserve and the only assessment in

that situation is whether a patient has a response following splenectomy.

Hairy Cell Leukemia

Hairy cell leukemia is a low-grade lymphoproliferative disorder with characteristic “hairy cells” due to

irregular filament projections from the cell surface that give an appearance of hair under light

microscopy.101 This leukemia is a B-lymphocyte tumor that infiltrates the bone marrow and spleen with

almost no peripheral lymphadenopathy. There may and may not be enlargement of the liver. The

disease is much more common in males than in females by a fourfold difference and the onset of disease

is typically in the fifth or sixth decade of life.

The initial symptoms most commonly relate to enlargement of the spleen either by direct effects of

splenomegaly or by pancytopenia due to hypersplenism (Fig. 73-11).102 Patients may have early satiety

or upper quadrant pain with a large palpable spleen infiltrated with leukemic cells. The enlarged spleen

often causes symptoms related to anemia with a transfusion requirement, bleeding due to

thrombocytopenia, and frequent infections due to leukopenia. In the past, hairy cell leukemia was

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described as the “surgical leukemia” as splenectomy was recommended as the primary treatment since

virtually all patients would have resolution of their symptoms of splenomegaly and splenectomy was

considered the standard of care.103 However, the vast majority of patients relapsed, some as early as 6

to 12 months later, and only 40% to 50% of patients received long-term benefit from the cytopenias due

to bone marrow replacement with hairy cell infiltrates.

Figure 73-11. Spleen from a patient with hairy cell leukemia. Note the whitened anterior edge of the spleen and the white “sugarcoating” spots on the surface.

In 1984, medical therapy initially with recombinant alpha-interferon led to improved responses.104

Newer trials with purine analogs such as pentostatin (2-doxycoformycin) and 2-chlorodoxydenosine

provided a beneficial nonsurgical therapy.105 A randomized trial comparing pentostatin with αinterferon showed a complete response rate of 78% with pentostatin versus 11% with α-interferon and

this has now become a first-line therapy.106 The 10-year survival rate for pentostatin is 96% and 100%

for cladribine.107 Five percent to 10% of patients who are resistant to medical therapy may be offered

splenectomy as a salvage therapy.

Myelodysplastic Syndrome

AMM or myelodysplastic syndrome (MDS) with myeloid metaplasia is a poorly understood disorder

characterized by a fibrotic replacement of the bone marrow compartment with extramedullary

hematopoiesis and massive splenomegaly.108 The pathophysiology of the disease is poorly understood

but includes a nonclonal proliferation of fibroblasts making a dense fibrous stroma that fills the marrow

space and contributes to hepatosplenomegaly and lymphadenopathy. This fibrous proliferation may be

under control of secreted growth factors such as transformin growth factor beta.109 Other

myeloproliferative diseases include polycythemia vera and essential or idiopathic thrombocytosis.

The clinical symptoms and features of MDS relate to anemia and splenomegaly via direct mass effects

or hypersplenism.110 Patients tend to be in the fifth decade of life or older. They present with

constitutional symptoms, including weight loss, fatigue, as well as abdominal fullness and discomfort

due to splenomegaly. There may be pain from splenic infarctions. Patients may present with bleeding

due to thrombocytopenia. Hepatomegaly is present in 50% to 75% of patients and splenomegaly is

present in virtually all patients. The massively enlarged spleens in MDS are often some of the largest

spleens by weight in most clinical series.

The combination of massive splenomegaly with increased blood flow via the enlarged spleen and

hepatomegaly with fibrosis leading to relative portal hypertension creates a unique situation in which

some of the clinical symptoms may be similar to portal hypertension from other cause as patients may

present with varices and ascites. The diagnosis is made by evaluation of peripheral blood smear that

shows immature red blood cells with poikilocytes and tear-shaped cells. There can be either

thrombocytopenia or thrombocytosis with platelet counts of greater than one million. Similarly, there

may be leukopenia or there may be elevated white blood cell counts similar to CML. Bone marrow

biopsy often produces a dry tap due to the fibrotic replacement of the marrows.

Treatment is generally targeted to palliate the symptoms that are present.110 Anemia and

thrombocytopenia can be treated with transfusions. There is some role for alkylating agents and

steroids, and in patients with thrombocytosis, hydroxyurea is of benefit.111 Splenectomy is indicated for

relief of significant symptoms of hypersplenism or splenomegaly.112 Hypersplenism is manifested by

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