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USMLE Step 2 CK
l Internal Medicine
Diagnosis. A normal to slightly decreased MCV anemia with the elevated LDH; indirect bilirubin and reticulocyte count similar to any kind of hemolysis. Although spherocytes may be
present with autoimmune hemolysis, hereditary spherocytosis has a negative Coombs test.
The cells have increased sensitivity to lysis in hypotonic solutions known as an osmotic fragility test. The mean corpuscular hemoglobin concentration (MCHC) is elevated.
Treatment. Most patients require no treatment beyond folate replacement chronically. In
those with more severe anemia, removal of the spleen will eliminate the site of the hemolysis.
The symptoms and jaundice will resolve but the spherocytes will remain.
Note
Decay accelerating factor
(DAF) is also known as CD55
and CD59. DAF are the main
proteins that protect RBCs from
complement destruction.
Copyright 2007 Gold Standard Multimedia Inc.
Figure 6-5. Features of Hereditary Spherocytosis
Seen on Peripheral Blood Smear
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Definition. A red cell membrane defect leading to intermittent dark urine and venous thrombosis and a chronic form of hemolysis.
Etiology. A red cell membrane defect in phosphatidyl inositol glycan A (PIG-A) allows
increased binding of complement to the red cell leading to increased intravascular hemolysis.
It is a clonal stem-cell disorder and therefore can develop into aplastic anemia and leukemia as
well. The cells are more susceptible to lysis by complement in an acid environment. Everyone
becomes a little acidotic at night because of a relative hypoventilation.
Clinical Presentation. In addition to symptoms of anemia, these patients characteristically
present with dark urine from intravascular hemolysis. Thrombosis of major venous structures, particularly the hepatic vein (Budd-Chiari syndrome), is a common cause of death in
these patients. The hemoglobinuria is most commonly in the first morning urine because the
hemolysis occurs more often when patients develop a mild acidosis at night.
Diagnosis. Besides the usual lab findings of hemolysis, such as an increased LDH, bilirubin,
and reticulocyte count, these patients have brisk intravascular hemolysis and therefore have
a low haptoglobin and hemoglobin in the urine. Hemosiderinuria occurs when the capacity of renal tubular cells to absorb and metabolize the hemoglobin is overwhelmed, and the
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sloughed off iron-laden cells are found in the urine. The gold standard test is flow cytometry
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for CD55 and CD59 on white and red cells. In PNH, levels are low or absent.
Treatment. Treatment for PNH depends on the severity of symptoms. Some patients with
few or no symptoms require only folic acid and possible iron supplementation. Over time, the
disease may progress and thus require more aggressive care.
• In the anemic patient with signs of hemolysis, prednisone is often given to slow the
rate of red blood cell destruction.
• In the patient with acute thrombosis, thrombolytic therapy (streptokinase, urokinase,
or tissue plasminogen activator) is often administered, followed by long-term anticoagulation drugs to help prevent further blood clots.
• Antiplatelet agents such as aspirin and ibuprofen may also help prevent blood clots.
Unfortunately, some patients will continue to develop blot clots despite aggressive
anti-coagulation agents.
• Avoid medications that increase the risk for thrombosis, such as oral birth control pills.
PNH is often associated with bone marrow failure. Occasionally patients will respond to antithymocyte globulin, but frequently they will continue to require red cell and/or platelet transfusions. Allogeneic bone marrow transplantation has been the mainstay of curative therapy
for PNH. Recently, the drug eculizumab (brand name Soliris) was approved by the FDA to
treat symptoms of the disease.
Chapter 6
l Hematology
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
Definition. The hereditary deficiency of an enzyme for producing the reducing capacity necessary for neutralizing oxidant stress to the red cell resulting in acute hemolysis.
Etiology. Various forms of oxidant stress result in sudden hemolysis. The most common type
of oxidant stress is actually from infections, not drugs. The most commonly implicated drugs
are sulfa drugs, primiquine, dapsone, quinidine, and nitrofurantoin.
Clinical Presentation. Patients are normal until exposed to the stress. A sudden, severe, intravascular hemolysis can occur including jaundice, dark urine, weakness, and tachycardia. The
history of recent drug ingestion is the main clue to the diagnosis.
Diagnosis. The usual findings of an intravascular hemolysis include high LDH, bilirubin, and
reticulocyte count with a normal MCV, low haptoglobin, and hemoglobinuria. Heinz bodies
are precipitated hemoglobin inclusions seen in red cells. Bite cells are seen on smear indicating the removal of the Heinz bodies. The definitive test is the G6PD level, which can be falsely
normal immediately after an episode of hemolysis. Hence, the level is best tested about 1 week
after the event.
Treatment. There is no specific therapy beyond hydration and transfusion if the hemolysis is
severe. The main therapy is to avoid oxidant stress in the future.
APLASTIC ANEMIA
Definition. Aplastic anemia is failure of all 3 cell lines produced in the bone marrow, resulting in anemia, leukopenia, and thrombocytopenia (pancytopenia). The marrow is essentially
empty with the absence of precursor cells.
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Etiology. Many things can cause bone marrow failure, but the most common cause of true
aplastic anemia is rarely precisely determined. Radiation, toxins such as benzene, drugs such
as NSAIDs, choramphenicol, alcohol, and chemotherapeutic alkylating agents can all cause
aplastic anemia. Infiltration of the marrow with infections such as tuberculosis or cancer such
as lymphoma can cause pancytopenia, but this is not truly aplastic anemia. Aplastic anemia can
also be caused by infections such as hepatitis, HIV, CMV, Epstein-Barr virus, or Parvovirus B19
in immunocompromised patients.
Clinical Presentation. Patients most commonly present with bleeding from the thrombocytopenia, but may present with a combination of the findings associated with deficiencies in
all 3 cell lines. Fatigue from anemia and infections from neutropenia may also occur. The
clinical presentation may give a clue to the presence of pancytopenia but is not sufficient to
determine a true aplastic anemia by clinical manifestations alone. The absence of a classical
association such as benzene, radiation, or chloramphenicol would most certainly not exclude
a diagnosis of aplastic anemia. The most common single etiology is idiopathic.
Diagnosis. Pancytopenia on a CBC is the first test. A bone marrow biopsy confirms the diagnosis when alternative etiologies for a pancytopenia are not present. In other words, the marrow is empty of almost all precursor cells as well as evidence of primary or metastatic cancer,
infection, or fibrosis. The marrow is hypoplastic and fat filled with no abnormal cells seen.
Treatment. Bone marrow transplantation should be carried out whenever the patient
is young and healthy enough to withstand the procedure and there is a donor available.
Allogeneic transplant can cure up to 80–90% of patients under 50. When a bone marrow
transplantation is not possible, immunosuppressive agents should be tried. This is a combination of antithymocyte globulin, cyclosporine, and prednisone. These agents can lead to remission in 60–70% of patients. It is believed that T lymphocytes are primarily causal in the bone
marrow failure, so drugs are used to decrease the T-cell response.
ACUTE LEUKEMIA
Definition. Acute leukemia is the rapid onset of bone marrow failure from the derangement
of the pluripotent stem cell, causing the relentless destruction of the normal production of
the entire bone marrow. The blood cells lose the ability to mature and function normally.
Etiology. Most cases of acute leukemia arise with no apparent cause, but there are several
well known associations: radiation exposure, benzene, chemotherapeutic agents such as melphalan and etoposide, and some retroviruses. Genetic disorders such as Down syndrome and
Klinefelter can result in an increased incidence of leukemia. Myelodysplasia and sideroblastic
anemia can also develop into acute leukemia.
Clinical Presentation. The most common presentation results from the effects of the leukemic blast cells crowding out the normal marrow cells, resulting in symptoms of bone marrow failure (even if total WBC count is elevated or normal). Fatigue from anemia is the most
common presenting complaint. Bleeding from thrombocytopenia occurs. Infection from the
underproduction or abnormal function of WBCs also occurs.
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Acute lymphocytic leukemia (ALL) is more common in children and acute myelogenous leukemia (AML) is more common in adults, but they are indistinguishable clinically. ALL is more
often associated with infiltration of other organs, but AML can do it as well. Enlargement of the
liver, spleen, and lymph nodes and bone pain are common at presentation. Disseminated intravascular coagulation (DIC) is associated with M3 promyelocytic leukemia. CNS involvement
resembling meningitis is present at the time of initial diagnosis in about 5% of patients. CNS
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involvement is most characteristic of M4 and M5 monocytic leukemia. Rarely, a syndrome of
“leucostasis” can occur when the white cell count is extremely elevated. This results from sludging of the leukemic cell in the vasculature, resulting in headache, dyspnea, confusion, and brain
hemorrhage.
Diagnosis. The CBC is the first clue to the diagnosis. Most commonly, WBC is elevated, along
with thrombocytopenia and anemia. In about 10% of acute leukemias, depression of all 3 cell
lines is evident (aleukemic leukemia). Many other disorders can present as pancytopenia similar
to leukemia such as aplastic anemia, infections involving the marrow, metastatic cancer involving the marrow, vitamin B12 deficiency, SLE, hypersplenism, and myelofibrosis. None of these
will have leukemic blasts circulating in the peripheral blood, however. A bone marrow biopsy
showing >20% blasts confirms the diagnosis of acute leukemia. The presence of blasts tells you
the patient has acute leukemia, but blast analysis cannot be relied upon to always tell which type
is present. AML is characterized by the presence of Auer rods, myeloperoxidase, and esterase.
ALL is characterized by the presence of the common ALL antigen (CALLA) and terminal deoxynucleotidyl transferase (TdT). Auer rods are most specific for M3. Ultimately, the diagnosis rests
upon the use of monoclonal antibodies, which recognize specific types of leukemia as well as the
expression of specific CD antigens on the surfaces of the cells. Nonspecific findings that are also
present are hyperuricemia and an increased level of LDH.
Chapter 6
l Hematology
Treatment. Chemotherapy is used initially in all patients to induce a remission. Inducing a
remission means a removal of over 99.9% of the leukemic cells in the body and the elimination
of peripheral blasts in circulation. This is followed by further rounds of chemotherapy to “consolidate” the leukemia further. After chemotherapy, adults with AML or ALL should be referred
for allogeneic bone marrow transplantation. The initial chemotherapy for AML is cytosine
arabinoside (AraC) and either daunorubicin or idarubicin. The initial chemotherapy for ALL is
daunorubicin, vincristine, and prednisone. Promyelocytic leukemia is managed with the addition of the vitamin A derivative all-trans-retinoic acid (ATRA). Leucostasis events are managed
with leukapheresis in addition to the chemotherapy.
ALL patients must also undergo prophylaxis of the central nervous system to prevent relapse
there. The best agent for this is intrathecal methotrexate.
CHRONIC LEUKEMIA
Chronic Myelogenous Leukemia (CML)
Definition. A chronic myeloproliferative disorder characterized by the massive overproduction
of myeloid cells. These cells retain most of their function until later in the course of the disease.
Etiology. Although the Philadelphia chromosome is characteristic of the disease, the cause
of the production of this chromosome is unknown. It is a clonal disorder of myelocytes. The
Philadelphia chromosome is a translocation between chromosomes 9 and 22, resulting in a
gene producing an enzyme with tyrosine kinase activity. Five percent of cases are Philadelphia
chromosome negative.
Note
CML can be confused with
a leukemoid reaction. They
are distinguishable based
upon the leukocyte alkaline
phosphatase score.
Clinical Presentation. A markedly elevated white blood cell count can be found on routine
blood count. The most common symptoms are fatigue, night sweats, and low-grade fever.
Abdominal pain from massive enlargement of the spleen is common. Bone pain from infiltration with white cells can occur. Enlarged lymph nodes are rare. Infection and bleeding are
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l Internal Medicine
uncommon because these white cells retain the majority of their function. Rarely, a leukostasis reaction can occur from extremely elevated amounts of white cells being produced in the
range of 200,000–500,000/mm3. The white cells then clog up the vasculature, resulting in dyspnea, blurry vision, priapism, thrombosis, and stroke.
Diagnosis. The main feature of the disease is an elevated white blood cell count consisting
predominantly of neutrophils with a left shift. Blasts are either absent or present in very small
amounts (<5%). The leukocyte alkaline phosphatase score (LAP) is diminished. Basophilia
is characteristic of CML and all myeloproliferative disorders such as polycythenia vera.
Although the B12 level is often elevated, this would not be enough to establish the diagnosis.
The Philadelphia chromosome is a far more specific test for CML and should be done in a
patient with a markedly elevated white cell count. A low LAP score is not as important as the
PCR for Bcr/Abl. The platelet count can also be markedly elevated.
Treatment. The best initial therapy for CML is imatinib, which is also known by the manufacturer’s name, Gleevec®. Imatinib is a direct inhibitor of the tyrosine kinase produced by
the Philadelphia chromosome. There is nearly a 90% hematologic response to imatinib, and
as many as 60 to 70% of patients may lose the Philadelphia chromosome. The milder the disease, the greater the degree of hematologic response. Bone marrow transplantation is no longer the clear first choice as therapy for CML. This is because of the extraordinary response to
imatinib, as well as the high mortality associated with the bone marrow transplantation itself.
If imatinib fails, then the therapy is bone marrow transplantation.
Chronic Lymphocytic Leukemia (CLL)
Definition. Massive overproduction of mature, but still leukemic, lymphocytes usually from
the monoclonal production of B lymphocytes.
Etiology. The etiology of CLL is unknown.
Clinical Presentation. CLL can often present as an asymptomatic elevation of white cells
found on routine evaluation of patients or during investigations for other problems. Patients
are exclusively older with 90% being age >50. When patients do have symptoms, they are
often nonspecific—fatigue, lethargy, and uncomfortable enlargement of lymph nodes.
Infiltration of other parts of the reticuloendothelial system such as the spleen, liver, and
bone marrow also occurs. Infection and bleeding are unusual presentations of the disease.
Staging for CLL is as follows:
Stage 0: lymphocytosis alone
Stage 1: lymphadenopathy
Stage 2: splenomegaly
Stage 3: anemia
Stage 4: thrombocytopenia
Staging is important because the survival of untreated stage 0 and stage 1 disease is 10–12
years even without treatment. The survival of stage 3 and stage 4 disease is 1–2 years. CLL can
be associated with various autoimmune phenomena such as thrombocytopenia and autoimmune hemolytic anemia.
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Diagnosis. CLL is strongly suspected when an older patient has a marked elevation in the
white cell count with a marked lymphocytic predominance in the range of 80–98% lymphocytes. The marrow is often infiltrated with the leukemic lymphocytes. CD19 is an antigen
strongly associated with CLL. The cell count is usually elevated in the range of 30,000–50,000,
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but may go as high as 150,000. “Smudge cells” seen on a smear are characteristic of CLL.
Treatment. Early stage CLL with only an elevated white cell count or enlargement of lymph
nodes is not treated. However, patients with symptomatic disease always need to be treated.
Those with more advanced-stage disease should receive initial therapy with fludarabine.
Fludarabine has greater efficacy than chlorambucil and should be considered the drug
of choice. Autoimmune hemolysis and thrombocytopenia are treated with prednisone.
Rituximab is used in those patients who express CD20, especially with autoimmune ITP or
hemolytic anemias.
Hairy cell leukemia
Hairy cell leukemia (HCL), classified as a subtype of chronic lymphoid leukemia, makes
up approximately 2% of all leukemias. HCL is characterized by an accumulation of abnormal B lymphocytes. The malignant B lymphocytes (“hairy cells” ) accumulate in the bone
marrow, interfering with the production of normal cells commonly causing pancytopenia.
Consequently, patients may develop infections, anemia and fatigue, or easy bleeding. Early
satiety may occur from massive splenomegaly.
Diagnosis. HCL is commonly considered in the differential diagnosis after routine blood
count shows unexpectedly low numbers of cell lines or after unexplained bruising or recurrent infections in an otherwise apparently healthy patient. Bone marrow biopsy is necessary
for final diagnosis: the biopsy is used to confirm both the presence of HCL and the absence
of any additional diseases. The diagnosis can be confirmed by viewing the cells with a special
stain known as TRAP (tartrate resistant acid phosphatase). Pancytopenia in HCL is caused
primarily by marrow failure and splenomegaly. Bone marrow failure is caused by the accumulation of hairy cells and reticulin fibrosis in the bone marrow, as well as by the unfavorable effects of dysregulated cytokine production.
Chapter 6
l Hematology
Treatment. Purine analogs cladribine (2CDA) and pentostatin are the most common firstline therapies. For cladribine-resistant disease, consider monoclonal antibodies (rituximab
most common) which destroy the malignant B cells. Alpha interferon is helpful in about
60% of patients, to stabilize the disease or produce a slow, minor improvement. More than
95% of new patients are treated well or at least adequately by cladribine or pentostatin. A
majority of new patients can expect a disease-free remission time span of 10 years or even
longer after taking one of these drugs just once.
Myelodysplastic Syndrome (MDS)
MDS is an idiopathic disorder that is considered “pre-leukemic,” in that a number of people go
on to develop acute myelogenous leukemia (AML). MDS is probably from a genetic defect. The
most common defect is 5q deletion or “5q–.” Patients are usually elderly and present with a
pancytopenia, elevated MCV, fatigue, infections, and/or bleeding because of the low cell counts.
There is a small number of blasts from 1–20% and, in fact, it is the percentage of blasts present
that tells how “close” a person is to AML.
Most patients die of infection or bleeding before they develop AML. This is because the disorder
is slowly progressive and older patients “wear out” so to speak from cytopenias, more often than
not going into the “blast phase” that characterizes AML. By definition, you must exclude B12
and folate deficiency because the disorder is so similar.
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l Internal Medicine
CBC and bone marrow are indispensible. You may find a bi-lobed neutrophil called a PelgerHuet cell which is characteristic. Genetic testing for the 5q– is essential.
Treatment is periodic transfusions and control of the infections as they arise. Disease-specific
therapy consists of the TNF inhibitor lenalidomide or thalidomide. Azacitidine or decitabine
is useful when the 5q- is present. Some patients who are young enough with a match can
undergo bone marrow transplantation.
Polycythemia Vera
Definition. A disorder of red cell production. Red cells are produced in excessive amounts in
the absence of hypoxia or increased erythropoietin levels.
Clinical Presentation. Patients present with:
• Markedly elevated hematocrit
• Splenomegaly
• Sometimes elevation of the platelet and white cell counts
• Thromobosis
• “Plethora” or redness and fullness of the face
• Pruritis (approximately 40% of patients), particularly after exposure to warm water
such as in a shower or bath; possibly caused by abnormal histamine or prostaglandin
production
Clinical Pearl
Multiple myeloma causes a
low anion gap.
Diagnosis. Diagnose with a high hematocrit in the absence of hypoxia, carbon monoxide poisoning, or elevated erythropoietin level. The most specific test is the Janus Kinase or JAK-2.
Treatment: Phlebotomy is the primary treatment; hydroxyurea may be used in addition to or
as an alternative. Aspirin is used to reduce the risk of thrombotic events.
Essential Thrombocythemia
Essential thrombocythemia is a type of platelet cancer. Platelet count may be over a million.
There is either thrombosis or bleeding. The most specific test is JAK-2. Treat with hydroxyurea
and sometimes anagrelide.
PLASMA CELL DISORDERS
Multiple Myeloma
Definition. A clonal abnormality of plasma cells resulting in their overproduction replacing
the bone marrow as well as the production of large quantities of functionless immunoglobulins. The disease is characterized by various systemic manifestations such as bone, kidney, and
infectious complications.
Etiology. The cause of multiple myeloma is unknown.
Clinical Presentation. Bone pain is the most common clinical manifestation. This is most com-
monly in the back and the ribs, secondary to pathologic fractures. Radiculopathy from the
compression of spinal nerve roots is also common. Infection particularly with encapsulated
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organisms such as Pneumococcus and Haemophilus is common. Renal failure and anemia are
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common. The symptoms of hypercalcemia such as polyuria, polydipsia, and altered mental status
may occur. Weakness, fatigue, and pallor are common. Rarely, symptoms of a hyperviscosity syndrome such as blurry vision, confusion, and mucosal bleeding may occur.
Diagnosis. Although a normochromic, normocytic anemia is the most common laboratory
finding, this is not specific for myeloma. A protein electrophoresis with a markedly elevated
monoclonal immunoglobulin spike is present in almost all cases. This is most commonly IgG
but may be IgA, IgD, or rarely a combination of two of these. In about 80% of individuals, routine x-ray will reveal the punched-out lytic lesion caused by the overproduction of osteoclast
activating factor from the plasma cells and/or pathologic fractures at the time of diagnosis.
Most commonly involved are the vertebrae, ribs, pelvic bones, and bones of the thigh and
upper arm. If multiple myeloma is suspected with normal x-ray, consider MRI, CT, or PET.
Serum B2 microglobulin is elevated in 75% of patients. Hypercalcemia from the destruction of
bone is common, as is an elevation in the BUN and creatinine from the damage to the kidney
from the immunoglobulins, Bence-Jones protein, calcium, and hyperuricemia. A bone marrow
biopsy with >10% plasma cells confirms a diagnosis of multiple myeloma. Bence-Jones protein
is often not detected by a standard protein test on a urinalysis, which mainly is meant to detect
albumin. A specific test for Bence-Jones protein involving acidification of the urine is required.
Increased gamma globulin levels will increase the total protein and decrease the albumin level.
Chapter 6
l Hematology
Treatment. Younger patients (age <70) should be treated with autologous bone marrow
transplantation in an attempt to cure the disease. Older patients should receive a combina-
tion of melphalan and prednisone. Patients who are candidates for transplants should receive
thalidomide (or lenalidomide) and dexamethasone. Patients who are not candidates for transplants should receive melphalan, prednisone, and thalidomide. Hypercalcemia is treated initially with hydration and loop diuretics and then with bisphosphonates such as pamidronate.
Bortezomib is a proteasome inhibitor useful for relapsed myeloma or in combination with the
other medications. It can be combined with steroids, melphalan, or lenalidomide (thalidomide).
Monoclonal Gammopathy of Uncertain Significance (MGUS)
Definition. The overproduction of a particular immunoglobulin by plasma cells without the systemic manifestations of myeloma such as bone lesions, renal failure, anemia, and hypercalcemia.
Etiology. The cause of MGUS is unknown. MGUS is a very common abnormality present in
1% of all patients age >50 and in 3% of those age >70. Some patients with MGUS may progress to multiple myeloma.
Clinical Presentation. Patients with MGUS have no symptoms. It is found on routine blood
testing for other reasons.
Diagnosis. An elevated monoclonal immunoglobulin spike of serum protein electrophoresis
(SPEP) in amounts lower than found in myeloma. The creatinine, calcium, and hemoglobin
levels are normal. An elevated total serum protein is the clue to the diagnosis. There are no
lytic bone lesions, and the bone marrow has <5% plasma cells. The beta-2 microglobulin level
will be normal in most patients.
Treatment. Treatment is neither effective nor necessary.
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LYMPHOMA
A 32-year-old woman comes to the office with a neck mass for the last several
weeks. She also has fever, weight loss, and sweats.
Hodgkin Disease
Definition. A neoplastic transformation of lymphocytes particularly in the lymph node. It is
characterized by the presence of Reed-Sternberg cells on histology which spreads in an orderly,
centripetal fashion to contiguous areas of lymph nodes.
Normal
lymphocyte
National Cancer Institute
Figure 6-6. Reed-Sternberg Cell
Etiology. Although there is a clear increase in Hodgkin disease among relatives of those with
the disease, there are no clear environmental or infectious etiologies for the disorder.
Hodgkin disease has bimodal age distribution—one peak in the 20s and 60s.
Clinical Presentation. Enlarged, painless, rubbery, nonerythematous, nontender lymph nodes
are the hallmark of the disease. Patients may also develop what are labeled “B” symptoms,
which are drenching night sweats, 10% weight loss, and fevers. Although pruritus is common in the disease, it is not one of the “B” symptoms. Cervical, supraclavicular, and axillary
lymphadenopathy are the most common initial signs of disease. Lymphadenopathy may
develop anywhere in the body, however. Extralymphatic sites such as splenic involvement,
skin, gastric, lung, CNS, or any other organ may possibly be involved. Extralymphatic involvement is more common with non-Hodgkin lymphoma.
Reed-Sternberg
Cell
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Staging is as follows:
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Stage 1: 1 lymphatic group or single extra lymphatic site
Stage 2: 2 lymphatic groups or extra lymphatic sites on same side of the diaphragm
Stage 3: Involvement of lymphatic groups on both sides of the diaphragm or involve-
ment of any extralymphatic organ contiguous to the primary nodal site
Chapter 6
l Hematology
Stage 4: Widespread disease with involvement of diffuse extralymphatic sites such as
bone marrow or liver
The staging is the same for both Hodgkin as well as non-Hodgkin lymphoma. In Hodgkin
lymphoma, staging is the single most important predictor of outcomes.
Diagnosis. An excisional lymph node biopsy is the essential first step in determining the diagnosis. After the initial diagnosis is determined by the biopsy, the most important step is to determine
the extent of disease because the stage will determine the nature of the therapy, i.e., radiation
versus chemotherapy. Chest x-ray or chest CT, abdominal CT, or MRI is used to determine if the
disease is localized to the supraclavicular area. Lymphangiography and laparotomy are no longer
routinely used for staging. CT scan is sensitive enough to detect any involved lymph nodes. A
bone marrow biopsy is used to definitively determine if the disease is truly localized.
Size alone is insufficient to determine the content of some enlarged nodes. PET scan can also
be used for that purpose.
Other labs tests that are often abnormal, but don’t directly alter the stage of the disease, include a
CBC looking for anemia as well as increased white cell or platelet count. Eosinophilia is common.
An elevated LDH level indicates an adverse prognosis. The ESR is useful prognostically. Elevated
liver function tests help determine the need for liver biopsy.
Treatment. Therapy is entirely based on the stage of the disease. Localized disease such as stage
IA and IIA is managed predominantly with radiation. In the early stages (IA, IIA), adjunct chemotherapy may be used with radiation. All patients with evidence of “B” symptoms as well as
stage III or stage IV disease are managed with chemotherapy. The most effective combination
chemotherapeutic regimen for Hodgkin disease is ABVD (adriamycin [doxorubicin], bleomycin,
vinblastine, and dacarbazine). ABVD is superior to MOPP (meclorethamine, oncovin [vincristine], prednisone, and procarbazine) because ABVD has fewer adverse effects such as permanent
sterility, secondary cancer formation, leukemia, aplastic anemia, and peripheral neuropathy.
Note
Adverse Prognostic Factors
• Large mediastinal
lymphadenopathy
• Age >40
• “B” symptoms
↑ ESR
•
Hodgkin disease has several histologic subtypes. Lymphocyte-predominant has the best prognosis, and lymphocyte-depleted has the worst prognosis. The histologic subtype does not alter
anything described above. The lab tests, staging, and treatments are the same.
Non-Hodgkin Lymphoma (NHL)
Definition. The neoplastic transformation of both the B and T cell lineages of lymphatic cells.
NHL causes the accumulation of neoplastic cells in both the lymph nodes as well as more often
diffusely in extralymphatic organs and the bloodstream. The Reed-Sternberg cell is absent.
Etiology. There are a number of infectious and autoimmune disorders associated with the
development of NHL. Their absence, however, by no means excludes the presence of NHL.
Infections such as HIV, hepatitis C, Epstein-Barr, HTLV-I, and Helicobacter pylori predispose to the development of NHL. HIV and Epstein-Barr are both more often associated
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