Page 72 - Williams Hematology ( PDFDrive )

48 Part I: Clinical Evaluation of the Patient Chapter 4: Consultative Hematology 49

Although there are several causes for the appearance of nRBCs, two Critical diagnostic elements include personal history, family his-
predominate: stress erythropoiesis and extramedullary hematopoiesis. tory, CBC, and the blood film. Has the diagnosis been made on physical
Stress erythropoiesis occurs as a response to severe anemia. The exam or was it detected incidentally on an imaging procedure? If prior
marrow attempts to compensate by increasing erythropoiesis (Chaps. studies are available for comparison, one may be able to use the EMR
32 and 33) and discharges reticulocytes of increasingly younger age to to determine how long the spleen has been enlarged. On exam, is the
the blood. If the anemic stress is not ameliorated or deepens further, spleen tip barely palpable or does it extend into the pelvis and cross the
nRBCs, usually late normoblasts, leave the marrow. The blood film often midline as might be the case with primary myelofibrosis (Chap. 86)?
shows abundant polychromasia, skip macrocytes, and late normoblasts. Evidence of cirrhosis or heart failure might suggest congestive
Extramedullary hematopoiesis can occur if the normal marrow is splenomegaly. Erythrocytosis and pruritus would raise concern for PV.
replaced by fibrosis or cancer or if somatic mutation such as seen in A blood film showing basophilia and myeloid immaturity might
primary myelofibrosis decreases stem cell adherence (Chap. 86). The indicate CML. If risk factors are present, HIV testing is appropriate.
hematopoietic stem cells travel through the blood to find suitable alter- Thalassemia can readily be identified via the blood film. Because the
native sites for growth, often settling in the spleen. However, the sinus- diagnostic possibilities are innumerable, it is critical to avoid a shot-
oidal structure there is not identical to that of the marrow. Hence, blood gun approach, identify the likely diagnostic possibilities, and focus the
cells, particularly nRBCs, are released in an uncoordinated manner. workup accordingly. It is almost never necessary to do a diagnostic
A leukoerythroblastic smear (nRBCs, teardrop RBCs, myeloid splenectomy.
immaturity, giant platelets) is a significant clue. If clinically indicated,
biopsy of the marrow will usually confirm the diagnosis.
MONOCLONAL GAMMOPATHY
IMMATURE MYELOID CELLS Monoclonal gammopathies are increasingly detected given the wide
The clinical lab may report the presence of metamyelocytes, myelo- availability of comprehensive metabolic panels and the subsequent use
of serum protein electrophoresis (SPEP) as a screening tool. Referring
cytes, promyelocytes, or blasts on the blood film. The differential is physicians often have already requested a SPEP in cases of suspected
enormous, ranging from normal pregnancy to myeloid malignancies myeloma, anemia, unexplained renal failure, or neuropathy. The finding
(Chaps. 61–63). One begins with a thorough history, CBC, and blood of elevated serum protein or globulin fractions, or the report of exten-
film. We inquire about recent stressors and the use of glucocorticoids. sive rouleaux formation on blood film may also trigger a request for
In patients with normal blood counts and rare metamyelocytes, obser- SPEP. The SPEP can demonstrate the presence of a monoclonal protein
vation is generally appropriate. The presence of peripheral blasts, par- whereas immunofixation defines the heavy-chain isotype and light-
ticularly in association with cytopenias, is never normal and mandates chain restriction.
examination of the marrow. A full spectrum of myeloid maturity, par- Rouleaux formation reported on a CBC is not synonymous with a
ticularly in association with basophilia, should raise concern for CML.
monoclonal protein. Rouleaux simply describes visible stacked red cells,
either as a result of poor smear preparation, inappropriate viewing in
LYMPHADENOPATHY the “thick” area of the slide, or as a consequence of increased plasma
proteins, such as immunoglobulins and fibrinogen. Although roule-
On occasion, consultation is requested for lymphadenopathy without aux may result from a monoclonal gammopathy, it may also be seen in
a tissue diagnosis. The differential diagnosis is vast, including benign chronic infections, autoimmune disorders, and liver disease.
adenopathy, viral infections, autoimmune disorders, and malignant When seeing referrals for monoclonal gammopathies, one should
lymphomas. A thorough history is critical (Chap. 1). Laboratory studies obtain a CBC, renal and liver function studies, blood film, immunoglob-
should include a CBC and blood film. ulin panel, free light-chain ratio, urine protein electrophoresis (UPEP)
Generally with this information, the diagnostic studies can be with immunofixation, and skeletal survey. This analysis seeks to identify
focused and lymph node biopsy is not always required. For example, any evidence of end organ damage attributable to the monoclonal pop-
in adolescents with fever, pharyngitis, and cervical adenopathy, tests ulation, such as hypercalcemia, anemia, renal dysfunction, or lytic bone
for infectious mononucleosis are pursued. If there is an accompanying disease. The physical exam focuses on the presence of adenopathy or
lymphocytosis, the diagnosis might be established via flow cytometry organomegaly that might suggest a lymphoproliferative disorder.
of the blood, as in CLL. If the patient is well appearing, asymptomatic, If there is no clear evidence of end organ damage, the term mono-
and the nodes are minimally enlarged, a short period of observation is clonal gammopathy of undetermined significance (MGUS) is often
often prudent. applied, and observation is pursued. The natural history, risk stratifica-
In patients with cytopenias, B symptoms, and organomegaly with- tion, and prognosis of such patients in discussed in Chaps. 106 and 107.
out obvious infections, lymph node biopsy is nearly always indicated. Monoclonal proteins may also be seen in association with several dis-
Fine-needle aspirates, although often more convenient, are discouraged orders, including plasma cell dyscrasias, lymphoproliferative disorders,
because the lack of lymph node architecture impairs pathologic analy- infections, and various autoimmune diseases. Notably, it is important to
sis. If a diagnosis of malignant lymphoma is suspected, treatment with identify patients with signs concerning for immunoglobulin light-chain
glucocorticoids prior to tissue diagnosis is also discouraged as it may amyloidosis (nephrotic range proteinuria, macroglossia, neuropathy).
impair diagnostic sensitivity. In cases of immunoglobulin (Ig) M paraproteins, look for evidence of
Waldenström macroglobulinemia (adenopathy, constitutional symp-
toms, organomegaly, bleeding). Although rare, in patients with anemia
SPLENOMEGALY and IgM κ paraproteins, one should inquire about cold sensitivity and
seek to exclude cold agglutinin hemolysis.
Referrals for splenomegaly open up an immense differential, including One is often faced with an elderly patient with multiple comorbid-
hemoglobinopathies, infection, liver disease, heart failure, autoimmune ities, such as chronic renal dysfunction, peripheral neuropathy, diabetes
disorders, and malignant leukemia or lymphoma (Chap. 56). mellitus, and osteoporosis in conjunction with a systemic paraprotein.

Kaushansky_chapter 04_p0041-0050.indd 48 17/09/15 5:43 pm