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1380 Part X: Malignant Myeloid Diseases Chapter 88: Acute Myelogenous Leukemia 1381

terminal ileum, cecum, and ascending colon, can be a presenting syn- LABORATORY FEATURES
drome or occur during treatment. 230–233 Fever, abdominal pain, bloody
diarrhea, or ileus may be present and occasionally mimic appendicitis. BLOOD CELL FINDINGS
Intestinal perforation, an inflammatory mass, and associated infection 197–201
with enteric gram-negative bacilli or clostridial species often are asso- Anemia is an almost constant feature. Red cell life span may be
ciated with a fatal outcome. Isolated involvement of the gastrointestinal mildly shortened, but the principal cause of anemia is inadequate
tract is rare. 234,235 Proctitis, especially common in the monocytic variant production of red cells. The reticulocyte count usually is between 0.5
of AML, can be a presenting sign or a vexing problem during periods of and 2.0 percent. Occasionally patients have rapid destruction of autol-
severe granulocytopenia and diarrhea. 227 ogous and transfused red cells as a result of an unknown mechanism,
The respiratory tract can be involved by infiltrates or tumors, lead- referred to as milieu hemolysis. The presence of red cell autoantibodies
ing to laryngeal obstruction, parenchymal infiltrates, alveolar septal (positive direct antiglobulin test) is very uncommon and may be non-
infiltration, or pleural seeding. Each of these events can result in severe specific (anti-C ), perhaps related to circulating immune complexes.
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symptoms and radiologic findings. 236–240 Red cell morphology is mildly abnormal, with exaggerated variation
Cardiac involvement is frequent but rarely causes symptoms. in cell size and occasional poikilocytes. Nucleated red cells or stippled
Symptomatic pericardial infiltrates, transmural ventricular infiltrates erythrocytes may be present. Less often, extreme abnormalities of red
with hemorrhage, and endocardial foci with associated intracavitary cell size, shape, and hemoglobin content occur (AML with trilineage
241
thrombi can occasionally cause heart failure, arrhythmia, and death. dysmorphia), but these changes are seen more often in oligoblastic mye-
Infiltration of the conducting system or valve leaflets or myocardial logenous leukemia (Chap. 87).
infarction has occurred. 242 Thrombocytopenia is nearly always present at the time of diagnosis.
The urogenital system can be affected. The kidneys are infiltrated The mechanism of thrombocytopenia is a combination of inadequate
with leukemic cells in a high proportion of cases, but functional abnor- production and decreased survival of platelets. More than half of
9
malities are rare. Hemorrhage in the pelvis or collecting system is patients have a platelet count less than 50 × 10 /L at the time of diag-
267
frequent. 243,244 Cases of vulvar, bladder neck, prostatic, and testicular nosis. Giant platelets and poorly granulated platelets with func-
268
involvement have been described. 245–247 tional abnormalities can occur. Defects in platelet aggregation and
268
Osteoarticular symptoms may occur. Bone pain, joint pain, and 5-hydroxytryptamine release are frequent. 9
bone necrosis can occur, and, rarely, arthritis with effusion is present. The total leukocyte count is less than 5 × 10 /L in approximately half
248
197–201
Crystal-induced arthritis of either calcium pyrophosphate dihydrate of patients at the time of diagnosis. The absolute neutrophil count
9
97–201
(pseudogout) or monosodium urate (gout) may be responsible for the is less than 1 × 10 /L in more than half of cases at diagnosis. Patients
synovitis in some cases. 249 with very elevated total leukocyte counts have a low proportion of mature
Central or peripheral nervous system involvement by infiltration of neutrophils but may have a normal absolute neutrophil count. Hyperse-
leukemic cells is very uncommon, although meningeal involvement is gmented, hyposegmented, and hypogranular mature neutrophils may be
an important consideration in the treatment of the monocytic type of present. Cytochemical abnormalities of blood neutrophils include low or
269
AML. 250,251 An association of CNS involvement and diabetes insipidus absent myeloperoxidase or low alkaline phosphatase activity. Defects
270,270A
252
in AML with monosomy 7 and inversion of chromosome 16 253,254 has in phagocytosis or microbial killing are common.
been reported. Myeloblasts almost always are present in the blood but may be
infrequent in severely leukopenic patients. Diligent search may uncover
MYELOID (GRANULOCYTIC) SARCOMA the myeloblasts, or examination of a white cell concentrate (buffy coat)
may permit their identification. Classic leukemic blast cells are agran-
Myeloid sarcoma (synonyms: granulocytic sarcoma, chloroma, mye- ular, but mixtures of immature cells, including agranular and slightly
loblastoma, monocytoma) is a tumor composed of myeloblasts, granular cells ranging up to overt progranulocytes, can occur. Auer rods
monoblasts, or megakaryocyes. 255–260 The tumor may occur as an are elliptical cytoplasmic inclusions approximately 1.0 to 1.5 μm long
extramedullary mass without evidence of leukemia in blood or mar- and 0.5 μm wide that derive from azurophilic granules (Fig. 88–2B). The
row, so-called nonleukemic myeloid sarcomas, or in association with inclusions are present in the blast cells of approximately 15 percent of
AML. When the tumor appears as an isolated lesion, it initially may be cases. When present, the inclusions are found in only a small percentage
misdiagnosed as extranodal lymphoma because they look like lymphoid of blast cells when examined with polychrome stains. An exception
193
cells on biopsy. They may be found in virtually any location, including is APL, in which a higher proportion of cells have Auer rods and some
257
the skin; orbit; paranasal sinuses; bone; chest wall; breast; heart; gas- have multiple (bundles) of rods (faggot cells). This finding can be dra-
trointestinal, respiratory, or genitourinary tract; central or peripheral matic if peroxidase stain is used to highlight the Auer rods.
nervous system; or lymph nodes and spleen. The tumors originally
were called chloromas because of the green color imparted by the high MARROW FINDINGS
concentration of the enzyme myeloperoxidase present in myelogenous
leukemic cells. Biopsy specimens are positive for chloracetate esterase, Morphology
lysozyme, myeloperoxidase, and cluster of differentiation (CD) markers The marrow always contains leukemic blast cells. From 3 to 95 per-
of myeloid cells. When myeloid sarcomas are the initial manifestation cent of marrow cells are blasts at the time of diagnosis or relapse (see
of AML, the appearance of the disease in the blood and marrow may Fig. 88–2A). The WHO has invoked an arbitrary threshold of 20 per-
follow weeks or months later. Abnormalities in chromosome 8 are the cent of marrow nucleated cells being blast cells to distinguish polyblastic
most frequent cytogenetic disturbance in myeloid sarcomas. Systemic AML (≥20 percent blasts) from oligoblastic myelogenous leukemia (<20
258
chemotherapy, rather than local therapy, should be used for treatment, percent blasts). 197–201 The latter situation is referred to as refractory ane-
although the long-term outcome in such cases usually is poor. 260–262 mia with excess blasts, a MDS (Chap. 87). The WHO choice of ≥20 per-
Patients having AML with t(8;21) or inv16 have a propensity to develop cent blasts is an arbitrary standard as acute monocytic leukemia, APL,
extramedullary leukemia, 263–266 and such patients with myeloid sarco- acute erythroid leukemia, and other variants often have less than 20 per-
271
mas have a poorer outcome after treatment than those who do not have cent blast cells at the time of diagnosis, and if any blasts are found with
extramedullary lesions. 263,265 a case of AML in which the cells have a t(8;21) or other CBF inversions or

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