I. AML with Recurrent Chromosomal Rearrangements
AML with t(8;21)(q22;q22); CBFa/ETO fusion gene Favorable
AML with inv(16)(p13;q22); CBFb/MYH11 fusion gene Favorable
AML with t(15;17)(q22;11-12); RARa/PML fusion gene Intermediate
AML with t(11q23;v); diverse MML fusion genes Poor
II. AML with Multilineage Dysplasia
With prior myelodysplastic syndrome Very poor
Without prior myelodysplastic syndrome Poor
III. AML, Therapy Related
Alkylating agent related Very poor
Epipodophyllotoxin related Very poor
IV. AML, not Otherwise Specified
Sub-classes defined by extent of differentiation and FAB classification (e.g., M0-M7) Intermediate
cells per microliter in about 50% of the patients. Occasionally, the peripheral smear might not contain any blasts(aleukemic leukemia). For this reason, bone marrow examination is
essential to exclude acute leukemia in pancytopenic patients.
Because it is difficult to distinguish myeloblasts and lymphoblasts morphologically in some cases, the diagnosis of AML is typically confirmed by staining cells for myeloid-specific
surface markers ( Fig. 14-28B, C ).
Special high-resolution banding techniques reveal chromosomal abnormalities in approximately 90% of all AML patients. In 50% to 70% of the cases, the karyotypic changes are detected
by standard cytogenetic techniques.
Particular chromosomal abnormalities correlate with the clinical setting in which the tumor occurs. AML arising de novo in patients with no risk factors are often associated with balanced
chromosomal translocations, particularly t(8;21), inv(16), and t(15;17). In contrast, AMLs following myelodysplastic syndromes or exposure to DNA-damaging agents (such as
chemotherapy or radiation therapy) are commonly associated with deletions or monosomies involving chromosomes 5 and 7 and usually lack chromosomal translocations. The exception to
this rule is AML occurring after treatment with topoisomerase II inhibitors, which is often associated with translocations involving the MLL gene on chromosome 11 at band q23.
The clinical findings in AML are similar to those in acute lymphoblastic leukemia/lymphoma (ALL). Most patients present within weeks or a few months of the onset of symptoms related
to anemia, neutropenia, and thromobocytopenia, most notably fatigue, fever, and spontaneous mucosal and cutaneous bleeding. Often, the bleeding diathesis caused by thrombocytopenia
is the most striking clinical feature.
Figure 14-28 A, Acute myelogenous leukemia (FAB M1 subtype). Myeloblasts have delicate nuclear chromatin, prominent nucleoli, and fine azurophilic granules in the cytoplasm. B, In
the flow cytometric analysis shown, the myeloid blasts, represented by the red dots, express CD34, a marker of multipotent stem cells, but do not express CD64, a marker of mature
myeloid cells. C, The same myeloid blasts express CD33, a marker of immature myeloid cells, and a subset express CD15, a marker of more mature myeloid cells. Thus, these blasts are
minimally differentiated myeloid cells. (A, courtesy of Dr. Robert W. McKenna Department of Pathology, University of Texas Southwestern Medical School, Dallas, TX; B and C, courtesy
of Dr. Louis Picker, Oregon Health Science Center, Portland, OR.)
Figure 14-29Acute myelogenous leukemia subtypes. A, Acute promyelocytic leukemia (FAB M3 subtype). Bone marrow aspirate shows neoplastic promyelocytes with abnormally coarse
and numerous azurophilic granules. Other characteristic findings include the presence of several cells with bilobed nuclei and a cell in the center of the field that contains multiple
needlelike Auer rods. B, Acute monocytic leukemia (FAB M5b subtype). Peripheral smear shows one monoblast and five promonocytes with folded nuclear membranes. (Courtesy of Dr.
Robert W. McKenna, Department of Pathology, University of Texas Southwestern Medical School, Dallas, TX.)
Figure 14-30Myelodysplasia. Characteristic forms of dysplasia are shown. A, Nucleated red cell progenitors with multilobated or multiple nuclei. B, Ringed sideroblasts, erythroid
progenitors with iron-laden mitochondria, seen as blue perinuclear granules (Prussian blue stain). C, Pseudo-Pelger-Hüet cells, neutrophils with only two nuclear lobes instead of the
normal three to four, are observed at the top and bottom of this field. D, Megakaryocytes with multiple nuclei instead of the normal single multilobated nucleus. (A, B, D, marrow aspirates;
C, peripheral blood smear.)
Figure 14-31Detection of a BCR-ABL fusion gene by fluorescence in situ hybridization. A, An idiogram depicting chromosomes 9 and 22 and the position of the ABL and BCR genes. The
Philadelphia chromosome (Ph) is created by a balanced chromosomal translocation that replaces the telomeric portion of 22q with the telomeric portion of 9q. At a molecular level, the
breaking and rejoining of the DNA results in the formation of fusion gene on the Ph derived from the 5' end of BCR and the 3' end of ABL and hence brings BCR and ABL sequences that
are normally far apart into close physical proximity. This abnormal colocalization of BCR and ABL can be detected by in situ hybridization with pairs of fluorescently tagged DNA probes
complementary to genomic DNA sequences lying near the BCR and ABL breakpoints. B, A green ABL probe and a red BCR probe have been hybridized to metaphase chromosomes and
interphase nuclei prepared from the peripheral blood cells of a normal individual. Because of the pairing of sister chromatids during mitosis, signals on metaphase chromosomes may be
seen as a single dot or a pair of closely spaced dots. Two pairs of red signals and two green signals are seen on the metaphase chromosomes, while two red and two green signals are
present in the interphase nucleus, indicating the presence of normal, spatially distant copies of ABL and BCR, respectively. C, In contrast, metaphase chromosomes and an interphase
nucleus prepared from the bone marrow cells of a patient with CML show one normal ABL signal, one normal BCR signal, and an abnormal yellow signal created by superimposition of
one BCR and one ABL signal, a finding indicative of the presence of a BCR-ABL fusion gene. (Courtesy of Dr. Cynthia Morton and Ms. Debbie Sandstrom, Department of Pathology,
Brigham and Women's Hospital, Boston, MA.)
Figure 14-32Chronic myelogenous leukemia. Peripheral blood smear shows many mature neutrophils, some metamyelocytes, and a myelocyte. (Courtesy of Dr. Robert W. McKenna,
Department of Pathology, University of Texas Southwestern Medical School, Dallas, TX.)
Figure 14-33Chronic myelogenous leukemia (spleen). Enlarged spleen (2630 gm; normal: 150 to 200 gm) with greatly expanded red pulp stemming from neoplastic hematopoiesis.
(Courtesy of Dr. Daniel Jones, Department of Pathology, M.D. Anderson Cancer Center, Houston, TX.)
Figure 14-34Polycythemia vera, spent phase. Massive splenomegaly (3020 gm; normal: 150 to 200 gm) largely owing to extramedullary hematopoiesis occurred in the setting of advanced
marrow myelofibrosis. (Courtesy of Dr. Mark Fleming, Department of Pathology, Brigham and Women's Hospital, Boston, MA.)
Figure 14-35Essential thrombocytosis. Peripheral blood smear shows marked thrombocytosis, including giant platelets approximating the size of surrounding red cells. (Courtesy of Dr.
Jacqueline Mitus, Brigham and Women's Hospital, Boston, MA.)
Figure 14-36Primary myelofibrosis (peripheral blood smear). Two nucleated erythroid precursors and several teardrop-shaped red cells (dacryocytes) are evident. Immature myeloid cells
were present in other fields. An identical picture can be seen in other diseases producing marrow distortion and fibrosis.
Figure 14-37Langerhans cell histiocytosis. An electron micrograph shows rodlike Birbeck granules with characteristic periodicity and dilated terminal end. (Courtesy of Dr. George
Murphy, University of Pennsylvania School of Medicine, Philadelphia, PA.)
Figure 14-38Normal splenic architecture. (Modified from Faller DV: Diseases of the spleen. In Wyngaarden JB, Smith LH (eds): Cecil Textbook of Medicine, 18th ed. Philadelphia, WB
Saunders, 1988, p. 1036.)
TABLE 14-9-- Disorders Associated with Splenomegaly
Nonspecific splenitis of various blood-borne infections (particularly infective endocarditis)
Date: 2016-04-22; view: 565