Atlas of Clinical Hematology - part 6 doc

IV Fig. 84 e – g e Same case as d shows macrophage with phagocytized cellular material, including Auer rods f Blood smear in complete remission following ATRA therapy. The neutrophilic granulocytes appear essentially normal g Hypersegmented neutrophil in the same patient 212 Chapter IV · Blood and Bone Marrow IV Fig. 85 a, b. Electron microscopic view of atypical promyelocytes in the M3 and M3 V subtypes of promyelocytic leukemia (Courtesy Prof. Dr. H. K. Mu¨ ller-Hermelink, Wu¨ rzburg) a Atypical promyelocyte in M3. Note the large, irregular primary granules b M3 V subtype. At center is a typical bilobed nucleus with a thin chromatin strand linking the two nuclear segments. At right is a large nucleolus. The cytoplasm contains small, sparse granules 213 5 · Bone Marrow IV Fig. 85 a Fig. 85 b 214 Chapter IV · Blood and Bone Marrow IV Fig. 86. Schematic diagram and partial karyotype of the translocation t(15;17)(q22;q12), which is found in both the M3 and M3 V subtypes of promyelocytic leukemia. In the rare cases where cytogenetic analysis is unrewarding – the so-called kryptic PML- RARA rearrangement – diagnosis can be ensured by means of FISH or PCR. The interphase FISH-figure demonstrates a normal cell with two red and two green signals as well as a cell with the t(15;17)/PML- RARA-rearrangement in which a red and a green signal for the uninvolved chromosomes and a red- green colocalization signal are seen. In addition to the t(15;17) there exist the extremely rare variants with the karyotypes t(11;17)(q13;q21) and the fusion transcript NuMA-RARA, the t(11;17)(q23;q21), PLZF-RARA, and the t(5;17)(q32;q12), NPM-RARA. Morphologically these variants do not exactly correspond in most cases to the classical subtypes M3 or M3V 215 5 · Bone Marrow IV Fig. 87 a – g. Acute myelomonocytic leukemia, M4 subtype a Bone marrow smear with undifferen- tiated blasts and precursors of the granulocytic and monocytic lines b Peroxidase reaction in the same patient shows peroxidase-positive blasts and later granulocytic precursors. Monocytic line is negative c Nonspecific esterase in the same patient shows strong, diffuse activity (brown) in four monocytes d Different patient. Blasts with grayish- blue cytoplasm (monocytic line). Several blasts contain coarse granules (granulo- cytic line) 216 Chapter IV · Blood and Bone Marrow IV Fig. 87 e – g e CE reaction in the same case (d) shows strong activity in some cells (granulocytic line) and no activity in others f Nonspecific esterase reaction in the same case shows strong, diffuse activity (grade 4) in most of the cells g Blood smear in M4 subtype demon- strates a large proportion of promono- cytes and monocytes. There was just over 20 % granulocytopoiesis in the bone marrow, confirming the diagnosis of the M4 subtype 217 5 · Bone Marrow IV Fig. 88 a – g. Acute myelomonocytic leukemia, M4 subtype a Pappenheim stain in bone marrow smear. Blasts and early precursors of granulocytopoiesis and monocytopoiesis are difficult to distinguish morphologi- cally b Bone marrow from the same patient. Peroxidase reaction. Almost 100 % of the cells are peroxidase-positive c Nonspecific esterase reaction in the same patient. Approximately 85 % of the cells are strongly and diffusely positive, confirming the diagnosis of M4. A large percentage of the leukemic cells have both monocytic and granulocytic prop- erties d Bone marrow from a different case of M4 218 Chapter IV · Blood and Bone Marrow IV Fig. 88 e – g e Blood smear from the patient in d.At center is a segmented neutrophil with Auer rods. Below it are two monocytes with atypical nuclei f Bone marrow histology in M4. Mega- karyocytes are increased, and some are dysplastic. HE stain g Blood smear from the same patient shows greatly increased platelets and two monocytes 219 5 · Bone Marrow IV Fig. 89 a – d. Variants of the M4 sub- type a Severely dysplastic erythropoiesis. At center are three erythroblasts, two of which are very immature forms. The cy- toplasm of the upper erythroblast is va- cuolated b PAS reaction in bone marrow from the same patient shows a strong, coarsely granular reaction in four atypical proerythroblasts and a diffuse reaction in an erythroblast at left. Three precursors of the white cell line show weak diffuse staining. There was less than 50 % erythropoiesis, excluding a diagnosis of erythroleukemia (M6 subtype) c Bone marrow in M4 shows increased numbers of basophilic granulocytes. Three basophils surround the center of the field d Increased basophilic granulocytes in the bone marrow from a different patient with M4. At top and right are two baso- phils with unusually fine granules. To- luidine blue stain confirms the meta- chromic reaction of the granules 220 Chapter IV · Blood and Bone Marrow IV Fig. 90 a – h. AML with abnormal eosi- nophils. M4Eo subtype a This bone marrow smear contains precursors of granulocytopoiesis, mono- cytopoiesis, and blasts along with a high percentage of eosinophils, some of which (left and right of center) contain abnormal dark purple-violet granules. There are also mature eosinophils, some with very small granules b Different case shows a striking abun- dance of abnormal eosinophils. These cells are easily mistaken for basophils with Pappenheim stain, but they do not show a metachromatic reaction with toluidine blue stain c Different case with many abnormal eosinophils. Note the pleomorphism of the abnormal granules d Different case with two dysplastic eosinophils at the center of the field 221 5 · Bone Marrow [...]... leukemia of the M4Eo subtype The arrows indicate the breakpoints b FISH technique for detecting the inv( 16) in interphase cells Note the bright red eosinophilic granules in the cytoplasm and, above the nucleus, a signal (blue-green dot at lower right) from the normal chromosome 16 and a two -part signal (two groups of small dots at left) from the inverted chromosome 16 (From Haferlach et al [19 96] Blood... detection of CE in the granules of at least some of the abnormal eosinophils This differentiates the abnormal eosinophils of M4Eo from reactive states and from eosinophils in other leukemias (e.g., M2 subtype of AML) in which eosinophils are increased An exception is “pure” acute eosinophilic leukemia (see p 253) This panel shows that a varying percentage of abnormal eosinophilic granules are CE-positive... the erythroblasts of the same patient This finding should not be mistaken for T-cell ALL f PAS reaction in the bone marrow of the same patient g Extremely immature form of M6a Some of the cells show vacuolated cytoplasm, and there is one abnormal mitosis h PAS reaction in a smear from the same patient IV 242 Chapter IV · Blood and Bone Marrow Fig 101 a – h Acute erythroleukemia, M6a subtype a Extremely... be detected d 231 5 · Bone Marrow Fig 96 a – h Monoblastic leukemia, M5a subtype Diagnostic criteria: at least 80 % of nonerythropoietic bone marrow cells must be of monocytic lineage, and at least 80 % of these must be monoblasts a Bone marrow smear consists exclusively of monoblasts with round, frequently eccentric nuclei, distinct nucleoli, and abundant gray-blue cytoplasm b Peripheral blood from... analysis IV 2 36 Chapter IV · Blood and Bone Marrow Fig 98b, c Bone marrow smears of two patients with the translocation t(8; 16) b Side by side heavy and only scanty granulated blasts Below the middle, erythrophagocytosis IV c High-power view In the center, one blast with erythrophagocytosis 237 5 · Bone Marrow Fig 98d A special type of cell is found in AML with the rare translocation t(8; 16) (p11;p13)... studies of seven cases, we find a type of cell which lies between monoblast and promyelocyte and in most cases shows as well strong diffuse esterase (naphthyl acetate) as peroxidase reaction Generally, there is erythrophagocytosis in a few, rarely in many blast cells Phagocytosis of leukocytes and platelets is very rare The translocation t(8: 16) leads to a CBP-MOZ fusion transcript It is relatively often... in therapy-associated AML IV 238 IV Chapter IV · Blood and Bone Marrow Fig 99 a – h Acute erythroleukemia subtype AML-M6 To meet the definition, erythroid progenitors must constitute at least 50 % of the marrow nucleated cells, and blasts must constitute at least 30 % of the nonerythroblastic cells (NEC) There are also “pure” erythroblastic leukemias (acute erythremia) with marked atypias of red cell... visible above and below the center of the field IV b PAS reaction in a bone marrow smear from the same patient demonstrates a very strong, predominantly diffuse reaction in the cytoplasm of the erythroblasts Generally the reaction is clumped and granular in earlier precursors and diffuse in more mature forms c Group of myeloblasts in another case of M6b d Peroxidase-positive myeloblast in a smear from... typical feature of mature eosinophilic granules are poorly visualized The small dark granules in the intergranular cytoplasm and in the pale rim of the condensed vacuole at upper left consist of glycogen g Normal eosinophil for comparison The granules contain typical crystalloid inclusions ! 227 5 · Bone Marrow Fig 93 a, b a Schematic diagram and partial karyotype of the inversion inv( 16) (p13;q22), which... Bone Marrow Fig 98a Karyotype of AML, FAB type M5a, with the translocation t(9;11)(p22;q23) Myelo-monocytic and monocytic or monoblastic leukemias (FAB subtypes M4, M5a, M5b) are mainly associated with translocations involving band q23 of chromosome 11, on which the MLL gene is localized Besides t(9;11), the most important of these translocations are t(11;19), t(10;11) and t (6; 11) The translocation t(9;11) . Variants of the M4 sub- type a Severely dysplastic erythropoiesis. At center are three erythroblasts, two of which are very immature forms. The cy- toplasm of the upper erythroblast is va- cuolated b. crystalloid inclusions ! 2 26 Chapter IV · Blood and Bone Marrow IV Fig. 93 a, b a Schematic diagram and partial karyo- type of the inversion inv( 16) (p13;q22), which is found in acute myeloid leukemia of the M4Eo. the inv( 16) in interphase cells. Note the bright red eosinophilic granules in the cyto- plasm and, above the nucleus, a signal (blue-green dot at lower right) from the normal chromosome 16 and a two -part signal