CORRESPONDENCE AND CORRECTIONS Acute Basophilic Leukemia
This state of confusion is emphasized by the panoply of basophilic leukemias that imbues the literature under such categories as chronic myelogenous leukemia with exaggerated basophils,3-4 acute basophilic transformation of chronic myelogenous leukemia,5 acute myelogenous leukemia with t(6;9), t(3;6), or inv (16) and marrow basophilia,6'7 acute promyelocytic leukemia with basophilic maturation,8 and acute basophilic leukemia.4,9 By analogy to AML-M4Eo, Catovsky and others10 recently proposed the establishment of a new FAB diagnostic category AML-M2 Baso to accommodate the Philadelphia chromosome-negative cases of basophilic leukemia, in preference to the creation of a completely new diagnostic category, AML-M8. Dick2 discussed the eight cases studied by Peterson and associates' in terms of current diagnostic techniques and then emphasized that two would be classified as M2 Baso (M2-AML with neutrophilic differentiation and an associated increase in basophils), one as M1 Baso (ultrastructural cytologic evidence of basophilic differentiation but light myeloperoxidase positive), and four remaining as MO Baso (negative for light myeloperoxidase). It might be added that if Philadelphia chromosome-positive cases are excluded, three of the eight cases would be eliminated. Whatever the outcome of any classification scheme, it will require rigidly defined criteria to classify accurately the acute basophilic leukemias.
This brings us to the crux of the matter concerning the article by Peterson and associates. Because conventional light microscopic features played such a minor definitive diagnostic role in most of their cases and because their diagnosis was almost entirely based on ultrastructural findings, the following queries are proposed: 1. How did the authors quantitate their ultrastructural results? Specifically, how many separate and distinct blasts were counted in determining the percentage of blasts showing basophilic differentiation? 2. Were many separate blocks used or were multiple sections from one block used? The latter obviously could give a false sense of increased basophils. 3. How can the authors be sure that the undifferentiated blasts without theta granules are basophilic blasts? 4. Which four cases in their series were studied for ultrastructural localization of peroxidase? Did these include any of the two cases already shown to be peroxidase positive by light microscopic examination? How many of the four so studied were positive for peroxidase and how strong (or weak) was the staining? The authors report that "both peroxidase-positive and negative granules were present in the leukemic cells, often adjacent to each other." To how many of the cases did this finding apply? Authoritative references are ambiguous on the significance of this finding as well, one (reference 11) stating that basophil granules are negative (0) to 1 + and mast cell granules uniformly negative and another (reference 12) stating that basophil granules are weakly positive ((+)) and mast cell granules are uniformly positive. 5. Although the acid mucopolysaccharides in the neoplastic basophils and mast cells may have been scarce and not demonstrable by toluidine blue at the light microscopic level, did the authors try to use any other stains (such as Giemsa or alcian or astra blue) that might have shown the granules? 6. Did the cases stained with Sudan Black B show a reddish metachromatic hue,
895
with only some black granules in abnormal basophils, a pattern sometimes observed in basophilic leukemias without conspicuous granules? A clear statement of the specific diagnostic criteria for acute basophilic leukemia used by Peterson and associates in evaluating their eight cases would be helpful to readers when confronted with this difficult heterogeneous disorder. Last, because basophilic leukemia represents such a heterogeneous disorder, we believe that only a multifaceted, unified approach, as used for the other acute leukemias, employing all available technology, will enable hematopathologists to classify clearly and correctly the basophilic leukemias.' 3 HAROLD R. SCHUMACHER, MILTON E. SKELLY,
M.D.
M.D.
Department of Pathology Loyola University Medical Center Maywood, Illinois REFERENCES 1. Peterson LC, Parkin JL, Arthur DC, et al. Acute basophilic leukemia: A clinical, morphologic, and cytogenetic study of eight cases. Am J Clin Pathol 1991;96: 160-170. 2. Dick FR. Evolution of the French-American-British (FAB) proposals. Is there a place for acute basophilic leukemia? Am J Clin Pathol 1991;96:153-155. 3. Goh K-O, Anderson FW. Cytogenetic studies in basophilic chronic myelocytic leukemia. Arch Pathol Lab Med 1979;103:288-290. 4. Kyle RA, Pease GL. Basophilic leukemia. Arch Intern Med 1966; 118:205-210. 5. Parkin JL, McKenna RW, Browning RD. Philadelphia chromosome-positive blastic leukemia: Ultrastructural and ultracytochemical evidence of basophil and mast cell differentiation. Br J Haematol 1982;52:663-677. 6. Pearson MG, Vardiman JW, LeBeau MM, et al. Increased numbers of marrow basophils may be associated with t(6:9) in ANLL. Am J Hematol 1985; 18:393403. 7. Hoyle CF, Sherrington P, Hayhoe FG. Translocation (3;6)(q21;p21) in acute myeloid leukemia with abnormal thrombopoiesis and basophilia. Cancer Genet Cytogenet 1988;30:261-267. 8. Umeda M, Nojima Z, Yamaguchi R, et al. Two cases of acute promyelocytic leukemia with marked basophilia—A vari-
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
To the Editor:—We read with great interest the article by Peterson and associates' and the editorial by Dick2 on acute basophilic leukemia. In Dick's discussion, he noted that the basophilic leukemias presented were somewhat heterogeneous in terms of morphology, immunology, and chromosome alterations. Of the eight cases studied by Peterson and associates, two showed some basophilic maturation identifiable by conventional light microscopy and the remaining six required ultrastructural evaluation to identify basophil or mast cell differentiation. Dick emphasized the great difficulty and confusion in classifying this entity in terms of current French-American-British (FAB) proposals. We concur!
896
CORRESPONDENCE AND CORRECTIONS
ant type of APL with the capability of differentiating into basophils. Rinsho Ketsueki 1987;28:2004-2009. 9. Cecio A, Dini E, Quattrin N. Preliminary observations with the electron microscope of two cases of acute basophilic leukemia. Boll Soc Ital Biol Sper 1970:46:459-462.
The Authors'
10. Catovsky D, Matutis E, Buccheri V, et al. A classification of acute leukemia for the 1990s. Ann Hematol 1991;62:16-21. 11. Sun T, et al. Atlas of Cytochemistry and Immunochemistry of Hematologic Neoplasms. Chicago: American Society of Clinical Pathologists Press, 1985, pp 26-27.
12. Zucker-Franklin D, et al. Atlas of Blood Cells: Function and Pathology, Volume 1, Second Edition, Philadelphia: Lea & Febiger, 1988, p. 287. 13. Schumacher HR, Shrit MA, Kowal-Vern A, et al. Acute leukemia and related entities: Impact of new technology. Arch Path Lab Med 1991;115:331-337.
ultrastructural methodology, we offer the following statements.
slide has been counterstained with Geimsa. 5. Cases 2, 4, 5, and 8 were examined for electron microscopic peroxidase. All four cases were peroxidase positive, ranging from moderate to strong intensity, and all four cases had both positive and negative granules. Case 2 was peroxidase positive by both light and electron microscopic examination.
Reply
We agree that a heterogeneous group of disorders has been called "basophilic leukemia" in the literature, although most appear to represent chronic myeloid leukemia (CML) with increased basophils or basophilic transformation of CML.1 Patients were not included in our study if there was a prior history of CML, or if morphologic evidence of CML was present. Obviously, cases of acute promyelocytic leukemia or other cases of acute myeloid leukemia with maturation into any lineage other than basophil were excluded. To answer the specific questions about Desmin-Negative Leiomyoma
1. More than 1,000 separate and distinct blasts from each case were counted to determine the percentage of blasts showing basophilic differentiation. 2. A minimum of three blocks was examined in each case. In addition, the blocks were oriented so that not just one layer but rather the entire spectrum of cells, including platelets, blasts, and red cells, was examined in each block. We think these procedures minimize but do not completely eliminate the possibility of biased cell selection. Therefore, light microscopic examination in parallel with the ultrastructural analysis was important in documenting this group of leukemias as basophilic without significant involvement of other cell lines. 3. We did not and do not identify "undifferentiated" blasts as basophils even though morphologic features of differentiation, when present, almost always indicated basophils. Undifferentiated blasts are undifferentiated. The presence of myeloid antigen on the surface of these blasts does not resolve the issue of specific lineage at this time. The development of lineage-specific antibodies may resolve this issue in the future. 4. We did not stain these cases with Geimsa or alcian or astra blue stains. We did not observe reddish granules with Sudan Black B. In this regard, it is important that the reddish granules on the Sudan Black B stain not be attributed to the Sudan Black B if the
We did not discuss or propose any French-American-British diagnostic category for acute basophilic leukemia, although Dr. Dick eloquently addressed this issue in the accompanying editorial.2 The important issue here is not the most appropriate classification but that these cases, in which the blasts may be undifferentiated or lymphoid in appearance by light microscopic examination, be recognized as myeloid so an appropriate chemotherapeutic regimen is used. L O A N N PETERSON, JANET PARKIN, DIANE ARTHUR,
M.D.
B.A. M.D.
RICHARD BRUNNING,
M.D.
University of Minnesota Minneapolis, Minnesota
REFERENCES 1. Peterson LC, Parkin JL, Arthur DC, Brunning RD. Acute basophilic leukemia: A clinical, morphologic, and cytogenetic study of eight cases. Am J Clin Pathol 1991;96:160-170. 2. Dick FR. Evolution of the French-American-British (FAB) proposals. Is there a place for acute basophilic leukemia? Am J Clin Pathol 1991;96:153-155.
Intranodal
To the Editor:—We read with interest the recent paper by Starasoler and associates' describing two intranodal
spindle cell neoplasms that were interpreted as leiomyomas. Recently, a type of spindle cell neoplasm of lymph nodes has
A.J.C.P. .June 1992
been characterized as a distinctive primary tumor of the lymph nodes and referred to as palisaded myofibroblastoma,2 intra-
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
To the Editor:—We appreciate the opportunity to address the comments and questions by Drs. Schumacher and Skelly regarding our article, "Acute Basophilic Leukemia: A Clinical and Cytogenetic Study of Eight Cases."1 It is true, as Schumacher and Skelly assert, that documentation of these leukemias as basophilic was based primarily on ultrastructural analysis. Differentiation of the blasts into basophils was not apparent by light microscopic examination in all cases and the evidence for basophil differentiation was evident only when ultrastructural analysis was done. However, examination by light microscopy also was important in determining that maturation was limited to the basophilic lineage. Cases with light microscopic evidence for maturation into lineages other than basophil, such as neutrophil, eosinophil, or monocyte, were not regarded as acute basophilic leukemia and were not included. They were excluded even if the electron microscopic findings suggested predominant basophil differentiation.
This state of confusion is emphasized by the panoply of basophilic leukemias that imbues the literature under such categories as chronic myelogenous leukemia with exaggerated basophils,3-4 acute basophilic transformation of chronic myelogenous leukemia,5 acute myelogenous leukemia with t(6;9), t(3;6), or inv (16) and marrow basophilia,6'7 acute promyelocytic leukemia with basophilic maturation,8 and acute basophilic leukemia.4,9 By analogy to AML-M4Eo, Catovsky and others10 recently proposed the establishment of a new FAB diagnostic category AML-M2 Baso to accommodate the Philadelphia chromosome-negative cases of basophilic leukemia, in preference to the creation of a completely new diagnostic category, AML-M8. Dick2 discussed the eight cases studied by Peterson and associates' in terms of current diagnostic techniques and then emphasized that two would be classified as M2 Baso (M2-AML with neutrophilic differentiation and an associated increase in basophils), one as M1 Baso (ultrastructural cytologic evidence of basophilic differentiation but light myeloperoxidase positive), and four remaining as MO Baso (negative for light myeloperoxidase). It might be added that if Philadelphia chromosome-positive cases are excluded, three of the eight cases would be eliminated. Whatever the outcome of any classification scheme, it will require rigidly defined criteria to classify accurately the acute basophilic leukemias.
This brings us to the crux of the matter concerning the article by Peterson and associates. Because conventional light microscopic features played such a minor definitive diagnostic role in most of their cases and because their diagnosis was almost entirely based on ultrastructural findings, the following queries are proposed: 1. How did the authors quantitate their ultrastructural results? Specifically, how many separate and distinct blasts were counted in determining the percentage of blasts showing basophilic differentiation? 2. Were many separate blocks used or were multiple sections from one block used? The latter obviously could give a false sense of increased basophils. 3. How can the authors be sure that the undifferentiated blasts without theta granules are basophilic blasts? 4. Which four cases in their series were studied for ultrastructural localization of peroxidase? Did these include any of the two cases already shown to be peroxidase positive by light microscopic examination? How many of the four so studied were positive for peroxidase and how strong (or weak) was the staining? The authors report that "both peroxidase-positive and negative granules were present in the leukemic cells, often adjacent to each other." To how many of the cases did this finding apply? Authoritative references are ambiguous on the significance of this finding as well, one (reference 11) stating that basophil granules are negative (0) to 1 + and mast cell granules uniformly negative and another (reference 12) stating that basophil granules are weakly positive ((+)) and mast cell granules are uniformly positive. 5. Although the acid mucopolysaccharides in the neoplastic basophils and mast cells may have been scarce and not demonstrable by toluidine blue at the light microscopic level, did the authors try to use any other stains (such as Giemsa or alcian or astra blue) that might have shown the granules? 6. Did the cases stained with Sudan Black B show a reddish metachromatic hue,
895
with only some black granules in abnormal basophils, a pattern sometimes observed in basophilic leukemias without conspicuous granules? A clear statement of the specific diagnostic criteria for acute basophilic leukemia used by Peterson and associates in evaluating their eight cases would be helpful to readers when confronted with this difficult heterogeneous disorder. Last, because basophilic leukemia represents such a heterogeneous disorder, we believe that only a multifaceted, unified approach, as used for the other acute leukemias, employing all available technology, will enable hematopathologists to classify clearly and correctly the basophilic leukemias.' 3 HAROLD R. SCHUMACHER, MILTON E. SKELLY,
M.D.
M.D.
Department of Pathology Loyola University Medical Center Maywood, Illinois REFERENCES 1. Peterson LC, Parkin JL, Arthur DC, et al. Acute basophilic leukemia: A clinical, morphologic, and cytogenetic study of eight cases. Am J Clin Pathol 1991;96: 160-170. 2. Dick FR. Evolution of the French-American-British (FAB) proposals. Is there a place for acute basophilic leukemia? Am J Clin Pathol 1991;96:153-155. 3. Goh K-O, Anderson FW. Cytogenetic studies in basophilic chronic myelocytic leukemia. Arch Pathol Lab Med 1979;103:288-290. 4. Kyle RA, Pease GL. Basophilic leukemia. Arch Intern Med 1966; 118:205-210. 5. Parkin JL, McKenna RW, Browning RD. Philadelphia chromosome-positive blastic leukemia: Ultrastructural and ultracytochemical evidence of basophil and mast cell differentiation. Br J Haematol 1982;52:663-677. 6. Pearson MG, Vardiman JW, LeBeau MM, et al. Increased numbers of marrow basophils may be associated with t(6:9) in ANLL. Am J Hematol 1985; 18:393403. 7. Hoyle CF, Sherrington P, Hayhoe FG. Translocation (3;6)(q21;p21) in acute myeloid leukemia with abnormal thrombopoiesis and basophilia. Cancer Genet Cytogenet 1988;30:261-267. 8. Umeda M, Nojima Z, Yamaguchi R, et al. Two cases of acute promyelocytic leukemia with marked basophilia—A vari-
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
To the Editor:—We read with great interest the article by Peterson and associates' and the editorial by Dick2 on acute basophilic leukemia. In Dick's discussion, he noted that the basophilic leukemias presented were somewhat heterogeneous in terms of morphology, immunology, and chromosome alterations. Of the eight cases studied by Peterson and associates, two showed some basophilic maturation identifiable by conventional light microscopy and the remaining six required ultrastructural evaluation to identify basophil or mast cell differentiation. Dick emphasized the great difficulty and confusion in classifying this entity in terms of current French-American-British (FAB) proposals. We concur!
896
CORRESPONDENCE AND CORRECTIONS
ant type of APL with the capability of differentiating into basophils. Rinsho Ketsueki 1987;28:2004-2009. 9. Cecio A, Dini E, Quattrin N. Preliminary observations with the electron microscope of two cases of acute basophilic leukemia. Boll Soc Ital Biol Sper 1970:46:459-462.
The Authors'
10. Catovsky D, Matutis E, Buccheri V, et al. A classification of acute leukemia for the 1990s. Ann Hematol 1991;62:16-21. 11. Sun T, et al. Atlas of Cytochemistry and Immunochemistry of Hematologic Neoplasms. Chicago: American Society of Clinical Pathologists Press, 1985, pp 26-27.
12. Zucker-Franklin D, et al. Atlas of Blood Cells: Function and Pathology, Volume 1, Second Edition, Philadelphia: Lea & Febiger, 1988, p. 287. 13. Schumacher HR, Shrit MA, Kowal-Vern A, et al. Acute leukemia and related entities: Impact of new technology. Arch Path Lab Med 1991;115:331-337.
ultrastructural methodology, we offer the following statements.
slide has been counterstained with Geimsa. 5. Cases 2, 4, 5, and 8 were examined for electron microscopic peroxidase. All four cases were peroxidase positive, ranging from moderate to strong intensity, and all four cases had both positive and negative granules. Case 2 was peroxidase positive by both light and electron microscopic examination.
Reply
We agree that a heterogeneous group of disorders has been called "basophilic leukemia" in the literature, although most appear to represent chronic myeloid leukemia (CML) with increased basophils or basophilic transformation of CML.1 Patients were not included in our study if there was a prior history of CML, or if morphologic evidence of CML was present. Obviously, cases of acute promyelocytic leukemia or other cases of acute myeloid leukemia with maturation into any lineage other than basophil were excluded. To answer the specific questions about Desmin-Negative Leiomyoma
1. More than 1,000 separate and distinct blasts from each case were counted to determine the percentage of blasts showing basophilic differentiation. 2. A minimum of three blocks was examined in each case. In addition, the blocks were oriented so that not just one layer but rather the entire spectrum of cells, including platelets, blasts, and red cells, was examined in each block. We think these procedures minimize but do not completely eliminate the possibility of biased cell selection. Therefore, light microscopic examination in parallel with the ultrastructural analysis was important in documenting this group of leukemias as basophilic without significant involvement of other cell lines. 3. We did not and do not identify "undifferentiated" blasts as basophils even though morphologic features of differentiation, when present, almost always indicated basophils. Undifferentiated blasts are undifferentiated. The presence of myeloid antigen on the surface of these blasts does not resolve the issue of specific lineage at this time. The development of lineage-specific antibodies may resolve this issue in the future. 4. We did not stain these cases with Geimsa or alcian or astra blue stains. We did not observe reddish granules with Sudan Black B. In this regard, it is important that the reddish granules on the Sudan Black B stain not be attributed to the Sudan Black B if the
We did not discuss or propose any French-American-British diagnostic category for acute basophilic leukemia, although Dr. Dick eloquently addressed this issue in the accompanying editorial.2 The important issue here is not the most appropriate classification but that these cases, in which the blasts may be undifferentiated or lymphoid in appearance by light microscopic examination, be recognized as myeloid so an appropriate chemotherapeutic regimen is used. L O A N N PETERSON, JANET PARKIN, DIANE ARTHUR,
M.D.
B.A. M.D.
RICHARD BRUNNING,
M.D.
University of Minnesota Minneapolis, Minnesota
REFERENCES 1. Peterson LC, Parkin JL, Arthur DC, Brunning RD. Acute basophilic leukemia: A clinical, morphologic, and cytogenetic study of eight cases. Am J Clin Pathol 1991;96:160-170. 2. Dick FR. Evolution of the French-American-British (FAB) proposals. Is there a place for acute basophilic leukemia? Am J Clin Pathol 1991;96:153-155.
Intranodal
To the Editor:—We read with interest the recent paper by Starasoler and associates' describing two intranodal
spindle cell neoplasms that were interpreted as leiomyomas. Recently, a type of spindle cell neoplasm of lymph nodes has
A.J.C.P. .June 1992
been characterized as a distinctive primary tumor of the lymph nodes and referred to as palisaded myofibroblastoma,2 intra-
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
To the Editor:—We appreciate the opportunity to address the comments and questions by Drs. Schumacher and Skelly regarding our article, "Acute Basophilic Leukemia: A Clinical and Cytogenetic Study of Eight Cases."1 It is true, as Schumacher and Skelly assert, that documentation of these leukemias as basophilic was based primarily on ultrastructural analysis. Differentiation of the blasts into basophils was not apparent by light microscopic examination in all cases and the evidence for basophil differentiation was evident only when ultrastructural analysis was done. However, examination by light microscopy also was important in determining that maturation was limited to the basophilic lineage. Cases with light microscopic evidence for maturation into lineages other than basophil, such as neutrophil, eosinophil, or monocyte, were not regarded as acute basophilic leukemia and were not included. They were excluded even if the electron microscopic findings suggested predominant basophil differentiation.
