288
CORRESPONDENCE AND CORRECTIONS
FADY K. BADDOURA WING C. CHAN
Division of Hematopathology Emory University School of Medicine Atlanta, Georgia
REFERENCES 1. Caldwell CW, Yesus YW, Loy TS, Bickel JT, Perry MC. Acute leukemia/lymphoma of plasmacytoid T-cell type. Am J Clin Pathol 1990;94:778-786. 2. Muller-Hermelink HK, Steinmann G, Stein H, Lennert K. Malignant lymphoma of plasmacytoid T cells. Morphologic and immunologic studies characterizing a special type of T cells. Am J Surg Pathol 1983;7:849-862. 3. Prasthofer EF, Prchal JT, Grizzle WE, Grossi CE. Plasmacytoid T-cell lym-
phoma associated with chronic myeloproliferative disorder. Am J Surg Pathol 1985;9:380-387. 4. Beiske K, Langholm R, Godal T, Marton PF. T-zone lymphoma with predominance of "plasmacytoid T-cells" associated with myelomonocytic leukemia. A distinct clinicopathological entity. J Pathol 1986;150:247-255. 5. Facchetti F, Wolf-Peeters CD, Kennes C, et al. Leukemia-associated lymph node infiltrates of plasmacytoid monocytes (so called plasmacytoid T cells). Evidence for two distinct histological and immunophenotypical patterns. Am J Surg Pathol 1990;14:101-112. 6. Koo CH, Mason DY, Miller R, et al. Additional evidence that "plasmacytoid Tcell lymphoma" associated with chronic myeloproliferative disorders is of macrophage/monocyte origin. Am J Clin Pathol 1990;93:822-827.
The Authors' Reply To the Editor:—In reference to our article, "Acute Leukemia/Lymphoma of Plasmacytoid T-cell Type", 1 Drs. Baddoura and Chan appropriately highlight the differences in clinical presentation, morphology, immunophenotypic markers, and evolution of the disease process in the patient reported by us and those reported by others, as referenced above. Certainly, the other cases all have demonstrated evidence of myelomonocytic differentiation. In contrast, our case was solely of T-cell lineage, as evidenced by immunologic and molecular biological probes. We acknowledge the unfortunate mislabeling error in the legend of Figure 5. However, the size of the rearranged
band in lane 2 of the same figure is closer to 10 Kb than the size of 8.5 Kb suggested by Drs. Baddoura and Chan. Furthermore, the presence of a rearrangement using a different restriction enzyme, BamHI, argues in favor of true clonal rearrangement, and therefore, true T-cell clonal proliferation rather than a normal germline variation due to polymorphism. We appreciate the comments of Drs. Baddoura and Chan. Until the lineage is unequivocally determined in cases displaying myelomonocytic markers, we agree with their contention that such cases might better be described as "plasmacytoid T-zone lymphomas" to separate them from true T-cell malignancies.
1. Caldwell CW, Yesus YW, Loy TS, Bickel JT, Perry MC: Acute leukemia/lymphoma of plasmacytoid T-cell type. Am J Clin Pathol 1990;94:778-786.
conclusion of ceftazidime-induced hemolysis may not be unequivocal. It is known that drugs supplied by pharmaceutical companies contain any number of additives or fillers2 and that these excipient compounds could, themselves, result in misinterpretation of an investigation of drug-induced immune hemolytic anemia.3-4 Furthermore, most excipient compounds will not be listed by the manufacturer. I raise this point to reemphasize4 the need for investigators to
rule out any other potential causative agents contained in a given pharmaceutical drug preparation. From a scientific point ofview, this is absolutely critical before we should implicate a specific drug contained in a pharmaceutical preparation. Furthermore, it is easy to obtain the chemically pure form of the drug, most of which are available from Sigma Chemical.Company, St. Louis,, Missouri.4 Obviously from a clinical point ofview it is crucial to use the actual pharmaceu-
CHARLES W. CALDWELL 1 YOHANNES W. YESUS 1 TIMOTHY S. LOY 1 JOHN T. BICKEL 1 MICHAEL C. PERRY 2
Departments ofl Pathology and 2Medicine University of Missouri School of Medicine Columbia, Missouri REFERENCES
Drug-Induced Immune Hemolytic Anemia To the Editor:—I read with interest the report by Chambers and co-workers' regarding possible drug-induced hemolytic anemia due to the administration of the third-generation cephalosporin, ceftazidime. However, it was unclear to me whether the in vitro serologic results were obtained using one of three pharmaceutical preparations available or using a chemically pure form of the drug. If only the pharmaceutical preparation was used in the serologic investigation then the
Vol. 96 • No. 2
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
to previously reported cases, the bone marrow was involved minimally in one and uninvolved in the other. Both cases were associated with a myeloproliferative disorder that progressed rapidly to an acute myeloid leukemia. To avoid further confusion awaiting an irrefutable confirmation of the monocytic lineage of plasmacytoid T cells, we support the use of the term "plasmacytoid T-zone lymphoma" previously advanced by Beiske and co-workers4 for this entity. The case of Caldwell and associates1 may be the only case that truly deserves the terminology "plasmacytoid T-cell lymphoma," which appears to be distinctive in terms of immunophenotype and clinical features when compared to plasmacytoid T-zone lymphoma.
CORRESPONDENCE AND CORRECTIONS
tical preparation that the patient is receiving in any initial investigation of druginduced hemolytic anemia. Because excipient compounds are used extensively by pharmaceutical companies and cases of drug-induced immune hemolysis are rare, it may seem unlikely that any other compound contained in the pharmaceutical could be responsible. Nonetheless, in vitro proof of a specific drug involvement can only be provided using a chemically pure form of the suspect drug or, if available, its metabolite(s).
289
adsorption mechanism. Am J Clin Pathol 1991;95:393-396.
DONALD R. BRANCH, P H . D .
Canadian Red Cross Society Blood Transfusion Service Toronto, Ontario, Canada
2. Brown JL. Incomplete labeling of pharmaceuticals: A list of "inactive" ingredients. N Engl J Med 1983,309:439441. 3. Law IP, Wickman CJ, Harrison BR. Coombs'-positive hemolytic anemia and ibuprofen. Southern Med J 1979;72:707.
REFERENCES 1. Chambers LA, Donovan LM, Kruskall MS. Ceftazidime-induced hemolysis in a patient with drug-dependent antibodies reactive by immune complex and drug
4. Petz LD, Branch DR. Drug-induced immune hemolytic anemia. In: Chaplin H, ed. Methods in Hematology: Immune Hemolytic Anemias. New York: Churchill Livingstone, 1985 pp 47-94.
The Authors' Reply dent that the active ingredient mediated the red cell sensitization and consequent hemolysis. Dr. Branch does well to remind us that additives should also be considered when investigating cases of drug-induced hemolysis and that confirmatory testing using chemically pure forms of implicated drugs may be required.
LINDA A. CHAMBERS,
M.D.
LILLIAN M. DONOVAN, B.A. MARGOT S. KRUSKALL,
M.D.
Harvard Medical School Beth Israel Hospital Boston, Massachusetts
Pneumocystis Ocular Infection To the Editor:—I read with interest the recent report by Dembinski and coworkers concerning disseminated Pneumocystis carinii infection associated with aerosolized pentamidine.' They reported widespread histologic evidence of such infection after death in a patient with acquired immune deficiency syndrome. Were the eyes examined clinically and/ or at autopsy, and if so, were they involved? The authors cite the report of Kwok and co-workers2 of retinal cottonwool spots in a patient with P. carinii but apparently were unaware of some other recent reports in the ophthalmic literature. The report by Kwok and co-workers2 was subsequently criticized by others as failing to demonstrate that the P. carinii organisms caused the cotton-wool spots.3,4 Subsequently, it has become clear that P. carinii typically causes a choroidal infection, clinically manifest by irregular yellow-white lesions deep to the retinal vessels.5"7 These three papers2,3,6 describe a total of six patients who developed disseminated infection after aerosolized pentamidine therapy, and one additional
patient who had not received this drug.6 On histologic examination, organisms were found within collections of dense amorphous eosinophilic material in the choroid. Generally, of course, this is demonstrated with autopsy examination, but one patient underwent transscleral choroidal biopsy to establish the diagnosis.6 The lesson for clinicians is that the ophthalmic manifestations of P. carinii infection may be the first evidence of extrapulmonary disease and that they may be asymptomatic.8 Pathologists should be aware that in select cases, transscleral biopsy is helpful in establishing the diagnosis and that postmortem examination of the eyes also may demonstrate the infection. MARILYN C. KJNCAID,
3.
4. 5.
6.
M.D.
St. Louis University Bethesda Eye Institute St. Louis, Missouri REFERENCES 1. Dembinski AS, Smith DM, Goldsmith JC, Woods GL. Widespread dissemination of Pneumocystis carinii infection in a patient with acquired immune defi-
AJ.C.P. • August 1991
2.
7.
8.
ciency syndrome receiving long-term treatment with aerosolized pentamidine. Am J Clin Pathol 1991;95:96-100. Kwok S, O'Donnell JJ, Wood IS. Retina! cotton-wool spots in a patient with Pneumocystis carinii infection. N Engl J Med 1982;307:184-185. Holland GN, Gottlieb MS, Foos RY. Retinal cotton-wool patches in acquired immunodeficiency syndrome. N Engl J Med 1982;307:1704. Sobel HJ. Retinal cotton-wool patches in acquired immunodeficiency syndrome. N Engl J Med 1982;307:1704-1705. Dugel PU, Rao NA, Forster DJ, et al. Pneumocystis carinii choroiditis after long-term aerosolized pentamidine therapy. Am J Ophthalmol 1990; 110: 113-117. Freeman WR, Gross JG, Labelle J, et al. Pneumocystis carinii choroidopathy. A new clinical entity. Arch Ophthalmol 1989;107:863-867. Rao NA, Zimmerman PL, Boyer D, et al. A clinical, histopathologic, and electron microscopic study of Pneumocystis carinii choroiditis. Am J Ophthalmol 1989;107:218-228. Teich SA, Rosenblatt M, Friedman A. Pneumocystis carinii choroiditis after long-term aerosolized pentamidine therapy. Am J Ophthalmol 1991:111: 118.
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
The serologic results were obtained using the pharmaceutical preparation Fortaz (Glaxo Pharmaceuticals, Research Triangle Park, NC). The preparation for injection is a dry, powdered mixture of ceftazidime and sodium carbonate, added to facilitate dissolution. Because the pharmacologic preparation in this case is essentially pure ceftazidime, we are confi-
CORRESPONDENCE AND CORRECTIONS
FADY K. BADDOURA WING C. CHAN
Division of Hematopathology Emory University School of Medicine Atlanta, Georgia
REFERENCES 1. Caldwell CW, Yesus YW, Loy TS, Bickel JT, Perry MC. Acute leukemia/lymphoma of plasmacytoid T-cell type. Am J Clin Pathol 1990;94:778-786. 2. Muller-Hermelink HK, Steinmann G, Stein H, Lennert K. Malignant lymphoma of plasmacytoid T cells. Morphologic and immunologic studies characterizing a special type of T cells. Am J Surg Pathol 1983;7:849-862. 3. Prasthofer EF, Prchal JT, Grizzle WE, Grossi CE. Plasmacytoid T-cell lym-
phoma associated with chronic myeloproliferative disorder. Am J Surg Pathol 1985;9:380-387. 4. Beiske K, Langholm R, Godal T, Marton PF. T-zone lymphoma with predominance of "plasmacytoid T-cells" associated with myelomonocytic leukemia. A distinct clinicopathological entity. J Pathol 1986;150:247-255. 5. Facchetti F, Wolf-Peeters CD, Kennes C, et al. Leukemia-associated lymph node infiltrates of plasmacytoid monocytes (so called plasmacytoid T cells). Evidence for two distinct histological and immunophenotypical patterns. Am J Surg Pathol 1990;14:101-112. 6. Koo CH, Mason DY, Miller R, et al. Additional evidence that "plasmacytoid Tcell lymphoma" associated with chronic myeloproliferative disorders is of macrophage/monocyte origin. Am J Clin Pathol 1990;93:822-827.
The Authors' Reply To the Editor:—In reference to our article, "Acute Leukemia/Lymphoma of Plasmacytoid T-cell Type", 1 Drs. Baddoura and Chan appropriately highlight the differences in clinical presentation, morphology, immunophenotypic markers, and evolution of the disease process in the patient reported by us and those reported by others, as referenced above. Certainly, the other cases all have demonstrated evidence of myelomonocytic differentiation. In contrast, our case was solely of T-cell lineage, as evidenced by immunologic and molecular biological probes. We acknowledge the unfortunate mislabeling error in the legend of Figure 5. However, the size of the rearranged
band in lane 2 of the same figure is closer to 10 Kb than the size of 8.5 Kb suggested by Drs. Baddoura and Chan. Furthermore, the presence of a rearrangement using a different restriction enzyme, BamHI, argues in favor of true clonal rearrangement, and therefore, true T-cell clonal proliferation rather than a normal germline variation due to polymorphism. We appreciate the comments of Drs. Baddoura and Chan. Until the lineage is unequivocally determined in cases displaying myelomonocytic markers, we agree with their contention that such cases might better be described as "plasmacytoid T-zone lymphomas" to separate them from true T-cell malignancies.
1. Caldwell CW, Yesus YW, Loy TS, Bickel JT, Perry MC: Acute leukemia/lymphoma of plasmacytoid T-cell type. Am J Clin Pathol 1990;94:778-786.
conclusion of ceftazidime-induced hemolysis may not be unequivocal. It is known that drugs supplied by pharmaceutical companies contain any number of additives or fillers2 and that these excipient compounds could, themselves, result in misinterpretation of an investigation of drug-induced immune hemolytic anemia.3-4 Furthermore, most excipient compounds will not be listed by the manufacturer. I raise this point to reemphasize4 the need for investigators to
rule out any other potential causative agents contained in a given pharmaceutical drug preparation. From a scientific point ofview, this is absolutely critical before we should implicate a specific drug contained in a pharmaceutical preparation. Furthermore, it is easy to obtain the chemically pure form of the drug, most of which are available from Sigma Chemical.Company, St. Louis,, Missouri.4 Obviously from a clinical point ofview it is crucial to use the actual pharmaceu-
CHARLES W. CALDWELL 1 YOHANNES W. YESUS 1 TIMOTHY S. LOY 1 JOHN T. BICKEL 1 MICHAEL C. PERRY 2
Departments ofl Pathology and 2Medicine University of Missouri School of Medicine Columbia, Missouri REFERENCES
Drug-Induced Immune Hemolytic Anemia To the Editor:—I read with interest the report by Chambers and co-workers' regarding possible drug-induced hemolytic anemia due to the administration of the third-generation cephalosporin, ceftazidime. However, it was unclear to me whether the in vitro serologic results were obtained using one of three pharmaceutical preparations available or using a chemically pure form of the drug. If only the pharmaceutical preparation was used in the serologic investigation then the
Vol. 96 • No. 2
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
to previously reported cases, the bone marrow was involved minimally in one and uninvolved in the other. Both cases were associated with a myeloproliferative disorder that progressed rapidly to an acute myeloid leukemia. To avoid further confusion awaiting an irrefutable confirmation of the monocytic lineage of plasmacytoid T cells, we support the use of the term "plasmacytoid T-zone lymphoma" previously advanced by Beiske and co-workers4 for this entity. The case of Caldwell and associates1 may be the only case that truly deserves the terminology "plasmacytoid T-cell lymphoma," which appears to be distinctive in terms of immunophenotype and clinical features when compared to plasmacytoid T-zone lymphoma.
CORRESPONDENCE AND CORRECTIONS
tical preparation that the patient is receiving in any initial investigation of druginduced hemolytic anemia. Because excipient compounds are used extensively by pharmaceutical companies and cases of drug-induced immune hemolysis are rare, it may seem unlikely that any other compound contained in the pharmaceutical could be responsible. Nonetheless, in vitro proof of a specific drug involvement can only be provided using a chemically pure form of the suspect drug or, if available, its metabolite(s).
289
adsorption mechanism. Am J Clin Pathol 1991;95:393-396.
DONALD R. BRANCH, P H . D .
Canadian Red Cross Society Blood Transfusion Service Toronto, Ontario, Canada
2. Brown JL. Incomplete labeling of pharmaceuticals: A list of "inactive" ingredients. N Engl J Med 1983,309:439441. 3. Law IP, Wickman CJ, Harrison BR. Coombs'-positive hemolytic anemia and ibuprofen. Southern Med J 1979;72:707.
REFERENCES 1. Chambers LA, Donovan LM, Kruskall MS. Ceftazidime-induced hemolysis in a patient with drug-dependent antibodies reactive by immune complex and drug
4. Petz LD, Branch DR. Drug-induced immune hemolytic anemia. In: Chaplin H, ed. Methods in Hematology: Immune Hemolytic Anemias. New York: Churchill Livingstone, 1985 pp 47-94.
The Authors' Reply dent that the active ingredient mediated the red cell sensitization and consequent hemolysis. Dr. Branch does well to remind us that additives should also be considered when investigating cases of drug-induced hemolysis and that confirmatory testing using chemically pure forms of implicated drugs may be required.
LINDA A. CHAMBERS,
M.D.
LILLIAN M. DONOVAN, B.A. MARGOT S. KRUSKALL,
M.D.
Harvard Medical School Beth Israel Hospital Boston, Massachusetts
Pneumocystis Ocular Infection To the Editor:—I read with interest the recent report by Dembinski and coworkers concerning disseminated Pneumocystis carinii infection associated with aerosolized pentamidine.' They reported widespread histologic evidence of such infection after death in a patient with acquired immune deficiency syndrome. Were the eyes examined clinically and/ or at autopsy, and if so, were they involved? The authors cite the report of Kwok and co-workers2 of retinal cottonwool spots in a patient with P. carinii but apparently were unaware of some other recent reports in the ophthalmic literature. The report by Kwok and co-workers2 was subsequently criticized by others as failing to demonstrate that the P. carinii organisms caused the cotton-wool spots.3,4 Subsequently, it has become clear that P. carinii typically causes a choroidal infection, clinically manifest by irregular yellow-white lesions deep to the retinal vessels.5"7 These three papers2,3,6 describe a total of six patients who developed disseminated infection after aerosolized pentamidine therapy, and one additional
patient who had not received this drug.6 On histologic examination, organisms were found within collections of dense amorphous eosinophilic material in the choroid. Generally, of course, this is demonstrated with autopsy examination, but one patient underwent transscleral choroidal biopsy to establish the diagnosis.6 The lesson for clinicians is that the ophthalmic manifestations of P. carinii infection may be the first evidence of extrapulmonary disease and that they may be asymptomatic.8 Pathologists should be aware that in select cases, transscleral biopsy is helpful in establishing the diagnosis and that postmortem examination of the eyes also may demonstrate the infection. MARILYN C. KJNCAID,
3.
4. 5.
6.
M.D.
St. Louis University Bethesda Eye Institute St. Louis, Missouri REFERENCES 1. Dembinski AS, Smith DM, Goldsmith JC, Woods GL. Widespread dissemination of Pneumocystis carinii infection in a patient with acquired immune defi-
AJ.C.P. • August 1991
2.
7.
8.
ciency syndrome receiving long-term treatment with aerosolized pentamidine. Am J Clin Pathol 1991;95:96-100. Kwok S, O'Donnell JJ, Wood IS. Retina! cotton-wool spots in a patient with Pneumocystis carinii infection. N Engl J Med 1982;307:184-185. Holland GN, Gottlieb MS, Foos RY. Retinal cotton-wool patches in acquired immunodeficiency syndrome. N Engl J Med 1982;307:1704. Sobel HJ. Retinal cotton-wool patches in acquired immunodeficiency syndrome. N Engl J Med 1982;307:1704-1705. Dugel PU, Rao NA, Forster DJ, et al. Pneumocystis carinii choroiditis after long-term aerosolized pentamidine therapy. Am J Ophthalmol 1990; 110: 113-117. Freeman WR, Gross JG, Labelle J, et al. Pneumocystis carinii choroidopathy. A new clinical entity. Arch Ophthalmol 1989;107:863-867. Rao NA, Zimmerman PL, Boyer D, et al. A clinical, histopathologic, and electron microscopic study of Pneumocystis carinii choroiditis. Am J Ophthalmol 1989;107:218-228. Teich SA, Rosenblatt M, Friedman A. Pneumocystis carinii choroiditis after long-term aerosolized pentamidine therapy. Am J Ophthalmol 1991:111: 118.
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
The serologic results were obtained using the pharmaceutical preparation Fortaz (Glaxo Pharmaceuticals, Research Triangle Park, NC). The preparation for injection is a dry, powdered mixture of ceftazidime and sodium carbonate, added to facilitate dissolution. Because the pharmacologic preparation in this case is essentially pure ceftazidime, we are confi-
