Nov 3, 2003 - Letters and correspondence submitted for possible publication must be identified as such. Text length must not exceed 500 words and.
American Journal of Hematology 75:262–265 (2004)
LETTERS AND CORRESPONDENCE
Letters and correspondence submitted for possible publication must be identified as such. Text length must not exceed 500 words and five bibliographic references. A single concise figure or table may be included if it is essential to support the communication. Letters not typed double-spaced will not be considered for publication. Letters not meeting these specifications will not be returned to authors. Letters to the Editor are utilized to communicate a single novel observation or finding. Correspondence is to be used to supplement or constructively comment on the contents of a publication in the journal and cannot exceed the restrictions for Letters to the Editor. The Editor reserves the right to shorten text, delete objectional comments, and make other changes to comply with the style of the journal. Permission for publication must be appended as a postscript. Submissions must be sent to Jay Umbreit, MD, PhD, Editor of Brief Reports/Letters to Editors, American Journal of Hematology, Winship Cancer Institute, Emory University, 1365-B Clifton Road, Suite B4100, Atlanta, GA 30322 to permit rapid consideration for publication.
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Granulocytic Sarcoma of the Urinary Bladder To the Editor: Granulocytic sarcomas are tumors of myeloid precursor cells presenting as extramedullary mass lesions, known to occur in clinical settings such as acute myeloid leukemia, chronic myeloid leukemia, and myelodysplastic syndrome. They can, however, occur in patients without a hematological disorder, in which case they are a harbinger of AML [1]. We would like to present a case of granulocytic sarcoma at an unusual location in a patient without history of a hematological malignancy.
A 57-year-old female patient complaining of urinary incontinence and fatigue was admitted to hospital. Physical examination was normal. Laboratory tests revealed elevation of creatinine (1.5 mg/dl) and anemia (Hb: 10.2 g/dl). Urine analysis revealed microproteinuria and hematuria. Bone marrow examination showed a normocellular bone marrow with no evidence of dysplasia. Abdominopelvic tomography showed a 74 21 mm mass in the trigone of the urinary bladder obliterating the ureteral orifices. A solid mass filling the trigone and base of the urinary bladder with extension to the ureter orifices was detected during cystoscopy and biopsied. Initially the patient was treated with idarubicin and cytosine arabinoside (3+7). Pelvic tomography revealed an 80% reduction in mass size 1 month after initiation of chemotherapy. External radiotherapy treatment followed. A month later, the mass had completely disappeared. Microscopically, the specimen represented muscular fragments diffusely infiltrated by discohesive cells showing focal crush artifact. On close inspection, the neoplastic cells had large lobulated nuclei, a blastic chromatin pattern, and some contained prominent nucleoli. The nucleocytoplasmic ratio was high, and the cytoplasm could barely be discerned (Fig. 1). Immunohistochemically, the neoplastic cells were LCA, UCHL-1, CD43, and CD68 positive and CD56, CD3, and CD20 negative. Myeloperoxidase was not taken into consideration due to intense background staining. Bone marrow biopsy was unremarkable. The findings were consistent with primary granulocytic sarcoma of the urinary bladder. Granulocytic sarcomas commonly involve the bones, periosteum, soft tissues, lymph nodes, and skin, but they have also been described in a variety of other sites [1]. When associated with a hematological malignancy, the diagnosis is straightforward. However, the diagnosis is challenging, even for well-differentiated cases displaying obvious features of myeloid differentiation in cases with no known hematological disorder. The misdiagnosis rate can be as high as 75% [2]. The differential diagnoses in undifferentiated cases like ours includes large-cell lymphoma, lymphoblastic lymphoma, and poorly differentiated carcinoma. LCA positivity rules out the latter but can lead to a diagnosis of lymphoma, especially when combined with CD43 positivity, commonly present in granulocytic sarcomas, or with TdT positivity seen in granulocytic sarcomas of the blastic type. Therefore, when confronted with an extramedullary undifferentiated tumor composed of cells with blastic nuclei and lobulated nuclear contours, it is important to include myeloid markers such as CD68 and myeloperoxidase in the immunohistochemistry panel [3]. When such markers are not included, the variable immunohistochemical characteristics of granulocytic sarcoma is a means of confusion. Granulocytic sarcomas have been described in the urinary tract in patients with known hematological malignancy. However, only two other cases of primary granulocytic sarcomas of the urinary bladder have been described in the literature [4,5]. Our case therefore once again reminds us that this tumor should enter the differential diagnoses of undifferentiated neoplasms of the region so that patients can receive the proper treatment [1].
AYSEGUL HASEGELI UNER1 KADRI ALTUNDAG2 ARZU SAGLAM1 GULTEN TEKUZMAN2 1
Fig. 1. A high magnification of the infiltrate demonstrating blastic cells with fine chromatin pattern and scattered eosinophils (magnification 630·). [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
ª 2004 Wiley-Liss, Inc.
Department of Pathology, Hacettepe University School of Medicine, Ankara, Turkey 2 Department of Medical Oncology, Hacettepe University School of Medicine, Ankara, Turkey Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/ajh.20022
Letters and Correspondence REFERENCES 1. Meis JM, Butler JJ, Osborne BM, et al. Granulocytic sarcoma in nonleukemic patients. Cancer 1986;58:2697–2709. 2. Menasce LP, Baneriee SS, Beckett E et al. Extramedullary myeloid tumour (granulocytic sarcoma) is often misdiagnosed: a study of 26 cases. Histopathology 1999; 34:391–398. 3. Chang CC, Eshoa C, Kampalath B, et al. Immunophenotypic profile of myeloid cells in granulocytic sarcoma by immunohistochemistry. Correlation with blast differentiation in bone marrow. Am J Clin Pathol 2000;114:807–811. 4. Chaitin BA, Manning JT, Ordonez NG. Hematologic neoplasms with initial manifestation in lower urinary tract. Urology 1984;23:35–42. 5. Aki H, Baslar Z, Uygun N, et al. Primary granulocytic sarcoma of the urinary bladder: case report and review of literature. Urology 2002;60:345.
———————— Case Report of Rituximab-Induced Thrombocytopenia To the Editor: A 57-year-old previously healthy man with stage IV BSM mantle cell lymphoma and massive splenomegaly received rituximab (375 mg/m2) as part of induction chemotherapy. The diagnosis of mantle cell lymphoma was confirmed by Fish analysis of the bone marrow, which showed, 46.6% cells positive for t(11,14). Rituximab is commonly used in the treatment of non-Hodgkin’s lymphomas that bear CD20 antigen and has significant efficacy in the management of relapsed and refractory ITP [1]. The patient was admitted to the hospital with WBC of 10,800, hemoglobin 9.4 g/dl, hematocrit 28.8%, and platelet count of 151,000. He received 638 mg of rituximab on day 1 (over 4 hr). He developed fever and rigors during the infusion and was treated with meperidine and acetaminophen. Blood and urine cultures showed no growth. On the next day, repeat hemogram showed WBC of 6,000, hgb 7.7 g/dl, hematocrit 23%, and platelet count of 8,000. The patient received a platelet transfusion, and a post-transfusion platelet count was 39,000. He received dose-intensified CHOP on day 4. By that time, the platelet count had rebounded to 82,000 without any intervention. The patient’s platelet count recovered after therapy as expected. He received a second cycle of chemoimmunotherapy on day 21. Within hours of receiving rituximab, the platelet count fell from 133,000 to 8,000. Serum sickness was unlikely since human antimouse antibody, C1Q, and C3D assays were within normal range. Episodes of neutropenia have been reported in patients treated with rituximab [2], but severe acute thrombocytopenia after the administration of rituximab is unusual. The mechanism remains unclear. It is possible that the patient had soluble CD20 antigen in the circulation that caused an antigen–antibody reaction and immune-mediated cell lysis by compliment activation. Another possibility would be the presence of CD20 antigen on the platelets themselves leading to antibody-mediated destruction. An enlarged spleen may have contributed to the rapidity of these processes.
CHIRAG SHAH SARA J. GRETHLEIN SUNY Upstate Medical University, Syracuse, New York Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/ajh.20028
REFERENCES 1. Staci R, Pagano A. Stipa E, Amadori S. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura. Blood 2001;98:952–957 2. Chaiwatanatorn K, Lee N, Grigg A, Filshie R, Firkin F. Delayed-onset neutropenia associated with rituximab therapy. Br J Haematol 2003;121:913–918.
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Isolated Hyperbilirubinemia Following Standard Dose Cytosine Arabinoside in a Patient With Relapsed Acute Myeloid Leukemia To the Editor: A 56-year-old woman was admitted to the hospital with a diagnosis of relapsed acute myeloblastic leukemia (AML). Four years earlier, she had presented with AML. The patient had been in complete remission after treatment with remission–induction regimen consisting of idarubicin (10 mg/m2, days 1–3) cytosine arabinoside (ARA-C) (100 mg/m2, days 1–7), and 2 consecutive cycles of consolidation regimen consisting of idarubicin (10 mg/m2, days 1 and 2), cytosine arabinoside (100 mg/m2, days 1–5). No hyperbilirubinemia was observed during or after the treatment of the patient. Upon readmission, her leukocyte count was 91,600/mm3; 96% were myeloblasts. Bone marrow aspiration biopsy showed total replacement with myeloblasts. She was taking allopurinol at the time of admission. Treatment was initiated with idarubicin 10 mg/m2/day 3 days plus ARA-C 100 mg/m2/ day 7 days. Ondansetron orally and intravenously was administered for prevention of nausea during the first 10 days. She developed pancytopenia on day 9 following the end of chemotherapy. On day 11, the patient became jaundiced with total bilirubin level was 12.5 mg/dl, direct bilirubin 8.5 mg/dl. Total bilirubin level increased to 42.9 mg/dl, and direct bilirubin level was 25.29 mg/dl. ALP was 145 IU/l; SGOT 1 IU/I, ALT 0 IU/I. Abdominal ultrasonography was normal. Viral markers for hepatitis were all negative. There was no prior history of chronic hepatitis. Results of evaluation for hemolysis, including direct antiglobulin test, were all negative. The patient’s neutropenic period was ended without any development of neutropenia and fever on day 29. Peripheral smear and bone marrow aspiration showed complete remission. The patient was discharged with her own decision on day 30 with total bilirubin level was 24.7 mg/dl and direct bilirubin, 16 mg/dl. Surprisingly, on day 60 the patient’s direct and total bilirubin level were within normal limits with a complete remission for AML. We report the case of a patient who developed severe jaundice during treatment with idarubicin and cytosine arabinoside. Clinically, jaundice due to cytosine arabinoside was characterized by conjugated hyperbilirubinemia, decreased aminotransferase levels, no significant elevations of alkaline phosphatase, and no evidence of obstruction, a pattern most consistent with intrahepatic cholestasis. Evaluation of hyperbilirubinemia and hepatic dysfunction in patients undergoing leukemic induction is complicated by the fact that most patients receive multiple pharmacologic agents, receive multiple blood transfusions, and frequently are in septic condition [1–3]. Severe jaundice following ARA-C induction has been rarely reported and usually appeared to be complex in origin. Clinical jaundice in our patient developed during the second week after treatment. Also, there was no septic condition at the onset of jaundice. Using standard-dose ARA-C, Goodell and colleagues [4] reported evidence of hepatic dysfunction, which they attributed to ARA-C in 22 of 49 patients. In 12 of those, the liver abnormalities resolved on continued therapy [4]. Toxicity was manifested as abnormalities of liver chemistries (bilirubin, alkaline phosphatase, and transaminase). No deaths were attributable to hepatic toxicity. One patient was reported to have experienced severe liver toxicity, but the exact clinical circumstances are not reported.
OZDEN ALTUNDAG KADRI ALTUNDAG ISMAIL CELIK ALEV TURKER AYSE KARS Department of Medical Oncology, Hacettepe University Faculty of Medicine, Ankara, Turkey Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/ajh.20029
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Letters and Correspondence
REFERENCES 1. George CB, Mansour RP, Redmond III J, et al. Hepatic dysfunction and jaundice following high-dose cytosine arabinoside. Cancer 1984;54:2360–2362. 2. Karanes C, Wolff SN, Herzig GP, et al. High dose cytosine arabinoside in the treatment of patients with refractory acute nonlymphocytic leukemia. Blood 1979; 54(Suppl):191A. 3. Rudnick SA, Cadman EC, Capizzi RL, et al. High dose cytosine arabinoside in refractory acute leukemia. Cancer 1979;44:1189–1193. 4. Goodell B, Leventhal B, Henderson E. Cytosine arabinoside in acute granulocytic leukemia. Clin Pharmacol Ther 1971;12:599–606.
———————— Relationship Between Blood Cells and Blood Viscosity To the Editor: Hematocrit or hemoglobin influences blood viscosity, but the effects of white blood cell (WBC) count and platelet count are less evaluated.
TABLE I. Whole Blood and Plasma Viscosity in Subgroups With Different Levels of Hemoglobin, Hematocrit, Red Cell Count, White Cell Count, and Platelet Counts (Presented as Mean ± SD (No. of Cases)) Whole blood viscosity Hemoglobin (g/dl) 16 Pa Hematocrit (%) 45 P Red blood cell count (1012/l) 5.5 P Platelet count (109/l) 600 P White blood cell count (109/l) 15 P a
Kruskal–Wallis ANOVA test.
2.43±0.95 2.50±0.71 2.83±0.50 3.15±0.35 3.39±0.61 3.84±0.54 4.69±0.82
