American Journal of Hematology 79:73–75 (2005)
Granulocytic Sarcoma Presenting as Bilateral Adrenal Masses Binod K. Singh, Sajive Aleyas, Youjun Hu, Kenneth W. Zamkoff, and Douglas E. Gladstone* Stony Brook University Health Sciences Center, Stony Brook, New York
Granulocytic sarcoma (GS) is a collection of immature myeloid cells contained outside the bone marrow often seen in association with acute myeloid leukemia or as a sign of leukemic transformation in myeloproliferative disorders. Rarely, GS is an isolated finding unaccompanied by another hematological disorder. GS can occur at a variety of sites, most commonly involving the bone, soft tissue, lymph nodes, or skin. We report GS presenting as bilateral adrenal masses in a patient without an antecedent hematologic illness. Am. J. Hematol. 79:73–75, 2005. ª 2005 Wiley-Liss, Inc. Key words: granulocytic sarcoma; adrenal mass
INTRODUCTION
Granulocytic sarcoma (GS) is an extramedullary tumor composed of dense aggregates of immature myeloid precursor cells. GS is an uncommon cancer, seen most frequently in male children. GS is often associated with myeloproliferative disorders or acute myelogenous leukemia [1]. Moreover, it rarely presents without bone marrow involvement, an antecedent hematologic disease or without concurrent neutropenia [2]. GS can occur throughout the body; however, bilateral organ presentation has not been reported in the English literature. Herein, we report GS presenting as bilateral adrenal masses in a patient without an antecedent hematologic illness. CASE REPORT
A 54-year-old male with known hypertension and hyperlipidemia presented with sudden-onset severe left flank pain without a history of infection or trauma. Abdominal examination revealed left flank tenderness. A complete blood count showed a hemoglobin of 11.5 g/dL, a white blood cell count of 15.9 103/mL with a normal differential without immature precursors. Chemistries were significant only for a serum creatinine of 1.6 mg/dL. Computerized tomography (CT) of the abdomen revealed bilateral heterogeneous adrenal masses, measuring 11 14 cm (left) and 3.5 2 cm (right) (Fig. 1). There was no hepatosplenomegaly or ª 2005 Wiley-Liss, Inc.
lymphadenopathy. After a complicated hospitalization, including a myocardial infarction and intubation with a negative work-up for pheochromocytoma, a repeated CT scan revealed enlarging adrenal masses 12.3 10.5 cm (left) and 4.5 3.5 cm (right). A left adrenalectomy was performed; the left mass was completely resected. Microscopic evaluation showed a pleomorphic cell infiltrate with a high nuclear grade, significant mitotic activity, and a starry-sky pattern. Immunostains showed the tumor cells to be positive for CD45 (LCA), CD68, BCL2, and CD117 and focally positive for UCHL1. Leder (chloroacetate esterase) and Ki-67 (90%) stains were positive (Fig. 2). CD34, CD20, CD79A, CD3, CD30, alk-1, light chains, and myeloperoxidase stains were negative. The bone marrow was uninvolved. The bone marrow karyotype was 46 XY. A diagnosis of granulocytic sarcoma with myelomonocytic differentiation was established. Fluorescence in situ hybridization studies on the adrenal mass did not reveal t(8;21) or trisomy 8. *Correspondence to: Douglas E. Gladstone, M.D., Stony Brook University Health Sciences, Long Island Cancer Center, T17-080, Stony Brook, NY 11794. E-mail:
[email protected] Received for publication 6 October 2004; Accepted 2 November 2004 Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/ajh.20316
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Fig. 1.
Brief Report: Singh et al.
GS presenting as bilateral adrenal masses.
DISCUSSION
Granulocytic sarcomas are difficult to identify in routine paraffin-embedded tissue sections and are often reported as non-Hodgkin lymphomas. Diagnosis of GS requires the presence of myeloid cells. Tumor immunohistochemistry studies and bone marrow and peripheral blood examinations are necessary for diagnosis of GS [2]. In this patient, the presence of CD45 (LCA), CD68, and CD117 on the neoplastic cells along
Fig. 2.
with a positive Leder stain demonstrated that the cells of the resected mass were of myeloid origin. Moreover, the presence of CD117 positive cells, a transmembrane tyrosine kinase receptor sensitive for GS [3], is in accordance with this diagnosis. In contrast to the majority of patients with GS, neutropenia was not observed. Cytogenetic analysis of GS patients are rarely reported in the literature. However, patients with trisomy 8 and t(8:21)-associated AML(M2) are more prone to develop GS [4]. There also have been cases of inv(16) associated with GS preceding AML(M4) [5]. Cytogenetic studies in this patient using fluorescence in situ hybridization were negative for the most common chromosomal translocation, t(8:21) AML1/ETO, as well as for trisomy 8. In the English literature, no randomized study exists regarding the treatment of GS [6]. Retrospective studies show the early use of AML-directed chemotherapy to lower significantly the transformation rate to frank leukemia and to prolong survival. Imrie et al. reported that chemotherapy given at the time of diagnosis of GS delays the onset of AML by 30 months (median 36 months vs. 6 months for nonchemotherapy) and was associated with a better prognosis [7]. Tsimberidou et al. showed that radiation therapy prolongs failure-free survival time and recommended its consideration in GS [8]. This patient lost left renal function after adrenalectomy; therefore, radiation therapy was not initiated for
Immunohistochemical stains: (A) Leder stain; (B) CD45; (C) CD117; (D) Ki-67 (low).
Brief Report: Granulocytic Sarcoma Presenting as Bilateral Adrenal Masses
the right adrenal mass. He received cytosine arabinoside and idarubicin in standard 7+3 fashion. Repeat imaging after induction chemotherapy showed resolution of the right adrenal mass. Subsequently, the patient received high-dose cytosine arabinoside and etoposide as the first consolidation therapy. Six months from initial therapy, the patient remains in CR1.
REFERENCES 1. Meis JM, Butler JJ, Osborne BM, Manning JT. Granulocytic sarcoma in nonleukemic patients. Cancer 1986;58:2697–709. 2. Greer JP, Baer MR, Kinney MC. Acute myeloid leukemia in adults. In: Greer JP, Foerster J, Lukens JN, editors. Wintrobe’s clinical hematology. 11th edition. Philadelphia: Lippincott Williams & Wilkins; 2003. p 2103.
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3. Chen J, Yanuck RR 3rd, Abbondanzo SL, Chu WS, Aguilera NS. c-Kit (CD117) reactivity in extramedullary myeloid tumor/granulocytic sarcoma. Arch Pathol Lab Med 2001;125:1448–1452. 4. Swirsky DM, Li YS, Matthews JG, Flemans RJ, Rees JK, Hayhoe FG. 8;21 translocation in acute granulocytic leukaemia: cytological, cytochemical and clinical features. Br J Haematol 1984;56:199–213. 5. Morel F, Herry A, Le Bris MJ, et al. Isolated granulocytic sarcoma followed by acute myelogenous leukemia type FAB-M2 associated with inversion 16 and trisomies 9 and 22. Leukemia 2002;16:2458–2459. 6. Yamauchi K, Yasuda M. Comparison in treatments of nonleukemic granulocytic sarcoma: report of two cases and a review of 72 cases in the literature. Cancer 2002;94:1739–1746. 7. Imrie KR, Kovacs MJ, Selby D, et al. Isolated chloroma: the effect of early antileukemic therapy. Ann Intern Med 1995;123: 351–353. 8. Tsimberidou AM, Kantarjian HM, Estey E, et al. Outcome in patients with nonleukemic granulocytic sarcoma treated with chemotherapy with or without radiotherapy. Leukemia 2003;17: 1100–1103.