A 3-year-old boy initially presented with fever, refusal to walk, night sweats, and pancytopenia. He was diagnosed with acute monoblastic leukemia (AML-MSa) and subsequently underwent induction therapy with daunorubicin, 6-thioguanine, and cytosine arabinoside. He achieved complete remission and underwent an allogeneic bone marrow transplant from his sibling 1 year later. His cytoreduction regimen consisted of busulfan/cyclophosphamide. His posttransplant course was uneventful, except for mild acute graft versus host disease of the skin, which was treated with prednisone, and shingles, which was treated with intravenous acyclovir. Bone marrow evaluation on day +30 and day +100 posttransplantation revealed no evidence of leukemic relapse.
His clinical course remained uneventful until December 2003, 15 months posttransplantation, when he was noted to have a small palpable left inguinal node. Over the ensuing month, the lymphadenopathy progressed to include the right inguinal, right axillary, and right cervical regions. He subsequently underwent computed tomographic scans of the chest, abdomen, and pelvis, along with bone marrow aspirate and biopsy in February 2004. The computed tomographic scans were negative for abnormalities, except for the noted lymphadenopathy. The bone marrow was morphologically normal, and no increased blast population was noted on flow cytometry of the marrow aspirate. A biopsy of a left inguinal lymph node was performed.
Grossly, the biopsy specimen consisted of a pink, oval, rubbery nodule, which measured 2.4 × 1.2 × 0.7 cm in greatest dimensions. The cut surface demonstrated a green-tan, homogeneous appearance. Histologie examination showed effaced lymph node architecture with a few small secondary follicles, which were pushed toward the thickened capsule (Figure 1, a). The tumor was composed of a relatively uniform population of medium-sized and large immature cells with abundant agranular cytoplasm. Most cells had a round to slightly convoluted nucleus with 1 or more prominent nucleoli (Figure 1, b). Immunohistochemical staining demonstrated diffusely positive CD43 staining of the cytoplasmic membranes of the malignant cells (Figure 1, c). Immunoreactivity for CD68 was focally positive (Figure 1, d). These cells were immunonegative with myeloperoxidase, chloroacetate esterase, and CD34. Scattered positivity for CD20 and CDS was noted in the background lymphocytes.
What is your diagnosis?
Pathologic Diagnosis: Myeloid Sarcoma
Myeloid sarcoma (granulocytic sarcoma) is an extramedullary accumulation of myeloblasts or immature myeloid cells.1 In the past, this tumor has been referred to as myeloblastoma, extramedullary myeloid tumor, chloroma, and chloroleukemia. Myeloid sarcoma is an uncommon variant of a myeloid malignancy, which may precede or occur concurrently with acute or chronic myeloid leukemia, or in association with other types of myeloproliferative or myelodysplastic syndromes. A myeloid sarcoma may be the first evidence of acute myelogenous leukemia (AML) and may precede the development of AML by months or, rarely, years. In addition, myeloid sarcoma is often the only indication of relapse in treated patients. Myeloid sarcoma has rarely been reported to be an early sign of blastic transformation of myelodysplastic syndrome or chronic myeloproliferative disorder.2 It occurs in approximately 5% of adults and 13% of children with myeloid malignancy, and can occur in various locations, including lymph nodes, bone, skin, spinal column, heart, nasopharynx, gastrointestinal tract, prostate, testis, breast, and female genital tract.3 The most common sites of bone involvement include the subperiosteal region of the skull, paranasal sinuses, orbit, sternum, ribs, vertebrae, and pelvis. Presenting symptoms are generally pain or other symptoms associated with the mass lesion.
Grossly, these soft tissue masses classically exhibit a green fresh cut surface due to the presence of myeloperoxidase in the tumor cells, an observation that led to the formerly used term chloroma.4 The green color, however, is not present in all chloromas; therefore, the less specific term myeloid sarcoma is preferred.2
Histologically, the tumor is characterized by a diffuse, monotonous population of medium-sized to large immature cells with round or folded nuclei, fine nuclear chromatin, 2 to 4 distinct nucleoli, and a slight to moderate amount of basophilic cytoplasm. The tumor is typically composed of mainly myeloblasts, but some myeloid-differentiated cells may also be present. The presence of eosinophilic precursors is often a clue to the diagnosis of myeloid sarcoma. The 3 major types of myeloid sarcoma are based on the degree of maturation. The blastic type is the least mature form and is composed primarily of myeloblasts. Eosinophilic precursors are less common in this type, and only an occasional cell will demonstrate cytoplasmic granularity. The immature type of myeloid sarcoma is composed predominately of myeloblasts and promyelocytes, along with eosinophilic myelocytes. The differentiated type is composed primarily of promyelocytes, mature neutrophils, and an abundance of eosinophilic myelocytes. The monoblastic form of myeloid sarcoma, referred to as monoblastic sarcoma, is relatively uncommon and consists of a population of mostly monoblasts. This form may be associated with translocations involving Ilq23.1 The karyotype of lymph node in our patient revealed a complex (10:11) translocation involving the MLL gene at Ilq23, a finding similar to that noted on the original bone marrow blasts.
Immunohistochemical stains are essential to confirm the diagnosis of myeloid sarcoma.5 Myeloperoxidase and chloroacetate esterase are often positive in the myeloblastic variant, while lysozyme and CD68 positivity can be seen in the rarer monoblastic variant. Paradoxically, most myeloid sarcomas will demonstrate positive staining with CD43, a T-cell marker.6 Other B- and T-cell markers are characteristically negative, including CD79a, CD20, CDS, and CD30. CD45 is often also positive, but may show only weak staining. The myeloid sarcoma in this case stained positive only with CD68 (focally) and CD43 (diffusely) and was negative for myeloperoxidase, chloroacetate esterase, B- and other T-cell markers. The lysozyme stain was not performed.
The differential diagnosis of myeloid sarcoma includes, but is not limited to, non-Hodgkin lymphoma (precursor B- and T-cell, Burkitt lymphoma, large B-cell lymphoma), small round cell tumors of childhood (neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, primitive neuroectodermal tumor, and medulloblastoma), carcinoma, and melanoma. Myeloid sarcoma is often misdiagnosed, most commonly as non-Hodgkin lymphoma, and especially in patients without a prior history of myeloid malignancy.7 A high index of suspicion is therefore necessary to avoid misdiagnosis, especially in poorly differentiated tumors of unknown origin.
The prognosis of patients with AML and myeloid sarcoma is generally considered to be less favorable than that of patients with AML alone. However, a more favorable prognosis is associated with the t(8;21).8 Patients are routinely treated with high-dose chemotherapy, with or without radiotherapy, but as many as 85% relapse within 1 year. Most cases of myeloid sarcoma that occur in patients without a previous diagnosis of leukemia will progress to AML within 1 year.9 In patients with isolated myeloid sarcoma without progression to leukemic disease, treatment with corticosteroids, chemotherapy, and radiotherapy may be curative and will prolong survival.1,10
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9. 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;94:1 739-1 746.
10. lmrie KR, Kovacs MJ, Selby D, et al. Isolated chloroma: the effect of early antileukemic therapy. Ann Intern Med. 1995;123:351-353.
Hach V. Turyan, MD; Danyel Bourgeois, MD; John Lazarchick, MD
Accepted for publication November 22, 2004.
From the Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston.
The authors have no relevant financial interest in the products or companies described in this article.
Reprints: John Lazarchick, MD, Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Children's Hospital, Room 222, PO Box 25908, Charleston, SC 29425 (e-mail: firstname.lastname@example.org).
Copyright College of American Pathologists Jul 2005
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