A 7-Year-Old Child With a History of Acute Myeloid Leukemia Presenting With Multiple Gastrointestinal Polyps

A 7-year-old Hispanic girl, with a medical history of acute myeloid leukemia with t(8;21) diagnosed 3 years previously, was admitted for abdominal pain, nausea, and watery diarrhea. She underwent endoscopic examination and biopsy 1 month after stem cell transplantation from a human leukocyte antigen (HLA)–matched related donor. The endoscopy showed scattered foci of mucosal redness with focal erosion, and multiple polypoid lesions between 0.5 and 1 cm in diameter (Figure 1) in the stomach and the second part of the duodenum. Bone marrow evaluation showed no evidence of relapse. In addition to mild graft versus host disease in the gastrointestinal biopsies, the polypoid lesions showed a diffuse mononuclear infiltrate within the lamina propria and between the glands. The infiltrate consisted predominantly of monotonous medium-to-large cells with round, oval, or slightly irregular nuclei with dispersed chromatin, conspicuous nucleoli, and a small-to-moderate amount of pale eosinophilic cytoplasm (Figure 2) with some azurophilic granules (Figure 3). Immunohistochemical studies showed that the infiltrating cells were immunoreactive for myeloperoxidase (Figure 4), CD43, CD45, and CD34, but negative for CD3, CD20, and CD117.What is your diagnosis?A 7-year-old girl with a history of acute myeloid leukemia with t(8;21) presented with abdominal pain, nausea, and watery diarrhea 1 month after stem cell transplantation from an HLA-matched related donor. Endoscopy revealed multiple small polypoid lesions in the stomach and second portion of the duodenum, but no evidence of relapse was seen in bone marrow biopsy. Histology of the biopsied polyps showed a diffuse lamina propria mononuclear infiltrate consisting of medium-to-large blastic cells with oval or slightly irregular nuclei with dispersed chromatin, conspicuous nucleoli, and pale eosinophilic cytoplasm with occasional azurophilic granules. Immunoreactivity of the blastic cells with CD45, CD34, CD43, and myeloperoxidase but not CD3 and CD20 confirmed a diagnosis of extramedullary myeloid sarcoma in this unusual location.Myeloid sarcoma is an extramedullary tumor that typically occurs in the setting of acute myeloid leukemia or myeloproliferative disorders. Myeloid sarcoma may occur de novo or as a manifestation of relapse in patients previously treated for primary or secondary acute myeloid leukemia. This tumor, currently referred to as myeloid sarcoma by the World Health Organization,1 is also known as chloroma,2 granulocytic sarcoma,3 or extramedullary myeloid (cell) tumor.4 The rate of occurrence is approximately 3% to 9% of patients with acute myeloid leukemia. The patients show a wide age range, with no age group being immune.56 Boys are affected more frequently than girls, and white Americans seem to be less vulnerable than other ethnic groups.7These tumors can involve any part of the body, but commonly involved sites include subperiosteal bone structures of the skull, paranasal sinuses, the sternum, ribs, vertebrae and pelvis; lymph nodes and skin are also common sites.1 A single tumor or sometimes multiple nodular masses of various sizes may occur.The most common type of myeloid sarcoma is granulocytic sarcoma, which is composed of myeloblasts and neutrophils and neutrophil precursors. The World Health Organization recognizes 3 major variants defined according to the predominant cell type and their degree of maturation: (1) a blastic variant with a predominance of myeloblasts, (2) an immature variant with a mix of myeloblasts and promyelocytes, and (3) a differentiated variant with promyelocytes and more-mature granulocytes.1 Less-common variants include monoblastic sarcoma composed of monoblasts associated with acute monoblastic leukemia, tumors with bilineage or trilineage hematopoiesis, and variants composed predominantly of erythroid precursors or megakaryocytes, usually in conjunction with transformation of a chronic myeloproliferative disorder.1 Other reported variants include a monocytic variant, a myelomonocytic variant, and a variant with intracytoplasmic Auer rods (most often associated with acute transformation of a myelodysplastic syndrome).15 Myeloid sarcomas have been associated with t(8;21), inv(16), t(16;16), and translocations involving 11q23 in monoblastic sarcoma.1Myeloid sarcoma is frequently mistaken for malignant lymphoma, especially when it presents without leukemic manifestation. An incomplete immunohistochemical workup may be misleading because malignant lymphoma and myeloid sarcoma both express some leukocytic antigens. Wright- or Giemsa-stained imprints are the best method to observe blast morphology. The most diagnostic immunohistochemical markers are myeloperoxidase and lysozyme. Myeloperoxidase is immunoreactive in most myeloblastic variants and in some myelomonocytic variants, whereas lysozyme is frequently expressed in monoblastic variants. Mature granulocytic cells are immunoreactive for CD15 and CD15 immunoreactivity is present in the differentiated variant, whereas CD68/phosphoglucomutase 1 is more specific for the monocytic series. A variable percentage of minimally differentiated blasts may be immunoreactive for CD13, CD33, CD34, CD117, or CD99.8 Terminal deoxynucleotidyl transferase immunoreactivity is generally negative but could be positive only in the most blastic variants. CD45 is usually expressed, demonstrating the leukocytic origin of the neoplastic cells, however, it may be lacking. Sometimes expression of aberrant markers, such as B-cell–, T-cell–, or natural killer (NK)-cell–associated antigens, including CD30, may be found.9 Immunoreactivity of tumor cells for CD43, a T-cell marker, without coexpression of CD3 should always prompt consideration of a myeloid tumor and not be misinterpreted as a neoplasm of T-cell origin. The use of only 4 antibodies (myeloperoxidase, CD68, lysozyme, and CD34) has been proposed to distinguish the more common variants of myeloid sarcomas.10 The monoblastic tumors may express nonspecific esterase. Naphthol AS-D chloroacetate esterase is an excellent histochemical marker for neutrophils but may be ablated by fixation and decalcifying agents.1 The differential diagnosis is lengthy and includes non-Hodgkin lymphomas (such as precursor B-cell or T-cell, Burkitt, some peripheral NK-cell/ T-cell and diffuse large B-cell lymphomas), small round cell tumors (such as neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, peripheral neuroectodermal tumor, and medulloblastoma), undifferentiated carcinoma, melanoma, malignant histiocytosis, and malignant mastocytosis with atypical mast cells. Chronic myeloproliferative diseases with extramedullary localizations without blast crisis should also be differentiated from myeloid sarcoma. Accurate diagnosis is important to prevent inappropriate medical or surgical treatment and to indicate the need for vigorous antileukemic chemotherapy. However, the prognosis in general is poor,67 although myeloid sarcomas occurring without blood and bone marrow involvement usually respond to local radiation therapy.