Granulocytic sarcoma is an unusual variant of myeloid malignancy in which there is an extramedullary tumor mass composed of myeloblasts or myeloblasts and more mature neutrophils. An association of granulocytic sarcoma and acute myeloid leukemia with the t(8;21) chromosome abnormality has been reported.The tumor may occur as an isolated finding or may be associated with acute myeloid leukemia, chronic myeloid leukemia, chronic idiopathic myelofibrosis, hypereosinophilic syndrome, and polycythemia vera.In earlier literature, the term chloroma was used for these lesions because of the green appearance of the freshly cut surface of the tumor. The green color, which is due to the presence of peroxidase in the leukemic cells, is not present in all tumors of this type, and the less specific designation of granulocytic sarcoma is preferred.
The granulocytic sarcomas are more frequent in children than adults and are most commonly associated with the subperiosteal bone structures; the most common sites are the skull, paranasal sinuses, sternum, ribs, vertebrae, and pelvis; lymph nodes and skin are also relatively frequently involved. Orbital masses leading to proptosis and spinal canal lesions resulting in neurologic manifestations are two of the clinical presentations associated with these tumors. A high incidence of granulocytic sarcomas involving the orbit has been reported in Turkish children with acute myelomonocytic leukemia.Granulocytic sarcomas may present as a mediastinal mass and clinically resemble a mediastinal lymphoma.
A granulocytic sarcoma may occur simultaneously with a typical blood and bone marrow pattern of acute myeloid leukemia or may antedate leukemia by many months or rarely years. It may be the first evidence of relapse in a patient with acute myeloid leukemia on maintenance chemotherapy and may be the only evidence of recurrence. These tumors may also represent the initial manifestation of a blast crisis of chronic myeloid leukemia, and an isolated tumor mass or enlarged lymph node in a patient with chronic myeloid leukemia should be evaluated for this possibility, including cytogenetic studies for the Ph` chromosome or molecular studies for evidence of the BCR/abl hybrid gene.
Histologically the tumor is composed of a relatively uniform population of immature cells and may be misdiagnosed as one of the poorly differentiated malignant lymphomas. Occasionally, the presence of immature eosinophils and maturing neutrophils may indicate the true nature of the lesion. Attempts at histopathologic classification have generally resulted in three levels of differentiation: blastic, immature, and differentiated.The blastic type is composed primarily of myeloblasts with little evidence of differentiation to the promyelocyte stage. The myeloblasts have a slight to moderate rim of basophilic cytoplasm, fine nuclear chromatin, and two to four nucleoli. Eosinophil myelocytes are not usually found with this degree of differentiation. The immature type with an intermediate degree of differentiation contains principally myeloblasts and promyelocytes; eosinophil myelocytes are usually present. The differentiated type comprises primarily promyelocytes and later stages of maturation. Eosinophil myelocytes are most abundant in this type. The chloroacetate esterase stain, which stains neutrophils and precursors in formalin-fixed tissue, is of considerable aid in establishing the diagnosis of a granulocytic sarcoma. Immunocytochemistry using anti-myeloperoxidase, anti-lysosome, and anti-CD68 (KP-1) antibodies may be particularly useful. Although tumors of monocytes are not generally classified with the granulocytic sarcomas, they represent a similar process with a similar predilection to leukemic evolution, primarily acute monoblastic leukemia. Monocytic lesions react with antibodies to lysozyme and CD68.
Imprint preparations of tumor masses may be particularly useful in identifying the myeloid nature of the cells. Auer rods may be found, and the myeloblasts may show intense staining with the myeloperoxidase cytochemical reaction.
Localized tumor masses occurring in the absence of blood or marrow involvement may respond to local radiation therapy. Eventually the process in the majority of patients will evolve into a form of acute myeloid leukemia or may be associated with additional tumor masses at other sites. The leukemic evolution may be characterized by a gradual increase in myeloblasts in the blood and marrow; frequently, blasts containing Auer rods are identified. In seven of sixteen patients with isolated granulocytic sarcomas reported by Meis et al., the process did not show a leukemic evolution although three of the seven patients developed granulocytic sarcomas at additional sites and died 2 to 8 months following initial presentation. The other four patients showed no evidence of recurrent disease from 3.5 to 16 years following presentation.
Unlike the granulocytic sarcomas that occur in patients with established hematologic disorders and are usually correctly diagnosed, the predominantly blastic granulocytic sarcomas occurring as isolated lesions may be misdiagnosed as a malignant lymphoma or poorly differentiated tumor because of the lack of diagnostic features.In lymph nodes involved by granulocytic sarcoma, the germinal centers are frequently preserved; the infiltrate is usually present in the sinuses and occasionally in the paracortex and medulla. In other tissues, the cells usually display an infiltrative pattern with the overall architecture remaining intact. The presence of immature eosinophils or cells with lobulated nuclei should evoke suspicion of a granulocytic sarcoma.