Multicentric extramedullary myeloid tumor.

Granulocytic sarcomas or extramedullary myeloid tumors represent the soft tissue counterpart of acute myeloid leukemia. The term is used for any solid collection of leukemic cells. There have been reports of these tumors occurring before the involvement of blood or bone marrow. Our patient had simultaneous involvement of three sites, which was diagnosed on cytology. Further confirmation was done on peripheral blood and bone marrow evaluation.

Introduction

Granulocytic sarcoma or extramedullary myeloid tumor (EMMT) is an uncommon neoplasm of immature hematopoetic cells. The term ‘chloroma’ was earlier used because the tumor acquires a greenish tint due to myeloperoxidase. These tumors are reported in 3.1-9.1% of patients with myeloblastic leukemia and occur concomitantly with, after, or rarely before the onset of leukemia. We report a case with multiple tumors involving the lymph nodes, breast and orbit. The diagnosis was established on fine needle aspiration cytology (FNAC) of the masses which subsequently led to the diagnosis of the underlying leukemia.

Case Report

A 15 year-old girl presented with bilateral, cervical lymphadenopathy, bilateral breast masses, and gradually developing proptosis of both eyes, in that order. She had complained of general malaise and weakness for six months. Examination revealed that there was bilateral cervical lymphadenopathy, the smallest measured 1.5 cm. Nodes were firm to hard with restricted mobility and the breast masses were 4.5 cm (left) and 5.0 cm (right) along their maximum dimension. Overlying skin was normal but the lumps were fixed on both sides. The proptosis was bilateral and uniform in both eyes. There was no hepatosplenomegaly or any other palpable lymphadenopathy.

Fine needle aspiration cytology (FNAC) was done from the lymph nodes and breast masses. Aspirate from breast masses was scant. Both wet-fixed and air-dried smears were prepared for Papanicolaou and May-Grünwald Giemsa (MGG) staining respectively.

Smears from lymph nodes and the breast showed similar features with a polymorphous population of large atypical cells scattered in a background of mostly mature and a few reactive lymphoid cells [Figures 1 and 2]. The cells were round, discrete, and twice the size of mature lymphocytes. The nuclei were round to oval with fine chromatin and 2–3 nucleoli. Cytoplasm was pale blue and a fair number of cells showed Auer rods and a few fine granules; the background showed lymphoglandular bodies. Smears from the breast did not show any ductal epithelial cell clusters. Cell morphology from both sites was suggestive of myeloid blasts, so a diagnosis of granulocytic sarcoma/extramedullary myeloid tumor was made.

Figure 1

Smears from lymph node show infiltration by numerous myelomonoblasts (MGG, ×400)

Figure 2

Aspirate from breast with leukemic cells (MGG, ×400)

The peripheral smear showed normocytic, normochromic anemia with leukocytosis. Total leucocyte count (TLC) was 48000 cells/mm3 with the differential count showing 70% blasts, 2% promyelocytes, 8% myelocytes, 8% metamyelocytes, 2% band forms, and 10% lymphocytes. Platelet count was adequate and the blasts were as described above with mostly indented nuclei and Auer rods [Figure 3]. Bone marrow showed increased cellularity with myeloid predominance. Megakaryocytes were normal and there were 29% blasts in the marrow. Out of these, a considerable proportion showed monocytoid features; the blasts were diffusely positive for Sudan Black B (SBB) and negative for periodic acid schiff (PAS). Non specific enolase (NSE) was noncontributory, based on which, a diagnosis of acute myeloid leukemia (AML)-M4 was given.

Figure 3

Peripheral smear shows myeloblasts with Auer rods and cells in mitosis (Giemsa, ×1000)

The patient was started on standard chemotherapy to which she responded well.

Discussion

Granulocytic sarcoma or extramedullary myeloid tumor may be seen in association with chronic myeloid leukemia (CML), myelodysplastic syndrome, (MDS), myeloproliferative syndrome (MPS), polycythemia vera, and essential thrombocytosis. A distinct association has been seen with FAB type AML M4 and M5. EMMT may be seen in known patients of AML or may occur (rarely) as the first manifestation of the disease. In other cases, it may be the first sign of systemic relapse of a case of treated AML.

EMMTs may occur at any site in the body, common ones being the skin (leukemia cutis), lymph nodes, and mediastinum. Other sites such as epidural, uterus, ovaries, testis, and orbits have also been reported. A few case reports have described it in the breast[1-3] where it is often misdiagnosed as lymphoma. Granulocytic sarcomas of the orbit have mostly been described as isolated masses which may precede systemic manifestations.[4] The soft tissue counterparts may present months before the involvement of peripheral blood and bone marrow.[5] They produce symptoms according to their anatomic location but they may be asymptomatic as well.

Problems in diagnosis arise when they are suspected in patients without a background of myeloprolifrative disease. They may often be misdiagnosed as non-Hodgkin's lymphomas, rhabdomyosarcomas, amelanotic melanomas, or undifferentiated carcinomas.[6]

Definitive diagnosis requires biopsy. Light microscopy reveals collections of cells that can be usually recognised as being myeloid. Undifferentiated or minimally differentiated blasts generally pose diagnostic problems and these are cases that are misdiagnosed as lymphoma. Diagnosis must be supported by cytochemistry and immunohistochemistry. Leder stain for naphthol-ASD chloracetate esterase is very useful. The cells in our case were positive for SBB and myeloperoxidase; PAS was negative. Immunostaining with monoclonal antibodies against myeloperoxidase; anti-CD43, and anti-lysozyme are the most sensitive antibodies; CD68 and CD20 are useful in differentiating it from lymphoma.

Prognostic significance of EMMT is not very well known. It is regarded as a poor prognostic indicator by some,[7] whereas others have not considered it as an independent prognostic factor.[7] If they are diagnosed in patients previously treated for AML, they signify relapse whereas in a patient of chronic myeloproliferative disease, they may be indicative of an impending blast crisis.

The mainstay of treatment of EMMT is treating the underlying leukemia. Most tumors, whether detected prior to or during the therapy of leukemia, respond well to standard chemotherapeutic agents. Evidence of residual tumor may be an indication of surgery or radiation therapy. Relapse during the course of treatment indicates poor outcome.