ISSN 0972-0200
Case Report
Orbital Granulocytic Sarcoma (Chloroma) as Initial Manifestation Of Acute Myeloid Leukaemia Delhi J Ophthalmol 2014; 24 (3): 174-177 DOI: http://dx.doi.org/10.7869/djo.37
Bagri PK, #Beniwal V, Beniwal SK, *Jakhar SL, * Sharma N, *Kumar HS, * Sharma A *
**
Department of Radiation Oncology, Department of Medical Oncology Acharya Tulsi Regional Cancer Treatment and Research Institute, # Department of Ophthalmology, S P Medical College, Bikaner *
**
*Address for correspondence
Puneet Kumar Bagri MD Acharya Tulsi Regional Cancer Treatment & Research Institute PBM hospital Campus, Bikaner-334001, Rajasthan, India. Email:
[email protected]
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Chloroma is an extramedullary manifestation of acute myeloid leukemia (AML). Chloroma may be found in a variety of locations throughout the body. The most common areas of involvement are the skin and the gums. Other tissues which can be involved include lymph nodes, small intestine, mediastinum, lung, epidural sites, uterus, ovaries and the orbit of the eye. A Chloroma is a solid tumor composed of immature white blood cells called myeloblasts. Children are affected more often than adults. There is a slight male predominance in these cases. The diagnosis is made by clinical examination, computed tomography and confirmed by haematological investigations. It may present at any time in the course of the disease. Diagnosis is particularly challenging in this situation. We report the case of a 11 year old male child who presented with bilateral exophthalmos (more in left eye) with computerized tomography (CT) evidence of a retro-orbital mass revealing acute myeloid leukemia. The patient was put on BFM-93 chemotherapy protocol. The patient has completed treatment of 1.5 years without relapse
Keywords : orbital chloroma • AML • chemotherapy A male child, aged 11 years was brought to the Regional cancer institute on June 2012 with the history of a rapidly increasing bilateral eye protrusion and ulcerated wound for the last two weeks. Ophthalmic examination revealed the presence of an axial, irreducible and non-pulsatile proptosis and ulcerated wound of the left eye with limitation of the movements of the globe. The skin of the upper eyelid was edematous. The right eye also showed the same lesion as in the left eye, but lesion was smaller and was with slightly limited movements of globe (Figure 1). Vision was lost in left eye, while decreased in right eye. General physical examination was normal. CECT head was showing a well defined 2.9 cms extraocular mass in superonasal quadrant of left orbit with partial intraconal and partial extraconal components (Figure 2). In laboratory investigations, Hb– 6.5 gm/ dl, TLC– 38900/cu.mm, platelets– 35000/ cumm was noted. Peripheral blood film was showing blasts– 62%, myelocytes & metamyelocytes – 6%, myeloperoxidase (MPO) positive and was suggestive of AML (Figure 3). Bone marrow examination showed 60% blasts (MPO positive) was suggestive of AML (Figure 4). Renal function test, liver function test, sonography of abdomen and X-ray chest were normal.
Figure 1: Bilateral proptosis before treatment : The left eye shows an axial, irreducible and non-pulsatile proptosis and ulcerated wound. The skin of the upper eyelid is edematous. The right eye is also showing a smaller ulcerated wound with proptosis.
Figure 2: CT head at time of presentation:CECT head is showing a well defined 2.9 cms extraocular mass in superonasal quadrant of left orbit with partial intraconal and partial extraconal components..
Del J Ophthalmol 2014;24(3)
E-ISSN 0976-2892 Orbital Granulocytic Sarcoma
Figure 3: Bone Marrow suggestive of AML : RBCs are normocytic normochromic
with mild anisopoikilocytosis. Myeloblasts seen with fine chromatin, prominent nucleoli and cytoplasm shows numerous Auer rods.
Case Report
Figure 4: MPO positive : Diluted with peripheral blood and marrow is replaced with blasts and increased M:E ratio. Blasts show moderate amount of cytoplasm with fine nuclear chromatin. Nuclei show prominent nucleolies (Arrow).
The patient was put on BFM-93(Berlin-FrankfurtMunich) chemotherapy protocol. After induction, patient showed partial response in orbital mass and bone marrow (12% blasts). As patient came in high risk group, so we gave high-dose cytosine arabinoside and mitoxantrone (HAM) regimen. After a period of 3 months, the patient was in complete bone marrow remission and orbital response (Figure 5 & 6).
Figure 6: CECT head after treatment shows no evidence of disease in orbit.
Discussion
Figure 5: Face of the patient after treatment of 3 months,
showing complete orbital response
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A myeloid sarcoma (chloroma, granulocytic sarcoma1, extramedullary myeloid tumor), is a solid tumor composed of immature white blood cells2 called myeloblasts. A chloroma is an extramedullary manifestation of acute myeloid leukemia; in other words, it is a solid collection of leukemic cells occurring outside of the bone marrow. The condition now known as chloroma was first described by the British physician Allen Burns in 18113, although the term chloroma did not appear until 1853.4 This name is derived from the Greek word chloros (green), as these tumors often
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ISSN 0972-0200
Case Report
Bagri P K et al
have a green tint due to the presence of myeloperoxidase. The link between chloroma and acute leukemia was first recognized in 1902 by Dock and Warthin.5 However, because up to 30% of these tumors can be white, gray, or brown rather than green, the more correct term granulocytic sarcoma was proposed by Rappaport in 19676 and has since become virtually synonymous with the term chloroma. Currently, any extramedullary manifestation of acute myeloid leukemia can be termed a granulocytic sarcoma or chloroma. Recent years, the term “myeloid sarcoma” has been favored.7 Chloromas are rare; exact estimates of their prevalence are lacking, but they are uncommonly seen even by physicians specializing in the treatment of leukemia. Chloromas may be somewhat more common in patients with the following disease features.8 Ø French-American-British (FAB) classification class M2 Ø those with specific cytogenetic abnormalities (e.g. t(8;21) or inv(16)) Ø those whose myeloblasts express T-cell surface markers, CD13, or CD14 Ø those with high peripheral white blood cell counts However, even in patients with the above risk factors, chloroma remains an uncommon complication of acute myeloid leukemia. Rarely, a chloroma can develop as the sole manifestation of relapse after apparently successful treatment of acute myeloid leukemia. In keeping with the general behavior of chloromas, such an event must be regarded as an early herald of a systemic relapse, rather than as a localized process. In one review of 24 patients who developed isolated chloromas after treatment for acute myeloid leukemia, the mean interval until bone marrow relapse was 7 months (range, 1 to 19 months).9 Chloromas may occur in patients with a diagnosis of myelodysplastic syndrome (MDS) or myeloproliferative syndromes (MPS). The detection of a chloroma is considered de facto evidence these premalignant conditions have transformed into an acute leukemia requiring appropriate treatment. For example, presence of a chloroma is sufficient to indicate chronic myelogenous leukemia has entered its ‘blast crisis’ phase. Very rarely, chloroma can occur without a known pre-existing or concomitant diagnosis of leukemia, this is known as primary chloroma. Diagnosis is particularly challenging in this situation. In almost all reported cases of primary chloroma, acute leukemia has developed shortly afterward (median time to development of acute leukemia7 months, range 1–25 months).8 Therefore, primary chloroma could be considered an initial manifestation of acute leukemia, rather than a localized process, and could be treated as such. Chloroma is predominantly a disease of childhood or young adults10 though a wide age range from infancy to 61 years of age is observed with mean of 7 years. Chloromas may occur in virtually any organ or tissue. Symptoms of chloroma at these sites are related to their anatomic location; chloromas may also be asymptomatic and be discovered
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incidentally in the course of evaluation of a person with acute myeloid leukemia. Central nervous system involvement, most often takes the form of meningeal leukemia, or invasion of the subarachnoid space by leukemic cells. This condition is usually considered separately from chloroma, as it requires different treatment modalities. True chloromas (i.e. solid leukemic tumors) of the central nervous system are exceedingly rare, but has been described. Definitive diagnosis of a chloroma usually requires a biopsy of the lesion. Historically, even with a tissue biopsy, pathologic misdiagnosis was an important problem, particularly in patients without a clear pre-existing diagnosis of acute myeloid leukemia to guide the pathologist. In one published series on chloroma, the authors stated that 47% of the patients were initially misdiagnosed, most often as having a malignant lymphoma.11 However, with advances in diagnostic techniques, the diagnosis of chloromas can be made more reliable. Traweek et al described the use of a commercially available panel of monoclonal antibodies, against myeloperoxidase, CD68, CD43, and CD20, to accurately diagnose chloroma via immunohistochemistry and differentiate it from lymphoma.12 Nowadays, immunohistochemical staining using monoclonal antibodies against CD34 and CD117 would be the mainstay of diagnosis. The increasingly refined use of flow cytometry has also facilitated more accurate diagnosis of these lesions. Evidence is conflicting on the prognostic significance of chloromas in patients with acute myeloid leukemia. In general, they are felt to augur a poorer prognosis, with a poorer response to treatment and worse survival13; however, others have reported chloromas associate, as a biologic marker, with other poor prognostic factors, and therefore do not have independent prognostic significance.14 As described above, chloromas should always be considered manifestations of systemic disease, rather than isolated local phenomena, and treated as such. In the patient with newly diagnosed leukemia and an associated chloroma, systemic chemotherapy against the leukemia is typically used as the first-line treatment, unless an indication for local treatment of the chloroma (e.g. compromise of the spinal cord) emerges. Chloromas are typically quite sensitive to standard antileukemic chemotherapy. If the chloroma is persistent after completion of induction chemotherapy, local treatment, such as surgery or radiation therapy, may be considered, though neither surgery nor radiotherapy has an effect on survival.15 Patients presenting with a primary chloroma typically receive systemic chemotherapy, as development of acute leukemia is nearly universal in the short term after detection of the chloroma. Patients treated for acute leukemia who relapse with an isolated chloroma are typically treated with systemic therapy for relapsed leukemia. However, as with any relapsed leukemia, outcomes are unfortunately poor. Patients with “preleukemic” conditions, such as myelodysplastic syndromes or myeloproliferative syndromes, who develop a chloroma are often treated as if they have transformed to acute leukemia.
Del J Ophthalmol 2014;24(3)
E-ISSN 0976-2892 Orbital Granulocytic Sarcoma
Conclusion
Chloroma is a rare manifestation of acute myeloid leukemia, but it should be included in differential diagnosis. Ophthalmologist who suspected this diagnosis should do CBC and PBF for rule out acute leukemia. Presence of chloroma is a poor prognostic sign. Being a neoplasm of high malignancy, the progress of the disease is very rapid and invariably fatal in a few weeks to a few months. For this rare and poor prognostic disease, aggressive management should be adopted. Systemic antileukaemic chemotherapy and radiotherapy is required.
Financial & competing interest disclosure
The authors do not have any competing interests in any product/ procedure mentioned in this study. The authors do not have any financial interests in any product / procedure mentioned in this study.
References 1. 2. 3. 4. 5.
James, William D, Berger, Timothy G, et al. Andrews’ Diseases of the Skin: clinical Dermatology. Saunders Elsevier. 2006; ISBN 0-7216-2921-0. Patil P, Bharambe BM, Binayke RS, Grace DC. Myeloid Sarcoma of Orbit in a Case of Acute Myeloid Leukemia. J Cytol Histol 2012; 3:157. Burns A. Observations of surgical anatomy in head and neck. London: Royce 1811; 364. King A. A case of chloroma. Monthly J Med 1853; 17: 17. Dock G, Warthin AS. A new case of chloroma with leukemia. Trans Assoc Am Phys 1904; 19:115.
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6. 7.
8. 9.
10.
11. 12.
13.
14. 15.
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Rappaport H. Tumors of the hematopoietic system. Atlas of Tumor Pathology, Section III, Fascicle 8. Washington DC: Armed Forces Institute of Pathology 1967; 241–7. Chevallier P, Mohty M, Lioure B, Michel G, Contentin N, Deconinck E, et al. Allogeneic hematopoietic stem-cell transplantation for myeloid sarcoma: a retrospective study from the SFGM-TC. J Clin Oncol 2008; 26:4940–3. Murthy R, Vemuganti GK, Honavar SG, Naik M, Reddy V. Extramedullary leukemia in children presenting with proptosis. J Hematol Oncol 2009; 24;2:4. Byrd JC, Weiss RB. Recurrent granulocytic sarcoma: an unusual variation of acute myeloid leukemia associated with 8;21 chromosomal translocation and blast expression of the neural cell adhesion molecule. Cancer 1994; 73:2107–12. Lee SG, Park TS, Cheong JW, Yang WI, Song J, Lee KA, Kim J, Park Y, Choi JR. Preceding orbital granulocytic sarcoma in an adult patient with acute myelogenous leukemia with t(8;21): a case study and review of the literature. Cancer Genet Cytogenet 2008; 185:51-4. 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; 94:1739–46. Traweek ST, Arber DA, Rappaport H, Brynes RK. Extramedullary myeloid cell tumors. An immunohistochemical and morphologic study of 28 cases. Am J Surg Pathol 1993; 17: 1011–9. Byrd JC, Weiss RB, Arthur DC, Lawrence D, Baer MR, Davey F, et al. Extramedullary leukemia adversely affects hematologic complete remission rate and overall survival in patients with t(8;21)(q22;q22): results from Cancer and Leukemia Group B 8461. J Clin Oncol 1997; 15:466-75. Bisschop MM, Revesz T, Bierings M, et al. Extramedullary infiltrates at diagnosis have no prognostic significance in children with acute myeloid. leukaemia 2001; 15:46–9. Batia Avni, Maya Koren-Michowitz. Myeloid Sarcoma: Current Approach and Therapeutic Options. Ther Adv Hem 2011; 2:309-16.
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