Myeloid sarcoma is a rare disease believed to be associated with a systemic condition rather than a localized disease, given that approximately 65% to 85% of the patients with myeloid sarcoma have preexisting acute myeloid leukemia or concurrent acute myeloid leukemia.1,2 Patients without preexisting acute myeloid leukemia are likely to develop it shortly after the diagnosis of myeloid sarcoma (mean: 7 months; range: 1 to 25 months).3 Myeloid sarcoma can appear in any site of the body, most commonly in the bone, periosteum, soft tissue, lymph nodes, and skin. Systemic chemotherapy against leukemia is typically used as the first-line treatment, unless an indication for local treatment emerges.
We report a case of orbital myeloid sarcoma in an 8-month-old male infant who presented with left proptosis and left orbital mass, revealing myeloid sarcoma.
The patient's legal guardian provided written consent for the publication of personal information, including medical record details and photographs.
An 8-month-old male infant presented to the Children's Hospital & Medical Center ophthalmology clinic in October 2015 for examination of a left orbital mass that had been enlarging over the previous 2 months. Systemic history was unremarkable, with no systemic medications or allergies to medications. The patient had been a full-term pregnancy with no complications at birth. The patient was taking timolol (Timoptic; Bausch & Lomb, Rochester, NY) in both eyes twice a day because the left orbital mass had previously been diagnosed as an infantile hemangioma.
Further examination revealed proptosis of the left eye and a 20 × 20 mm left temporal subconjunctival mass, with inferior-nasal displacement of the globe. The lesion was reddish-brown in color, most pronounced temporally and inferiorly with a salmon patch colored appearance. The movement of the affected eye was slightly impaired, with 15 prism diopters of esotropia and limited abduction. Intra-ocular pressure and funduscopic examination were normal. The working differential diagnosis at this point was infantile hemangioma, orbital lymphoma, rhabdomyosarcoma, metastatic neuroblastoma, and granulocytic sarcoma.
Magnetic resonance imaging (MRI) was ordered and performed the next day; findings demonstrated an infiltrative left orbital soft tissue mass that demonstrated enhancement, diffusion restriction, and subtle scalloping of the adjacent zygoma (Figure 1). Infantile hemangioma was ruled out at this point.
Magnetic resonance imaging. (A) Coronal view revealed soft tissue mass involving the temporal orbit of the left eye. (B) Axial view revealed left orbital soft tissue mass.
An incision biopsy was performed (Figure 2), as were a complete blood count (CBC) and peripheral blood smear. Pathologic findings demonstrated myeloid sarcoma with early monocytic differentiation (Figure 3). A panel of immunoperoxidase stains of paraffin sections revealed the infiltrating cells to be positive for CD45, CD43, myeloperoxidase, and CD68, and negative for CD1a, CD3, CD10, CD20, CD30, MYO D1, myogenin, CD34, CD117, and terminal deoxynucleotidyl transferase.
Evaluation before and after biopsy. (A) Left proptosis prior to biopsy. (B) Left orbital mass prior to incisional biopsy. (C) Left orbital mass after incisional biopsy.
Pathologic findings demonstrated myeloid sarcoma with early monocytic differentiation using immunosuppressive strains. Original magnification (A) 40× and (B) 200×.
CBC revealed a normal total leukocyte count (9,510 cells/mm3). The differential leukocyte count was also normal for the patient's age (27.4% neutrophils, 50.8% lymphocytes, 19.8% monocytes, 1.2% eosinophils, and 0.4% basophils). The peripheral blood smear, often performed in conjunction with a CBC when blood disorders may be diagnosed, also indicated that some of the monocytes exhibited reactive features, such as cytoplasmic vacuoles. The patient was referred to pediatric hematology/oncology for further staging and treatment.
Whole-spine MRI and short tau inversion recovery MRI, used for fat suppression, indicated negative results for any enhancing lesions. Cerebrospinal fluid was negative for any evidence of leukemia. Bone marrow aspiration and biopsy revealed no evidence of leukemia by flow cytometry, cytogenetic analysis, and fluorescent in situ hybridization. Chemotherapy was initiated per the Children's Hospital Oncology Group protocol for acute myeloid leukemia with induction cycle A with intrathecal cytarabine, daunorubicin, and etoposide. The size of the mass significantly decreased, and the mass was barely visible at the completion of induction cycle A (Figure 4), 1 month after treatment was initiated. The occupational therapist noticed possible torticollis; otherwise, the patient had no complaints and experienced no adverse events. Repeated bone marrow aspiration revealed no evidence of leukemia after induction cycle A.
Magnetic resonance imaging. (A) Coronal view after chemotherapy induction cycle A. (B) Axial view after chemotherapy induction cycle A.
To our knowledge, this report describes the youngest case of orbital myeloid sarcoma, highlighting the importance of tissue analysis in diagnosis. The patient was an 8-month-old male infant who had been initially diagnosed as having ocular infantile hemangioma. Due to its rarity, diagnosis of orbital myeloid sarcoma without preexisting leukemia is challenging. The most common pediatric orbital mass is infantile hemangioma, followed by lymphoma, neuroblastoma, and rhabdomyosarcoma. Clinical presentation is non-specific. Although infantile hemangioma can be excluded by MRI, radiological imaging cannot distinguish orbital myeloid sarcoma from tumors of other origins. Therefore, biopsy is essential for diagnosis. Given that a typical myeloid sarcoma is often not well-differentiated, histopathological confirmation is still difficult. In this case, histopathology myeloperoxidase stain and flow cytometry were essential for diagnosis.
After histopathology and flow cytometry of biopsied tissue revealed myeloid sarcoma, the patient began chemotherapy, to which he responded well. Because orbital myeloid sarcoma is considered a systemic disease rather than a localized one, multi-agent chemotherapy is the standard with respect to underlying hematological malignancy. Local radiation or surgery alone is not adequate for the treatment of orbital myeloid sarcoma.4 Local radiation could be considered if patients fail or are unfit for intense chemotherapy or when there is persistent myeloid sarcoma.5 Although our patient had a negative bone barrow aspiration and negative body MRI, bone marrow disease is likely to develop, as reported previously,3 and therefore acute myeloid leukemia chemotherapy was also initiated. After induction cycle A was completed, the orbital mass was barely visible. The patient then proceeded through all four cycles of chemotherapy and currently is in complete remission.
Myeloid sarcoma, also known as chloroma or extramedullary granulocytic sarcoma, is a rare disease that can present as an isolated extramedullary leukemic tumor, concurrently with or during a relapse of acute myeloid leukemia. This disease was first described by the British physician A. Burns in 1811,3 although the name chloroma did not appear until 1853. Chloroma is derived from the Greek word chloros (“green”) because the presence of myeloperoxidase often gives these tumors a green tint. In 1967, because approximately 30% of these tumors could be gray, white, or brown, the alternative term of granulocytic sarcoma was proposed by Rappaport7 due to the tumor's composition of granulocytic myeloid precursor cells. The relationship between myeloid sarcoma and acute leukemia was first recognized in 1902 by Dock and Warthin.8 Myeloid sarcoma could be an extramedullary manifestation of acute myeloid leukemia or certain other chronic myeloproliferative disorders, such as chronic myelogenous leukemia, multiple myeloma, myelodysplastic syndrome, or myelofibrosis. Although most often unilateral, bilateral orbital involvement is a strong diagnostic indicator of myeloid sarcoma, as presented by Shields et al.2
The most commonly involved extramedullary areas are the skin, lymph nodes, soft tissue, and bone; it rarely involves the small intestine, mediastinum, lung, epidural sites, uterus, and orbit. Orbital myeloid sarcoma can involve both the globe and orbital bone, and is more frequently located on the superior temporal side of the orbit. Our patient did have subtle scalloping of the adjacent zygoma, demonstrated by MRI, but this was most likely due to the mass effect of the myeloid sarcoma of the eye.
Patient age at extramedullary myeloid sarcoma diagnosis ranges from 2 to 70 years, but the average age range is 35.8 to 47 years.9–13 It is predominant in males, with a 1.5:1 to 4:1 male-to-female ratio reported.
However, orbital myeloid sarcoma is mostly seen in the pediatric population. In 2007, Bidar et al. reported the median age at diagnosis of orbital leukemic tumor of 8 years (range: 1 to 18 years), and 19 of 27 patients were male.14 Zimmerman and Font reported 33 cases of orbital myeloid sarcoma and confirmed that the tumor was mainly encountered in children, with boys affected more frequently than girls.15 Another case series reported the median age of 6 years (mean: 8.6 years; range: 10 months to 17 years); in contrast to other studies, a slight female preponderance of 0.7:1 was observed in this series.16 Our case report describes the youngest patient, an 8-month-old male infant, known to have developed orbital myeloid sarcoma without preexisting acute myeloid leukemia.
The clinical diagnosis of orbital myeloid sarcoma is difficult in the pediatric population given its rarity. This report highlights the importance of biopsy in diagnosis of an orbital mass that does not clearly fit the imaging characteristics of a hemangioma. Because myeloid sarcoma may present before, during, or after the development of acute myeloid leukemia, early diagnosis is important for patient outcome.
- Avni B, Koren-Michowitz M. Myeloid sarcoma: current approach and therapeutic options. Ther Adv Hematol. 2011;2:309–316. doi:10.1177/2040620711410774 [CrossRef]
- Shields JA, Stopyra GA, Marr BP, et al. Bilateral orbital myeloid sarcoma as initial sign of acute myeloid leukemia: case report and review of the literature. Arch Ophthalmol. 2003;121:138–142. doi:10.1001/archopht.121.1.138 [CrossRef]
- Byrd JC, Edenfield WJ, Shields DJ, Dawson NA. Extramedullary myeloid cell tumors in acute nonlymphocytic leukemia: a clinical review. J Clin Oncol. 1995;13:1800–1816.
- Imrie KR, Kovacs MJ, Selby D, et al. Isolated chloroma: the effect of early antileukemic therapy. Ann Intern Med. 1995;123:351–353. doi:10.7326/0003-4819-123-5-199509010-00005 [CrossRef]
- Solh M, Solomon S, Morris L, Holland K, Bashey A. Extramedullary acute myelogenous leukemia. Blood Rev. 2016;30:333–339. doi:10.1016/j.blre.2016.04.001 [CrossRef]
- Burns A. Observations of Surgical Anatomy, in Head and Neck. London: Royce; 1811:364.
- Rappaport H. Tumors of the hematopoietic system. In: Rappaport H, ed. Atlas of Tumor Pathology, Section III, Fascicle 8. Washington DC: Armed Forces Institute of Pathology. 1966;241–247.
- Dock G, Warthin AS. A new case of chloroma with leukemia. Trans Assoc Am Phys. 1904;19:115.
- Wang JH, Zhao WP, Tian C, et al. Clinical characteristics and therapeutic efficacy evaluation of 14 cases of solitary myeloid sarcoma [article in Chinese]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2015;23:1156–1160.
- Kaygusuz G, Kankaya D, Ekinci C, Topcuoglu P, Kuzu I. Myeloid sarcomas: a clinicopathologic study of 20 cases. Turk J Haemotol. 2015;32:35–42. doi:10.4274/tjh.2013.0087 [CrossRef]
- Hou ZB, Shi HY, Liang X, Wang XM. Granulocytic sarcoma: a clinical and pathologic analysis of ten cases [article in Chinese]. Zhonghua Bing Li Xue Za Zhi. 2012;41:331–334.
- Liu HY, Yin HL, Du J, et al. Clinicopathologic features of granulocytic sarcoma: a study of 38 cases [article in Chinese]. Zhonghua Bing Li Xue Za Zhi. 2010;41:172–176.
- Paydas S, Zorludemir S, Ergin M. Granulocytic sarcoma: 32 cases and review of the literature. Leuk Lymphoma. 2006;47:2527–2541. doi:10.1080/10428190600967196 [CrossRef]
- Bidar M, Wilson MW, Laquis SJ, et al. Clinical and imaging characteristics of orbital leukemic tumors. Ophthal Plast Reconstr Surg. 2007;23:87–93. doi:10.1097/IOP.0b013e3180333a85 [CrossRef]
- Zimmerman LE, Font RL. Ophthalmologic manifestations of granulocytic sarcoma (myeloid sarcoma and chloroma). The third Pan American Association of Ophthalmology and American Journal of Ophthalmology lecture. Am J Ophthalmol. 1975;80:975–990. doi:10.1016/0002-9394(75)90326-8 [CrossRef]
- Murthy R, Vemuganti GK, Honavar SG, Naik M, Reddy V. Extramedullary leukemia in children presenting with proptosis. J Hematol Oncol. 2009;2:4. doi:10.1186/1756-8722-2-4 [CrossRef]