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Journal of Clinical Oncology, Vol 26, No 24 (August 20), 2008: pp. 4041-4043 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2008.17.3997
Extramedullary Myeloid Sarcoma of the BreastDepartment of Medicine, Division of Haematology Oncology, European Institute of Oncology, Milan, Italy
Department of Pathology, European Institute of Oncology, Milan, Italy
Department of Medicine, Division of Haematology Oncology, European Institute of Oncology, Milan, Italy
Department of Nuclear Medicine, European Institute of Oncology, Milan, Italy
Department of Diagnostic Radiology, European Institute of Oncology, Milan, Italy
Department of Medicine, Division of Haematology Oncology, European Institute of Oncology, Milan, Italy A 52-year-old white woman presented to our outpatient clinic in January 2007 with a short history of an accidentally discovered painless left breast lump. Clinical examination showed a 4-cm mass located in the left upper outer quadrant. An ultrasound-guided biopsy was performed and pathology revealed a picture consistent with myeloid sarcoma (MS). Histologically, there was a proliferation of large immature cells with eosinophilic cytoplasm and single or multiple nucleoli, diffusely infiltrating the mammary parenchyma and sparing a few ductal and lobular structures (Fig 1A). Malignant cells were immunoreactive for myeloperoxidase and CD43 (Fig 1B and 1C) and focally for CD34 and TdT, in the absence of lymphoid (CD3, CD8, CD20, CD56, CD79a) and epithelial (cytokeratin) markers, and were characterized by a high labeling index (Ki-67, 80%; Fig 1D). Complete blood count showed a hemoglobin level of 13.9 g/dL, with 6,540 leukocytes/µl, neutrophils at 75%, lymphocytes at 21% with no abnormal forms, and 371,000 platelets/µl. Bone marrow aspirate and biopsy were normal. Breast magnetic resonance imaging (MRI) showed a 30 x 20 mm enhancing mass in the left breast at the 2 o'clock position with no axillary lymphadenopathy (Fig 2A). Computed tomography/positron emission tomography (CT/PET) showed localized activity in the left breast (Fig 2B). She was then started on acute myeloid leukemia (AML) –induction chemotherapy consisting of idarubicin (12 mg/m2, daily for 3 days) and cytosine arabinoside (200 mg/m2 continuous infusion for 7 days). Follow-up breast MRI done afterwards showed a partial response, with reduction in both tumor size and enhancement. The patient went on to receive the first consolidation course with acridinyl anisidide (50 mg/m2 daily for 5 days) and etoposide (80 mg/m2 continuous infusion for 5 days), with complete clinical and radiological response as assessed by CT/PET scan. She then received radiotherapy to the left breast (36Gy/18 fractions) followed by one more course of consolidation chemotherapy with high-dose cytosine arabinoside (2000 mg/m2 twice daily for 5 days) and idarubicin (12 mg/sqm daily for 3 days). Three months later, MRI and CT/PET (Fig 3A and 3B) confirmed a complete remission with normal bone marrow aspirate and biopsy. After 1 year from initial diagnosis, she is still maintaining a complete remission.
MSs are solid tumors composed of immature myeloid cells which may rise in a variety of extramedullary anatomic sites. Although they usually develop synchronously or following the diagnosis of AML,1 the occurrence of bona fide primary MS without blood or bone marrow involvement has been described. Affected sites include skin, lymph nodes, bone, small intestine, and less commonly, the breast.2 Breast MSs are more commonly encountered in the natural history of a myeloid neoplasm originating from the bone marrow. Around 6% of MSs, though, originate primarily from the breast,2 without bone marrow involvement. Several literature reviews were performed aiming to identify the number of cases, clinical course, and behavior of this rare disease.2,3,4 The most recent was reported by Cunningham4 in 2006. Cunningham described 27 patients with primary MS of the breast, four of whom had bilateral breast involvement. Since her analysis, we were able to identify three more cases including our report.5,6 Due to the rarity of the tumor, diagnosis is a real challenge, and misdiagnosis is consequently high. Differential diagnosis include a variety of hematopoietic (diffuse large B-cell lymphoma, anaplastic large-cell lymphoma)7,8 and nonhematopoietic (breast carcinoma, melanoma)8,9 malignancies, and thus accurate diagnosis requires extensive immunophenotyping to ascertain the myeloid origin of the neoplastic cells. Our case showed the typical profile of myeloid neoplasms, with an immunoreactivity diffuse and intense for myeloperoxidase and CD43, focal for CD34 and TdT, and absent for markers of lymphoma and carcinoma. There is no definitive consensus regarding the optimal treatment of primary extramedullary MS. However, available evidence strongly favors the application of systemic chemotherapy despite the apparent localized nature of the disease. In the systemic review,4 12 patients received local therapy alone (surgery and/or radiotherapy), 11 (92%) of whom relapsed. In those who received chemotherapy, only five patients (42%) relapsed at a median time of 15 months. The pattern of relapse in these patients was mostly in the bone marrow (60%). Those who did not relapse remained disease-free at a median follow-up period of 95 months. Even if direct comparison with other regimens can not be made, AML chemotherapy regimens appear to be the treatment of choice.2,10 It remains to be determined whether chemoradiotherapy is superior to chemotherapy alone. In our case, we administered AML chemotherapy and incorporated local radiotherapy as well. Response assessment was performed by breast MRI and CT/PET scans, which were positive at diagnosis. To our knowledge, PET scan was reported in only one patient.11 Given the previously mentioned pattern of relapse, bone marrow examination is recommended during the follow-up period. The highest risk of relapse was witnessed during the first 2 years, and thus it is recommended to have frequent follow-up visits during this period. Longer follow-up has shown that patients who achieve complete response enjoy durable remissions and could be probably cured. The outcome of treatment in those who relapsed following first-line chemotherapy is not well described. In one patient with bone marrow relapse, allogeneic bone marrow transplantation resulted in long-term remission (> 10 years).12 Given the paucity of data in primary MS of the breast, we believe that our case provides a clear and adequate management strategy in terms of diagnostic procedures, choice of therapy, and treatment assessment, and could serve as a good reference for managing similar cases. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
ACKNOWLEDGMENTS We acknowledge Isabel Cunningham, MD, for her fruitful discussion during the preparation of the work. REFERENCES 1. Brunnung RD, Matutes E, Flandrin G, et al: Acute myeloid leukemia: World Health Organization Classification of Tumors, in Jaffe ES, Harris NL, Stein H, et al (eds): Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissue. Lyon, France, International Agency for Research of Cancer Press, 2001, pp 77-105 2. Byrd JC, Edenfield WJ, Shields DJ, et al: Extramedullary myeloid cell tumors in acute nonlymphocytic leukaemia: A clinical review. J Clin Oncol 13:1800-1816, 1995 3. Shea B, Reddy V, Abbitt P, et al: Granulocytic sarcoma (chloroma) of the breast: A diagnostic dilemma and review of literature. Breast J 10:48-53, 2004[CrossRef][Medline] 4. Cunningham I: A clinical review of breast involvement in acute leukaemia. Leuk Lymphoma 47:2517-2526, 2006[CrossRef][Medline] 5. Thachil J, Richards RM, Copeland G: Granulocytic sarcoma: A rare presentation of a breast lump. Ann R Coll Surg Engl 89:W7-9, 2007[Medline] 6. D'Costa GF, Hastak MS, Patil YV: Granulocytic sarcoma of breast: An aleukemic presentation. Indian J Med Sci 61:152-155, 2007[Medline] 7. Menasce LP, Banerjee SS, Beckett E, et al: Extra-medullary myeloid tumor (granulocytic sarcoma) is often misdiagnosed: A study of 26 cases. Histopathology 34:391-398, 1999[CrossRef][Medline] 8. Valbuena JR, Admirand JH, Gualco G, et al: Myeloid sarcoma involving the breast. Arch Pathol Lab Med 129:32-38, 2005[Medline] 9. Ellis IO, Schnitt SJ, Sastre-Garau X, et al: Invasive lobular carcinoma, in Tavassoli FA, Devilee P (eds): Pathology and Genetics of Tumours of the Breast and Female Genital Organs. Lyon, France, International Agency for Research of Cancer Press, 2003, pp 23-25 10. Pileri SA, Ascani S, Cox MC, et al: Myeloid sarcoma: Clinico-pathologic, phenotypic, and cytogenetic analysis of 92 adult patients. Leukemia 21:340-350, 2007[CrossRef][Medline] 11. Oyama K, Suzuki T, Yoshimura S, et al: Isolated granulocytic sarcoma in the breast [in Japanese]. Rinsho Ketsueki 44:952-956, 2003[Medline] 12. Quitt M, Ellmalach I, Dar H, et al: Isolated chloroma of the breast preceding acute nonlymphatic leukaemia. Leukemia 11:1995-1996, 1997[Medline]
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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