- Open Access
Myeloid sarcomas: a histologic, immunohistochemical, and cytogenetic study
© Alexiev et al; licensee BioMed Central Ltd. 2007
- Received: 24 September 2007
- Accepted: 31 October 2007
- Published: 31 October 2007
Myeloid sarcoma (MS) is a neoplasm of immature granulocytes, monocytes, or both involving any extramedullary site. The correct diagnosis of MS is important for adequate therapy, which is often delayed because of a high misdiagnosis rate.
To evaluate the lineage differentiation of neoplastic cells in MS by immunohistochemistry, and to correlate the results with clinicopathologic findings and cytogenetic studies.
Histologic and immunohistochemical examinations were performed on formalin-fixed paraffin-embedded tissue samples from 13 cases of MS. They were classified according to the World Health Organization criteria. Chromosomal analysis data were available in 11 cases. Clinical, pathological, and cytogenetic findings were analyzed.
The study included six male and seven female patients with an age range of 25 to 72 years (mean, 49.3 years) and a male to female ratio of 1:1.2. MS de novo occurred in 4/13 (31%) of cases examined. The most sensitive immunohistochemical markers were CD43 and lysozyme present in all cases with MS (13/13, 100%). All de novo MS showed a normal karyotype, monoblastic differentiation, and lack of CD34. The most common chromosomal abnormalities in MS associated with a hematopoietic disorder were trisomy 8 and inv(16) (2/11, 18%).
An immunohistochemical panel including CD43, lysozyme, myeloperoxidase (MPO), CD68 (or CD163), CD117, CD3 and CD20 can successfully identify the vast majority of MS variants in formalin-fixed paraffin-embedded tissue sections. The present report expands the spectrum of our knowledge showing that de novo MS has frequent monoblastic differentiation and frequently carries a normal karyotype.
- Acute Myeloid Leukemia
- Neoplastic Cell
- Normal Karyotype
- Myeloproliferative Disorder
Myeloid sarcoma (MS) is a tumor mass of myeloblasts or immature myeloid cells occurring in an extramedullary site or in the bone . The tumor can involve any part of the body, but commonly involved sites include subperiosteal bone structures of the skull, paranasal sinuses, sternum, ribs, vertebrae, and pelvis; lymph nodes and skin are also common sites . MS may occur de novo or concurrently with acute myeloid leukemia (AML) or a myeloproliferative disorder . The rate of occurrence is approximately 1.4% to 9% of patients with AML [2, 3]. MS is frequently mistaken for non-Hodgkin lymphoma (NHL), small round cell tumor (neuroblastoma, rhabdomyosarcoma, Ewing sarcoma/PNET, and medulloblastoma), and undifferentiated carcinoma. The diagnosis is missed in about 50% of cases when immunohistochemistry is not used . The most common suggested diagnosis was that of a NHL .
The present study was designated to evaluate the lineage differentiation of neoplastic cells in MS by immunohistochemistry, and correlate the results with clinicopathologic findings and cytogenetic studies.
Thirteen patients with a histologic diagnosis of myeloid sarcoma were included in the present study. The initial diagnosis was made on core biopsies (3 cases) and surgical specimens (10 cases). The specimens were fixed in 10% formaldehyde and embedded in paraffin. Five-micron tissue sections were stained with hematoxylin-eosin. The use of paraffin blocks for this study meets Institutional Review Board and Health Insurance Portability and Accountability Act requirements, and has been approved by the Institutional Review Board at the University of Maryland.
Immunohistochemical staining was performed using an automated slide preparation system (Benchmark XT, Ventana, Tuscon, AZ), a Ventana Enhanced DAB Detection Kit (Ventana, Tucson, AZ), and commercially available prediluted monoclonal antibodies: CD163 (NeoMarkers), CD4 (Biocare Medical), myeloperoxidase, lysozyme, CD3, CD4, CD8, CD15, CD20, CD34, CD43, CD68, CD79a, CD117, Factor VIII (FVIII), and glycophorin A (all Ventana, Tucson, AZ).
Chromosomal analysis was performed on tumor specimens from 11 patients at diagnosis. Cells were cultured in RPMI 1640 medium with 20% fetal bovine serum for 24 and 48 hours, respectively. Metaphase cells were analyzed following standard G-banding method. Their karyotypes were interpreted according to the International System for Human Cytogenetic Nomenclature.
Clinical findings in patients with myeloid sarcoma
Sites of involvement
MS occurred in a variety of extramedullary sites (Table 1). Nine of thirteen cases with MS (69%) had a synchronous involvement of the bone marrow by acute leukemia, myeloproliferative, or myelodysplastic disorder.
Histology and immunohistochemistry
Pathologic diagnosis in patients with myeloid sarcomas
Granulocytic sarcoma, differentiated
Granulocytic sarcoma, differentiated
Granulocytic sarcoma, immature
Granulocytic sarcoma, differentiated
Granulocytic sarcoma, immature
Immature granulocytic sarcomas (IGS) were characterized by the presence of numerous (> 90%) blasts with high N/C ratio, round or oval nucleus, dispersed chromatin and prominent nucleolus. The cytoplasm of the majority of neoplastic cells was agranular with a varying degree of basophilia. Eosinophilic granulation was notable in a minority of a cell population. The neoplastic cells in IGS showed reactivity with CD34, CD43, CD117, and lysozyme. MPO was present in a variable number of blasts, but always <10%. Focal weak reactivity of the neoplastic cells with antibodies to CD68 and/or CD163 was also noted. Differentiated granulocytic sarcomas (DGS) showed maturation to more mature neutrophils (>10% of neoplastic cells). The neoplastic cells in DGS showed strong reactivity with CD43, MPO, CD15, lysozyme, and variably expressed CD117. CD68 and CD163 were positive in <20% of neoplastic cells.
Myelomonocytic sarcomas (MMS) were characterized by proliferation of both neutrophilic and monocytic precursors with above described morphologic and immunohistochemical features each comprising >20% of neoplastic cells. The cases were notable for increased numbers of eosinophils containing large eosinophilic granules in the cytoplasm.
The neoplastic cells in all MS examined did not react with antibodies to FVIII, and glycophorin A. T and B lymphocyte lineage-specific antigens such as CD3, CD20, and CD79a were typically absent.
All MS were morphologically and immunophenotypically analogous to their leukemic counterparts.
Cytogenetic findings in patients with myeloid sarcoma
47, XY, +21
46, XY, del(8)(q24.2)
47, XY, +8, t(9;22)(q34;q11.2)
48, XX, +8, +13
47, XX, t(4;7)(p12;p11.2), Inv(9)(p12q13), inv(16)(p13.1q22)
46, XX, inv (16)(p13.1q22)
- Brunnung RD, Matutes E, Flandrin G, Vardiman J, Bennett J, Head D, Harris NL: Acute myeloid leukemias. World Health Organization Classification of Tumors. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissue. Edited by: Jaffe ES, Harris NL, Stein H, Vardiman JW. 2001, IARC Press, 77-105.Google Scholar
- Tsimberidou AM, Kantarjian HM, Estey E, Cortes JE, Verstovsek S, Faderl S, Thomas DA, Garcia-Manero G, Ferrajoli A, Manning JT, Keating MJ, Albitar M, O'Brien S, Giles FJ: Outcome in patients with nonleukemic granulocytic sarcoma treated with chemotherapy with or without radiotherapy. Leukemia. 2003, 17: 1100-1103. 10.1038/sj.leu.2402958.View ArticlePubMedGoogle Scholar
- Zekry N, Klooster MJ, Raghavan R, Wang J: A 7-year-old child with a history of acute myeloid leukemia presenting with multiple gastrointestinal polyps. Arch Pathol Lab Med. 2006, 130: 3-4.Google Scholar
- Audouin J, Comperat E, Le Tourneau A, Camilleri-Broet S, Adida C, Molina T, Diebold J: Myeloid sarcoma: clinical and morphological criteria useful for diagnosis. Int J Surg Pathol. 2003, 11: 271-282. 10.1177/106689690301100404.View ArticlePubMedGoogle Scholar
- Menasce LP, Banerjee SS, Beckett E, Harris M: Extra-medullary myeloid tumour (granulocytic sarcoma) is often misdiagnosed: a study of 26 cases. Histopathol. 1999, 34: 391-398. 10.1046/j.1365-2559.1999.00651.x.View ArticleGoogle Scholar
- Valbuena JR, Admirand JH, Gualco G, Medeiros LJ: Myeloid sarcoma involving the breast. Arch Pathol Lab Med. 2005, 129: 32-38.PubMedGoogle Scholar
- Colella G, Tirelli A, Capone R, Rubini C, Guastafierro S: Myeloid sarcoma occuring in the maxillary gingiva: a case without leukemic manifestations. Int J Hematol. 2005, 81: 138-41. 10.1532/IJH97.E0410.View ArticlePubMedGoogle Scholar
- Antmen B, Haytac MC, Sasmaz I, Dogan MC, Ergin M, Tanyelli A: Granulocytic sarcoma of gingival: an unusual case with aleukemic presentation. J Periodontol. 2003, 74: 1514-1519. 10.1902/jop.2003.74.10.1514.View ArticlePubMedGoogle Scholar
- Stein-Wexler R, Wootton-Gorges SL, West DC: Orbital granulocytic sarcoma: an unusual presentation of acute myelocytic leukemia. Pediatr Radiol. 2003, 33: 136-139.View ArticlePubMedGoogle Scholar
- Ojima H, Hasegawa T, Matsuno Y, Sakamoto M: Extramedullary myeloid tumour (EMMT) of the gallbladder. J Clin Pathol. 2005, 58: 211-213. 10.1136/jcp.2004.019729.PubMed CentralView ArticlePubMedGoogle Scholar
- Yavuz S, Paydas S, Disel U, Erdogan S: Ovarian granulocytic sarcoma. Leuk Lymphoma. 2004, 45: 183-185. 10.1080/10428109031000149331.View ArticlePubMedGoogle Scholar
- Oliva E, Ferry JA, Young RH, Prat J, Srigley JR, Scully RE: Granulocytic sarcoma of the female genital tract: a clinicopathologic study of 11 cases. Am J Surg Pathol. 1997, 21: 1156-1165. 10.1097/00000478-199710000-00005.View ArticlePubMedGoogle Scholar
- Valbuena JR, Admirand JH, Lin P, Medeiros LJ: Myeloid sarcoma involving the testis. Am J Clin Pathol. 2005, 124: 445-452. 10.1309/NXLC-J1B1-6YDF-QWND.View ArticlePubMedGoogle Scholar
- Garcia MG, Deavers MT, Knoblock RJ, Chen W, Tsimberidou AM, Manning JT, Medeiros LJ: Myeloid sarcoma involving the gynecologic tract: a report of 11 cases and review of the literature. Am J Clin Pathol. 2006, 125: 783-790.View ArticlePubMedGoogle Scholar
- Al-Quran SZ, Olivares A, Lin P, Stephens TW, Medeiros LJ, Abruzzo LV: Myeloid sarcoma of the urinary bladder and epididymis as a primary manifestation of acute myeloid leukemia with inv(16). Arch Pathol Lab Med. 2006, 130: 862-866.PubMedGoogle Scholar
- Gopal S, Marcussen S, Dobin SM, Koss W, Donner LR: Primary myeloid sarcoma of the testicle with t(15;17). Cancer Gen Cytogen. 2005, 157: 148-150. 10.1016/j.cancergencyto.2004.06.010.View ArticleGoogle Scholar
- Li JM, Liu WP, Zhang MH, Wei X, Gu JM, Han AJ, Wu WQ, Chen XY: Clinicopathologic and immunophenotypic analysis of myeloid sarcoma. Zhonghua Bing Li Xue Za Zhi. 2006, 35: 606-611.PubMedGoogle Scholar
- Liu YH, Zhuang HG, Liao XB, Luo XL, Cai XL, Luo DL: Diagnosis and differential diagnosis of granulocytic sarcomas. Zhonghua Xue Ye Xue Za Zhi. 2003, 24: 568-571.PubMedGoogle Scholar
- Ritter JH, Goldstein NS, Argenyi Z, Wick MR: Granulocytic sarcoma: an immunohistologic comparison with peripheral T-cell lymphoma in paraffin sections. J Cutan Pathol. 1994, 21: 207-216. 10.1111/j.1600-0560.1994.tb00262.x.View ArticlePubMedGoogle Scholar
- Chang CC, Eshoa C, Kampalath B, Shidham VB, Perkins S: Immunophenotypic profile of myeloid cells in granulocytic sarcoma by immunohistochemistry. Correlation with blast differentiation in bone marrow. Am J Clin Pathol. 2000, 114: 807-811. 10.1309/WWW7-DG6X-HC16-D7J2.View ArticlePubMedGoogle Scholar
- Hudock J, Chatten J, Miettinen M: Immunohistochemical evaluation of myeloid leukemia infiltrates (granulocytic sarcomas) in formaldehyde-fixed, paraffin-embedded tissue. Am J Clin Pathol. 1994, 102: 55-60.PubMedGoogle Scholar
- Traweek ST, Arber DA, Rappaport H, Brynes RK: Extramedullary myeloid cell tumors. An immunohistochemical and morphological study of 28 cases. Am J Surg Pathol. 1993, 17: 1011-1019.View ArticlePubMedGoogle Scholar
- Hirose Y, Masaki Y, Shimoyama K, Sugai S, Nojima T: Granulocytic sarcoma of megakaryoblastic differentiation in the lymph nodes terminating as acute megakaryoblastic leukemia in a case of chronic idiopathic myelofibrosis persisting for 16 years. Eur J Hematol. 2001, 67: 194-198. 10.1046/j.0902-4441.2001.492umedoc.492.x.View ArticleGoogle Scholar
- Deeb G, Baer MR, Gaile DP, Sait SN, Barcos M, Wetzler M, Conroy JM, Nowak NJ, Cowell JK, Cheney RT: Genomic profiling of myeloid sarcoma by array comparative genomic hybridization. Genes Chromosomes Cancer. 2005, 44: 373-383. 10.1002/gcc.20239.View ArticlePubMedGoogle Scholar
- Pileri SA, Ascani S, Cox MC, Campidelli C, Bacci F, Piccioli M, Piccaluga PP, Agostinelli C, Asioli S, Novero D, Bisceglia M, Ponzoni M, Gentile A, Rinaldi P, Franco V, Vincelli D, Pileri A, Gasbarra R, Falini B, Zinzani PL, Baccarani M: Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients. Leukemia. 2007, 21: 340-350. 10.1038/sj.leu.2404491.View ArticlePubMedGoogle Scholar
- Chen W, Rassidakis GZ, Medeiros LJ: Nucleophosmin gene mutations in acute myeloid leukemia. Arch Pathol Lab Med. 2006, 130: 1687-1692.PubMedGoogle Scholar
- Cignetti A, Vallario A, Roato I, Circosta P, Strola G, Scielzo C, Allione B, Garetto L, Caligaris-Cappio F, Ghia P: The characterization of chemokine production and chemokine receptor expression reveals possible functional cross-talks in AML blasts with monocytic differentiation. Exp Hematol. 2003, 31: 495-503. 10.1016/S0301-472X(03)00066-3.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.