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Erythroblastic sarcoma, an extremely rare variant of myeloid sarcoma
Human Pathology (2012) 43, 2080–2083
www.elsevier.com/locate/humpath
Case study
Erythroblastic sarcoma, an extremely rare variant of myeloid sarcoma☆ Dennis B. Cornfield MD Department of Pathology, Lehigh Valley Health Network, Cedar Crest site, 1200 S. Cedar Crest Blvd., Allentown, PA 18103, USA Received 6 February 2012; revised 10 March 2012; accepted 28 March 2012
Keywords: Erythroblastic sarcoma; Myeloid sarcoma; Extramedullary; Myelodysplasia
Summary A 79-year-old man was admitted to the hospital because of a 20-lb weight loss, low back pain, and leg weakness. He had a 1-year history of fibrotic myelodysplasia, possibly therapy related, with a highly complex chromosome karyotype. Radiologic evaluation showed extensive destructive bone lesions, retroperitoneal lymphadenopathy, and evidence for thoracic spinal cord compression. Core biopsies of a retroperitoneal lymph node showed groups of large, immature-appearing mononuclear cells which, on Wright-stained touch preparation, appeared similar to dysplastic erythroid precursors noted on recent marrow aspirate smears. Immunohistochemical staining showed negativity of neoplastic cells to an extensive panel of nonhematopoietic and myeloid markers, and positivity for CD117, glycophorin A, and CD71, consistent with a diagnosis of erythroblastic sarcoma. This lesion is a very unusual variant of myeloid sarcoma and has been described only rarely in the medical literature. © 2012 Elsevier Inc. All rights reserved.
1. Introduction Myeloid sarcoma (MS) is a relatively uncommon extramedullary tumor which occurs in the setting of acute myeloid leukemias, chronic myeloproliferative neoplasms, myelodysplastic syndromes (MDS), or de novo [1]. In a series of 21 cases of MS diagnosed at MD Anderson Cancer Center over a 13-year period, MS was reported as occurring in 1.4% of patients with acute myeloid leukemia and in 5.2% of patients with high-risk MDS, including the category previously termed refractory anemia with excess
blasts, in transformation [2]. MS is usually composed of myeloblasts or monoblasts, rarely of megakaryoblasts. Although the 2008 World Health Organization classification of hematolymphoid neoplasms mentions tumors composed predominantly of erythroid precursors [1], this tumor, perhaps best termed erythroblastic sarcoma, has been described only rarely in the medical literature. The present report describes a case of erythroblastic sarcoma in a man with a 1-year history of myelodysplasia.
2. Case report ☆
Conflict of interest and Source of funding: The author has no conflicts of interest to disclose. There was no funding involved in this manuscript. E-mail addresses: dennis.cornfi[email protected], [email protected]. 0046-8177/$ – see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.humpath.2012.03.026
A 79-year-old man with a 1-year history of fibrotic myelodysplasia, possibly therapy related, was admitted to the hospital with low back pain, progressive lower extremity weakness, and a 20-lb weight loss. He had
Erythroblastic sarcoma, a very rare form of myeloid sarcoma received 4 courses of treatment with azacytidine and weekly erythropoietin (EPO) for the MDS, with mild improvement in his transfusion requirement. Twenty years earlier, he underwent treatment with adjuvant radiation and chemotherapy for rectal adenocarcinoma. Physical examination on admission showed leg weakness, but otherwise no specific abnormalities. Complete blood count showed hemoglobin of 9.2 g/dL, white blood cell count of 2400/ μL, and platelet count of 375 000/μL. Radiologic studies demonstrated osseous metastatic disease in the thoracic, lumbar, and sacral spines; extensive retroperitoneal lymphadenopathy; destructive changes of 2 ribs; and paravertebral and epidural soft tissue masses, with spinal cord compression at the level of the seventh thoracic vertebra. Despite radiation therapy and medical support, the patient's condition progressively deteriorated, and he expired 2 weeks later.
3. Results The original bone marrow at the time of the diagnosis of MDS showed moderate cellularity, scattered dysplastic morphologic features in all cell lines, and extensive reticulin fibrosis. Absence of human leukocyte antigen DR expression on two thirds of monocytes was demonstrated by flow cytometry. Cytogenetics study of the original marrow revealed the following complex karyotype: 61-62,XY,+add(1)(q12)x2,del(1)(q42)x2,+2,+del(3)(q11.2),+4, add(4)(p16)x2, + 5,del(5)(q13q33)x2,+6,del(6)(p21)x2,+7,+8, der(8)t(1;8)(q25;p23)x2,+9,+11,+13,add(15)(q25),i(15)(q10), +16,+19,+20,+21,+22[cp14]/46,XY[6]
Subsequent bone marrow samples over the next year showed a progressive increase in dysplastic-appearing immature erythroid precursors but no overt increase in myeloblasts (Figure A-C). A limited cytogenetics study on bone marrow obtained 2 weeks before the final hospitalization showed no new abnormalities in 2 cells available for analysis. During the hospitalization, core biopsies were taken of an enlarged retroperitoneal lymph node (Figure D-F). Wright-stained touch preparations showed numerous large, discohesive cells with 1 to 2 nuclei, typically a very prominent central nucleolus, and deeply basophilic cytoplasm. Hematoxylin and eosin–stained fixed tissue sections showed sheets of large atypical cells with basophilic to amphophilic cytoplasm, present in trabecular and nested patterns. An extensive panel of immunohistochemical stains was applied. The neoplastic cells showed positivity for CD71, glycophorin A, CD117, epithelial membrane antigen, and vimentin, supporting a diagnosis of erythroblastic sarcoma. There was negativity for all other markers applied, including stains for epithelial cells (cytokeratins), melanoma, T and B lymphocytes, leukocytes (CD45), plasma cells, and a variety of nonhematopoietic malignancies.
2081
4. Discussion The 2008 version of the World Health Organization classification of hematopoietic neoplasms alludes to tumors of predominantly erythroid precursors as unusual subtypes of myeloid sarcomas [1]. Based on numerous PubMed literature searches performed for the present report, this entity is extraordinarily rare. Using the term “erythroblastic sarcoma” for a PubMed search, we found only a single case report, an infant with ovarian masses and pure erythroid leukemia [3]. With the key search words “granulocytic sarcoma” and “erythroid,” “myeloid sarcoma” and “erythroid,” and “extramedullary myeloid tumor” and “erythroid,” only the above case report emerged. The antiquated word “erythroblastoma(s)” yielded 5 entries in the medical literature, all between 1950 and 1966: 3 in German, 1 in Italian, and 1 in English. The “erythroblastomas” diffusely involved bone marrow in most of the above reports and were sometimes associated with other entities like metastatic carcinoma of the prostate [4] and a cavernous, hemangiomatous malignancy of the liver [5]. The difficulty in evaluating reports like the above, written in a different medical era and in foreign languages, is compounded by the frequent change in the terminology applied to erythroleukemia over the past century and by the changes in the criteria used to differentiate forms of erythroleukemia from myelodysplasia. In any case, detailed reports of an extramedullary tumor consisting predominantly of neoplastic erythroid precursors are exceedingly rare. The present case validates erythroblastic sarcoma as a distinct type of myeloid sarcoma. The patient described herein was being treated with average doses of EPO to combat MDS-related anemia, raising the theoretical possibility of a relationship between the neoplastic erythroid masses and the use of exogenous EPO. This scenario is considered extremely unlikely in view of the widespread use of EPO in patients with MDS and the absence of any reports of similar tumor development. However, a very peculiar sensitivity of the erythroid component of this patient's MDS to EPO is not entirely excluded. The cytogenetic alterations responsible for the erythroblastic sarcoma in our case are a matter of speculation, as no particular cytogenetic abnormality has been linked specifically to neoplastic dyserythropoiesis. However, the additional copies of chromosomes 6, 7, 11,16,19, and 20 noted in this case may have altered the expression of one or more of the following erythropoiesis-related genes [6]: FGFR1OP at 6q27, involved in proliferation and differentiation of cells of the erythroid lineage; IKZF1 at 7p13-p11.1, involved in the regulation of apoptosis of adult erythroid cells; EPO at 7q22, which initiates hemoglobin synthesis and regulates erythroid differentiation; LMO2 at 11p13, involved in yolk sac erythropoiesis and red cell development; CBFA2T3 at
2082
D. B. Cornfield
Figure Iliac crest bone marrow (A-C). A, Aspirate smear shows very large, dysplastic erythroid precursors (Wright stain, original magnification × 1000) that exhibit block positivity for periodic acid Schiff (inset, original magnification × 400). B, Biopsy is cellular with a moderate increase in erythroid precursors (hematoxylin and eosin, original magnification × 400). C, Biopsy shows numerous clusters of erythroid precursors, including some large forms (glycophorin A, original magnification × 400). Retroperitoneal lymph node mass (D-F). D, Core biopsy shows sheets and nests of large mononuclear cells (hematoxylin and eosin, original magnification ×400) that, on touch preparation (inset, Wright stain, original magnification ×1000), closely resemble the dysplastic erythroid precursors of the bone marrow aspirate smear in (A). E and F, Erythroid precursors are highlighted by glycophorin A (E, original magnification ×400) and CD71 (F, original magnification × 400) immunostains.
16q24, which regulates the proliferation and differentiation of erythroid progenitors; EPOR at 19p13.3, which encodes the erythropoietin (EPO) receptor; and SEC23B at 20p11.23, a gene in which at least 20 different mutations have been described in patients with type 2 congenital dyserythropoietic anemia. A case that satisfied morphologic, cytochemical, and immunophenotypic criteria for erythroblastic sarcoma was presented at the combined Society of Hematopathology/ European Association of Hematopathology (SH/EAHP) meeting in 2007 [7,8]. A 42-year-old man with a 7-month history of fibrotic myelodysplasia developed lytic bone
lesions and retroperitoneal and neck lymphadenopathy. A supraclavicular lymph node showed effacement by sheets of neoplastic mononuclear cells that stained positive for periodic acid Schiff, hemoglobin A1, and glycophorin C. Flow cytometry showed most of the population of interest to express glycophorin A and CD71. Cytogenetics study performed on the lymph node was described as showing extra copies of chromosomes 5 and 8; monosomies of chromosomes Y and 15; an unbalanced 5;15 translocation; a deleted chromosome 8q; a deleted chromosome 10q; derivative chromosomes 19 and 20; and isochromosome 20q. One of the 7 cells analyzed appeared to be a broken
Erythroblastic sarcoma, a very rare form of myeloid sarcoma tetraploid. In addition to these changes, the karyotype included ring and marker chromosomes not previously documented in this patient's bone marrow. He was treated with standard chemotherapy for acute myeloid leukemia, but his bone marrow 6 weeks after treatment showed 80% neoplastic-appearing erythroid precursors. The above case and our own case have the following features in common: (1) fibrotic myelodysplasia; (2) extra copies of chromosomes 5 and 8 in an otherwise highly complex chromosome karyotype; (3) myelodysplasia with a prominent erythroid component. These features are not unusual for MDS in general and would not be useful in predicting the possible emergence of a myeloid or an erythroid sarcoma. The presence of erythroblastic sarcoma in both cases would appear to represent a late event in the evolution of a neoplastic, predominantly erythroid clone. It is analogous to the more common granulocytic and monocytic varieties of MS, which usually emerge in the setting of a preexisting myeloid disorder with numerous cytogenetic abnormalities, presumably acquired over an extended period of time [9]. The specific molecular or genetic abnormalities responsible for the development of extramedullary masses in conditions ordinarily confined to the bone marrow and peripheral blood are entirely unknown at the present time.
2083
References [1] Swerdlow SH, Campo E, Harris NL, et al, editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. World Health Organization Classification of Tumours, 4th ed. Lyon: IARC Press; 2008. p. 140-1. [2] Tsimberidou AM, Kantarjian HM, Estey E, et al. Outcome in patients with nonleukemic granulocytic sarcoma treated with chemotherapy with or without radiotherapy. Leukemia 2003;17:1100-3. [3] Wang HY, Huang LJ, Liu Z, Garcia R, Li S, Galliani CA. Erythroblastic sarcoma presenting as bilateral ovarian masses in an infant with pure erythroid leukemia. HUM PATHOL 2011;42:749-58. [4] Dimitrov D, Babinov L, Pavlov K. Question of erythroblastoma; diffuse erythroblastomatosis and carcinoma of the prostate gland [Article in Italian]. Haematologica 1959;44(2):153-64. [5] Corwin WC, Nettleship A. A solitary erythroblastoma of the liver; report of a case. J Lab Clin Med 1959;53:882-7. [6] Genetics Home Reference. National Library of Medicine. Available at: http://ghr.nlm.nih.gov. [7] Dunphy C. Extramedullary manifestation of neoplastic myeloid disorder: case #017. Presented at: 2007 Workshop of Society for Hematopathology and European Association for Haematopathology; November 1-3, 2007; Indianapolis, IN. http://www.iupui.edu/~pathol/ HematopathologyWorkshop/login_successful/cases/22.html. [8] Campidelli C, Agostinelli C, Stitson R, Pileri SA. Myeloid sarcoma: extramedullary manifestation of myeloid disorders. Am J Clin Pathol 2009;132:426-37. [9] Pileri SA, Ascani S, Cox MC, et al. Myeloid sarcoma: clinicopathologic, phenotypic and cytogenetic analysis of 92 adult patients. Leukemia 2007;21:340-50.
www.elsevier.com/locate/humpath
Case study
Erythroblastic sarcoma, an extremely rare variant of myeloid sarcoma☆ Dennis B. Cornfield MD Department of Pathology, Lehigh Valley Health Network, Cedar Crest site, 1200 S. Cedar Crest Blvd., Allentown, PA 18103, USA Received 6 February 2012; revised 10 March 2012; accepted 28 March 2012
Keywords: Erythroblastic sarcoma; Myeloid sarcoma; Extramedullary; Myelodysplasia
Summary A 79-year-old man was admitted to the hospital because of a 20-lb weight loss, low back pain, and leg weakness. He had a 1-year history of fibrotic myelodysplasia, possibly therapy related, with a highly complex chromosome karyotype. Radiologic evaluation showed extensive destructive bone lesions, retroperitoneal lymphadenopathy, and evidence for thoracic spinal cord compression. Core biopsies of a retroperitoneal lymph node showed groups of large, immature-appearing mononuclear cells which, on Wright-stained touch preparation, appeared similar to dysplastic erythroid precursors noted on recent marrow aspirate smears. Immunohistochemical staining showed negativity of neoplastic cells to an extensive panel of nonhematopoietic and myeloid markers, and positivity for CD117, glycophorin A, and CD71, consistent with a diagnosis of erythroblastic sarcoma. This lesion is a very unusual variant of myeloid sarcoma and has been described only rarely in the medical literature. © 2012 Elsevier Inc. All rights reserved.
1. Introduction Myeloid sarcoma (MS) is a relatively uncommon extramedullary tumor which occurs in the setting of acute myeloid leukemias, chronic myeloproliferative neoplasms, myelodysplastic syndromes (MDS), or de novo [1]. In a series of 21 cases of MS diagnosed at MD Anderson Cancer Center over a 13-year period, MS was reported as occurring in 1.4% of patients with acute myeloid leukemia and in 5.2% of patients with high-risk MDS, including the category previously termed refractory anemia with excess
blasts, in transformation [2]. MS is usually composed of myeloblasts or monoblasts, rarely of megakaryoblasts. Although the 2008 World Health Organization classification of hematolymphoid neoplasms mentions tumors composed predominantly of erythroid precursors [1], this tumor, perhaps best termed erythroblastic sarcoma, has been described only rarely in the medical literature. The present report describes a case of erythroblastic sarcoma in a man with a 1-year history of myelodysplasia.
2. Case report ☆
Conflict of interest and Source of funding: The author has no conflicts of interest to disclose. There was no funding involved in this manuscript. E-mail addresses: dennis.cornfi[email protected], [email protected]. 0046-8177/$ – see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.humpath.2012.03.026
A 79-year-old man with a 1-year history of fibrotic myelodysplasia, possibly therapy related, was admitted to the hospital with low back pain, progressive lower extremity weakness, and a 20-lb weight loss. He had
Erythroblastic sarcoma, a very rare form of myeloid sarcoma received 4 courses of treatment with azacytidine and weekly erythropoietin (EPO) for the MDS, with mild improvement in his transfusion requirement. Twenty years earlier, he underwent treatment with adjuvant radiation and chemotherapy for rectal adenocarcinoma. Physical examination on admission showed leg weakness, but otherwise no specific abnormalities. Complete blood count showed hemoglobin of 9.2 g/dL, white blood cell count of 2400/ μL, and platelet count of 375 000/μL. Radiologic studies demonstrated osseous metastatic disease in the thoracic, lumbar, and sacral spines; extensive retroperitoneal lymphadenopathy; destructive changes of 2 ribs; and paravertebral and epidural soft tissue masses, with spinal cord compression at the level of the seventh thoracic vertebra. Despite radiation therapy and medical support, the patient's condition progressively deteriorated, and he expired 2 weeks later.
3. Results The original bone marrow at the time of the diagnosis of MDS showed moderate cellularity, scattered dysplastic morphologic features in all cell lines, and extensive reticulin fibrosis. Absence of human leukocyte antigen DR expression on two thirds of monocytes was demonstrated by flow cytometry. Cytogenetics study of the original marrow revealed the following complex karyotype: 61-62,XY,+add(1)(q12)x2,del(1)(q42)x2,+2,+del(3)(q11.2),+4, add(4)(p16)x2, + 5,del(5)(q13q33)x2,+6,del(6)(p21)x2,+7,+8, der(8)t(1;8)(q25;p23)x2,+9,+11,+13,add(15)(q25),i(15)(q10), +16,+19,+20,+21,+22[cp14]/46,XY[6]
Subsequent bone marrow samples over the next year showed a progressive increase in dysplastic-appearing immature erythroid precursors but no overt increase in myeloblasts (Figure A-C). A limited cytogenetics study on bone marrow obtained 2 weeks before the final hospitalization showed no new abnormalities in 2 cells available for analysis. During the hospitalization, core biopsies were taken of an enlarged retroperitoneal lymph node (Figure D-F). Wright-stained touch preparations showed numerous large, discohesive cells with 1 to 2 nuclei, typically a very prominent central nucleolus, and deeply basophilic cytoplasm. Hematoxylin and eosin–stained fixed tissue sections showed sheets of large atypical cells with basophilic to amphophilic cytoplasm, present in trabecular and nested patterns. An extensive panel of immunohistochemical stains was applied. The neoplastic cells showed positivity for CD71, glycophorin A, CD117, epithelial membrane antigen, and vimentin, supporting a diagnosis of erythroblastic sarcoma. There was negativity for all other markers applied, including stains for epithelial cells (cytokeratins), melanoma, T and B lymphocytes, leukocytes (CD45), plasma cells, and a variety of nonhematopoietic malignancies.
2081
4. Discussion The 2008 version of the World Health Organization classification of hematopoietic neoplasms alludes to tumors of predominantly erythroid precursors as unusual subtypes of myeloid sarcomas [1]. Based on numerous PubMed literature searches performed for the present report, this entity is extraordinarily rare. Using the term “erythroblastic sarcoma” for a PubMed search, we found only a single case report, an infant with ovarian masses and pure erythroid leukemia [3]. With the key search words “granulocytic sarcoma” and “erythroid,” “myeloid sarcoma” and “erythroid,” and “extramedullary myeloid tumor” and “erythroid,” only the above case report emerged. The antiquated word “erythroblastoma(s)” yielded 5 entries in the medical literature, all between 1950 and 1966: 3 in German, 1 in Italian, and 1 in English. The “erythroblastomas” diffusely involved bone marrow in most of the above reports and were sometimes associated with other entities like metastatic carcinoma of the prostate [4] and a cavernous, hemangiomatous malignancy of the liver [5]. The difficulty in evaluating reports like the above, written in a different medical era and in foreign languages, is compounded by the frequent change in the terminology applied to erythroleukemia over the past century and by the changes in the criteria used to differentiate forms of erythroleukemia from myelodysplasia. In any case, detailed reports of an extramedullary tumor consisting predominantly of neoplastic erythroid precursors are exceedingly rare. The present case validates erythroblastic sarcoma as a distinct type of myeloid sarcoma. The patient described herein was being treated with average doses of EPO to combat MDS-related anemia, raising the theoretical possibility of a relationship between the neoplastic erythroid masses and the use of exogenous EPO. This scenario is considered extremely unlikely in view of the widespread use of EPO in patients with MDS and the absence of any reports of similar tumor development. However, a very peculiar sensitivity of the erythroid component of this patient's MDS to EPO is not entirely excluded. The cytogenetic alterations responsible for the erythroblastic sarcoma in our case are a matter of speculation, as no particular cytogenetic abnormality has been linked specifically to neoplastic dyserythropoiesis. However, the additional copies of chromosomes 6, 7, 11,16,19, and 20 noted in this case may have altered the expression of one or more of the following erythropoiesis-related genes [6]: FGFR1OP at 6q27, involved in proliferation and differentiation of cells of the erythroid lineage; IKZF1 at 7p13-p11.1, involved in the regulation of apoptosis of adult erythroid cells; EPO at 7q22, which initiates hemoglobin synthesis and regulates erythroid differentiation; LMO2 at 11p13, involved in yolk sac erythropoiesis and red cell development; CBFA2T3 at
2082
D. B. Cornfield
Figure Iliac crest bone marrow (A-C). A, Aspirate smear shows very large, dysplastic erythroid precursors (Wright stain, original magnification × 1000) that exhibit block positivity for periodic acid Schiff (inset, original magnification × 400). B, Biopsy is cellular with a moderate increase in erythroid precursors (hematoxylin and eosin, original magnification × 400). C, Biopsy shows numerous clusters of erythroid precursors, including some large forms (glycophorin A, original magnification × 400). Retroperitoneal lymph node mass (D-F). D, Core biopsy shows sheets and nests of large mononuclear cells (hematoxylin and eosin, original magnification ×400) that, on touch preparation (inset, Wright stain, original magnification ×1000), closely resemble the dysplastic erythroid precursors of the bone marrow aspirate smear in (A). E and F, Erythroid precursors are highlighted by glycophorin A (E, original magnification ×400) and CD71 (F, original magnification × 400) immunostains.
16q24, which regulates the proliferation and differentiation of erythroid progenitors; EPOR at 19p13.3, which encodes the erythropoietin (EPO) receptor; and SEC23B at 20p11.23, a gene in which at least 20 different mutations have been described in patients with type 2 congenital dyserythropoietic anemia. A case that satisfied morphologic, cytochemical, and immunophenotypic criteria for erythroblastic sarcoma was presented at the combined Society of Hematopathology/ European Association of Hematopathology (SH/EAHP) meeting in 2007 [7,8]. A 42-year-old man with a 7-month history of fibrotic myelodysplasia developed lytic bone
lesions and retroperitoneal and neck lymphadenopathy. A supraclavicular lymph node showed effacement by sheets of neoplastic mononuclear cells that stained positive for periodic acid Schiff, hemoglobin A1, and glycophorin C. Flow cytometry showed most of the population of interest to express glycophorin A and CD71. Cytogenetics study performed on the lymph node was described as showing extra copies of chromosomes 5 and 8; monosomies of chromosomes Y and 15; an unbalanced 5;15 translocation; a deleted chromosome 8q; a deleted chromosome 10q; derivative chromosomes 19 and 20; and isochromosome 20q. One of the 7 cells analyzed appeared to be a broken
Erythroblastic sarcoma, a very rare form of myeloid sarcoma tetraploid. In addition to these changes, the karyotype included ring and marker chromosomes not previously documented in this patient's bone marrow. He was treated with standard chemotherapy for acute myeloid leukemia, but his bone marrow 6 weeks after treatment showed 80% neoplastic-appearing erythroid precursors. The above case and our own case have the following features in common: (1) fibrotic myelodysplasia; (2) extra copies of chromosomes 5 and 8 in an otherwise highly complex chromosome karyotype; (3) myelodysplasia with a prominent erythroid component. These features are not unusual for MDS in general and would not be useful in predicting the possible emergence of a myeloid or an erythroid sarcoma. The presence of erythroblastic sarcoma in both cases would appear to represent a late event in the evolution of a neoplastic, predominantly erythroid clone. It is analogous to the more common granulocytic and monocytic varieties of MS, which usually emerge in the setting of a preexisting myeloid disorder with numerous cytogenetic abnormalities, presumably acquired over an extended period of time [9]. The specific molecular or genetic abnormalities responsible for the development of extramedullary masses in conditions ordinarily confined to the bone marrow and peripheral blood are entirely unknown at the present time.
2083
References [1] Swerdlow SH, Campo E, Harris NL, et al, editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. World Health Organization Classification of Tumours, 4th ed. Lyon: IARC Press; 2008. p. 140-1. [2] Tsimberidou AM, Kantarjian HM, Estey E, et al. Outcome in patients with nonleukemic granulocytic sarcoma treated with chemotherapy with or without radiotherapy. Leukemia 2003;17:1100-3. [3] Wang HY, Huang LJ, Liu Z, Garcia R, Li S, Galliani CA. Erythroblastic sarcoma presenting as bilateral ovarian masses in an infant with pure erythroid leukemia. HUM PATHOL 2011;42:749-58. [4] Dimitrov D, Babinov L, Pavlov K. Question of erythroblastoma; diffuse erythroblastomatosis and carcinoma of the prostate gland [Article in Italian]. Haematologica 1959;44(2):153-64. [5] Corwin WC, Nettleship A. A solitary erythroblastoma of the liver; report of a case. J Lab Clin Med 1959;53:882-7. [6] Genetics Home Reference. National Library of Medicine. Available at: http://ghr.nlm.nih.gov. [7] Dunphy C. Extramedullary manifestation of neoplastic myeloid disorder: case #017. Presented at: 2007 Workshop of Society for Hematopathology and European Association for Haematopathology; November 1-3, 2007; Indianapolis, IN. http://www.iupui.edu/~pathol/ HematopathologyWorkshop/login_successful/cases/22.html. [8] Campidelli C, Agostinelli C, Stitson R, Pileri SA. Myeloid sarcoma: extramedullary manifestation of myeloid disorders. Am J Clin Pathol 2009;132:426-37. [9] Pileri SA, Ascani S, Cox MC, et al. Myeloid sarcoma: clinicopathologic, phenotypic and cytogenetic analysis of 92 adult patients. Leukemia 2007;21:340-50.