Korean J Hematol 2011; 46(1):
Published online March 31, 2011
https://doi.org/10.5045/kjh.2011.46.1.52
© The Korean Society of Hematology
Department of Hematology, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
Correspondence to : Correspondence to Xavier Thomas, M.D., Ph.D. Department of Hematology, Hôpital Edouard Herriot, 5 place d'Arsonval, 69437 Lyon, France. Tel: +33-4-72117395, Fax: +33-1-72117404, xavier.thomas@chu-lyon.fr
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
This study reports a case of promyelocytic sarcoma that developed as a solitary sternal mass without any clinical evidence of acute promyelocytic leukemia. The case presented the diagnostic difficulties common to all aleukemic granulocytic sarcomas, and diagnosis was made possible by local identification of the
Keywords Promyelocytic sarcoma,
Myeloid sarcoma (MS) (initially known as granulocytic sarcoma, and then chloroma) is a rare localized tumor composed of immature granulocytic precursor cells. This extramedullary tumor can affect any organ and can present before, in concurrence with, or after the diagnosis of acute myeloid leukemia (AML) or other myeloproliferative disorders, or as a manifestation of disease relapse [1]. The World Health Organization (WHO) classification recognizes different variants of this tumor based on the predominant cell type and the degree of cell maturation [2]. Extramedullary disease is associated with every cytological subset of French-American-British (FAB) individuals; the disease is frequently found in patients with a monocytic component (FAB M4 and M5), but it is seldom found in patients with acute promyelocytic leukemia (APL) [3].
APL accounts for approximately 10% of AML cases, and is characterized by a favorable clinical outcome [4]. Several types of extramedullary leukemic infiltrates have been reported in APL patients; the skin (leukemia cutis) and the central nervous system (CNS) are the preferred sites of extramedullary involvement in APL. Among primary extramedullary localizations, chloroma is an uncommon pathognomonic lesion, and it is more appropriately termed as promyelocytic sarcoma (PS) when it occurs in this subset of leukemia.
In this report, we present a case of PS that presented as a solitary sternal mass without any clinical evidence of hemopathy. A conclusive diagnosis of PS was made only after local identification of the
A 19-year-old man who had a history of asthma and resultant steroid treatment presented with sternal pain, fever, and fatigue in December 2009. Physical examination revealed a solid sternal extramedullary mass with local erythema, and the patient reported persistent pain. Neither trauma nor infection was reported. Magnetic resonance imaging (MRI) scans showed edema, periosteal reaction, and irregular signals from the bone marrow (Fig. 1). Antibiotic therapy was initiated because of the putative diagnosis of osteomyelitis. However, the pain persisted, thereby prompting reevaluation. The blood cell count was normal: hemoglobin, 15.9 g/dL; red blood cells, 5.5×1012/L; white blood cells, 7.4×109/L (with neutrophils, 3.2×109/L; eosinophils, 0.4×109/L; lymphocytes, 2.9×109/L; and monocytes, 0.4×109/L); and platelets, 202×109/L. In March 2010, the patient underwent surgery. A lobulated tumor that was stuck to the sternum but did not infiltrate it was removed during surgery. Complementary biopsies of the sternum and the peri-sternal tissue were performed. Histopathological examination of the tissue revealed an infiltration by myeloid cells, of which some cells had a promyelocytic morphology and contained azurophilic granulations and Auer rods. The immunophenotypic study was limited to specific antigens, but most of the cells did not express CD34. Cytogenetic studies of the
The problems related to the diagnosis and prognosis of MS can be attributed to its clinical mode of appearance. Since most patients never develop systemic disease, a correct and timely diagnosis may be rather difficult. Diagnosis is easier when MS is concomitant with leukemia [5-7], or when MS develops in patients previously treated for leukemia [8]. Diagnosis is more problematic when MS precedes acute leukemia. Cases of MS are often misdiagnosed as other neoplasms, mainly as malignant lymphomas. In the cases of APL, extramedullary disease is generally observed at the time of relapse and presents as a solitary localization or in association with the hematological features of the disease. The occurrence of extramedullary disease in patients with APL has been increasing since the introduction of all-
The presence of an isolated localization is much more uncommon in APL at the time of initial diagnosis. In rare cases, MS originates in the subperiosteal regions of the bones (ribs, sternum, or orbital bones) several months before the clinical detection of leukemia, and subsequently spreads to soft tissues. MS can also originate in other regions, such as the spinal epidural space, thereby showing signs and symptoms of spinal compression. PS may have totally gone undetected on initial diagnosis [10-12], and it may actually be diagnosed later with bone marrow infiltration by promyelocytic malignant cells at the time of relapse. PS may be correctly diagnosed initially by identifying the specific translocation and/or molecular rearrangement in the tumor cells and also by assessing the molecular hematological features, even though the bone marrow aspirate does not show any blastic infiltration [13, 14] (Table 1).
A diagnosis of MS is considered as a possible sign of APL. In this report, we report a rare case of MS; diagnosis of the disease was made after surgical intervention and cytogenetic analysis of the tumor cells. Correct and timely diagnosis is a prerequisite for optimal treatment and outcome. Therefore, establishing an accurate histological diagnosis is a fundamental requirement. The optimal management of patients with this form of APL has not been critically assessed. In some MS cases, the patients do not show any clear leukemic transformation in the later stages. However, the consensus is that all patients showing MS should be treated with intensive chemotherapy [15]. When left untreated, most cases progress to overt leukemia; a majority of the cases show AML transformation in about 10 months [10-12, 14]. Similarly, therapy restricted to local procedures increases the risk of systemic disease. Radiation and intensive systemic therapy may therefore certainly be considered [15], and treatment might involve the same chemotherapeutic schedules that are generally used in leukemia with a "classic" presentation. The standard treatment for APL consists of ATRA combined with conventional chemotherapy [4]. Our patient could not be included into the French APL-2006 clinical trial, but he was treated similarly with an induction course combining ATRA with chemotherapy followed by 2 courses of consolidation chemotherapy and a 2-year maintenance therapy. Furthermore, complementary sternal irradiation was scheduled between the consolidation and maintenance phases.
Magnetic resonance imaging of the sternum. Sagittal-weighted images
The reciprocal and balanced t(15;21), involving the
Table 1 Published cases of isolated myeloid sarcoma in APL at diagnosis.
Abbreviations: APL, acute promyelocytic leukemia; ATRA, all-
Korean J Hematol 2011; 46(1): 52-56
Published online March 31, 2011 https://doi.org/10.5045/kjh.2011.46.1.52
Copyright © The Korean Society of Hematology.
Xavier Thomas*, and Youcef Chelghoum
Department of Hematology, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
Correspondence to: Correspondence to Xavier Thomas, M.D., Ph.D. Department of Hematology, Hôpital Edouard Herriot, 5 place d'Arsonval, 69437 Lyon, France. Tel: +33-4-72117395, Fax: +33-1-72117404, xavier.thomas@chu-lyon.fr
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
This study reports a case of promyelocytic sarcoma that developed as a solitary sternal mass without any clinical evidence of acute promyelocytic leukemia. The case presented the diagnostic difficulties common to all aleukemic granulocytic sarcomas, and diagnosis was made possible by local identification of the
Keywords: Promyelocytic sarcoma,
Myeloid sarcoma (MS) (initially known as granulocytic sarcoma, and then chloroma) is a rare localized tumor composed of immature granulocytic precursor cells. This extramedullary tumor can affect any organ and can present before, in concurrence with, or after the diagnosis of acute myeloid leukemia (AML) or other myeloproliferative disorders, or as a manifestation of disease relapse [1]. The World Health Organization (WHO) classification recognizes different variants of this tumor based on the predominant cell type and the degree of cell maturation [2]. Extramedullary disease is associated with every cytological subset of French-American-British (FAB) individuals; the disease is frequently found in patients with a monocytic component (FAB M4 and M5), but it is seldom found in patients with acute promyelocytic leukemia (APL) [3].
APL accounts for approximately 10% of AML cases, and is characterized by a favorable clinical outcome [4]. Several types of extramedullary leukemic infiltrates have been reported in APL patients; the skin (leukemia cutis) and the central nervous system (CNS) are the preferred sites of extramedullary involvement in APL. Among primary extramedullary localizations, chloroma is an uncommon pathognomonic lesion, and it is more appropriately termed as promyelocytic sarcoma (PS) when it occurs in this subset of leukemia.
In this report, we present a case of PS that presented as a solitary sternal mass without any clinical evidence of hemopathy. A conclusive diagnosis of PS was made only after local identification of the
A 19-year-old man who had a history of asthma and resultant steroid treatment presented with sternal pain, fever, and fatigue in December 2009. Physical examination revealed a solid sternal extramedullary mass with local erythema, and the patient reported persistent pain. Neither trauma nor infection was reported. Magnetic resonance imaging (MRI) scans showed edema, periosteal reaction, and irregular signals from the bone marrow (Fig. 1). Antibiotic therapy was initiated because of the putative diagnosis of osteomyelitis. However, the pain persisted, thereby prompting reevaluation. The blood cell count was normal: hemoglobin, 15.9 g/dL; red blood cells, 5.5×1012/L; white blood cells, 7.4×109/L (with neutrophils, 3.2×109/L; eosinophils, 0.4×109/L; lymphocytes, 2.9×109/L; and monocytes, 0.4×109/L); and platelets, 202×109/L. In March 2010, the patient underwent surgery. A lobulated tumor that was stuck to the sternum but did not infiltrate it was removed during surgery. Complementary biopsies of the sternum and the peri-sternal tissue were performed. Histopathological examination of the tissue revealed an infiltration by myeloid cells, of which some cells had a promyelocytic morphology and contained azurophilic granulations and Auer rods. The immunophenotypic study was limited to specific antigens, but most of the cells did not express CD34. Cytogenetic studies of the
The problems related to the diagnosis and prognosis of MS can be attributed to its clinical mode of appearance. Since most patients never develop systemic disease, a correct and timely diagnosis may be rather difficult. Diagnosis is easier when MS is concomitant with leukemia [5-7], or when MS develops in patients previously treated for leukemia [8]. Diagnosis is more problematic when MS precedes acute leukemia. Cases of MS are often misdiagnosed as other neoplasms, mainly as malignant lymphomas. In the cases of APL, extramedullary disease is generally observed at the time of relapse and presents as a solitary localization or in association with the hematological features of the disease. The occurrence of extramedullary disease in patients with APL has been increasing since the introduction of all-
The presence of an isolated localization is much more uncommon in APL at the time of initial diagnosis. In rare cases, MS originates in the subperiosteal regions of the bones (ribs, sternum, or orbital bones) several months before the clinical detection of leukemia, and subsequently spreads to soft tissues. MS can also originate in other regions, such as the spinal epidural space, thereby showing signs and symptoms of spinal compression. PS may have totally gone undetected on initial diagnosis [10-12], and it may actually be diagnosed later with bone marrow infiltration by promyelocytic malignant cells at the time of relapse. PS may be correctly diagnosed initially by identifying the specific translocation and/or molecular rearrangement in the tumor cells and also by assessing the molecular hematological features, even though the bone marrow aspirate does not show any blastic infiltration [13, 14] (Table 1).
A diagnosis of MS is considered as a possible sign of APL. In this report, we report a rare case of MS; diagnosis of the disease was made after surgical intervention and cytogenetic analysis of the tumor cells. Correct and timely diagnosis is a prerequisite for optimal treatment and outcome. Therefore, establishing an accurate histological diagnosis is a fundamental requirement. The optimal management of patients with this form of APL has not been critically assessed. In some MS cases, the patients do not show any clear leukemic transformation in the later stages. However, the consensus is that all patients showing MS should be treated with intensive chemotherapy [15]. When left untreated, most cases progress to overt leukemia; a majority of the cases show AML transformation in about 10 months [10-12, 14]. Similarly, therapy restricted to local procedures increases the risk of systemic disease. Radiation and intensive systemic therapy may therefore certainly be considered [15], and treatment might involve the same chemotherapeutic schedules that are generally used in leukemia with a "classic" presentation. The standard treatment for APL consists of ATRA combined with conventional chemotherapy [4]. Our patient could not be included into the French APL-2006 clinical trial, but he was treated similarly with an induction course combining ATRA with chemotherapy followed by 2 courses of consolidation chemotherapy and a 2-year maintenance therapy. Furthermore, complementary sternal irradiation was scheduled between the consolidation and maintenance phases.
Magnetic resonance imaging of the sternum. Sagittal-weighted images
The reciprocal and balanced t(15;21), involving the
Table 1 . Published cases of isolated myeloid sarcoma in APL at diagnosis..
Abbreviations: APL, acute promyelocytic leukemia; ATRA, all-
Gi-June Min, Byung-Sik Cho, Sung-Soo Park, Silvia Park, Young-Woo Jeon, Seung-Ah Yahng, Seung-Hawn Shin, Jae-Ho Yoon, Sung-Eun Lee, Ki-Seong Eom, Yoo-Jin Kim, Seok Lee, Chang-Ki Min, Seok-Goo Cho, Jong Wook Lee, Hee-Je Kim
Blood Res 2022; 57(3): 197-206Myoung-Hyun Kim, Cheol-Soon Choi, Jae Wook Lee, Pil-Sang Jang, Nak-Gyun Chung, Bin Cho, Dae-Chul Jeong, and Hack-Ki Kim
Korean J Hematol 2010; 45(4): 236-241Sunhyun Ahn, Joon Seong Park, Seong Hyun Jeong, Hyun Woo Lee, Jun Eun Park, Mi Hyang Kim, Yang Soo Kim, Ho Sup Lee, Tae Sung Park, Eunkyoung You, Insoo Rheem, Joowon Park, JI Young Huh, Myung Seo Kang, and Sung Ran Cho
Blood Res 2013; 48(1): 31-34
Magnetic resonance imaging of the sternum. Sagittal-weighted images
The reciprocal and balanced t(15;21), involving the