Myeloid sarcoma causing airway obstruction Aaron R. Belknap, MD, and John R. Krause, MD
Myeloid sarcoma is an extramedullary collection of blasts of the myeloid series that partially or totally effaces the architecture of the tissue in which it is found. These tumors have been described in many sites of the body, but the skin, lymph nodes, gastrointestinal tract, bone, soft tissue, and testes are most common. They can arise in a patient following the diagnosis of acute myeloid leukemia, but they may also be precursors of leukemia and should be considered diagnostic for acute myeloid leukemia. The differential diagnosis of this neoplasm includes malignant lymphoma, with which it is often mistaken, leading to diagnostic and therapeutic delays. We present the case of an 84-year-old African American man with a history of renal disease secondary to hypertension and coronary artery disease without any prior history of malignancies who presented with airway obstruction. He was diagnosed with a myeloid sarcoma of the mediastinum compressing his trachea.
M
yeloid sarcoma, also known as granulocytic sarcoma, extramedullary myeloid leukemia, or chloroma, is the soft tissue equivalent of acute myeloid leukemia. It is found in less than 1% of patients with acute myeloid leukemia (1), but can also be found as a precursor lesion in patients who have not been diagnosed with acute myeloid leukemia. In up to 47% of patients, myeloid sarcoma is initially misdiagnosed as malignant lymphoma (2). It is important to properly diagnose this entity because it should be treated as acute myeloid leukemia. We present the case of an 84-year-old man with no prior history of malignancies presenting with airway obstruction, initially believed to be caused by non-Hodgkin lymphoma, that was treated unsuccessfully with steroids while the biopsy was being evaluated. The biopsy of the lesion was diagnosed as a myeloid sarcoma. CASE REPORT An 84-year-old man with previous end-stage renal disease, type 2 diabetes mellitus, hypertension, and coronary artery disease presented with dyspnea that had progressively worsened over a 3-week period. The dyspnea was present at rest and worsened in the supine position. He had a mild cough with minimal sputum production. Additionally, the patient had recently noticed that his appetite had decreased and he had been losing weight. He did not have fever or night sweats. A chest computed tomography scan showed a superior mediastinal mass measuring up to 7.3 cm in greatest dimension.
Proc (Bayl Univ Med Cent) 2017;30(2):195–196
Figure 1. Computed tomography image showing compression of the trachea (arrowhead) by a soft tissue mass (arrows). A calcified left thyroid nodule (star) extended into the mass.
It entirely encased the trachea and narrowed the lumen to 4 mm at one point (Figure 1). The mass also compressed the right brachiocephalic vein and the upper third of the esophagus. The patient’s white blood cell count was 2.2 K/μL; hemoglobin, 10.4 g/dL; hematocrit, 33.3%; and platelets, 81 K/μL. A biopsy of the mediastinal mass disclosed large atypical discohesive cells percolating through a background of sclerotic tissue. Most cells had prominent nucleoli, and a few cells had small indistinct granules. On initial morphologic assessment, the mass was most likely a lymphocytic neoplasm, and a diffuse large cell lymphoma was considered. A battery of immunostains (CD3, CD20, CD10, BCL-1, BCL-2, BCL-6, Mum-1, cMyc, Ki-67, EBER, CD34, CD79a, CD4, and CD30) was performed, but of these stains only BCL-2 (90%), CD34 (100%), and Ki-67 (40%– 45%) were positive. Additional stains (pancytokeratin, TdT, myeloperoxidase, CD15, CD68, and CD33) were performed to From the Department of Pathology (Belknap) and Division of Hematopathology (Krause), Baylor University Medical Center at Dallas and the Charles A. Sammons Cancer Center, Dallas, Texas. Corresponding author: Aaron R. Belknap, MD, Department of Pathology, Baylor University Medical Center at Dallas, 3500 Gaston Avenue, Dallas, TX 75246 (e-mail: [email protected]). 195
involvement to airway obstruction from a mediastinal mass (6, 7). Due to the broad range of symptoms that can be caused by primary myeloid sarcoma, a high index of suspicion is necessary to avoid missing or delaying this diagnosis. These lesions often are initially diagnosed or worked up and treated as a lymphoma. In our case, the patient initially was treated with high-dose steroids for presumed lymphoma while the tissue was being examined by pathology. The first suspicion that this might be a myeloid sarcoma came Figure 2. (a) Hematoxylin and eosin stain showing cells with prominent nucleoli. (b) Myeloperoxidase immunohistochemical when the initial round of immunostain showing positive-staining cells. histochemical stains, which were designed to identify a high-grade lymphoma, failed to establish that diagnosis. On the day of marrow elucidate the origin of the tumor cells, and myeloperoxidase, TdT, biopsy, the clinical team visited pathology to discuss the failure of CD15, and CD33 were positive (Figure 2). With this immunothe patient to respond to high-dose steroids. Further immunohisstaining profile, the tumor was diagnosed as a myeloid sarcoma. tochemical stains for myeloid sarcoma were ordered and the correct The patient then had a bone marrow biopsy that showed 25% diagnosis was established. It is important to distinguish between a cellularity with trilineage hematopoiesis and only 1% myeloblasts large-cell lymphoma and a myeloid sarcoma for treatment purposes. by morphology, 1% to 2% by CD34 immunohistochemistry, Acute myeloid sarcomas are generally treated in the same and no evidence of a high-grade hematopoietic neoplasm by flow manner as acute myeloid leukemia. Overall prognosis is extremecytometry. Mild megakaryocytic dyspoiesis was identified. A myely poor, with a median survival of 9.5 months; this includes both lodysplastic syndrome fluorescence in situ hybridization study primary and secondary myeloid sarcomas (8). One older series on the patient’s bone marrow came back positive for deletions of of 90 patients with primary myeloid sarcoma showed a median chromosomes 5q and 20q in 74% and 22% of the cells examined, survival of 22 months (9). Due to the numerous locations in respectively, which is sufficient in the context of refractory cytowhich myeloid sarcoma can present, it is likely that the prognosis penia for a presumptive diagnosis of myelodysplastic syndrome, is largely dependent on the location and symptoms. even in the absence of overt morphologic evidence. The patient remained intubated without any clinical im1. Dores GM, Devesa SS, Curtis RE, Linet MS, Morton LM. Acute leukemia provement following high-dose corticosteroid therapy. Due to incidence and patient survival among children and adults in the United the patient’s multiple comorbidities and age, chemotherapy was States, 2001-2007. Blood 2012;119(1):34–43. considered to be detrimental to the patient. By request of the 2. Yamauchi K, Yasuda M. Comparison in treatments of nonleukemic family, he was transferred to the local Veteran’s Administration hosgranulocytic sarcoma: report of two cases and a review of 72 cases in the pital, intubated, and sedated without plans for further treatment. literature. Cancer 2002;94(6):1739–1746. a
b
3.
DISCUSSION This patient developed a myeloid sarcoma likely arising in a lymph node or the soft tissue of the mediastinum leading to immediately life-threatening airway obstruction. Myeloid sarcoma is an extremely aggressive extramedullary manifestation of acute myeloid leukemia. Primary myeloid sarcoma, defined as myeloid sarcoma without evidence of acute myeloid leukemia in the bone marrow, is rare (3). It is generally considered a precursor lesion for acute myeloid leukemia; one series prior to the advent of effective chemotherapy showed 29 of 30 cases progressing to overt acute myeloid leukemia in a median time of 7 months (4). Granulocytic sarcomas have been described in myelodysplastic and myeloproliferative disorders (5). Previous case reports of myeloid sarcomas described compression-related symptoms as the initial presentation. The symptoms can vary dramatically based on the site of presentation, ranging from back pain and bilateral leg weakness from spinal cord compression to intestinal obstruction and appendicitis from mesenteric 196
4.
5.
6.
7.
8. 9.
Byrd JC, Edenfield WJ, Shields DJ, Dawson NA. Extramedullary myeloid cell tumors in acute nonlymphocytic leukemia: a clinical review. J Clin Oncol 1995;13(7):1800–1816. Chan JK, Lau WH, Saw D. Extradural granulocytic sarcoma of the spine: a unique case of long survival after local therapy. Am J Hematol 1986;22(4):439–441. Shah C, Gopaluni S, Husain J, Rajan A, Shah H. Granulocytic sarcoma in a patient with myelodysplastic syndrome. Oncology (Williston Park) 2008;22(8):950–952. Kyaw TZ, Maniam JA, Bee PC, Chin EF, Nadarajan VS, Shanmugam H, Kadir KA. Myeloid sarcoma: an unusual presentation of acute promyelocytic leukemia causing spinal cord compression. Turk J Haematol 2012;29(3):278–282. McCusker S, Trangucci J, Frederick W, Richi AA, Abunnaja S. Primary myeloid sarcoma of the small intestine: case report and literature review. Conn Med 2016;80(6):349–352. Paydas S, Zorludemir S, Ergin M. Granulocytic sarcoma: 32 cases and review of the literature. Leuk Lymphoma 2006;47(12):2527–2541. Imrie KR, Kovacs MJ, Selby D, Lipton J, Patterson BJ, Pantalony D, Poldre P, Ngan BY, Keating A. Isolated chloroma: the effect of early antileukemic therapy. Ann Intern Med 1995;123(5):351–353.
Baylor University Medical Center Proceedings
Volume 30, Number 2
Myeloid sarcoma is an extramedullary collection of blasts of the myeloid series that partially or totally effaces the architecture of the tissue in which it is found. These tumors have been described in many sites of the body, but the skin, lymph nodes, gastrointestinal tract, bone, soft tissue, and testes are most common. They can arise in a patient following the diagnosis of acute myeloid leukemia, but they may also be precursors of leukemia and should be considered diagnostic for acute myeloid leukemia. The differential diagnosis of this neoplasm includes malignant lymphoma, with which it is often mistaken, leading to diagnostic and therapeutic delays. We present the case of an 84-year-old African American man with a history of renal disease secondary to hypertension and coronary artery disease without any prior history of malignancies who presented with airway obstruction. He was diagnosed with a myeloid sarcoma of the mediastinum compressing his trachea.
M
yeloid sarcoma, also known as granulocytic sarcoma, extramedullary myeloid leukemia, or chloroma, is the soft tissue equivalent of acute myeloid leukemia. It is found in less than 1% of patients with acute myeloid leukemia (1), but can also be found as a precursor lesion in patients who have not been diagnosed with acute myeloid leukemia. In up to 47% of patients, myeloid sarcoma is initially misdiagnosed as malignant lymphoma (2). It is important to properly diagnose this entity because it should be treated as acute myeloid leukemia. We present the case of an 84-year-old man with no prior history of malignancies presenting with airway obstruction, initially believed to be caused by non-Hodgkin lymphoma, that was treated unsuccessfully with steroids while the biopsy was being evaluated. The biopsy of the lesion was diagnosed as a myeloid sarcoma. CASE REPORT An 84-year-old man with previous end-stage renal disease, type 2 diabetes mellitus, hypertension, and coronary artery disease presented with dyspnea that had progressively worsened over a 3-week period. The dyspnea was present at rest and worsened in the supine position. He had a mild cough with minimal sputum production. Additionally, the patient had recently noticed that his appetite had decreased and he had been losing weight. He did not have fever or night sweats. A chest computed tomography scan showed a superior mediastinal mass measuring up to 7.3 cm in greatest dimension.
Proc (Bayl Univ Med Cent) 2017;30(2):195–196
Figure 1. Computed tomography image showing compression of the trachea (arrowhead) by a soft tissue mass (arrows). A calcified left thyroid nodule (star) extended into the mass.
It entirely encased the trachea and narrowed the lumen to 4 mm at one point (Figure 1). The mass also compressed the right brachiocephalic vein and the upper third of the esophagus. The patient’s white blood cell count was 2.2 K/μL; hemoglobin, 10.4 g/dL; hematocrit, 33.3%; and platelets, 81 K/μL. A biopsy of the mediastinal mass disclosed large atypical discohesive cells percolating through a background of sclerotic tissue. Most cells had prominent nucleoli, and a few cells had small indistinct granules. On initial morphologic assessment, the mass was most likely a lymphocytic neoplasm, and a diffuse large cell lymphoma was considered. A battery of immunostains (CD3, CD20, CD10, BCL-1, BCL-2, BCL-6, Mum-1, cMyc, Ki-67, EBER, CD34, CD79a, CD4, and CD30) was performed, but of these stains only BCL-2 (90%), CD34 (100%), and Ki-67 (40%– 45%) were positive. Additional stains (pancytokeratin, TdT, myeloperoxidase, CD15, CD68, and CD33) were performed to From the Department of Pathology (Belknap) and Division of Hematopathology (Krause), Baylor University Medical Center at Dallas and the Charles A. Sammons Cancer Center, Dallas, Texas. Corresponding author: Aaron R. Belknap, MD, Department of Pathology, Baylor University Medical Center at Dallas, 3500 Gaston Avenue, Dallas, TX 75246 (e-mail: [email protected]). 195
involvement to airway obstruction from a mediastinal mass (6, 7). Due to the broad range of symptoms that can be caused by primary myeloid sarcoma, a high index of suspicion is necessary to avoid missing or delaying this diagnosis. These lesions often are initially diagnosed or worked up and treated as a lymphoma. In our case, the patient initially was treated with high-dose steroids for presumed lymphoma while the tissue was being examined by pathology. The first suspicion that this might be a myeloid sarcoma came Figure 2. (a) Hematoxylin and eosin stain showing cells with prominent nucleoli. (b) Myeloperoxidase immunohistochemical when the initial round of immunostain showing positive-staining cells. histochemical stains, which were designed to identify a high-grade lymphoma, failed to establish that diagnosis. On the day of marrow elucidate the origin of the tumor cells, and myeloperoxidase, TdT, biopsy, the clinical team visited pathology to discuss the failure of CD15, and CD33 were positive (Figure 2). With this immunothe patient to respond to high-dose steroids. Further immunohisstaining profile, the tumor was diagnosed as a myeloid sarcoma. tochemical stains for myeloid sarcoma were ordered and the correct The patient then had a bone marrow biopsy that showed 25% diagnosis was established. It is important to distinguish between a cellularity with trilineage hematopoiesis and only 1% myeloblasts large-cell lymphoma and a myeloid sarcoma for treatment purposes. by morphology, 1% to 2% by CD34 immunohistochemistry, Acute myeloid sarcomas are generally treated in the same and no evidence of a high-grade hematopoietic neoplasm by flow manner as acute myeloid leukemia. Overall prognosis is extremecytometry. Mild megakaryocytic dyspoiesis was identified. A myely poor, with a median survival of 9.5 months; this includes both lodysplastic syndrome fluorescence in situ hybridization study primary and secondary myeloid sarcomas (8). One older series on the patient’s bone marrow came back positive for deletions of of 90 patients with primary myeloid sarcoma showed a median chromosomes 5q and 20q in 74% and 22% of the cells examined, survival of 22 months (9). Due to the numerous locations in respectively, which is sufficient in the context of refractory cytowhich myeloid sarcoma can present, it is likely that the prognosis penia for a presumptive diagnosis of myelodysplastic syndrome, is largely dependent on the location and symptoms. even in the absence of overt morphologic evidence. The patient remained intubated without any clinical im1. Dores GM, Devesa SS, Curtis RE, Linet MS, Morton LM. Acute leukemia provement following high-dose corticosteroid therapy. Due to incidence and patient survival among children and adults in the United the patient’s multiple comorbidities and age, chemotherapy was States, 2001-2007. Blood 2012;119(1):34–43. considered to be detrimental to the patient. By request of the 2. Yamauchi K, Yasuda M. Comparison in treatments of nonleukemic family, he was transferred to the local Veteran’s Administration hosgranulocytic sarcoma: report of two cases and a review of 72 cases in the pital, intubated, and sedated without plans for further treatment. literature. Cancer 2002;94(6):1739–1746. a
b
3.
DISCUSSION This patient developed a myeloid sarcoma likely arising in a lymph node or the soft tissue of the mediastinum leading to immediately life-threatening airway obstruction. Myeloid sarcoma is an extremely aggressive extramedullary manifestation of acute myeloid leukemia. Primary myeloid sarcoma, defined as myeloid sarcoma without evidence of acute myeloid leukemia in the bone marrow, is rare (3). It is generally considered a precursor lesion for acute myeloid leukemia; one series prior to the advent of effective chemotherapy showed 29 of 30 cases progressing to overt acute myeloid leukemia in a median time of 7 months (4). Granulocytic sarcomas have been described in myelodysplastic and myeloproliferative disorders (5). Previous case reports of myeloid sarcomas described compression-related symptoms as the initial presentation. The symptoms can vary dramatically based on the site of presentation, ranging from back pain and bilateral leg weakness from spinal cord compression to intestinal obstruction and appendicitis from mesenteric 196
4.
5.
6.
7.
8. 9.
Byrd JC, Edenfield WJ, Shields DJ, Dawson NA. Extramedullary myeloid cell tumors in acute nonlymphocytic leukemia: a clinical review. J Clin Oncol 1995;13(7):1800–1816. Chan JK, Lau WH, Saw D. Extradural granulocytic sarcoma of the spine: a unique case of long survival after local therapy. Am J Hematol 1986;22(4):439–441. Shah C, Gopaluni S, Husain J, Rajan A, Shah H. Granulocytic sarcoma in a patient with myelodysplastic syndrome. Oncology (Williston Park) 2008;22(8):950–952. Kyaw TZ, Maniam JA, Bee PC, Chin EF, Nadarajan VS, Shanmugam H, Kadir KA. Myeloid sarcoma: an unusual presentation of acute promyelocytic leukemia causing spinal cord compression. Turk J Haematol 2012;29(3):278–282. McCusker S, Trangucci J, Frederick W, Richi AA, Abunnaja S. Primary myeloid sarcoma of the small intestine: case report and literature review. Conn Med 2016;80(6):349–352. Paydas S, Zorludemir S, Ergin M. Granulocytic sarcoma: 32 cases and review of the literature. Leuk Lymphoma 2006;47(12):2527–2541. Imrie KR, Kovacs MJ, Selby D, Lipton J, Patterson BJ, Pantalony D, Poldre P, Ngan BY, Keating A. Isolated chloroma: the effect of early antileukemic therapy. Ann Intern Med 1995;123(5):351–353.
Baylor University Medical Center Proceedings
Volume 30, Number 2
