CASE REPORT
The Clinical Respiratory Journal
Myeloid sarcoma: an unusual presentation for acute tracheal stenosis Eitan Podgaetz1, Mark Kriegsmann2, Erhan H. Dincer3 and James S. Allan4 1 2 3 4
Department of Surgery, Section of Thoracic Surgery, University of Minnesota, Minneapolis, MN, USA MVZ for Histology, Cytology and Molecular Diagnostics, Institute of Molecular Pathology, Trier, Germany Division of Pulmonary Medicine and Critical Care, University of Minnesota, Minneapolis, MN, USA Division of Thoracic Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
Abstract Background and Aims: Extramedullary involvement of acute myelogenous leukemia (AML) is rare and has been reported under the terms myeloid sarcoma (MS), granulocytic sarcoma, chloroma, extramedullary acute myeloid leukemia, myeloblastoma and myelosarcoma. The most common extramedullary involvement includes soft tissues and lymph nodes, but it may arise in different sites of the body. There are only very few reports about MS in the pulmonary system, and involvement of the trachea is extremely rare. Methods: This is the first report of initial presentation of MS by severe acute tracheal stenosis. Results: After failed tracheal dilatation, a tracheostomy was performed where tracheal tissue was submitted for pathology. Histology of the tracheal biopsy and bone marrow revealed AML. The patient was subsequently referred to our oncology service for further management. Conclusion: Myeloid sarcoma should be part of the differential for acute tracheal stenosis. Please cite this paper as: Podgaetz E, Kriegsmann M, Dincer HE and Allan JS. Myeloid sarcoma: an unusual presentation for acute tracheal stenosis. Clin Respir J 2015; ••: ••–••. DOI:10.1111/crj.12287.
Key words airway obstruction – AML – chloroma – ganulocytic sarcoma – myeloid sarcoma – tracheal stenosis Correspondence Eitan Podgaetz, MD, MPH, Division of Thoracic Surgery, University of Minnesota, 55 Fruit Street, Blake 1570, Boston, 02114 Minnesota, USA. Tel: 617 724 1103 Fax: 612-6259657 email: [email protected] Received: 10 January 2015 Accepted: 01 March 2015 DOI:10.1111/crj.12287 Authorship and contributorship Eitan Podgaetz designed and performed the study, discussed and analyzed finding, and wrote the paper. Mark Kriegsmann designed and performed the study, discussed and analyzed findings and worte the paper. Erhan H. Dincer discussed and analyzed findings. James S. Allan discussed and analyzed findings. Ethics This study has been reviewed by the appropriate ethics committee and been performed in accordance with the ethical standards laid down in the Declaration of Helsinki. Conflict of interest The authors have stated explicitly that there are no conflicts of interest in connection with this article.
Introduction Myeloid sarcoma (MS), also referred to as granulocytic sarcoma, chloroma, extramedullary acute myeloid leukemia, myeloblastoma and myelosarcoma, has an inci-
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 John Wiley & Sons Ltd
dence of 2.5%–9.1% in patients with acute myelogenous leukemia (AML) (1). The most common extramedullary sites of involvement are the bones, soft tissues and lymph nodes (2–4). Lung involvement is rare, and patients presenting with tracheal stenosis are unique (5).
1
Myeloid sarcoma presenting as tracheal stenosis
Case report A 62-year-old nonsmoking woman with a past medical history significant for total thyroidectomy for follicular thyroid carcinoma 8 years previously and total neck irradiation 50 years ago for what she recalls as adenoid disease was referred from an outside hospital with acute stridor. She described progressing dyspnea, wheezing and hoarseness for 4 weeks and was originally thought to have laryngitis for which she received a course of azithomycin. Her condition acutely deteriorated 4 days prior to presentation. Her primary care physician prescribed prednisone and inhalers. Because her symptoms continued to worsen, she presented to an outside hospital with stridor, where she received intravenous (IV) solumedrol and epinephrine with minimal relief. A flexible laryngoscopy performed by an otorhinolaryngologist showed severe subglottic stenosis. Chest X-ray demonstrated tracheal narrowing at the level of the fifth cervical vertebrae (Fig. 1). She was urgently transferred to our institution from one otolaryngologist (ENT) service to our ENT service. Once our ENT service realized that the obstruction was subglottic, the thoracic surgical service was consulted for further evaluation. In the emergency department, her temperature was 37.5°C, sinus rhythm at 89 beats/min, respiratory rate of 20 breaths/min and oxygen saturation of 97% on 4 L by nasal cannula.
Podgaetz et al.
Her breathing was labored with loud inspiratory and expiratory stridor and high-pitched wheezing over the trachea. She used accessory muscles to breath and was unable to phonate. Her physical examination was otherwise unrevealing. Her sole home medication was levothyroxine. She was immediately placed on 80/20% heliox with clear symptomatic benefit. Laboratory studies showed an elevated white blood cell count of 78.4 × 109/L with 25% blasts, hemoglobin at 9.8 g/dL and platelets at 107 × 109/L. Antinuclear antibodies and anti-neutrophil cytoplasmic antibodies were negative. The patient was taken emergently to the operating room to perform flexible and rigid bronchoscopy and attempt dilation. Many operative and anesthetic considerations occurred to be able to secure optimal operative conditions. Our main concern was that soon after anesthetic induction, the patient would lose muscle tone and we would lose the ability to ventilate her effectively. We established adequate IV access and arterial line while awake. Once the team and all equipment were ready (flexible and rigid bronchoscopes, open tracheostomy tray and jet ventilation), the patient was anesthetized and rigid bronchsocopy performed. A tight sublgottic stenosis with an opening of 4 mm in antero-posterior diameter and 1–2 mm in lateral direction was found. The total length of the stenosis was approximately 1 cm, and it appeared only to involve the subglottic
Figure 1. X-rays of the trachea. Detail of (A) postero-anterior and lateral (B) chest X-ray demonstrates a 4-cm subglottic narrowing at the level of C5.
2
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 John Wiley & Sons Ltd
Podgaetz et al.
Myeloid sarcoma presenting as tracheal stenosis
Figure 2. Histology. Bone marrow biopsy shows (A) increased cellularity and (B) large cells with indented nuclei, inconspicuous nucleoli and moderate cytoplasm consistent with blasts. (C,D) Tracheal biopsy specimen demonstrates a dense, nodular and diffuse infiltrate of primitive-appearing cells with features suggesting monocytic differentiation. Hematoxylin and eosin stain. Original magnification: (A) ×100, (B) ×400, (C) ×100, (D) ×400.
larynx right to the level of the cricoid. The subglottic stenosis was serially dilated with Montgomery dilators without much benefit. The stricture appeared to be rigid and fixed. Given the repeated manipulation of the airway and worsening subglottic swelling, the patient became very hard to ventilate and commenced to desaturate down to 60%. We elected to perform cricothyrotomy, which was intentionally performed high, going through the diseased area in order to establish a safe airway and preserve normal healthy trachea. Tracheal biopsies taken during the procedure showed findings consistent with MS (Fig. 2). The patient recovered well from the procedure and was referred to our hematology/oncology service, which performed a bone marrow biopsy showing a cellularity of approximatively 95% with an increased fraction of immature monocytes with fine chromatin (Fig. 2). Immunophenotyping revealed 11% myeloid blasts (CD33dim+, CD13+, MPO−/+, CD117+, CD34−, CD14+/−, HLA-DR+, CD11c+, CD64+, CD7+), 2% polyclonal B cells, 5% CD3+ T cells and 2% NK cells. These findings were consistent with AML. Giemsa chromosomic banding banding and fluorescence in situ hybridization demonstrated cytogenetics (t1;14) (q21:31) aberrations in 18/20 metaphases and no IgH rearrangement. Final pathological classification was acute myeloid leukemia with mutated NPM1 and FLT3 ITD mutation. She then received ‘7 + 3’ (cytarabine + idarubicin) chemotherapy with good response and was dis-
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 John Wiley & Sons Ltd
charged home. She developed a skin rash that proved to be leukemia cutis, and her chemotherapy regimen was intensified to 6 days of intermediate dosecytarabine with mitoxantrone. Given a magnetic resonance image showing dural enhancement and lumbar puncture (LP) with AML cells, she also received intrathecal (IT)-chemotherapy. She had repeated LPs with IT-chemo until resolution. After her complete response was verified, she underwent intensity unrelated donor stem cell transplant and is now on sorafenib maintenance 282 days after initial presentation. She was decannulated and is now on regular bronchoscopic surveillance for her residual scar-like stenosis.
Discussion Acute stridor in an otherwise healthy individual (nonasthmatic) can be attributed to various causes. The most common etiologies of tracheal stenosis are idiopathic, postintubation tracheal stenosis and primary tracheal neoplasms. Secondary tracheal neoplasms can also present with an acute airway. Establishing and maintaining a secure airway are paramount in managing these patients. Our patient clearly had stridor but was still communicative and was able to ventilate albeit with some difficulties. While waiting for the operating room setup, we commonly employ heliox in an 80/20% mix. Helium 3
Myeloid sarcoma presenting as tracheal stenosis
density is less than nitrogen’s, so at any given gas flow, there is less turbulence, hence lowering airway resistance and reducing work of breathing, which was the case for our patient. We believe that this is an important part in the management of these types of complicated patients. After endoscopic tracheal evaluation revealed an extremely tight and recalcitrant stenosis despite appropriate dilation attempts, we believe that her airway became more swollen given the manipulation; she had to evaluate this at two different institutions. When deciding to perform a surgical airway, it is of utmost importance to plan the location of the tracheostomy/cricothyrotomy with aims first to establish a safe airway and second to preserve normal healthy trachea in case the patient requires future tracheal resection and reconstruction as definitive management. First described by Burns in 1811 (1, 2, 4), MS, also known as granulocytic sarcoma, chloroma, extramedullary acute myeloid leukemia, myeloblastoma and myelosarcoma, was found to be a rare neoplastic lesion characterized by immature cells of the myeloid lineage (2). MS develops in a variety of organs. The most common sites are bone, soft tissue adjacent to bone and lymph nodes, but any site may be affected (2–5). However, pulmonary manifestation is very rare, and there is only one case report describing tracheal involvement in a 69-year-old man with MS (5). The tumor does not have age or gender predominance. It may be encountered isolated or in association with hematologic diseases such as acute myeloid leukemia, chronic lymphocytic leukemia, myeloid dysplastic syndrome or myeloproliferative disorders. Case studies have found a relationship between MS and AML in 40% of patients (2, 3). It may be the first clinical presentation of AML, preceded by disease in the bone marrow in months or years, or it may represent a relapse from previously treated AML in remission (4). Whereas patients with acute leukemia and bone marrow infiltration often present with anemia, thrombocytopenia and neutropenia, the clinical presentation of extramedullary involvement is nonspecific and highly depends on the impaired organ. Jiang et al. reported cough, hemoptysis and exertional dyspnea, which are the most common symptoms in patients with primary tracheal tumors (5). Furthermore, dyspnea may result from secondary tracheal compression by enlarged lymph nodes or
4
Podgaetz et al.
anterior mediastinal masses, which has been described in patients with leukemia. The trachea may be involved in other hematologic disorders such as non-Hodgkins lymphoma (6), Hodgkins lymphoma (7) or chronic lymphatic leukemia (8); however, airway obstruction as a presenting feature of MS or acute leukemia is highly unusual (5). Histologically, MS consists of immature cells of the myelocytic lineage and may be divided into three subtypes: blastic type, momoblastic/myelomonocytic type and micellous (2). MS of the trachea is unusual, and the histological morphology in hematoxylin and eosin sections may mimic malignant lymphoma or undifferentiated carcinoma. Therefore, the application of histochemical and immunohistochemical stains are mandatory to establish the correct diagnosis. Key markers include CD68/KP1, myeloperoxidase, CD117, CD99, CD68/PG-M1, lysozym, CD43. However, the immunohistochemical spectrum in MS may be broad, and other antigens that may be positive are CD34, terminal deoxynucleotidyl transferase, CD56, CD61/linker of activated T lymphocyte/factor VIII–related antigen, CD30, alpha1-antitrypsin, alpha1-antichymotrypsin, glycophorin A and CD4 (2, 4). It is recommended to perform a complete blood count, a peripheral blood smear and a bone marrow biopsy to search for an underlying hematological disease, because it has been shown that isolated MS is associated with improved survival compared to MS with bone marrow involvement (1). MS is generally considered an additional poor prognostic factor in the evaluation of AML (1, 2). The optimal treatment of MS must be individually tailored and is still matter of debate. It includes chemotherapy and radiation. Additionally, allogenic or autologous bone marrow transplantation should be considered in MS with associated AML, especially in otherwise healthy patients (1). The remote history of radiation therapy 50 years ago in this patient raises the possibility of a therapy-related acute myeloid leukemia. The fate of the tracheal stenosis after chemotherapy cannot be predicted. Although complete resolution of the tracheal disease is possible, the patient may ultimately require tracheal resection and reconstruction. Repeat bronchoscopic surveillance is scheduled in future dates. In summary, we report the first case of acute tracheal stenosis secondary to MS as an initial presentation of AML. Besides epithelial neoplasms, lymphoproliferative disorders or tumors of the myeloid system may
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 John Wiley & Sons Ltd
Podgaetz et al.
cause tracheal stenosis and should be included in differential diagnosis of acute stridor.
References 1. Bakst RL, Tallman MS, Douer D, Yahalom J. How I treat extramedullary acute myeloid leukemia. Blood. 2011;118: 3785–93. 2. Pileri SA, Ascani S, Cox MC, et al. Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients. Leukemia. 2007;21: 340–50. 3. Neiman RS, Barcos M, Berard C, Bonner H, Mann R, Rydell RE, Bennett JM. Granulocytic sarcoma: a clinicopathologic study of 61 biopsied cases. Cancer. 1981;48: 1426–37.
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 John Wiley & Sons Ltd
Myeloid sarcoma presenting as tracheal stenosis
4. Campidelli C, Agostinelli C, Stitson R, Pileri SA. Myeloid sarcoma: extramedullary manifestation of myeloid disorders. Am J Clin Pathol. 2009;132: 426–37. 5. Jiang J, Zhou J, Shen Y. Acute myeloblastic leukemia with initial manifestations in the central airway. J Thorac Oncol. 2009;4: 409–10. 6. Cobzeanu MD, Costinescu V, Rusu CD, Mihailovici S, Grigoras M, Miron L, Paduraru D, Arama A. Laryngotracheal non-Hodgkin’s lymphoma. Chirurgia (Bucur). 2010;105: 131–6. 7. Msaad S, Yangui I, Ketata W, Ayoub A, Ayedi H. Tracheal involvement revealing Hodgkin’s disease. A case report. Rev Pneumol Clin. 2007;63: 323–5. 8. Winkler CF, Corpus R. Tracheal obstruction in chronic lymphocytic leukemia. Chest. 1980;77: 244–5.
5
The Clinical Respiratory Journal
Myeloid sarcoma: an unusual presentation for acute tracheal stenosis Eitan Podgaetz1, Mark Kriegsmann2, Erhan H. Dincer3 and James S. Allan4 1 2 3 4
Department of Surgery, Section of Thoracic Surgery, University of Minnesota, Minneapolis, MN, USA MVZ for Histology, Cytology and Molecular Diagnostics, Institute of Molecular Pathology, Trier, Germany Division of Pulmonary Medicine and Critical Care, University of Minnesota, Minneapolis, MN, USA Division of Thoracic Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
Abstract Background and Aims: Extramedullary involvement of acute myelogenous leukemia (AML) is rare and has been reported under the terms myeloid sarcoma (MS), granulocytic sarcoma, chloroma, extramedullary acute myeloid leukemia, myeloblastoma and myelosarcoma. The most common extramedullary involvement includes soft tissues and lymph nodes, but it may arise in different sites of the body. There are only very few reports about MS in the pulmonary system, and involvement of the trachea is extremely rare. Methods: This is the first report of initial presentation of MS by severe acute tracheal stenosis. Results: After failed tracheal dilatation, a tracheostomy was performed where tracheal tissue was submitted for pathology. Histology of the tracheal biopsy and bone marrow revealed AML. The patient was subsequently referred to our oncology service for further management. Conclusion: Myeloid sarcoma should be part of the differential for acute tracheal stenosis. Please cite this paper as: Podgaetz E, Kriegsmann M, Dincer HE and Allan JS. Myeloid sarcoma: an unusual presentation for acute tracheal stenosis. Clin Respir J 2015; ••: ••–••. DOI:10.1111/crj.12287.
Key words airway obstruction – AML – chloroma – ganulocytic sarcoma – myeloid sarcoma – tracheal stenosis Correspondence Eitan Podgaetz, MD, MPH, Division of Thoracic Surgery, University of Minnesota, 55 Fruit Street, Blake 1570, Boston, 02114 Minnesota, USA. Tel: 617 724 1103 Fax: 612-6259657 email: [email protected] Received: 10 January 2015 Accepted: 01 March 2015 DOI:10.1111/crj.12287 Authorship and contributorship Eitan Podgaetz designed and performed the study, discussed and analyzed finding, and wrote the paper. Mark Kriegsmann designed and performed the study, discussed and analyzed findings and worte the paper. Erhan H. Dincer discussed and analyzed findings. James S. Allan discussed and analyzed findings. Ethics This study has been reviewed by the appropriate ethics committee and been performed in accordance with the ethical standards laid down in the Declaration of Helsinki. Conflict of interest The authors have stated explicitly that there are no conflicts of interest in connection with this article.
Introduction Myeloid sarcoma (MS), also referred to as granulocytic sarcoma, chloroma, extramedullary acute myeloid leukemia, myeloblastoma and myelosarcoma, has an inci-
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 John Wiley & Sons Ltd
dence of 2.5%–9.1% in patients with acute myelogenous leukemia (AML) (1). The most common extramedullary sites of involvement are the bones, soft tissues and lymph nodes (2–4). Lung involvement is rare, and patients presenting with tracheal stenosis are unique (5).
1
Myeloid sarcoma presenting as tracheal stenosis
Case report A 62-year-old nonsmoking woman with a past medical history significant for total thyroidectomy for follicular thyroid carcinoma 8 years previously and total neck irradiation 50 years ago for what she recalls as adenoid disease was referred from an outside hospital with acute stridor. She described progressing dyspnea, wheezing and hoarseness for 4 weeks and was originally thought to have laryngitis for which she received a course of azithomycin. Her condition acutely deteriorated 4 days prior to presentation. Her primary care physician prescribed prednisone and inhalers. Because her symptoms continued to worsen, she presented to an outside hospital with stridor, where she received intravenous (IV) solumedrol and epinephrine with minimal relief. A flexible laryngoscopy performed by an otorhinolaryngologist showed severe subglottic stenosis. Chest X-ray demonstrated tracheal narrowing at the level of the fifth cervical vertebrae (Fig. 1). She was urgently transferred to our institution from one otolaryngologist (ENT) service to our ENT service. Once our ENT service realized that the obstruction was subglottic, the thoracic surgical service was consulted for further evaluation. In the emergency department, her temperature was 37.5°C, sinus rhythm at 89 beats/min, respiratory rate of 20 breaths/min and oxygen saturation of 97% on 4 L by nasal cannula.
Podgaetz et al.
Her breathing was labored with loud inspiratory and expiratory stridor and high-pitched wheezing over the trachea. She used accessory muscles to breath and was unable to phonate. Her physical examination was otherwise unrevealing. Her sole home medication was levothyroxine. She was immediately placed on 80/20% heliox with clear symptomatic benefit. Laboratory studies showed an elevated white blood cell count of 78.4 × 109/L with 25% blasts, hemoglobin at 9.8 g/dL and platelets at 107 × 109/L. Antinuclear antibodies and anti-neutrophil cytoplasmic antibodies were negative. The patient was taken emergently to the operating room to perform flexible and rigid bronchoscopy and attempt dilation. Many operative and anesthetic considerations occurred to be able to secure optimal operative conditions. Our main concern was that soon after anesthetic induction, the patient would lose muscle tone and we would lose the ability to ventilate her effectively. We established adequate IV access and arterial line while awake. Once the team and all equipment were ready (flexible and rigid bronchoscopes, open tracheostomy tray and jet ventilation), the patient was anesthetized and rigid bronchsocopy performed. A tight sublgottic stenosis with an opening of 4 mm in antero-posterior diameter and 1–2 mm in lateral direction was found. The total length of the stenosis was approximately 1 cm, and it appeared only to involve the subglottic
Figure 1. X-rays of the trachea. Detail of (A) postero-anterior and lateral (B) chest X-ray demonstrates a 4-cm subglottic narrowing at the level of C5.
2
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 John Wiley & Sons Ltd
Podgaetz et al.
Myeloid sarcoma presenting as tracheal stenosis
Figure 2. Histology. Bone marrow biopsy shows (A) increased cellularity and (B) large cells with indented nuclei, inconspicuous nucleoli and moderate cytoplasm consistent with blasts. (C,D) Tracheal biopsy specimen demonstrates a dense, nodular and diffuse infiltrate of primitive-appearing cells with features suggesting monocytic differentiation. Hematoxylin and eosin stain. Original magnification: (A) ×100, (B) ×400, (C) ×100, (D) ×400.
larynx right to the level of the cricoid. The subglottic stenosis was serially dilated with Montgomery dilators without much benefit. The stricture appeared to be rigid and fixed. Given the repeated manipulation of the airway and worsening subglottic swelling, the patient became very hard to ventilate and commenced to desaturate down to 60%. We elected to perform cricothyrotomy, which was intentionally performed high, going through the diseased area in order to establish a safe airway and preserve normal healthy trachea. Tracheal biopsies taken during the procedure showed findings consistent with MS (Fig. 2). The patient recovered well from the procedure and was referred to our hematology/oncology service, which performed a bone marrow biopsy showing a cellularity of approximatively 95% with an increased fraction of immature monocytes with fine chromatin (Fig. 2). Immunophenotyping revealed 11% myeloid blasts (CD33dim+, CD13+, MPO−/+, CD117+, CD34−, CD14+/−, HLA-DR+, CD11c+, CD64+, CD7+), 2% polyclonal B cells, 5% CD3+ T cells and 2% NK cells. These findings were consistent with AML. Giemsa chromosomic banding banding and fluorescence in situ hybridization demonstrated cytogenetics (t1;14) (q21:31) aberrations in 18/20 metaphases and no IgH rearrangement. Final pathological classification was acute myeloid leukemia with mutated NPM1 and FLT3 ITD mutation. She then received ‘7 + 3’ (cytarabine + idarubicin) chemotherapy with good response and was dis-
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 John Wiley & Sons Ltd
charged home. She developed a skin rash that proved to be leukemia cutis, and her chemotherapy regimen was intensified to 6 days of intermediate dosecytarabine with mitoxantrone. Given a magnetic resonance image showing dural enhancement and lumbar puncture (LP) with AML cells, she also received intrathecal (IT)-chemotherapy. She had repeated LPs with IT-chemo until resolution. After her complete response was verified, she underwent intensity unrelated donor stem cell transplant and is now on sorafenib maintenance 282 days after initial presentation. She was decannulated and is now on regular bronchoscopic surveillance for her residual scar-like stenosis.
Discussion Acute stridor in an otherwise healthy individual (nonasthmatic) can be attributed to various causes. The most common etiologies of tracheal stenosis are idiopathic, postintubation tracheal stenosis and primary tracheal neoplasms. Secondary tracheal neoplasms can also present with an acute airway. Establishing and maintaining a secure airway are paramount in managing these patients. Our patient clearly had stridor but was still communicative and was able to ventilate albeit with some difficulties. While waiting for the operating room setup, we commonly employ heliox in an 80/20% mix. Helium 3
Myeloid sarcoma presenting as tracheal stenosis
density is less than nitrogen’s, so at any given gas flow, there is less turbulence, hence lowering airway resistance and reducing work of breathing, which was the case for our patient. We believe that this is an important part in the management of these types of complicated patients. After endoscopic tracheal evaluation revealed an extremely tight and recalcitrant stenosis despite appropriate dilation attempts, we believe that her airway became more swollen given the manipulation; she had to evaluate this at two different institutions. When deciding to perform a surgical airway, it is of utmost importance to plan the location of the tracheostomy/cricothyrotomy with aims first to establish a safe airway and second to preserve normal healthy trachea in case the patient requires future tracheal resection and reconstruction as definitive management. First described by Burns in 1811 (1, 2, 4), MS, also known as granulocytic sarcoma, chloroma, extramedullary acute myeloid leukemia, myeloblastoma and myelosarcoma, was found to be a rare neoplastic lesion characterized by immature cells of the myeloid lineage (2). MS develops in a variety of organs. The most common sites are bone, soft tissue adjacent to bone and lymph nodes, but any site may be affected (2–5). However, pulmonary manifestation is very rare, and there is only one case report describing tracheal involvement in a 69-year-old man with MS (5). The tumor does not have age or gender predominance. It may be encountered isolated or in association with hematologic diseases such as acute myeloid leukemia, chronic lymphocytic leukemia, myeloid dysplastic syndrome or myeloproliferative disorders. Case studies have found a relationship between MS and AML in 40% of patients (2, 3). It may be the first clinical presentation of AML, preceded by disease in the bone marrow in months or years, or it may represent a relapse from previously treated AML in remission (4). Whereas patients with acute leukemia and bone marrow infiltration often present with anemia, thrombocytopenia and neutropenia, the clinical presentation of extramedullary involvement is nonspecific and highly depends on the impaired organ. Jiang et al. reported cough, hemoptysis and exertional dyspnea, which are the most common symptoms in patients with primary tracheal tumors (5). Furthermore, dyspnea may result from secondary tracheal compression by enlarged lymph nodes or
4
Podgaetz et al.
anterior mediastinal masses, which has been described in patients with leukemia. The trachea may be involved in other hematologic disorders such as non-Hodgkins lymphoma (6), Hodgkins lymphoma (7) or chronic lymphatic leukemia (8); however, airway obstruction as a presenting feature of MS or acute leukemia is highly unusual (5). Histologically, MS consists of immature cells of the myelocytic lineage and may be divided into three subtypes: blastic type, momoblastic/myelomonocytic type and micellous (2). MS of the trachea is unusual, and the histological morphology in hematoxylin and eosin sections may mimic malignant lymphoma or undifferentiated carcinoma. Therefore, the application of histochemical and immunohistochemical stains are mandatory to establish the correct diagnosis. Key markers include CD68/KP1, myeloperoxidase, CD117, CD99, CD68/PG-M1, lysozym, CD43. However, the immunohistochemical spectrum in MS may be broad, and other antigens that may be positive are CD34, terminal deoxynucleotidyl transferase, CD56, CD61/linker of activated T lymphocyte/factor VIII–related antigen, CD30, alpha1-antitrypsin, alpha1-antichymotrypsin, glycophorin A and CD4 (2, 4). It is recommended to perform a complete blood count, a peripheral blood smear and a bone marrow biopsy to search for an underlying hematological disease, because it has been shown that isolated MS is associated with improved survival compared to MS with bone marrow involvement (1). MS is generally considered an additional poor prognostic factor in the evaluation of AML (1, 2). The optimal treatment of MS must be individually tailored and is still matter of debate. It includes chemotherapy and radiation. Additionally, allogenic or autologous bone marrow transplantation should be considered in MS with associated AML, especially in otherwise healthy patients (1). The remote history of radiation therapy 50 years ago in this patient raises the possibility of a therapy-related acute myeloid leukemia. The fate of the tracheal stenosis after chemotherapy cannot be predicted. Although complete resolution of the tracheal disease is possible, the patient may ultimately require tracheal resection and reconstruction. Repeat bronchoscopic surveillance is scheduled in future dates. In summary, we report the first case of acute tracheal stenosis secondary to MS as an initial presentation of AML. Besides epithelial neoplasms, lymphoproliferative disorders or tumors of the myeloid system may
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 John Wiley & Sons Ltd
Podgaetz et al.
cause tracheal stenosis and should be included in differential diagnosis of acute stridor.
References 1. Bakst RL, Tallman MS, Douer D, Yahalom J. How I treat extramedullary acute myeloid leukemia. Blood. 2011;118: 3785–93. 2. Pileri SA, Ascani S, Cox MC, et al. Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients. Leukemia. 2007;21: 340–50. 3. Neiman RS, Barcos M, Berard C, Bonner H, Mann R, Rydell RE, Bennett JM. Granulocytic sarcoma: a clinicopathologic study of 61 biopsied cases. Cancer. 1981;48: 1426–37.
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 John Wiley & Sons Ltd
Myeloid sarcoma presenting as tracheal stenosis
4. Campidelli C, Agostinelli C, Stitson R, Pileri SA. Myeloid sarcoma: extramedullary manifestation of myeloid disorders. Am J Clin Pathol. 2009;132: 426–37. 5. Jiang J, Zhou J, Shen Y. Acute myeloblastic leukemia with initial manifestations in the central airway. J Thorac Oncol. 2009;4: 409–10. 6. Cobzeanu MD, Costinescu V, Rusu CD, Mihailovici S, Grigoras M, Miron L, Paduraru D, Arama A. Laryngotracheal non-Hodgkin’s lymphoma. Chirurgia (Bucur). 2010;105: 131–6. 7. Msaad S, Yangui I, Ketata W, Ayoub A, Ayedi H. Tracheal involvement revealing Hodgkin’s disease. A case report. Rev Pneumol Clin. 2007;63: 323–5. 8. Winkler CF, Corpus R. Tracheal obstruction in chronic lymphocytic leukemia. Chest. 1980;77: 244–5.
5
