Pediatric Hematology and Oncology, 31:140–142, 2014 C Informa Healthcare USA, Inc. Copyright ISSN: 0888-0018 print / 1521-0669 online DOI: 10.3109/08880018.2013.867557
LETTER TO THE EDITOR Myeloid Leukemias and Myeloproliferative Disease
Pediatr Hematol Oncol Downloaded from informahealthcare.com by University of Bath on 10/04/14 For personal use only.
Disseminated Myeloid Sarcomas—A Rare Presentation of Acute Myeloid Leukemia Aditya Kumar Gupta, MD, Nita Radhakrishnan, MD, FNB, and Anupam Sachdeva, MD, DCH Sir Ganga Ram Hospital, Pediatric Hemato-Oncology and BMT, Old Rajinder Nagar, New Delhi, India
Acute Myeloid Leukemias (AML) may present rarely as anatomical distortions at extramedullary sites, termed as Myeloid Sarcomas (MS). Though MS can involve different sites, concomitant involvement of multiple sites is very rare. Here, we describe an adolescent girl who presented with disseminated MS at multiple sites. Such a presentation of AML has not been described before. The delay in presentation of the patient to a proper medical center is also to be noted here. Keywords Acute leukemias, AML, pediatric oncology
Myeloid Sarcomas (MS) are deposits of blasts due to proliferation of blast cells at an extramedullary site [1] and the most common sites involved are bone, orbits, skin, and the lymph nodes [2]. MS can occur concomitantly or after the onset of systemic bone marrow Acute Myeloid Leukemia (AML). Rarely, it may antedate systemic disease by a median time of about 7 months [3]. MS as a presentation of relapse in treated cases of AML has also been described. We recently treated an 18 years old girl with AML and disseminated MS that is being reported. An 18 years old girl had history of fever and generalized body pain for duration of 3 months and swelling of both eyes for 1 week. The girl was being treated on alternative forms of medicine for the past 3 months. Since the last 48 hours before presentation she had developed acute onset paraplegia of both the lower limbs associated with retention of urine and failure to pass stools. On examination, the girl was drowsy, febrile, hypertensive, and tachypneic. The breath sounds on auscultation were absent on the right side and diminished on the left side. Pallor was present along with bleeding manifestations in form of skin bleeds and per vaginum bleed. There was generalized tenderness over the skull, spine, sternum and bilateral shoulders. There was a flaccid paralysis of both the lower limbs and the sensory level of her weakness clinically was around the T4 dermatome. Retention of urine was present. There was no apparent cranial nerve deficit. On investigation her hemoglobin (Hb) was 8.8 gm/dL, total leukocyte count (TLC) was 2690/mm3 and the platelet counts were 11,000/mm3 . The peripheral smear revealed 42% blasts that were MPO positive with M2 morphology. The bone marrow Received 9 September 2013; accepted 17 November 2013. Address correspondence to Dr Anupam Sachdeva, Sir Ganga Ram Hospital, Pediatric Hemato-Oncology and BMT, Old Rajinder Nagar, New Delhi 110060, India. E-mail: [email protected]
Pediatr Hematol Oncol Downloaded from informahealthcare.com by University of Bath on 10/04/14 For personal use only.
Letter to the Editor
Figure 1 Magnetic Resonance Imaging of the patient (clockwise from top left) (Arrows are indicative of extramedullary deposits): –Involvement of cavernous sinus and bilateral temporal bones with MS. –Involvement of the spinal cord by tumor deposits along with pre- and retro-sternal MS. Also seen are prevertebral deposits. –Bilateral pleural effusion due to spread to the pleura. –MRI thorax showing deposits in the cervical region and the peri-articular region of the left shoulder.
examination revealed 73% blasts consistent with AML M2 and the flowcytometry done on the bone marrow aspirate was suggestive of AML M2 with aberrant expression of CD19 and CD7. The pleural aspirate too had numerous blasts. The cytogenetic analysis and the molecular work up for common mutations in AML, including NPM1 were negative. Magnetic resonance imaging (MRI) of the cranium, spine and body was done and was suggestive of disseminated involvement with MS and its description is given along with the figure 1. The condition of the patient was not hemodynamically stable enough to perform a lumbar puncture hence the status of the CSF positivity could not be ascertained. However, the patient had CNS involvement in the form of intra-cranial MS involving the cavernous sinuses. The patient was started on induction chemotherapy as per the UKAML XII protocol with Cytarabine, Doxorubicin, and Etoposide. Although her sensorium improved, she remained paraplegic. She also developed refractory thrombocytopenia. Subsequently, the patient developed Staphylococcal sepsis, mucositis, and hypotension. A repeat MRI could not be obtained in the patient so the response of the MS to our treatment could not be ascertained. C Informa Healthcare USA, Inc. Copyright
Pediatr Hematol Oncol Downloaded from informahealthcare.com by University of Bath on 10/04/14 For personal use only.
A. K. Gupta et al.
The family abandoned treatment post day 15 of induction due to financial constrains. The patient was subsequently lost to follow-up. A telephonic follow-up after a period of 2 months confirmed the death of the patient. Whereas the incidence rate of MS in patients with AML of all ages is estimated to be about 9%, recently Ohanian et al., found it to be upto 40% in the pediatric population [4] and they found that both cutaneous and noncutaneous MS are commonly associated with AML M4 and AML M5 subtype [4]. The clinical presentations of EML vary depending on the site and extent of involvement. Most cases reported in literature are of isolated MS but very few have mentioned the use of imaging modalities to verify the true extent of the disease [4]. MS that involve multiple anatomic sites in a disseminated manner, as seen in our case, is rare [5] and worth reporting. Many studies have found that t(8,21) is a common chromosomal alteration associated with MS in AML [6]. Although there is fewer data on the molecular abnormalities in AML with MS, mutation in the nucleophosmin (NPM-1) gene has a strong association with MS [7]. Both t(8, 21) and NPM-1 mutation were not detected in our patient. A better event free and overall survival has been reported for MS patients with AML in comparison to classical AML, when treated on AML like protocols [4]. A similar treatment approach was adopted for our patient but she could not be salvaged. The fact that the patient was treated on alternative forms of medicines for three months, which may have eventually caused the widespread dissemination of the MS, is also worth taking notice. Un-scientific treatment practices that are common in this part of the world are a barrier to optimal outcomes. Ramzan and Yadav, similarly found a higher mortality in children of cancer who opted for alternative forms of treatment [8]. Declaration of Interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article. REFERENCES [1] Jaffe ES, Harris NL, Stein H, Vardiman JW. Pathology and Genetics. Tumors of Hematopoietic and Lymphoid Tissues. Lyon: IARC Press; 2001:104–105. [2] Kasahara S, Tsurumi H, Hara T, et al. Idiopathic myelofibrosis developing isolated granulocytic sarcoma with der(1;7)(q10; p10) after splenectomy and finally transforming to acute myelogenous leukemia. Leuk Lymphoma. 2000;39:427–433. [3] Krause JR. Granulocytic sarcoma preceding acute leukemia: a report of six cases. Cancer 1979;44(3):1017–1021. [4] Ohanian M, Faderal S, Ravandi F, et al. Is acute myeloid leukemia a liquid tumor? Int J Cancer. 2013;133(3):534–543. [5] Zhou J, Minimo C, Balasubramanian M. A case report of myeloid sarcoma of the gastrointestinal system. J Hematopathology. 2012;5(4):329–334. [6] Felice MS, Zubizarreta P, Alfaro E, et al. Good outcome of children with acute myeloid leukemia and t(8;21)(q22;q22) even when associated with granulocytic sarcoma: a report from a Single Institution in Argentina. Cancer 2000;88:1939–1944. [7] Falini B, Mecucci C, Tiacci E, et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med. 2005;352:254–266. [8] Ramzan M, Yadav SP. Treatment Abandonment is a Major Hurdle to Improving Survival in Childhood Cancer in the Developing World. Pediatr Blood Cancer 2013;60:159–160.
Pediatric Hematology and Oncology
LETTER TO THE EDITOR Myeloid Leukemias and Myeloproliferative Disease
Pediatr Hematol Oncol Downloaded from informahealthcare.com by University of Bath on 10/04/14 For personal use only.
Disseminated Myeloid Sarcomas—A Rare Presentation of Acute Myeloid Leukemia Aditya Kumar Gupta, MD, Nita Radhakrishnan, MD, FNB, and Anupam Sachdeva, MD, DCH Sir Ganga Ram Hospital, Pediatric Hemato-Oncology and BMT, Old Rajinder Nagar, New Delhi, India
Acute Myeloid Leukemias (AML) may present rarely as anatomical distortions at extramedullary sites, termed as Myeloid Sarcomas (MS). Though MS can involve different sites, concomitant involvement of multiple sites is very rare. Here, we describe an adolescent girl who presented with disseminated MS at multiple sites. Such a presentation of AML has not been described before. The delay in presentation of the patient to a proper medical center is also to be noted here. Keywords Acute leukemias, AML, pediatric oncology
Myeloid Sarcomas (MS) are deposits of blasts due to proliferation of blast cells at an extramedullary site [1] and the most common sites involved are bone, orbits, skin, and the lymph nodes [2]. MS can occur concomitantly or after the onset of systemic bone marrow Acute Myeloid Leukemia (AML). Rarely, it may antedate systemic disease by a median time of about 7 months [3]. MS as a presentation of relapse in treated cases of AML has also been described. We recently treated an 18 years old girl with AML and disseminated MS that is being reported. An 18 years old girl had history of fever and generalized body pain for duration of 3 months and swelling of both eyes for 1 week. The girl was being treated on alternative forms of medicine for the past 3 months. Since the last 48 hours before presentation she had developed acute onset paraplegia of both the lower limbs associated with retention of urine and failure to pass stools. On examination, the girl was drowsy, febrile, hypertensive, and tachypneic. The breath sounds on auscultation were absent on the right side and diminished on the left side. Pallor was present along with bleeding manifestations in form of skin bleeds and per vaginum bleed. There was generalized tenderness over the skull, spine, sternum and bilateral shoulders. There was a flaccid paralysis of both the lower limbs and the sensory level of her weakness clinically was around the T4 dermatome. Retention of urine was present. There was no apparent cranial nerve deficit. On investigation her hemoglobin (Hb) was 8.8 gm/dL, total leukocyte count (TLC) was 2690/mm3 and the platelet counts were 11,000/mm3 . The peripheral smear revealed 42% blasts that were MPO positive with M2 morphology. The bone marrow Received 9 September 2013; accepted 17 November 2013. Address correspondence to Dr Anupam Sachdeva, Sir Ganga Ram Hospital, Pediatric Hemato-Oncology and BMT, Old Rajinder Nagar, New Delhi 110060, India. E-mail: [email protected]
Pediatr Hematol Oncol Downloaded from informahealthcare.com by University of Bath on 10/04/14 For personal use only.
Letter to the Editor
Figure 1 Magnetic Resonance Imaging of the patient (clockwise from top left) (Arrows are indicative of extramedullary deposits): –Involvement of cavernous sinus and bilateral temporal bones with MS. –Involvement of the spinal cord by tumor deposits along with pre- and retro-sternal MS. Also seen are prevertebral deposits. –Bilateral pleural effusion due to spread to the pleura. –MRI thorax showing deposits in the cervical region and the peri-articular region of the left shoulder.
examination revealed 73% blasts consistent with AML M2 and the flowcytometry done on the bone marrow aspirate was suggestive of AML M2 with aberrant expression of CD19 and CD7. The pleural aspirate too had numerous blasts. The cytogenetic analysis and the molecular work up for common mutations in AML, including NPM1 were negative. Magnetic resonance imaging (MRI) of the cranium, spine and body was done and was suggestive of disseminated involvement with MS and its description is given along with the figure 1. The condition of the patient was not hemodynamically stable enough to perform a lumbar puncture hence the status of the CSF positivity could not be ascertained. However, the patient had CNS involvement in the form of intra-cranial MS involving the cavernous sinuses. The patient was started on induction chemotherapy as per the UKAML XII protocol with Cytarabine, Doxorubicin, and Etoposide. Although her sensorium improved, she remained paraplegic. She also developed refractory thrombocytopenia. Subsequently, the patient developed Staphylococcal sepsis, mucositis, and hypotension. A repeat MRI could not be obtained in the patient so the response of the MS to our treatment could not be ascertained. C Informa Healthcare USA, Inc. Copyright
Pediatr Hematol Oncol Downloaded from informahealthcare.com by University of Bath on 10/04/14 For personal use only.
A. K. Gupta et al.
The family abandoned treatment post day 15 of induction due to financial constrains. The patient was subsequently lost to follow-up. A telephonic follow-up after a period of 2 months confirmed the death of the patient. Whereas the incidence rate of MS in patients with AML of all ages is estimated to be about 9%, recently Ohanian et al., found it to be upto 40% in the pediatric population [4] and they found that both cutaneous and noncutaneous MS are commonly associated with AML M4 and AML M5 subtype [4]. The clinical presentations of EML vary depending on the site and extent of involvement. Most cases reported in literature are of isolated MS but very few have mentioned the use of imaging modalities to verify the true extent of the disease [4]. MS that involve multiple anatomic sites in a disseminated manner, as seen in our case, is rare [5] and worth reporting. Many studies have found that t(8,21) is a common chromosomal alteration associated with MS in AML [6]. Although there is fewer data on the molecular abnormalities in AML with MS, mutation in the nucleophosmin (NPM-1) gene has a strong association with MS [7]. Both t(8, 21) and NPM-1 mutation were not detected in our patient. A better event free and overall survival has been reported for MS patients with AML in comparison to classical AML, when treated on AML like protocols [4]. A similar treatment approach was adopted for our patient but she could not be salvaged. The fact that the patient was treated on alternative forms of medicines for three months, which may have eventually caused the widespread dissemination of the MS, is also worth taking notice. Un-scientific treatment practices that are common in this part of the world are a barrier to optimal outcomes. Ramzan and Yadav, similarly found a higher mortality in children of cancer who opted for alternative forms of treatment [8]. Declaration of Interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article. REFERENCES [1] Jaffe ES, Harris NL, Stein H, Vardiman JW. Pathology and Genetics. Tumors of Hematopoietic and Lymphoid Tissues. Lyon: IARC Press; 2001:104–105. [2] Kasahara S, Tsurumi H, Hara T, et al. Idiopathic myelofibrosis developing isolated granulocytic sarcoma with der(1;7)(q10; p10) after splenectomy and finally transforming to acute myelogenous leukemia. Leuk Lymphoma. 2000;39:427–433. [3] Krause JR. Granulocytic sarcoma preceding acute leukemia: a report of six cases. Cancer 1979;44(3):1017–1021. [4] Ohanian M, Faderal S, Ravandi F, et al. Is acute myeloid leukemia a liquid tumor? Int J Cancer. 2013;133(3):534–543. [5] Zhou J, Minimo C, Balasubramanian M. A case report of myeloid sarcoma of the gastrointestinal system. J Hematopathology. 2012;5(4):329–334. [6] Felice MS, Zubizarreta P, Alfaro E, et al. Good outcome of children with acute myeloid leukemia and t(8;21)(q22;q22) even when associated with granulocytic sarcoma: a report from a Single Institution in Argentina. Cancer 2000;88:1939–1944. [7] Falini B, Mecucci C, Tiacci E, et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med. 2005;352:254–266. [8] Ramzan M, Yadav SP. Treatment Abandonment is a Major Hurdle to Improving Survival in Childhood Cancer in the Developing World. Pediatr Blood Cancer 2013;60:159–160.
Pediatric Hematology and Oncology
