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 Table of Contents  
CASE REPORT
Year : 2021  |  Volume : 8  |  Issue : 1  |  Page : 52-55

Chronic myeloid leukemia with solitary extramedullary bone deposit: A unique presentation


1 Department of Radiation Oncology, Christian Medical College and Hospital, Ludhiana, Punjab, India
2 Department of Clinical Haematology and Bone Marrow (Stem Cell) Transplant, Christian Medical College and Hospital, Ludhiana, Punjab, India
3 Department of Orthopedics, Christian Medical College and Hospital, Ludhiana, Punjab, India

Date of Submission10-Jan-2020
Date of Acceptance04-Jun-2020
Date of Web Publication18-Jun-2021

Correspondence Address:
Pamela Alice Kingsley
Department of Radiation Oncology, Christian Medical College and Hospital, Ludhiana, Punjab
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/cjhr.cjhr_2_20

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  Abstract 


Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm, characterized by a hematopoietic stem cell carrying BCR-ABLl fusion protein. Common sites of extramedullary deposits in CML are lymph nodes, bones, and central nervous system. We present a case of a 39-year-old male diagnosed case of CML who presented with extramedullary deposit in the right femur in spite of complete hematological remission and major molecular response on real-time quantitative reverse transcriptase polymerase chain reaction in the blood. Extramedullary deposit is almost always followed by hematological reemergence of disease and is considered as an early sign of disease in the bone marrow. Bone, lymph nodes, skin and soft tissues, and central nervous system are the common sites for extramedullary deposits in a case of CML. A thorough literature review revealed limited case reports on extramedullary deposits in a case of CML in major molecular response. Therefore, the possibility of being confronted with unusual signs and symptoms which could be indicative of extramedullary deposits should be kept in mind.

Keywords: BCR-ABL positive, bone marrow, chronic myeloid leukemia, hematopoietic stem cells, myeloproliferative disorders


How to cite this article:
Negi P, Jomi C, Philip C, Mahajan A, Kingsley PA. Chronic myeloid leukemia with solitary extramedullary bone deposit: A unique presentation. CHRISMED J Health Res 2021;8:52-5

How to cite this URL:
Negi P, Jomi C, Philip C, Mahajan A, Kingsley PA. Chronic myeloid leukemia with solitary extramedullary bone deposit: A unique presentation. CHRISMED J Health Res [serial online] 2021 [cited 2022 Jul 7];8:52-5. Available from: https://www.cjhr.org/text.asp?2021/8/1/52/318788




  Introduction Top


Extramedullary blast crisis in chronic myeloid leukemia (CML) is defined as the detection of extramedullary disease (EMD) as a result of infiltration of leukemic blasts irrespective of the proliferation of blasts in the bone marrow.[1] Several studies have reported that EMD is almost always followed by hematological reemergence of disease and is considered as an early sign of disease in the bone marrow.[2],[3] The prevalence of EMD in CML is around 15% and commonly involves bone, lymph nodes, skin, spleen, soft tissue, or central nervous system.[1]


  Case Report Top


A 39-year-old male presented with leukocytosis with a total white blood cell count of 1.53 lakhs/mm3 during his routine health checkup in April 2017. Bone marrow examination showed solidly cellular marrow with relatively depressed erythropoiesis, myeloid predominance, and increased megakaryopoiesis suggestive of possibly CML in chronic phase. BCR-ABL1/ABL1 transcript ratio (t [9:22] [q34:q11]) from blood was 23.3% as assessed by fluorescent in situ hybridization analysis consistent with a diagnosis of CML. The patient was started on hydroxyurea 500 mg thrice a day orally.

After 1 month, hydroxyurea was stopped owing to development of drug-induced myelosuppression [Table 1]. The cell count began to recover, and imatinib was stared initially at a lower dose of 200 mg and gradually increased to 400 mg once a day. Repeat blood examination at regular intervals showed gradual improvement in hematological parameters with no immature cells on differential leukocyte count analysis. After starting imatinib, his BCR/ABL1 translocation levels were 0.195% and 0.158% at 3 and 6 months, respectively. He achieved complete hematological response and major molecular response with imatinib.
Table 1: Hematological parameters pre- and post-treatment values

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3 months following this, he complained of severe pain in the right hip with the inability to bear weight on the right leg. Local examination revealed tenderness over the outer aspect of the hip joint around the greater trochanter and along the area of the neck. No distal neurovascular deficits were noted. Noncontrast computed tomography of pelvis showed an ill-defined round lytic area measuring 2.6 cm × 2.7 cm involving head of femur on the right side with central sclerotic changes and surrounding ill-defined area of mixed lytic sclerotic changes [Figure 1].
Figure 1: Computed tomography pelvis showing lytic area measuring approximately 2.6 cm × 2.7 cm involving head of femur on right side

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This was further evaluated with magnetic resonance imaging of hip which revealed marrow edema with joint effusion in right femur? Secondary to stress fracture? Focal osteitis [Figure 2]. Biopsy showed bone marrow infiltration by blasts, probably of myeloid/myelomonocytic lineage with a predominance of eosinophils [Figure 3].
Figure 2: Magnetic resonance imaging pelvis showing marrow edema with joint effusion in right femur? Secondary to stress fracture? Focal osteitis

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Figure 3: Bone biopsy showing sheets of monotonous round cells. H and E, ×400

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Immunohistochemical stains showed diffuse positivity for CD45, CD34, CD68, and CD117 in the neoplastic cells. Ki-67 proliferative index was approximately 50%. Anti-MPO highlighted myeloid population within hematopoietic island with negativity in blasts and CD3, CD20, and CD138 highlighting reactive T-cells, B-cells, and plasma cells supporting the diagnosis of extramedullary blast deposition [Figure 4].
Figure 4: Immunohistochemistry showing round cells positive for CD34, CD117, and CD68. Proliferative fraction is approximately 50%. DAB chromogen, ×400

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Bone marrow biopsy showed bone marrow in morphological remission with no increase in blasts or evidence of myeloproliferation. At this time, BCR-ABL1/ABL1 transcript ratio of the peripheral blood was negative. The peripheral blood counts remained normal. Whole-body 18[F]-fluorodeoxyglucose positron emission tomography (FDG-PET/CT scan) revealed FDG uptake with lytic changes involving the head and neck of the right femur with FDG-avid subcentrimetric right external iliac lymph nodes measuring approximately 1.9 cm × 1.1 cm (maximum standardized uptake value 4.6). Hence, final diagnosis of isolated extramedullary blast deposits involving the right femur in a diagnosed case of CML on imatinib in major molecular response was made. In view of associated severe pain and the risk of pathological fracture, he was treated with local radiotherapy to femur with 45 Gy in 20 fractions, thereby achieving good pain relief. As a definitive plan, he is planned to undergo allogeneic stem cell transplantation.


  Discussion Top


A study on 349 patients with Philadelphia-positive CML reported that 14 (4%) patients developed EMD during the course of their disease. The common sites of EMD are bone (57%), lymph nodes (29%), skin and soft tissues (21%), and central nervous system (14%).[2]

The presentation of CML patients with extramedullary involvement during the course of the disease reportedly has been highly variable. Earliest report of extramedullary blast crisis in a CML patient who had complete cytogenetic response to interferon-alpha has been described by O'Brien et al.[4] These presentations in literature vary from massive ascites during chronic phase CML[5] to extramedullary blast crisis in abdominal lymph nodes.[6]

Extramedullary blast crisis (T-lymphoid/ myeloid bilineage phenotype) in chronic phase CML patients, as a presenting symptom of the disease, is extremely rare.[7],[8] Ganessan et al.[7] reported a 14-year-old child who presented with generalized lymphadenopathy and massive hepatosplenomegaly. Bone marrow examination showed CML in chronic phase. Lymph node biopsy was suggestive of extramedullary blast crisis with evidence of myeloid and T-cell markers in blasts as a presenting symptom of the disease.

Yilmaz et al.[8] reported extramedullary relapse in a CML patient after allogeneic stem cell transplantation, a rare occurrence. This 28-year-old male underwent allogeneic stem cell transplantation in view of CML disease refractory to tyrosine kinase inhibitors. After 5 years, he developed EMD in the form of granulocytic sarcoma in spite of complete molecular and cytogenetic remission.

Similar to our patient, thorough search of the literature revealed a case report of CML with isolated extramedullary bone disease, although, in a 3-year-old girl.[9] Femoral head as site of extramedullary blast crisis has also been reported by Tsukamoto et al.[1]

Specchia et al.[10] indicated that the appearance of EMD is more commonly associated with chronic phase or accelerated phase features in the bone marrow. However, our patient bone marrow showed major morphological response with no increase in blasts or evidence of myeloproliferation at the time of diagnosis of EMD. Our patient developed EMD in bone (femur) at 16 months in the course of the treatment with complete hematological remission and major molecular response in the bone marrow.

This case serves as a caveat against ignoring any unusual symptoms in a CML patient with major molecular response on treatment. There is an ample evidence to suggest that extramedullary blast crisis is almost always followed by hematological blast crisis, within a few months and therefore, representing an early sign of blast crisis in the bone marrow.[2],[3] In this light, it is meaningful to direct future efforts for early diagnosis of extramedullary relapse in CML patients even when complete remission has been achieved.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Tsukamoto S, Ota S, Ohwada C, Takeda Y, Takeuchi M, Sakaida E, et al. Extramedullary blast crisis of chronic myelogenous leukemia as an initial presentation. Leuk Res Rep 2013;2:67-9.  Back to cited text no. 1
    
2.
Inverardi D, Lazzarino M, Morra E, Bernasconi P, Merante S, Canevari A, et al. Extramedullary disease in Ph'-positive chronic myelogenous leukemia: Frequency, clinical features and prognostic significance. Haematologica 1990;75:146-8.  Back to cited text no. 2
    
3.
Kantarjian HM, Keating MJ, Talpaz M, Walters RS, Smith TL, Cork A, et al. Chronic myelogenous leukemia in blast crisis. Analysis of 242 patients. Am J Med 1987;83:445-54.  Back to cited text no. 3
    
4.
O'Brien S, Witt R, Talpaz M, Kantarjian H. Extramedullary blast crisis in a patient with Philadelphia chromosome-positive chronic myelogenous leukemia in complete cytogenetic remission. Cancer 1991;67:1946-9.  Back to cited text no. 4
    
5.
Aleem A, Siddiqui N. Chronic myeloid leukemia presenting with extramedullary disease as massive ascites responding to imatinib mesylate. Leuk Lymphoma 2005;46:1097-9.  Back to cited text no. 5
    
6.
Shune L, Cayci Z, Rogosheske J, Brunstein C, Ustun C. Extramedullary blastic crisis in abdominal lymph nodes in a patient with chronic myelogenous leukemia on imatinib. Leuk Res 2012;36:e131-2.  Back to cited text no. 6
    
7.
Ganessan K, Goel R, Kumar K, Bakhshi S. Biphenotypic extramedullary blast crisis as a presenting manifestation of Philadelphia chromosome-positive CML in a child. Pediatr Hematol Oncol 2007;24:195-8.  Back to cited text no. 7
    
8.
Yilmaz AF, Soyer N, Ozsan N, Cagirgan S, Gunes A, Comert M, et al. Extramedullary relapse in a CML patient after allogeneic stem cell transplantation. Case Rep Hematol 2017;2017:6350267.  Back to cited text no. 8
    
9.
Yu HH, Lu MY, Lin DT, Lin KH, Tang JL, Jou ST. Pathological fracture as a manifestation of extramedullary blastic crisis in chronic myelogenous leukemia: Report of one case. Acta Paediatr Taiwan 2006;47:150-4.  Back to cited text no. 9
    
10.
Specchia G, Palumbo G, Pastore D, Mininni D, Mestice A, Liso V. Extramedullary blast crisis in chronic myeloid leukemia. Leuk Res 1996;20:905-8.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
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