Korean J Hematol 2012; 47(3):
Published online September 25, 2012
https://doi.org/10.5045/kjh.2012.47.3.229
© The Korean Society of Hematology
1Department of Pathology, Government Medical College and Hospital, Chandigarh, India.
2Department of Medicine, Government Medical College and Hospital, Chandigarh, India.
Correspondence to : Correspondence to Pratibha Dhiman, M.D. Department of Pathology, Government Medical College and Hospital, Chandigarh 32, India. Tel: +01712651277, dhimandrpratibha@yahoo.com
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.
A 23-year-old male presented with pulmonary tuberculosis and swelling of both lower limbs. He was put on antitubercular treatment. Hemogram showed mild anemia and Pseudo Pelger-huet cells. The bone marrow (BM) examination showed 52% promyelocytes with regular round to oval nuclei, few granules and were positive for CD13 and CD33, and negative for HLA-DR. Cytogenetic analysis of the BM aspirate revealed an apparently balanced t(11;17)(q23;q21). Final diagnosis rendered was acute promyelocytic leukemia (APL) with t(11;17)(q23;q21);
Keywords
Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) with a defined clinical course and a biology that are distinct from other forms of AML [1]. Several key clinical features set APL apart, underlining the need for accurate diagnosis. These include a potentially devastating coagulopathy that carries a high risk of mortality, unless specifically addressed, and a sensitivity to retinoid-differentiating agents, including all-
Several hematological alterations ranging from various cytopenias to leukemoid reaction and even frank leukemia in association with tuberculosis have been reported [4]. To the best of our knowledge, this variant of APL with this clinical presentation and associated tuberculosis has not been reported so far. Here, we present a case of APL with morphological and cytogenetic studies compatible with the
A 23-year-old man presented with a history of fever, shortness of breath, and pain with swelling in both lower limbs that had lasted one month. An area of dullness on the chest and mild hepatosplenomegaly were found on physical examination, and a chest radiograph revealed bilateral pleural effusion. The pleural tap was hemorrhagic and showed myelocytes and metamyelocytes. The biochemical parameters studied revealed increased adenosine deaminase (98 U/L), and the polymerase chain reaction was positive for tuberculosis. The patient was started on antitubercular therapy. The hemogram showed mild anemia with a hemoglobin level of 9.2 g/dL, a high total leukocyte count of 19.1×109/L, and a platelet count of 160×109/L. The differential count was 36% neutrophils, 24% lymphocytes, 1% monocytes, 1% eosinophils, 2% promyelocytes, 22% myelocytes, and 14% metamyelocytes. Many pseudo-Pelger-Huet cells were seen along with the occasional promyelocyte (Fig. 1). The coagulation profile was deranged with a positive D-dimer test. Doppler ultrasonography of the lower limbs was performed to rule out thrombosis and was non-contributory.
A bone marrow (BM) examination was conducted based on the presence of anemia and immature cells in the peripheral blood. BM aspirate and biopsy revealed hypercellular marrow spaces. The myeloid to erythroid ratio was 20:1 with 52% cells being promyelocytes. These promyelocytes had regular round to oval nuclei, a moderate amount of cytoplasm with few granules, and occasional Auer rods (Fig. 2) and were smaller than usual promyelocytes. However, cytochemical stains performed on the BM aspirate smear showed intense staining of most of these cells with myeloperoxidase stain (MPO, Fig. 3) and Sudan black B (SBB), confirming the promyelocyte morphology. Due to the massive maturation arrest, other causes related to infections and drug intakes were ruled out. This was important since drug-induced or
Immunophenotyping revealed that the abnormal promyelocytes were positive for CD13 and CD33 and negative for HLA DR. Moreover, cytogenetics analysis of the BM aspirate showed an apparently balanced t(11;17)(q23;q21) in all 20 of the examined G-banded cells (Fig. 4). The final diagnosis rendered was APL with t(11;17)(q23;q21);
The patient was lost to follow-up for 3 months after diagnosis and returned after taking ayurvedic medicines. The follow-up hemogram showed similar findings while he was receiving antitubercular therapy. His platelet count was still within normal limits, and D-dimer was still strongly positive. The patient refused chemotherapy and expired after 1 month.
The initial presentation of this case was active pulmonary tuberculosis with a high total leukocyte count and immature cells in peripheral blood. A leukemoid blood picture simulating acute myeloblastic leukemia has been previously described in association with disseminated tuberculosis [6], and in this case, BM and cytogenetic study confirmed the diagnosis of APL with t(11;17)(q23;q21). Retrospectively, the patient probably had an impaired immune response that caused reactivation of a latent focus of tuberculosis. Possible relationships between tuberculosis and blood dyscrasias can include: (i) Activation and dissemination of latent tuberculosis focus due to loss of immune mechanism, particularly, cell-mediated immunity in BM failure and leukemia; (ii) Blood dyscrasias might be an unusual immunological response to tubercle bacilli [7].
APL is a distinct subtype of AML. Morphologically, it is identified as AML-M3 by the French-American-British classification. Cytogenetically, APL is characterized by a balanced reciprocal translocation between chromosomes 15 and 17, which results in the fusion of the promyelocytic leukemia (
Kang et al. [9] reported 2 cases of acute myeloid leukemia with t(11;17) associated with varying morphology and immunophenotype. Their first case had a prominent monocytic component based on flow cytometric analysis and nonspecific esterase staining of BM core biopsy touch preparations. Cytogenetic analysis of BM aspirate revealed 2 normal cells and 18 cells with an apparently balanced t(11;17)(q23; q21). The second case was more consistent with APL morphologically and immunophenotypically. The leukemic cells had a moderate amount of eosinophilic cytoplasm with numerous granules and Auer rods, and irregular nuclear contours with morphology similar to promyelocytes. These leukemic cells displayed strong positivity with MPO, SBB, and chloroacetate esterase stains. α-Naphthyl acetate esterase and α-naphthyl butyrate esterase stains revealed positive staining in less than 20% of the total BM cells. These morphological findings were similar to our case.
In APL with the variant t(11;17), the
In addition, Sainty et al. reviewed 67 cases of APL. The majority of cases (49) were due to insertion events with documented formation of PML/RARA. Of the 18 cases lacking a
In conclusion, this case illustrates a rare presentation of
Peripheral blood smear showing occasional promyelocyte (Leishman's stain; magnification, ×1,000).
Bone marrow aspirate showing promyelocytes having round to oval nuclei (May-Grunwald-Giemsa; magnification, ×1,000).
Bone marrow aspirate showing promyelocytes having myeloperoxidase (MPO) positivity (MPO stain; magnification, ×1,000).
Korean J Hematol 2012; 47(3): 229-232
Published online September 25, 2012 https://doi.org/10.5045/kjh.2012.47.3.229
Copyright © The Korean Society of Hematology.
Anshu Palta1, Pratibha Dhiman1*, and Sanjay D. Cruz2
1Department of Pathology, Government Medical College and Hospital, Chandigarh, India.
2Department of Medicine, Government Medical College and Hospital, Chandigarh, India.
Correspondence to: Correspondence to Pratibha Dhiman, M.D. Department of Pathology, Government Medical College and Hospital, Chandigarh 32, India. Tel: +01712651277, dhimandrpratibha@yahoo.com
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.
A 23-year-old male presented with pulmonary tuberculosis and swelling of both lower limbs. He was put on antitubercular treatment. Hemogram showed mild anemia and Pseudo Pelger-huet cells. The bone marrow (BM) examination showed 52% promyelocytes with regular round to oval nuclei, few granules and were positive for CD13 and CD33, and negative for HLA-DR. Cytogenetic analysis of the BM aspirate revealed an apparently balanced t(11;17)(q23;q21). Final diagnosis rendered was acute promyelocytic leukemia (APL) with t(11;17)(q23;q21);
Keywords:
Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) with a defined clinical course and a biology that are distinct from other forms of AML [1]. Several key clinical features set APL apart, underlining the need for accurate diagnosis. These include a potentially devastating coagulopathy that carries a high risk of mortality, unless specifically addressed, and a sensitivity to retinoid-differentiating agents, including all-
Several hematological alterations ranging from various cytopenias to leukemoid reaction and even frank leukemia in association with tuberculosis have been reported [4]. To the best of our knowledge, this variant of APL with this clinical presentation and associated tuberculosis has not been reported so far. Here, we present a case of APL with morphological and cytogenetic studies compatible with the
A 23-year-old man presented with a history of fever, shortness of breath, and pain with swelling in both lower limbs that had lasted one month. An area of dullness on the chest and mild hepatosplenomegaly were found on physical examination, and a chest radiograph revealed bilateral pleural effusion. The pleural tap was hemorrhagic and showed myelocytes and metamyelocytes. The biochemical parameters studied revealed increased adenosine deaminase (98 U/L), and the polymerase chain reaction was positive for tuberculosis. The patient was started on antitubercular therapy. The hemogram showed mild anemia with a hemoglobin level of 9.2 g/dL, a high total leukocyte count of 19.1×109/L, and a platelet count of 160×109/L. The differential count was 36% neutrophils, 24% lymphocytes, 1% monocytes, 1% eosinophils, 2% promyelocytes, 22% myelocytes, and 14% metamyelocytes. Many pseudo-Pelger-Huet cells were seen along with the occasional promyelocyte (Fig. 1). The coagulation profile was deranged with a positive D-dimer test. Doppler ultrasonography of the lower limbs was performed to rule out thrombosis and was non-contributory.
A bone marrow (BM) examination was conducted based on the presence of anemia and immature cells in the peripheral blood. BM aspirate and biopsy revealed hypercellular marrow spaces. The myeloid to erythroid ratio was 20:1 with 52% cells being promyelocytes. These promyelocytes had regular round to oval nuclei, a moderate amount of cytoplasm with few granules, and occasional Auer rods (Fig. 2) and were smaller than usual promyelocytes. However, cytochemical stains performed on the BM aspirate smear showed intense staining of most of these cells with myeloperoxidase stain (MPO, Fig. 3) and Sudan black B (SBB), confirming the promyelocyte morphology. Due to the massive maturation arrest, other causes related to infections and drug intakes were ruled out. This was important since drug-induced or
Immunophenotyping revealed that the abnormal promyelocytes were positive for CD13 and CD33 and negative for HLA DR. Moreover, cytogenetics analysis of the BM aspirate showed an apparently balanced t(11;17)(q23;q21) in all 20 of the examined G-banded cells (Fig. 4). The final diagnosis rendered was APL with t(11;17)(q23;q21);
The patient was lost to follow-up for 3 months after diagnosis and returned after taking ayurvedic medicines. The follow-up hemogram showed similar findings while he was receiving antitubercular therapy. His platelet count was still within normal limits, and D-dimer was still strongly positive. The patient refused chemotherapy and expired after 1 month.
The initial presentation of this case was active pulmonary tuberculosis with a high total leukocyte count and immature cells in peripheral blood. A leukemoid blood picture simulating acute myeloblastic leukemia has been previously described in association with disseminated tuberculosis [6], and in this case, BM and cytogenetic study confirmed the diagnosis of APL with t(11;17)(q23;q21). Retrospectively, the patient probably had an impaired immune response that caused reactivation of a latent focus of tuberculosis. Possible relationships between tuberculosis and blood dyscrasias can include: (i) Activation and dissemination of latent tuberculosis focus due to loss of immune mechanism, particularly, cell-mediated immunity in BM failure and leukemia; (ii) Blood dyscrasias might be an unusual immunological response to tubercle bacilli [7].
APL is a distinct subtype of AML. Morphologically, it is identified as AML-M3 by the French-American-British classification. Cytogenetically, APL is characterized by a balanced reciprocal translocation between chromosomes 15 and 17, which results in the fusion of the promyelocytic leukemia (
Kang et al. [9] reported 2 cases of acute myeloid leukemia with t(11;17) associated with varying morphology and immunophenotype. Their first case had a prominent monocytic component based on flow cytometric analysis and nonspecific esterase staining of BM core biopsy touch preparations. Cytogenetic analysis of BM aspirate revealed 2 normal cells and 18 cells with an apparently balanced t(11;17)(q23; q21). The second case was more consistent with APL morphologically and immunophenotypically. The leukemic cells had a moderate amount of eosinophilic cytoplasm with numerous granules and Auer rods, and irregular nuclear contours with morphology similar to promyelocytes. These leukemic cells displayed strong positivity with MPO, SBB, and chloroacetate esterase stains. α-Naphthyl acetate esterase and α-naphthyl butyrate esterase stains revealed positive staining in less than 20% of the total BM cells. These morphological findings were similar to our case.
In APL with the variant t(11;17), the
In addition, Sainty et al. reviewed 67 cases of APL. The majority of cases (49) were due to insertion events with documented formation of PML/RARA. Of the 18 cases lacking a
In conclusion, this case illustrates a rare presentation of
Peripheral blood smear showing occasional promyelocyte (Leishman's stain; magnification, ×1,000).
Bone marrow aspirate showing promyelocytes having round to oval nuclei (May-Grunwald-Giemsa; magnification, ×1,000).
Bone marrow aspirate showing promyelocytes having myeloperoxidase (MPO) positivity (MPO stain; magnification, ×1,000).
Cytogenetic profile showing t(11;17)(q23;q21).
Jee Sook Hahn, Yong Chan Lee, Yung Ki Kim, Sun Ju Lee, Yun Woong Ko, Joon Chang, Won Young Lee
Korean J Hematol 1990; 25(1): 161-169
Peripheral blood smear showing occasional promyelocyte (Leishman's stain; magnification, ×1,000).
|@|~(^,^)~|@|Bone marrow aspirate showing promyelocytes having round to oval nuclei (May-Grunwald-Giemsa; magnification, ×1,000).
|@|~(^,^)~|@|Bone marrow aspirate showing promyelocytes having myeloperoxidase (MPO) positivity (MPO stain; magnification, ×1,000).
|@|~(^,^)~|@|Cytogenetic profile showing t(11;17)(q23;q21).