|Year : 2016 | Volume
| Issue : 1 | Page : 129-131
Hypoplastic acute myeloid leukemia-M4: A rare case report
Harsh Kumar1, Archana Buch1, Banyameen Iqbal1, Arjun Lal Kakrani2
1 Department of Pathology, Dr. D.Y Patil Medical College, Hospital and Research Centre, Pimpri, Pune, Maharashtra, India
2 Department of Medicine, Dr. D.Y Patil Medical College, Hospital and Research Centre, Pimpri, Pune, Maharashtra, India
|Date of Web Publication||22-Dec-2015|
Department of Pathology, Dr. D.Y Patil Medical College, Hospital and Research Centre, Pimpri, Pune - 411 018, Maharashtra
Source of Support: None, Conflict of Interest: None
Hypocellular acute myeloid leukemia (AML) is defined as AML with bone marrow cellularity <20%. Hypocellular AML is an infrequent entity. Its frequency ranges between 5% and 12% of all cases of AML. Hypocellular variants of acute leukemia almost always have a myeloid phenotype and usually develop secondary to radiation or chemotherapy. We report a rare case of Hypocellular AML-M4 occurring in a 60-year-old woman who was incidentally found to be positive for HIV.
Keywords: Hypoplastic acute myeloid leukemia-M4, hypoplastic leukemia, myelogenous leukemia
|How to cite this article:|
Kumar H, Buch A, Iqbal B, Kakrani AL. Hypoplastic acute myeloid leukemia-M4: A rare case report
. Med J DY Patil Univ 2016;9:129-31
| Introduction|| |
Hypocellular acute myeloid leukemia (AML) is an infrequent entity. Its frequency ranges between 5% and 12% of all cases of AML. , The infrequent occurrence of hypocellularity at presentation of acute leukemia has been widely recognized. Hypocellular variants of acute leukemia almost always have a myeloid phenotype and usually develop secondary to radiation or chemotherapy. , They thus occur mainly in adults.  Hypo cellular AML is currently defined as AML with a bone marrow cellularity <20%, although in some earlier reports, cellularity <40% or 50% was considered to be hypo cellular. , Its diagnosis poses a challenge to hematopathologists because of the features common between hypocellular AML, hypocellular myelodysplastic syndrome and aplastic anemia, including cytopenias and dysplasia, this is particularly the case in which cellularity is extremely low. Guidelines were, therefore, proposed to facilitate the diagnosis.  We report a rare case of hypocellular AML-M4 occurring in a 60-year-old woman.
| Case Report|| |
A 60-year-old male patient presented in our medicine outpatient department with complaints of fever, which is mild grade and intermittent in nature, cough with scanty whitish expectorant since last 15 days. Patient has dyspnea on exertion gradually progressive since last 15 days. Patient had a h/o hypertension since 3 years and is on treatment. On examination, pulse was 94/min, regular, BP 110/70 Pallor ++, no lymphadenopathy, clubbing, cyanosis, edema or icterus. P/A-Hepatomegaly 4 cm below costal margin in right midclavicular line. Splenomegaly 3 cm below costal margin. Cardiovascular, R/S, central nervous system- nicotinamide adenine dinucleotide.
Hemoglobin (Hb) -5.6 g%, total leukocyte count (TLC) -10,600 cells/cumm, differential leukocyte count: P 48 L 40 E 03 M 9 , Platelet count 24,000 cells/cumm, peripheral blood smear (PBS) microctic hypochromic with few tear drop cell and pencil cells with monocytosis [Figure 1]a]. Occassional atypical cells were seen on PBS examination, and no hemoparasite was seen. Mean corpuscular volume -77.7, mean corpuscular hemoglobin (MCH) -27, MCH concentration -30.5, blood sugar, serum protein, blood urea nitrogen, creatinine and serum electrolytes were within normal range. Urine routine and microscopy was normal. Patient was incidentally found to be HIV positive with CD4 counts of 143. Rapid malaria, Widal, dengue immunoglobulin G and immunoglobulin M, venereal disease research laboratory were all negative, blood culture showed no growth.
Ultrasound sonography abdomen and pelvis showed liver 16.4 cm, enlarged in size with normal echotexture and no focal lesions. Spleen was 12.4 cm, mildly enlarged with normal echotexture. Peripancreatic, periportal and paraaortic lymph nodes measuring around 2 cm in size. Patient's platelet count was persistently on lower side despite which she never developed any bleeding tendencies. Her Hb dropped to 4.0 g% and TLC-3200 cu mm, P-50, L-38, E-2, M-10 and platelets were 24000. In view of pancytopenic picture bone marrow aspiration with biopsy was done [Figure 1]b]. Bone marrow aspiration revealed a dry tap. Imprint and bone marrow trephine biopsy showed hypoplastic marrow with myeloid to erythroid ratio of 20:1, markedly suppressed erythropoiesis, myelopoiesis shows increased in blast population about 30% with myelomonocytic appearance, folded nuclei and abundant cytoplasm, megakaryocytes were markedly reduced [Figure 2]. No hemoparasite or granuloma was noted. Cytochemically, these blasts were myeloperoxidase (MPO) positive [Figure 3]. Based on all these features, diagnosis of hypocellular AML French-American-British subtype M4 (AML-M4) was made. The patient was referred to a tertiary health care center for further management.
|Figure 2: Photomicrograph of bone marrow biopsy showing hypocellular (Leishman ×40)|
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|Figure 3: Photomicrograph showing myeloperoxidase (MPO) positivity in the myelomonocytic blasts (MPO ×40)|
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| Discussion|| |
Hypoplastic AML can be challenging for both pathologist and treating physician. AML The frequency of hypocellular AML has been reported to be between 5% and 7% among all patients with AML. This is based mainly on older reports, in which the definition of AML required 30% of myeloblasts while the current definition restricts it to <20%.  The occurrence of hypoplastic acute leukemia is widely recognized as atypical leukemia and is defined as hypocellular marrow with ≥20% blasts and none or few blasts in the circulating blood  The pathogenesis of the hypocellularity remains speculative. It is unclear whether the leukemia is secondary to the hypocellularity or if it is the primary event. It has been suggested that leukemia cell populations inhibit myelopoiesis through a humoral mechanism or an increased susceptibility of myeloid precursors to the inhibitor in older patients might play a role in the genesis of hypoplasia.  Hypocellular AML is seen more frequently in older patients  in our case patient was also a 60-year-old female, and patients tend to have more profound presenting cytopenias, same as in our patient who presented with pancytopenia. There are many case series and individual case reports of hypoplastic acute leukemia available in the literature. Nagai et al.  proposed the following diagnostic criteria: Pancytopenia with rare appearance of blasts in peripheral blood; <40% bone marrow hypocellularity; >30% blasts in bone marrow of all nucleated cells; and myeloid phenotypes of leukemic blasts by MPO staining. Our case also presents with similar finding. With the help of immunohistochemical markers which are capable of reacting with routinely fixed-paraffin-embedded bone marrow material has provided additional assistance in the blast identification. CD34, an antigen expressed in progenitor and early precursor marrow cells, has been proved among the most useful ones in this regard.  Other antibodies that may be useful include CD117, MPO, lysozyme and CD68 AML. Hypoplastic acute AML needs to be differentiated from hypoplastic MDS. Lack of dysplastic features on erythroid, myeloid and megakaryocytic series and blast counts of >20% in marrow helped us to confirm the diagnosis.  Incidentally we found that the patient was seropositive for HIV. Cases of AML-M4 with HIV have been reported and AML-M4 is known to be common in HIV patients  Needleman et al.  has reported their experience with hypoplastic acute leukemia and suggested that patients with hypocellular bone marrow experience a more indolent course, and can commonly achieve a good response to remission induction therapy. Recently, the beneficial effects of hematopoietic growth factors have been reported in the treatment of hypoplastic AML. It has been observed that chemotherapy may be necessary to maintain remission in hypoplastic AML after hematopoietic reconstitution by granulocyte colony stimulating factor 
| Conclusion|| |
Hypocellular acute myelomonocytic leukemia is a rare entity, and it can be challenging for both the pathologist and the physician. This entity is more frequently seen in older patients, and patients tend to have more profound presenting pancytopenias. The limited published information about the clinical and prognostic parameters of this entity makes specific clinical recommendations difficult.
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[Figure 1], [Figure 2], [Figure 3]