Hypocellular AML versus MDS-diagnostic challenge case report with review of literature.

Am J Blood Res 2022;12(5):172-176 www.AJBlood.us /ISSN:2160-1992/AJBR0137866 Case Report Hypocellular AML versus MDS-diagnostic challenge case report with review of literature Ravi Jacob1, Himanshu Dhanda1, Sartaj Ali1, Pooja Gupta1, Sandeep Rai2, Bhavika Rishi1*, Aroonima Misra1* ICMR-National Institute of Pathology, Safdarjung Hospital Campus, New Delhi, India; 2Department of Laboratory Oncology, DR B R A IRCH, All India Institute of Medical Sciences, New Delhi, India. *Co-corresponding authors. 1 Received July 31, 2021; Accepted August 3, 2022; Epub October 15, 2022; Published October 30, 2022 Abstract: Hypocellular AML being a rare entity with considerable overlapping features and characteristics with various other entities brings a need to have a better and clear understanding of hypocellular AML to differentiate in the decision-making process for therapeutic patient management. With some degree of dysplasia inherently associated with AML it is challenging to differentiate hypocellular AML from Myelodysplastic syndromes. We present a case report where the diagnostic dilemma in an elderly male patient who presented with fever, pallor, weight loss and fatiguability. On clinical examination, the patient had hepatomegaly. The patient was non-affording and was hence given supportive treatment, and he died soon after. Here the diagnostic dilemma is discussed along with the review of literature on hypocellular AML. A better and clear understanding of hypocellular AML is required to differentiate it from other entities due to the considerable overlap in presentation hence improving the decision-making process for therapeutic patient management. The shortcomings are realised, especially when the bone marrow cellularity is less than 10%. Our case report is written to enrich more understanding of the limited published literature on the subject. Keywords: Hypocellular AML, myelodysplastic syndrome Introduction Acute myeloid leukemia (AML) is a group of hematopoietic cell malignancies derived from myeloid precursor cells. In these groups of hematopoietic cell malignancies, hypercellular bone marrow is usually observed, and hypocellularity is infrequently seen because of the increased number of malignant cells. Among these, there are some rare entities called hypocellular AML [1]. Hypocellular AML accounts for 5-12% of all cases of AML and is mainly seen in the elderly age group [2]. Although cases have been reported in childhood and adolescence, but these occurrences were infrequent [1]. In addition, it is also noted that 50% of the hypocellular AML is composed of secondary AML with a history of previous hematologic disorder or history of chemotherapy or radiotherapy [3]. Hypocellular AML is defined as bone marrow hypocellularity <20%, although some earlier reports considered less than 40% or 50% as hypocellular. Hypocellular AML is challenging to diagnose because the overlapping feature of hypoplasia in the marrow are also seen in other conditions like hypocellular myelodysplastic syndrome and aplastic anemia. There have been experiences in the past when a case diagnosed as MDS based on cytogenetics results turns out to be AML with recurrent cytogenetic abnormality. Also, the similar clinical features and lack of prompt investigations are often challenging to clinicians [4, 5]. We report a rare case of hypocellular AML in a 56-yearold male encountered in our institution. Case report A 56-year-old previously healthy male patient presented with fever, which was mild, on and off for the past six months. The fever was initially low grade over two months and progressed to high-grade fever in the last month. In addition, the patient also had complaints of pallor, weight loss and progressive fatigability leading Hypocellular AML mimicking as MDS Figure 1. BM biopsy of Patient showing hypocellularity and presence of Blasts. A. Hypocellular region 4×, B. Normocellular focal area with predominantly lymphocytes and abnormal precursor cells 20×, C and D. Hypocellular areas 4×, E. A focal collection of abnormal precursor cells 4×. to hospitalisation s on and off for the same period. On examination, pulse was 92/min, regular, BP 110/70, Pallor ++, no lymphadenopathy, clubbing, cyanosis, edema or icterus. P/AHepatomegaly was palpated 4 cm below the costal margin in the right midclavicular line, and splenomegaly was palpable at 3 cm below the costal margin. Diagnosis Lab investigations On examination patient had Pancytopenia TLC: 3000/cu mm, Differential count of Polymorphs 10%, Lymphocytes-Monocytes-02%, Myelocytes-1% and Blasts 1%, Platelet count was 80,000/dl, and Hemoglobin was 7 gm%. There was evidence of Mild dyspoiesis in neutrophils, and suspicion of Myelodysplastic syndrome was made. Serum biochemistry Serum LDH was 1700 IU/L, LFT was mildly deranged, and USG abdomen showed non-fatty hepatomegaly. 173 Bone marrow examination A bone marrow examination was done, and 16% blasts were identified in hypocellular marrow cellularity less than 10% for age. Bone marrow biopsy also confirmed similar findings Figure 1. Immunophenotyping Flowcytometry suggested the blasts (18% of the maximum gated population) to be of myeloid origin, as shown in Figure 2 (CD34+, CD33+, CD13+, CD117+). A Cytogenetics panel was outsourced for the patient and revealed normal karyotype and no chromosomal abnormality. Hence based on the above laboratory investigations, the patient was diagnosed with AML and lack of chromosomal abnormality excluded MDS. Patient outcome The patient refused treatment due to financial constraints and was given supportive treat- Am J Blood Res 2022;12(5):172-176 Hypocellular AML mimicking as MDS Figure 2. Flowcytometry of BM sample of Patient showing (18% of the maximum gated population) to be of myeloid origin CD34+, CD33+, CD13+, CD117+. 174 Am J Blood Res 2022;12(5):172-176 Hypocellular AML mimicking as MDS ment to control infections and pancytopenia. The patient succumbed to death after six months of diagnosis. Discussion In our experience, diagnosis of hypocellular AML is based on pancytopenia and microscopic examination of both peripheral blood film and bone marrow by counting 100 cells and 500 cells, respectively [5]. However, in our experience, these features are also seen in MDS, where presentation and clinical characteristics are alike. The examination exhibits less than 20% bone marrow hypocellularity in contrast to the hypercellularity seen in the more common non-hypocellular AML. Also, the degree of dysplasia extends to other lineages in MDS like megakaryocytes and Erythroids except in MDS-RCUD, MDS with Unilineage Dysplasia. With many differences being discussed below, Al-Kali et al. showed that there are also some similarities in terms of cytogenetic and molecular characteristics between hypocellular AML and non-hypocellular AML, except for the low frequency of RAS and FLT3 mutations in the former entity [3]. The pathogenesis of hypocellularity is unclear (...truncated)