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 Table of Contents  
CASE REPORT
Year : 2018  |  Volume : 9  |  Issue : 2  |  Page : 68-71

Leishmaniasis presenting as myelodysplasia: A diagnostic dilemma


Department of Pathology, Maulana Azad Medical College, New Delhi, India

Date of Web Publication18-Jun-2018

Correspondence Address:
Dr. Richa Gupta
Department of Pathology, Room No. 263, Maulana Azad Medical College, Bahadur Shah Zafar Marg, New Delhi - 110 002
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/joah.joah_53_17

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  Abstract 

Kala azar is a chronic parasitic infection which usually presents with fever, splenomegaly, and pancytopenia. Here is a case of a 9-month-old girl who presented with history of repeated blood transfusions for 3 months and later with fever and splenomegaly. Complete blood count showed bicytopenia with significant dysplasia seen in marrow aspiration smears. Secondary causes of dysplasia such as vitamin deficiency, drugs and toxins, and viral infections were ruled out and the patient was advised cytogenetic study to rule out refractory cytopenia of childhood. Subsequently, RK39 antigen result came out to be positive, and on reexamination, the slides showed few amastigote forms of Leishmania donovani. Hence, a diagnosis of Leishmaniasis with secondary dysplasia was made. Some cases may have the classic clinical features of LD infection although it has been emphasized here that myelodysplasia is a relatively uncommon presentation of LD infection. Hence, serological tests for Leishmania should be carried out along with a careful search for the parasite in all smears to avoid a grave diagnosis of myelodysplastic syndrome.

Keywords: Bone marrow, leishmaniasis, myelodysplasia


How to cite this article:
Gupta AJ, Gupta R, Rani P. Leishmaniasis presenting as myelodysplasia: A diagnostic dilemma. J Appl Hematol 2018;9:68-71

How to cite this URL:
Gupta AJ, Gupta R, Rani P. Leishmaniasis presenting as myelodysplasia: A diagnostic dilemma. J Appl Hematol [serial online] 2018 [cited 2019 Dec 6];9:68-71. Available from: http://www.jahjournal.org/text.asp?2018/9/2/68/234554


  Introduction Top


Kala azar is a chronic parasitic infection which usually presents with fever, splenomegaly, and pancytopenia.[1] Rarely, it may be associated with myelodysplasia in the blood or bone marrow.[1],[2],[3],[4] Severe myelodysplasia may be a confounding factor for diagnosis, especially if the parasitic load is very low. Confirmation requires a high suspicion and diligent search for demonstration of parasite in bone marrow or rarely splenic aspirate.[1] We hereby present the case of a 9-year-old child with leishmaniasis presenting as myelodysplastic syndrome (MDS). This case is being presented due to rarity of such association and importance of a detailed morphological evaluation of bone marrow aspirate smears.


  Case Report Top


A 9-month-old female child presented with a history of repeated blood transfusions for 3 months. She had fever for 1 week and was on antibiotics for the same. There was no history of chemical/toxin/chemotherapeutic drug exposure or viral illness.

General examination revealed mild pallor. On examination, the patient had splenomegaly (4 cm below costal margin). There was no hepatomegaly or lymphadenopathy. Complete blood count showed bicytopenia (hemoglobin 8.5 g/dl; total leukocyte count 3580/mm 3; platelet count 1.6 lacs/mm 3 [age-matched normal range: hemoglobin 10.5–12.9 g/dl; total leukocyte count 6.0–17.5/mm 3; platelet count 2.0–5.5 lacs/mm 3]). Red cells were normocytic normochromic. No features of hemolysis were noted. Leukocytes were mildly reduced in number and morphologically unremarkable. Differential leukocyte count revealed predominance of lymphocytes (neutrophils 10%, lymphocytes 78%, monocytes 10%, and eosinophils 2%). No atypical cells or parasite was seen. The reticulocyte count was also low. Subsequent bone marrow aspiration (BMA) smears revealed normocellular marrow with erythroid hyperplasia (M:E ratio 1:1.5) [[Figure 1] inset]. There was significant dysplasia in erythroid series (affecting 25% of cells) in the form of nuclear budding, binucleation, and karyorrhexis [Figure 1]. Dysplasia was also seen in myeloid series (affecting 12% of cells) in the form of multinucleation, ring forms, and pseudo-Pelger–Huet anomaly [Figure 2]. The megakaryocytic series was normal in morphology and number. Bone marrow iron was Grade 2 (normal) and no ring sideroblasts were seen. Based on the above findings, a differential diagnosis of childhood MDS versus congenital dyserythropoietic anemia was kept. A detailed history of toxin exposure (especially lead) and ayurvedic medicine intake revealed no significant finding. B12 and folate levels were carried out but were found within normal limits. The patient was nonreactive for human immunodeficiency virus (HIV) and toxoplasma, rubella, cytomegalovirus (CMV), and herpes simplex group of infections. A hereditary erythroblastic multinuclearity with positive acidified serum lysis test was also done which came out to be negative. The patient was advised cytogenetic study to rule out refractory cytopenia of childhood (RCC). Meanwhile, RK39 antigen (serological test for kala azar) was also performed in the patient as a part of workup for splenomegaly and cytopenia which came out to be positive. Therefore, the BMA slides were reexamined with additional smears stained to carefully search for parasite. Few amastigote forms of Leishmania donovani (LD body) were then found lying both intracellularly and extracellularly [Figure 3]. The patient was started on amphotericin B (1 mg/kg/day) for 3 weeks to which she responded well. There was resolution of fever while on therapy and blood counts were corrected to normal range within a 3-week follow-up period (hemoglobin 10.5 g/dl; total leukocyte count 6580/mm 3; platelet count 1.5 lacs/mm 3). The spleen also regressed and became nonpalpable within the same time period. Hence, bicytopenia and dysplasia were attributable to this parasitic infection rather than a part of hematological disorder. Cytogenetic study was not done after the patient responded to treatment for leishmaniasis.
Figure 1: Bone marrow aspirate smear showing erythroid hyperplasia and features of dyserythropoiesis: Mitosis (dotted arrow) and binucleate cells (arrow) (×400 Giemsa) (Inset) Bone marrow aspirate showing normocellular particles (×100 Giemsa)

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Figure 2: Bone marrow aspirate smear showing features of myeloid dysplasia: Multinucleation (dotted arrow) and pseudo-Pelger–Heut anomaly (arrow) (×400 Giemsa)

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Figure 3: Bone marrow aspirate smear: Amastigote form of Leishmania (arrow) (×400 Giemsa)

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  Discussion Top


Visceral leishmaniasis/kala azar is a parasitic disorder caused by LDwhich is endemic in the eastern belt of India (Bihar, West Bengal, and Uttar Pradesh).[1] Rarely, it may be associated with myelodysplasia in the blood or bone marrow.[1],[2],[3],[4] Severe myelodysplasia may be a confounding factor for diagnosis, especially if the parasitic load is very low. Multiple hematological manifestations are known to occur with leishmaniasis, the most common being pancytopenia. However, it may also be associated with myelofibrosis, hemophagocytosis, increase in plasma cells, gelatinous marrow transformation, and, in very few isolated cases, myelodysplasia.[1],[2],[3],[4] The diagnosis requires demonstration of LD body in bone marrow/splenic aspirate. These can be found both intracellularly and extracellularly.[1] In the present case, the diagnosis of leishmaniasis was suggested when RK39 serological test for kala azar was positive and then a repeat extensive search for LD body was done on BMA smears. Due to paucity of LD body on smears, the diagnosis was initially missed. In resource-limited settings where expensive serological tests are not available, a high suspicion followed by detailed morphological evaluation of BMA is essential.

Myelodysplastic features observed with kala azar in other studies include bilineage and trilineage myelodysplasia in the form of karyorrhexis, bi- and multinuclearity of erythroid precursors, hyposegmented myeloid precursors, and hypolobated and dwarf megakaryocytes.[1],[2],[3],[4] Dyserythropoiesis may be present alone without other lineages being affected.[5] The present case showed significant dysplasia affecting two cell lines (myeloid and erythroid), with the megakaryocytes being unremarkable leading to the normal platelet count of the patient.

The pathogenesis of myelodysplasia in kala azar has been suggested as increase in tumor necrosis factor-alpha (TNF-alpha).[3] Macrophages have been postulated as a source of TNF and are increased in number in MDS as well as parasitic infection.[3] Furthermore, TNF has been linked with apoptosis and decreased glutathione, thus causing oxygen-free radical damage in marrow.[3],[6],[7],[8] Pancytopenia in these patients is also a consequence of myelodysplasia apart from hypersplenism and suppression of bone marrow function by Leishmania and leads to further reduction in patient's counts.[3],[9] Furthermore, this can be attributed to hemolysis and hemophagocytosis in other cases of visceral leishmaniasis where these findings are noted.[1],[3] Yarali et al. observed that myelodysplastic features reversed to normal after treatment for Leishmania, thus indicating that the features of dysplasia were attributable to infection.[3] An extensive search for LD body is recommended in such cases since kala azar is a treatable cause and prevents further investigations and cytotoxic treatment.

Myelodysplasia is rare in children with an incidence of 1.8 per million population per year, with RCC being the most common subtype.[10] In children, it is commonly presented as refractory thrombocytopenia and refractory neutropenia with clinical features of bleeding, fever, and infection.[10] Bone marrow is more often hypocellular in children (75% of cases) in contrast to adults in whom it is hypercellular.[10] Considering the rarity of the disease, all causes of secondary dysplasia should be excluded. These include deficiency of Vitamin B12 and folate, viral infections (parvovirus B19, CMV, herpes, Epstein–Barr virus, and HIV), chemotherapeutic agents, toxins (ethanol, benzene, or lead), autoimmune diseases (rheumatoid arthritis), and inherited bone marrow failure syndromes in addition to leishmaniasis. A comprehensive investigative workup and repeat evaluation of bone marrow aspirate slides with staining of additional smears helped us to arrive at the correct diagnosis in the present case. Cytogenetic evaluation was not done since the diagnosis of leishmaniasis was made and the patient responded well. The present case report emphasizes the importance of morphological examination of bone marrow aspirate in such cases. This case report creates awareness among young pathologists of such association as myelodysplasia is a relatively uncommon presentation of LD infection and serological tests for Leishmania may not be carried out in such cases, thus leading to a grave diagnosis of MDS.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Dhingra KK, Gupta P, Saroha V, Setia N, Khurana N, Singh T, et al. Morphological findings in bone marrow biopsy and aspirate smears of visceral Kala Azar: A review. Indian J Pathol Microbiol 2010;53:96-100.  Back to cited text no. 1
[PUBMED]  [Full text]  
2.
Kopterides P, Halikias S, Tsavaris N. Visceral leishmaniasis masquerading as myelodysplasia. Am J Hematol 2003;74:198-9.  Back to cited text no. 2
[PUBMED]    
3.
Yarali N, Fişgin T, Duru F, Kara A. Myelodysplastic features in visceral leishmaniasis. Am J Hematol 2002;71:191-5.  Back to cited text no. 3
    
4.
Sipahi T, Tavil B, Oksal A. Visceral leishmaniasis and pseudomonas septicemia associated with hemophagocytic syndrome and myelodysplasia in a Turkish child. Turk J Pediatr 2005;47:191-4.  Back to cited text no. 4
[PUBMED]    
5.
Shahriar D, Reza MP, Reza AM, Faramarz S. Cytological clues of bone marrow findings in Kala-Azar. Diagn Cytopathol 1999;20:208-11.  Back to cited text no. 5
[PUBMED]    
6.
Sen G, Mukhopadhyay R, Ghosal J, Biswas T. Oxidative damage of erythrocytes: A possible mechanism for premature hemolysis in experimental visceral leishmaniasis in hamsters. Ann Hematol 2001;80:32-7.  Back to cited text no. 6
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7.
Salomão R, Castelo Filho A, de Medeiros IM, Sicolo MA. Plasma levels of tumor necrosis factor-alpha in patients with visceral leishmaniasis (Kala-azar). Association with activity of the disease and clinical remission following antimonial therapy. Rev Inst Med Trop Sao Paulo 1996;38:113-8.  Back to cited text no. 7
    
8.
Kemp K, Theander TG, Hviid L, Garfar A, Kharazmi A, Kemp M, et al. Interferon-gamma- and tumour necrosis factor-alpha-producing cells in humans who are immune to cutaneous leishmaniasis. Scand J Immunol 1999;49:655-9.  Back to cited text no. 8
    
9.
Rodrigues V, Cordeiro-da-Silva A, Laforge M, Silvestre R, Estaquier J. Regulation of immunity during visceral leishmania infection. Parasit Vectors 2016;9:118.  Back to cited text no. 9
    
10.
Baumann I, Niemeyer CM, Benett JM, Shannon K. Childhood myelodysplastic syndrome. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, PileriA, Stein H, et al, eds. World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2008. p. 105-7.  Back to cited text no. 10
    


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