112 Indian J. Hematol. Blood Transfus 23(3–4):112–115
Indian J. Hematol. Blood Transfus 23(3–4):112–115
CASE REPORT
Chronic eosinophilic leukemia: a case report and review of literature Ashutosh Kumar · Swasti Sinha · Anil Kumar Tripathi
Abstract Chronic Eosinophilic Leukemia (CEL) is a rare type of chronic myeloproliferative disorder of unknown etiology with no available true incidence. The vaguely overlapping clinico – pathological picture of CEL with idiopathic hypereosinophilic syndrome (IHES) often adds to the diagnostic confusion. An evidence of genetic clonality of eosinophils or an increase in blast cells in the blood or bone marrow is mandatory for diagnosis of CEL while no specific diagnostic tests exist for IHES; making it an entity of exclusion. Till date, CEL is a rarely reported entity in India. We add yet another case of eosinophilic leukemia along with review of available literature. Keywords Chronic eosinophilic leukemia · Idiopathic Hypereosinophilic syndrome
Introduction Chronic eosinophilic leukemia (CEL) is a chronic myeloproliferative disease of unknown etiology in which a clonal proliferation of eosinophilic precursors results in a persistently elevated number of eosinophils in blood, bone marrow or peripheral tissues. Reliable data on the frequency of CEL do not yet exist and the true incidence is still unknown [1] owing to the dilemma in distinguishing CEL from hypereosinophilic syndrome. However, according to available data, the incidence is highest in the fourth decade of life and the disease most commonly affects males [1]. The rarity of CEL is further compounded by a variety of other disease processes accompanied by chronically persistent eosinophilia.
Case report
A. Kumar1 () · S. Sinha2 · A. K. Tripathi3 Professor, Department of Pathology 2 Junior Resident, Department of Pathology 3 Professor, Department of Medicine King George’s Medical University, Lucknow - 226 003, India
1
Ph: 0522- 2001846 E-mail:
[email protected]
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The patient was a thirty five year old male, fruit seller by occupation who had recurrent episodes of loose motions and pain in abdomen for last 10 months. He took symptomatic treatment with minimal relief, and presented at our institution with a gradually progressive swelling over left side of his abdomen for 10 months. There was a history of marked decrease in appetite and generalized weakness in the same duration. He also had off and on bouts of pyrexia, sometimes associated with chills for the latter 6 months. The past history of the patient revealed a course of antitubercular treatment for 2 years, almost a decade ago and markedly decreased vision in left eye 1 year back for which he took treatment with moderate improvement in his vision. There was no history of any allergic disease.
Indian J. Hematol. Blood Transfus 23(3–4):112–115
On examination, the patient was afebrile and mildly anemic. There was no lymphadenopathy, skin rashes or icterus. His spleen was firm, nontender and was markedly enlarged (7 cms below the costal margin.). On investigation, his haemogram showed haemoglobin 10.0 g/dl, TLC 1,03,000 / cmm. The differential counts showed markedly increased eosinophils (87 %) and presence of increased numbers of basophils (7 %) [Fig. 1]. Absolute eosinophil count was 89,610. Platelet count was 3,00,000/cmm Red blood cells were microcytic, hypochromic. Fair number of dysplastic eosinophils along with occasional granulocytic precursors and abnormal blasts were also seen in the peripheral blood smear [Fig. 2]. ESR was increased (38 mm). Liver function tests and serum electrolytes were normal. Urine analysis revealed few pus cells without cellular casts or haematuria. Stool microscopy was
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Fig. 3 Bone Marrow aspiration smear: showing megakaryocyte clump with micromegakaryocytes. Leishman stain (x 1000)
negative for parasitic ova, cysts or blood cells. Serology was negative for Hepatitis A, B or E and HIV.
Discussion
Fig. 1 Peripheral blood smear: showing predominantly Eosinophilic population with Basophils. Leishman stain (x 1000)
Fig. 2 Peripheral blood smear: Dysplastic eosinophils and an undifferentiated blast cell. Leishman stain (x 1000)
Presently, an unexplained chronic persistent eosinophilia with a demonstrable cytogenetic abnormality or an increase in blast cells is considered as eosinophilic leukemia. There have been several major reviews in recent years with newly emerging criteria in an attempt to define CEL. Some of the earlier classic reviews [2, 3, 4, 5, 6, 7, 8] relied mainly on the clinico-morphologic attributes of the entity. Evidently, CEL lies on one pole of the continuum of the hypereosinophilic states and may arise from either a multipotent, pluripotent or eosinophil committed progenitor cell [1]. The disease is also characterized by a chronic phase that may progress to blast crisis. The eosinophils as part of the neoplastic clone may show a spectrum of characteristic morphological features including marked dysplasia manifested as trilobed or ring formed nuclei, marked cytoplasmic vacuolation, hyper or hypo granulation and small or “microeosinophils” [9] Some cells may even show basophilic and eosinophilic granulations together. The neoplastic, monoclonal nature of eosinophils has been further substantiated by various cytogenetic studies showing a multitude of chromosomal abnormalities especially trisomy 15 [10], trisomy 8 [11], isochromosome 17 [12], translocations t (2; 5) (p23; q31] [13] and t(5; 12) (q33; p13) [14] and molecular genetic abnormalities particularly linked to eosinophil differentiation (such as formation of a FIP1L1- PDGFRA fusion gene) [15].
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Indian J. Hematol. Blood Transfus 23(3–4):112–115
The modern diagnostic criteria as proposed by World Health Organization [1] for CEL include: • • • • •
•
Persistent eosinophilia ≥1.5 x 109/L in blood, increased bone marrow eosinophils > 5% but 2% in the peripheral blood Clonality of myeloid cells No reactive eosinophilia due to allergy, parasitic, infectious, pulmonary, or collagen vascular disease No reactive eosinophilia due to other malignancies:
and rapidly aggressive clinically course in such patients resulting from release of cytokines and other enzymes from eosinophilic granules (major basic protein and eosinophilic cationic protein) as well as leukemic tissue infiltration, calls for prompt identification and institution of therapy. However, the effective management in our setup often depends upon the urgent control of eosinophil counts and amelioration of factors that cause tissue damage. Thus, the differentiation of the leukemic state becomes vital for effective management, as apart from treatment related to symptomatic relief (as for hypereosinophilic syndromes), it should also include anti-leukemic regimen.
*T-cell lymphomas
*Mastocytosis
*Acute lymphoblastic leukemia/lymphoma
*Hodgkin’s lymphoma
*Other myeloproliferative diseases
*Myelodysplastic syndrome
References
*Acute myeloid leukemia including inv (16), t (16; 16)
*CML
1. Vardiman JW et al (2001) Chronic myeloproliferative diseases and Myelodysplastic / myeloproliferative diseases. World Health Organization Classificationof Tumours. Pathology and Genetics.Tumours of Haematopoietic and Lymphoid Tumours. H. N. Jaffe ES, Stein H, Vardiman JW. Lyon, France, IARC Press: 17–31, 47–52 2. Bently HP Jr, Reardon AE, and Knoedler JP (1961) Eosinophilic leukemia. American Journal of Medicine 30:310–322 3. Odeberg B (1965) Eosinophilic leukemia and disseminated eosinophilic collagen disease-a disease entity ? Acta Medica Scandinavica 177:129–144 4. Bengtsson E (1968) Eosinophilic leukemia- an immunopathological reaction? Acta Paediatrica Scandinavica 57: 245–249 5. Benvenisti DS, and Ultmann JE (1969) Eosinophilic leukemia. Report of five cases and review of literature. Annals of Internal Medicine 71:731–745 6. Flannery EP, Dillon DE, Freeman MVR, Levy JD, d’Ambrosio U and Bedynek JL (1972) Eosinophilic leukemia with fibrosing endocarditis and short Y chromosome. Annals of Internal Medicine 77:223–228 7. Zucker-Franklin D (1974) Eosinophil function and disorders. Advances in Internal Medicine 19:1–25 8. Chusid MJ, Dale DC, West BC and Wolff SM (1975) The hypereosinophilic syndrome: analysis of fourteen cases with review of the literature. Medicine(Baltimore) 54:1–27 9. Rudolf WHR, Yasemien M, Martin W, Ulrich K, Ulf S, Christian G, and Klaus H (1997) Chronic eosinophilic leukemia ( CEL ): a distinct myeloproliferative disease. British Journal of Haematology 96:117–123 10. Oliver JWDI, Morgan DL, Tonk VS (1998) Chronic eosinophilic leukemia and hypereosinophilic syndromes. proposal for classification, literature review, and report of a case with a unique chromosomal abnormality. Cancer genet Cytogenet 107(2):111–117 11. Ma SK, K Y, Shek TW, Wan TS, Chow EY, Chan JC, Chan LC (1999) The role of trisomy 8 in the pathogenesis of chronic eosinophilic leukemia. Hum Pathol 30(7): 864–868 12. Saitoh TSM, Inoue M, Ishizuka H, Kura Y, Yamazaki T, Itoh T, Sawada U, Horie T (2002) CD25 positive chronic eosinophilic leukemia with myelofibrosis.[Article in Japanese]. Rinsho Ketsueki 43(10):918–923
No T-cell population with abnormal cytokine production and aberrant phenotype
Almost all reported cases in Indian subcontinent belong to hypereosinophilic syndrome [16, 17, 18]; majority of them being associated with parasitic involvement [19] or allergic respiratory disease conditions. Our case meets the morphologic criteria of CEL. Though the karyotype could not be investigated, a presumptive diagnosis of Eosinophilic leukemia is justified in view of the markedly high absolute eosinophil count (as above mentioned to be approximately 90,000; higher than that seen in any of the reported cases of idiopathic hypereosinophilia so far) and peripheral basophilia. Besides, the characteristic morphology showing obvious proliferation of eosinophilic precursors (8%) including eosinophilic promyelocytes along with dysplastic features, confirms to the neoplastic nature of eosinophils [20], excluding hypereosinophilic syndrome where the increased eosinophilic population is largely reactive. In this respect, our case falls in the category as reported by Chusid [8] in a series of 14 patients; out of these, 4 cases were classified as eosinophilic leukemia depending upon the presence of raised eosinophil counts and immature eosinophilic precursors especially promyelocytes. Splenomegaly was present in 3 of his cases. Our case study is an attempt to highlight the need for caution in diagnosing patients with unexplained eosinophilia, even when conclusive cytogenetic proof of the neoplastic nature of the disease is lacking. To this date, CEL is not a well-defined entity, and differentiating between CEL and HES can be challenging. In many instances, a correct diagnosis can only be established after serial observations and investigations over time [17]. The multiorgan damage
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