Acute Lymphoblastic Leukemia Presenting as Nephromegaly - A Rare Case Report

Introduction

Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood.¹ It accounts for 20% of all the malignancies and 77% of malignancies of childhood. The signs and symptoms develop due to infiltration of leukemic cells in marrow and extramedullary sites. The usual presentation involves the peripheral blood and bone marrow, like fever, malaise and recurrent infection. The extramedullary involvement is usually lymph nodes, central nervous system, liver, spleen and skin.² In this case report, a rare presentation of ALL as nephromegaly is being highlighted.

Case Presentation

A three years old male child presented with recurrent episodes of fever for one month. On general examination, the child was found to have pallor and just palpable liver. Hemogram of the child showed hemoglobin 9.9 g/dL, total leukocyte count 8.6x103 cells/µl and platelet count 240 x103 /µl. The peripheral smear examination showed microcytic, hypochromic blood picture with relative neutrophilia. Bone marrow aspiration showed a blood mixed marrow with 29% blasts which are medium sized cells, with coarse chromatin, 0-1 inconspicuous nucleoli and scant cytoplasm (Figure 1). The imprint smears showed sheets of blasts. Blasts were negative for Sudan Black B. Bone marrow biopsy (Figure 2) showed features consistent with acute lymphoblastic leukemia. The immunophenotyping analysis by flow cytometry on the bone marrow sample showed bright positivity for CD19, CD79a, Tdt and CD10. Dim positivity of CD34 and CD10, negative for Myeloperoxidase, CD33 and CD117, confirming the diagnosis of B-cell acute lymphoblastic leukemia. Aberrant expression of CD13 was seen. Abdominal ultrasound showed bilateral symmetrically enlarged, heteroechoic echogenic kidneys. MRI scan showed bilateral nephromegaly with no focal lesions and normal collecting system, the possibility to rule out nephroblastomatosis. The patient underwent renal biopsy which showed features of infiltration by B-cell acute lymphoblastic leukemia, confirmed by Immunohistochemistry (LCA, CD20, Tdt, CD10, Bcl 2, CD79A were positive).

Discussion

Acute lymphoblastic leukemia is a neoplasm of precursor lymphoid cells committed to the B cell lineage, typically composed of small to medium sized blasts cells with scant cytoplasm, moderately coarse chromatin and inconspicuous nucleoli involving bone marrow and blood.¹ The bone marrow is involved in all cases classified as B-Cell Acute Lymphoblastic Leukemia and usually peripheral blood. Central Nervous system (CNS), lymph nodes, spleen, liver and testicles are the common sites of extramedullary involvement.² In late stages of ALL, kidneys are involved. Bilateral symmetrical involvement of the kidneys at presentation is very rare. Sometimes leukemic infiltration of the kidneys is detected incidentally by imaging during the course of disease or during testing, prior to treatment. A study done by Hilmes et al. reported 12 children with renal involvement by leukemia, detected by contrast-enhanced abdominal computed tomography³ . Focal and multifocal parenchymal abnormalities are more frequently seen than nephromegaly. The interaction of chemokine receptor CXCR⁴, which is expressed on leukocytes and ALL cells may be the potential mechanism of trafficking of leukemia cells in the kidneys. Crazzolara et al reported a high expression of chemokine receptor CXCR4 in ALL which can predict the extramedullary infiltrate.⁴ The renal involvement does not necessarily cause renal dysfunction. A study done by Banday et al.in patients with hematological malignancies showed 57% of leukemia patients had leukemic infiltration of kidneys.⁵ Bhatia et al. reported three cases of acute lymphoblastic leukemia who presented with renal failure at the time of presentation. In all the three cases, bone marrow showed features of acute lymphoblastic leukemia which were confirmed by flow cytometry.⁶ Thakore et al. had described a 4-year-old child with history of fever and abdominal pain of short duration. Complete blood count and computed tomography were done to rule out appendicitis. The patient was discharged with diagnosis of viral gastritis. CT imaging revealed bilateral renal enlargement with multiple small subcortical and cortical medullary lesions, which were consisting with features of nephrogenic rests. The child came back to hospital after 14 days, with complaint of abdominal pain and fever. Complete blood counts were repeated and it showed blasts. The child was diagnosed as ALL in the bone marrow aspirate and was confirmed by flow cytometry.⁷

Conclusion

In conclusion, this was a case of pediatric ALL where the child presented with isolated bilateral nephromegaly, with no evidence of peripheral blood smear abnormalities and showed sheets of blasts in the bone marrow aspirate, imprint smears and bone marrow biopsy. Lymphoblastic infiltration should be suspected in any child who presents with enlarged kidneys. Renal biopsy is important in differential diagnosis of renal involvement and it should be done for diagnosis and therapy.