Precursor B-cell acute lymphoblastic leukemia: An unusual cause of bilateral nephromegaly in an infant.

Acute lymphoblastic leukemia (ALL) accounts for approximately 77% of all cases of childhood leukemia.[1] Renal involvement in leukemia is well known, however, presentation in the form of nephromegaly is very rare (only 3%–5% of ALL cases).[2] Furthermore, only 2% cases of childhood leukemia occur in the age group of <1 year and are termed as infant leukemia.[1] ALL in an infant presenting as bilateral nephromegaly has been rarely documented.[234]

We report a 2-month-old male child, second by birth order (birth weight 3.5 kg), born of a nonconsanguineous marriage, who presented with increasing pallor, progressive abdominal distension, and mild intermittent fever for 1 month. On examination, the infant had severe pallor, but no icterus, edema, or lymphadenopathy. His weight was 6 kg and length was 56 cm (50–75 per centile and 25–50 per centile on standard WHO growth charts). The liver was palpable 4 cm below right costal margin, firm, nontender with a span of 7 cm. The spleen was palpable 5 cm below left costal margin. Both kidneys were palpable and ballotable. Rest of the physical examination was normal.

Investigations revealed severe anemia (hemoglobin 35 g/L), leukocytosis (white cell count of count 28.4 × 109/L (20% neutrophils and 80% lymphocytes), and thrombocytopenia (platelet count 40 × 109/L). No abnormal cells were seen on peripheral blood smear examination. A peripheral blood flow cytometry did not reveal any cells with aberrant markers suggestive of blasts. Serum aminotransferases (alanine transaminase 530 U/L, aspartate transaminase 289 U/L) and serum lactate dehydrogenase (1522.3 U/L) were elevated. Renal function tests and serum electrolytes were normal. Urine routine examination was normal. Ultrasonography of the abdomen revealed bilateral homogeneously enlarged kidneys [Figure 1a and b] with preserved corticomedullary junction along with hepatosplenomegaly. Bone marrow biopsy examination revealed the marrow to be diffusely replaced by blast cells [Figure 2a]. Sheets of dyspoietic megakaryocytes were seen. No normal hematopoietic elements were seen. Immunohistochemical staining showed the blasts were TdT and Pax5 positive [Figure 2b and c]; and CD3, CD20 negative. Few blasts were positive for MPO. A diagnosis of precursor B-cell ALL was confirmed.

Figure 1

(a) Ultrasonography of right kidney measuring 94.88 mm × 48.98 mm; (b) left kidney measuring 49.12 mm × 43.6 mm

Figure 2

(a) Bone marrow biopsy showing blasts: large cells having high nuclear to cytoplasmic ratio and hyperchromatic nuclei (H and E, ×40); (b) blasts showing strong nuclear immunopositivity for immature/precursor lymphoid cell marker TdT (×40); (c) blasts showing nuclear immunopositivity for pre-B cell marker Pax5 (×40)

The child was managed symptomatically with packed red cell and platelet concentrate transfusions. The patient was referred to a tertiary care hematooncology unit for chemotherapy. Unfortunately, the child died within 3 weeks of presentation pending initiation of chemotherapy due to financial constraints.

Although ALL in children has a favorable prognosis (overall survival rate being near 80%),[1] infant leukemia has a poor prognosis which worsens with decreasing age.[456] Renal involvement and kidney size usually do not affect the outcome in afflicted older children, but its significance in infant leukemia is uncertain.[7] Known predictors of poor outcome include very young age, high initial leukocyte count, lack of CD10 expression, presence of myeloid-associated antigen expression, presence of 11q23 translocations (or MLL rearrangements), and poor response to initial chemotherapy.[68] Due to financial constraints, further immunophenotypic and molecular characterization of the disease could not be done. The purpose of reporting this case is to highlight that infant with precursor B-cell ALL can rarely develop bilateral nephromegaly. A high degree of clinical suspicion is required for its early diagnosis and initiation of therapy as the disease has a rapid downhill course.

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Nil.

Conflict of interest

Dr. Sunil Karande is the Editor of the Journal of Postgraduate Medicine.