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Case Reports Indian Pediatrics 2002; 39:497-500 |
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Congenital Leukemia |
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Rohit Shamsher Sethi
Leukemia rarely occurs in the first month of life. Reaman et al.(1) reported that only 2 of the 115 cases entered on children cancer group had congenital leukemia. Furthermore they observed that 18% of all children of acute nonlymphocytic leukemia and 3% of all children with acute lymphoblastic leukemia were below 1 year of age. Most of neonatal cases reported so far have acute non-lymphocytic leukemia, in contrast to the predominance of acute lymphoblastic leukemia found in children. Instances of familial neonatal leukemia are also extremely rare(2). Only few cases of congenital leukemia have been reported in literature. We report here a rare case of congenital lymphoblastic leukemia in a two month male baby with striking features of leukemia cutis. Case Report A 2-month-old male baby was admitted with the complaints of nodular skin lesions over the trunk and extremities since birth, fever since 1˝ months, loose stools 5 to 6 times/day for 15 days, and cough, breathlessness and abdominal distension since 8 days. There was no history of jaundice, any form of bleeding diathesis or serosanguinous discharge from the nose. The anetenatal, natal and immediate postnatal history was uneventful. Special emphasis was given to elicit the history of maternal fever, rash or lymphadenopathy in the mother in the first trimester to rule out TORCH infections. There was no history of abortion or still birth and no history suggestive of syphilis in the parents. The baby was born full term, weighed 3 kg at birth, had not been vaccinated and was on breast feeding since birth. Examination revealed a 4 kg baby, having extreme pallor, and showing evidence of 0.5 to 1 cm size nodular fibroma like masses over the trunk and extremities, sparing the face and hands. They were gray to bluish in color, nontender and freely mobile over the subcutaneous tissues. Child was febrile, tachypneic, had rales in the chest and manifested with hepato-splenomegaly. Liver was palpable 3.5 cm below costal margin, firm and nontender, while the spleen was 2.5 cm in size. There was no evidence of facial dysmorphism, micro-cephaly, cataract, jaundice, lymphadeno-pathy, skin bleeds, moist lesions in the mucocutaneous areas of mouth, anus and external genitalia or pseudo paralysis. Neurological and cardiovascular systems were normal. Fundoscopy was essentially normal with no evidence of chorioretinites. Laboratory investigations on admission revealed a hemoglobin of 5.6 g/dl and total leukocyte count of 28,000 per cu mm with 69% lymphoblasts, 13% neutrophils and 18% lymphocytes. The platelet count was 66,000 per cu mm and reticulcyte count was 1.5%. The general blood picture showed normocytic normochomic erythrocytes showing diffuse basophillia and no parasite. Bleeding time and clotting time were within normal limits. Bone marrow aspiration revealed findings suggestive of acute lymphoblastic leukemia. The smear was hypercellular with diffuse infiltration of immature cells of lymphoid series (lymphoblasts). These cells were big rounded with moderate cytoplasm and 1 or 2 prominent nucleoli. Myeloid and erythroid series of cells were reduced in number. Erythropoiesis was normoblastic. Megakaryo-cytes were also reduced. Cerebrospinal fluid cytopathology revealed infiltration by few rounded cells (65 cells/cu mm) showing dark nucleus and prominent nucleoli suggestive of leukemic infliltration. Specific tests to rule out congenital infections, namely TORCH, WR and VDRL were within normal limits. Urine culture and sensitivity was normal. X-ray skull did not reveal any calcification. Both mother and baby’s blood group was B positive. After confirmation of the diagnosis of acute lymphoblastic leukemia, the child was put on remission induction therapy of vincristine (1.5 mg/m2 IV/week) and predni-solone (40 mg/m2 or 2 mg/kg orally/day) along with weekly intrathecal methorexate and hydrocortisone. The baby received two blood transfusions. After completion of remission induction and intrathecal therapy, there was clinical amelioration of symptoms, child became afebrile, hepatosplenomegaly regressed and the skin lesion (Leukemia cutis) started to wane. Hemogram after 15 days of induction therapy revealed a hemoglobin of 10 g/dl, total leukocyte count became normal (6,900 cell/cu mm), platelet count improved to 75,000 per cu/mm and lymphoblasts decreased from 69% to 39%. However, after 4 weeks of remission induction therapy, though the child remained symptomatically normal, complete remission was not observed, as lymphoblasts on general blood picture were still 42%. After completion of remission induction therapy, the baby was put on maintenance therapy of methotrexate and 6 merceptopurine. Discussion Congenital leukemia is a rarity and seldom occurs in the first month of life(1). Most of the neonatal cases reported have acute non-lymphocytic leukemia, in contrast to the pre-dominance of acute lymphoblastic leukemia found in later childhood(3). Familial neonatal leukemia is extremely rare and no child born to a mother with leukemia has been found to have the disease during the neonatal period(2). Con-genital leukemia is occasionally associated with number of congenital anomalies and with chromosomal disorders such as Down’s syndrome, trisomies D and E and a number of nonspecific chromosomal abnormalities. Subtle cytogenetic abnormalities may occur more commonly in the affected infants and their parents, when studied with newer cytogenetic techniques(4). The clinical signs of leukemia may be evident at birth with hepatosplenomegaly, petechiae and ecchymosis. Leukemic cell infiltration into the skin (leukemia cutis) is commonly found when the disease appears at birth and has also been noted in still born premature infants with leukemia(2). These nodular fibroma like masses are blue to grayish in color and freely movable over the subcutaneous tissue. At birth many of the infants have respiratory distress from either leukemic infiltration in the lungs or atelectasis. In those infants in whom the disease develops within first month (not at birth), the symptoms are ill defined with low grade fever, diarrhea, hepatomegaly and failure to gain weight. Leukemia cutis is less common. Our patient had almost all the classical features of congenital leukemia presenting at birth, with leukemia cutis, severe anemia, thrombo-cytopenia and hepatosplenomegaly which was confirmed by hemogram, general blood picture and bone marrow examination. Some of the clinical features confusing it with other disorders mentioned above were excluded by investigations. The child responded to specific antileukemic chemotherapy with amelioration of clinical symptomatology, decrease in leukemia cutis, hepatosplenomegaly and also decrease in the lymphoblasts on general blood picture. The diagnosis of congenital lympho-blastic leukemia was therefore not difficult in the present case. Cellular morphology(4), immunopheno-type(5) and chromosomal studies differen- tiate acute lymphoblastic from acute non lymphoblastic leukemia found in newborns. FAB classification based on cell morphology reveals that the most common subtype in infantile and neonatal acute nonlymphocytic leukemia is the monocytic variety(6,7). The most common chromosome involved in translocation in infantile acute lympho-blastic leukemia is the 11q 23 found in atleast 50% of infant leukemia and in predominance of neonatal cases(8). The differential diagnosis of congenital leukemia includes leukemoid reactions, congenital infections, severe erythroblastosis and neonatal neuroblastoma. Severe erythro-blastosis fetalis may mimic leukemia. The course of congenital leukemia is one of rapid deterioration and death from hemorrhage and infection. Specifically, it is a more aggressive disease with increased incidence of leukocytosis, massive hepatosplenomegaly, CNS involvement, thrombocytopenia, hypo-gammaglobenimia, DIC and less frequent remission induction by 14 days of age(9). The current improved success of remission induction with treatment of acute non-lymphocytic leukemia in infant younger than 1 year is similar to that in older children using combination chemotherapy. However, the experience with newborns is limited, but between 1984 to 1989, 5 of 12 newborns with acute nonlymphocytic leukemia sustained complete remission with chemotherapy, all were in the myelomonocytic or monocytic category(6,8). However, in acute lympho-blastic leukemia, the treatment outcome is significantly poorer in infants younger than 1 year at diagnosis (23% disease free survival compared with 70% for older children) and may be even lower in newborns. Only 10% to 20% survival for infants younger than 6 months of age at diagnosis has been reported as compared to 40% for those, older than 6 months(9,10). Fewer than 15% of new- borns with acute lymphoblastic leukemia have remission lasting more than few months. The therapy of congenital lymphoblastic leukemia remains the same as for older children, with the precaution that dosage needs to be altered to prevent undue toxicity of hypotonia, poor cry and flaccid paralysis with vincristine(11). Contributors: Both authors were involved in managing the case and drafting the manuscript; and both will act as guarantors. Funding: None. Competing interests: None stated.
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