[Spontaneous remission of congenital leukemia cutis]. / Lésions cutanées à type de leucémie congénitale "aleucémique" de rémission spontanée.

BACKGROUND: Aleukaemic leukaemia--without blasts in the blood or the bone marrow--with isolated cutaneous manifestations has been very rarely reported since only seven patients have been described to date. The prognosis is variable, and the indications for an aggressive treatment such as polychemotherapy are currently unclear. We report a case of spontaneously remitting aleukaemic leukaemia in a newborn child and compare it with other cases in the literature. CASE REPORT: A male newborn presented diffuse, violaceous skin nodules reminiscent of the so-called "blueberry muffin syndrome" present since birth. Blood and marrow examinations did not show any blasts and karyotype was normal. Biopsy of a nodule established the diagnosis of acute myeloid leukaemia type 5. The course was spontaneously favourable despite the absence of specific therapy and the boy was asymptomatic after one year of follow-up. DISCUSSION: Of the eight reported infants (including ours), three died, including two through acute transformation of the leukaemia. The prognosis seems to be highly dependent on cytogenetic features with the 11q23 rearrangement being at higher risk of acute transformation, prompting recourse to aggressive chemotherapy. Our case further illustrates the favourable prognostic value of a normal karyotype, a situation in which therapeutic abstention seems possible, and is even recommended.

[Congenital acute monoblastic leukemia: about one case and differential diagnosis]. / Leucémie monoblastique aiguë congénitale : à propos d'un cas et diagnostic différentiel.

Congenital leukemia is a rare disease in the newborns. It poses, however, many problems both for the clinician and for the biologist. Although of unknown etiology, the development of neonatal acute leukemia suggests a chromosomal rearrangement. Several specific chromosome rearrangements, common in cases of congenital leukemia, have been identified; it implies frequently the MLL gene. The differential diagnosis is difficult and includes different diseases frequently found in the neonatal period. We report the case of a newborn developing acute monocytic leukemia one hour after birth. Cytogenetics revealed a rearrangement of the MLL gene. The child was treated according to the protocol ELAM 02. Unfortunately, she developed multiple organ failure a few days later and died at 5 weeks.

Congenital monoblastic leukemia presenting as jaundice, pleural effusion, and ascites: case report and literature review.

Congenital leukemias are a rare group of hematologic neoplasms with a wide range of clinical signs and symptoms. Here we reported a neonate presenting with jaundice, pleural effusion and ascites. The total protein and serum albumin were markedly low at 48 and 12 g/L. Computerized tomography showed the density of liver was asymmetry with several hypoechoic regions. Initial blood routine examination revealed only thrombocytopenia while blood white cells increased to 30.0×10(9)/L with 17% blast cells several days later. Bone marrow biopsy showed the proportion of blasts and promonocytes increased and she was diagnosed as acute monoblastic leukemia.

Complex and cryptic chromosomal rearrangements involving the MLL gene in acute leukemia: a study of 7 patients and review of the literature.

Chromosomal rearrangements involving the MLL gene have been associated with many different types of hematological malignancies. Most of them are easily recognized by conventional cytogenetics. However, in some cases, complex, unusual or cryptic rearrangements make the MLL involvement difficult or impossible to be detected by conventional cytogenetics. Fluorescent in situ hybridization with a panel of probes coupled with long distance inverse-PCR was used to identify chromosomal rearrangements involving the MLL gene. Seven unusual chromosomal rearrangements were identified, including two complex translocations, three insertions of material of chromosome 11 in another chromosome and one insertion of chromosome material into the MLL gene. Conventional cytogenetics showed three patients to have a deletion of 11q; one had an unexpected t(6;11)(q27;q23) whereas the other two patients had also an insertion of MLL material in another chromosome. Concurrent 3' deletion in the MLL rearrangement was observed in two patients. We recommend a systematic approach to be used in all cases of acute leukemia starting with FISH analyses using a commercially available MLL split signal probe. Should an abnormality be discovered, the analysis has to be completed by further molecular cytogenetic and genomic PCR methods in order to unravel the recombination mechanism.

Rearrangement of MLL in a patient with congenital acute monoblastic leukemia and granulocytic sarcoma associated with a t(1;11)(p36;q23) translocation.

Band 11q23 is known to be involved in translocations and insertions with a variety of partner chromosomes. In most cases, they lead to MLL rearrangements, resulting in a fusion with numerous genes. We report here a newborn girl who had disseminated intravascular coagulation and cutaneous tumors (granulocytic sarcomata) in whom a diagnosis of acute myeloblastic leukemia (AML) FAB-M5 was made. Conventional cytogenetics using R-banding showed 11 of the 17 metaphases observed to have a 46,XX,t(1;11)(p36.2;q23) karyotype. FISH analysis confirmed the disruption of the MLL gene. Two adult patients solely have been found to have a t(1;11)(p36;q23); however, no FISH analysis with a MLL probe was performed in both cases. Since the diagnosis was made at birth, this implies that the MLL rearrangement and the onset of the disease occurred in utero. Twenty children, including 3 newborns, have been reported to have granulocytic sarcoma associated with 11q23/MLL rearrangement. To the best of our knowledge, this is the first report of a case of congenital AML with GS arising in a patient with proven MLL rearrangement.

Disseminated linear calcinosis cutis associated with the Koebner phenomenon in an infant with congenital acute monocytic leukaemia.

We present a unique case of an infant with acute monocytic leukaemia who presented at birth with multiple rubbery, erythematous to violaceous subcutaneous nodules secondary to leukaemia cutis. As these infiltrates regressed with chemotherapy, numerous white to yellow linear confluent papules appeared in a scratch-like pattern. These lesions were widely disseminated but were concentrated across her face, trunk and extremities with relative sparing of the napkin area and back. We propose that these lesions represent a form of dystrophic calcinosis cutis that occurred secondary to koebnerization in an infant with congenital leukaemia cutis.

Prenatal presentation supports the in utero development of congenital leukemia: a case report.

Congenital leukemia is a rare disease developing within the first 4 to 6 weeks of life. We report a female infant born with facial mass and multiple subcutaneous nodules. The facial mass was discovered by ultrasound during a routine prenatal examination at the 36th week of gestation. Biopsies were consistent with the diagnosis of acute monoblastic leukemia (AML, FAB M5b). Cytogenetic studies showed 46 XX, t(11;19)(q23;p13.1), which is only found in acute monoblastic leukemia and involves the gene. The infant died at 12 days of age and autopsy revealed a large leukemic tumor burden in several body organs. The discovery of the facial mass prenatally and massive extramedullary leukemic burden support the notion of the in utero development of congenital leukemia.

Is t(10;11)(p11.2;q23) involving MLL and ABI-1 genes associated with congenital acute monocytic leukemia?

Congenital, or perinatal, leukemias are rarely observed, but retrospective molecular studies seem to suggest a more frequent onset in prenatal life. Myelocytic types are common, and chromosome band 11q23 rearrangements at the MLL locus are characteristic genetic markers. The fusion of the MLL gene with one of its partners, ABI-1, has recently been described in two infant leukemia patients with monocytic involvement and good clinical outcome. We report a case of congenital monocytic leukemia with the same gene involvement and good response to chemotherapy. The blast metaphases were probed by fluorescence in situ hybridization, and t(10;11)(p11.2;q23) involving MLL and ABI-1 genes was demonstrated with the same breakpoint in ABI-1. The congenital presentation of this case suggests a possible relationship of this genetic event with in utero leukemogenesis.

Congenital monoblastic leukemia with 9;11 translocation in monozygotic twins : a case report.

We report an autopsy case of congenital monoblastic leukemia that developed in monozygotic twins. The twin presented with progressive hepatosplenomegaly at 4 weeks after birth. One twin died of massive bleeding and hypovolemic shock before the treatment started. At autopsy, the liver was diffusely enlarged and showed a diffuse whitish discoloration except for the subcapsular and perivenular areas. Microscopic examination disclosed infiltration of histiocyte-like atypical cells along the sinusoids and portal areas of the liver. Spleen, lymph nodes and choroid plexus were also infiltrated by the tumor cells. However, bone marrow involvement of the tumor was minimal although multifocal. On immunohistochemical staining, these atypical cells were reactive for CD68 (PGM-1) and lysozyme, suggesting that the tumor cells might have been derived from mono- histiocyte. Cytogenetic study revealed 9;11 translocation, which is frequently associated with acute monoblastic leukemia. To the best of our knowledge, this is the first report of congenital monoblastic leukemia of monozygotic twins in Korea.

Coexistence of lymphoblastic and monoblastic populations with identical mixed lineage leukemia gene rearrangements and shared immunoglobulin heavy chain rearrangements in leukemia developed in utero.

Congenital leukemia often provides insight into mechanisms of in utero leukemogenesis. A 10-day-old boy with clinical features of skin nodules, marked hepatosplenomegaly, and subcutaneous bleeding received a diagnosis of congenital leukemia. This patient initially had a dominant B progenitor lymphoblast population and minor monocyte component. Treatment with prednisolone, vincristine, and doxorubicin resulted in a loss of lymphoblast population and a rapid increase and dominance of the monocyte component within 10 days. Complete remission initially was obtained with additional combination chemotherapy with epipodophyllotoxin (VP-16) and cytosine arabinoside (Ara-C), but relapse characterized by a lymphoblastic population in the bone marrow was subsequently observed. The authors hypothesize that the leukemic cells originated from a common B-monocyte lineage stem cell during fetal hematopoiesis.

Congenital leukemia: successful treatment of a newborn with t(5;11)(q31;q23).

A male neonate presented with a high white cell count, an 11q23 translocation, and M5b leukemia. He was treated at 3 days of age with intensive combination chemotherapy after progressing despite exchange transfusions. The patient achieved complete remission at 28 days of age. Therapy was completed at the age of 6 months. At the time of this report, the patient is 17 months old and remains in remission. Twenty-nine patients with congenital acute myeloid leukemia were also reviewed. Twenty of these patients received varying therapies. Ten of the treated patients achieved complete remission; two died of toxicity; and eight died of progressive disease. Two patients had a translocation affecting 11q23. Congenital leukemia is a rare and usually fatal condition in patients without Down syndrome. The patient reported here shows that survival may be achieved with very intensive chemotherapy plus supportive care, despite extremely high white blood cell counts and unfavorable translocation.

["Blueberry muffin baby"]. / "Blueberry muffin baby".

BACKGROUND: Blueberry muffin baby is a characteristic neonatal syndrome characterized by multiple dark-bluish skin nodules. The clinical significance and prognosis of this syndrome are variable. CASE REPORT: A male child was born to non-consanguinous parents. At birth, a polymalformative syndrome associated macrostomy, bilateral cryptochidy and hexadactyly. There were also about twenty firm dark-bluish skin nodules disseminated over the entire body. These skin lesions regressed spontaneously within one month. Pathology examination of a skin nodule showed lymphomonocyte proliferation. Immunostaining favored T cell infiltration without monoclonal proliferation. Medullar genome mapping showed evidence of a fragile site on the end of chromosome 20. At 8 months the child had normal development. DISCUSSION: We attributed this blueberry muffin baby syndrome to T cell proliferation but we were unable to distinguish between extramedullary leukopoiesis and leukemia. Despite the absence of systematic disease and the complete regression, no exact diagnosis and prognosis could be established in the case. The association of blueberry muffin baby syndrome with a polymalformative syndrome was probably related to a genetic anomaly on chromosome 20 not previously reported.