The n e w e ng l a n d j o u r na l
case records of the massachusetts general hospital
From the Departments of Pediatric Der-
matology (M.M.B.), Pediatric Hematolo-
gy–Oncology (M.S.H.), and Pathology
(R.M.S.), Massachusetts General Hospi-
tal, Boston; the Department of Pediatric
Dermatology, Cambridge Hospital (Cam-
bridge Health Alliance), Cambridge, MA
(M.M.B.); and the Departments of Der-
matology (M.M.B.), Pediatrics (M.S.H.),
and Pathology (R.M.S.), Harvard Medi-
cal School, Boston.
N Engl J Med 2007;357:2616-23.
Copyright © 2007 Massachusetts Medical Society.
2616
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of m e dic i n e
Founded by Richard C. Cabot
Nancy Lee Harris, m.d., Editor Eric S. Rosenberg, m.d., Associate Editor
Jo-Anne O. Shepard, m.d., Associate Editor Alice M. Cort, m.d., Associate Editor
Sally H. Ebeling, Assistant Editor Christine C. Peters, Assistant Editor
Case 39-2007: A 5-Month-Old Girl
with Skin Lesions
Melissa M. Burnett, M.D., Mary S. Huang, M.D., and Rania M. Seliem, M.D.
Pr e sen tat ion of C a se
Dr. Ruth Ann Vleugels (Dermatology): A 5-month-old girl was seen in the pediatric der-
matology clinic because of a rash. She had been well until 3 months of age, when her
parents noticed a red, slightly raised lesion on her left cheek, 2 mm in diameter,
which did not seem to cause discomfort. It grew slowly over the next several weeks,
with swelling at times but no frank blistering. Approximately 1 week before the cur-
rent evaluation, additional reddish-brown papules, 2 to 5 mm in diameter, appeared,
first on the forehead and then on the chest, abdomen, back, arms, and legs. The fore-
head lesion regressed, and the new lesions did not seem to cause discomfort. The pa-
tient was seen by her pediatrician, who referred her to the pediatric dermatology clinic
of this hospital.
The patient was born by spontaneous vaginal delivery at 40 weeks 5 days of ges-
tation to a healthy 39-year-old mother after an uncomplicated pregnancy. The pa-
tient’s mother had taken fertility medications briefly before conception. Trisomy 21
was not detected in chorionic villus sampling. The birth weight was 3345 g, and the
Apgar scores were 7 and 9 at 1 and 5 minutes, respectively. No skin lesions were
noted at birth. The baby’s growth and development had been normal. Evaluation for
ureteral reflux was negative 31 ∕2 months before the current visit, and a 6-week course
of amoxicillin was completed. The patient had been given no other medications and
had no known drug allergies. The patient’s mother had a history of mild eczema and
onychomycosis; the father had no skin conditions. A maternal first cousin died at
2 months of age from the VATER complex (vertebral anomalies, vascular anomalies,
anal atresia, tracheoesophageal fistula, esophageal atresia, renal anomalies, and
radial dysplasia). There was a maternal family history of breast and bladder cancer
and a paternal family history of diabetes mellitus and breast cancer.
At the time of evaluation, the patient’s diet consisted of breast milk, formula, and
solids that had been added 3 weeks before presentation. She was at the 75th percen-
tile for height and the 90th percentile for weight. She had not had diarrhea, wheez-
ing, shortness of breath, flushing, obvious bone or joint pain, or aversion to bearing
weight when pushing up. She had had no fevers or recent symptoms of viral illness.
On examination, the patient appeared well and was well nourished. On the left
cheek, there was a reddish-brown, mildly edematous plaque, 2 cm in diameter
(Fig. 1A). There were several scattered reddish-brown papules, 2 to 5 mm, on the face,
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The New England Journal of Medicine
 case records of the massachuset ts gener al hospital

predominantly on the forehead. The conjunctivae,

mucous membranes, and oropharynx were clear. A
There were approximately 100 reddish-brown,
barely palpable papules, 2 to 5 mm, primarily on
the chest and abdomen (Fig. 1B) as well as the
back, with some involvement of the lower sacrum
and buttocks and less prominent involvement of
the upper arms and legs. There was no involve-
ment of the genitalia. Two of the small lesions
were rubbed vigorously without causing a wheal
at either site. There was no palpable lymphade-
nopathy or hepatosplenomegaly. Laboratory-test
results are shown in Table 1.
A diagnostic procedure was performed. B

Differ en t i a l Di agnosis

Dr. Melissa M. Burnett: I participated in the care of

this patient and am aware of the diagnosis. The
first consideration when evaluating this patient is
whether the lesion on the left cheek and the more
diffuse and acute cutaneous eruption are related.
If we consider the cheek lesion separately, the dif-
ferential diagnosis includes cutaneous lymphoid
hyperplasia, mastocytoma, solitary histiocytoma,
juvenile xanthogranuloma, and myeloid sarcoma Figure 1. Clinical Photographs of the Patient.
(a solitary form of leukemia cutis) (Fig. 2). By far, There was a large, erythematous, raised lesion on the
the most likely of these would be cutaneous lym- left cheek (Panel A), with multiple small, erythema-
tous, AUTHOR
ICMraised lesionsBurnett RETAKE
on the trunk (Panel B). 1st
phoid hyperplasia or mastocytoma in this other- REG F FIGURE 1a&b of 2nd
wise healthy patient. If we consider the acute, gen- CASE TITLE Revised
3rd

eralized eruption independently of the lesion on months

EMail to years; and resolvesLine spontaneously.
4-C Oc-
Enon SIZE
the left cheek, then a viral exanthem is certainly casionally,
FILL
individual
ARTIST: mst lesions
H/T are
Combo
H/Tpruritic,
16p6 but in
a possible diagnosis, given the slightly erythema- general, they are asymptomatic,
AUTHOR, PLEASE NOTE:
as the lesions in
tous and finely papular quality of the individual this patient were.
Figure has been Extracutaneous
redrawn and type has involvement
been reset. is
Please check carefully.
lesions. I suspected, however, that the plaque on exceptionally rare.
the left cheek and the generalized eruption were When the lesions are traumatized,
JOB: 35725
or rubbed
ISSUE: 12-20-07
related. Thus, my differential diagnosis included firmly, the cutaneous mast cells may release pro-
urticaria pigmentosa, disseminated juvenile xan- inflammatory mediators, causing edema, erythe-
thogranuloma, generalized eruptive histiocytosis, ma, and even vesicle formation. This phenomenon,
and, although less likely, leukemia cutis. known as Darier’s sign, is helpful in making a
diagnosis, but it is not always positive. I was un-
Urticaria Pigmentosa able to elicit Darier’s sign in this patient; however,
The most common form of mastocytosis in child- her parents noted that the lesion on the left cheek
hood is urticaria pigmentosa.1,2 In this disorder, occasionally became more swollen, and a small
mast cells accumulate in the skin, forming reddish- vesicle did develop spontaneously within one of
brown papules and plaques, typically between 0.5 the lesions on her thigh.
and 1.0 cm in diameter, although smaller and larg- The lesion on the left cheek was not typical of
er lesions have been reported. The lesions are typi- urticaria pigmentosa because of its size, but it
cally distributed on the trunk and proximal ex- could be a solitary mastocytoma, which accounts
tremities, with rare involvement of the face, scalp, for 15 to 20% of cases of childhood mastocyto-
palms, or soles.2,3 Urticaria pigmentosa usually sis.3 Mastocytoma typically develops in the first
arises in early childhood, which is consistent with few months of life, as in this case, appearing as
its appearance in this patient; lasts for several a skin-colored or yellowish plaque, with a peau

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 The n e w e ng l a n d j o u r na l of m e dic i n e

the macronodular variant of juvenile xanthogran-

Table 1. Results of Laboratory Tests.
uloma on the left cheek and the disseminated mi-
Reference cronodular variant on the trunk and the arms and
Range, 1 Day after legs, but her lesions do not have the characteris-
Variable Adults* Presentation
tic yellow color.
White-cell count (per mm3) 5,000–19,500 12,800
Differential count (%) Generalized Eruptive Histiocytosis
Neutrophils 20–46 17 Fewer than 50 cases of generalized eruptive his-
Lymphocytes 50–85 76 tiocytosis, a form of non–Langerhans’-cell histio-
Monocytes 4–11 2
cytosis in the skin, have been reported in the lit-
erature, and only 9 cases in children have been
Eosinophils 0–8 5
reported.6,7 Clinically, the disorder is manifested
Hematocrit (%) 29.0–41.0 31.0 as hundreds of reddish-brown, firm papules, usu-
Hemoglobin (g/dl) 9.5–13.5 11.0 ally smaller than 1 cm in diameter, in an axial
Platelet count (per mm3) 150,000–450,000 505,000 distribution. The papules appear and disappear,
Aspartate aminotransferase (U/liter) 9–80 64 leaving some postinflammatory hyperpigmenta-
Alanine aminotransferase (U/liter) 7–30 52 tion. In general, there is no systemic involvement.
There has been a single report of progression to
Bilirubin (mg/dl)†
xanthoma disseminatum, with clinically similar le-
Total 0–1.0 0.3
sions involving the skin and mucous membranes in
Direct 0–0.4 0.0 association with diabetes insipidus.8 Given the rar-
ity of this disorder, I did not favor this diagnosis.
* Reference values are affected by many variables, including the patient popula-
tion and the laboratory methods used. The ranges used at Massachusetts
General Hospital are for adults who are not pregnant and do not have medi- Leukemia Cutis
cal conditions that could affect the results. They may therefore not be appro- The infiltration of leukemic cells in the skin is
priate for all patients.
† To convert the values for total and direct bilirubin to micromoles per liter, called leukemia cutis.9 Cutaneous infiltrates can
multiply by 17.1. be seen with any type of leukemia but are most
common in acute myeloid leukemia (AML), partic-
ularly when there is monocytic differentiation.5
d’orange quality of the skin. If this lesion were Leukemia cutis is typically manifested as reddish-
associated with a disseminated eruption, it would brown to violaceous papules, nodules, or plaques
probably be simply an unusually large lesion of in the skin, particularly on the head and neck, but
urticaria pigmentosa. the trunk and the arms and legs are also common-
ly involved. The disorder may also be manifested
Disseminated Juvenile Xanthogranuloma as a solitary nodule, known as myeloid sarcoma,
The most common form of non–Langerhans’-cell granulocytic sarcoma, or chloroma.5 Congenital
histiocytosis in childhood is juvenile xanthogran- leukemia cutis is often manifested as blue–violet,
uloma.4 Two variants have been described: a mac- subcutaneous nodules that represent regions of
ronodular variant, with few to several lesions that extramedullary hematopoiesis in the skin (a con-
are larger than 1 cm in diameter, and a micronod- dition called blueberry-muffin baby). Cutaneous
ular variant, with multiple lesions that are small- macules, ecchymoses, vesicles, bullae, ulcers,5
er than 1 cm. These two variants frequently coex- a seborrheic dermatitis–like condition,10 and le-
ist. Juvenile xanthogranuloma usually develops in sions resembling urticaria pigmentosa, with Dari-
infancy or early childhood, with 15 to 20% of cas- er’s sign,11 may occur.
es present at birth.4 Extracutaneous involvement Aleukemic leukemia cutis is the presence of
occurs in rare cases.5 Juvenile xanthogranuloma leukemia cutis without involvement of the bone
typically resolves spontaneously over the course of marrow or blood.12 This condition is defined as
several years and is generally asymptomatic. Ini- the presence of skin involvement for longer than
tially, the lesions may appear as pink to reddish- 1 month without involvement of the blood or bone
brown papules or plaques, but a more yellowish marrow and with no evidence of trisomy 21. At
coloration quickly develops. Our patient could have birth or shortly thereafter, patients with trisomy

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 case records of the massachuset ts gener al hospital

21 often have skin lesions that resemble leukemia

cutis clinically and histologically; these lesions are
part of a transient myeloproliferative disorder
that may resolve spontaneously over a period of
weeks.13,14 Differential Diagnosis Combined Differential Diagnosis
I considered the possibility that the lesion on for Solitary Cheek Lesion Differential Diagnosis for Generalized Eruption
the left cheek of this infant represented a granu- Cutaneous lymphoid Urticaria pigmentosa Viral exanthem
hyperplasia Disseminated juvenile
locytic sarcoma and that the generalized eruption Mastocytoma xanthogranuloma
was leukemia cutis. However, because the infant Solitary histiocytoma Generalized eruptive
Juvenile xantho- histiocytosis
was otherwise healthy, with a normal complete granuloma Leukemia cutis
blood count and no hepatosplenomegaly or lymph- Myeloid sarcoma
adenopathy, this diagnosis seemed unlikely. In
view of the patient’s age, the appearance and dis-
tribution of the lesions, and her generally good
health, I favored a diagnosis of urticaria pigmen- Figure 2. Differential Diagnosis of Solitary and Multiple Cutaneous Lesions
tosa. A biopsy of a lesion on the left trunk was in an Infant. ICM AUTHOR: Burnett RETAKE 1st
performed. The most important FIGURE: 2 of 3 2nd
REG F consideration in this case is whether the solitary cheek
3rd
Dr. Nancy Lee Harris (Pathology): Was Langer- lesion and theCASE
generalized eruption are independent ofRevised
each other or mani-
hans’-cell histiocytosis part of your differential di- festations of the same process.
EMail
ARTIST: ts
Line 4-C SIZE
H/T H/T 22p3
agnosis? Enon
Combo
Dr. Burnett: Typically, Langerhans’-cell histiocy- AUTHOR, PLEASE NOTE:
tosis in infancy is manifested as waxy papules with cell tryptase, andFigure
myeloperoxidase. These
has been redrawn and type hasresults
been reset.
Please check carefully.
purpuric or petechial centers. These lesions can are most consistent with cutaneous infiltration by
AML with monocytic 15
be generalized, but they are usually most promi- JOB: 35725 differentiation. ISSUE: 12-20-07
nent on the scalp and in the diaper region. This Since most cases of acute monocytic leukemia
patient did not have petechial lesions, and her in infants are characterized by a translocation in-
genitalia were unaffected. volving the MLL gene at chromosome 11q23, fluo­
r­es­cence in situ hybridization (FISH) was performed
on nuclei extracted from the paraffin block to de-
DR . MEL IS S A M. BUR NE T T ’S
DI AGNOSIS tect abnormalities of chromosome 11q23; we also
looked for the t(8;21) translocation, which is also
Urticaria pigmentosa (cutaneous mastocytosis). frequently involved in acute leukemias with extra-
medullary involvement; and trisomy 21. Rearrange-
Pathol o gic a l Dis cus sion ment at 11q23 was observed in 28 of 50 nuclei,
which exceeded the normal range (up to 1%) (Fig.
Dr. Rania M. Seliem: Pathological examination of 3C). Chromosomes 8 and 21 were normal. A di-
the skin-biopsy specimen showed an infiltrate of agnosis of acute monoblastic leukemia involving
mononuclear cells involving the upper and deep the skin, with 11q23 rearrangement involving the
dermis, with a periadnexal pattern, and sparing MLL gene, was made. Translocations involving
the epidermis. The infiltrating cells were of me- 11q23 are seen in both lymphoid and myeloid leu-
dium size, with a moderate amount of cytoplasm, kemias and occur most often in children, particu-
folded irregular nuclei, finely dispersed chroma- larly infants, and in patients with therapy-related
tin, and small nucleoli (Fig. 3A). The morphologic acute leukemias.16 Multiple other chromosomes
differential diagnosis included mast-cell disease, may be involved as partners in 11q23 transloca-
Langerhans’-cell histiocytosis, and leukemia cutis. tions.
Immunohistochemical stains revealed that the tu- After the diagnosis was made, bone marrow
mor cells expressed the monocyte-associated an- biopsy and aspiration were performed. There was
tigens CD68 and lysozyme, as well as CD117 (Fig. trilineage hematopoiesis, with 13% blast cells
3B) and CD34, antigens associated with early my- showing monocytic differentiation (Fig. 3D). Re-
eloid precursors; the cells were negative for the view of the peripheral-blood smear showed no
Langerhans’-cell associated antigen CD1a, mast- blast cells. Flow cytometry performed on the bone

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 The n e w e ng l a n d j o u r na l of m e dic i n e

A B

C D

Figure 3. Skin-Biopsy Specimen.

There is an infiltrate of primitive-appearing, medium-size cells (Panel A, hematoxylin and eosin) with a moderate
amount of cytoplasm, folded irregular nuclei, and finely dispersed chromatin (inset, Giemsa). Immunoperoxidase
staining shows that the atypical cells AUTHOR for
ICMare positive Burnett RETAKE
the early myeloid-associated 1st
antigen CD117 (Panel B); they also
FIGURE
REG F(not 3a-d of 3immunophenotype identifies 2nd
expressed CD68, lysozyme, and CD34 shown). This the cells as myeloid blasts.
CASE 3rd
Nuclei were extracted from formalin-fixed, paraffin-embedded tissue from Revised
TITLE the skin-biopsy specimen and placed on
EMail
a glass slide. Use of a dual-color, break-apart rearrangement probe 4-C
Line (Vysis) to evaluate the MLL locus on chromo-
Enon SIZE
some 11q23 shows split signals (one red ARTIST: mst
and one green) inH/T
two of the
H/Tfour nuclei (Panel C, arrows), indicating a
FILL Combo 33p9
break in the MLL gene on one copy of chromosome 11; the other two nuclei contain only yellow signals, indicating
AUTHOR,photograph
an intact MLL locus (fluorescence in situ hybridization; PLEASE NOTE: courtesy of Dr. Paola Dal Cin, Pathology,
Figure has been redrawn and type has been reset.
Brigham and Women’s Hospital). The bone marrow aspirate contained rare blast cells with irregular nuclei, which
Please check carefully.
are features of monoblasts (Panel D, Wright–Giemsa). Histochemical staining for nonspecific esterase is positive
in the blast cells, confirming monocytic
JOB: differentiation
35725 (Panel D, ISSUE:
inset, alpha-naphthyl
12-20-07 butyrate esterase).

marrow aspirate revealed 6% myeloid blast cells
expressing CD33, CD117, HLA-DR, and CD34,
a normal immunophenotype. The percentage of
blast cells did not meet the World Health Orga-
nization criterion for the diagnosis of AML (20%
blasts in the bone marrow or the peripheral
blood). Cytogenetic analysis revealed a normal fe-
male karyotype, and FISH analysis for MLL rear-
rangement disclosed no rearrangement. Thus, the
bone marrow findings were considered to be sug-
gestive, but not diagnostic, of acute monoblas-
tic leukemia.
Dis cus sion of M a nage men t
Dr. Mary S. Huang: After the initial review of the
skin-biopsy specimen raised the possibility of leu-
kemia cutis in this infant, the patient was seen in
consultation in the pediatric hematology–oncology
clinic. On evaluation, she had a normal physical
examination, except for the rash. We repeated a
complete blood count, complete metabolic pan-
el, and liver-function tests and reviewed the periph-
eral-blood smear, which was normal. Although
there were blast cells with monocytic features in

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 case records of the massachuset ts gener al hospital
the bone marrow, the percentage of blast cells was
not diagnostic of AML. The cytogenetic analysis
did not reveal a clonal population, and although
flow cytometry showed increased myeloblasts, they
did not have an aberrant immunophenotype di-
agnostic of cancer. Nonetheless, we believed that
in the face of a firm diagnosis of leukemia cutis
with a rearrangement at chromosome 11q23, the
increased number of monocytoid blast cells in the
bone marrow, although less than 20%, was suffi-
cient to make a diagnosis of AML. Cytologic analy-
sis of the cerebrospinal fluid was negative for leu-
kemic cells.
Acute Leukemia in Infancy
Acute leukemia is the most common cancer in
childhood. The majority of these cancers are lym-
phoid, with AML accounting for about 20% of cas-
es. Leukemias in infancy and congenital leukemia
have unique features.17 In the newborn period,
AML accounts for almost two thirds of cases.16,18
AML in infants is frequently manifested as leuke-
mia cutis, with central nervous system involve-
ment,19 monocytic differentiation, and translo-
cations involving the MLL locus at chromosome
11q23. This case illustrates many of the character-
istic features of AML in infants, including cutane-
ous involvement, monocytic differentiation, and a
break in the MLL locus at chromosome 11q23.
Treatment of Pediatric AML
Selection of treatment for this patient depended
first on the classification of the process as myeloid
or lymphoid and then on an assessment of risk fac-
tors for a poor outcome with standard therapy.
Treatment for childhood AML consists of chemo-
therapy to induce remission, followed by a rela-
tively short course of additional therapy. The ad-
ditional therapy may be intensive chemotherapy
for 3 to 6 months, high-dose therapy with autolo-
gous stem-cell rescue, or allogeneic bone marrow
transplantation early in the first remission. This
short, intensive approach is different from the
strategy used to treat childhood acute lymphoblas-
tic leukemia (ALL), which involves prolonged treat-
ment for 2 to 3 years and reserves bone marrow
transplantation for the small subgroup of patients
with very-high-risk features.
The most active drugs for AML include the an-
thracyclines (daunorubicin and idarubicin), cyta-
rabine, and etoposide; data suggest that intensive
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induction chemotherapy, followed by high doses
of cytarabine for consolidation, is important to the
long-term success of treatment. Despite an aggres-
sive approach, however, about half of all children
with AML have a relapse.20,21 Allogeneic bone
marrow transplantation is considered in patients
whose leukemias have high-risk features.
Risk Stratification
In selecting optimal treatment for children with
AML, we attempt to stratify therapy on the basis
of clinical or biologic features. This patient did not
have several features associated with a poor prog-
nosis, including monosomy 7, FLT3-activating mu-
tations,16,22 or a therapy-related leukemia; she also
lacked several favorable prognostic factors, such
as trisomy 21, inv(16), t(8;21), and t(15;17). In de-
ciding on treatment for this patient, I focused on
three main features to assess her risk: age at pre-
sentation, extramedullary skin involvement with
minimal bone marrow involvement, and the 11q23
translocation.
Age Less Than 1 Year
This patient presented in the first year of life. Out-
comes for infant leukemia, both ALL and AML,
have historically been dismal, meaning that an
age of less than 1 year was recognized early as an
adverse prognostic indicator in both AML and ALL.
For ALL, such a young age remains a poor prog-
nostic factor. In contrast, with the aggressive ther-
apy that is now available, outcomes for AML in
infancy have improved dramatically. Some groups
have now gone so far as to suggest that age of less
than a year is a favorable prognostic feature, cit-
ing 3- and 4-year event-free survival rates as high
as 55 to 70%.19,23 Thus, the patient’s age by itself
does not warrant more aggressive therapy.
Leukemia Cutis
Leukemia cutis is the most common form of ex-
tramedullary leukemia in pediatric AML, occurring
in about 6% of the cases in one series.24 Children
with skin involvement tend to be younger, to more
often have monocytic differentiation, and to have
an increased incidence of central nervous system
involvement and poorer survival than patients with
nonskin or no extramedullary leukemia. In con-
genital and neonatal leukemia, leukemia cutis of-
ten precedes overt bone marrow involvement, as it
did in this case, and there are anecdotal reports
2621
 The n e w e ng l a n d j o u r na l of m e dic i n e

of spontaneous remission in such patients, some
lasting months to years, even when there is bone
marrow involvement.12,25,26 However, other reports
describe aggressive and progressive disease.27
There are no specific clinical features at presen-
tation to predict which infants with leukemia cu-
tis require immediate aggressive therapy and which
may have a spontaneous remission. However, when
there is cytogenetic evidence of an 11q23 translo-
cation or of progressive disease, therapy is indi-
cated.
In this case, we had confirmed evidence of an
11q23 translocation, despite the absence of overt
leukemia in the bone marrow, and although we
followed the patient for only a short time without
treatment, her parents had been watching her skin
lesions progress over several weeks. We thus felt
confident that prompt therapy was indicated.
Abnormalities of Chromosome 11q23
at the MLL Locus
Translocations involving the MLL locus at 11q23
are adverse prognostic factors in infants with ALL
and in patients in whom translocations are caused
by prior chemotherapy; however, they appear to
be less important as predictors of a poor outcome
in cases of infant AML.12 The t(9;11) translocation
has been reported to be associated with improved
survival in some but not all series.28,29 We do not
know the other chromosome that was involved in
the translocation in this patient, and there are in-
sufficient data to support modifying therapy based
on the cytogenetic findings in this case.
We chose to treat this infant with a standard
regimen for AML, consisting of daunorubicin
and cytarabine, with hematopoietic growth-fac- Acute myeloid leukemia with a t(11q23) translo-
tor support.
Dr. Howard J. Weinstein (Pediatric Hematology– cutis).
Oncology): I want to reemphasize the importance
of ruling out the transient myeloproliferative syn- other potential conflict of interest relevant to this article was re-
drome associated with trisomy 21 and trisomy 21 ported.
mosaicism before proceeding with chemotherapy
in a neonate with a presumptive diagnosis of AML,
because the majority of these infants have hema-
tologic improvement without therapy. In some
cases, only the leukemic clone carries the trisomy,
and the infant may have no stigmata of Down’s
syndrome.30 The other neonates with suspected
AML who may warrant observation only are those
with very rare cases of leukemia cutis in which
there is neither an increase in blast cells in the
bone marrow nor a clonal chromosomal abnor-
mality in the blast cells infiltrating the skin; they
may have long-term, spontaneous remissions.
Dr. Huang: Within a few days after the start of
therapy, there was noticeable regression of skin
lesions, and within a week, they had almost
completely resolved. The patient had a complete
remission and completed both induction and con-
solidation chemotherapy without difficulty. Un-
fortunately, 1 month after completion of consoli-
dation therapy, the rash recurred, and biopsy of
the skin revealed recurrent AML, still with mini-
mal bone marrow involvement. Reinduction che-
motherapy resulted in disappearance of the le-
sions, and transplantation of allogeneic bone
marrow from the infant’s father was performed
early in the second remission. Skin lesions re-
curred within 6 weeks after transplantation. De-
spite salvage chemotherapy and donor lymphocyte
infusions, progressive cutaneous and then central
nervous system involvement developed, and the
patient died at 15 months of age.
A nat omic a l Di agnosis
cation, with involvement of the skin (leukemia
Dr. Burnett reports receiving lecture fees from Novartis. No

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