Review

DOI: 10.1111/j.1610-0387.2011.07842.x

Leukemia cutis epidemiology, clinical presentation,

and differential diagnoses
Gunnar Wagner1, Klaus Fenchel2, Walter Back3, Alina Schulz1, Michael Max Sachse1
(1) Department of Dermatology, Allergology, and Phlebology, Bremerhaven Reinkenheide Hospital, Germany
(2) Department of Internal Medicine, Division of Hematology and Oncology, Cuxhaven Hospital, Germany
(3) Pathological Institute of Bremerhaven, Germany

JDDG; 2012 10:2736

Submitted: 7.6.2011 | Accepted: 28.9.2011

Keywords

Summary

Leukemia cutis is an extramedullary manifestation of leukemia. The frequency

and age distribution depend on the leukemia subtype. The clinical and
morphological findings have a wide range of cutaneous manifestations and
may present with nodular lesions and plaques. Rare manifestations include
erythematous macules, blisters and ulcers which can each occur alone or in
combination. Apart from solitary or grouped lesions, leukemia cutis may also
present with an erythematous rash in a polymorphic clinical pattern.
Consequently, leukemia cutis has to be distinguished from numerous differential
diagnoses, i. e. cutaneous metastases of visceral malignancies, lymphoma, drug
eruptions, viral infections, syphilis, ulcers of various origins, and blistering
diseases. In the oral mucosa, gingival hyperplasia is the main differential
diagnosis.
The knowledge of the clinical morphology is of tremendously importance in
cases in which leukemia was not yet known.

leukemia cutis
acute myeloid leukemia
chronic lymphocytic leukemia
chloroma
myeloid sarcoma
granulocytic sarcoma
gingival hyperplasia

Introduction
Leukemia is a malignant neoplasm
affecting the hematopoietic system. Following a generalization phase in the bone
marrow and subsequent appearance of
leukemic cells in the peripheral blood,
extramedullary manifestation can occur
in various organs of the body, including
the skin. The classification of various
types of leukemia is based on the biological behavior of disease as well as the
morphological, immunophenotypical,
and cytogenetic characteristics of neoplastic cells in acute and chronic, lymphocytic or myeloid forms of disease
[1, 2]. Acute leukemia has been divided
into sub-types by the French-AmericanBritish (FAB) Cooperative Group: acute
lymphocytic leukemia (ALL) has been
sub-divided into types L1L3 and acute
myeloid leukemia (AML) into types
M0M7 [3, 4].
The clinical symptoms of acute leukemia
are caused by the often rapidly developing bone marrow insufficiency. The

resulting, often serious, clinical picture

is characterized by a high fever as well
as gastrointestinal and pulmonary symptoms, accompanied by progressively
severe anorexia, muscle and joint pain,
and hemorrhage. Chronic leukemia, especially chronic lymphocytic leukemia
(CLL), is often discovered incidentally
after a routine blood test or following
identification of splenomegaly on upper
abdominal ultrasound [1, 2]. Dermatological symptoms seen in leukemia are
divided by clinical and histopathological
criteria into unspecific and specific skin
changes. Unspecific skin changes are
mostly dermatological diseases which
have been associated with leukemia and
which develop on the basis of abnormal
hematopoiesis or as an expression of
a cutaneous paraneoplastic disorder.
While thrombocytopenia may give rise
to hemorrhagic skin diseases, e.g.,
thrombocytopenic purpura, inadequate
granulocytopoiesis can lead to opportunistic, often clinically unusually severe

The Authors Journal compilation Blackwell Verlag GmbH, Berlin JDDG 1610-0379/2012/1001

infections such as generalized herpes

zoster, furunculosis, and fungal abscess.
Cutaneous paraneoplastic disease includes include pyoderma gangrenosum,
Sweet syndrome, and insect-sting-like
skin changes [57]. Specific skin changes
include all lesions that are characterized
by a leukemic infiltrate and which may
be characterized, irrespective of the clinical morphology, as leukemia cutis (LC)
[6, 8]. This traditional classification,
which differentiates between unspecific
and specific skin changes, is based on
previously available histopathological
examination methods for the detection
of cutaneous leukemic infiltration. In
practical terms, it is still valid today. Yet
with the availability of modern immunohistochemical and molecular genetic
techniques, leukemic cells can now be
identified in unspecific skin changes seen
in leukemia and other skin diseases.
Leukemic cells have been identified in
herpes simplex lesions, psoriasis vulgaris,
and in various epidermal neoplasms

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[912]. The diagnosis of LC can therefore no longer be based solely on the appearance of intralesional leukemia cells,
but instead improved histopathological,
immunohistological, and molecular
pathology detection methods should be
used. In this sense, LC is a separate disease entity, distinguishable from other
dermatological disorders as an extramedullary cutaneous manifestation of
leukemia.
Epidemiology/pathogenesis
In 2006 about 9 300 people were diagnosed with leukemia in Germany. In
2010 an estimated 9 790 new reports of
disease may be expected. The ratio of
men to women with leukemia is 1.1 : 1.0
with a slight preponderance of men [13].
For both sexes, the proportion of
leukemia patients relative to the total
number of cancer patients is about 2.1 %
[14]. The average age of disease for men
is 68 years and for women 69 years of age
[15]. The incidence rates of individual
forms of leukemia are age-dependent.
Of particular interest to dermatology are
CLL and, for AML, acute myelomonocytic leukemia (AMMoL, FAB-M4)
and acute monocytic leukemia (AMoL,
FAB-M5), because skin changes are most
often seen in these forms of disease.
In the literature on hematological
disease, the overarching terms myeloid
sarcoma and granulocytic sarcoma are
also used, given that, along with classic
LC, other manifestations such as involvement of the pancreas or vertebral
bodies are also included [1619]. The
frequency is reported at 2.130 %
depending on the underlying form of
leukemia and can precede apparent
leukemia by several months or even
years. Thus knowledge of these diseases
is of particular importance [20].
In addition to acute forms of leukemia,
myeloid sarcoma or LC can also occur in
conjunction with chronic leukemia, i.e.,
CLL and myeloproliferative syndromes,
especially chronic myeloid leukemia
(CML).
CLL accounts for about 30 % of all types
of leukemia, making it the most common type of leukemia in western industrialized nations. The incidence of disease is age-dependent. Up to age 40,
CLL is rare. At later ages, the incidence
continually increases to a maximum of
30 : 100 000 among 80-year-olds [21].
In 310 % of CLL patients, there is

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Leukemia cutis

transformation into secondary highly

malignant non-Hodgkin lymphoma
(Richter syndrome). There are also isolated reports of primary cutaneous forms
of disease [22].
AML is seldom reported in children and
young adults up to age 30. Among 70year-olds the incidence is 10 : 100 000
[23]. In terms of AML, the frequency of
AMMoL is reported at 20 % and AMoL
at 10 % [1].
Epidemiological data on the incidence
and prevalence of LC are lacking. This
rare skin disease is also seen in different
forms of leukemia with various frequencies. Statistics on the incidence of LC are
based on analyses of various groups of
patients with defined forms of leukemia
and comparison with one another. Patients with CLL and AML have a greater
tendency toward disease [8]. The frequency of LC in CLL is reported at
427 % [2427]. Considering that in
terms of numbers, CLL is the most common form of leukemia and usually has
course that spans many years, one would
expect LC to be most often reported in
patients with CLL. When comparing absolute numbers, however, LC is most
common in AML. Agis and colleagues
performed an analysis of the data from
381 patients with AML [28]. Fourteen
patients were found to have LC, corresponding to a prevalence of 3.7 %. Of
these 14 patients, 10 had AMMoL or
AMoL. At 71.4 %, the rate of these types
of leukemia was quite large, a finding
that has also been reported by other authors (50.0 % and 72.2 %) [29, 30]. The
age and sex distribution of patients with
LC do not differ from leukemia patients
without cutaneous involvement [28, 29,
31].
The molecular pathogenetic causes for
the invasion of leukemic cells into the
skin have not been fully elucidated. A
recently published review has suggested
various hypotheses. One model was
proposed in 2008 by Cho-Vega and
colleagues and has since been further
developed. This hypothesis holds that
specific, T-cell-bound antigens (e.g.,
CD56) and different chemokines or adhesion molecules mediate the migration
of leukemic sub-populations to the skin
(skin selective homing) [32, 33].
Clinical appearances
The time between the appearance of LC
and the diagnosis of the underlying

leukemia varies. In the majority of

patients (according to the literature, 55
to 77 %), LC develops in patients who
have already been diagnosed with
leukemia.
The simultaneous cutaneous and systemic manifestation of leukemia is less
frequent at 2338 %. In the rarely occurring aleukemic LC, which affects up to
7 % of patients, specific cutaneous signs
of leukemia may precede hematologic
detection of disease in the peripheral
blood or bone marrow by several months
or years [6, 8].
There are no preferred sites of involvement in LC. The trunk, extremities, and
head are equally affected. LC less often
appears on palmoplantar surfaces and
the oral mucosa [8]. Clinical lesions seen
in LC may be solitary or multiple, either
affecting circumscribed areas or disseminated in an exanthematous rash. Generalized distribution of cutaneous lesions
may be an indication of an acute form of
leukemia. Solitary, scattered, or grouped
lesions are seen in both acute and
chronic leukemia [30]. The different
growth dynamics of cutaneous forms
may also serve as an indication as to
which form of leukemia the patient has.
Rapid growth, sometimes in spurts,
tends to be characteristic for acute
leukemia while in chronic forms gradual,
progressive growth is more common [5].
Clinical morphology is not useful for
diagnosis of leukemia type in LC given
that individual lesions are not pathognomic for the different forms of
leukemia, although chloroma and
gingival hyperplasia may be exceptions
[6, 29]. The most common clinical findings in LC are nodular structures such as
papules, nodules, and larger tumors
(Table 1). Their frequency has been
analyzed in a study by Su and colleagues
that included 42 patients with different
forms of leukemia [8]. Dome-shaped
papules, sometimes as large as a pea, are
usually soft rather than firm (Figures 1,
2). Larger nodules or plaques with diameters measuring several centimeters may
be flat or raised in calotte-like fashion
and may have a rubbery consistency
or possibly more firm (Figures 35).
Harder LC tumors, sometimes as large as
a fist, may also be covered with crusts or
scale, with or without ulceration [6, 8,
30]. Nodular lesions vary widely in color
from yellowish to brown, red, or purple.
Some authors have even reported a blue,

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Leukemia cutis

Table 1: Clinical morphology in

leukemia cutis.
Common findings
Papules, nodules, tumors
Plaques
Rare findings (combined
appearance and transitions
between individual morphologies
are possible)
Erythema
Erythroderma
Ulcer
Blisters
Colors
Red, red-brown
Brown, yellowish
Bluish, gray
Hemorrhagic, purpuric
Deep lesions may have skincolored surfaces

Figure 2: Red-brown papules on the lower leg; chronic lymphocytic leukemia.

Distribution
No predilection sites
Singular, grouped, or disseminated
Exanthematous spread
Involvement of oral mucosa
Gingival hyperplasia
Nodules, ulcers
Special features
Chloroma
Leonine facies
Affecting scars

Figure 3: Infiltrated nodules on the forehead; acute myelomonocytic leukemia (chloroma).

Figure 1: Lichenoid papules on the left forearm;

chronic lymphocytic leukemia.

Figure 4: Nodule on the lower lip; chronic lymphocytic leukemia.

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Leukemia cutis

Figure 5: Erythematous solid nodules on the right hand in a paraungual distribution; chronic lymphocytic leukemia.

Figure 6: Hemorrhagic nodules on the trunk; acute myelomonocytic leukemia.

Figure 7: Purple erythema and hair loss in the parietal region; acute monocytic leukemia.

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blue-gray, or hemorrhagic tinge (Figures 6, 7) [3437]. Less often there may

be superficial oozing erosions or craterlike ulcerations [8, 29, 31, 3841].
A separate entity as a nodular manifestation of LC is chloroma (syn.: myelosarcoma). Originally reported in the orbital
periosteum, this tumor usually affects
the dermis, the lymph nodes, or the gastrointestinal tract. The lesions often
measure several centimeters in diameter,
and are dome-shaped and erythematous.
Chloromas ( = green-yellow)
have a green color when cut which is presumably due to the peroxidase content of
the myeloid cells (Figure 3). Chloromas
are considered a specific form of AML,
although they have also been reported in
other myeloproliferative diseases [35, 42,
43]. In terms of size, the lesions may be
coin-sized or as large as the palm of the
hand, or they may coalesce to form even
larger lesions. They are usually red or
brown-red in color and have a firm consistency. In men, the appearance of
plaque-like infiltration affecting both
mammillae is considered a specific
finding of LC [5]. There is an increased
incidence of chloromas in children with
AML [4446]. Usually they are the
initial manifestation of disease or are an
indication of recurrence. A large study
with 92 adult patients with myelosarcoma (chloroma) found that up to 27 %
had de novo tumors [47].
Excluding nodular and plaque-like
forms, all other clinical forms of LC are
rare. Macular rashes have only occasionally been reported; lesions are coin-sized
to as large as the palm of the hand with a
poorly-defined border and usually with
an already palpable infiltrate (Figure 8)
[4851]. With increasing infiltration of
the erythematous areas, there may be
polymorphism with maculae, plaques,
papules, and nodules, developing into a
maculopapular exanthem [2729, 34,
37, 38, 42, 48, 52]. On the face, the
transition from erythema to nodular or
plaque-like infiltration can lead to a
grotesque appearance known as leonine
facies [5, 8]. Another clinical feature of
LC is the development of nodules and
infiltration of scars [29, 32, 39, 53, 54].
If the erythema spreads, erythroderma
may occur, accompanied by marked sebostasis and pityriasiform or exfoliative
scaling [5, 8, 55].
Erythroderma is considered an unspecific
cutaneous manifestation of leukemia.

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Leukemia cutis

Figure 8: Maculopapular rash on the lateral hemithorax; chronic lymphocytic leukemia.

In the previously mentioned article by

Su and colleagues, of the 42 patients
with LC, only 2 had erythroderma [8].
Both of these patients had CLL. In
another case report on a patient with
exfoliative erythroderma, there was underlying prelymphocytic T-cell leukemia
[56].
LC ulcers, which usually appear as
solitary lesions and only occasionally as
multiple lesions, often measure only a
few centimeters in diameter. The ulcer
base contains a firmly adherent purulent
or hemorrhagic coating, and the ulcer
margin is soft and raised. Ulcers may also
affect unusual sites such as the groin,
scrotum, or face [31, 52, 57, 58].
Leukemic ulcers are resistant to the usual
treatment measures for ulcers which, in
some cases may help lead to diagnosis.
Blisters are a clinical-morphological
rarity of LC. They have been reported on
the fingers, hands, and arms in symmetrical arrangement, on the trunk in irregular distribution, and may be the size of
a fingernail or coin-sized, or occasionally
even larger, on a red background and
containing clear, purulent, or hemorrhagic material [8, 59, 60].
The most common change affecting the
oral mucosa in LC is gingival hyperplasia. The clinical appearance consists of
light pink or bright red, circumscribed
tumor-like or flat-elevated gingival
swelling, sometimes nearly engulfing the
teeth. The mucosal surface may be
smooth or covered with small bumps.
The vulnerable gingiva has a tendency to
blood and become necrotic [34, 61].

Gingival hyperplasia is often observed

in combination with AML, especially
AMMoL and AMoL. In a study by
Kaddu and colleagues, gingival hyperplasia
was found in 7 out of 17 patients with
AML, of whom 6 had either AMMoL or
AMoL [29]. In a study by Su and colleagues, gingival hyperplasia was reported
in 2 patients with AMMoL and AMoL
[8]. The literature contains very rare reports of gingival hyperplasia in CML [35].
Unlike gingival hyperplasia, papules or
nodules, as well as ulcers of the oral
mucosa may also occur in other forms of
leukemia such as CLL [5, 52, 62].
Histopathology/cytology/
immunochemistry
The histopathological diagnosis of LC is
based on an evaluation of the pattern
of distribution, cytologic findings, and
immunohistochemical characteristics of
the tumor cells. The histological appearance generally varies, also over the course
of disease, and does not necessarily correlate with clinical appearances [6, 63]. In
making the conclusive diagnosis, hematologic results from the peripheral blood and
bone marrow as well as the clinical course
should be taken into account.
In a study by Klco and colleagues, about
one-third of patients with LC had a
diffuse pattern of infiltration with involvement of the superficial and deep
dermis [47]. Focal, perivascular, or
adnexal patterns of growth have also
been reported [64].
In LC with underlying CLL, about half
of patients have epidermal infiltration,

The Authors Journal compilation Blackwell Verlag GmbH, Berlin JDDG 1610-0379/2012/1001

which is usually focal [65]. The leukemic

infiltrate may be diffuse or nodular, with
perivascular or periadnexal involvement
and generally has a well-defined boundary (Figure 9a) [6]. The cytologic appearance of ALL is characterized by a
monomorphic infiltrate of moderatelysized or large lymphoid cells with pleomorphic nuclei and a thin basophilic cytoplasm. In CLL, small or medium-sized
lymphocytes with hyperchromatic nuclei
and sparse cytoplasm predominate [29,
65, 66]. Immunohistochemistry shows a
heterogeneous appearance. The B lymphoblasts in ALL are positive for CD79a
and TdT, while T lymphoblasts are positive for CD1a, CD3, CD43 and TdT. In
CLL the tumor cells may express CD5,
CD19, CD20, CD43 and occasionally
CD5 (Figure 9b) [29, 32, 66, 67].
The cytologic appearance of individual
AML forms is characterized by various
monomorphic cell lines, which in
myeloblastic leukemia (FAB-M1 and -M2)
are characterized by medium-sized to
large mononuclear cells with a light
cytoplasm and large, basophilic cell
nuclei. AMMoL and AMoL are generally
dominated by medium-sized, round or
oval-shaped mononuclear cells which
may have an eosinophilic cytoplasm and
segmented or kidney-shaped basophilic
nuclei (Figure 10a). A working group led
by Bnet and colleagues recently
reported various indications of a possible
association between individual histological patterns and different forms of
leukemia. In LC lesions with underlying
AMMoL/AMoL the authors reported
that a granuloma-annulare-like pattern
was frequently seen [64].
In CML, the pleomorphic infiltrate is
composed of myelocytes, metamyelocytes,
eosinophilic metamyelocytes, and segmented neutrophilic granulocytes [29]
(Figure 10a). Immunohistochemistry
studies show that in 5065 % of patients
with AML and 7080 % with CML,
NASD is positive [29, 66]. Lysozyme,
MPO, CD74, CD43 and other antibodies are also among the most frequently
used markers for myeloid leukemia
(Figure 10b). It is not possible to classify
the different forms of leukemia by skin
biopsy alone; additional cytochemical and
molecular genetic studies (e.g., bone
marrow biopsy) are needed [32, 66]. A diagnosis of LC was confirmed, however, in
173 skin biopsies using an antibody panel
(CD33, CD68, and MPO) [64, 33].

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Leukemia cutis

Figure 9: (a) Histology of B-CLL. Skin biopsy with regular epidermis und with cuff-like, quite monotonous infiltration of lymphoid cells around the
superficial and deep dermal capillaries; no infiltration of lymphocytes in the epidermis (Giemsa 10). (b) CD5 positive B-lymphocytes (CD5, 10).

Figure 10: Histology of AMoL. Perivascular and perifollicular infiltrates of relatively small round cells with poor cytoplasm and grooved (monocytelike) nuclei. (a) Between the blast infiltrates some nuclear debris (Giemsa, 10). (b) Some spotted positivity of the cytoplasm of these cells for ASDchloroacetate-esterase, typical for monocytoid myeloid blasts (ASD-chloracetate-esterase, 40).

Molecular pathology
The complex migration of leukemic cells
to the skin (skin selective homing, see
Epidemiology/Pathogenesis) is the subject
of intense study, especially on molecular
pathological features. Numerous chromosomal mutations have already been described for AML [33]. In regard to LC,
there have also been a number of reports
of various chromosomal anomalies (especially affecting chromosomes 8 and 21)
[68, 69].
Differential diagnoses
LC lesions, and their number and distribution, can provide important clues for
differential diagnosis (Table 2). If there
are solitary lesions or only a few papules

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and nodules, in addition to CL, metastasis of visceral malignancy should also be

considered, although then the lesions are
usually are very firm or even rock-hard
(e.g., breast cancer) [70]. Hemorrhagic
or purpuric nodules and plaques on the
trunk, and especially on the lower legs,
should be distinguished from vasculitis
allergica and Kaposi sarcoma [31,
3638, 48]. Flat nodules and infiltrated
erythema, which also occur on the lower
legs, should raise suspicion of possible
erythema nodosum [8, 51, 71]. Depending on the severity of infiltration, the
erythematous bright red, or red-brown
plaques in LC may imitate erythema exudativum multiforme, panniculitis, or
the clinical appearance of mycosis fun-

goides [32, 40, 49, 51]. Unlike bacterial

paronychia, paraungual manifestation of
leukemic infiltrates appears on several
fingers simultaneously and is characterized by more severe elevation of the nail
wall region [72].
If there is exanthematous spread of
nodular lesions, papular drug eruptions,
sarcoidosis, a syphilitic exanthem, and
lymphoma are among the most important differential diagnoses in LC [5, 32,
35, 48]. Circumscribed facial erythema
may raise suspicion of seborrheic dermatitis or lupus erythematosus. An increased infiltrate may cause the clinical
appearance of Morbihan disease before
development of leonine facies [31, 50].
Unlike LC of the face, Morbihan disease

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Table 2: Differential diagnosis of leukemia cutis (localization/clinical morphology).

Trunk and extremities
Metastasis of visceral malignancy, lymphoma, Kaposi sarcoma, basal cell
carcinoma, squamous cell carcinoma
Drug eruption, viral exanthem, syphilitic exanthem, pityriasis rosea, vasculitis
allergica, bullous autoimmune skin disease, erythroderma of various origins
Ulcers of various origins
Extremities
Dyshidrotic eczema, pompholyx
Paronychia of various origins
Face
Seborrheic dermatitis
Lupus erythematosus
Morbihan disease
Oral mucosa
Idiopathic gingival fibromatosis
Drug-induced gingival hyperplasia
Plaut-Vincent angina
Primary syphilis, gummata

has a much longer history which initially

involves fluctuating severity of the puffy
areas of swelling and which is characterized by edematous findings on palpation
[73]. Macular or maculopapular exanthems related to LC may be mistaken
for viral exanthems, drug eruptions,
syphilis, or pityriasis rosea [5, 35, 74].
The paraclinical features of acute forms
of leukemia make it more difficult to distinguish the disease from viral infections
or drug-induced hypersensitivity syndromes [75]. The maximum variant of
an erythematous manifestation of LC is
erythroderma, which should be differentiated from similarly severe skin diseases
of another origin [55]. Blisters on
the fingers, may resemble findings in
dyshidrotic eczema or pompholyx [59].
Large blisters on the trunk should be distinguished from bullous autoimmune
diseases [55]. Ulcers in unusual locations
such as on the face, trunk, thighs, or genital area, as have been reported in LC,
should be distinguished from pyoderma
gangrenosum and ulcus molle [52, 57].
Leukemic ulcers on the lower legs do not
differ clinically/morphologically from
leg ulcers due to other causes, but may
occur at unusual sites and may have an
undermined or raised margin [52, 58].
In the differential diagnosis of leukemic
gingival hyperplasia, idiopathic gingival
fibromatosis and gingival hyperplasia

due to medication use, should be taken

into consideration. Idiopathic gingival
fibromatosis is an autosomal dominant
inherited disease that manifests in early
childhood [76]. Typical drugs that can
cause gingival hyperplasia include cyclosporine A, phenytoin, and nifedipine
[77]. Nodules and ulcers appearing on
the oral mucosa in LC should be differentiated from Plaut-Vincent angina,
from lesions seen in influenza infections,
and from primary syphilis or gummata
[35, 61].
Therapy and prognosis
Rubin and colleagues proposed the hypothesis in 1985 that LC may develop
independently of AMoL. They reported
on a 13-month old girl with AMoL and
LC. After the disease had been in remission for five months (with continued systemic chemotherapy), the infant experienced an isolated recurrence of LC.
Except for the head region, there were
disseminated multiple cutaneous nodules. Upon initial diagnosis of AMoL,
the infant had undergone whole-brain
radiotherapy. The recurrence of LC
resolved completely after whole body
surface electron irradiation. The girl was
still in remission after 12 months.
The authors concluded that the
leukemic cells in the skin may have survived the multiple chemotherapy regime

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due to an unspecified escape mechanism,

but that they had been destroyed in the
head region by the whole-brain radiotherapy performed at that time [78].
This hypothesis is still current. For instance, recurrent chloroma reportedly
occurs more frequently in organ systems
that are less accessible to systemic
chemotherapy or radiation therapy (e.g.,
CNS, ovaries, uterus) [33].
Given the high sensitivity of LC to radiation, even today under certain conditions exanthematous spread or isolated
LC lesions may be treated with radiation
therapy [29, 33].
In LC the treatment of the underlying
leukemia is a primary goal [1, 2]. Parallel
to remission of hematological findings,
there is generally also complete or partial
resolution of cutaneous manifestation
[2830]. Studies by Kaddu and colleagues [29] have shown the influence
of chemotherapy on the course of LC in
15 patients with AML. The authors
reported that remission occurred in all
patients, and in 10 patients, there were
no recurrences of LC over the course of
disease. Yet 9 of the 10 patients died
within 12 months of causes related to
leukemia. Thus the resolution of LC in
response to chemotherapy cannot be
assumed to be a prognostic indicator for
the course of disease.
LC has been interpreted by a few authors
as a systemic manifestation and is thus
considered an unfavorable factor in
prognosis [6, 2932]. Thirty-seven
(88 %) out of 42 patients with various
forms of leukemia died, most within
one year of diagnosis with LC. With an
average survival time of only 1.3 and
3.6 months after diagnosis of LC, the
prognosis for AMMoL and AMoL was
especially poor [8].
The prognostic significance of LC is
undisputed. Agis and colleagues compared the results of chemotherapy in
AML between patients with and without
LC. They found no difference in
the number of patients with complete
remission or the number of premature
fatalities. Nor were there significant differences in the recurrence-free survival
and average duration of complete remission [28]. Other working groups have
shown that there is no direct relationship
between the extent of infiltration of
the skin in LC or a specific histological
infiltration pattern and prognostic significance [27, 67].

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In the future, the molecular pathological

diagnosis of various gene mutations
(e.g., NPM1, FLT3) will be very important for the pathogenetic interpretation
and prognosis of LC and underlying
forms of leukemia [33].
Conclusion
The clinical appearances of LC are
highly variable and include mainly
papules, maculae, nodules, and plaques.
Conclusions about the histopathological
type of underlying leukemia are only
possible with immunohistochemical and
molecular genetic methods.
In more than half of patients, LC develops only after diagnosis of the underlying leukemia. In up to 7 % of patients it
may occur as the initial manifestation. A
skin biopsy is the method of choice for
early confirmation of the presumptive
diagnosis.
Interdisciplinary hematologic/dermatologic
follow-up is essential, even for patients in
remission with underlying leukemic disease for prompt identification of cutaneous recurrences.
<<<

Leukemia cutis

Conflict of interest
None.

Correspondence to
Dr. med. Gunnar Wagner
Klinikum Bremerhaven Reinkenheide
Postbrookstrae 103
D-27574 Bremerhaven
Tel.: +49-471-299-3273
Fax: +49-471-299-3518
E-mail: gunnar.wagner@klinikum-bremerhaven.de

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ABW?Wissenschaftsverlag,
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