DOI: 10.1111/j.1610-0387.2011.07842.x
Keywords
Summary
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
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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
Leukemia cutis
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Leukemia cutis
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
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Figure 5: Erythematous solid nodules on the right hand in a paraungual distribution; chronic lymphocytic leukemia.
Figure 7: Purple erythema and hair loss in the parietal region; acute monocytic leukemia.
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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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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
References
1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
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29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
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71
72
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